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To determine the Final ICU Need in the 24 hours prior to ICU discharge for children with cardiac disease by utilising a single-centre survey.
A cross-sectional survey was utilised to determine Final ICU Need, which was categorised as “Cardiovascular”, “Respiratory”, “Feeding”, “Sedation”, “Systems Issue”, or “Other” for each encounter. Survey responses were obtained from attending physicians who discharged children (≤18 years of age with ICU length of stay >24 hours) from the Cardiac ICU between April 2016 and July 2018.
Measurements and results:
Survey response rate was 99% (n = 1073), with 667 encounters eligible for analysis. “Cardiovascular” (61%) and “Respiratory” (26%) were the most frequently chosen Final ICU Needs. From a multivariable mixed effects logistic regression model fitted to “Cardiovascular” and “Respiratory”, operations with significantly reduced odds of having “Cardiovascular” Final ICU Need included Glenn palliation (p = 0.003), total anomalous pulmonary venous connection repair (p = 0.024), truncus arteriosus repair (p = 0.044), and vascular ring repair (p < 0.001). Short lengths of stay (<7.9 days) had significantly higher odds of “Cardiovascular” Final ICU Need (p < 0.001). “Cardiovascular” and “Respiratory” Final ICU Needs were also associated with provider and ICU discharge season.
Final ICU Need is a novel metric to identify variations in Cardiac ICU utilisation and clinical trajectories. Final ICU Need was significantly influenced by benchmark operation, length of stay, provider, and season. Future applications of Final ICU Need include targeting quality and research initiatives, calibrating provider and family expectations, and identifying provider-level variability in care processes and mental models.
This paper examines the determinants of financial industry actors’ regulatory preferences—examining why some financial industry actors prefer less stringent financial regulations while others prefer more stringent regulations. The determination of preferences, we argue, can be understood as mutually dependent. How an organization is connected to other organisations through network ties may help to explain its regulatory preferences. Our empirical point of focus is financial industry lobbying in the context of the European Union (EU). Using data from nearly nine hundred lobbying letters related to legislation on banking, insurance, and securities regulation, we map out a “socialization network” that models connections between financial industry firms, their associations, as well as a broad range of other organisations and actors that are auxiliary to this community of organizations. Using these data we find evidence that organizations’ preferences are informed by their location within this socialization network. Controlling for a range of other plausible factors, we find that 1) those connected via common associational ties, 2) those closer to one another in the network and 3) those more “embedded” in this network are all less likely to diverge in terms of their preferences from one another.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Since our last report on the voluntary Hungarian Twin Registry (HTR) in 2012, the number of pairs or multiplets included increased from 310 to 1044. Efforts to turn the registry into a population-based one are on the way. Nearly 128,000 twins living in Hungary (98,500 adults) will be mailed information on how to register on the new HTR website. Twins will be asked to invite their spouses and immediate family members. Meanwhile, strong cooperation through exchange programs has been developed with other foreign twin registries. Current research focuses on radiogenomics, musculoskeletal, cardiovascular and respiratory diseases, gut microbiome as well as basic molecular research and yielded new awards and further publications.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
One major challenge facing policy-makers is to design education and workplace training programs that are appropriately challenging. We review previous research that suggests that difficult training is better than easy training. However, surveys we conducted of students and of expert sport coaches showed that many prescribed easy rather than difficult training for those they coached. We analyzed the performance of National Collegiate Athletic Association (NCAA) basketball teams in postseason tournaments to see whether the existing research, largely on individuals in short-term situations, would generalize to teams in the long run. Indeed, playing difficult nonconference (training) games modestly improved performance for NCAA teams in the postseason. Difficult training particularly benefitted teams that lost many nonconference games, and the effect of difficulty was positive within the range of difficulty NCAA teams actually encounter, making it clear that difficult training is superior. We suggest that our results can be generalized beyond sports, although with careful consideration of differences between NCAA basketball teams and other teams that may limit generalizability. These results suggest that policy-makers might consider amplifying the difficulty of team training exercises under certain conditions.
