Integrating Function‐Directed Treatments into Palliative Care

The growing acceptance of palliative care has created opportunities to increase the use of rehabilitation services among populations with advanced disease, particularly those with cancer. Broader delivery has been impeded by the lack of a shared definition for palliative rehabilitation and a mismatch between patient needs and established rehabilitation service delivery models. We propose the definition that, in the advanced cancer population, palliative rehabilitation is function‐directed care delivered in partnership with other clinical disciplines and aligned with the values of patients who have serious and often incurable illnesses in contexts marked by intense and dynamic symptoms, psychological stress, and medical morbidity to realize potentially time‐limited goals. Although palliative rehabilitation is most often delivered by inpatient physical medicine and rehabilitation consultation/liaison services and by physical therapists in skilled nursing facilities, outcomes in these settings have received little scrutiny. In contrast, outpatient cancer rehabilitation programs have gained robust evidentiary support attesting to their benefits across diverse settings. Advancing palliative rehabilitation will require attention to historical barriers to the uptake of cancer rehabilitation services, which include the following: patient and referring physicians’ expectation that effective cancer treatment will reverse disablement; breakdown of linear models of disablement due to presence of concurrent symptoms and psychological distress; tension between reflexive palliation and impairment‐directed treatment; palliative clinicians’ limited familiarity with manual interventions and rehabilitation services; and challenges in identifying receptive patients with the capacity to benefit from rehabilitation services. The effort to address these admittedly complex issues is warranted, as consideration of function in efforts to control symptoms and mood is vital to optimize patients’ autonomy and quality of life. In addition, manual rehabilitation modalities are effective and drug sparing in the alleviation of adverse symptoms but are markedly underused. Realizing the potential synergism of integrating rehabilitation services in palliative care will require intensification of interdisciplinary dialogue.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146938/1/pmr2s335.pd

Admixture mapping and subsequent fine-mapping suggests a biologically relevant and novel association on chromosome 11 for type 2 diabetes in African Americans.

Type 2 diabetes (T2D) is a complex metabolic disease that disproportionately affects African Americans. Genome-wide association studies (GWAS) have identified several loci that contribute to T2D in European Americans, but few studies have been performed in admixed populations. We first performed a GWAS of 1,563 African Americans from the Vanderbilt Genome-Electronic Records Project and Northwestern University NUgene Project as part of the electronic Medical Records and Genomics (eMERGE) network. We successfully replicate an association in TCF7L2, previously identified by GWAS in this African American dataset. We were unable to identify novel associations at p<5.0×10(-8) by GWAS. Using admixture mapping as an alternative method for discovery, we performed a genome-wide admixture scan that suggests multiple candidate genes associated with T2D. One finding, TCIRG1, is a T-cell immune regulator expressed in the pancreas and liver that has not been previously implicated for T2D. We performed subsequent fine-mapping to further assess the association between TCIRG1 and T2D in >5,000 African Americans. We identified 13 independent associations between TCIRG1, CHKA, and ALDH3B1 genes on chromosome 11 and T2D. Our results suggest a novel region on chromosome 11 identified by admixture mapping is associated with T2D in African Americans

Demonstrating paths for unlocking the value of cloud genomics through cross cohort analysis

Abstract Recently, large scale genomic projects such as All of Us and the UK Biobank have introduced a new research paradigm where data are stored centrally in cloud-based Trusted Research Environments (TREs). To characterize the advantages and drawbacks of different TRE attributes in facilitating cross-cohort analysis, we conduct a Genome-Wide Association Study of standard lipid measures using two approaches: meta-analysis and pooled analysis. Comparison of full summary data from both approaches with an external study shows strong correlation of known loci with lipid levels (R2 ~ 83–97%). Importantly, 90 variants meet the significance threshold only in the meta-analysis and 64 variants are significant only in pooled analysis, with approximately 20% of variants in each of those groups being most prevalent in non-European, non-Asian ancestry individuals. These findings have important implications, as technical and policy choices lead to cross-cohort analyses generating similar, but not identical results, particularly for non-European ancestral populations

Candidate region targeted for fine-mapping.

<p>Using Seattle SNPs genome browser, the candidate genes located within 100<i>TCIRG1</i> gene, their orientation, and gene structure are displayed. SNPs annotated for these genes are located at the top of the figure denoted by hash marks. (Image generated from <a href="http://pga.gs.washington.edu/" target="_blank">http://pga.gs.washington.edu/</a>).</p

Comparison of global European ancestry in African American T2D cases and controls.

<p>Genome-wide estimates of percent European ancestry were calculated for each individual using ANCESTRYMAP. Average European ancestry was compared between cases (20.3%) and controls (20.6%, p = 0.72).</p