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Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.
Methods
Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.
Results
Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).
Conclusions
Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.
Cardiometabolic disease risk factors are disproportionately prevalent in bipolar disorder (BD) and are associated with cognitive impairment. It is, however, unknown which health risk factors for cardiometabolic disease are relevant to cognition in BD. This study aimed to identify the cardiometabolic disease risk factors that are the most important correlates of cognitive impairment in BD; and to examine whether the nature of the relationships vary between mid and later life.
Methods
Data from the UK Biobank were available for 966 participants with BD, aged between 40 and 69 years. Individual cardiometabolic disease risk factors were initially regressed onto a global cognition score in separate models for the following risk factor domains; (1) health risk behaviors (physical activity, sedentary behavior, smoking, and sleep) and (2) physiological risk factors, stratified into (2a) anthropometric and clinical risk (handgrip strength, body composition, and blood pressure), and (2b) cardiometabolic disease risk biomarkers (CRP, lipid profile, and HbA1c). A final combined multivariate regression model for global cognition was then fitted, including only the predictor variables that were significantly associated with cognition in the previous models.
Results
In the final combined model, lower mentally active and higher passive sedentary behavior, higher levels of physical activity, inadequate sleep duration, higher systolic and lower diastolic blood pressure, and lower handgrip strength were associated with worse global cognition.
Conclusions
Health risk behaviors, as well as blood pressure and muscular strength, are associated with cognitive function in BD, whereas other traditional physiological cardiometabolic disease risk factors are not.
We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.
To determine the proportion of hospitals that implemented 6 leading practices in their antimicrobial stewardship programs (ASPs). Design: Cross-sectional observational survey.
Setting:
Acute-care hospitals.
Participants:
ASP leaders.
Methods:
Advance letters and electronic questionnaires were initiated February 2020. Primary outcomes were percentage of hospitals that (1) implemented facility-specific treatment guidelines (FSTG); (2) performed interactive prospective audit and feedback (PAF) either face-to-face or by telephone; (3) optimized diagnostic testing; (4) measured antibiotic utilization; (5) measured C. difficile infection (CDI); and (6) measured adherence to FSTGs.
Results:
Of 948 hospitals invited, 288 (30.4%) completed the questionnaire. Among them, 82 (28.5%) had <99 beds, 162 (56.3%) had 100–399 beds, and 44 (15.2%) had ≥400+ beds. Also, 230 (79.9%) were healthcare system members. Moreover, 161 hospitals (54.8%) reported implementing FSTGs; 214 (72.4%) performed interactive PAF; 105 (34.9%) implemented procedures to optimize diagnostic testing; 235 (79.8%) measured antibiotic utilization; 258 (88.2%) measured CDI; and 110 (37.1%) measured FSTG adherence. Small hospitals performed less interactive PAF (61.0%; P = .0018). Small and nonsystem hospitals were less likely to optimize diagnostic testing: 25.2% (P = .030) and 21.0% (P = .0077), respectively. Small hospitals were less likely to measure antibiotic utilization (67.8%; P = .0010) and CDI (80.3%; P = .0038). Nonsystem hospitals were less likely to implement FSTGs (34.3%; P < .001).
Conclusions:
Significant variation exists in the adoption of ASP leading practices. A minority of hospitals have taken action to optimize diagnostic testing and measure adherence to FSTGs. Additional efforts are needed to expand adoption of leading practices across all acute-care hospitals with the greatest need in smaller hospitals.
This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
Clinically significant weight gain (CSWG) is associated with increased morbidity and mortality. This study describes CSWG and comorbidities observed in patients with bipolar I disorder (BD-I) and schizophrenia (SZ) after initiating select second-generation antipsychotics (SGAs).
Methods
Percent change in weight, CSWG (=7% weight increase), and incident comorbidities within 12 months of treatment were assessed among patients initiating oral SGAs of moderate-to-high weight gain risk using medical records/claims (OM1 Real-World Data Cloud; January 2013-February 2020). Oral SGAs included clozapine (SZ), iloperidone (SZ), paliperidone (SZ), olanzapine, olanzapine/fluoxetine (BD-I), quetiapine, and risperidone. Outcomes were stratified by baseline body mass index and reported descriptively.
Results
Among patients with BD-I (N = 9142) and SZ (N = 8174), approximately three-quarters were overweight/obese at baseline. During treatment (mean duration = 30 weeks), average percent weight increase was 3.7% (BD-I) and 3.3% (SZ). Average percent weight increase was highest for underweight/normal weight patients (BD-I = 5.5%; SZ = 4.8%), followed by overweight (BD-I = 3.8%; SZ = 3.4%) and obese patients (BD-I = 2.7%; SZ = 2.3%). Within 3 months of treatment, 12% of all patients experienced CSWG. A total of 11.3% (BD-I) and 14.7% (SZ) of patients developed coronary artery disease, hypertension, dyslipidemia, or type 2 diabetes within 12 months of treatment; development of comorbidities was highest among overweight/obese patients and those with CSWG.
Conclusions
Patients who were underweight/normal weight at baseline had the greatest percent change in weight during treatment. Increased comorbidities were observed within 12 months of treatment, specifically among overweight/obese patients and those with CSWG. The magnitude of weight gain and development of comorbidities were similar for patients with BD-I and SZ.
During the late nineteenth and early twentieth centuries, arsenic was used as an embalming agent in the United States. In 1996, Konefes and McGee brought the potential danger of arsenic poisoning during excavation to the attention of archaeologists. They developed methodology that was later refined by the present authors. This article discusses the history of arsenic as an embalming agent, explores socioeconomic and demographic factors that might suggest the presence of arsenic in certain burials, and presents methods for testing arsenic in archaeological contexts. We also discuss environmental impact mitigation considerations and review examples of arsenic testing in archaeological contexts.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
Methods
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.
Results
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).
Conclusions
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.
OBJECTIVES/SPECIFIC AIMS: To create a searchable public registry of all Quality Improvement (QI) projects. To incentivize the medical professionals at UF Health to initiate quality improvement projects by reducing startup burden and providing a path to publishing results. To reduce the review effort performed by the internal review board on projects that are quality improvement Versus research. To foster publication of completed quality improvement projects. To assist the UF Health Sebastian Ferrero Office of Clinical Quality & Patient Safety in managing quality improvement across the hospital system. METHODS/STUDY POPULATION: This project used a variant of the spiral software development model and principles from the ADDIE instructional design process for the creation of a registry that is web based. To understand the current registration process and management of quality projects in the UF Health system a needs assessment was performed with the UF Health Sebastian Ferrero Office of Clinical Quality & Patient Safety to gather project requirements. Biweekly meetings were held between the Quality Improvement office and the Clinical and Translational Science – Informatics and Technology teams during the entire project. Our primary goal was to collect just enough information to answer the basic questions of who is doing which QI project, what department are they from, what are the most basic details about the type of project and who is involved. We also wanted to create incentive in the user group to try to find an existing project to join or to commit the details of their proposed new project to a data registry for others to find to reduce the amount of duplicate QI projects. We created a series of design templates for further customization and feature discovery. We then proceed with the development of the registry using a Python web development framework called Django, which is a technology that powers Pinterest and the Washington Post Web sites. The application is broken down into 2 main components (i) data input, where information is collected from clinical staff, Nurses, Pharmacists, Residents, and Doctors on what quality improvement projects they intend to complete and (ii) project registry, where completed or “registered” projects can be viewed and searched publicly. The registry consists of a quality investigator profile that lists contact information, expertise, and areas of interest. A dashboard allows for the creation and review of quality improvement projects. A search function enables certain quality project details to be publicly accessible to encourage collaboration. We developed the Registry Matching Algorithm which is based on the Jaccard similarity coefficient that uses quality project features to find similar quality projects. The algorithm allows for quality investigators to find existing or previous quality improvement projects to encourage collaboration and to reduce repeat projects. We also developed the QIPR Approver Algorithm that guides the investigator through a series of questions that allows an appropriate quality project to get approved to start without the need for human intervention. RESULTS/ANTICIPATED RESULTS: A product of this project is an open source software package that is freely available on GitHub for distribution to other health systems under the Apache 2.0 open source license. Adoption of the Quality Improvement Project Registry and promotion of it to the intended audience are important factors for the success of this registry. Thanks goes to the UW-Madison and their QI/Program Evaluation Self-Certification Tool (https://uwmadison.co1.qualtrics.com/SE/?SID=SV_3lVeNuKe8FhKc73) used as example and inspiration for this project. DISCUSSION/SIGNIFICANCE OF IMPACT: This registry was created to help understand the impact of improved management of quality projects in a hospital system. The ultimate result will be to reduce time to approve quality improvement projects, increase collaboration across the UF Health Hospital system, reduce redundancy of quality improvement projects and translate more projects into publications.
Children with CHD and acquired heart disease have unique, high-risk physiology. They may have a higher risk of adverse tracheal-intubation-associated events, as compared with children with non-cardiac disease.
Materials and methods
We sought to evaluate the occurrence of adverse tracheal-intubation-associated events in children with cardiac disease compared to children with non-cardiac disease. A retrospective analysis of tracheal intubations from 38 international paediatric ICUs was performed using the National Emergency Airway Registry for Children (NEAR4KIDS) quality improvement registry. The primary outcome was the occurrence of any tracheal-intubation-associated event. Secondary outcomes included the occurrence of severe tracheal-intubation-associated events, multiple intubation attempts, and oxygen desaturation.
Results
A total of 8851 intubations were reported between July, 2012 and March, 2016. Cardiac patients were younger, more likely to have haemodynamic instability, and less likely to have respiratory failure as an indication. The overall frequency of tracheal-intubation-associated events was not different (cardiac: 17% versus non-cardiac: 16%, p=0.13), nor was the rate of severe tracheal-intubation-associated events (cardiac: 7% versus non-cardiac: 6%, p=0.11). Tracheal-intubation-associated cardiac arrest occurred more often in cardiac patients (2.80 versus 1.28%; p<0.001), even after adjusting for patient and provider differences (adjusted odds ratio 1.79; p=0.03). Multiple intubation attempts occurred less often in cardiac patients (p=0.04), and oxygen desaturations occurred more often, even after excluding patients with cyanotic heart disease.
Conclusions
The overall incidence of adverse tracheal-intubation-associated events in cardiac patients was not different from that in non-cardiac patients. However, the presence of a cardiac diagnosis was associated with a higher occurrence of both tracheal-intubation-associated cardiac arrest and oxygen desaturation.
The government publishes 3 different public report surgical site infection (SSI) metrics, all called standardized infection ratios (SIRs), that impact perceived hospital quality. We conducted a non-random cross-sectional observational pilot study of 20 California hospitals that voluntarily submitted colon surgery and SSI data. Discordant SIR values, leading to contradictory conclusions, occurred in 35% of these hospitals.
Recurring associations of the trilobite ichnogenus Rusophycus with various “worm” burrows suggest an interaction between the two tracemakers, specifically, capture of the worm by the trilobite. An exceptional ichnofossil from the Upper Ordovician of southwestern Ohio shows characters consistent with previously described “trilobite hunting burrows” from Cambrian and Silurian strata. Preserved in convex hyporelief is R. carleyi, attributable to the trilobite Isotelus, on which is superimposed the case of a worm burrow of the ichnogenus Palaeophycus. The cast of the worm burrow appears to have been truncated by the digging activities of the trilobite, suggesting its predation of the worm. The exquisite preservation of ventral axial morphology of the trilobite distinguishes this Rusophycus from simpler bilobate forms attributable to filter-feeding behavior. Congruency in the preservation of worm and trilobite trace supports the conclusion that both were created at the same time, as the trilobite exited the intrastratal burrow. This is the first report of a trilobite hunting burrow from the Ordovician, and the first evidence for predatory behavior for the trilobite genus Isotelus.
A consensus conference on the reasons for the undertreatment of depression was organized by the National Depressive and Manic Depressive Association (NDMDA) on January 17–18,1996. The target audience included health policymakers, clinicians, patients and their families, and the public at large. Six key questions were addressed: (1) Is depression undertreated in the community and in the clinic? (2) What is the economic cost to society of depression? (3) What have been the efforts in the past to redress undertreatment and how successful have they been? (4) What are the reasons for the gap between our knowledge of the diagnosis and treatment of depression and actual treatment received in this country? (5) What can we do to narrow this gap? (6) What can we do immediately to narrow this gap?
Activists try to use high profile trials to advance their political agendas, and we want to understand why they occasionally succeed in promoting policy reforms. We begin by reviewing literature on agenda setting and social problem construction, conceptualising high profile trials as “focusing events” that offer activists a chance to advance their definitions and remedies for particular social problems. We next outline the feminist movement against sexual violence as a useful example of activists trying to use trials for their own political purposes. Using events data from the New York Times and the secondary treatment of 13 high profile trials from 1960 to 1997, we examine factors that help or hinder activists’ efforts to use a trial to forward their cause. We see that both the nature of the trial and the political context surrounding it affect the likelihood that a movement gains control of its meaning and secures policy reform.