Antibiotic prescriptions upon hospital discharge: A blind spot of antimicrobial stewardship

Background: Transitions of care are a known source of patient vulnerability. The incidence of medication errors during transitions of care is well-documented.1 Discharge from the hospital has proven to be one area where antimicrobial stewardship is absent or lacking and can result in: poor clinical outcomes, adverse drug events, and emergence of multidrug resistant organisms. In one study, 53% of cases reviewed found antibiotics prescribed at discharge were inappropriate.1 Large discrepancies exist between guideline recommendations and antimicrobials prescribed upon hospital discharge.2 At this time, no prior study at OSU Medical Center has analyzed the impact of antimicrobial stewardship at hospital discharge.Methods: This study will be a retrospective chart review based on a report of patients age 18 years and older discharged from OSUMC from 7/1/2018 to 6/30/2019 with CAP or uncomplicated UTI. This data will be used to determine whether optimal antibiotic therapy was prescribed upon hospital discharge. Optimal therapy is defined as: prescription in accordance with nationally-approved guidelines for the management of CAP and UTI; effective and narrowest spectrum of activity; correct dose for indication, organ dysfunction, and medication allergies; and correct duration of therapy. This study will also the assess antibiotic classes most frequently involved in errors, as well as the most commonly occurring types of errors (incorrect drug, dose, or duration). Patients with multiple types of infection will be excluded from the study. Data collected will be organized and evaluated using REDCapTM. The following data will be obtained: date of discharge, days of optimal inpatient antibiotic therapy, discharge antibiotics regimen, infection type (CAP vs. uncomplicated UTI), pertinent laboratory and microbiology data, and bacteria cultured with source and date results finalized.Results: Data collection is still ongoing. At this time, 1402 patient charts have been reviewed, and 168 patient charts met inclusion criteria. Of those included, patients were primarily female (63%) with an average age of 62 (range 21-95), and 43% were discharged on a suboptimal antibiotic regimen. The most common reason for a suboptimal regimen was an inappropriate duration of therapy (92%) followed by an incorrect medication dose (26%).Conclusions: At the time of this writing, duration of therapy far outweighs any other cause for a suboptimal discharge antibiotic regimen. By completing this study, we hope to gain more insight into how we can better serve our institution by educating physicians, reducing errors, and optimizing transitions of care

Trajectory of Substance Use Disorders and Collegiate Recovery in Emerging Adults

Abstract Collegiate Recovery Programs (CRPs) provide services to support emerging adults achieve academic success, while maintaining substance use disorder recovery. College and university campuses can often be considered abstinence-hostile environments, giving rise to the need of support services for students in recovery. A nationwide survey to understand the efficacy of services provided by CRPs was conducted to assess the demographics and academic profiles of students involved with CRPs. Co-occurring disorders including mental health issues, criminal histories, utilizations of recovery services and 12-step groups, and work histories of students were also assessed. CRPs can provide services and an environment to students that increase recovery capital domains. Recovery capital domains such as spirituality, health and wellness, academics, critical thinking and discernment, personal achievement, and service opportunities may be related to metrics of academic success such as grade point average. However, measuring success for those in substance use disorder recovery through academics metrics alone could present a barrier to improving recovery services. Assessing the effectiveness of CRP programs through the lens of recovery capital offers a strengths-based, wholistic approach to improving services for students in recovery. Future directions include administering comprehensive measurements for recovery success, in addition to academic metrics, for students that are members of CRP. Keywords: Substance Use Recovery; Emerging Adults; Collegiate Recovery Program

Average Household Exposure to Newspaper Coverage about the Harmful Effects of Hormone Therapy and Population-Based Declines in Hormone Therapy Use

BACKGROUND: The news media facilitated the rapid dissemination of the findings from the estrogen plus progestin therapy arm of the Women’s Health Initiative (EPT-WHI). OBJECTIVE: To examine the relationship between the potential exposure to newspaper coverage and subsequent hormone therapy (HT) use. DESIGN/POPULATION: Population-based cohort of women receiving mammography at 7 sites (327,144 postmenopausal women). MEASUREMENTS: The outcome was the monthly prevalence of self-reported HT use. Circulation data for local, regional, and national newspapers was used to create zip-code level measures of the estimated average household exposure to newspaper coverage that reported the harmful effects of HT in July 2002. RESULTS: Women had an average potential household exposure of 1.4 articles. There was substantial variation in the level of average household exposure to newspaper coverage; women from rural sites received less than women from urban sites. Use of HT declined for all average potential exposure groups after the publication of the EPT-WHI. HT prevalence among women who lived in areas where there was an average household exposure of at least 3 articles declined significantly more (45 to 27%) compared to women who lived in areas with <1 article (43 to 31%) during each of the subsequent 5 months (relative risks 0.86–0.92; p < .006 for all). CONCLUSIONS: Greater average household exposure to newspaper coverage about the harms associated with HT was associated with a large population-based decline in HT use. Further studies should examine whether media coverage directly influences the health behavior of individual women

Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Multidimensional signals and analytic flexibility: Estimating degrees of freedom in human speech analyses

Recent empirical studies have highlighted the large degree of analytic flexibility in data analysis which can lead to substantially different conclusions based on the same data set. Thus, researchers have expressed their concerns that these researcher degrees of freedom might facilitate bias and can lead to claims that do not stand the test of time. Even greater flexibility is to be expected in fields in which the primary data lend themselves to a variety of possible operationalizations. The multidimensional, temporally extended nature of speech constitutes an ideal testing ground for assessing the variability in analytic approaches, which derives not only from aspects of statistical modeling, but also from decisions regarding the quantification of the measured behavior. In the present study, we gave the same speech production data set to 46 teams of researchers and asked them to answer the same research question, resulting insubstantial variability in reported effect sizes and their interpretation. Using Bayesian meta-analytic tools, we further find little to no evidence that the observed variability can be explained by analysts’ prior beliefs, expertise or the perceived quality of their analyses. In light of this idiosyncratic variability, we recommend that researchers more transparently share details of their analysis, strengthen the link between theoretical construct and quantitative system and calibrate their (un)certainty in their conclusions

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Perceptions of Substance Use as a Motivator to Use Substances

Abstract Understanding motivations of young adults to initiate substance use is important to tailor prevention and intervention efforts to reduce risk of long-term consequences such as addiction and mental health disorders. Previous studies have shown that there is a genetic and social component to adolescent and young adult substance use disorders (SUDs). For example, a longitudinal case-controlled studies of both genders done by Yule et.al showed a strong correlation between exposure to maternal SUDs and an increase in SUDs in their children with and without ADHD. Other studies have shown the effects of parental use, social interactions, and brain development to conclude that those around substance use and receiving peer pressure from those who use substances will be at an increased risk (O’Brien and Hill, 2019). Articles by Arria et.al and King and Chassin showed through using data to represent a national sample and an ongoing longitudinal study that there are environmental factors that increase the risk of adolescent and young adult substance use. In households with lower levels of disciplinary action, lack of control, and decreased behavioral control there is an increased chance of adolescent and young adult SUDs with or without parental SUDs. However, a survey study by Hoth concluded that there was no connection between parent-child SU instead there was a higher correlation between peer substance use and adolescent and young adult SUDs. Though these studies prove that there is an increased chance of young adult SUDs due to parental SUDs there is a gap in the research in identifying how child SU and perceptions of SU are influenced by parental SU. Even though young adults will develop a SUD due to their parents, some of their perceptions might change their perceptions to initiate substance use and needs further exploration. Key Words: Addiction, Heritability, Motivations for Substance Use, Substance Use Disorder, Substance Us