The initial classic Fontan utilising a direct right atrial appendage to pulmonary artery anastomosis led to numerous complications. Adults with such complications may benefit from conversion to a total cavo-pulmonary connection, the current standard palliation for children with univentricular hearts.
A single institution, retrospective chart review was conducted for all Fontan conversion procedures performed from July, 1999 through January, 2017. Variables analysed included age, sex, reason for Fontan conversion, age at Fontan conversion, and early mortality or heart transplant within 1 year after Fontan conversion.
A total of 41 Fontan conversion patients were identified. Average age at Fontan conversion was 24.5 ± 9.2 years. Dominant left ventricular physiology was present in 37/41 (90.2%) patients. Right-sided heart failure occurred in 39/41 (95.1%) patients and right atrial dilation was present in 33/41 (80.5%) patients. The most common causes for Fontan conversion included atrial arrhythmia in 37/41 (90.2%), NYHA class II HF or greater in 31/41 (75.6%), ventricular dysfunction in 23/41 (56.1%), and cirrhosis or fibrosis in 7/41 (17.1%) patients. Median post-surgical follow-up was 6.2 ± 4.9 years. Survival rates at 30 days, 1 year, and greater than 1-year post-Fontan conversion were 95.1, 92.7, and 87.8%, respectively. Two patients underwent heart transplant: the first within 1 year of Fontan conversion for heart failure and the second at 5.3 years for liver failure.
Fontan conversion should be considered early when atrial arrhythmias become common rather than waiting for severe heart failure to ensue, and Fontan conversion can be accomplished with an acceptable risk profile.
ALKS 3831, currently under development for the treatment of schizophrenia, is composed of olanzapine (OLZ) and a fixed dose of 10mg of samidorphan. In a Phase 2 study in stable patients with schizophrenia, ALKS 3831mitigated OLZ-associated weight gain while maintaining an antipsychotic efficacy profile similar to OLZ.
To assess the efficacy and safety of ALKS 3831 in patients with acute exacerbation of schizophrenia.
This was a Phase 3, 4-week, randomized, double-blind, active and placebo (PBO)-controlled study of ALKS 3831 in patients with acute exacerbation of schizophrenia (ClinicalTrials.gov: NCT02634346). Eligible patients (N=403) were randomized 1:1:1 to receive ALKS 3831, OLZ, or PBO. Patients were treated in an inpatient setting for the first 2weeks of the study and could be treated as inpatients or outpatients for the remaining 2weeks. Patients were excluded if they received OLZ within 6months prior to screening. Antipsychotic efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression–Severity (CGI-S) and CGI–Improvement (CGI-I) scales. Safety and tolerability were assessed as adverse events (AEs).
Of 401 randomized patients who received ALKS 3831, OLZ, or PBO, 91%, 89%, and 83% of patients, respectively, completed treatment. The most common reason for discontinuation was withdrawal by patient (6% in both the ALKS 3831and PBO groups, and 7% in the OLZ group). Baseline characteristics were generally similar between groups; however, baseline mean body mass index was higher in the OLZ group than in the ALKS 3831 group. Baseline mean±standard deviation scores were 101.7±11.9 for PANSS total score and 5.1±0.7 for CGI-S scale score. The mean OLZ dose was 18.4mg/day in both active treatment arms. Least squares (LS) mean difference±standard error (SE) vs PBO from baseline to Week 4 in PANSS total score was –6.4±1.8 (P<.001) for the ALKS 3831 group and –5.3±1.8 (P=.004) for the OLZ group. LS mean difference±SE vs PBO from baseline to Week 4 in CGI-S scale score was −0.4±0.1 (P=.002) for the ALKS3831 group and −0.4±0.1 (P<.001) for the OLZ group. The percentage of patients with improvement in PANSS response (≥30% from baseline) at Week 4 was 60%, 54%, and 38% in the ALKS 3831, OLZ, and PBO groups, respectively. The percentage of patients with an improvement in CGI-I scale response (score of ≤2) at Week 4 was 58%, 51%, and 33% in the ALKS 3831, OLZ, and PBO groups, respectively. Discontinuation due to AEs was low in all groups. Common AEs (≥5% in any group) included weight gain, somnolence, dry mouth, anxiety, headache, and schizophrenia.
