Governance informatics: Managing the performance of inter-organizational governance networks

This article introduces an informatics approach to managing the performance of inter-organizational governance networks that are designed to create, implement and evaluate public policies and the range of activities undertaken by practicing public administrators. We label this type of information flow process management governance informatics and lay out a range of theoretical constructs that may be used to collect, categorize, and analyze performance in inter-organizational governance networks. We discuss how governance informatics may be able to assess and re-design the accountability and transparency regimes of information flows in inter-organizational governance networks. The integration of a governance informatics-driven performance management system into an existing regional transportation planning network is presented as an application of the framework

Client Service Receipt Inventory as a standardised tool for measurement of socio-economic costs in the rare genetic disease population (CSRI-Ra)

The measurement of costs is fundamental in healthcare decision-making, but it is often challenging. In particular, standardised methods have not been developed in the rare genetic disease population. A reliable and valid tool is critical for research to be locally meaningful yet internationally comparable. Herein, we sought to develop, contextualise, translate, and validate the Client Service Receipt Inventory for the RAre disease population (CSRI-Ra) to be used in cost-of-illness studies and economic evaluations for healthcare planning. Through expert panel discussions and focus group meetings involving 17 rare disease patients, carers, and healthcare and social care professionals from Hong Kong, we have developed the CSRI-Ra. Rounds of forward and backward translations were performed by bilingual researchers, and face validity and semantic equivalence were achieved through interviews and telephone communications with focus group participants and an additional of 13 healthcare professional and university students. Intra-class correlation coefficient (ICC) was used to assess criterion validity between CSRI-Ra and electronic patient record in a sample of 94 rare disease patients and carers, with overall ICC being 0.69 (95% CI 0.56–0.78), indicating moderate to good agreement. Following rounds of revision in the development, contextualisation, translation, and validation stages, the CSRI-Ra is ready for use in empirical research. The CSRI-Ra provides a sufficiently standardised yet adaptable method for collecting socio-economic data related to rare genetic diseases. This is important for near-term and long-term monitoring of the resource consequences of rare diseases, and it provides a tool for use in economic evaluations in the future, thereby helping to inform planning for efficient and effective healthcare. Adaptation of the CSRI-Ra to other populations would facilitate international research

Evaluating the health-related quality of life of the rare disease population in Hong Kong using EQ-5D 3-level

Objectives This study aimed to establish a normative profile of health-related quality of life (HRQOL) of the rare disease (RD) population in Hong Kong (HK) and identify potential predictors. Methods Between March 2020 and October 2020, patients with RD and caregivers were recruited through Rare Disease Hong Kong, the largest RD patient group alliance in HK. HRQOL was derived using the EQ-5D 3-Level with reference to the established HK value set. Utility scores were stratified according to demographics and disease-related information. Multiple linear regression was performed to explore the associations between patient characteristics and HRQOL. Results A total of 286 patients, covering 107 unique RDs, reported a mean utility score of 0.53 (SD 0.36). Thirty patients (10.5%) reported negative utility scores, indicating worse-than-death health states. More problems were recorded in the “usual activities” and “self-care” dimensions. Univariate analyses revealed that neurologic diseases, high out-of-pocket expenditure, home modification, and living in public housing or subdivided flats/units were significantly associated with lower HRQOL. A total of 99 caregivers reported a mean utility score of 0.78 (SD 0.17), which was significantly associated with the utility score of patients they took care of (r = 0.32; P = .001). Conclusions The normative profile of the RD population was established, which revealed lower HRQOL in the RD population than other chronic disease groups and general population in HK. Findings were corroborated by evidence from other cohorts using EQ-5D, combined as part of a meta-analysis. Identifying predictors highlight areas that should be prioritized to improve HRQOL of RD population through clinical and psychosocial dimensions

Gut microbes shape microglia and cognitive function during malnutrition

Fecal-oral contamination promotes malnutrition pathology. Lasting consequences of early life malnutrition include cognitive impairment, but the underlying pathology and influence of gut microbes remain largely unknown. Here, we utilize an established murine model combining malnutrition and iterative exposure to fecal commensals (MAL-BG). The MAL-BG model was analyzed in comparison to malnourished (MAL mice) and healthy (CON mice) controls. Malnourished mice display poor spatial memory and learning plasticity, as well as altered microglia, non-neuronal CNS cells that regulate neuroimmune responses and brain plasticity. Chronic fecal-oral exposures shaped microglial morphology and transcriptional profile, promoting phagocytic features in MAL-BG mice. Unexpectedly, these changes occurred independently from significant cytokine-induced inflammation or blood-brain barrier (BBB) disruption, key gut-brain pathways. Metabolomic profiling of the MAL-BG cortex revealed altered polyunsaturated fatty acid (PUFA) profiles and systemic lipoxidative stress. In contrast, supplementation with an ω3 PUFA/antioxidant-associated diet (PAO) mitigated cognitive deficits within the MAL-BG model. These findings provide valued insight into the malnourished gut microbiota-brain axis, highlighting PUFA metabolism as a potential therapeutic target

