Leg muscle volume during 30-day 6-degree head-down bed rest with isotonic and isokinetic exercise training

Magnetic resonance imaging (MRI) was used to compare the effect of two modes of lower-extremity exercise training on the mass (volume) of posterior leg group (PLG) muscles (soleus, flexor hallucis longus, tibialis posterior, lateral and medial gastrocnemius, and flexor digitorum longus) on 19 men (ages 32-42 years) subjected to intense dynamic-isotonic (ITE, cycle ergometer, number of subjects (N) = 7), isokinetic (IKE, torque egrometer, N = 7), and no exercise (NOE, N = 5) training for 60 min/day during head-down bed rest (HDBR). Total volume of the PLG muscles decreased (p less than 0.05) similarly: ITE = 4.3 +/- SE 1.6%, IKE = 7.7 +/- 1.6%, and NOE = 6.3 +/- 0.8%; combined volume (N = 19) loss was 6.1 +/- 0.9%. Ranges of volume changes were 2.6% to -9.0% (ITE), -2.1% to -14.9% (IKE), and -3.4% to -8/1% (NOE). Correlation coefficients (r) of muscle volume versus thickness measured with ultrasonography were: ITE r + 0.79 (p less than 0.05), IKE r = 0.27 (not significant (NS)), and NOE r = 0.63 (NS). Leg-muscle volume and thickness were highly correlated (r = 0.79) when plasma volume was maintained during HDBR with ITE. Thus, neither intensive lower extremity ITE nor IKE training influence the normal non-exercised posterior leg muscle atrophy during HDBR. The relationship of muscle volume and thickness may depend on the mode of exercise training associated with the maintenance of plasma volume

Modeling human papillomavirus and cervical cancer in the United States for analyses of screening and vaccination

Background: To provide quantitative insight into current U.S. policy choices for cervical cancer prevention, we developed a model of human papillomavirus (HPV) and cervical cancer, explicitly incorporating uncertainty about the natural history of disease. Methods: We developed a stochastic microsimulation of cervical cancer that distinguishes different HPV types by their incidence, clearance, persistence, and progression. Input parameter sets were sampled randomly from uniform distributions, and simulations undertaken with each set. Through systematic reviews and formal data synthesis, we established multiple epidemiologic targets for model calibration, including age-specific prevalence of HPV by type, age-specific prevalence of cervical intraepithelial neoplasia (CIN), HPV type distribution within CIN and cancer, and age-specific cancer incidence. For each set of sampled input parameters, likelihood-based goodness-of-fit (GOF) scores were computed based on comparisons between model-predicted outcomes and calibration targets. Using 50 randomly resampled, good-fitting parameter sets, we assessed the external consistency and face validity of the model, comparing predicted screening outcomes to independent data. To illustrate the advantage of this approach in reflecting parameter uncertainty, we used the 50 sets to project the distribution of health outcomes in U.S. women under different cervical cancer prevention strategies. Results: Approximately 200 good-fitting parameter sets were identified from 1,000,000 simulated sets. Modeled screening outcomes were externally consistent with results from multiple independent data sources. Based on 50 good-fitting parameter sets, the expected reductions in lifetime risk of cancer with annual or biennial screening were 76% (range across 50 sets: 69–82%) and 69% (60–77%), respectively. The reduction from vaccination alone was 75%, although it ranged from 60% to 88%, reflecting considerable parameter uncertainty about the natural history of type-specific HPV infection. The uncertainty surrounding the model-predicted reduction in cervical cancer incidence narrowed substantially when vaccination was combined with every-5-year screening, with a mean reduction of 89% and range of 83% to 95%. Conclusion: We demonstrate an approach to parameterization, calibration and performance evaluation for a U.S. cervical cancer microsimulation model intended to provide qualitative and quantitative inputs into decisions that must be taken before long-term data on vaccination outcomes become available. This approach allows for a rigorous and comprehensive description of policy-relevant uncertainty about health outcomes under alternative cancer prevention strategies. The model provides a tool that can accommodate new information, and can be modified as needed, to iteratively assess the expected benefits, costs, and cost-effectiveness of different policies in the U.S

Elimination of image blurring due to double scatter events in. gamma. imaging MWPC detectors

In multiwire proportional chambers used with honeycomb lead converters for detecting 511 KeV ..gamma.. rays from positron annihilation, a source of image blurring is generated by multiple interaction events due to the escape photoelectric x-ray or from the Compton scattered photon. Using the delay line readout method the majority of these double events are eliminated by using the fact that the sum of the time intervals from the prompt anode signal to the signal arrival at each end of the delay line is a constant to within the timing accuracy for a single interaction. Double interaction events produce a time sum which is shorter. Good improvement in image quality is obtained. The observed number of multiple events is larger than calculations would predict

