General parity between trio and pairwise breeding of laboratory mice in static caging.

Changes made in the 8th edition of the Guide for the Care and Use of Laboratory Animals included new recommendations for the amount of space for breeding female mice. Adopting the new recommendations required, in essence, the elimination of trio breeding practices for all institutions. Both public opinion and published data did not readily support the new recommendations. In response, the National Jewish Health Institutional Animal Care and Use Committee established a program to directly compare the effects of breeding format on mouse pup survival and growth. Our study showed an overall parity between trio and pairwise breeding formats on the survival and growth of the litters, suggesting that the housing recommendations for breeding female mice as stated in the current Guide for the Care and Use of Laboratory Animals should be reconsidered.

One Year Later: Family Members of Patients with COVID-19 Experience Persistent Symptoms of Posttraumatic Stress Disorder.

Rationale: Family members of critically ill patients with coronavirus disease (COVID-19) have described increased symptoms of posttraumatic stress disorder (PTSD). Little is known about how these symptoms may change over time. Objectives: We studied changes in PTSD symptoms in family members of critically ill patients with COVID-19 over 12 months. Methods: This prospective, multisite observational cohort study recruited participants at 12 hospitals in five states. Calls were made to participants at 3-4 months, 6 months, and 12 months after patient admission to the intensive care unit. Results: There were 955 eligible family members, of whom 330 (53.3% of those reached) consented to participate. Complete longitudinal data was acquired for 115 individuals (34.8% consented). PTSD symptoms were measured by the IES-6 (Impact of Events Scale-6), with a score of at least 10 identifying significant symptoms. At 3 months, the mean IES-6 score was 11.9 ± 6.1, with 63.6% having significant symptoms, decreasing to 32.9% at 1 year (mean IES-6 score, 7.6 ± 5.0). Three clusters of symptom evolution emerged over time: persistent symptoms (34.8%, n = 40), recovered symptoms (33.0%, n = 38), and nondevelopment of symptoms (32.2%, n = 37). Although participants identifying as Hispanic demonstrated initially higher adjusted IES-6 scores (2.57 points higher [95% confidence interval (CI), 1.1-4.1; P < 0.001]), they also demonstrated a more dramatic improvement in adjusted scores over time (4.7 greater decrease at 12 months [95% CI, 3.2-6.3; P < 0.001]). Conclusions: One year later, some family members of patients with COVID-19 continue to experience significant symptoms of PTSD. Further studies are needed to better understand how various differences contribute to increased risk for these symptoms.

Sex-Specific Differences in MicroRNA Expression During Human Fetal Lung Development.

Background: Sex-specific differences in fetal lung maturation have been well described; however, little is known about the sex-specific differences in microRNA (miRNA) expression during human fetal lung development. Interestingly, many adult chronic lung diseases also demonstrate sex-specific differences in prevalence. The developmental origins of health and disease hypothesis suggests that these sex-specific differences in fetal lung development may influence disease susceptibility later in life. In this study, we performed miRNA sequencing on human fetal lung tissue samples to investigate differential expression of miRNAs between males and females in the pseudoglandular stage of lung development. We hypothesized that differences in miRNA expression are present between sexes in early human lung development and may contribute to the sex-specific differences seen in pulmonary diseases later in life. Methods: RNA was isolated from human fetal lung tissue samples for miRNA sequencing. The count of each miRNA was modeled by sex using negative binomial regression models in DESeq2, adjusting for post-conception age, age2, smoke exposure, batch, and RUV factors. We tested for differential expression of miRNAs by sex, and for the presence of sex-by-age interactions to determine if miRNA expression levels by age were distinct between males and females. Results: miRNA expression profiles were generated on 298 samples (166 males and 132 females). Of the 809 miRNAs expressed in human fetal lung tissue during the pseudoglandular stage of lung development, we identified 93 autosomal miRNAs that were significantly differentially expressed by sex and 129 miRNAs with a sex-specific pattern of miRNA expression across the course of the pseudoglandular period. Conclusion: Our study demonstrates differential expression of numerous autosomal miRNAs between the male and female developing human lung. Additionally, the expression of some miRNAs are modified by age across the pseudoglandular stage in a sex-specific way. Some of these differences in miRNA expression may impact susceptibility to pulmonary disease later in life. Our results suggest that sex-specific miRNA expression during human lung development may be a potential mechanism to explain sex-specific differences in lung development and may impact subsequent disease susceptibility.

