Implementation of an Extubation Readiness Guideline for Preterm Infants.

BACKGROUND: Intubated preterm infants 32 6 / 7 weeks or less of gestation in a mid-Atlantic level IV neonatal intensive care unit (NICU) faced a high number of ventilator days. Based on 6 weeks of electronic health record (EHR) chart audits of extubations in this NICU in 2021, 44% of preterm infants 32 6 / 7 weeks or less of gestation were intubated for more than 28 days, with an average of 23 days on a ventilator. This NICU lacked a standardized extubation guideline providing criteria to drive extubation eligibility. PURPOSE: The purpose of this quality improvement (QI) project was to implement and evaluate the effectiveness of an extubation readiness guideline in preterm infants 32 6 / 7 weeks or less of gestation in a mid-Atlantic level IV NICU. METHODS: This project occurred over a 17-week period in 2021. Implementation included a multidisciplinary committee formation, identification of champions, NICU staff education, completion of a guideline checklist by bedside nursing (for eligible patients), clinician reminders, and chart audits for collection of pre-/postimplementation data. Staff education completion, guideline use and compliance, demographic patient data, ventilator days, time to first extubation, and need for reintubation were tracked. RESULTS: Postimplementation data indicated decreased need for intubation for more than 28 days, ventilator days, and days to first extubation attempt. IMPLICATIONS FOR PRACTICE AND RESEARCH: Results suggested that implementation of the evidence-based guideline was effective in decreasing average total ventilator days for preterm infants 32 6 / 7 weeks or less of gestation.

Improving Safe Infant Sleep Compliance Through Implementation of a Safe Sleep Bundle.

BACKGROUND: Sleep-related infant deaths continue to be a significant public health issue that nondiscriminately impacts family units with increased risk notably in premature infants discharged home from the neonatal intensive care unit (NICU). The American Academy of Pediatrics endorses the use of safe sleep practices with specific recognition of the unique challenges faced in the NICU setting. PURPOSE: The purpose of this quality improvement (QI) project was to implement a safe sleep bundle and evaluate its effectiveness in improving caregiver compliance to safe sleep practices in a level III NICU at a large joint military medical facility. METHODS: A QI initiative with a pre- and postanalysis was performed using a convenience method of sampling. Infants 32 weeks or more post-menstrual age in a level III NICU were analyzed pre- and post-interventions. The intervention included a safe sleep bundle that encompassed: (1) policy update, (2) standardized sleep sacks, (3) crib cards and certificates, and (4) creation of a provider order set in the electronic health record (EHR). A standardized crib audit tool evaluated sleep and bed position, items in the crib, order set in the EHR with consideration of special medical circumstances. RESULTS: Postintervention assessment after the implementation resulted in a significant improvement of overall safe sleep compliance modeled by NICU staff, increasing to 100% from a baseline of 18% pre-intervention (P = .029). IMPLICATIONS FOR PRACTICE AND RESEARCH: Role-modeling behaviors of clinical staff may reduce the risk of sleep-related infant deaths upon discharge. A multifactorial approach can leverage successful strategies for improving safe sleep compliance in a NICU setting.

Patient-reported outcome measures in MS: Do development processes and patient involvement support valid quantification of clinically important variables?

Background: Patient-reported outcomes (PROs) are widely measured in multiple sclerosis (MS) studies. However, the quality of instrument development processes varies, raising concerns about the meaningfulness of associated data. Objectives: To review the development of selected PROs commonly used in MS studies, including definitions of the concepts measured, use of conceptual frameworks, and degree of input from people living with MS (PlwMS). To gain insights and recommendations from PlwMS on their experience with these PROs. Methods: We assessed 6 PROs (FSIQ-RMS, modified-FIS, MSQoL-54, Leeds 8-item MSQoL, MSIS-29 and EQ-5D) for alignment with regulatory and scientific requirements on PRO structure/development. PlwMS evaluated the degree to which the PROs reflect disease aspects they perceive important. Results: Definitions, clarifications and conceptualisations of the measurement variables were often lacking. PlwMS were variably involved in PRO development. Ethnic diversity was rarely documented. PlwMS identified individualisation, ease of understanding, time burden, and mode of administration as factors affecting PRO usability. Conclusions: To date, the PRO development process has consistently lacked clear definitions of concepts of interest, use of conceptual frameworks and patient involvement, thereby compromising the validity of data they generate. PRO instrument development must be conducted more robustly to maximise the value of pivotal clinical trials.

