Critical analysis of the confounding of clinical trials

To provide a comprehensive overview of issues confounding clinical trials, Chapter 2 will discuss the parties involved in the research and development of medications and detail the individual responsibilities of each. However, the ambition of these individual entities often produces a conflict of interest especially when profits are involved [9]. Organizations and individuals such as insurance corporations, pharmaceutical companies (sponsors), pharmacy benefit managers, investigators (doctors/medical professionals) and most importantly patients, are all involved in carrying out clinical research and have definitive responsibilities they are required to follow for unbiased results. However, many rules are overlooked and biases go unrecorded causing the “good” in these institutions to be marred with unethical behavior and unreliable results [1]. After the completion of this section, the biases each entity, including investigators, can and do bring about in the clinical research process will be clear. It is sometimes not particularly obvious as to how selection bias can occur therefore the means of confounding trials by investigators is discussed in Chapter 3. Chapter 4 will provide a critical analysis of the randomized clinical trial quality guidelines presented in the Consolidated Standards of Reporting Trials (CONSORT) Statement. This document serves to increase the accuracy and precision of results reporting of clinical trial results, however does not include repercussions for falsely recording data. Real trials where biasing events have occurred and caused the confounding of trials continue to be published despite the existence of such guidelines. Some of these trials proceed further, in some cases to be fully published and accessible to the public, with no adequate consequences or repercussions. Even if there are consequences for biasing actions, they are not sufficient or efficient enough to ensure the protection of patients exposed to biased studies or the results of such studies. Critical analysis of these “guidelines,” requires familiarity with current standards for the conduct of clinical trials in the Consolidated Standards of Reporting Trials (CONSORT) statement introduced in this chapter. Lastly, Chapter 5 will propose and detail a new selection bias detection mechanism entitled the rank correlation coefficient

CRYSTALLOIDS OR COLLOIDS… WHAT’S IN YOUR IV? Determining Fluid Type for Septic Shock Resuscitation

Objective: To compare the efficacy of crystalloid versus colloid solutions, specifically normal saline versus albumin, in decreasing mortality among patients with septic shock requiring resuscitation fluids in the intensive care unit (ICU) setting. Design: Systematic literature review. Methods: Research was conducted in PubMed and UpToDate, utilizing the search terms sepsis, septic shock, fluid resuscitation, colloids and crystalloids. Specifically, in PubMed, the following limits and terms were used: randomized control trial, human subjects, English, and within the last 7 years. Results: The Annane et al study found no significant difference in colloid fluid resuscitation versus crystalloid fluid resuscitation in the decreasing 28-day mortality in hypovolemic shock patients specifically in the ICU setting. The Finfer et al study found no significant difference between albumin and normal saline when assessing 28-day mortality and morbidity for patients in the ICU with severe sepsis. The Caironi et al study found no significant difference in albumin and crystalloids co-administration compared to crystalloids alone in 28-day mortality and morbidity outcomes for those with septic shock admitted to the ICU. Conclusion: The choice of fluid in aggressive resuscitation has no significant effect on patient mortality in those with septic shock in the intensive care unit (ICU)

Development and implementation of the ECHO model in a school setting to address youth electronic cigarette use in Kansas: A protocol

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Introduction: Schools remain at the frontlines of addressing issues, such as e-cigarette use, that impact students. Despite e-cigarette use remaining a significant public health concern in the U.S., schools have limited resources (e.g., staff, capacity, programming) to address it, especially in rural and frontier areas. This ECHO Pilot Project aimed to build capacity and equip schools and school staff in the state of Kansas to address high rates of youth e-cigarette use by providing prevention support and information on best practices for e-cigarette cessation. Methods and analysis: The pilot used the established Project ECHO model to disseminate evidence-based strategies for e-cigarette prevention and cessation among youth to schools across Kansas. The pilot selected 20 interdisciplinary school teams representing both rural and urban middle and high schools across the state to participate in seven ECHO sessions. ECHO sessions proceeded throughout Fall 2021, with the final session in Spring 2022. School participants completed pre-post surveys as well as component-specific surveys following each ECHO session. In addition, each school team created an individualized action plan to comprehensively address e-cigarette use at their school based on the information provided throughout the ECHO. Survey data, school tobacco/nicotine policies, and action plans will be analyzed to assess process and final outcomes. Discussion: If successful, this pilot will demonstrate that the ECHO model is an effective platform for building school staff knowledge and skills to implement evidence-based strategies in both urban and rural settings. It is anticipated that the pilot will build capacity and equip schools and school staff to address high rates of youth e-cigarette use by providing support for school-based prevention programs and referrals for e-cigarette cessation which will lessen the burden of nicotine-related problems in Kansas schools and communities. Finally, the pilot will provide evidence that the ECHO model can be successfully and equitably applied in a school setting and may be a viable method for addressing other public health-related issues faced by schools

Variation in Mycobacterium bovis genetic richness suggests that inwards cattle movements are a more important source of infection in beef herds than in dairy herds

