Yours sincerely 2 MANUSCRIPT Highlights: Empirical impacts of past integration experiments were explored through a global review Positive outcomes for patients and clinicians without incurring additional financial costs were found Improvements were incremental hence integration should not be considered a fundamental 'game-changer'. AbstractUniversal Health Coverage (UHC) is at the heart of the new 2030 Agenda for Sustainable Development. Health service integration is seen by World Health Organization as an essential requirement to achieve UHC. However, to date the debate on service integration has focused on perceived benefits rather than empirical impact. We conducted a global review in a systematic manner searching for empirical outcomes of service integration experiments in UHC countries and those on the path to UHC. Sixty-seven articles and reports were found. We grouped results into a unique integration typology with six categories -Medical staff from different disciplines; Patients and Medical Staff; Care Package for One Medical Condition; Care Package for Two or More Medical Conditions; Specialist standalone services with GP services; Community locations. We showed that it is possible to integrate services in different human development contexts delivering positive outcomes for patients and clinicians without incurring additional costs. However, the improved outcomes shown were incremental rather than radical and suggest that integration is likely to enhance already well established systems rather than fundamentally changing the outcomes of care.
Introduction 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is commonly used to estimate neuronal injury in Alzheimer's disease (AD). Here, we evaluate the utility of dynamic PET measures of perfusion using 11 C-Pittsburgh compound B (PiB) to estimate neuronal injury in comparison to FDG PET. Methods FDG, early frames of PiB images, and relative PiB delivery rate constants (PiB-R1) were obtained from 110 participants from the Dominantly Inherited Alzheimer Network. Voxelwise, regional cross-sectional, and longitudinal analyses were done to evaluate the correlation between images and estimate the relationship of the imaging biomarkers with estimated time to disease progression based on family history. Results Metabolism and perfusion images were spatially correlated. Regional PiB-R1 values and FDG, but not early frames of PiB images, significantly decreased in the mutation carriers with estimated year to onset and with increasing dementia severity. Discussion Hypometabolism estimated by PiB-R1 may provide a measure of brain perfusion without increasing radiation exposure.
We have developed and validated a search filter (FSF1) to identify studies reporting HSUVs with high sensitivity (95 percent) and two other search filters (FSF2 and FSF3) with reasonably high sensitivity (92 percent and 88 percent) but greater precision, resulting in a lower NNR. These seem to be the first validated filters available for HSUVs. The availability of filters with a range of sensitivity and precision options enables researchers to choose the filter which is most appropriate to the resources available for their specific research.
Pathological cerebral white matter changes in Alzheimer’s disease have been shown using diffusion tensor imaging. Superficial white matter changes are relatively understudied despite their importance in cortico-cortical connections. Measuring superficial white matter degeneration using diffusion tensor imaging is challenging due to its complex organizational structure and proximity to the cortex. To overcome this, we investigated diffusion MRI changes in young-onset Alzheimer’s disease using standard diffusion tensor imaging and Neurite Orientation Dispersion and Density Imaging to distinguish between disease-related changes that are degenerative (e.g. loss of myelinated fibres) and organizational (e.g. increased fibre dispersion). Twenty-nine young-onset Alzheimer’s disease patients and 22 healthy controls had both single-shell and multi-shell diffusion MRI. We calculated fractional anisotropy, mean diffusivity, neurite density index, orientation dispersion index and tissue fraction (1-free water fraction). Diffusion metrics were sampled in 15 a priori regions of interest at four points along the cortical profile: cortical grey matter, grey/white boundary, superficial white matter (1 mm below grey/white boundary) and superficial/deeper white matter (2 mm below grey/white boundary). To estimate cross-sectional group differences, we used average marginal effects from linear mixed effect models of participants’ diffusion metrics along the cortical profile. The superficial white matter of young-onset Alzheimer’s disease individuals had lower neurite density index compared to controls in five regions (superior and inferior parietal, precuneus, entorhinal and parahippocampus) (all P < 0.05), and higher orientation dispersion index in three regions (fusiform, entorhinal and parahippocampus) (all P < 0.05). Young-onset Alzheimer’s disease individuals had lower fractional anisotropy in the entorhinal and parahippocampus regions (both P < 0.05) and higher fractional anisotropy within the postcentral region (P < 0.05). Mean diffusivity was higher in the young-onset Alzheimer’s disease group in the parahippocampal region (P < 0.05) and lower in the postcentral, precentral and superior temporal regions (all P < 0.05). In the overlying grey matter, disease-related changes were largely consistent with superficial white matter findings when using neurite density index and fractional anisotropy, but appeared at odds with orientation dispersion and mean diffusivity. Tissue fraction was significantly lower across all grey matter regions in young-onset Alzheimer’s disease individuals (all P < 0.001) but group differences reduced in magnitude and coverage when moving towards the superficial white matter. These results show that microstructural changes occur within superficial white matter and along the cortical profile in individuals with young-onset Alzheimer’s disease. Lower neurite density and higher orientation dispersion suggests underlying fibres undergo neurodegeneration and organizational changes, two effects previously indiscernible using standard diffusion tensor metrics in superficial white matter.
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