Use of opioids to treat chronic, noncancer pain.
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Chronic Disease↗
Biomedical subjects
R D Altman
Publications and source records attributed to R D Altman.
Prevalence of pelvic Paget's disease of bone in the United States.
The objective of this article was to estimate the prevalence of Paget's disease of bone in the United States from a statistically derived sample of the general population. Pelvic radiographs obtained in the First National Health and Nutrition Examination Survey (NHANES-I) were reviewed for the presence of Paget's disease. Age, sex, and geographic distribution of Paget's disease of the pelvic region were determined. The overall prevalence of Paget's disease in the United States was estimated. Pelvic Paget's disease is estimated to be present in 0.71 + 0.18% of the radiographs of the general population. The disease was higher in frequency in people who were in the older decades of life with the highest prevalence of 2.32 + 0.54% in the 65- to 74-year-old people. There is a slight male predominance in the 45- to 74-year age group. The regional distribution suggests the highest prevalence in the Northeast (1.48 + 0.52%) with the lowest prevalence in the South (0.26+0.25%). The prevalence was equal in white people and black people. An estimate of the overall prevalence of Paget's disease in the United States was at least 1% and perhaps as much as 2 % of the general population with near equal sex distribution and the highest prevalence in the northeastern United States.
Adult↗
Safety of over-the-counter inhalers for asthma: report of the council on scientific affairs.
The occasional use of over-the-counter (OTC) epinephrine inhalers appears to be safe and effective when used according to labeled instruction by individuals with mild, intermittent asthma. However, gross misuse of these products can cause severe adverse reactions, including death. Limited survey data suggest that approximately 20% of individuals using OTC epinephrine inhalers have mild-to-moderate persistent asthma. According to recent consensus guidelines, these individuals should be under a physician's care and receiving corticosteroid therapy. If these products continue to be marketed, labeling should be strengthened to better educate users about appropriate and inappropriate use of OTC epinephrine inhalers intended for patients with mild, intermittent asthma.
Administration, Inhalation↗
Treatment with calcitonin suppresses the responses of bone, cartilage, and synovium in the early stages of canine experimental osteoarthritis and significantly reduces the severity of the cartilage lesions.
OBJECTIVE: To relate the rate of bone resorption to serum levels of both hyaluronan (HA) and antigenic keratan sulfate (KS) in canine experimental osteoarthritis (OA) and to evaluate the effects of calcitonin on these parameters and the OA lesions of the unstable knee. METHODS: Twenty-two dogs underwent anterior cruciate ligament transection (ACLT) and 6 dogs underwent sham operation. Urinary pyridinium crosslinks were quantified by high-performance liquid chromatography. Immunoassays quantified hyaluronan (HA) and antigenic KS. Macroscopic and histologic OA lesions were scored. Calcitonin treatment was started on day 14 postsurgery and stopped on either day 49 or day 104 postsurgery. Control dogs and all treated dogs were killed on day 105. RESULTS: All ACLT joints developed OA. In contrast to sham-operated animals, all operated dogs exhibited an early and sustained rise in the levels of their urinary and serum markers. Calcitonin markedly reduced the levels of these markers and the severity of OA lesions. Furthermore, the longer the period of calcitonin therapy, the lower the score of the OA lesions. CONCLUSION: Bone, synovium, and articular cartilage all appear to be involved in the state of hypermetabolism that develops in unstable joints. Furthermore, the rate of bone resorption increases markedly in the early stages of this OA model and is likely to contribute to cartilage breakdown. Since calcitonin reduced the severity of OA changes, this form of therapy may have benefits for humans who have recently experienced a traumatic knee injury.
Amino Acids↗
Arthritis in Paget's disease of bone.
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Back Pain↗
Paget's disease of bone: rheumatologic complications.
Pain is the most common reason people consult a physician when suffering from Paget's disease of bone. The most common reason for patients' pain is osteoarthritis, either directly or indirectly induced by Paget's disease. The physician should make a concerted effort to target the origin of the pain, because effective treatments for the two conditions seem to be different. Back pain is particularly common and one must be careful before attributing back pain to Paget's disease; otherwise, both the physician and patient may be disappointed in the results of therapy.
Humans↗
Cyclosporine A in rheumatoid arthritis: randomized, placebo controlled dose finding study.
OBJECTIVE: To determine the lowest effective starting dose and residual benefit of cyclosporine A (CSA) in patients with rheumatoid arthritis (RA) refractory to other agents. METHODS: In a double blind (masked observer), controlled, multicenter study, patients with RA started CSA 0 (placebo; n = 61), 1.5 (n = 89), or 2.5 (n = 94) mg/kg/day in a 21 week study that permitted dose escalation after 8 weeks, 1 week tapering of dose at 16 weeks, and post-therapy observation for 4 weeks. RESULTS: Patients with RA taking CSA 2.5 mg/kg/day fared better than those in the placebo or CSA 1.5 mg/kg/day groups in Patient Global Assessment, Examiner Global Assessment, Pain/Tender Joint Count and Index, Swollen Joint Count, and the "Ability at this moment" part of a modified Health Assessment Questionnaire. There was no difference in response between CSA 1.5 mg/kg/day and placebo groups. In the CSA 2.5 mg/kg/day group: improvement occurred between 8 and 12 weeks of therapy; average CSA dose escalation resulted in CSA 2.85 mg/kg/day by Week 16; benefit was not maintained during post-therapy observation and 7 patients discontinued the study because of an adverse event. Adverse events were common in all groups and included gastrointestinal discomfort, hypertension, and increased creatinine. Adverse events remitted with adjustment of dose or after washout in most patients. CONCLUSION: In RA, treatment of patients with CSA 2.5 mg/kg/day, but not 1.5 mg/kg/day, resulted in improvement of 4 of 5 primary efficacy variables when compared to placebo. Adverse events were mostly manageable. CSA was an effective therapy for patients with RA who had failed at least one second line agent.
Adult↗
A randomized clinical trial of intra-articular sodium hyaluronate in patients with osteoarthritis of the knee: a summary.
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Adjuvants, Immunologic↗
Hip osteoarthritis prevalence estimates by three radiographic scoring systems.
OBJECTIVE: To estimate and compare the age- and sex-specific prevalence of radiographic hip osteoarthritis (RHOA) in a population-based study of the Pima Indians, using 3 atlas-based methods for assessing features of RHOA. METHODS: Pelvic radiographs from 755 Pima Indians age > or = 45 years enrolled in a population-based study were read using the Kellgren/Lawrence (K/L) grading scale (grade 0-4) and 2 validated individual-radiographic-features (IRF) scales (grades 0-3 for narrowing and osteophytes). RESULTS: The age- and sex-specific prevalence of RHOA among Pima Indians assessed using the K/L scale was < 10% in all age and sex groups. The prevalence of grade > or = 2 osteophytes assessed using the 2 IRF scales were similar to each other in all age and sex groups. However, differences between the 2 IRF scoring systems were found for the prevalence of grade > or = 2 joint space narrowing. CONCLUSION: Pima Indians have an age- and sex-specific prevalence of RHOA similar to that found in the US population. Our finding of different joint space narrowing prevalence by the 2 IRF grading scales supports the use of the same atlas-based case definitions for determining disease prevalence for comparative studies.
Age Distribution↗
Clinical research: assessing the future in a changing environment; summary report of conference sponsored by the American Medical Association Council on Scientific Affairs, Washington, DC, March 1996.
Concerns about funding of clinical research underlie all other problems identified at the Council on Scientific Affairs conference. Future National Institutes of Health (NIH) budgets are likely to be constant at best, and the general public expects cost containment to be an ongoing goal; this is exacerbated by the impending Medicare Trust Fund crisis. Meanwhile, traditional financial support of clinical research in academic medical centers (AMCs) through cross-subsidization is imperiled by competitive pressures largely caused by managed care. Although managed care organizations (MCOs) are potentially rich sources of funding and other resources, and some not-for-profit companies are conducting some research, for-profit MCOs have not demonstrated an understanding of the importance of clinical research. Young physicians are being discouraged from careers as clinical researchers and established investigators are "dropping out" because of demands for clinical productivity and competition for research grants, loss of patients/research subjects to managed care, perceived lack of status and compensation, and overall uncertainty about continued financial support. Efforts to assist current and potential clinical investigators are discussed in this report. Loss of patients, denial of reimbursement, and competition with MCOs and contract research organizations (CROs) have placed AMCs under unprecedented pressure. However, research centers located in AMCs have allowed investigators to conduct clinical research by providing a "protected environment." Furthermore, many AMCs are determined to continue conducting clinical research and are addressing related problems. Although the NIH will continue to be a major source of funding for clinical research, partnerships between various private and public entities provide important opportunities to maximize the productivity of all individuals and institutions involved. Potential partnerships include MCOs, AMCs, CROs, pharmaceutical companies and other industry, the Department of Defense, the Veterans Health Administration, practice-based physicians, and private foundations and patient support groups. "Partnerships in advocacy" for clinical research will be essential. Efforts to recruit for-profit MCOs to the clinical research endeavor identified in this report include (1) emphasizing issues of interest to them (eg, outcomes research); (2) stressing the significance of some research to the marketplace; (3) developing criteria to distinguish individual MCOs on the basis of their contribution to the public interest; (4) equating money spent on research with "R&D dollars" spent in nonmedical business enterprises; and (5) educating purchasers of health care (eg, corporate health plan directors) about clinical research. Conducting clinical research in all managed care settings requires leadership, the understanding and cooperation of physicians and support staff, wise use of limited resources (ie, funding only the best research projects), sound methodology, and above all, the perception that the research will ultimately improve patient care.
American Medical Association↗
Practice guidelines in the management of osteoarthritis.
Osteoarthritis (OA) is the most common articular rheumatic disease. Practice guidelines have been developed to assist the practitioner in the care of patients with hip and knee OA. The guidelines divide the treatment strategy into nonpharmacologic and pharmacologic modalities. The nonpharmacologic or nonmedicinal approaches include patient education, psychosocial interventions, physical and surgical measures. Each of these are as important as the pharmacologic or medicinal measures. Medicinal measures can be subdivided into symptomatic therapy and disease modifying therapy. Even though all present therapies are aimed at symptoms, experimental therapies are being developed to alter the disease process.
Anti-Inflammatory Agents, Non-Steroidal↗
Risedronate in the treatment of Paget's disease of bone: an open label, multicenter study.
An open-label, multicenter study was conducted to determine the efficacy and safety of oral risedronate (a pyridinyl bisphosphonate) in 162 patients (102 men, 60 postmenopausal women; mean age, 68 years) with moderate to severe Paget's disease of bone (mean serum alkaline phosphatase [ALP] approximately seven times the upper limit of normal). Patients were treated with oral risedronate, 30 mg/day for 84 days, followed by 112 days without treatment. This 196-day cycle was repeated once if serum ALP did not normalize or increased from the nadir value by > or = 25%. At the end of the first and second cycles, the mean percentage decreases for serum ALP were 65.7% and 69.1%, and for urinary hydroxyproline/creatinine 50.4% and 66.9%, respectively. The decreases from baseline in ALP and urinary hydroxyproline/creatinine were significant (p < 0.001). Normalization of serum ALP was observed in 86 patients (53.8%): 53 during the first treatment cycle and 33 during the second. There was a significant proportion of patients reporting a decrease in the pagetic bone pain at days 84 and 196 (p < 0.001). Overall, risedronate was well tolerated. Five patients withdrew due to adverse events, none of which were considered to be drug related. In conclusion, 30 mg of oral risedronate administered daily for 84 days significantly reduced the biochemical indices of disease activity and was associated with pain reduction in patients with moderate to severe Paget's disease of bone. Normalization of ALP was observed in the majority of patients. Repeated administration of risedronate was shown to be beneficial. In general, risedronate was well tolerated and demonstrated a good safety profile.
Administration, Oral↗
Digital clubbing and lung cancer.
OBJECTIVES: To determine the relative frequency of clubbing in small cell lung carcinoma (SCLC) versus non-small cell lung carcinoma (NSCLC). DESIGN: Examine patients with lung cancer for digital clubbing and relate the findings to the histopathologic subtype of lung cancer. SETTING: Cancer center at a tertiary teaching hospital. PATIENTS OR PARTICIPANTS: One hundred and eleven consecutive patients with a pathological diagnosis of lung cancer examined by one physician (KSS). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Clubbing was present in 32 (29%) of the 111 patients with lung cancer. Clubbing was more common in women (40%) than in men (19%; chi2 test p = 0.011), and was more common in patients with NSCLC (35%) than those with SCLC (4%; chi2 test p = 0.0036). CONCLUSION: In a prospective study, digital clubbing was less frequently observed in men than women and in patients with SCLC than NSCLC. These clinical observations may assist in the initial evaluation of patients for planning workup and therapy.
Carcinoma, Non-Small-Cell Lung↗
Intraarticular sodium hyaluronate (Hyalgan) in the treatment of patients with osteoarthritis of the knee: a randomized clinical trial. Hyalgan Study Group.
