Prelude to a Systematic Review of Activity-based Funding of Hospitals: Potential Effects on Cost, Quality, Access, Efficiency, and Equity

Until recently, hospital funding in Canada has been based predominantly on global budgets, but health care system decision-makers throughout the country are now seriously considering an alternative funding model referred to as activity-based funding (ABF). Under this system, hospital services are classified prospectively into clinically meaningful "bundles" of care that use similar levels of resources. Opinion is divided as to whether ABF would help the Canadian health care system to achieve any of the putative benefits originally achieved by ABF in other countries, or whether the risks would outweigh the benefits. As yet, there has been no systematic review of the evidence. In March 2012 our research team launched a systematic review to inform Canadian policy-makers about how this funding model affects health care systems around the world. Of the more than 16 000 potentially eligible titles and abstracts screened, 261 studies, representing 64 countries (either singly or in aggregate), provide data on at least one of the cost, quality, access, efficiency, and equity outcomes of interest to our research team. We are now in the process of analyzing data from the eligible studies most germane to the Canadian context. This commentary is intended to alert decision-makers to the upcoming release of a series of papers based on our systematic review of ABF, in the hope that our synthesis will soon provide a more robust evidence base to better inform decision-makers

Standardising Costs or Standardising Care? Qualitative Evaluation of the Implementation and Impact of a Hospital Funding Reform in Ontario, Canada

Background  Since 2011, the Government of Ontario, Canada, has phased in hospital funding reforms hoping to encourage standardised, evidence-based clinical care processes to both improve patient outcomes and reduce system costs. One aspect of the reform – quality-based procedures (QBPs) – replaced some of each hospital’s global budget with a pre-set price per episode of care for patients with specific diagnoses or procedures. The QBP initiative included publication and dissemination of a handbook for each of these diagnoses or procedures, developed by an expert technical group. Each handbook was intended to guide hospitals in reducing inappropriate variation in patient care and cost by specifying an evidence-based episode of care pathway. We explored whether, how and why hospitals implemented these episode of care pathways in response to this initiative. Methods  We interviewed key informants at three levels in the healthcare system, namely individuals who conceived and designed the QBP policy, individuals and organisations supporting QBP adoption, and leaders in five case-study hospitals responsible for QBP implementation. Analysis involved an inductive approach, incorporating framework analysis to generate descriptive and explanatory themes from data. Results  The 46 key informants described variable implementation of best practice episode of care pathways across QBPs and across hospitals. Handbooks outlining evidence-based clinical pathways did not address specific barriers to change for different QBPs nor differences in hospitals’ capacity to manage change. Hospitals sometimes found it easier to focus on containing and standardising costs of care than on implementing standardised care processes that adhered to best clinical practices. Conclusion  Implementation of QBPs in Ontario’s hospitals depended on the interplay between three factors, namely complexity of changes required, internal capacity for organisational change, and availability and appropriateness of targeted external facilitators and supports to manage change. Variation in these factors across QBPs and hospitals suggests the need for more tailored and flexible implementation supports designed to fit all elements of the policy, rather than one-size-fits-all handbooks alone. Without such supports, hospitals may enact quick fixes aimed mainly at preserving budgets, rather than pursue evidence- and value-based changes in care management. Overestimating hospitals’ change management capacity increases the risk of implementation failure

Digital Collection Contexts: iConference 2014 Workshop Report

The "Digital Collection Contexts: Intellectual and Organizational Functions at Scale" workshop was held March 4, 2014, at the iConference in Berlin, Germany. The aim was to unite a community of faculty, students, system designers, and developers interested in digital collections, particularly in the context of cultural heritage aggregations. Organized by a team from the University of Illinois, the Europeana Foundation, and the University of Texas at Austin, the one-day workshop brought together an international group of experts representing diverse threads of current research and development to engage on the role of collections in the digital environment and to identify new directions for inquiry.This report compiles the position papers and includes synopses of the presentations by the authors and ensuing discussions.Ope

Hepatitis E virus (HEV) in Scotland:evidence of recent increase in viral circulation in humans

Background: Previous studies showed low levels of circulating hepatitis E virus (HEV) in Scotland. We aimed to reassess current Scottish HEV epidemiology. Methods: Blood donor samples from five Scottish blood centres, the minipools for routine HEV screening and liver transplant recipients were tested for HEV antibodies and RNA to determine seroprevalence and viraemia. Blood donor data were compared with results from previous studies covering 2004-08. Notified laboratory-confirmed hepatitis E cases (2009-16) were extracted from national surveillance data. Viraemic samples from blood donors (2016) and chronic hepatitis E transplant patients (2014-16) were sequenced. Results: Anti-HEV IgG seroprevalence varied geographically and was highest in Edinburgh where it increased from 4.5% in 2004-08) to 9.3% in 2014-15 (p = 0.001). It was most marked in donors < 35 years. HEV RNA was found in 1:2,481 donors, compared with 1:14,520 in 2011. Notified laboratory-confirmed cases increased by a factor of 15 between 2011 and 2016, from 13 to 206. In 2011-13, 1 of 329 transplant recipients tested positive for acute HEV, compared with six cases of chronic infection during 2014-16. Of 10 sequenced viraemic donors eight and all six patients were infected with genotype 3 clade 1 virus, common in European pigs. Conclusions: The seroprevalence, number of viraemic donors and numbers of notified laboratory-confirmed cases of HEV in Scotland have all recently increased. The causes of this change are unknown, but need further investigation. Clinicians in Scotland, particularly those caring for immunocompromised patients, should have a low threshold for testing for HEV

Qualitative Analysis of the Dynamics of Policy Design and Implementation in Hospital Funding Reform

Background  As in many health care systems, some Canadian jurisdictions have begun shifting away from global hospital budgets. Payment for episodes of care has begun to be implemented. Starting in 2012, the Province of Ontario implemented hospital funding reforms comprising three elements: Global Budgets; Health Based Allocation Method (HBAM); and Quality-Based Procedures (QBP). This evaluation focuses on implementation of QBPs, a procedure/diagnosis-specific funding approach involving a pre-set price per episode of care coupled with best practice clinical pathways. We examined whether or not there was consensus in understanding of the program theory underpinning QBPs and how this may have influenced full and effective implementation of this innovative funding model. Methods  We undertook a formative evaluation of QBP implementation. We used an embedded case study method and in-depth, one-on-one, semi-structured, telephone interviews with key informants at three levels of the health care system: Designers (those who designed the QBP policy); Adoption Supporters (organizations and individuals supporting adoption of QBPs); and Hospital Implementers (those responsible for QBP implementation in hospitals). Thematic analysis involved an inductive approach, incorporating Framework analysis to generate descriptive and explanatory themes that emerged from the data. Results  Five main findings emerged from our research: (1) Unbeknownst to most key informants, there was neither consistency nor clarity over time among QBP designers in their understanding of the original goal(s) for hospital funding reform; (2) Prior to implementation, the intended hospital funding mechanism transitioned from ABF to QBPs, but most key informants were either unaware of the transition or believe it was intentional; (3) Perception of the primary goal(s) of the policy reform continues to vary within and across all levels of key informants; (4) Four years into implementation, the QBP funding mechanism remains misunderstood; and (5) Ongoing differences in understanding of QBP goals and funding mechanism have created challenges with implementation and difficulties in measuring success. Conclusions  Policy drift and policy layering affected both the goal and the mechanism of action of hospital funding reform. Lack of early specification in both policy goals and hospital funding mechanism exposed the reform to reactive changes that did not reflect initial intentions. Several challenges further exacerbated implementation of complex hospital funding reforms, including a prolonged implementation schedule, turnover of key staff, and inconsistent messaging over time. These factors altered the trajectory of the hospital funding reforms and created confusion amongst those responsible for implementation. Enacting changes to hospital funding policy through a process that is transparent, collaborative, and intentional may increase the likelihood of achieving intended effects

Application of pharmacogenomics and bioinformatics to exemplify the utility of human <i>ex vivo</i> organoculture models in the field of precision medicine

Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. Diseased tissue ethically acquired from patients suffering from chronic obstructive pulmonary disease (COPD), was used to investigate inter-patient variability in drug efficacy using ex vivo organocultures of fresh lung tissue as the test system. The reduction in inflammatory cytokines in the presence of various test drugs was used as the measure of drug efficacy and the individual patient responses were then matched against genotype and microRNA profiles in an attempt to identify unique predictors of drug responsiveness. Our findings suggest that genetic variation in CYP2E1 and SMAD3 genes may partly explain the observed variation in drug response

Telomere disruption results in non-random formation of de novo dicentric chromosomes involving acrocentric human chromosomes