Voices from the Pandemic: A Qualitative Study of Family Experiences and Suggestions regarding the Care of Critically Ill Patients.

Rationale: Intensive care unit (ICU) visitation restrictions during the coronavirus disease (COVID-19) pandemic have drastically reduced family-engaged care. Understanding the impact of physical distancing on family members of ICU patients is needed to inform future policies. Objectives: To understand the experiences of family members of critically ill patients with COVID-19 when physically distanced from their loved ones and to explore ways clinicians may support them. Methods: This qualitative study of an observational cohort study reports data from 74 family members of ICU patients with COVID-19 at 10 United States hospitals in four states, chosen based on geographic and demographic diversity. Adult family members of patients admitted to the ICU with COVID-19 during the early phase of the pandemic (February-June 2020) were invited to participate in a phone interview. Interviews followed a semistructured guide to assess four constructs: illness narrative, stress experiences, communication experiences, and satisfaction with care. Interviews were transcribed verbatim and analyzed using an inductive approach to thematic analysis. Results: Among 74 interviewees, the mean age was 53.0 years, 55% were white, and 76% were female. Physical distancing contributed to substantial stress and harms (nine themes). Participants described profound suffering and psychological illness, unfavorable perceptions of care, and weakened therapeutic relationship between family members and clinicians. Three communication principles emerged as those most valued by family members: contact, consistency, and compassion (the 3Cs). Family members offered suggestions to guide clinicians faced with communicating with physically distanced families. Conclusions: Visitation restrictions impose substantial psychological harms upon family members of critically ill patients. Derived from the voics of family members, our findings warrant strong consideration when implementing visitation restrictions in the ICU and advocate for investment in infrastructure (including staffing and videoconferencing) to support communication. This study offers family-derived recommendations to operationalize the 3Cs to guide and improve communication in times of physical distancing during the COVID-19 pandemic and beyond.

L-Citrulline increases nitric oxide and improves control in obese asthmatics.

BACKGROUNDThe airways of obese asthmatics have been shown to be NO deficient, and this contributes to airway dysfunction and reduced response to inhaled corticosteroids. In cultured airway epithelial cells, L-citrulline, a precursor of L-arginine recycling and NO formation, has been shown to prevent asymmetric dimethyl arginine-mediated (ADMA-mediated) NO synthase (NOS2) uncoupling, restoring NO and reducing oxidative stress.METHODSIn a proof-of-concept, open-label pilot study in which participants were analyzed before and after treatment, we hypothesized that 15 g/d L-citrulline for 2 weeks would (a) increase the fractional excretion of NO (FeNO), (b) improve asthma control, and (c) improve lung function. To this end, we recruited obese (BMI >30) asthmatics on controller therapy, with a baseline FeNO of ≤30 ppb from the University of Colorado Medical Center and Duke University Health System.RESULTSA total of 41 subjects with an average FeNO of 17 ppb (95% CI, 15-19) and poorly controlled asthma (average asthma control questionnaire [ACQ] 1.5 [95% CI, 1.2-1.8]) completed the study. Compared with baseline, L-citrulline increased whereas ADMA and arginase concentration did not (values represent the mean Δ and 95% CI): plasma L-citrulline (190 µM, 84-297), plasma L-arginine (67 µM, 38-95), and plasma L-arginine/ADMA (ratio 117, 67-167). FeNO increased by 4.2 ppb (1.7-6.7 ppb); ACQ decreased by -0.46 (-0.67 to 0.27 points); the forced vital capacity and forced exhalation volume in 1 second, respectively, changed by 86 ml (10-161 ml) and 52 ml (-11 to 132 ml). In a secondary analysis, the greatest FEV1 increments occurred in those subjects with late-onset asthma (>12 years) (63 ml [95% CI, 1-137]), in females (80 ml [95% CI, 5-154]), with a greater change seen in late-onset females (100 ml, [95% CI, 2-177]). The changes in lung function or asthma control were not significantly associated with the changes before and after treatment in L-arginine/ADMA or FeNO.CONCLUSIONShort-term L-citrulline treatment improved asthma control and FeNO levels in obese asthmatics with low or normal FeNO. Larger FEV1 increments were observed in those with late-onset asthma and in females.TRIAL REGISTRATIONClinicalTrials.gov NCT01715844.FUNDINGNIH NHLBI R01 HL146542-01.

