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OBJECTIVES/GOALS: Using the covariate-rich Veteran Health Administration data, estimate the association between Proton Pump Inhibitor (PPI) use and severe COVID-19, rigorously adjusting for confounding using propensity score (PS)-weighting. METHODS/STUDY POPULATION: We assembled a national retrospective cohort of United States veterans who tested positive for SARS-CoV-2, with information on 33 covariates including comorbidity diagnoses, lab values, and medications. Current outpatient PPI use was compared to non-use (two or more fills and pills on hand at admission vs no PPI prescription fill in prior year). The primary composite outcome was mechanical ventilation use or death within 60 days; the secondary composite outcome included ICU admission. PS-weighting mimicked a 1:1 matching cohort, allowing inclusion of all patients while achieving good covariate balance. The weighted cohort was analyzed using logistic regression. RESULTS/ANTICIPATED RESULTS: Our analytic cohort included 97,674 veterans with SARS-CoV-2 testing, of whom 14,958 (15.3%) tested positive (6,262 [41.9%] current PPI-users, 8,696 [58.1%] non-users). After weighting, all covariates were well-balanced with standardized mean differences less than a threshold of 0.1. Prior to PS-weighting (no covariate adjustment), we observed higher odds of the primary (9.3% vs 7.5%; OR 1.27, 95% CI 1.13-1.43) and secondary (25.8% vs 21.4%; OR 1.27, 95% CI 1.18-1.37) outcomes among PPI users vs non-users. After PS-weighting, PPI use vs non-use was not associated with the primary (8.2% vs 8.0%; OR 1.03, 95% CI 0.91-1.16) or secondary (23.4% vs 22.9%;OR 1.03, 95% CI 0.95-1.12) outcomes. DISCUSSION/SIGNIFICANCE: The associations between PPI use and severe COVID-19 outcomes that have been previously reported may be due to limitations in the covariates available for adjustment. With respect to COVID-19, our robust PS-weighted analysis provides patients and providers with further evidence for PPI safety.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear.
Methods:
Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response.
Results:
Compared to participants with WBC counts of 4.5–10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses.
Conclusions:
An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.
This history of the scientific field of human motivation is demarcated by several distinct phases, each of which evolved toward a new general hypothesis. We begin that history with the speculations of Darwin on the adaptive nature of certain propensities and emotional reactions. Early work by Karl Groos, Robert Woodworth, and others explored play and interest as important natural tendencies in primates and humans. Yet the advent of behaviorism, through both drive theory (Hullian) and operant (Skinnerian) schools, crowded out these ideas, instead focusing the field on how external reinforcements shape and maintain behaviors. The significance of cognitive mediators, especially people's expectancies and value for reinforcements soon became the focus of psychology’s cognitive revolution, as exemplified in work by Julian Rotter and Albert Bandura. Simultaneously, especially spawned by the work of Robert White, interest grew in the intrinsic motivations underlying much learning and development, leading to today’s focus on topics such as achievement motivation, personal goals, self-determination, and volition. Across this history we see the important role played by normal science and advancements in methods in both developing and ultimately revealing the limitations of preceding paradigms, leading to systematic growth, as well as ongoing debates within the field.
The mental health and social functioning of millions of forcibly displaced individuals worldwide represents a key public health priority for host governments. This is the first longitudinal study with a representative sample to examine the impact of interpersonal trust and psychological symptoms on community engagement in refugees.
Methods
Participants were 1894 resettled refugees, assessed within 6 months of receiving a permanent visa in Australia, and again 2–3 years later. Variables measured included post-traumatic stress disorder symptoms, depression/anxiety symptoms, interpersonal trust and engagement with refugees’ own and other communities.
Results
A multilevel path analysis was conducted, with the final model evidencing good fit (Comparative Fit Index = 0.97, Tucker–Lewis Index = 0.89, Root Mean Square Error of Approximation = 0.05, Standardized Root-Mean-Square-Residual = 0.05). Findings revealed that high levels of depression symptoms were associated with lower subsequent engagement with refugees’ own communities. In contrast, low levels of interpersonal trust were associated with lower engagement with the host community over the same timeframe.
Conclusions
Findings point to differential pathways to social engagement in the medium-term post-resettlement. Results indicate that depression symptoms are linked to reduced engagement with one's own community, while interpersonal trust is implicated in engagement with the broader community in the host country. These findings have potentially important implications for policy and clinical practice, suggesting that clinical and support services should target psychological symptoms and interpersonal processes when fostering positive adaptation in resettled refugees.
The Arctic marine environment is undergoing a transition from thick multi-year to first-year sea-ice cover with coincident lengthening of the melt season. Such changes are evident in the Baffin Bay-Davis Strait-Labrador Sea (BDL) region where melt onset has occurred ~8 days decade−1 earlier from 1979 to 2015. A series of anomalously early events has occurred since the mid-1990s, overlapping a period of increased upper-air ridging across Greenland and the northwestern North Atlantic. We investigate an extreme early melt event observed in spring 2013. (~6σ below the 1981–2010 melt climatology), with respect to preceding sub-seasonal mid-tropospheric circulation conditions as described by a daily Greenland Blocking Index (GBI). The 40-days prior to the 2013 BDL melt onset are characterized by a persistent, strong 500 hPa anticyclone over the region (GBI >+1 on >75% of days). This circulation pattern advected warm air from northeastern Canada and the northwestern Atlantic poleward onto the thin, first-year sea ice and caused melt ~50 days earlier than normal. The episodic increase in the ridging atmospheric pattern near western Greenland as in 2013, exemplified by large positive GBI values, is an important recent process impacting the atmospheric circulation over a North Atlantic cryosphere undergoing accelerated regional climate change.
Intracranial volume (ICV) has been proposed as a measure of maximum lifetime brain size. Accurate ICV measures require neuroimaging which is not always feasible for epidemiologic investigations. We examined head circumference as a useful surrogate for ICV in older adults.
Methods:
99 older adults underwent Magnetic Resonance Imaging (MRI). ICV was measured by Statistical Parametric Mapping 8 (SPM8) software or Functional MRI of the Brain Software Library (FSL) extraction with manual editing, typically considered the gold standard. Head circumferences were determined using standardized tape measurement. We examined estimated correlation coefficients between head circumference and the two MRI-based ICV measurements.
Results:
Head circumference and ICV by SPM8 were moderately correlated (overall r = 0.73, men r = 0.67, women r = 0.63). Head circumference and ICV by FSL were also moderately correlated (overall r = 0.69, men r = 0.63, women r = 0.49).
Conclusions:
Head circumference measurement was strongly correlated with MRI-derived ICV. Our study presents a simple method to approximate ICV among older patients, which may prove useful as a surrogate for cognitive reserve in large scale epidemiologic studies of cognitive outcomes. This study also suggests the stability of head circumference correlation with ICV throughout the lifespan.
This study introduces a special series on validity studies of the Cognition Battery (CB) from the U.S. National Institutes of Health Toolbox for the Assessment of Neurological and Behavioral Function (NIHTB) (Gershon, Wagster et al., 2013) in an adult sample. This first study in the series describes the sample, each of the seven instruments in the NIHTB-CB briefly, and the general approach to data analysis. Data are provided on test–retest reliability and practice effects, and raw scores (mean, standard deviation, range) are presented for each instrument and the gold standard instruments used to measure construct validity. Accompanying papers provide details on each instrument, including information about instrument development, psychometric properties, age and education effects on performance, and convergent and discriminant construct validity. One study in the series is devoted to a factor analysis of the NIHTB-CB in adults and another describes the psychometric properties of three composite scores derived from the individual measures representing fluid and crystallized abilities and their combination. The NIHTB-CB is designed to provide a brief, comprehensive, common set of measures to allow comparisons among disparate studies and to improve scientific communication. (JINS, 2014, 20, 1–12)