At least two factors relating to pain management using oral analgesics suggest that combination strategies merit consideration: many pains arise from more than one physiological cause and current analgesics have adverse effect profiles that might be reduced by combination with another agent in smaller doses or with less frequent dosing. In addition to increased convenience, combinations sometimes also result in the unexpected benefit of synergy. But not all pains, clinical settings or combinations merit the extra expense or other potential negative features of fixed-ratio products. This review examines the multiple basic science, clinical and pharmacoeconomic issues relating to analgesic combinations and the methodologies available for assessing these issues.

Rationale A number of cancer chemotherapeutic agents have been associated with a loss of memory in breast cancer patients although little is known of the causality of this effect. Objectives To assess the potential cognitive effects of repeated exposure to chemotherapeutic agents, we administered the selective estrogen receptor modulator tamoxifen or the antimetabolite chemotherapy, methotrexate, and 5-fluorouracil, alone and in combination to mice and tested them in a learning and memory assay. Methods Swiss-Webster male mice were injected with saline, 32 mg/kg tamoxifen, 3.2 or 32 mg/kg methotrexate, 75 mg/kg 5-fluorouracil, 3.2 or 32 mg/kg methotrexate in combination with 75 mg/kg 5-fluorouracil once per week for 3 weeks. On days 23 and 24, mice were tested for acquisition and retention of a nose-poke response in a learning procedure called autoshaping. In addition, the acute effects of tamoxifen were assessed in additional mice in a similar procedure. Results The chemotherapeutic agents alone and in combination reduced body weight relative to saline treatment over the course of 4 weeks. Repeated treatment with tamoxifen produced both acquisition and retention effects relative to the saline-treated group although acute tamoxifen was without effect except at a behaviorally toxic dose. Repeated treatment with methotrexate in combination with 5-fluorouracil produced effects on retention, but the magnitude of these changes depended on the methotrexate dose. Conclusions These data demonstrate that repeated administration of tamoxifen or certain combination of methotrexate and 5-fluorouracil may produce deficits in the acquisition or retention of learned responses which suggest potential strategies for prevention or remediation might be considered in vulnerable patient populations.

Previous studies examining EEG and LORETA in patients with chronic pain discovered an overactivation of high theta (6–9 Hz) and low beta (12–16 Hz) power in central regions. MEG studies with healthy subjects correlating evoked nociception ratings and source localization described delta and gamma changes according to two music interventions. Using similar music conditions with chronic pain patients, we examined EEG in response to two different music interventions for pain. To study this process in-depth we conducted a mixed-methods case study approach, based on three clinical cases. Effectiveness of personalized music therapy improvisations (entrainment music – EM) versus preferred music on chronic pain was examined with 16 participants. Three patients were randomly selected for follow-up EEG sessions three months post-intervention, where they listened to recordings of the music from the interventions provided during the research. To test the difference of EM versus preferred music, recordings were presented in a block design: silence, their own composed EM (depicting both “pain” and “healing”), preferred (commercially available) music, and a non-participant’s EM as a control. Participants rated their pain before and after the EEG on a 1–10 scale. We conducted a detailed single case analysis to compare all conditions, as well as a group comparison of entrainment-healing condition versus preferred music condition. Power spectrum and according LORETA distributions focused on expected changes in delta, theta, beta, and gamma frequencies, particularly in sensory-motor and central regions. Intentional moment-by-moment attention on the sounds/music rather than on pain and decreased awareness of pain was experienced from one participant. Corresponding EEG analysis showed accompanying power changes in sensory-motor regions and LORETA projection pointed to insula-related changes during entrainment-pain music. LORETA also indicated involvement of visual-spatial, motor, and language/music improvisation processing in response to his personalized EM which may reflect active recollection of creating the EM. Group-wide analysis showed common brain responses to personalized entrainment-healing music in theta and low beta range in right pre- and post-central gyrus. We observed somatosensory changes consistent with processing pain during entrainment-healing music that were not seen during preferred music. These results may depict top–down neural processes associated with active coping for pain.

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Although highly active antiretroviral therapy (HAART) has revolutionized the treatment of human immunodeficiency virus (HIV)-positive patients, malignancies in the setting of HIV infection remain an appreciable problem. We evaluated the changing epidemiology of HIV-related malignancies, optimal neoplastics and their effect on viral dynamics, and evidence regarding drug interactions between chemotherapy and antiretrovirals. A MEDLINE search (January 1966-June 2006) was performed to identify clinical trials, review articles, and meta-analyses; abstracts from HIV conferences were also searched. Survival of patients with HIV-related malignancies has substantially improved since the advent of HAART. Chemotherapy for malignancies in the HIV-positive population generally resembles that for the HIV-negative population, with trials revealing an elevated frequency of toxicities in HIV-positive patients. Studies of antineoplastics have shown no long-term adverse effects on viral dynamics in terms of immunologic or virologic HIV markers. Limited pharmacokinetic data with antineoplastics and antiretrovirals suggest possible changes in some pharmacokinetic parameters, but these results should be interpreted cautiously because of the small numbers of patients enrolled in the trials. Researchers also report an increased frequency of chemotherapy-related toxicities when HAART was coadministered with antineoplastics. This increase was likely due to impairment of cytochrome P450 metabolism of antineoplastics by protease inhibitors. Because of the survival benefits of HAART, the integration of antiretrovirals with chemotherapy is now preferred for patients with HIV-related malignancies. However, because the metabolic pathways of many of these agents are similar, the effectiveness of antineoplastic therapy and its related toxicities should be vigilantly monitored in this patient population.