Hepatocellular carcinoma survival in uninsured and underinsured patients.

BACKGROUND: The incidence of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC) is increasing. The purpose of this study is to establish baseline survival in a medically-underserved population and to evaluate the effect of HCV seropositivity on our patient population. MATERIALS AND METHODS: We reviewed clinicopathologic parameters from a prospective tumor registry and medical records from the Harris County Hospital District (HCHD). Outcomes were compared using Kaplan-Meier survival analysis and log-rank tests. RESULTS: A total of 298 HCC patients were identified. The median survival for the entire cohort was 3.4 mo. There was no difference in survival between the HCV seropositive and the HCV seronegative groups (3.6 mo versus 2.6 mo, P = 0.7). Patients with a survival \u3c1 mo had a significant increase in\u3eαfetoprotein (AFP), international normalized ratio (INR), model for end-stage liver disease (MELD) score, and total bilirubin and decrease in albumin compared with patients with a survival ≥ 1 mo. CONCLUSIONS: Survival for HCC patients in the HCHD is extremely poor compared with an anticipated median survival of 7 mo reported in other studies. HCV seropositive patients have no survival advantage over HCV seronegative patients. Poorer liver function at diagnosis appears to be related to shorter survival. Further analysis into variables contributing to decreased survival is needed

Adherence to Opioid Patient Prescriber Agreements at a Safety Net Hospital

Patient prescriber agreements, also known as opioid contracts or opioid treatment agreements, have been recommended as a strategy for mitigating non-medical opioid use (NMOU). The purpose of our study was to characterize the proportion of patients with PPAs, the rate of non-adherence, and clinical predictors for PPA completion and non-adherence. This retrospective study covered consecutive cancer patients seen at a palliative care clinic at a safety net hospital between 1 September 2015 and 31 December 2019. We included patients 18 years or older with cancer diagnoses who received opioids. We collected patient characteristics at consultation and information regarding PPA. The primary purpose was to determine the frequency and predictors of patients with a PPA and non-adherence to PPAs. Descriptive statistics and multivariable logistic regression models were used for the analysis. The survey covered 905 patients having a mean age of 55 (range 18-93), of whom 474 (52%) were female, 423 (47%) were Hispanic, 603 (67%) were single, and 814 (90%) had advanced cancer. Of patients surveyed, 484 (54%) had a PPA, and 50 (10%) of these did not adhere to their PPA. In multivariable analysis, PPAs were associated with younger age (odds ratio [OR] 1.44

Pancreatic adenocarcinoma in a patient with Situs Inversus: a case report of this rare coincidence

<p>Abstract</p> <p>Background</p> <p><it>Situs inversus </it>(SI) is a relatively rare occurrence in patients with pancreatic adenocarcinoma. Pancreatic resection in these patients has rarely been described. CT scan imaging is a principle modality for detecting pancreatic cancer and its use in SI patients is seldom reported.</p> <p>Case Presentation</p> <p>We report a 48 year old woman with SI who, despite normal CT scan 8 months earlier, presented with obstructive jaundice and a pancreatic head mass requiring a pancreaticoduodenectomy. The surgical pathology report demonstrated pancreatic adenocarcinoma.</p> <p>Conclusion</p> <p>SI is a rare condition with concurrent pancreatic cancer being even rarer. Despite the rarity, pancreaticoduodenectomy in these patients for resectable lesions is safe as long as special consideration to the anatomy is taken. Additionally, radiographic imaging has significantly improved detection of early pancreatic cancer; however, there continues to be a need for improved detection of small neoplasms.</p

Whiteness and diasporic Irishness: nation, gender and class

Whiteness is often detached from the notion of diaspora in the recent flurry of interest in the phenomenon, yet it is a key feature of some of the largest and oldest displacements. This paper explores the specific contexts of white racial belonging and status over two centuries in two main destinations of the Irish diaspora, the USA and Britain. Its major contribution is a tracing of the untold story of ‘How the Irish became white in Britain’ to parallel and contrast with the much more fully developed narrative in the USA. It argues that, contrary to popular belief, the racialisation of the Irish in England did not fade away at the end of the nineteenth century but became transmuted in new forms which have continued to place the ‘white’ Irish outside the boundaries of the English nation. These have been strangely ignored by social scientists, who conflate Irishness and working-class identities in England without acknowledging the distinctive contribution of Irish backgrounds to constructions of class difference. Gender locates Irish women and men differently in relation to these class positions, for example allowing mothers to be blamed for the perpetuation of the underclass. Class and gender are also largely unrecognised dimensions of Irish ethnicity in the USA, where the presence of ‘poor white’ neighbourhoods continues to challenge the iconic story of Irish upward mobility. Irishness thus remains central to the construction of mainstream ‘white’ identities in both the USA and Britain into the twenty-first century

Genome-wide Association Study of Borderline Personality Disorder Reveals Genetic Overlap with Bipolar Disorder, Major Depression and Schizophrenia

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case–control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10−7) and PKP4 (P=8.67 × 10−7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [P=2.99 × 10−3]), SCZ (rg=0.34 [P=4.37 × 10−5]) and MDD (rg=0.57 [P=1.04 × 10−3]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n similar to 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders

Improving Genetic Prediction by Leveraging Genetic Correlations Among Human Diseases and Traits

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7 for height to 47 for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. © 2018 The Author(s)

Multi-polygenic score approach to trait prediction

A primary goal of polygenic scores, which aggregate the effects of thousands of trait-associated DNA variants discovered in genome-wide association studies (GWASs), is to estimate individual-specific genetic propensities and predict outcomes. This is typically achieved using a single polygenic score, but here we use a multi-polygenic score (MPS) approach to increase predictive power by exploiting the joint power of multiple discovery GWASs, without assumptions about the relationships among predictors. We used summary statistics of 81 well-powered GWASs of cognitive, medical and anthropometric traits to predict three core developmental outcomes in our independent target sample: educational achievement, body mass index (BMI) and general cognitive ability. We used regularized regression with repeated cross-validation to select from and estimate contributions of 81 polygenic scores in a UK representative sample of 6710 unrelated adolescents. The MPS approach predicted 10.9% variance in educational achievement, 4.8% in general cognitive ability and 5.4% in BMI in an independent test set, predicting 1.1%, 1.1%, and 1.6% more variance than the best single-score predictions. As other relevant GWA analyses are reported, they can be incorporated in MPS models to maximize phenotype prediction. The MPS approach should be useful in research with modest sample sizes to investigate developmental, multivariate and gene-environment interplay issues and, eventually, in clinical settings to predict and prevent problems using personalized interventions

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons