Cycle-to-cycle control of swing phase of paraplegic gait induced by surface electrical stimulation

Parameterised swing phase of gait in paraplegics was obtained using surface electrical stimulation of the hip flexors, hamstrings and quadriceps; the hip flexors were stimulated to obtain a desired hip angle range, the hamstrings to provide foot clearance in the forward swing, and the quadriceps to acquire knee extension at the end of the swing phase. We report on two main aspects; optimisation of the initial stimulation parameters, and parameter adaption (control). The initial stimulation patterns were experimentally optimised in two paraplegic subjects using a controlled stand device, resulting in an initial satisfactory swinging motion in both subjects. Intersubject differences appeared in the mechanical output (torque joint) per muscle group. During a prolonged open-loop controlled trial with the optimised but unregulated stimulation onsets and burst duration for the three muscle groups, the hip angle range per cycle initially increased above the desired value and subsequently decreased below it. The mechanical performance of the hamstrings and quadriceps remained relatively unaffected. A cycle-to-cycle controller was then designed, operating on the basis of the hip angle ranges obtained in previous swings. This controller successfully adapted the burst duration of the hip flexors to maintain the desired hip angle range.     

Left ventricular ejection fraction and volumes from gated single photon emission tomographic myocardial perfusion images: Comparison between two algorithms working in three-dimensional space

Objective. Two different algorithms operating in three-dimensional space, one dependent on surface detection developed at Cedars-Sinai Medical Center (CS) and another dependent on statistical parameters and developed at Stanford University Medical School (SU), were compared in the same patients to assess the left ventricular volumes and the left ventricular ejection fractions (LVEFs) from gated single-photon emission tomography (SPECT) myocardial perfusion images.Methods. Perfusion SPECT images gated in eight time bins were recorded in 40 patients with coronary artery disease 60 minutes after the injection of 925 MBq^99mTc-labeled tetrofosmin at rest. The LVEF values were validated against planar gated ^99mTc-labeled blood pool studies (ERNA).Results. The software success rates were 95% (38/40 patients) for CS and 100% for SU. Agreement between LVEFs measured with CS and SU and agreement between both methods and ERNA were excellent (LVEF_CS = 0.89LVEF_SU + 6.21, r = 0.93; LVEF_SU = 0.92LVEF_ERNA + 0.99, r = 0.94; and LVEF_CS = 0.88LVEF_ERNA + 4.58, r = 0.93). Bland-Altman plots showed that differences between LVEFs from SU and CS and from ERNA were similar across a wide range (20% to 80%) of LVEF values. No relationship between these differences and the severity of perfusion defects was observed. For left ventricular volumes, linear regression analysis showed an excellent correlation between both methods (end-diastolic volume R = 0.97 end-systolic volume R = 0.98), but systematically higher values were obtained with SU (p = 0.013).Conclusion. Measurements of LVEF obtained with CS and SU correspond well with those from the standard, ERNA, even in patients with severe perfusion defects. A close relationship is observed between SU and CS when left ventricular volumes are considered. Measurements of LVEF (and left ventricular volumes) should be considered as an integral part of myocardial perfusion studies whenever possible.     

Real‐world health care costs of relapsed/refractory multiple myeloma during the era of novel cancer agents

What is known and objective: High costs of novel agents increasingly put pressure on limited healthcare budgets. Demonstration of their real‐world costs and cost‐effectiveness is often required for reimbursement. However, few published economic evaluations of novel agents for multiple myeloma exist. Moreover, existing cost analyses were heavily based on conventionally treated patients. We investigated real‐world health care costs of relapsed/refractory multiple myeloma in Dutch daily practice. Methods: A retrospective medical chart review was conducted for 139 patients treated between January 2001 and May 2009. Total monthly costs attributable to each cost component were described across all regimens and for bortezomib‐, thalidomide‐ and lenalidomide‐based treatment regimens. Results: Mean monthly total costs (€3,981) varied depending on the sequence of therapy (range: €442–€31,318). Significant cost drivers across all regimens included costs of therapy and hospital admissions. The acquisition costs for novel agents in particular accounted for 32% of mean total monthly costs. Prognostic factors associated with increased mean total monthly costs in multivariate regression analysis included low platelet counts (P = 0·01) and worsening performance status (P < 0·001). Mean total monthly costs of bortezomib‐ and lenalidomide‐based regimens were significantly higher than those for thalidomide‐based regimens in second, third and fourth treatment line. What is new and conclusions: Real‐world costs during treatment of relapsed/refractory multiple myeloma vary greatly. Cost drivers include hospital admissions and acquisition costs of novel agents. Costs also vary by prognostic factors and treatment‐related resource use. Future studies assessing the costs of combination therapy consisting of two or more novel agents are encouraged.     

Defining the valid hemizona assay: accounting for binding variability within zonae pellucidae and within semen samples from fertile males.

