Shock volume: Patient-specific cumulative hypoperfusion predicts organ dysfunction in a prospective cohort of multiply injured patients

BACKGROUND: Multiply injured patients are at risk of developing hemorrhagic shock and organ dysfunction. We determined how cumulative hypoperfusion predicted organ dysfunction by integrating serial Shock Index measurements. METHODS: In this study, we calculated shock volume (SHVL) which is a patient-specific index that quantifies cumulative hypoperfusion by integrating abnormally elevated Shock Index (heart rate/systolic blood pressure ≥ 0.9) values acutely after injury. Shock volume was calculated at three hours (3 hr), six hours (6 hr), and twenty-four hours (24 hr) after injury. Organ dysfunction was quantified using Marshall Organ Dysfunction Scores averaged from days 2 through 5 after injury (aMODSD2–D5). Logistic regression was used to determine correspondence of 3hrSHVL, 6hrSHVL, and 24hrSHVL to organ dysfunction. We compared correspondence of SHVL to organ dysfunction with traditional indices of shock including the initial base deficit (BD) and the lowest pH measurement made in the first 24 hr after injury (minimum pH). RESULTS: SHVL at all three time intervals demonstrated higher correspondence to organ dysfunction (R2 = 0.48 to 0.52) compared to initial BD (R2 = 0.32) and minimum pH (R2 = 0.32). Additionally, we compared predictive capabilities of SHVL, initial BD and minimum pH to identify patients at risk of developing high-magnitude organ dysfunction by constructing receiver operator characteristic curves. SHVL at six hours and 24 hours had higher area under the curve compared to initial BD and minimum pH. CONCLUSION: SHVL is a non-invasive metric that can predict anticipated organ dysfunction and identify patients at risk for high-magnitude organ dysfunction after injury. LEVEL OF EVIDENCE: Prognostic study, level III

The Family Caregiving Dilemma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146879/1/pmr290.pd

Prospective parents’ perspectives on antenatal decision making for the anticipated birth of a periviable infant

Objective: To examine prospective parents’ perceptions of management options and outcomes in the context of threatened periviable delivery, and the values they apply in making antenatal decisions during this period. Study design: Qualitative analysis of 46 antenatal interviews conducted at three tertiary-care hospitals with 54 prospective parents (40 pregnant women, 14 partners) who had received counseling for threatened periviable delivery (40 cases). Results: Participants most often recalled being involved in resuscitation, cerclage, and delivery mode decisions. Over half (63.0%) desired a shared decision-making role. Most (85.2%) recalled hearing about morbidity and mortality, with many reiterating terms like “brain damage”, “disability”, and “handicap”. The potential for disability influenced decision making to variable degrees. In describing what mattered most, participant spoke of giving their child a “fighting chance”; others voiced concerns about “best interest”, a “healthy baby”, “pain and suffering”, and religious faith. Conclusions: Our findings underscore the importance of presenting clear information on disability and eliciting the factors that parents deem most important in making decisions about periviable birth

Parent perceptions of early prognostic encounters following children’s severe traumatic brain injury: ‘Locked up in this cage of absolute horror’

Little guidance exists for discussing prognosis in early acute care with parents following children’s severe traumatic brain injury (TBI). Providers’ beliefs about truth-telling can shape what is said, how it is said, and how providers respond to parents

Divergent Views of Hope Influencing Communications Between Parents and Hospital Providers

This study evaluates parents’ and health care providers’ (HCPs) descriptions of hope following counseling of parents at risk of delivering an extremely premature infant. Data came from a longitudinal multiple case study investigation that examined the decision-making and support needs of 40 families and their providers. Semi-structured interviews were conducted before and after delivery. Divergent viewpoints of hope were found between parents and many HCPs and were subsequently coded using content analysis. Parents relied on hope as an emotional motivator, whereas most HCPs described parents’ notions of hope as out of touch with reality. Parents perceived that such divergent beliefs about the role of hope negatively shaped communicative interactions and reduced trust with some of their providers. A deeper understanding of how varying views of hope might shape communications will uncover future research questions and lead to theory-based interventions aimed at improving the process of discussing difficult news with parents