Mentoring during Medical School and Match Outcome among Emergency Medicine Residents.

INTRODUCTION: Few studies have documented the value of mentoring for medical students, and research has been limited to more subjective (e.g., job satisfaction, perceived career preparation) rather than objective outcomes. This study examined whether having a mentor is associated with match outcome (where a student matched based on their rank order list [ROL]). METHODS: We sent a survey link to all emergency medicine (EM) program coordinators to distribute to their residents. EM residents were surveyed about whether they had a mentor during medical school. Match outcome was assessed by asking residents where they matched on their ROL (e.g., first choice, fifth choice). They were also asked about rank in medical school, type of degree (MD vs. DO), and performance on standardized tests. Residents who indicated having a mentor completed the Mentorship Effectiveness Scale (MES), which evaluates behavioral characteristics of the mentor and yields a total score. We assessed correlations among these variables using Pearson's correlation coefficient. Post-hoc analysis using independent sample t-test was conducted to compare differences in the MES score between those who matched to their first or second choice vs. third or higher choice. RESULTS: Participants were a convenience sample of 297 EM residents. Of those, 199 (67%) reported having a mentor during medical school. Contrary to our hypothesis, there was no significant correlation between having a mentor and match outcome (r=0.06, p=0.29). Match outcome was associated with class rank (r=0.13, p=0.03), satisfaction with match outcome (r= -0.37, p<0.001), and type of degree (r=0.12, p=0.04). Among those with mentors, a t-test revealed that the MES score was significantly higher among those who matched to their first or second choice (M=51.31, SD=10.13) compared to those who matched to their third or higher choice (M=43.59, SD=17.12), t(194)=3.65, p<0.001, d=0.55. CONCLUSION: Simply having a mentor during medical school does not impact match outcome, but having an effective mentor is associated with a more favorable match outcome among medical students applying to EM programs.

Infection after primary total hip arthroplasty.

The number of primary total hip arthroplasties (THAs) performed in the United States each year continues to climb, as does the incidence of infectious complications. The changing profile of antibiotic-resistant bacteria has made preventing and treating primary THA infections increasingly complex. The goal of this review was to summarize (1) the published data concerning the risk of surgical site infection (SSI) after primary THA by type of bacteria and (2) the effect of potentially modifying factors. The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, EMBASE, Web of Science, and PubMed were searched. Studies dated between 2001 and 2011 examining primary THA in adults were included. Meta-analysis of the collected data was performed. The pooled SSI rate was 2.5% (95% confidence interval [Cl], 1.4%-4.4%; P<.001; n=28,883). The pooled deep prosthetic joint infection (PJI) rate was 0.9% (95% Cl, 0.4%-2.2%; P<.001; n=28,883). The pooled rate of methicillin-resistant Staphylococcus aureus SSI was 0.5% (95% Cl, 0.2%-1.5%; P<.001; n=26,703). This is approximately 20% of all SSI cases. The pooled rate of intraoperative bacterial wound contamination was 16.9% (95% Cl, 6.6%-36.8%; P=.003; n=2180). All these results had significant heterogeneity. The postoperative risk of SSI was significantly associated with intraoperative bacterial surgical wound contamination (pooled rate ratio, 2.5; 95% Cl, 1.4%-4.6%; P=.001; n=19,049).