Autonomy-connection tensions, stress, and attachment: The case of COVID-19.

The COVID pandemic, and actions taken by governments worldwide to deal with it, have placed stress on couple relationships. Reports from many countries have documented substantial increases in relationship difficulties, conflict, and violence. We propose that issues concerning autonomy and connection are central to these problems, particularly as couples face changing situations with regard to lockdowns, social distancing, and border closures. We further propose that a fruitful approach to understanding these difficulties comes from integrating attachment theory with key concepts of stress and coping theories. Based on these principles and concepts, emotionally focused couples therapy (EFT) offers guidelines to help couples navigate the multiple stressors associated with the pandemic.

Approaches to Test the Neurotoxicity of Environmental Contaminants in the Zebrafish Model: From Behavior to Molecular Mechanisms.

The occurrence of neuroactive chemicals in the aquatic environment is on the rise and poses a potential threat to aquatic biota of currently unpredictable outcome. In particular, subtle changes caused by these chemicals to an organism's sensation or behavior are difficult to tackle with current test systems that focus on rodents or with in vitro test systems that omit whole-animal responses. In recent years, the zebrafish (Danio rerio) has become a popular model organism for toxicological studies and testing strategies, such as the standardized use of zebrafish early life stages in the Organisation for Economic Co-operation and Development's guideline 236. In terms of neurotoxicity, the zebrafish provides a powerful model to investigate changes to the nervous system from several different angles, offering the ability to tackle the mechanisms of action of chemicals in detail. The mechanistic understanding gained through the analysis of this model species provides a good basic knowledge of how neuroactive chemicals might interact with a teleost nervous system. Such information can help infer potential effects occurring to other species exposed to neuroactive chemicals in their aquatic environment and predicting potential risks of a chemical for the aquatic ecosystem. In the present article, we highlight approaches ranging from behavioral to structural, functional, and molecular analysis of the larval zebrafish nervous system, providing a holistic view of potential neurotoxic outcomes. Environ Toxicol Chem 2021;40:989-1006. © 2020 SETAC.

Hypoxia modifies the response to flutamide and linuron in male three-spined stickleback (Gasterosteus aculeatus).

Hypoxia is a major stressor in aquatic environments and it is frequently linked with excess nutrients resulting from sewage effluent discharges and agricultural runoff, which often also contain complex mixtures of chemicals. Despite this, interactions between hypoxia and chemical toxicity are poorly understood. We exposed male three-spined stickleback during the onset of sexual maturation to a model anti-androgen (flutamide; 250 µg/L) and a pesticide with anti-androgenic activity (linuron; 250 µg/L), under either 97% or 56% air saturation (AS). We assessed the effects of each chemical, alone and in combination with reduced oxygen concentration, by measuring the transcription of spiggin in the kidney, as a marker of androgen signalling, and 11 genes in the liver involved in some of the molecular pathways hypothesised to be affected by the exposures. Spiggin transcription was strongly inhibited by flutamide under both AS conditions. In contrast, for linuron, a strong inhibition of spiggin was observed under 97% AS, but this effect was supressed under reduced air saturation, likely due to interactions between the hypoxia inducible factor and the aryl hydrocarbon receptor (AhR) pathways. In the liver, hypoxia inducible factor 1α was induced following exposure to both flutamide and linuron, however this was independent of the level of air saturation. This work illustrates the potential for interactions between hypoxia and pollutants with endocrine or AhR agonist activity to occur, with implications for risk assessment and management.

Hydronephrosis Due to Bilateral Tubo-ovarian Abscess.