On the Interplay of Telomeres, Nevi and the Risk of Melanoma

The relationship between telomeres, nevi and melanoma is complex. Shorter telomeres have been found to be associated with many cancers and with number of nevi, a known risk factor for melanoma. However, shorter telomeres have also been found to decrease melanoma risk. We performed a systematic analysis of telomere-related genes and tagSNPs within these genes, in relation to the risk of melanoma, dysplastic nevi, and nevus count combining data from four studies conducted in Italy. In addition, we examined whether telomere length measured in peripheral blood leukocytes is related to the risk of melanoma, dysplastic nevi, number of nevi, or telomere-related SNPs. A total of 796 cases and 770 controls were genotyped for 517 SNPs in 39 telomere-related genes genotyped with a custom-made array. Replication of the top SNPs was conducted in two American populations consisting of 488 subjects from 53 melanoma-prone families and 1,086 cases and 1,024 controls from a case-control study. We estimated odds ratios for associations with SNPs and combined SNP P-values to compute gene region-specific, functional group-specific, and overall P-value using an adaptive rank-truncated product algorithm. In the Mediterranean population, we found suggestive evidence that RECQL4, a gene involved in genome stability, RTEL1, a gene regulating telomere elongation, and TERF2, a gene implicated in the protection of telomeres, were associated with melanoma, the presence of dysplastic nevi and number of nevi, respectively. However, these associations were not found in the American samples, suggesting variable melanoma susceptibility for these genes across populations or chance findings in our discovery sample. Larger studies across different populations are necessary to clarify these associations

Supporting Pharmacovigilance Signal Validation and Prioritization with Analyses of Routinely Collected Health Data: Lessons Learned from an EHDEN Network Study

Introduction: Individual case reports are the main asset in pharmacovigilance signal management. Signal validation is the first stage after signal detection and aims to determine if there is sufficient evidence to justify further assessment. Throughout signal management, a prioritization of signals is continually made. Routinely collected health data can provide relevant contextual information but are primarily used at a later stage in pharmacoepidemiological studies to assess communicated signals. Objective: The aim of this study was to examine the feasibility and utility of analysing routine health data from a multinational distributed network to support signal validation and prioritization and to reflect on key user requirements for these analyses to become an integral part of this process. Methods: Statistical signal detection was performed in VigiBase, the WHO global database of individual case safety reports, targeting generic manufacturer drugs and 16 prespecified adverse events. During a 5-day study-a-thon, signal validation and prioritization were performed using information from VigiBase, regulatory documents and the scientific literature alongside descriptive analyses of routine health data from 10 partners of the European Health Data and Evidence Network (EHDEN). Databases included in the study were from the UK, Spain, Norway, the Netherlands and Serbia, capturing records from primary care and/or hospitals. Results: Ninety-five statistical signals were subjected to signal validation, of which eight were considered for descriptive analyses in the routine health data. Design, execution and interpretation of results from these analyses took up to a few hours for each signal (of which 15–60 minutes were for execution) and informed decisions for five out of eight signals. The impact of insights from the routine health data varied and included possible alternative explanations, potential public health and clinical impact and feasibility of follow-up pharmacoepidemiological studies. Three signals were selected for signal assessment, two of these decisions were supported by insights from the routine health data. Standardization of analytical code, availability of adverse event phenotypes including bridges between different source vocabularies, and governance around the access and use of routine health data were identified as important aspects for future development. Conclusions: Analyses of routine health data from a distributed network to support signal validation and prioritization are feasible in the given time limits and can inform decision making. The cost–benefit of integrating these analyses at this stage of signal management requires further research

Genome-wide Association Study Identifies Two Susceptibility Loci for Osteosarcoma

Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. In order to better understand the genetic etiology of osteosarcoma, we performed a multi-stage genome-wide association study (GWAS) consisting of 941 cases and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: rs1906953 at 6p21.3, in the glutamate receptor metabotropic 4 [GRM4] gene (P = 8.1 ×10-9), and rs7591996 and rs10208273 in a gene desert on 2p25.2 (P = 1.0 ×10-8 and 2.9 ×10-7). These two susceptibility loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types

Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands