Can we derive an 'exchange rate' between descriptive and preference-based outcome measures for stroke? Results from the transfer to utility (TTU) technique

<p>Abstract</p> <p>Background</p> <p>Stroke-specific outcome measures and descriptive measures of health-related quality of life (HRQoL) are unsuitable for informing decision-makers of the broader consequences of increasing or decreasing funding for stroke interventions. The quality-adjusted life year (QALY) provides a common metric for comparing interventions over multiple dimensions of HRQoL and mortality differentials. There are, however, many circumstances when – because of timing, lack of foresight or cost considerations – only stroke-specific or descriptive measures of health status are available and some indirect means of obtaining QALY-weights becomes necessary. In such circumstances, the use of regression-based transformations or mappings can circumvent the failure to elicit QALY-weights by allowing predicted weights to proxy for observed weights. This regression-based approach has been dubbed 'Transfer to Utility' (TTU) regression. The purpose of the present study is to demonstrate the feasibility and value of TTU regression in stroke by deriving transformations or mappings from stroke-specific and generic but descriptive measures of health status to a generic preference-based measure of HRQoL in a sample of Australians with a diagnosis of acute stroke. Findings will quantify the additional error associated with the use of condition-specific to generic transformations in stroke.</p> <p>Methods</p> <p>We used TTU regression to derive empirical transformations from three commonly used descriptive measures of health status for stroke (NIHSS, Barthel and SF-36) to a preference-based measure (AQoL) suitable for attaching QALY-weights to stroke disease states; based on 2570 observations drawn from a sample of 859 patients with stroke.</p> <p>Results</p> <p>Transformations from the SF-36 to the AQoL explained up to 71.5% of variation in observed AQoL scores. Differences between mean predicted and mean observed AQoL scores from the 'severity-specific' item- and subscale-based SF-36 algorithms and from the 'moderate to severe' index- and item-based Barthel algorithm were neither clinically nor statistically significant when 'low severity' SF-36 transformations were used to predict AQoL scores for patients in the NIHSS = 0 and NIHSS = 1–5 subgroups and when 'moderate to severe severity' transformations were used to predict AQoL scores for patients in the NIHSS ≥ 6 subgroup. In contrast, the difference between mean predicted and mean observed AQoL scores from the NIHSS algorithms and from the 'low severity' Barthel algorithms reached levels that could mask minimally important differences on the AQoL scale.</p> <p>Conclusion</p> <p>While our NIHSS to AQoL transformations proved unsuitable for most applications, our findings demonstrate that stroke-relevant outcome measures such as the SF-36 and Barthel Index can be adequately transformed to preference-based measures for the purposes of economic evaluation.</p

The Salmonella enterica Pan-genome

Salmonella enterica is divided into four subspecies containing a large number of different serovars, several of which are important zoonotic pathogens and some show a high degree of host specificity or host preference. We compare 45 sequenced S. enterica genomes that are publicly available (22 complete and 23 draft genome sequences). Of these, 35 were found to be of sufficiently good quality to allow a detailed analysis, along with two Escherichia coli strains (K-12 substr. DH10B and the avian pathogenic E. coli (APEC O1) strain). All genomes were subjected to standardized gene finding, and the core and pan-genome of Salmonella were estimated to be around 2,800 and 10,000 gene families, respectively. The constructed pan-genomic dendrograms suggest that gene content is often, but not uniformly correlated to serotype. Any given Salmonella strain has a large stable core, whilst there is an abundance of accessory genes, including the Salmonella pathogenicity islands (SPIs), transposable elements, phages, and plasmid DNA. We visualize conservation in the genomes in relation to chromosomal location and DNA structural features and find that variation in gene content is localized in a selection of variable genomic regions or islands. These include the SPIs but also encompass phage insertion sites and transposable elements. The islands were typically well conserved in several, but not all, isolates—a difference which may have implications in, e.g., host specificity

Variability in Working Memory Performance Explained by Epistasis vs Polygenic Scores in the ZNF804A Pathway

Importance: We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the relative contribution of the polygenic score vs epistasis in variation explained. Objectives To (1) assess the association between SNPs in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis and (2) assess whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score. Design, Setting, and Participants: Patients with psychosis (n = 424) were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention, and social cognition. We used the Psychiatric GWAS Consortium 1 schizophrenia genome-wide association study to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (n = 170), which was used to develop linear regression models containing the polygenic score and 2-SNP interactions. The best-fitting models were tested for replication in 2 independent test sets of cases: (1) 170 individuals with schizophrenia or schizoaffective disorder and (2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder, and other psychosis). Main Outcomes and Measures: Participants completed a neuropsychological assessment battery designed to target the cognitive deficits of schizophrenia including general cognitive function, episodic memory, working memory, attentional control, and social cognition. Results: Higher polygenic scores were associated with poorer performance among patients on IQ, memory, and social cognition, explaining 1% to 3% of variation on these scores (range, P = .01 to .03). Using a narrow psychosis training set and independent test sets of narrow phenotype psychosis (schizophrenia and schizoaffective disorder), broad psychosis, and control participants (n = 89), the addition of 2 interaction terms containing 2 SNPs each increased the R2 for spatial working memory strategy in the independent psychosis test sets from 1.2% using the polygenic score only to 4.8% (P = .11 and .001, respectively) but did not explain additional variation in control participants. Conclusions and Relevance: These data support a role for the ZNF804A pathway in IQ, memory, and social cognition in cases. Furthermore, we showed that epistasis increases the variation explained above the contribution of the polygenic score

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700