Efficacy and safety of tramadol HCl in breakthrough musculoskeletal pain attributed to osteoarthritis

OBJECTIVE: To evaluate the efficacy of tramadol as adjunctive therapy in patients with musculoskeletal pain attributed to osteoarthritis (OA) who experienced breakthrough pain while taking a nonsteroidal antiinflammatory drug (NSAID). METHODS: This single center, parallel, placebo controlled, 2 phase study was conducted in adults who experienced breakthrough OA pain while undergoing stable NSAID therapy. In a 24 h open label phase, patients took 100 mg of tramadol followed by 50 mg every 6 h (total 250 mg) in addition to their daily NSAID regimen. Supplemental analgesics were prohibited. Patients who met entry criteria and were willing to continue therapy were randomized to a 13 day double blind phase of adjunctive therapy with tramadol (50-100 mg every 4-6 h as needed for pain) or placebo; NSAID therapy was continued. The primary efficacy endpoint was the time to exit from the study because of therapeutic failure (i.e., insufficient pain relief or an inability to perform activities of daily living). RESULTS: The time to exit from the study because of insufficient pain relief tended to be longer in the tramadol group (250 mg/day) compared with the placebo group (p = 0.066). At the end of the double blind phase, pain at rest was significantly less severe in tramadol treated patients (p = 0.046). In addition, severity of pain on motion tended to be less severe in tramadol treated patients (p = 0.059). General severity of current pain and ability to perform activities of daily living were not significantly different with tramadol or placebo. Patients' overall assessment of therapy (p = 0.022) and investigator's rating of global improvement (p = 0.004) were significantly better with tramadol than with placebo. CONCLUSION: Tramadol may have a role as adjunctive treatment for breakthrough pain in patients receiving NSAID therapy for musculoskeletal pain attributed to OA.     

Pharmacokinetic and bioequivalence study of two gemfibrozil preparations

A comparative pharmacokinetic study has been performed in 19 healthy male volunteers in a single-dose, randomized, two way cross-over design with two preparations of gemfibrozil (CAS 25812-30-0) capsules each of them containing 300 mg active ingredient. The test preparation was Innogem 300 mg capsule. The plasma concentration of gemfibrozil was determined by a validated HPLC-UV analytical method. The statistical comparison of individual pharmacokinetic parameters (AUC0-16, AUC0-oc Cmax, tmax) of the two capsule preparations was performed by three-way analysis of variance (ANOVA), Wilcoxon's, Westlake's, Schuirmann's and Hanck-Anderson's method as well as by the calculation of confidence intervals on the ratio of test/reference. The relative bioavailability of the test preparation with respect to the reference preparation in terms of the AUC0-oc was 104.06 +/- 21.61%. No statistically significant difference was found between the pharmacokinetic parameters, calculated from plasma concentration-time curves, indicating that the two preparations were bioequivalent.     

Pharmacokinetics of cefdinir and its transfer to dialysate in patients with chronic renal failure undergoing continuous ambulatory peritoneal dialysis

Cefdinir (CAS 91832-40-5) was administered orally as a 100-mg capsule (Cefzon) to a total of 12 patients with chronic renal failure undergoing continuous ambulatory peritoneal dialysis (CAPD) to investigate changes in the serum concentrations, excretion rate into the dialysate and serum-protein binding of cefdinir. Cmax values were 1.64-4.34 micrograms/ml, t1/2 values were 10.8-21.9 h., and AUC values were 31.1-73.1 micrograms.h/ml (0-30 h) in four patients given a single oral dose of 100 mg of cefdinir as a capsule. About 1 microgram/ml of cefdinir had still remained in the blood of all the patients 24 h after administration. The serum concentrations of cefdinir were dose-dependent in four patients of each group who were given an oral daily dose of 100 mg for 3 to 8 days and 200 mg (2 capsules) for 4 to 14 consecutive days. No marked change in laboratory test values or clinical symptoms before and after administration were observed in these dose regimes. Protein levels of 5.17-5.71 g/day were eliminated from the peritoneal dialysate and urine. Cefdinir inhibited 90 to 100% of the clinical isolates such as Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and other enteric bacteria causing catheter infection and peritonitis, and its antibacterial activity was stronger than that of amoxicillin (CAS 26787-78-0) or cefaclor (CAS 53944-73-3) against these clinical isolates.     

The course of back pain in primary care

STUDY DESIGN: Review paper of outcome studies among primary care back pain patients. OBJECTIVES: To determine the short-term and long-term pain and functional outcomes of patients with back pain who are seeking treatment in primary care settings. SUMMARY OF BACKGROUND DATA: Back pain has been viewed as running either an acute or a chronic course, but most patients experience recurrent back pain. This review summarizes outcome studies in light of the episodic course of back pain. METHODS: Studies reporting pain and functional outcome data for consecutive primary care patients with back pain were reviewed. RESULTS: Back pain among primary care patients typically is a recurrent condition for which definitions of acute and chronic pain based on a single episode are inadequate. Because a majority of patients experience recurrences, describing only the outcome of the initial back pain episode may convey a more favorable picture of long-term outcome than warranted. For the short-term follow-up evaluation, most patients improve considerably during the first 4 weeks after seeking treatment. Sixty-six percent to 75% continue to experience at least mild back pain 1 month after seeking care. At 1 month, approximately 33% report continuing pain of at least moderate intensity, whereas 20-25% report substantial activity limitations. For the long-term follow-up (1 year or more) period, approximately 33% report intermittent or persistent pain of at least moderate intensity, one in seven continue to report back pain of severe intensity, and one in five report substantial activity limitations. CONCLUSION: Results from existing studies suggest that back pain among primary care patients typically runs a recurrent course characterized by variation and change, rather than an acute, self-limiting course.     

Successful hormonal treatment of pulmonary parenchymal endometriosis

OBJECTIVE: Tobacco use and other behavioral factors are associated with chronic back pain. Anecdotes suggest excess caffeine use may also be associated with chronic back pain. We compared caffeine consumption by chronic back pain patients with caffeine consumption by controls. DESIGN: Retrospective case-control study. SETTING: A multispecialty outpatient facility. PATIENTS: Sixty new, consecutive patients with chronic back pain compared to 60 new, consecutive patients without chronic back pain. INTERVENTION: Patients were prospectively asked to complete an intake questionnaire. MAIN OUTCOME MEASURE: Daily caffeine consumption was estimated by analyzing the intake questionnaire. Differences between groups were analyzed by both normal and nonparametric statistics. RESULTS: Consumption of caffeine by patients with chronic back pain averaged 392.4 mg/day. Controls consumed 149.8 mg/ day, a significant difference (p = .0001). Men consumed 86% more caffeine per day than women (p = .02). Age and caffeine consumption showed little correlation (r = .126). CONCLUSIONS: Patients with chronic back pain consume over twice as much caffeine as patients without chronic back pain. Confounding variables and possible mechanisms associating caffeine with chronic back pain are discussed.     

Comparison of operant behavioral and cognitive-behavioral group treatment for chronic low back pain.

To evaluate and compare the efficacy of two widely used behavioral approaches for the treatment of chronic pain, 81 mildly dysfunctional chronic low back pain patients were randomly assigned to operant behavioral (OB) treatment, cognitive-behavioral (CB) treatment, or a waiting-list (WL) control condition. Both treatments, which were conducted in eight-session outpatient groups, resulted in decreased physical and psychosocial disability. The OB patients showed greater pre- to posttreatment improvement as rated by patients and their spouses than did the CB patients. Generally, the OB patients showed a leveling off in improvement at 6- and 12-month follow-ups, whereas the CB patients generally continued to improve over the 12 months following treatment. At 12-month follow-up, patients in both treatments remained significantly improved, with no significant differences between conditions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Topiramate use in pediatric patients

Topiramate (TPM), a new antiepileptic medication, is efficacious as adjunctive therapy in adults with partial onset seizures. Its efficacy as adjunctive therapy in children was evaluated in two randomized double-blind placebo-controlled trials involving childhood epileptic encephalopathy (the Lennox-Gastaut syndrome) and partial onset seizures. In these studies, topiramate adjunctive therapy resulted in a significant reduction in drop attacks (tonic or atonic seizures) in patients with the Lennox Gastaut syndrome and a significant reduction in partial onset seizures in children with refractory partial epilepsy. In both trials, TPM's efficacy improved as the dose escalated from the double-blind phase to the open-label portion. The minimally effective topiramate dose for adjunctive therapy in children with refractory epilepsy appears to be 6 mg/kg/day. Topiramate was well tolerated with mild or moderate side effects, predominantly related to the central nervous system. Practical tips are provided that may increase the chance that topiramate will be effective and well tolerated. The most important advice is a "start low, go slow" approach. An initial TPM dose of 0.5-1 mg/kg/day followed by weekly increments of 0.5-1 mg/kg is usually well tolerated. Based on these studies, topiramate appears to be an important addition to our pediatric AED armamentarium.     

Amizon in the treatment of nervous system involvement in herpes zoster

The authors submit results of treatment of patients having suffered from postherpetic pain syndrome (herpetic ganglionitis of the cervical, thoracic, lumbosacral localization, postherpetic intercostal neuralgia, ganglionitis of the trigeminal nerve). In viral diseases, amizone has marked analgetic, antiinflammatory, and immunomodulating effects. The drug is well tolerated by patients, is not associated with side effects under prescribed doses (0.25-0.75 as one dose on a three- or four-times daily schedule during the course of treatment lasting three or four weeks). The drug preparation in question is less effective in the treatment of chronic recurring post-therapeutic intercostal neuralgias, radiculalgia.     

A prospective study of long-term intrathecal morphine in the management of chronic nonmalignant pain

OBJECTIVE: To examine in a prospective manner the long-term safety and efficacy of chronic intrathecal morphine in patients with severe, nonmalignant pain refractory to less invasive modalities. METHODS: Forty patients with severe, chronic nonmalignant pain poorly managed by systemic medications were identified as candidates for intraspinal trial of morphine. Thirty participants reported successful pain relief during trial and were implanted with an intraspinal delivery system. Standardized measures of pain and functional status were assessed before treatment was begun and at defined intervals during the subsequent 24 months. Intrathecal opioid use and pharmacological and device-related complications were also monitored. RESULTS: The participants had a mean age of 58 +/- 13 years and a mean pain duration of 8 +/- 9 years. Fifty-three percent of the study participants were women. Pain type was characterized as mixed neuropathic-nociceptive (15 of 30 patients, 50%), peripheral neuropathic (10 of 30 patients, 33%), deafferentation (4 of 30 patients, 13%), or nociceptive (1 of 30 patients, 3%). Forty-seven percent of the patients were diagnosed with failed back surgery syndrome. Significant improvement over baseline levels of visual analog scale pain was measured at each follow-up examination after implant. Overall, 50% (11 of 22 patients) of the population reported at least a 25% reduction in visual analog scale pain after 24 months of treatment. In addition, the McGill Pain Questionnaire, visual analog scale measures of functional improvement and pain coping, and several subscales of the Chronic Illness Problem Inventory showed improvement throughout the follow-up period. Pharmacological side effects were managed medically by morphine dose reduction, addition of bupivacaine, or replacement of morphine with hydromorphone. Device-related complications requiring repeat operations were experienced by 20% of the patients. CONCLUSION: Continuous intrathecal morphine can be a safe, effective therapy for the management of severe, nonmalignant pain among a carefully selected patient population and can result in long-term improvement in several areas of daily function.     

A phase I study of paclitaxel and 5-fluorouracil in advanced gastric cancer

This is a phase I study to determine the maximum tolerated dose (MTD) and toxicity of a combination of paclitaxel and 5-Fluorouracil (5-FU) in advanced gastric cancer patients. The patients, refractory to the PELF regimen (5-FU, leucovorin, cisplatin, epidoxorubicin), received weekly 5-FU at the fixed dose of 500 mg/m2, and escalating doses of paclitaxel every 3 weeks with a starting dose of 150 mg/m2 given as in 3-h infusion. The dose was escalated by 25 mg/m2 every 3 patients. Fifteen patients entered the study. The upper paclitaxel dose (225 mg/m2) was given to 6 patients. Up to this dose, no severe toxicity (grade 3-4) was recorded. Apart from alopecia, grade 1-2 leukopenia occurred in 5 patients and grade 1-2 neurotoxicity in 2 patients. All patients were evaluable for response (at least 2 cycles): 2 patients achieved an objective response (200 and 225 mg/m2). In 6 patients, treatment resulted in notable relief from symptoms. Out-patient paclitaxel given over 3 h and 5-FU may be combined safely for the treatment of patients with advanced gastric cancer. The recommended doses for phase II study are paclitaxel 225 mg/m2 and 5-FU 500 mg/m2.     

Assessment of spinal musculature using surface electromyographic spectral color mapping

STUDY DESIGN: A technique is described for analyzing electromyogram data from lumbar spinal muscles, with special reference to discrimination of people with back pain. The ability to discriminate was evaluated in 99 people (61 healthy and 38 with chronic or acute back pain), and the influence of load was assessed. OBJECTIVES: To evaluate methods of analysis of complex electromyogram data and to assess correlation of electromyogram information with clinical condition in people with and without back pain. SUMMARY OF BACKGROUND INFORMATION: In previous analyses of electromyogram data, only a small part of the data have been used. Spinal muscular decompensation has been postulated in chronic low back pain, but there has been no direct demonstration of this phenomenon. Objective measures are still elusive. METHODS: Lumbar spinal surface electromyograms were recorded during an isometric lifting task. The data were represented graphically as color-coded plots of electromyogram frequency, time, and electromyogram amplitude. Spectral width at half-peak amplitude (spectral half width) was calculated from the digitized, summed data. Ninety-nine people were tested: 48 men (29 with no recent [in the past 2 years] history of back pain, 16 with chronic back pain, 3 with acute back pain) and 51 women (32 with no recent back pain and 19 with chronic back pain). RESULTS: Spectral color maps in people with chronic back pain were markedly different from those in healthy people. Spectral half width was greater in people with chronic back pain than in healthy people (P < 0.01). Blinded analysis of spectral color maps allowed discrimination of people with back pain from healthy people with a sensitivity of 76% and a specificity of 81%. People with a history of back pain had markedly variable half widths. CONCLUSIONS: A new method of analysis of electromyogram data from lumbar spinal muscles has allowed discrimination between people with back pain and healthy people. This provides direct evidence of a correlation between muscular electrical function, measured by electromyogram, and low back pain. This technique may have potential as an objective measurement tool.     

The bioequivalence of a new amitriptyline tablet formulation in comparison with a reference preparation

An investigation of the bioequivalence of a new tablet formulation (amitriptylin 25 von ct) with 28.3 mg amitriptyline hydrochloride (CAS 549-18-8) was performed in a two-way cross-over study with 18 subjects. The relative bioavailability with respect to a reference preparation for AUC related to amitriptyline (CAS 50-48-6) was 99.3% and for Cmax 100.4%. A positive decision for bioequivalence derived from the usual confidence intervals for both parameters related to amitriptyline and the metabolite nortriptyline (CAS 72-69-5), respectively tmax showed no difference. The new formulation was bioequivalent to the reference.     

Oral tramadol and buprenorphine in tumour pain. An Italian multicentre trial

In this multicentre trial tramadol and buprenorphine were compared for the treatment of neoplastic pain no longer responsive to non-steroidal antiinflammatory drugs. A total of 131 adults (86 M, 45F) were treated with tramadol (one 100-mg slow-release tablet every 8-12 h), or buprenorphine (one sublingual 0.2-mg tablet every 6-8 h). The trial was to continue for up to six months. Most patients started treatment with 2-3 tablets/day in both groups, and the mean treatment period was 58 days for tramadol and 51 for buprenorphine. Almost all dose changes needed were made in the first fortnight in both treatment groups, and the largest number of patients dropped out because of inadequate pain relief or progression of the underlying disease. The results achieved in the first two weeks persisted throughout the rest of the trial, and the investigator's assessments on each patient's clinical chart corresponded closely with those that patients made in their own daily diaries. In the four hours after the first dose both drugs virtually halved the severity of pain (measured using a visual analogue scale), and this relief lasted throughout treatment. By the end of the first week the proportion of patients with strong/unbearable pain in the tramadol group had fallen significantly (from 98.4% to 48.1%, p < 0.05), as compared to a drop from 92% to 66.7% for buprenorphine. The quality of sleep also tended to improve in the tramadol group, with the proportion of patients enjoying good or deep sleep rising from 37% to 50%, as compared to 33% to 40-44% with buprenorphine. Karnofsky's and Spitzer's indices reflecting the quality of life did not change in the tramadol group; in the buprenorphine group the Karnofsky index dropped slightly after a fortnight (p < 0.05 between treatments). In the first two months of the trial the number of patients with no/moderate pain rose continuously in the tramadol group (71% and 80% after one and two months); the rise was less marked in the buprenorphine group (number of patients with mild/moderate pain, 45% and 65%). In both the short term and in the longer term, it was found that the levels of efficacy and acceptability were always significantly better in the tramadol group than in the buprenorphine group. General and biological safety in both drugs was good. The most typical side-effects were those characteristic of opioids (nausea and/or vomiting, drowsiness). Adverse reactions were reported in 17 patients taking tramadol (25%) and in 16 taking buprenorphine (26%). There were six drop-outs in the first group (9%) and seven in the second (11%). Serious symptoms arose more frequently in the buprenorphine group (19% cf. 10%). No signs of dependence or tolerance were noted.     

Lack of interaction between tramadol and coumarins

The objective of this study was to investigate whether the central analgesic tramadol influences the effects of the coumarin anticoagulant phenprocoumon during multiple-dose administration. Nineteen patients receiving long-term anticoagulant therapy who had been in a stable hypothrombinemic state for at least 3 months completed a double-blind, placebo-controlled, crossover study. Tramadol was administered in the usual therapeutic dose of 50 mg three times daily. The average daily phenprocoumon dose was identical for individual patients in both treatment periods. The equivalence ratio (tramadol/placebo) of the international normalized ratio (INR) values was 0.99 (90% confidence interval 0.89-1.10), thus fulfilling predetermined bioequivalence criteria (0.70-1.43). Therefore, tramadol does not affect INR in patients being treated with phenprocoumon. These data suggest a lack of interaction between tramadol and coumarin anticoagulants.     

Clinical tolerance of oral loading with elevated doses of amiodarone in a group of patients with heart failure

Amiodarone is a choice drug for the treatment of patients suffering from life-threatening hyperkinetic ventricular arrhythmias and depressed ventricular function. The drug is characterized by a remarkably long halflife and a delayed initial activity after oral administration of the usual loading levels. The aim of this study was to establish: -the clinical tolerance to elevated doses in patients with heart failure presenting complex, hyperkinetic ventricular arrhythmias; -the possibility to shorten hospitalization as a result of the oral loading; -whether this administration route would take less time to be efficacious. For this purpose, 30 patients with heart failure and complex, hyperkinetic ventricular arrhythmias were treated with 0.50 mg/kg body weight of amiodarone for three days and with 0.30 mg/kg on the 4th and 5th days, followed by a maintenance period of treatment with 200-400 mg daily. All patients underwent a 24-h Holter test before and after administration and an echocardiographic examination showing an average ejection fraction of approximately 30%. Amiodarone was clinically well tolerated; only 2 patients required discontinuation of therapy whereas, among the the remaining 28 patients, 2 cases of transient hypotension and 3 cases of gastroenteric disorders were observed. It was concluded that elevated doses of amiodarone were well tolerated, which allowed to reduce the loading period and, therefore, hospitalization.     

Narcosynthesis in the treatment of posttraumatic chronic pain: A case study.

Presents the case history of a 49-yr-old White male with chronic traumatically induced pain complaints who was treated with narcosynthesis. Narcosynthesis was indicated because of the lack of initial success with behavioral treatment strategies, such as psychodrama-assisted implosion techniques and hypnosis-assisted desensitization. The use of sodium-amytal-assisted psychotherapy in the treatment of the condition proved singularly efficacious in the short term. In this therapy, the S was administered iv sodium amytal to induce narcosis and then regressed back by the therapist to the day of the industrial accident that had injured him. Repetition of emotionally laden material allowed the anxiety to subside. Upon awakening, all symptoms were absent. However, the symptoms began to worsen 3 mo later when the S found out that he would be returning to the same work. The role of narcosynthesis in the treatment of traumatically induced chronic pain is discussed, with special reference to a behavioral interpretation of the results obtained. (9 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intraarticular hip treatment with triamcinolonehexacetonide in juvenile chronic arthritis

To evaluate the effect and tolerance of intraarticular Triamcinolonehexacetonide (TCH) in the course of chronic coxitis in juvenile chronic arthritis (JCA) in an open uncontrolled study. Since 1990 we treated patients < 16 years of age suffering from chronic coxitis with 1 mg/TCH/KG body weight. The patients were checked again 4-8 weeks after the treatment. Clinical and ultrasound courses were recorded with the help of ultrasound and joint scores. The evaluation took place 6, 12, 24 and 36 months after the treatment. At that time we give a report on the 12 months follow-up of 37 hip joints and the 24 months follow-up of 20 hip joints. The immediate effect of TCH influencing mobility, pain sensitivity and joint effusions of the patients is impressing. The long term effect of TCH has to be evaluated by regular check ups for at least 2 years. An individual comparison with the not treated contralateral joint would be desired if ethically justifiable. Most patients suffering from polyarticular diseases with a long course of coxitis needed more than one injection of TCH (mean reinjection time 5.8 months). Any avascular necrosis of the femoral heads or other complications were not observed.     

Does intrathecal morphine in the treatment of cancer pain induce the development of tolerance?

OBJECTIVE: This retrospective study was designed to investigate whether chronic lumbar intrathecal administration of morphine leads to the development of opioid tolerance in patients suffering from intractable cancer pain. METHODS: Between 1978 and 1995, 159 patients with refractory cancer pain were treated with intrathecal morphine in our Multidisciplinary Pain Center. The treatment consisted of preservative-free morphine administered through an access port as a single bolus. In this series of patients (n = 159), the daily doses of intrathecal morphine were determined as a function of duration of follow-up. RESULTS: The mean follow-up period was 95 days (range, 5-909 d), the mean starting daily dose of intrathecal morphine was 2.69 mg (range, 1-7.5 mg), and the mean terminal dose was 7.82 mg (range, 1-80 mg). The results demonstrated that only a moderate increase in daily dose of intrathecal morphine was required during the course of treatment (a two- to threefold increase for a 3-mo period). Furthermore, the dose increment was similar for patients followed up for more or less than 60 days. This increase did not result in any central opioid-related side effects, and the pain was managed satisfactorily. CONCLUSION: The requirement for a moderate increase in intrathecal opioid doses reflects the development of tolerance but did not limit the patients' ability to obtain adequate analgesia during the course of their painful disease.     

Paclitaxel plus high-dose cyclophosphamide with G-CSF support in patients with relapsed and refractory aggressive non-Hodgkin's lymphoma

Based on the single-agent activity of both paclitaxel and cyclophosphamide in the treatment of non-Hodgkin's lymphoma (NHL), we conducted a phase II study to evaluate the efficacy of the combination of the two drugs in patients with refractory and relapsed aggressive NHL. All patients received 900 mg/m2 bolus of cyclophosphamide intravenously daily for 3 consecutive days with a concurrent infusion of 150 mg/m2 of paclitaxel over 72 h (50 mg/m2/d). 24 h after the completion of chemotherapy, patients received subcutaneous injections of 5 microg/kg of granulocyte-colony stimulating factor (G-CSF) daily until white cell count recovery. Treatment was repeated every 3 weeks. Patients who had at least a partial response (PR) after two courses continued to receive a maximum of four courses. Patients with responding disease were allowed to undergo high-dose chemotherapy followed by stem-cell/bone marrow transplantation if they were eligible. Of the 77 patients who were eligible for the study, 74 (96%) were evaluable for toxicity and treatment response. The overall response rate was 45% (95% CI 33-57%). Patients who received treatment after their disease relapsed from a complete response (CR) had an 81% response rate (38% CRs), whereas those with primary refractory disease had a 22% response rate. Toxicities of > grade 2 included alopecia (100%) and stomatitis (25%). Neutropenic fever of grade > 2 occurred after 18% of the courses, and platelet count of < or = 20 x 10(9)/l developed after 20% of the courses. Thus, the combination of paclitaxel plus high-dose cyclophosphamide is an effective new regimen in the treatment of refractory and relapsed NHL.