Treatment with ALKS 3831 was more effective than PBO, as measured by the PANSS and CGI-S scale, and its antipsychotic efficacy was similar to the active control OLZ. The safety profile of ALKS 3831 was similar toOLZ.
Funding Acknowledgements: This study was funded by Alkermes, Inc.
The joint effects of an insoluble surfactant and gravity on the linear stability of a two-layer Couette flow in a horizontal channel are investigated. The inertialess instability regimes are studied for arbitrary wavelengths and with no simplifying requirements on the system parameters: the ratio of thicknesses of the two fluid layers; the viscosity ratio; the base shear rate; the Marangoni number
; and the Bond number
. As was established in the first part of this investigation (Frenkel, Halpern & Schweiger, J. Fluid Mech., vol. 863, 2019, pp. 150–184), a quadratic dispersion equation for the complex growth rate yields two, largely continuous, branches of the normal modes, which are responsible for the flow stability properties. This is consistent with the surfactant instability case of zero gravity studied in Halpern & Frenkel (J. Fluid Mech., vol. 485, 2003, pp. 191–220). The present paper focuses on the mid-wave regimes of instability, defined as those having a finite interval of unstable wavenumbers bounded away from zero. In particular, the location of the mid-wave instability regions in the (
)-plane, bounded by their critical curves, depending on the other system parameters, is considered. The changes of the extremal points of these critical curves with the variation of external parameters are investigated, including the bifurcation points at which new extrema emerge. Also, it is found that for the less unstable branch of normal modes, a mid-wave interval of unstable wavenumbers may sometimes coexist with a long-wave one, defined as an interval having a zero-wavenumber endpoint.
A linear stability analysis of a two-layer plane Couette flow of two immiscible fluid layers with different densities, viscosities and thicknesses, bounded by two infinite parallel plates moving at a constant relative velocity to each other, with an insoluble surfactant monolayer along the interface and in the presence of gravity is carried out. The normal modes approach is applied to the equations governing flow disturbances in the two layers. These equations, together with boundary conditions at the plates and the interface, yield a linear eigenvalue problem. When inertia is neglected the velocity amplitudes are the linear combinations of certain hyperbolic functions, and a quadratic dispersion equation for the increment, that is the complex growth rate, is obtained, where coefficients depend on the aspect ratio, the viscosity ratio, the basic velocity shear, the Marangoni number
that measures the effects of surfactant and the Bond number
that measures the influence of gravity. An extensive investigation is carried out that examines the stabilizing or destabilizing influences of these parameters. Since the dispersion equation is quadratic in the growth rate, there are two continuous branches of the normal modes: a robust branch that exists even with no surfactant, and a surfactant branch that, to the contrary, vanishes when
. Regimes have been uncovered with crossings of the two dispersion curves, their reconnections at the point of crossing and separations as
changes. Due to the availability of the explicit forms for the growth rates, in many instances the numerical results are corroborated with analytical asymptotics.
To assess trends of mortality attributable to child and maternal undernutrition (CMU), overweight/obesity and dietary risks of non-communicable diseases (NCD) in sub-Saharan Africa (SSA) using data from the Global Burden of Disease (GBD) Study 2015.
For each risk factor, a systematic review of data was used to compute the exposure level and the effect size. A Bayesian hierarchical meta-regression analysis was used to estimate the exposure level of the risk factors by age, sex, geography and year. The burden of all-cause mortality attributable to CMU, fourteen dietary risk factors (eight diets, five nutrients and fibre intake) and overweight/obesity was estimated.
All age groups and both sexes.
In 2015, CMU, overweight/obesity and dietary risks of NCD accounted for 826204 (95 % uncertainty interval (UI) 737346, 923789), 266768 (95 % UI 189051, 353096) and 558578 (95 % UI 453433, 680197) deaths, respectively, representing 10·3 % (95 % UI 9·1, 11·6 %), 3·3 % (95 % UI 2·4, 4·4 %) and 7·0 % (95 % UI 5·8, 8·3 %) of all-cause mortality. While the age-standardized proportion of all-cause mortality accounted for by CMU decreased by 55·2 % between 1990 and 2015 in SSA, it increased by 63·3 and 17·2 % for overweight/obesity and dietary risks of NCD, respectively.