Publication history: Accepted - 25 June 2019; Published online - July 2019Background We used genetic Multi-Locus VNTR Analysis (MLVA) data gathered from surveillance efforts to better understand the ongoing bovine tuberculosis (bTB) epidemic in Northern Irish cattle herds. We modelled the factors associated with Mycobacterium bovis MLVA genotype richness at three analytical scales; breakdown level, herd level, and patch level, and compared the results between dairy and non-dairy production types. Results In 83% of breakdowns and in 63% of herds, a single MLVA genotype was isolated. Five or more MLVA genotypes were found in less than 3 % of herds. Herd size and the total number of reactors were important explanatory variables, suggesting that increasing MLVA genotype richness was positively related to increases in the number of host animals. Despite their smaller relative size, however, the highest MLVA genotype richness values were observed in non-dairy herds. Increasing inwards cattle movements were important positive predictors of MLVA genotype richness, but mainly in non-dairy settings. Conclusions The principal finding is that low MLVA genotype richness indicates that small-scale epidemics, e.g. wildlife, contiguous farms, and within-herd recrudescence, are important routes of M. bovis infection in cattle herds. We hypothesise that these mechanisms will maintain, but may not explicitly increase, MLVA genotype richness. The presence of elevated MLVA richness is relatively rare and likely indicates beef fattening enterprises, which purchase cattle from over long distances. Cattle movements were furthermore an important predictor of MLVA genotype richness in non-dairy herds, but not in dairy herds; this may represent reduced cattle purchasing levels in dairy enterprises, compared to beef. These observations allude to the relative contribution of different routes of bTB infection between production types; we posit that infection associated with local factors may be more evident in dairy herds than beef herds, however in beef herds, inwards movements offer additional opportunities for introducing M. bovis into the herd

The Iowa Homemaker vol.3, no.2

Table of Contents It Is Not Always May by Maybelle A. Payton, page 1 The Why of a Home Economics Course by Florence Busse, page 2 Why I Came to Iowa State compiled by Clara Jordan, page 2 Picnic Ingredients by Grata Thorn, page 3 Iowa State Women Attend Voters’ Convention by Eleanor Murray and Jeanette Beyer, page 4 A Modern Version of the Hope Box by N. Beth Bailey, page 5 A Summer Living Room by Mildred Boyt, page 7 Canning Early Fruits and Vegetables by Helen G. Lamb, page 8 Hazards of Bird Life by J. E. Guthrie, page 9 Nile Styles by Harriett Schleiter, page 10 Shall Mother Have a Vacation? by Eda Lord Murphy, page 10 The Fallacy of An Expensive Standard of Living by Claude L. Benner, page 11 What Shall We Take? by Lucille Barta, page 12 Who’s There and Where by Helen Reidy, page 1

DYNamic assessment of multi‐organ level dysfunction in patients recovering from COVID‐19: DYNAMO COVID‐19

We evaluated the impacts of COVID‐19 on multi‐organ and metabolic function in patients following severe hospitalised infection compared to controls. Patients (n = 21) without previous diabetes, cardiovascular or cerebrovascular disease were recruited 5–7 months post‐discharge alongside controls (n = 10) with similar age, sex and body mass. Perceived fatigue was estimated (Fatigue Severity Scale) and the following were conducted: oral glucose tolerance (OGTT) alongside whole‐body fuel oxidation, validated magnetic resonance imaging and spectroscopy during resting and supine controlled exercise, dual‐energy X‐ray absorptiometry, short physical performance battery (SPPB), intra‐muscular electromyography, quadriceps strength and fatigability, and daily step‐count. There was a greater insulin response (incremental area under the curve, median (inter‐quartile range)) during the OGTT in patients [18,289 (12,497–27,448) mIU/min/L] versus controls [8655 (7948–11,040) mIU/min/L], P < 0.001. Blood glucose response and fasting and post‐prandial fuel oxidation rates were not different. This greater insulin resistance was not explained by differences in systemic inflammation or whole‐body/regional adiposity, but step‐count (P = 0.07) and SPPB scores (P = 0.004) were lower in patients. Liver volume was 28% greater in patients than controls, and fat fraction adjusted liver T1, a measure of inflammation, was raised in patients. Patients displayed greater perceived fatigue scores, though leg muscle volume, strength, force‐loss, motor unit properties and post‐exercise muscle phosphocreatine resynthesis were comparable. Further, cardiac and cerebral architecture and function (at rest and on exercise) were not different. In this cross‐sectional study, individuals without known previous morbidity who survived severe COVID‐19 exhibited greater insulin resistance, pointing to a need for physical function intervention in recovery

Neuroinvasion and Neurotropism by SARS-CoV-2 Variants in the K18-hACE2 Mouse

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) not only affects the respiratory tract but also causes neurological symptoms such as loss of smell and taste, headache, fatigue or severe cerebrovascular complications. Using transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2), we investigated the spatiotemporal distribution and pathomorphological features in the CNS following intranasal infection with SARS-CoV-2 variants, as well as after prior influenza A virus infection. Apart from Omicron, we found all variants to frequently spread to and within the CNS. Infection was restricted to neurons and appeared to spread from the olfactory bulb mainly in basally oriented regions in the brain and into the spinal cord, independent of ACE2 expression and without evidence of neuronal cell death, axonal damage or demyelination. However, microglial activation, microgliosis and a mild macrophage and T cell dominated inflammatory response was consistently observed, accompanied by apoptotic death of endothelial, microglial and immune cells, without their apparent infection. Microgliosis and immune cell apoptosis indicate a potential role of microglia for pathogenesis and viral effect in COVID-19 and the possible impairment of neurological functions, especially in long COVID. These data may also be informative for the selection of therapeutic candidates and broadly support the investigation of agents with adequate penetration into relevant regions of the CNS

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges