Lithium dilution measurement of cardiac output and arterial pulse waveform analysis: an indicator dilution calibrated beat-by-beat system for continuous estimation of cardiac output

Lithium dilution cardiac output (LiDCO trade mark; LiDCO, London, UK) is a minimally invasive indicator dilution technique for the measurement of cardiac output. It was primarily developed as a simple calibration for the PulseCO trade mark (LiDCO, London, UK) continuous arterial waveform analysis monitor. The technique is quick and simple, requiring only an arterial line and central or peripheral venous access. These lines would probably already have been inserted in critical care patients. A small dose of lithium chloride is injected as an intravenous bolus, and cardiac output is derived from the dilution curve generated by a lithium-sensitive electrode attached to the arterial line. Studies in humans and animals have shown good agreement compared with results obtained with other techniques, and the efficacy of LiDCO trade mark in pediatric patients has also been proven. Compared with thermodilution, lithium dilution showed closer agreement in clinical studies with electromagnetic flow measurement.PulseCO trade mark is a beat-to-beat cardiac output monitor that calculates stroke volume from the arterial pressure waveform using an autocorrelation algorithm. The algorithm is not dependent on waveform morphology, but, rather, it calculates nominal stroke volume from a pressure-volume transform of the entire waveform. The nominal stroke volume is converted to actual stroke volume by calibration of the algorithm with LiDCO trade mark. Initial studies indicate good fidelity, and the results from centers in the United States and the United Kingdom are extremely encouraging. The PulseCO trade mark monitor incorporates software for interpretation of the hemodynamic data generated and provides a real-time analysis of arterial pressure variations (ie, stroke volume variation, pulse pressure variation, and systolic pressure variation) as theoretical guides to intravascular and cardiac filling.     

Outcomes of multiple myeloma patients receiving bortezomib,lenalidomide, and carfilzomib

New classes of drugs including the proteasome inhibitors (PI) bortezomib and, more recently, carfilzomib and the immunomodulatory agent lenalidomide have shown improved outcomes for multiple myeloma (MM) patients during the past decade. However, most of the studies reporting outcomes for patients receiving these drugs have relied on older data sets derived from large institutions that included patients not receiving their treatment at those facilities and represented only those eligible for clinical trials or were from sites where treatment options were limited. We have analyzed data from 258 MM patients who have received treatment with at least one of three agents: bortezomib, carfilzomib, and lenalidomide in a single clinic specializing in MM with respect to their responses and other outcomes to treatment regimens including these agents. Response rates were similar between these three drugs when used for the first time and again during subsequent treatment regimens. As expected, the clinical benefit rates (CBRs) were better for patients receiving their first treatment when compared to their use in subsequent treatment regimens. The CBRs were similar during their 2nd, 3rd, and 4th treatments containing these agents. Many patients refractory to these agents showed responses to regimens containing these same drugs when used in different combinations. In addition, patients refractory to one PI often responded to the other PI. The results of this study demonstrate that novel agents can be used repeatedly in novel combinations with significant clinical benefit for patients with MM.     

Randomized clinical trial of supervised tapering and cognitive behavior therapy to facilitate benzodiazepine discontinuation in older adults with chronic insomnia

OBJECTIVE: This study evaluated the effectiveness of a supervised benzodiazepine taper, singly and combined with cognitive behavior therapy, for benzodiazepine discontinuation in older adults with chronic insomnia. METHOD: Seventy-six older adult outpatients (38 women, 38 men; mean age of 62.5 years) with chronic insomnia and prolonged use (mean duration of 19.3 years) of benzodiazepine medication for sleep were randomly assigned for a 10-week intervention consisting of a supervised benzodiazepine withdrawal program (N=25), cognitive behavior therapy for insomnia (N=24), or supervised withdrawal plus cognitive behavior therapy (N=27). Follow-up assessments were conducted at 3 and 12 months. The main outcome measures were benzodiazepine use, sleep parameters, and anxiety and depressive symptoms. RESULTS: All three interventions produced significant reductions in both the quantity (90% reduction) and frequency (80% reduction) of benzodiazepine use, and 63% of the patients were drug-free within an average of 7 weeks. More patients who received medication taper plus cognitive behavior therapy (85%) were benzodiazepine-free after the initial intervention, compared to those who received medication taper alone (48%) and cognitive behavior therapy alone (54%). The patients in the two groups that received cognitive behavior therapy perceived greater subjective sleep improvements than those who received medication taper alone. Polysomnographic data showed an increase in the amount of time spent in stages 3 and 4 sleep and REM sleep and a decrease in total sleep time across all three conditions from baseline to posttreatment. Initial benzodiazepine reductions were well maintained up to the 12-month follow-up, and sleep improvements became more noticeable over this period. No significant withdrawal symptoms or adverse events were associated with benzodiazepine tapering. CONCLUSIONS: A structured, time-limited intervention is effective in assisting chronic users of benzodiazepine medication to discontinue or reduce their use of medication. The addition of cognitive behavior therapy alleviates insomnia, but sleep improvements may become noticeable only after several months of benzodiazepine abstinence.