Overregulation of Health Care: Musings on Disruptive Innovation Theory

Disruptive innovation theory provides one lens through which to describe how regulations may stifle innovation and increase costs. Basing their discussion on this theory, Curtis and Schulman consider some of the effects that regulatory controls may have on innovation in the health sector

Alzheimer's Disease-Associated Cerebrospinal Fluid (CSF) Biomarkers do not Correlate with CSF Volumes or CSF Production Rate

BACKGROUND: Neuropathologically, Alzheimer’s disease (AD) is characterized by accumulation of a 42 amino acid peptide called amyloid-β (Aβ42) in extracellular senile plaques together with intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles and neuronal degeneration. These changes are reflected in the cerebrospinal fluid (CSF), the volumes and production rates of which vary considerably between individuals, by reduced concentration of Aβ42, increased concentration of phosphorylated tau (P-tau) protein, and increased concentration of total tau (T-tau) protein, respectively. OBJECTIVE: To examine the outstanding question if CSF concentrations of AD associated biomarkers are influenced by variations in CSF volumes, CSF production rate, and intracranial pressure in healthy individuals. Methods: CSF concentrations of Aβ42, P-tau, and T-tau, as well as a number of other AD-related CSF biomarkers were analyzed together with intracranial subarachnoid, ventricular, and spinal CSF volumes, as assessed by magnetic resonance imaging volumetric measurements, and CSF production rate in 19 cognitively normal healthy subjects (mean age 70.6, SD 3.6 years). RESULTS: Negative correlations were seen between the concentrations of three CSF biomarkers (albumin ratio, Aβ38, and Aβ40), and ventricular CSF volume, but apart from this finding, no significant correlations were observed. CONCLUSION: These results speak against inter-individual variations in CSF volume and production rate as important confounds in the AD biomarker research field

Cerebrospinal fluid markers before and after shunting in patients with secondary and idiopathic normal pressure hydrocephalus

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to explore biochemical changes in the cerebrospinal fluid (CSF) induced by shunt surgery and the relationship between these changes and clinical improvement.</p> <p>Methods</p> <p>We measured clinical symptoms and analysed lumbar CSF for protein content, neurodegeneration and neurotransmission markers in patients with secondary (SNPH, n = 17) and idiopathic NPH (INPH, n = 18) before and 3 months after shunt surgery. Patients were divided into groups according to whether or not there was improvement in clinical symptoms after surgery.</p> <p>Results</p> <p>Preoperatively, the only pathological findings were elevated neurofilament protein (NFL), significantly more so in the SNPH patients than in the INPH patients, and elevated albumin content. Higher levels of NFL correlated with worse gait, balance, wakefulness and neuropsychological performance. Preoperatively, no differences were seen in any of the CSF biomarkers between patients that improved after surgery and those that did not improve. Postoperatively, a greater improvement in gait and balance performance correlated with a more pronounced reduction in NFL. Levels of albumin, albumin ratio, neuropeptide Y, vasoactive intestinal peptide and ganglioside GD3 increased significantly after shunting in both groups. In addition, Gamma amino butyric acid increased significantly in SNPH and tau in INPH.</p> <p>Conclusion</p> <p>We conclude that a number of biochemical changes occur after shunt surgery, but there are no marked differences between the SNPH and INPH patients. The results indicate that NFL may be a marker that can predict a surgically reversible state in NPH.</p

Attenuation correction in quantitative SPECT of cerebral blood flow: a Monte Carlo study

Monte Carlo simulation has been used to produce projections from a voxel-based brain phantom, simulating a 99mTc-HMPAO single photon emission computed tomography (SPECT) brain investigation. For comparison, projections free from the effects of attenuation and scattering were also simulated, giving ideal transaxial images after reconstruction. Three methods of attenuation correction were studied: (a) a pre-processing method, (b) a post-processing uniform method and (c) a post-processing non-uniform method using a density map. The accuracy of these methods was estimated by comparison of the reconstructed images with the ideal images using the normalized mean square error, NMSE, and quantitative values of the regional cerebral blood flow, rCBF. A minimum NMSE was achieved for the effective linear attenuation coefficient mu(eff) = 0.07 (0.09) cm(-1) for the uniform(pre) method, the effective mass attenuation coefficient mu(eff)/rho = 0.08 (0.10) cm2 g(-1) for the uniform(post) method and mu(eff)/rho = 0.12 (0.13) cm2 g(-1) for the non-uniform(post) method. Values in parentheses represent the case of dual-window scatter correction. The non-uniform(post) method performed better, as measured by the NMSE, both with and without scatter correction. Furthermore, the non-uniform(post) method gave, on average, more accurate rCBF values. Although the difference in rCBF accuracy was small between the various methods, the same method should be used for patient studies as for the reference material

Selection of collimator for rCBF studies and evaluation of triple-headed SPET using noise-resolution plots

We investigated the effect of collimator selection on image quality in regional cerebral blood flow (rCBF) studies of the brain performed with 99Tc(m)-HMPAO. A triple-headed SPET system (GE/CGR Neurocam) was used, together with three sets of parallel-hole collimators - general-purpose (GP), high-resolution (HR) and ultra-high-resolution (UHR). Two image quality parameters were used to describe the image quality, namely, noise and resolution. Noise was measured in experimental and Monte-Carlo simulated SPET studies of a cylinder phantom of uniform activity as the pixel root mean square error (RMS) and as the coefficient of variation (CV) of quantitative rCBF values. Resolution was measured as full-width at half-maximum in experimental SPET studies of a line-source. Plots of noise versus resolution for the different collimators were obtained by varying the cut-off frequency of the Hanning filter applied in the reconstruction of transaxial slices. From these noise-resolution plots, we were able to determine which collimator gave the best resolution for a specific noise level. A lowest reasonable noise level may be established by comparison with the inter-observer CV of the quantification method

Dual-window scatter correction and energy window setting in cerebral blood flow SPECT: a Monte Carlo study

The image quality in SPECT studies of the regional cerebral blood flow (rCBF) performed with 99mTc-HMPAO is degraded by scattered photons. The finite energy resolution of the gamma camera makes the detection of scattered photons unavoidable, and this is observed in the image as an impaired contrast between grey and white matter structures. In this work, a Monte Carlo simulated SPECT study of a realistic voxel-based brain phantom was used to evaluate the resulting contrast-to-noise ratio for a number of energy window settings, with and without the dual-window scatter correction. Values of the scaling factor k, used to obtain the fraction of scattered photons in the photopeak window, were estimated for each energy window. The use of a narrower, asymmetric, energy discrimination window improved the contrast, with a subsequent increase in statistical noise due to the lower number of counts. The photopeak-window setting giving the best contrast-to-noise ratio was found to be the same whether or not scatter correction was applied. Its value was 17% centred at 142 keV. At the optimum photopeak-window setting, the contrast was improved by using scatter correction, but the contrast-to-noise ratio was made worse