Copyright: © 2010 Stimpson et al.Genome rearrangement often produces chromosomes with two centromeres (dicentrics) that are inherently unstable because of bridge formation and breakage during cell division. However, mammalian dicentrics, and particularly those in humans, can be quite stable, usually because one centromere is functionally silenced. Molecular mechanisms of centromere inactivation are poorly understood since there are few systems to experimentally create dicentric human chromosomes. Here, we describe a human cell culture model that enriches for de novo dicentrics. We demonstrate that transient disruption of human telomere structure non-randomly produces dicentric fusions involving acrocentric chromosomes. The induced dicentrics vary in structure near fusion breakpoints and like naturally-occurring dicentrics, exhibit various inter-centromeric distances. Many functional dicentrics persist for months after formation. Even those with distantly spaced centromeres remain functionally dicentric for 20 cell generations. Other dicentrics within the population reflect centromere inactivation. In some cases, centromere inactivation occurs by an apparently epigenetic mechanism. In other dicentrics, the size of the alpha-satellite DNA array associated with CENP-A is reduced compared to the same array before dicentric formation. Extrachromosomal fragments that contained CENP-A often appear in the same cells as dicentrics. Some of these fragments are derived from the same alpha-satellite DNA array as inactivated centromeres. Our results indicate that dicentric human chromosomes undergo alternative fates after formation. Many retain two active centromeres and are stable through multiple cell divisions. Others undergo centromere inactivation. This event occurs within a broad temporal window and can involve deletion of chromatin that marks the locus as a site for CENP-A maintenance/replenishment.This work was supported by the Tumorzentrum Heidelberg/Mannheim grant (D.10026941)and by March of Dimes Research Foundation grant #1-FY06-377 and NIH R01 GM069514

Aesthetic response to color combinations: preference, harmony, and similarity

Previous studies of preference for and harmony of color combinations have produced confusing results. For example, some claim that harmony increases with hue similarity, whereas others claim that it decreases. We argue that such confusions are resolved by distinguishing among three types of judgments about color pairs: (1) preference for the pair as a whole, (2) harmony of the pair as a whole, and (3) preference for its figural color when viewed against its colored background. Empirical support for this distinction shows that pair preference and harmony both increase as hue similarity increases, but preference relies more strongly on component color preference and lightness contrast. Although pairs with highly contrastive hues are generally judged to be neither preferable nor harmonious, figural color preference ratings increase as hue contrast with the background increases. The present results thus refine and clarify some of the best-known and most contentious claims of color theorists

Corrigendum to “Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy” [Neuromuscular Disorders, Vol. 30 (6) 2020, 492-502] (Neuromuscular Disorders (2020) 30(6) (492–502), (S0960896620301188), (10.1016/j.nmd.2020.05.002))

This article reported on the results from a phase 2 trial of domagrozumab and its open-label extension in patients with Duchenne muscular dystrophy (Clinicaltrials.gov identifiers: NCT02310763 and NCT02907619). The manuscript also provided results on two secondary endpoints for magnetic resonance imaging (MRI), muscle volume and muscle volume index. The authors regret that, following publication of the results and in preparation for a separate publication on MRI results from this trial, the MRI images were reviewed and segmentation errors were identified. As a result, the team worked to (1) Perform a rigorous quality inspection of all analysed data; (2) Identify cases where there were incorrect segmentations; (3) correct segmentation errors; (4) Re-analyse all data with correct segmentation. Using the updated MRI data, the MMRM analysis showed there was a change in the significance of secondary endpoints evaluating Thigh Muscle Volume and Muscle Volume Index. No significant differences between treatment groups in muscle volume measures were found in the original analysis. These results have not altered the overall interpretation of the study results but do necessitate revisions to the article. These data confirm that the trial design and execution adequately tested the hypothesis that myostatin inhibition would slow or delay the loss of function in patients with Duchenne muscular dystrophy (DMD). The increase in muscle volume observed by MRI in patients with DMD treated with domagrozumab is in accordance with mechanism of action for domagrozumab, which targets myostatin, a negative regulator of muscle growth. The increase in muscle volume did not lead to a clinical benefit in patients with DMD. The primary endpoint (4 stair climb) did not meet statistical significance, nor did the other functional tests. The study was terminated due to lack of efficacy. Full details of the needed revisions are as follows: 1. In the results section 3.6 (page 8, second paragraph), we reported no significant differences in mean percent change from baseline between domagrozumab and placebo for both muscle volume and muscle volume index. This paragraph was replaced with the following text: “There was a significant difference between domagrozumab and placebo in the mean percent change from baseline in thigh muscle volume at Week 17 (difference 2.945%, P=0.0087) and Week 49 (differences 4.087%, P=0.0298), and in muscle volume index at Week 33 (difference 2.612%, P=0.0376) and Week 49 (differences3.208%, P=0.0411).” 2. In the discussion (page 9), the following sentence, “Although neither muscle volume nor muscle volume index measures were statistically significant in this study, they are both consistent with a potential anabolic effect.” was replaced with, “The increase in muscle volume observed on MRI in patients with DMD treated with domagrozumab, is in accordance with mechanism of action for this compound which targets myostatin, a negative regulator of muscle growth. However, the increase in muscle volume did not lead to a clinical benefit (improved function) in patients with DMD.” 3. In view of the correction to the Results section, this is now reflected in the abstract which has changed to read: “There were no significant between-group differences in secondary clinical endpoints, except for the thigh muscle volume and muscle volume index measures (P\u3c0.05).” The authors would like to apologise for any inconvenience caused