A 27-year-old female presented to the emergency department with fevers, nausea, chills, and non-specific bilateral lower quadrant abdominal pain. A pregnancy test was negative. Computed tomography demonstrated moderate left hydronephrosis secondary to tubo-ovarian abscess (TOA). The abscess was so large it distorted local anatomy and compressed the ureters. She was prescribed merepenem and admitted for care by obstetrics/gynecology.

Sublethal exposure to copper supresses the ability to acclimate to hypoxia in a model fish species.

Hypoxia is one of the major threats to biodiversity in aquatic systems. The association of hypoxia with nutrient-rich effluent input into aquatic systems results in scenarios where hypoxic waters could be contaminated with a wide range of chemicals, including metals. Despite this, little is known about the ability of fish to respond to hypoxia when exposures occur in the presence of environmental toxicants. We address this knowledge gap by investigating the effects of exposures to different levels of oxygen in the presence or absence of copper using the three-spined sticklebacks (Gasterosteus aculeatus) model. Fish were exposed to different air saturations (AS; 100%, 75% and 50%) in combination with copper (20 µg/L) over a 4 day period. The critical oxygen level (Pcrit), an indicator of acute hypoxia tolerance, was 54.64 ± 2.51% AS under control conditions, and 36.21 ± 2.14% when fish were chronically exposed to hypoxia (50% AS) for 4 days, revealing the ability of fish to acclimate to low oxygen conditions. Importantly, the additional exposure to copper (20 µg/L) prevented this improvement in Pcrit, impairing hypoxia acclimation. In addition, an increase in ventilation rate was observed for combined copper and hypoxia exposure, compared to the single stressors or the controls. Interestingly, in the groups exposed to copper, a large increase in variation in the measured Pcrit was observed between individuals, both under normoxic and hypoxic conditions. This variation, if observed in wild populations, may lead to selection for a tolerant phenotype and alterations in the gene pool of the populations, with consequences for their sustainability. Our findings provide strong evidence that copper reduces the capacity of fish to respond to hypoxia by preventing acclimation and will inform predictions of the consequences of global increases of hypoxia in water systems affected by other pollutants worldwide.

New insights into organ-specific oxidative stress mechanisms using a novel biosensor zebrafish.

BACKGROUND: Reactive oxygen species (ROS) arise as a result from, and are essential in, numerous cellular processes. ROS, however, are highly reactive and if left unneutralised by endogenous antioxidant systems, can result in extensive cellular damage and/or pathogenesis. In addition, exposure to a wide range of environmental stressors can also result in surplus ROS production leading to oxidative stress (OS) and downstream tissue toxicity. OBJECTIVES: Our aim was to produce a stable transgenic zebrafish line, unrestricted by tissue-specific gene regulation, which was capable of providing a whole organismal, real-time read-out of tissue-specific OS following exposure to a wide range of OS-inducing environmental contaminants and conditions. This model could, therefore, serve as a sensitive and specific mechanistic in vivo biomarker for all environmental conditions that result in OS. METHODS: To achieve this aim, we exploited the pivotal role of the electrophile response element (EpRE) as a globally-acting master regulator of the cellular response to OS. To test tissue specificity and quantitative capacity, we selected a range of chemical contaminants known to induce OS in specific organs or tissues, and assessed dose-responsiveness in each using microscopic measures of mCherry fluorescence intensity. RESULTS: We produced the first stable transgenic zebrafish line Tg (3EpRE:hsp70:mCherry) with high sensitivity for the detection of cellular RedOx imbalances, in vivo in near-real time. We applied this new model to quantify OS after exposure to a range of environmental conditions with high resolution and provided quantification both of compound- and tissue-specific ROS-induced toxicity. DISCUSSION: Our model has an extremely diverse range of potential applications not only for biomonitoring of toxicants in aqueous environments, but also in biomedicine for identifying ROS-mediated mechanisms involved in the progression of a number of important human diseases, including cancer.

Prevalence of Post-Traumatic Stress Disorder in Emergency Physicians in the United States.

INTRODUCTION: There is increasing concern about the effects of occupational stressors on the wellness of healthcare providers. Given high patient acuity, circadian rhythm disruption, and other workplace stressors, emergency physicians (EP) would be predicted to have high rates of occupational stress. We conducted this study to assess the prevalence of post-traumatic stress disorder (PTSD) in attending EPs practicing in the United States. METHODS: A link to an electronic questionnaire was distributed through the emergency medicine-centric publication Emergency Medicine News. We compared the prevalence of PTSD in EPs to the general population using a chi-square goodness of fit test, and performed logistic regression to assess for significance of risk factors. RESULTS: We received survey responses from 526 persons. In this study, EPs had a PTSD point prevalence of 15.8%. Being a victim of a prior trauma or abuse is the primary predictor of PTSD (odds ratio [OR] [95% confidence interval {CI}, 2.16 (1.21 - 3.86)], p = 0.009) and PTSD severity score (OR [95% CI, 1.16 (1.07 - 1.26)], p <0.001). CONCLUSION: Emergency physicians have a substantial burden of PTSD, potentially jeopardizing their own health and career longevity. Future studies should focus on identifying subgroups at higher risk for PTSD and modifiable risk factors. Prevention and treatment strategies should be developed and tested in healthcare providers.

Emergence of consistent intra-individual locomotor patterns during zebrafish development.

The analysis of larval zebrafish locomotor behavior has emerged as a powerful indicator of perturbations in the nervous system and is used in many fields of research, including neuroscience, toxicology and drug discovery. The behavior of larval zebrafish however, is highly variable, resulting in the use of large numbers of animals and the inability to detect small effects. In this study, we analyzed whether individual locomotor behavior is stable over development and whether behavioral parameters correlate with physiological and morphological features, with the aim of better understanding the variability and predictability of larval locomotor behavior. Our results reveal that locomotor activity of an individual larva remains consistent throughout a given day and is predictable throughout larval development, especially during dark phases, under which larvae demonstrate light-searching behaviors and increased activity. The larvae's response to startle-stimuli was found to be unpredictable, with no correlation found between response strength and locomotor activity. Furthermore, locomotor activity was not associated with physiological or morphological features of a larva (resting heart rate, body length, size of the swim bladder). Overall, our findings highlight the areas of intra-individual consistency, which could be used to improve the sensitivity of assays using zebrafish locomotor activity as an endpoint.

Munson's Sign: An Obvious Finding to Explain Acute Vision Loss.

Keratoconus is a progressive disorder affecting the cornea, which causes the cornea to become weakened and conical in appearance. The resultant decrease in structural integrity of the cornea predisposes affected individuals to acute corneal hydrops, a break in Descemet's membrane, the deepest layer of the cornea, resulting in pain and acute vision loss. We present here a case of this little-known cause of acute vision loss, and an example of Munson's sign, which is a v-shaped protrusion of the lower eyelid on downward gaze that is characteristic of advanced keratoconus. We hope to highlight Munson's sign as a simple identifier of keratoconus in an otherwise undiagnosed individual suspected of having acute corneal hydrops.

Attachment, conflict and relationship quality: laboratory-based and clinical insights.

Severe or persistent conflict is disturbing for romantic partners and can jeopardize the couple relationship, hence activating the attachment system. In this paper we integrate recent laboratory-based and clinical research into attachment processes and couple conflict. Three main tenets are addressed. First, attachment security and insecurity have pervasive effects in conflict situations, shaping perceptual, physiological and behavioral responses to conflict. Second, attachment insecurity and associated conflict behaviors tend to erode relationship quality. Third, attachment-related interventions are effective not only in reducing the maladaptive responses that lead to conflict escalation, but also in promoting security and emotional connection within the couple bond. These findings attest to the key role of attachment processes in conflict interactions, while offering a clear, theory-based framework for intervention.

An Emergency Department Pilot Study to Save Money for Patients through use of Retail Pharmacy Generic Drug Discount Programs.

OBJECTIVE: The objective was to assess the number of emergency department patients with selected chronic medical conditions having medicine on a generic drug discount program list (GDDP), and to see if providing information about GDDPs would lead to cost savings. METHODS: A survey was given to consenting patients with at least one of 16 chronic medical conditions. Participants were offered education, which provided information about the three pharmacies closest to the participant. Participants were called after 30 days after to assess GDDP use and money saved. RESULTS: Nearly all (96%) of the 116 participants had at least one medicine on a GDDP list; 80% were unaware of GDDPs. Of the 45 participants enrolled in the intervention component, 37 patients were reached for 30-day follow-up. Of those reached, 26 (70%) reported switching to a GDDP and saving money. CONCLUSION: Discussing GDDPs with patients in the ED may produce cost-savings.

Association of Oral Health Literacy and Dental Visitation in an Inner-City Emergency Department Population.

To examine the association between oral health literacy (OHL) with sociodemographic variables and dental visitation in adults presenting to an urban emergency department (ED). Methods: This was a cross-sectional study of a convenience sample of 556 adults aged 18⁻90. Interview data from the study were used to collect self-reported sociodemographic characteristics and dental visitation history. The OHL of the study participants was measured using the Health Literacy in Dentistry scale (HeLD-14), and the score was dichotomized into low and high OHL. Bivariate associations between sociodemographic variables and OHL were conducted using chi-square tests, and logistic regression was used to examine the association between OHL and dental visitation within the past year. Results: Sixty percent of participants reported having visited a dentist within the past year. Over two-thirds of the sample was classified as having low OHL. Low OHL was more common in non-White races, less-educated, single, unemployed, and lower-income individuals, and those without a primary care physician or dental insurance (p < 0.05). Patients with low oral health literacy were 39% less likely to have visited the dentist in the past year (OR = 0.61; 95% CI 0.38, 0.96). Conclusions: This study highlights significant disparities in OHL. Interventions targeted toward the unique needs of underserved populations should be developed to improve health outcomes.

Relationship between Physical Activity and Fatigue in Adults with Cystic Fibrosis.

Purpose: We examined the relationship between the amount of physical activity and level of fatigue in adults with cystic fibrosis (CF). Method: Participants were recruited from the Toronto Adult Cystic Fibrosis Centre at St. Michael's Hospital. Participants completed the Habitual Activity Estimation Scale, the Multidimensional Fatigue Inventory, and the Depression subscale of the Hospital Anxiety and Depression Scale, in that order. Descriptive statistics and linear and multiple regressions were computed. Results: Over a 6-month period, 51 individuals were approached, and 22 (10 men, 12 women) participated in this study. The participants' median age was 33, and forced expiratory volume in 1 second (FEV1) was 64% predicted. When holding both FEV1 and depression constant, a significant negative correlation was found between total active hours per weekday and general fatigue (ß=-0.735, p=0.03); there was a negative trend between total active hours per weekday and physical fatigue (ß=-0.579, p=0.09). Conclusions: This study is the first to demonstrate that among adults with CF, a higher level of physical activity is associated with a lower level of general and physical fatigue when controlling for lung function and level of depression. Physical activity may be used as a means of mitigating the levels of general and physical fatigue in people with CF.

Objectif : des chercheurs ont examiné la relation entre la quantité d'activité physique et le taux de fatigue chez des adultes atteints de fibrose kystique (FK). Méthodologie : les chercheurs ont recruté les sujets au sein du centre de FK pour adultes du St. Michael's Hôpital de Toronto. Ils leur ont fait remplir, dans l'ordre, l'échelle d'évaluation de l'activité habituelle, l'inventaire de fatigue multidimensionnelle et la sous-échelle de dépression de l'échelle d'anxiété et de dépression en milieu hospitalier. Ils ont calculé les statistiques descriptives et les régressions linéaires et multiples. Résultats : Sur une période de six mois, les chercheurs ont sollicité 51 personnes, dont 22 (10 hommes) ont participé à l'étude. Ceux-ci avaient un âge médian de 33 ans, et leur volume expiratoire maximal par seconde (VEMS) s'établissait à 64 % de celui prévu. Lorsque le VEMS et la dépression des participants étaient maintenus constants, les chercheurs constataient une corrélation négative significative entre le total des heures d'activité par jour et l'état de fatigue général (ß=­0,735, p=0,03). Ils remarquaient également une tendance négative entre le total des heures d'activité par jour et la fatigue physique (ß=­0,579, p=0,09). Conclusion : la présente étude est la première à démontrer que, chez les adultes atteints de FK, un plus fort taux d'activité s'associe à une diminution de la fatigue générale et physique lors des contrôles de la fonction pulmonaire et de la dépression. Ainsi, l'activité physique peut réduire le taux de fatigue générale et physique chez les personnes atteintes de FK.

RAD sequencing reveals genomewide divergence between independent invasions of the European green crab (Carcinus maenas) in the Northwest Atlantic.

Genomic studies of invasive species can reveal both invasive pathways and functional differences underpinning patterns of colonization success. The European green crab (Carcinus maenas) was initially introduced to eastern North America nearly 200 years ago where it expanded northwards to eastern Nova Scotia. A subsequent invasion to Nova Scotia from a northern European source allowed further range expansion, providing a unique opportunity to study the invasion genomics of a species with multiple invasions. Here, we use restriction-site-associated DNA sequencing-derived SNPs to explore fine-scale genomewide differentiation between these two invasions. We identified 9137 loci from green crab sampled from 11 locations along eastern North America and compared spatial variation to mitochondrial COI sequence variation used previously to characterize these invasions. Overall spatial divergence among invasions was high (pairwise FST ~0.001 to 0.15) and spread across many loci, with a mean FST ~0.052 and 52% of loci examined characterized by FST values >0.05. The majority of the most divergent loci (i.e., outliers, ~1.2%) displayed latitudinal clines in allele frequency highlighting extensive genomic divergence among the invasions. Discriminant analysis of principal components (both neutral and outlier loci) clearly resolved the two invasions spatially and was highly correlated with mitochondrial divergence. Our results reveal extensive cryptic intraspecific genomic diversity associated with differing patterns of colonization success and demonstrates clear utility for genomic approaches to delineating the distribution and colonization success of aquatic invasive species.

Contrasting effects of hypoxia on copper toxicity during development in the three-spined stickleback (Gasterosteus aculeatus).

Hypoxia is a global problem in aquatic systems and often co-occurs with pollutants. Despite this, little is known about the combined effects of these stressors on aquatic organisms. The objective of this study was to investigate the combined effects of hypoxia and copper, a toxic metal widespread in the aquatic environment. We used the three-spined stickleback (Gasterosteus aculeatus) as a model because of its environmental relevance and amenability for environmental toxicology studies. We focused on embryonic development as this is considered to be a sensitive life stage to environmental pollution. We first investigated the effects of hypoxia alone on stickleback development to generate the information required to design subsequent studies. Our data showed that exposure to low oxygen concentrations (24.7 ± 0.9% air saturation; AS) resulted in strong developmental delays and increased mortalities, whereas a small decrease in oxygen (75.0 ± 0.5%AS) resulted in premature hatching. Stickleback embryos were then exposed to a range of copper concentrations under hypoxia (56.1 ± 0.2%AS) or normoxia (97.6 ± 0.1%AS), continuously, from fertilisation to free swimming larvae. Hypoxia caused significant changes in copper toxicity throughout embryonic development. Prior to hatching, hypoxia suppressed the occurrence of mortalities, but after hatching hypoxia significantly increased copper toxicity. Interestingly, when exposures were conducted only after hatching, the onset of copper-induced mortalities was delayed under hypoxia compared to normoxia, but after 48 h, copper was more toxic to hatched embryos under hypoxia. This is the second species for which the protective effect of hypoxia on copper toxicity prior to hatching, followed by its exacerbating effect after hatching is demonstrated, suggesting the hypothesis that this pattern may be common for teleost species. Our research highlights the importance of considering the interactions between multiple stressors, as understanding these interactions is essential to facilitate the accurate prediction of the consequences of exposure to complex stressors in a rapidly changing environment.