Budget impact of somatostatin analogs as treatment for metastatic gastroenteropancreatic neuroendocrine tumors in US hospitals

Jesse D Ortendahl,1 Sonia J Pulgar,2 Beloo Mirakhur,3 David Cox,3 Tanya GK Bentley,1 Alexandria T Phan4 1Health Economics, Partnership for Health, LLC, Beverly Hills, CA, USA; 2Health Economics and Outcomes Research, Ipsen Biopharmaceuticals, Basking Ridge, NJ, USA; 3Medical Affairs, Oncology, Ipsen Biopharmaceuticals, Basking Ridge, NJ, USA; 4GI Medical Oncology, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA Objective: With the introduction of new therapies, hospitals have to plan spending limited resources in a cost-effective manner. To assist in identifying the optimal treatment for patients with locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors, budget impact modeling was used to estimate the financial implications of adoption and diffusion of somatostatin analogs (SSAs). Patients and methods: A hypothetical cohort of 500 gastroenteropancreatic neuroendocrine tumor patients was assessed in an economic model, with the proportion with metastatic disease treated with an SSA estimated using published data. Drug acquisition, preparation, and administration costs were based on national pricing databases and published literature. Octreotide dosing was based on published estimates of real-world data, whereas for lanreotide, real-world dosing was unavailable and we therefore used the highest indicated dosing. Alternative scenarios reflecting the proportion of patients receiving lanreotide or octreotide were considered to estimate the incremental budget impact to the hospital. Results: In the base case, 313 of the initial 500 gastroenteropancreatic neuroendocrine tumor patients were treated with an SSA. The model-predicted per-patient cost was US$83,473 for lanreotide and US$89,673 for octreotide. With a hypothetical increase in lanreotide utilization from 5% to 30% of this population, the annual model-projected hospital costs decreased by US$488,615. When varying the inputs in one-way sensitivity analyses, the results were most sensitive to changes in dosing assumptions. Conclusion: Results suggest that factors beyond drug acquisition cost can influence the budget impact to a hospital. When considering preparation and administration time, and real-world dosing, use of lanreotide has the potential to reduce health care expenditures associated with metastatic gastroenteropancreatic neuroendocrine tumor treatments. Keywords: health economics, oncology, model, costs, real-world evidence, lanreotid

TWO DETECTOR POSITRON CAMERA WITH HONEYCOMB LEAD CONVERTERS FOR MEDICAL IMAGING: PERFORMANCE AND DEVELOPMENTS

A Multiwire Proportional Chamber (MWPC) camera for Emission Tomography with positron emitting isotopes has been built. The coincident 511 KeV gammas are detected by their interaction with lead-on-plastic honeybomc converters coupled to planar MWPC detectors with sensitive area 48 x 48 cm{sup 2} placed 50 cm apart with clear space in between for the patient. Each detector box has two MWPC: the innermost MWPC are coupled to two converters, while the outer ones have only 1 converter. This configuration leads to an effective sensitivity of 1600 coincidence cts./min.{mu}Ci for a source placed in the center of the median plane between the detectors. With the present electronics and lead-on-plastic honeycomb converters the spatial resolution is 8 mm FWHM and the event rate at which images are taken with the camera is 30,000-40,000 events/min. The camera can be improved both in maximum event rate and spatial resolution by changing the dimensions of the converters. Decreasing the aperture size of the converters for the same thickness of lead wall leads to an increase in detection efficiency and hence improved count rate, as well as a decrease in the FWHM of the spatial resolution. They are continuing to investigate the use of surface conducting glass tube arrays with high concentrations of lead oxide (50% or more) and with hole size between 1.5 and 2 mm. Figure 2b shows the expected detection efficiency of various converters as a function of lead content and wall thickness. Alternative techniques under investigation are the use of etched hole patterns on stacks of thin lead-antimony or tungsten sheets. All of these gamma converters can be made with hole sizes 1.5-2.0 mm, compared to the 3.5 mm of the present honeycomb converters. Other factors which contribute to image degradation are multiple scattering of the 511 KeV gammas in the converters; effects of this are seen in the images of point sources which have long tails outside the main peak. Electronic techniques which they have developed are capable of rejecting over 95% of these scatter events. Data acquisition at high rates introduces a background distribution in the images due to accidental coincidence events of two 511 KeV gammas not originating from the same positron annihilation. Duplicate electronics, which is being implemented, can map out this accidentals distribution and will allow them to make a properly normalized pixel by pixel correction. These modifications, when implemented in a new camera, are expected to yield a sensitivity and event rate a factor of 10 better than the present camera. The spatial resolution is expected to be between 4-6 mm, depending on the amount of scatter within the object