OBJECTIVE: To determine efficacy and safety of intraarticular (IA) hyaluronic acid (HA; Hyalgan) versus placebo and a nonsteroidal antiinflammatory drug for osteoarthritis (OA) of the knee. METHOD: A series of 5 weekly IA injections of HA (20 mg each) was compared to placebo or oral naproxen in a 26 week, double blind, masked observer, multicenter trial of 495 patients with idiopathic OA. Acetaminophen was permitted for escape analgesia. The primary measurement was pain experienced on a 50 foot walk test for those completing the study (completers) as measured on a 10 cm visual analog scale (VAS). Also measured were the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index (pain, stiffness, function) and categorical assessments of pain. RESULTS: Patients receiving HA improved more with respect to pain on the 50 foot walk compared to placebo at Week 26 (HA vs placebo difference 8.8 mm; p < 0.005); 56% of HA treated patients compared to 41 % of placebo treated patients had > or = 20 mm reduction in the VAS from Week 5 continuously through Week 26 (p=0.031). At 26 weeks, more HA treated patients (47.6%) had slight pain or were pain-free in contrast to placebo treated (33.1%; p=0.039) or naproxen treated (36.9%; p=0.22) [corrected] patients. Improvement in secondary outcome variables was generally superior in the HA group compared to those receiving placebo and was significantly better at Week 26 with respect to the WOMAC pain (p=0.041) and WOMAC physical function (p=0.047) subscales. The HA group also tended to have better results relative to the naproxen group in both primary and secondary assessments. For all randomized patients, there was a > or = 20 mm improvement in pain experienced on the 50 foot walk in 28% [corrected] of placebo treated patients vs 36% [corrected] of the HA treated patients (p=0.127; 67% of patients completed the trial). Injection site pain, more commonly reported in the HA group (38/164=23%) than in the placebo group (22/168=13%; p < 0.001), resulted in withdrawal in 6 patients (4%). One withdrawal was associated with the HA injection (< 1%). Gastrointestinal adverse events were significantly more common in the naproxen group than the HA or the placebo groups and 14 naproxen treated patients (8.3%) discontinued prematurely due to these events. CONCLUSION: This large, controlled randomized clinical trial confirms that 5 weekly IA injections of HA (Hyalgan) in patients with OA of the knee are generally well tolerated, provide sustained relief of pain and improved patient function, and were at least as effective with fewer adverse reactions as continuous treatment with naproxen for 26 weeks.
Adjuvants, Immunologic↗
Chronic pain states: invasive procedures.
OBJECTIVE: To provide a review of chronic pain states, focusing on neuroanatomic pathways and their influence on treatment strategies (part 2 of a two-part series). DATA SOURCE: A thorough literature review of published articles available in Medline from 1966 to 1996 on the topic of pain management, including diagnosis, pathophysiology, interventions, and treatment. CONCLUSIONS: Understanding the pathophysiology of chronic pain and the role of chemical mediators, such as enkephalins, norepinephrine, serotonin, and substance P, may improve pain management. As a result, pain control measures can target inhibition of the descending pain modulation pathways of the spinal cord, in addition to the peripheral or central actions of traditional analgesics. Fewer ablative surgical interventions are performed for pain control, because they often provide only temporary relief at the expense of significant permanent neurological deficits. However, there are more augmentative procedures now available for the patient with intractable and unresponsive pain, although referral to specialized pain clinics may benefit particularly difficult cases.
Chronic Disease↗
Chronic pain states: pathophysiology and medical therapy.
OBJECTIVE: The pathophysiology and management of chronic pain are reviewed in this two-part article, with an emphasis on pharmacological therapies and surgical interventions. DATA SOURCES: A thorough literature review of published articles available in Medline from 1966 to 1996 on the topic of pain management, including diagnosis, pathophysiology, interventions, and treatment. CONCLUSIONS: Despite the development of new instruments and treatments to assess and manage pain, chronic pain is often poorly understood and inadequately addressed. Caregivers often lack sufficient skills to intervene promptly and effectively. Traditionally, drug therapy has relied on the nonsteroidal antiinflammatory drugs (NSAIDs) and opioid analgesics for chronic nociceptive pain. A newer analgesic choice for moderate to moderately severe pain is tramadol, a centrally acting agent with at least two complementary mechanisms of action and minimal gastrointestinal or renal toxicity. Adjuvant agents, including tricyclic antidepressants (TCAs), anticonvulsants, and local anesthetics, also help manage chronic neuropathic pain. Although significant advances in the understanding of chronic pain and its pathophysiological mechanisms and newer techniques (noninvasive and invasive) for chronic pain management have become available, reduced patient morbidity and improved quality of life may only be realized with an improved understanding of available resources.
Analgesics↗
The syndrome of osteoarthritis.
The syndrome called osteoarthritis (OA) is characterized by change in structure and function of the joint. It is only symptomatic in about half of afflicted subjects. There is no diagnostic test. Progression is followed by a set of clinical variables that can be standardized for use in clinical trials.
Age Factors↗
Design and conduct of clinical trials in osteoarthritis: preliminary recommendations from a task force of the Osteoarthritis Research Society.
In 1994, a combined committee of the World Health Organization and the International League of Associations for Rheumatology published recommendations for clinical trials for 2 classes of agents for treatment of osteoarthritis (OA) that relieved symptoms but differed in their onset and duration of response, and a third class of agents that may alter the disease process. Recently, the European Group for the Respect of Ethics and Excellence in Science made recommendations for methods to be used in the registration of drugs for OA. Following the 2nd international meeting of the Osteoarthritis Research Society in December 1994, a task force was convened to develop recommendations for the design and conduct of clinical trials in patients with OA. The Task Force had several meetings over the past 16 months, resulting in the preliminary recommendations summarized here.
Clinical Trials as Topic↗