Teens, Technology, and Transportation: An exploration of the digital lives of high schoolers

In the face of increasing sprawl and car-dependence in US metropolitan areas, young people – especially teens in middle-class suburbs – may be experiencing new mobilities generated by their near-universal adoption of cell phones and increasing access to private automobiles. The growth in the adoption of hand-held mobile devices that can be used for communication and information may enhance accessibility and independent mobility for certain segments of the youth population, especially those in higher socio-economic status households. In a project with teens in two high schools in Chittenden County, Vermont, we used a mix of methods to explore the rapid changes in teens’ lives fostered by tools such as cell phones, texting, mobile internet access, and various forms of messaging. In this study, we find that millennial teens use digital devices to construct new intersections between communication, information, and transportation. By also actively employing these devices in our research, we are using novel methods for understanding the "digital lives" of teens, which represent a mix of traditional analog techniques and exploratory digital methodologies. In this presentation we examine issues including how often and in what ways high school students use advanced electronic communication tools to arrange transportation, what travel needs are being met and modes used, and how social processes contextualize the use of digital tools for mobility. We conclude by reflecting on how the daily lives of these teens may serve as a harbinger of emerging intersections of mobility, communication, and place

Socio-economic costs of rare diseases and the risk of financial hardship: a cross-sectional study

Background: To achieve universal healthcare coverage (UHC), the rare disease (RD) population must also receive quality healthcare without financial hardship. This study evaluates the impact of RDs in Hong Kong (HK) by estimating cost from a societal perspective and investigating related risk of financial hardship. Methods: A total of 284 RD patients and caregivers covering 106 RDs were recruited through HK's largest RD patient group, Rare Disease Hong Kong, in 2020. Resource use data were collected using the Client Service Receipt Inventory for Rare disease population (CSRI-Ra). Costs were estimated using a prevalence-based, bottom-up approach. Risk of financial hardship was estimated using catastrophic health expenditure (CHE) and impoverishing health expenditure (IHE) indicators. Multivariate regression was performed to identify potential determinants. Findings: Annual total RD costs in HK were estimated at HK$484,256/patient (United States (US)$62,084). Direct non-healthcare cost (HK$193,555/US$24,814) was the highest cost type, followed by direct healthcare (HK$187,166/US$23,995), and indirect (HK$103,535/US$13,273) costs. CHE at the 10% threshold was estimated at 36.3% and IHE at the $3.1 poverty line was 8.8%, both significantly higher than global estimates. Pediatric patients reported higher costs than adult patients (p < 0.001). Longer years since genetic diagnosis was the only factor significantly associated with both total costs (p = 0.026) and CHE (p = 0.003). Interpretation: This study serves as the first in the Asia Pacific region to simultaneously assess the societal costs and financial hardship related to RDs and highlights the importance of an early genetic diagnosis. These results contribute to existing evidence on the globally ubiquitous high costs of RDs, warranting collaboration between different stakeholders to include RD population in UHC planning. Funding: Health and Medical Research Fund, and the Society for the Relief of Disabled Children

O'Donnell-Luria-Rodan syndrome: Description of a second multinational cohort and refinement of the phenotypic spectrum

Background: O'Donnell-Luria-Rodan syndrome (ODLURO) is an autosomal-dominant neurodevelopmental disorder caused by pathogenic, mostly truncating variants in KMT2E. It was first described by O'Donnell-Luria et al in 2019 in a cohort of 38 patients. Clinical features encompass macrocephaly, mild intellectual disability (ID), autism spectrum disorder (ASD) susceptibility and seizure susceptibility. Methods: Affected individuals were ascertained at paediatric and genetic centres in various countries by diagnostic chromosome microarray or exome/genome sequencing. Patients were collected into a case cohort and were systematically phenotyped where possible. Results: We report 18 additional patients from 17 families with genetically confirmed ODLURO. We identified 15 different heterozygous likely pathogenic or pathogenic sequence variants (14 novel) and two partial microdeletions of KMT2E. We confirm and refine the phenotypic spectrum of the KMT2E-related neurodevelopmental disorder, especially concerning cognitive development, with rather mild ID and macrocephaly with subtle facial features in most patients. We observe a high prevalence of ASD in our cohort (41%), while seizures are present in only two patients. We extend the phenotypic spectrum by sleep disturbances. Conclusion: Our study, bringing the total of known patients with ODLURO to more than 60 within 2 years of the first publication, suggests an unexpectedly high relative frequency of this syndrome worldwide. It seems likely that ODLURO, although just recently described, is among the more common single-gene aetiologies of neurodevelopmental delay and ASD. We present the second systematic case series of patients with ODLURO, further refining the mutational and phenotypic spectrum of this not-so-rare syndrome

Functional impact of global rare copy number variation in autism spectrum disorders.

International audienceThe autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways

Extending thrombolysis to 4·5–9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data

Background: Stroke thrombolysis with alteplase is currently recommended 0–4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis. Methods: In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0–1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. Findings: We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI 1·15–2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [&lt;1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23–76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81–2·96, p=0·66). Interpretation: Patients with ischaemic stroke 4·5–9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis