Topiramate vs placebo in painful diabetic neuropathy: analgesic and metabolic effects.

BACKGROUND: Using identical methods, three simultaneous placebo-controlled trials of topiramate for painful diabetic neuropathy (PDN) did not reach significance. This independent yet concurrent placebo-controlled trial used different methods to assess topiramate efficacy and tolerability in PDN. METHODS: This 12-week, multicenter, randomized, double-blind trial included 323 subjects with PDN and pain visual analog (PVA) score of at least 40 on a scale from 0 (no pain) to 100 (worst possible pain). Topiramate (n = 214) or placebo (n = 109) was titrated to 400 mg daily or maximum tolerated dose. Short-acting rescue analgesics were permitted only during the first 6 weeks. RESULTS: Baseline characteristics were comparable between groups except for mean body weight (topiramate, 101.4 kg; placebo, 95.7 kg; p = 0.028). Twelve weeks of topiramate treatment reduced PVA scale score (from 68.0 to 46.2 mm) more effectively than placebo (from 69.1 to 54.0 mm; p = 0.038). Fifty percent of topiramate-treated subjects and 34% of placebo-treated subjects responded to treatment, defined as >30% reduction in PVA scale score (p = 0.004). Topiramate monotherapy also reduced worst pain intensity (p = 0.003 vs placebo) and sleep disruption (p = 0.020 vs placebo). Diarrhea, loss of appetite, and somnolence were the most commonly reported adverse events in the topiramate group. Topiramate reduced body weight (-2.6 vs +0.2 kg for placebo; p < 0.001) without disrupting glycemic control. CONCLUSIONS: Topiramate monotherapy reduced pain and body weight more effectively than placebo in patients with painful diabetic neuropathy.

The management of pain in the oncology patient.

The treatment of cancer pain is improving, but pain remains a significant problem. Although better analgesics with greater efficacy and fewer side effects are needed, the most significant problem regarding the appropriate management of cancer pain remains a lack of knowledge among physicians treating cancer patients. Cancer management should be undertaken within a palliative care model, in which autonomy and respect for individuals and their families guides all aspects of care.

The use of NMDA-receptor antagonists in the treatment of chronic pain.

Chronic pain can be maintained by a state of sensitization within the central nervous system that is mediated in part by the excitatory amino acids glutamate and aspartate binding to the N-methyl-D-aspartate (NMDA) receptor. A number of antagonists to the NMDA receptor are antinociceptive in animal models but are associated with significant dose-limiting side effects. Commercially available NMDA-receptor antagonists include ketamine, dextromethorphan, memantine, and amantadine. The opioids methadone, dextropropoxyphene, and ketobemidone are also antagonists at the NMDA receptor. The NMDA-receptor antagonists have a significant impact on the development of tolerance to opioid analgesics. Consequently, NMDA-receptor antagonists may represent a new class of analgesics and may have potential as coanalgesics when used in combination with opioids.

Disseminated intravascular coagulation in a patient treated with strontium-89 for metastatic carcinoma of the prostate.

Strontium-89 is effective in the palliation of bone pain caused by skeletal metastases. Its primary side effect is mild thrombocytopenia that typically recovers in 3 or 4 months. Subclinical disseminated intravascular coagulation is reported to be present in approximately 10% to 20% of patients with advanced prostate cancer. These patients may be at increased risk for severe marrow depression after radionuclide therapy for bone pain palliation. This report describes a patient with painful bony metastases resulting from prostate carcinoma. He had a normal platelet count and no clinical evidence of a coagulation disorder at the time of strontium-89 therapy, and a severe disseminated intravascular coagulation developed and lead to death after treatment. A normal platelet count before strontium-89 therapy does not preclude subsequent disseminated intravascular coagulation, and we support the Society of Nuclear Medicine's bone pain treatment procedure guideline that patients referred for bone palliation should be screened for disseminated intravascular coagulation before therapy.

Pain syndromes and etiologies in ambulatory AIDS patients.

Ambulatory AIDS patients participating in a quality of life study were recruited for an assessment of pain syndromes. Of 274 patients with pain, 151 (55%) consented to the assessment which included a clinical interview, neurologic examination, and review of medical records. The number, type, and etiology of pains were evaluated in terms of risk factors, age, sex, CD4+ lymphocyte count, and performance status. The average number of pains per patient was 2.7 (range, 1-7), yielding a total of 405 pains. The most common pain diagnoses were headache (46% of patients; 17% of all pains), joint pain (31% of patients; 12% of pains), pain due to polyneuropathy (28% of patients; 10% of pains), and muscle pain (27% of patients; 12% of pains). Pathophysiology was inferred for all pain syndromes (except for headache), 45% of pain syndromes were somatic in nature, 15% were visceral, 19% were neuropathic, and 4% were unknown, psychogenic, or idiopathic; 17% of pains were classified as headache, hence pathophysiology could not be determined. Pain resulted from diverse etiologies, including the direct effects of HIV/AIDS-related conditions (30%) pre-existing unrelated conditions (24%), and therapies for HIV/AIDS and related conditions (4%). The latter category, pain related to HIV therapies, occurred in 11% of patients. In 37% of the pains, the etiology could not be determined from the information available. In univariate analyses, lower CD4+ cell counts were significantly associated with polyneuropathy (P < 0.05) and headache (P < 0.05), and female gender was significantly associated with the presence of headache (P < 0.05) and radiculopathy (P < 0.001). These data confirm the diversity of pain syndromes in AIDS patients, clarify the prevalence of common pain types, and suggest associations between specific patient characteristics and pain syndromes. The large proportion of patients who could not be given a diagnosis underscores the need for a careful diagnostic evaluation of pain in this population.

Investigation of arsenic exposure from soil at a superfund site.

The purpose of this study was to determine if significant arsenic exposure was occurring at a Superfund site with elevated surface soil arsenic concentrations. A second objective was to determine the statistical relationship between the various methods of measuring arsenic exposure in humans. Random urine, 24-hr urine, hair, and fingernail samples were collected at the end of the workweek from 40 employees at an active pesticide manufacturing facility which had formerly produced arsenical pesticides. There was no indication of adverse health effects among the employees attributable to arsenic exposure. Mean urinary, hair, and fingernail concentrations of arsenic were well within normal values and indicated that significant arsenic exposure was not occurring among the employees. Random and 24-hr urine measurements were significantly correlated. Hair and fingernail results also were significantly correlated. Urine results did not correlate well with hair or fingernail results. Results of this study suggest that although there may be some individual variation, random and 24-hr urine arsenic results are not substantially different. For the purpose of screening for arsenic exposure, random urine samples may be an adequate and preferable test for those populations in equilibrium with their environment.

Content and design of laboratory report forms for human immunodeficiency virus type 1 antibody testing.

In a pilot study involving proficiency testing for human immunodeficiency virus, markedly diverse and potentially confusing test report forms were encountered among participating laboratories. Therefore, a comprehensive study of human immunodeficiency virus type 1 report forms was conducted from state-licensed testing laboratories in California. Participants analyzed three serum samples of known human immunodeficiency virus type 1 antibody reactivity and reported their results on forms that they would normally submit to clinicians. Report forms from 84 laboratories were evaluated for content, design, and clarity. Differences were found among commercial, hospital, and public health laboratories. The significance of these findings is discussed. This technique also may be applied to evaluate laboratory report form design and content for other diagnostic test results.

Identification of nonanalytic issues in HIV-1 antibody testing using blind proficiency testing.

Blind proficiency testing was used to examine nonanalytic performance indicators for human immunodeficiency virus type 1 (HIV-1) antibody testing. Physician offices, clinics, and hospitals located throughout Southern California submitted simulated patient specimens to laboratories as routine test requests. A total of 32 laboratories were involved during five blind proficiency testing surveys. Turnaround time for a reactive specimen ranged from three to 17 days. Laboratory charges for evaluating a reactive specimen varied depending on the volume of testing, prevalence of reactive specimens, and whether screening and confirmatory tests were billed separately or as a package price. Charges for an enzyme immunoassay screening test plus supplemental tests ranged from $11.75 to $114.50, with a median of $31.00 for 24 laboratories that participated in one of the five surveys. Evaluation of laboratory report content revealed that 37% of the 16 screening reports and 71% of the 14 supplemental reports contained information that was unrelated to the patient results. Evaluation of the testing system documents the need to monitor multiple outcomes of the total laboratory testing process, not just the analytic testing phase.