History of Health Services Research Project: Interview with Kerr White

The interview conducted in 1998 with Kerr L. White (1917-2014) is presented, translated into Spanish. White, an economist, epidemiologist, statistician, general physician, and health advocate, was highly critical of the separation between research, clinical practice, epidemiology, public health, and health policies. He was one of the pioneers in healthcare services research. His primary concern was society’s responsibility to allocate healthcare resources in the most appropriate way to improve the health of populations. White’s work critically addresses the absence of a population perspective in epidemiology applied to healthcare services and systems, and the lack of evaluation of the social and economic impact of practices. He also highlights the dehumanization of care processes. Despite being undercited in health literature, we reintroduce his figure with the aim of disseminating the relevance of his thoughts and contributions

Impairment Rating Ambiguity in the United States: The Utah Impairment Guides for Calculating Workers' Compensation Impairments

Since the implementation of workers' compensation, accurately and consistently rating impairment has been a concern for the employee and employer, as well as rating physicians. In an attempt to standardize and classify impairments, the American Medical Association (AMA) publishes the AMA Guides ("Guides"), and recently published its 6th edition of the AMA Guides. Common critiques of the AMA Guides 6th edition are that they are too complex, lacking in evidence-based methods, and rarely yield consistent ratings. Many states mandate use of some edition of the AMA Guides, but few states are adopting the current edition due to the increasing difficulty and frustration with their implementation. A clearer, simpler approach is needed. Some states have begun to develop their own supplemental guides to combat problems in complexity and validity. Likewise studies in Korea show that past methods for rating impairment are outdated and inconsistent, and call for measures to adapt current methods to Korea's specific needs. The Utah Supplemental Guides to the AMA Guides have been effective in increasing consistency in rating impairment. It is estimated that litigation of permanent impairment has fallen below 1% and Utah is now one of the least costly states for obtaining workers' compensation insurance, while maintaining a medical fee schedule above the national average. Utah's guides serve as a model for national or international impairment guides

Single-cell resolution imaging of retinal ganglion cell apoptosis in vivo using a cell-penetrating caspase-activatable peptide probe

Peptide probes for imaging retinal ganglion cell (RGC) apoptosis consist of a cell-penetrating peptide targeting moiety and a fluorophore-quencher pair flanking an effector caspase consensus sequence. Using ex vivo fluorescence imaging, we previously validated the capacity of these probes to identify apoptotic RGCs in cell culture and in an in vivo rat model of N-methyl- D-aspartate (NMDA)-induced neurotoxicity. Herein, using TcapQ488, a new probe designed and synthesized for compatibility with clinically-relevant imaging instruments, and real time imaging of a live rat RGC degeneration model, we fully characterized time- and dose-dependent probe activation, signal-to-noise ratios, and probe safety profiles in vivo. Adult rats received intravitreal injections of four NMDA concentrations followed by varying TcapQ488 doses. Fluorescence fundus imaging was performed sequentially in vivo using a confocal scanning laser ophthalmoscope and individual RGCs displaying activated probe were counted and analyzed. Rats also underwent electroretinography following intravitreal injection of probe. In vivo fluorescence fundus imaging revealed distinct single-cell probe activation as an indicator of RGC apoptosis induced by intravitreal NMDA injection that corresponded to the identical cells observed in retinal flat mounts of the same eye. Peak activation of probe in vivo was detected 12 hours post probe injection. Detectable fluorescent RGCs increased with increasing NMDA concentration; sensitivity of detection generally increased with increasing TcapQ488 dose until saturating at 0.387 nmol. Electroretinography following intravitreal injections of TcapQ488 showed no significant difference compared with control injections. We optimized the signal-to-noise ratio of a caspase-activatable cell penetrating peptide probe for quantitative non-invasive detection of RGC apoptosis in vivo. Full characterization of probe performance in this setting creates an important in vivo imaging standard for functional evaluation of future probe analogues and provides a basis for extending this strategy into glaucoma-specific animal models

The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature

<p>Abstract</p> <p>Background</p> <p>Human height is considered highly heritable and correlated with certain disorders, such as type 2 diabetes and cancer. Despite environmental influences, genetic factors are known to play an important role in stature determination. A number of genetic determinants of adult height have already been established through genome wide association studies.</p> <p>Methods</p> <p>To examine 51 single nucleotide polymorphisms (SNPs) corresponding to the 46 previously reported genomic loci for height in 8,184 European American children with height measurements. We leveraged genotyping data from our ongoing GWA study of height variation in children in order to query the 51 SNPs in this pediatric cohort.</p> <p>Results</p> <p>Sixteen of these SNPs yielded at least nominally significant association to height, representing fifteen different loci including <it>EFEMP1-PNPT1, GPR126, C6orf173, SPAG17</it>, Histone class 1, HLA class III and <it>GDF5-UQCC</it>. Other loci revealed no evidence for association, including <it>HMGA1 and HMGA2</it>. For the 16 associated variants, the genotype score explained 1.64% of the total variation for height z-score.</p> <p>Conclusion</p> <p>Among 46 loci that have been reported to associate with adult height to date, at least 15 also contribute to the determination of height in childhood.</p

Association Analysis of the FTO Gene with Obesity in Children of Caucasian and African Ancestry Reveals a Common Tagging SNP

Recently an association was demonstrated between the single nucleotide polymorphism (SNP), rs9939609, within the FTO locus and obesity as a consequence of a genome wide association (GWA) study of type 2 diabetes in adults. We examined the effects of two perfect surrogates for this SNP plus 11 other SNPs at this locus with respect to our childhood obesity cohort, consisting of both Caucasians and African Americans (AA). Utilizing data from our ongoing GWA study in our cohort of 418 Caucasian obese children (BMI≥95th percentile), 2,270 Caucasian controls (BMI<95th percentile), 578 AA obese children and 1,424 AA controls, we investigated the association of the previously reported variation at the FTO locus with the childhood form of this disease in both ethnicities. The minor allele frequencies (MAF) of rs8050136 and rs3751812 (perfect surrogates for rs9939609 i.e. both r2 = 1) in the Caucasian cases were 0.448 and 0.443 respectively while they were 0.391 and 0.386 in Caucasian controls respectively, yielding for both an odds ratio (OR) of 1.27 (95% CI 1.08–1.47; P = 0.0022). Furthermore, the MAFs of rs8050136 and rs3751812 in the AA cases were 0.449 and 0.115 respectively while they were 0.436 and 0.090 in AA controls respectively, yielding an OR of 1.05 (95% CI 0.91–1.21; P = 0.49) and of 1.31 (95% CI 1.050–1.643; P = 0.017) respectively. Investigating all 13 SNPs present on the Illumina HumanHap550 BeadChip in this region of linkage disequilibrium, rs3751812 was the only SNP conferring significant risk in AA. We have therefore replicated and refined the association in an AA cohort and distilled a tag-SNP, rs3751812, which captures the ancestral origin of the actual mutation. As such, variants in the FTO gene confer a similar magnitude of risk of obesity to children as to their adult counterparts and appear to have a global impact