The increasing burden of diet- and obesity-related diseases and the reduction of mortality attributable to CMU indicate that SSA is undergoing a rapid nutritional transition. To tackle the impact in SSA, interventions and international development agendas should also target dietary risks associated with NCD and overweight/obesity.
The Pueblo population of Chaco Canyon during the Bonito Phase (AD 800–1130) employed agricultural strategies and water-management systems to enhance food cultivation in this unpredictable environment. Scepticism concerning the timing and effectiveness of this system, however, remains common. Using optically stimulated luminescence dating of sediments and LiDAR imaging, the authors located Bonito Phase canal features at the far west end of the canyon. Additional ED-XRF and strontium isotope (87Sr/86Sr) analyses confirm the diversion of waters from multiple sources during Chaco’s occupation. The extent of this water-management system raises new questions about social organisation and the role of ritual in facilitating responses to environmental unpredictability.
This study examines GP perceptions, attitudes and knowledge of complementary medicine (CM), and to understand contextual factors that influence these perceptions, attitudes and knowledge.
CM use is increasing, and its influence on primary care becoming increasingly significant. Although general practitioners (GPs) often have central primary care gate-keeper roles within health systems, few studies have looked specifically at GPs’ perceptions, attitudes and knowledge of CM.
A questionnaire was mailed to all 1486 GPs registered as practicing in non-metropolitan areas of New South Wales. The survey included one free-text qualitative question, where respondents were invited to highlight issues associated with CM in their own words. Free-text responses were analyzed qualitatively using thematic analysis.
In total, 585 GPs responded to the survey (adjusted response rate 40.1%), with 152 (26.0%) filling in the free-text question. Central themes which emerged were risk as a primary concern; opposition to, resistance to and the inappropriateness of complementary therapies; struggles with complexity and ambivalent tolerance.
GPs in Australia have a wide variety of perceptions toward CM. A minority of GPs have absolute views on CM, with most GPs having numerous caveats and qualifications of individual CM. Efficacy is only one aspect of CM critically evaluated by GPs when gauging support for individual therapies – risk, alignment with medical principles and an openness to exploring new avenues of treatment where others have failed, all appear to be equally important considerations when GPs form their views around CM.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
We identify characteristics of local health departments, which enhance collaborations with community- and faith-based organizations (CFBOs) for emergency preparedness and response.
Online survey data were collected from a sample of 273 disaster preparedness coordinators working at local health departments across the United States between August and December 2011.
Using multiple linear regression models, we found that perceptions of CFBO trust were associated with more successful partnership planning (β=0.63; P=0.02) and capacity building (β=0.61; P=0.01). Employee layoffs in the past 3 years (β=0.41; P=0.001) and urban location (β=0.41; P=0.005) were positively associated with higher ratings of resource sharing between health agencies and CFBOs. Having 1-3 full-time employees increased the ratings of success in communication and outreach activities compared with health departments having less than 1 full-time employee (β=0.33; P=0.05). Positive attitudes toward CFBOs also enhanced communication and outreach (β=0.16; P=0.03).
Staff-capacity factors are important for quick dissemination of information and resources needed to address emerging threats. Building the trust of CFBOs can help address large-scale disasters by improving the success of more involved activities that integrate the CFBO into emergency plans and operations of the health department and that better align with federal-funding performance measures. (Disaster Med Public Health Preparedness. 2018;12:57–66)
Critical to the development of improved HIV elimination efforts is a greater understanding of how social networks and their dynamics are related to HIV risk and prevention. In this paper, we examine network stability of confidant and sexual networks among young black men who have sex with men (YBMSM). We use data from uConnect (2013–2016), a population-based, longitudinal cohort study. We use an innovative approach to measure both sexual and confidant network stability at three time points, and examine the relationship between each type of stability and HIV risk and prevention behaviors. This approach is consistent with a co-evolutionary perspective in which behavior is not only affected by static properties of an individual's network, but may also be associated with changes in the topology of his or her egocentric network. Our results indicate that although confidant and sexual network stability are moderately correlated, their dynamics are distinct with different predictors and differing associations with behavior. Both types of stability are associated with lower rates of risk behaviors, and both are reduced among those who have spent time in jail. Public health awareness and engagement with both types of networks may provide new opportunities for HIV prevention interventions.
