Psychological factors associated with idiopathic arm pain

BACKGROUND: Psychological and personality factors may be as important as, or more important than, pathological processes in the experience of pain, particularly in patients whose pain has a vague or uncertain source. METHODS: Validated measures of psychological factors were used to prospectively evaluate fifty-six patients with a single, discrete pain complaint and fifty-one patients with vague, diffuse idiopathic arm pain. Pain was assessed with use of 10-point Likert scales, the Pain Anxiety Symptoms Scale, the Pain Catastrophizing Scale, the Wahler Physical Symptom Inventory, the Body Consciousness Questionnaire, and the Multidimensional Health Locus of Control Scale. RESULTS: Patients with idiopathic arm pain reported more severe pain at rest (p = 0.02) and with repeated movements (p = 0.01); exhibited higher levels of cognitive anxiety (p = 0.008); demonstrated greater helplessness (p = 0.002), pain magnification (p = 0.007), and overall catastrophic coping mechanisms for dealing with pain (p = 0.005); and showed a tendency for increased somatic complaining (p = 0.07). A multiple logistic regression model identified the total score on the Pain Catastrophizing Scale as the sole predictor of idiopathic pain complaints. CONCLUSIONS: Pain complaints without a clear physical cause are common and are frustrating for both patients and physicians. Awareness of the psychological factors associated with idiopathic arm pain may lead to more effective interventions designed to improve coping mechanisms while at the same time limiting the use of meddlesome and potentially harmful diagnoses and treatments.     

Evidence for strong synaptic coupling between single tactile afferents from the sole of the foot and motoneurons supplying leg muscles

It has been known for some time that populations of cutaneous and muscle afferents can provide short-latency facilitation of motoneuron pools. Recently, it has been shown that the input from individual low-threshold mechanoreceptors in the glabrous skin of the hand can modulate ongoing activity in muscles acting on the fingers via spinally mediated pathways. We have extended this work to examine whether such strong synaptic coupling exists between tactile afferents in the sole of the foot and motoneurons supplying muscles that act about the ankle. We recorded from 53 low-threshold mechanoreceptors in the glabrous skin of the foot via microelectrodes inserted percutaneously into the tibial nerve of awake human subjects. Reflex modulation of ongoing whole muscle electromyography (EMG) was observed for each of the four classes of low-threshold cutaneous mechanoreceptors (17 of 21 rapidly adapting type I; 2 of 4 rapidly adapting type II; 7 of 18 slowly adapting type I; and 4 of 10 slowly adapting type II). Reflex modulation of the firing probability in single motor units (5 of 11) was also observed. These results indicate that strong synaptic coupling between tactile afferents and spinal motoneurons is not a specialization of the hand and emphasizes the potential importance of cutaneous inputs from the sole of the foot in the control of gait and posture.     

Prediction of nephrotoxicant action and identification of candidate toxicity-related biomarkers

A vast majority of pharmacological compounds and their metabolites are excreted via the urine, and within the complex structure of the kidney,the proximal tubules are a main target site of nephrotoxic compounds. We used the model nephrotoxicants mercuric chloride, 2-bromoethylamine hydrobromide, hexachlorobutadiene, mitomycin, amphotericin, and puromycin to elucidate time- and dose-dependent global gene expression changes associated with proximal tubular toxicity. Male Sprague-Dawley rats were dosed via intraperitoneal injection once daily for mercuric chloride and amphotericin (up to 7 doses), while a single dose was given for all other compounds. Animals were exposed to 2 different doses of these compounds and kidney tissues were collected on day 1, 3, and 7 postdosing. Gene expression profiles were generated from kidney RNA using 17K rat cDNA dual dye microarray and analyzed in conjunction with histopathology. Analysis of gene expression profiles showed that the profiles clustered based on similarities in the severity and type of pathology of individual animals. Further, the expression changes were indicative of tubular toxicity showing hallmarks of tubular degeneration/regeneration and necrosis. Use of gene expression data in predicting the type of nephrotoxicity was then tested with a support vector machine (SVM)-based approach. A SVM prediction module was trained using 120 profiles of total profiles divided into four classes based on the severity of pathology and clustering. Although mitomycin C and amphotericin B treatments did not cause toxicity, their expression profiles were included in the SVM prediction module to increase the sample size. Using this classifier, the SVM predicted the type of pathology of 28 test profiles with 100% selectivity and 82% sensitivity. These data indicate that valid predictions could be made based on gene expression changes from a small set of expression profiles. A set of potential biomarkers showing a time- and dose-response with respect to the progression of proximal tubular toxicity were identified. These include several transporters (Slc21a2, Slc15, Slc34a2), Kim 1, IGFbp-1, osteopontin, alpha-fibrinogen, and Gstalpha.     

A survey of characteristics of smokeless tobacco users in a treatment program

OBJECTIVE: To determine the characteristics and outcomes of smokeless tobacco (ST) users receiving interventions in an outpatient tobacco-dependence treatment program. METHODS: Survey was mailed with telephone follow-up to ST users treated during a 2-year period. RESULTS: Nicotine replacement therapy and family and social support were the most helpful intervention components in maintaining tobacco abstinence. Continuing ST users face significant barriers to abstinence such as high levels of nicotine dependence, lack of motivation, nicotine withdrawal symptoms, and stress. CONCLUSIONS: Enhancing confidence in their ability to quit, managing stress, prescribing bupropion SR, offering nicotine replacement therapy to relieve withdrawal symptoms, and providing ongoing support may be important for ST users in tobacco- dependence treatment programs.     

Outcomes of COPD lung transplant recipients after lung volume reduction surgery

STUDY OBJECTIVES: We sought to assess the outcomes of COPD lung transplant recipients who had previously undergone lung volume reduction surgery (LVRS), and to compare these patients to those COPD lung recipients who had not previously undergone LVRS. DESIGN: Retrospective analysis of the United Network for Organ Sharing transplant database over the period between October 25, 1999, and December 31, 2002. PATIENTS: All COPD patients who were listed and underwent transplantation during the time period were analyzed and categorized according to who did and did not have a history of LVRS. The two groups were compared for demographics, severity of illness, and various measures of outcomes after transplantation, including survival. RESULTS: There were 791 COPD patients who underwent transplantation, of whom 50 had a history of LVRS. The two groups had similar demographics and severity of disease. There was no difference in the need for reoperation, hospital length of stay, or survival between the groups. CONCLUSION: A history of LVRS does not impact on outcomes after lung transplantation and should not influence a patient's candidacy for transplantation. Similarly, a patient's potential need for lung transplantation should not impact on the decision-making process for undergoing LVRS.     

Are claims of equivalency in digestive diseases trials supported by the evidence?

BACKGROUND & AIMS: Traditionally, randomized controlled trials (RCTs) have attempted to show the superiority of one intervention over another. However, when effective treatment already exists, it is sometimes more useful to prove that an intervention is equivalent, or at least not inferior, to the standard of care. Our aim was to determine whether claims of equivalency in digestive diseases trials are supported by the evidence. METHODS: Medline was searched for RCTs published between 1989 and 2002 using the MeSH headings "exp therapeutic equivalency" and "exp digestive diseases" and the text words "equivalence," "equal," "equals," or "equivalent," yielding 902 articles. Of these, 73 articles met the inclusion criteria. These articles were evaluated using previously published criteria for equivalency. RESULTS: Of the included articles, 33% stated an a priori research aim of equivalency, 92% reported differences of <20% between "equal" interventions, 34% set an equivalency boundary and tested it appropriately, and 19% performed a sample size calculation for equivalency. Overall, 12% of the reviewed articles met all 5 criteria. Fifty-two percent of our sample inappropriately used a failed superiority test (i.e., a P value > 0.05) as statistical "proof" of equivalency. Nonsurgical trials and those published between 1996 and 2002 were more likely to meet criteria than were surgical trials (P = 0.07) or trials published before 1996 (P = 0.003). CONCLUSIONS: Claims of equivalency between interventions in digestive diseases trials tend to be poorly supported by the evidence. Erroneous claims of equivalency are potentially dangerous and may lead to substandard patient care.     

Costs of treatment and outcomes associated with second-line therapy and greater for relapsed ovarian cancer

OBJECTIVES: Most women with epithelial ovarian cancer (EOC) will develop disease progression or recurrence with resistance to platinum therapy. We report overall costs and treatment outcomes associated with topotecan or gemcitabine administration in platinum- and paclitaxel-resistant EOC patients. METHODS: Patients who received topotecan (n = 51) or gemcitabine (n = 56) as second-line therapy or greater for platinum- and paclitaxel-resistant EOC were retrospectively identified. Per patient costs for each regimen were determined and compared. RESULTS: The mean total direct cost per cycle per patient of gemcitabine was $2732.28, with a median total direct cost per cycle of $1382.73. The mean total direct cost per cycle per patient of topotecan was $7832.07, with a median total direct cost per cycle of $4219.02. By comparison of the means, total direct cost per cycle per patient was significantly more expensive for topotecan (P = 0.001). Fifty-six patients received a total of 415 cycles of gemcitabine, median 5 cycles per patient (range, 1-59). Thirteen (23.2%; 95% CI, 11.9-34.5%) of 56 patients displayed clinical benefit, with median PFS of 1.8 months and median overall survival (OS) of 8.2 months. Fifty-one patients received topotecan, for a total of 264 cycles, median 4 cycles per patient (range, 1-42). Twenty-eight (56%; 95% CI, 42.0-70.0%) of 50 patients achieved clinical benefit, with PFS and OS medians of 3.6 and 16.8 months, respectively. CONCLUSIONS: Gemcitabine and topotecan are active agents in heavily pretreated, platinum- and paclitaxel-resistant EOC patients. Topotecan was more costly to deliver. Although a larger percentage of patients received clinical benefit with topotecan use, this likely reflects physician selection for use of topotecan earlier in the course of disease.