OBJECTIVE: To achieve a better understanding of the variability in sperm and oocyte binding capacities will optimize use of the hemizona assay (HZA) as a predictor of sperm function. DESIGN: Limitations of the HZA were more clearly delineated by current studies: (1) variability of sperm binding capacity of men over a 90-day interval; (2) variability of sperm binding using different oocytes; and (3) lower limits of the number of sperm bound from the fertile control in two laboratories. PATIENTS: Semen was obtained from proven fertile men and one subfertile individual. MAIN OUTCOME MEASURE: The number of sperm tightly bound to the hemizona were measured and compared. RESULTS: In the initial study, 6 fertile control men exhibited a similar degree of variability in zona binding when studied over a 90-day interval. Average sperm binding for individuals ranged from 68 to 127. Second, 3 of the 15 simultaneous assays showed very low numbers of sperm bound, indicating that 20% of the zonae had poor binding. Third, from 18 men who had 0% fertilization in an in vitro fertilization system using mature oocytes, evaluation of their sperm by HZA was performed. The sperm bound poorly and the 95% confidence interval was 20 sperm bound. Thus, the fertile controls should bind greater than 20 sperm to distinguish them from the infertile group in the HZA system resulting in a valid assay. CONCLUSIONS: With these guidelines, applications of the HZA may be made with greater reassurance of a valid bioassay of sperm fertilizing potential.     

Hemizona assay: assessment of sperm dysfunction and prediction of in vitro fertilization outcome

The hemizona assay (HZA) was used in a prospective, blinded study to assess the relationship between tight sperm binding in the HZA and sperm fertilizing ability in in vitro fertilization (IVF). In each controlled assay, the authors compared sperm binding of proven fertile men with that of patients undergoing IVF. Human oocytes stored in a salt solution were used in the study, and binding results were correlated with the fertilization rate of preovulatory oocytes during IVF. Patients with poor fertilization rates in IVF had significantly lower binding than those cases with successful fertilization (7.3 +/- 1.4 versus 62.1 +/- 10.9, respectively; mean +/- standard error, P less than 0.02). Based on current standards, the HZA was able to predict fertilization accurately in 26 of 28 cases (sensitivity of 83%, specificity of 95%, positive predictive value of 83%). The authors conclude that the HZA is a valuable tool for evaluating dysfunctional sperm-zona pellucida binding, with good predictive value for fertilization in vitro.     

Magnetic resonance imaging of children with Duchenne muscular dystrophy

Eight children representing a spectrum of clinical states of biopsy-proven Duchenne muscular dystrophy (DMD) underwent magnetic resonance (MR) scans to assess the degree of muscular involvement and disease progression. Five muscle groups (neck, shoulder girdle, pelvic girdle, thigh and calf) were evaluated. In each case, involved muscles were clearly demarcated. Image estimates of disease severity by degree of muscle involvement correlated well with clinical staging. In our experience MR is useful for assessment of disease stage, selection of appropriate muscles for biopsy and planning for courses of physical and rehabilitation therapy.     

Gated myocardial perfusion tomography versus gated blood pool tomography for the calculation of left ventricular volumes and ejection fraction

Left ventricular (LV) volume, and not only ejection fraction (EF), is a crucial parameter for assessing the severity of cardiac disease and determining the patient's prognosis. The purpose of this study was to compare LV volumes and EF computed automatically from gated blood pool tomography (gBPT), using QUBE, and from gated myocardial perfusion tomography (gMPT), using QGS, in the same patients with a known history of myocardial infarction. The effects of the extent and severity of the myocardial perfusion defects were investigated. Thirty-seven patients were injected in a random sequence with 740 MBq of technetium-99m human serum albumin and 925 MBq of (99m)Tc-tetrofosmin, within an interval of 2 days. gBPT and gMPT were acquired on the same triple-head gamma camera using the following acquisition parameters: 360 degrees step-and shoot rotation, 32 stops (96 projections), 30 s per stop, 64x64 matrix (pixel size 5.8 mm), 8 time bins (75% forward/backward framing). Projection data were reconstructed by filtered back-projection using a Butterworth filter. LV volumes calculated from gBPT correlated well with LV volumes measured on gMPT ( r=0.93 for end-diastolic volume and 0.95 for end-systolic volume). Volumes above 200 ml, however, were substantially higher with gMPT than with gBPT. These discrepancies were related to the severity, but not the extent, of the perfusion defects. There was also good agreement between gBPT and gMPT for the LVEF ( r=0.91). On the Bland-Altman plot, no trend but a systematic error of 5.57% and a random error of 6.85% could be found. For the LVEF, the differences between the gated tomographic techniques were related neither to the extent nor to the severity of the perfusion defects. In conclusion, LV volumes and EF computed on gMPT correlated well with those measured on gBPT. Discrepancies were observed for large volumes presumably because of inaccuracies of gMPT in patients with severe perfusion defects.