Research in the area of social networks and health has demonstrated that lay social network members play a critical role in the early stages of the illness career, influencing key decisions and pathways to formal care. Here, we revisit and extend this body of work, examining how the lay social network context can moderate the influence of treatment experiences on recovery outcomes as the illness career unfolds. To achieve this goal, we address two research questions, drawing on a longitudinal sample of people making their initial contact with the mental health treatment system: First, we explore how treatment experiences, lay social network characteristics, and recovery outcomes change over 2 years, beginning with the point of entry into treatment. Second, we examine whether the relationship between perceived treatment experiences and recovery outcomes is contingent on characteristics of the lay network context in which clients are socially embedded, focusing on the network's cultural orientation toward medical professionals. We find that positive treatment interactions facilitate improved self-esteem, mastery, role functioning, recovery optimism, and global functioning when the lay network culture is pro-medical, but largely have null effects on the recovery process when the lay network is more hostile to medical professionals.
Fontan survivors have depressed cardiac index that worsens over time. Serum biomarker measurement is minimally invasive, rapid, widely available, and may be useful for serial monitoring. The purpose of this study was to identify biomarkers that correlate with lower cardiac index in Fontan patients.
Methods and results
This study was a multi-centre case series assessing the correlations between biomarkers and cardiac magnetic resonance-derived cardiac index in Fontan patients ⩾6 years of age with biochemical and haematopoietic biomarkers obtained ±12 months from cardiac magnetic resonance. Medical history and biomarker values were obtained by chart review. Spearman’s Rank correlation assessed associations between biomarker z-scores and cardiac index. Biomarkers with significant correlations had receiver operating characteristic curves and area under the curve estimated. In total, 97 cardiac magnetic resonances in 87 patients met inclusion criteria: median age at cardiac magnetic resonance was 15 (6–33) years. Significant correlations were found between cardiac index and total alkaline phosphatase (−0.26, p=0.04), estimated creatinine clearance (0.26, p=0.02), and mean corpuscular volume (−0.32, p<0.01). Area under the curve for the three individual biomarkers was 0.63–0.69. Area under the curve for the three-biomarker panel was 0.75. Comparison of cardiac index above and below the receiver operating characteristic curve-identified cut-off points revealed significant differences for each biomarker (p<0.01) and for the composite panel [median cardiac index for higher-risk group=2.17 L/minute/m2 versus lower-risk group=2.96 L/minute/m2, (p<0.01)].
Higher total alkaline phosphatase and mean corpuscular volume as well as lower estimated creatinine clearance identify Fontan patients with lower cardiac index. Using biomarkers to monitor haemodynamics and organ-specific effects warrants prospective investigation.
Recent archaeological investigations at Pueblo Bonito in Chaco Canyon reveal that residents constructed a large diversion channel during the eleventh century A.D. as dramatic growth resulted in the expansion of the building onto the main valley floor. Sediments in the diversion channel reflect repeated episodes of flooding, rather than slow moving water typically found in irrigation canals, and archaeobotanical data indicate deposition during late summer or early fall. Although an agricultural function is possible, the channel may have been built primarily to divert floodwaters away from Pueblo Bonito while providing a nearby water source for construction and domestic use. The diversion channel was destroyed by the entrenchment of the “Bonito paleo-channel” in the late A.D. 1000s, and then buried by a combination of cultural debris and valley flooding. Although the canyon stream system changed throughout the occupation of Pueblo Bonito, there is no evidence that the formation of a deep natural channel in the floodplain had any negative effect on the growth of the great house