Within-Response Force Variations Accompanying Differentiation of Duration in Rats

By using a force-sensing isometric manipulandum, response force waveforms were recorded from rats performing a duration differentiation. For 2 rats exteroceptive cues were correlated with response force exceeding the force criterion and with attainment of the 1.60-sec. duration required for reinforcement. The other 3 rats received no exteroceptive support, the water reinforcer being delivered upon response termination. In the last phase of the experiment, reinforcement was contingent upon holding response force within a force “band” for a specified time. Relative frequency distributions of response duration indicated that differentiation of duration was more accurate in the presence of exteroceptive cues than in the absence of such stimuli. Spectral analysis of individual response waveforms indicated that rhythmic force oscillations (2 to 6 hz) predominated, despite the subjects' reliance on exteroceptive stimuli. Introduction of the joint force-band-duration contingency reduced but did not completely abolish the oscillations for both cued and uncued subjects. Over-all the results suggest that the rhythmic force variations observed here may be unselected or elicited components of the response rather than manifestations of a proprioceptive self-cueing process. </jats:p

Safety of rapid rituximab infusion in adult cancer patients: A systematic review

The purpose of this study is to critically appraise, synthesize and present the best available evidence related to the safety of rapid rituximab infusion in adult non-Hodgkin lymphoma and chronic lymphocytic leukaemia patients. Data are from published and unpublished studies from electronic databases, grey literature and reference lists. The studies that met the inclusion criteria were critically appraised by two independent reviewers for methodological validity using standardized critical appraisal instruments. Proportional meta-analysis based on DerSimonian–Laird weights using a random effects model was used for statistical pooling through Stats Direct. Heterogeneity is assessed using Cochran Q. When statistical pooling is not possible, the findings were presented in narrative summary. Rapid rituximab infusion is safe for non-Hodgkin lymphoma patients at a 90 min regimen. However, there is insufficient evidence to support rapid rituximab infusions for chronic lymphocytic leukaemia patients.Dora SP Lang, Christina Hagger, Alan Pearso

Rapid Infusion Rituximab in Combination with Steroid Containing Chemotherapy Can Be Given Safely and Substantially Reduces Resource Utilization.

Abstract Background Administration of rituximab, a chimeric anti-CD20 monoclonal antibody, can be associated with substantial infusion-related toxicity, including hypersensitivity reactions causing fever, rash, cardiovascular and respiratory compromise and rarely a fatal cytokine release syndrome. The risk of grade 3/4 infusion reactions is greatest with the first infusion (7%), and lower for all subsequent infusions (2% for fourth infusion). To minimize the risk of reaction, strict guidelines for administration have been developed, requiring lengthy infusion times (average 5–6 h for first infusion and 3–4 h for remaining infusions). As more patients are now receiving rituximab in combination with steroid containing chemotherapy regimens, the risk of reaction may be lower and the need for lengthy infusion unnecessary. Methods In March 2004, we began a pilot study investigating the safety of a rapid infusion rituximab schedule for all patients with non-Hodgkin’s lymphoma receiving rituximab in combination with CHOP or CVP chemotherapy. The schedule of administration for cycle 1 of therapy was unaltered and delivered according to the product monograph. All further cycles were administered the same day of chemotherapy, over a total infusion time of 90 minutes (20% of the dose in the first 30 min then the remaining 80% over 60 min; total dose delivered in 250 mL). Patients took their daily prednisone dose prior to receiving rituximab. Safety information was monitored prospectively using an infusion monitoring record. Results 67 patients have been treated for a total of 163 infusions (median infusions per patient: 2). Patient characteristics are as follows: median age, 64 y (range 21–90); 67% male; 66% stage III/IV; PS &amp;gt; 1, 19%; IPI score high/high-intermediate, 36%. Histology: 42 DLBCL, 6 follicular, 8 transformed, 4 mantle cell, 7 other. No patients had increased numbers of circulating lymphocytes. Chemotherapy regimen: 57 CHOP, 9 CVP, 1 other. The 90-minute rituximab infusion schedule was extremely well tolerated with no grade 3/4 adverse infusion related events observed. One patient developed mild transient asymptomatic hypotension, BP 97/71, grade 1 toxicity, which was managed with a 30-minute infusion delay. Four patients (6%) had an adverse event with their first cycle (administered at the standard rate) and subsequently tolerated the rapid infusion schedule without event. Five patients did not receive steroids with their treatment due to a prior history of hepatitis exposure and none of these patients developed an adverse event with the rapid infusion. The overall rate of grade 3/4 infusion related reactions observed with the rapid infusion protocol was 0% (95% CI 0–0.044), which is at least as low as the expected rate following the standard infusion schedule. No increased incidence in minor reactions was noted. Introduction of this shortened infusion schedule has enabled us to cut rituximab infusion times in half, allowing more patients to be conveniently treated and ensuring that both chemotherapy and rituximab can be given in one rather than two days. Conclusion A rapid (90-minute) rituximab infusion schedule in combination with a steroid containing chemotherapy regimen is well tolerated and safe when administered from the second infusion onward. This shortened infusion schedule has resulted in a substantial reduction in resource utilization.</jats:p