Changing consumption of resources for respiratory support and short-term outcomes in four consecutive geographical cohorts of infants born extremely preterm over 25 years since the early 1990s

OBJECTIVES:It is unclear how newer methods of respiratory support for infants born extremely preterm (EP; 22-27 weeks gestation) have affected in-hospital sequelae. We aimed to determine changes in respiratory support, survival and morbidity in EP infants since the early 1990s. DESIGN:Prospective longitudinal cohort study. SETTING:The State of Victoria, Australia. PARTICIPANTS:All EP births offered intensive care in four discrete eras (1991-1992 (24 months): n=332, 1997 (12 months): n=190, 2005 (12 months): n=229, and April 2016-March 2017 (12 months): n=250). OUTCOME MEASURES:Consumption of respiratory support, survival and morbidity to discharge home. Cost-effectiveness ratios describing the average additional days of respiratory support associated per additional survivor were calculated. RESULTS:Median duration of any respiratory support increased from 22 days (1991-1992) to 66 days (2016-2017). The increase occurred in non-invasive respiratory support (2 days (1991-1992) to 51 days (2016-2017)), with high-flow nasal cannulae, unavailable in earlier cohorts, comprising almost one-half of the duration in 2016-2017. Survival to discharge home increased (68% (1991-1992) to 87% (2016-2017)). Cystic periventricular leukomalacia decreased (6.3% (1991-1992) to 1.2% (2016-2017)), whereas retinopathy of prematurity requiring treatment increased (4.0% (1991-1992) to 10.0% (2016-2017)). The average additional costs associated with one additional infant surviving in 2016-2017 were 200 (95% CI 150 to 297) days, 326 (183 to 1127) days and 130 (70 to 267) days compared with 1991-1992, 1997 and 2005, respectively. CONCLUSIONS:Consumption of resources for respiratory support has escalated with improved survival over time. Cystic periventricular leukomalacia reduced in incidence but retinopathy of prematurity requiring treatment increased. How these changes translate into long-term respiratory or neurological function remains to be determined.Jeanie L Y Cheong, Joy E Olsen, Li Huang, Kim M Dalziel, Rosemarie A Boland, Alice C Burnett ... et al

Reading, metacognition, and motivation: A follow-up study of German students in Grades 7 and 8

This follow-up study to van Kraayenoord and Schneider (1999) examined the performance in reading, metacognition and motivation related to reading of students in Grades 7 and 8. Results showed significant correlations between all of the variables. A multivariate analysis of variance showed that good and poor readers differed in reading self-concept and metacognitive measures related to reading and memory. A stepwise regression analysis suggested that the metacognitive variables were the best predictors of reading. Furthermore, a comparison of the results of the previous study with those of the current investigation revealed that the findings were stable over time. Since the period between the two studies is the time during which students make important decisions related to enrolment in one of three distinct school-types in Germany, we examined the results of various groups of students: those in Gymnasium (high educational track), Realschule (middle educational track), and Hauptschule (low educational track). Students in the Gymnasium scored significantly better than students in the other two groups on almost all variables related to reading. A re-analysis of the data from our first investigation found that the results of the Gymnasium students in the second study could be predicted from their results obtained during elementary school

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Analysis of shared heritability in common disorders of the brain

Paroxysmal Cerebral Disorder

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Health literacy, information provision and satisfaction in advanced cancer consultations: two observational studies using level of education as a proxy.

Objectives Patients with low health literacy (LHL) might feel less informed and satisfied with provided information than patients with high health literacy (HHL). In the setting of advanced cancer, we explored whether LHL patients, compared with HHL patients are: (1) often less informed, and (2) less satisfied with clinicians’ communication (a) in general and (b) following information provision specifically. Methods Data from two observational studies using recorded consultations were combined. Clinicians’ provided information and patients’ health literacy level—defined by educational levels—and satisfaction were measured. Χ2 tests and regression (moderation) analyses assessed the relation between health literacy and information provision, and between information provision and satisfaction, meanwhile exploring moderating influences of health literacy. Results Of 61 included patients, 25 (41%) had LHL. LHL and HHL patients were equally seldom informed about the disease’s incurability (36% vs 42%, p=0.66). LHL patients were more often informed about the option of not pursuing anticancer therapy than HHL patients (28% vs 8%, p=0.04). LHL patients were more satisfied with clinicians’ communication than HHL patients (M=9.3 vs M=8.5, p=0.03), especially when the option of no anticancer treatment was discussed (p=0.04). Discussing the disease’s incurability did not influence satisfaction levels (p=0.58) for LHL and HHL patients. Conclusions LHL patients were not less informed, yet more satisfied than HHL patients. Both groups were equally seldom informed about the disease’s incurability. No anticancer therapy was mostly discussed with LHL patients who were more satisfied following this information. Clinicians should be encouraged to inform all patients about the disease status and (non)treatment options, while not overlooking empathic support