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

Why is management research irrelevant?

At least since 1980, there has been a practically continuous, but somewhat fragmented discussion on the relevance of management research. This discussion has addressed practically all fields of management; here, besides general management, operations management, project management and construction management are examined in more detail. Although many different proposals have been made to rectify the situation, no definitive resolution has been found. In this paper, it is argued that prior analyses have not reached the root causes of the irrelevance problem. By an analysis of the recent history of management research, the following novel findings are reached. First, the root cause of the irrelevance is argued to lie in the 1959 reports on American business education, written by Pierson and Gordon & Howell. Second, while the proposed direction in the 1959 reports was deficient in several ways, the rejection of production as an integral part of organizations and management has been perhaps the most damaging feature of those reports. Third, current research on management suffers from a variety of immediate causes for irrelevance, insufficiently recognized by the scholarly community. It is suggested that reaching the root causes for irrelevance will facilitate finding suitable cures

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

Effect of weight-loss diets prior to elective surgery on postoperative outcomes in obesity : a systematic review and meta-analysis

This systematic review investigated the effects of weight-loss diets before elective surgery on preoperative weight loss and postoperative outcomes in people with obesity. Electronic databases were searched from inception to May 2021. Inclusion criteria were prospective cohort or randomised controlled studies that compared effects of weight-loss diets to standard care on postoperative outcomes in adults with obesity awaiting surgery. Participants with cancer or undergoing bariatric surgery were excluded. Data on preoperative weight change, length of stay, postoperative complications and patient-reported outcome measures were extracted and synthesised in meta-analyses. One randomised controlled trial involving total knee arthroplasty and two that investigated general surgery were eligible that included 173 participants overall. Each study compared low-calorie diets using meal replacement formulas to usual care. There is very-low-quality evidence of a statistically significant difference favouring the intervention for preoperative weight loss (mean difference [MD] -6.67 kg, 95% confidence interval [CI] -12.09 to -1.26 kg; p = 0.02) and low-quality evidence that preoperative weight-loss diets do not reduce postoperative complications to 30 days (odds ratio [OR] 0.34, 95% CI 0.08-1.42; p = 0.14) or length of stay (MD -3.72 h, 95% CI -10.76 to 3.32; p = 0.30). From the limited data that is of low quality, weight loss diets before elective surgery do not reduce postoperative complications

Changes in long-term prognosis with increasing postnatal survival and the occurrence of postnatal morbidities in extremely preterm infants offered intensive care: a prospective observational study

Background: Decisions regarding provision of intensive care and post-discharge follow-up for infants born extremely preterm (<28 weeks' gestation) are based on the risks of mortality and neurodevelopmental disability. We aimed to elucidate the changes in probability of three outcomes (death, survival with major disability, and survival without major disability) with postnatal age in extremely preterm infants offered intensive care, and the effect of postnatal events on the probability of survival without major disability. Methods:In this prospective observational study, we used data from three geographical cohorts composed of all extremely preterm live births offered intensive care at birth during three distinct periods (1991–92, 1997, and 2005) in Victoria, Australia. Participants were assessed at 8 years' corrected age for major neurodevelopmental disability, defined as moderate or severe cerebral palsy, general intelligence more than 2 SDs below term-born control means, blindness, or deafness. Probabilities of outcomes conditional on survival to different postnatal ages were calculated by logistic regression. Multivariable logistic regression was used to assess factors predictive of survival with major disability. Findings: 751 (82%) of 915 extremely preterm live births free of lethal anomalies were offered intensive care, of whom 546 (73%) survived to age 8 years. Of the 499 survivors assessed, 86 (17%) had a major disability. With increasing gestational age at birth or days of postnatal survival, the probability of death decreased and of survival without major disability increased. By contrast, the probability of survival with major disability varied little with gestational age or postnatal survival. In survivors, major disability was associated with the occurrence of four important postnatal events: grade 3 or 4 intraventricular haemorrhage (odds ratio 2·61 [95% CI 1·11–6·15]), cystic periventricular leukomalacia (9·17 [3·57–23·53]), postnatal corticosteroid use (1·99 [1·03–3·85]), and surgery (2·78 [1·51–5·13]). 241 survivors (48%) had no major postnatal events during the newborn period, and had the lowest prevalence of major disability (17 participants [7%]). The probability of survival without major disability decreased with increasing number of major events (0·93 [0·89–0·96] for no events vs 0·31 [0·11–0·59] for three or more events). Interpretation: Long-term prognosis in terms of death and major neurodevelopmental disability changes rapidly after birth for extremely preterm infants. Counselling of families and post-discharge planning should be individualised to changing circumstances following birth.J. L. Y. Cheong, K. J. Lee , R. A. Boland, A. J. Spittle, G. F. Opie ... P.J. Anderson ... et al

Association between minor elevations of creatine kinase-MB level and mortality in patients with acute coronary syndromes without ST-segment elevation.

CONTEXT: Controversy surrounds the diagnostic and prognostic importance of slightly elevated cardiac markers in patients with acute coronary syndromes without ST-segment elevation. OBJECTIVES: To investigate the relationship between peak creatine kinase (CK)-MB level and outcome and to determine whether a threshold CK-MB level exists below which risk is not increased. DESIGN AND SETTING: Retrospective observational analysis of data from the international Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, conducted from November 1995 to January 1997. PATIENTS: A total of 8250 patients with acute coronary syndromes without ST-segment elevation who had at least 1 CK-MB sample collected during their index hospitalization. MAIN OUTCOME MEASURE: Mortality at 30 days and 6 months, was assessed by category of index-hospitalization peak CK-MB level (0-1, >1-2, >2-3, >3-5, >5-10, or >10 times the upper limit of normal). Multivariable logistic regression was used to determine the independent prognostic significance of peak CK-MB level after adjustment for baseline predictors of 30-day and 6-month mortality. RESULTS: Mortality at 30 days and 6 months increased from 1.8% and 4.0%, respectively, in patients with normal peak CK-MB levels, to 3.3% and 6.2 % at peak CK-MB levels 1 to 2 times normal, to 5.1% and 7.5% at peak CK-MB levels 3 to 5 times normal, and to 8.3% and 11.0% at peak CK-MB levels greater than 10 times normal. Log-transformed peak CK-MB levels were predictive of adjusted 30-day and 6-month mortality (P<.001 for both). CONCLUSIONS: Our data show that elevation of CK-MB level is strongly related to mortality in patients with acute coronary syndromes without ST-segment elevation, and that the increased risk begins with CK-MB levels just above normal. In the appropriate clinical context, even minor CK-MB elevations should be considered indicative of myocardial infarction