Controlling peripheral intravenous catheter failure by needleless connector design: A pilot randomised controlled trial.

AIM: To test the feasibility of a study protocol that compared the efficacy of neutral- and negative-pressure needleless connectors (NCs). DESIGN: A single-centre, parallel-group, pilot randomised control trial. METHODS: Our study compared neutral-(intervention) and negative-pressure (control) NCs among adult patients in an Australian hospital. The primary feasibility outcome was measured against predetermined criteria (e.g. eligibility, attrition). The primary efficacy outcome was all-cause peripheral intravenous catheter failure, analysed as time-to-event data. RESULTS: In total, 201 (100 control; 101 intervention) participants were enrolled between March 2020 and September 2020. All feasibility criteria were met except eligibility, which was lower (78%) than the 90% criterion. All-cause peripheral intravenous catheter failure was significantly higher in the intervention group (39%) compared to control (19%). CONCLUSION: With minor modifications to participant screening for eligibility, this randomised control trial is feasible for a large multicentre randomised control trial. The neutral NC was associated with an increased risk of peripheral intravenous catheter failure. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: There are several NC designs available, often identified by their mechanism of pressure (positive, negative and neutral). However, NCs can contribute to peripheral intravenous catheter failure. This is the first randomised controlled trial to compare neutral and negative NC designs. Negative pressure NCs had lower PIVC failure compared to neutral NCs, however the results might not be generalisable to other brands or treatment settings. Further high-quality research is needed to explore NC design. REPORTING METHOD: Study methods and results reported in adherence to the CONSORT Statement. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Does longer peripheral intravenous catheter length optimise antimicrobial delivery? Protocol for the LEADER study.

BACKGROUND: Hospitalised patients receiving intravenous antimicrobial therapy require a reliable device through which this is delivered. Short peripheral intravenous catheters (PIVCs) are the default device for antimicrobial therapy but up to half fail before therapy completion, leading to suboptimal drug dosing, patient distress from repeated insertions, and increased healthcare costs. This study will investigate the use of long PIVCs to determine if they are more reliable at delivering antimicrobial therapy. METHODS: A two-arm, parallel randomised controlled trial of hospitalised adults requiring at least 3 days of peripherally compatible intravenous antimicrobials. Participants will be randomised to a short (<4 cm) or long (4.5-6.4 cm) PIVC. After interim analysis ( n=70) for feasibility and safety, 192 participants will be recruited. Primary outcome is disruption to antimicrobial administration from all-cause PIVC failure. Secondary outcomes include: number of devices to complete therapy, patient-reported pain and satisfaction, and a cost analysis. Ethical and regulatory approvals have been received.

The magnitude of germinal center reactions is restricted by a fixed number of preexisting niches.

Antibody affinity maturation occurs in the germinal center (GC), a highly dynamic structure that arises upon antigen stimulation and recedes after infection is resolved. While the magnitude of the GC reaction is highly fluctuating and depends on antigens or pathological conditions, it is unclear whether GCs are assembled ad hoc in different locations or in preexisting niches within B cell follicles. We show that follicular dendritic cells (FDCs), the essential cellular components of the GC architecture, form a predetermined number of clusters. The total number of FDC clusters is the same on several different genetic backgrounds and is not altered by immunization or inflammatory conditions. In unimmunized and germ-free mice, a few FDC clusters contain GC B cells; in contrast, immunization or autoimmune milieu significantly increases the frequency of FDC clusters occupied by GC B cells. Excessive occupancy of GC niches by GC B cells after repeated immunizations or in autoimmune conditions suppresses subsequent antibody responses to new antigens. These data indicate that the magnitude of the GC reaction is restricted by a fixed number of permissive GC niches containing preassembled FDC clusters. This finding may help in the future design of vaccination strategies and in the modulation of antibody-mediated autoimmunity.

Sleep attitudes as a predictor of sleep outcomes: a secondary data analysis.

OBJECTIVES: Attitudes have been widely studied as predictors of a number of social and health behaviors. However, attitudes predicting sleep outcomes have only recently been examined, despite sleep being conceptualized as an important health behavior. Prior research has demonstrated that attitudes toward sleep are associated with sleep hygiene, sleep duration and quality (Peach & Gaultney, 2017; Peach, Gaultney, Ruggiero, 2018). Sleep attitudes interact with varying demographic identities, such as age, gender, race, and perceived socioeconomic status (SES) (Ruggiero, Peach, & Gaultney, 2019). The present study hypothesized that (1) sleep attitudes would be indirectly associated with sleep outcomes (duration and quality) via sleep hygiene, and, (2) this indirect effect would be modified by specific demographic variables (age, gender, race, and perceived SES; moderated mediation). METHOD: One hundred and seventy-two adults from the United States completed an anonymous survey on sleep characteristics and health. RESULTS: Results confirmed the first hypothesis, indicating that sleep attitudes were significantly and indirectly associated with both sleep duration and sleep quality via sleep hygiene. Additionally, gender and SES further modified these significant indirect effects, meaning hypothesis two was partially supported. CONCLUSIONS: Results are discussed in terms of their implications for the importance and variability of sleep attitudes, and future research directions are considered.

Distinct Polysaccharide Utilization Profiles of Human Intestinal Prevotella copri Isolates.

Gut-dwelling Prevotella copri (P. copri), the most prevalent Prevotella species in the human gut, have been associated with diet and disease. However, our understanding of their diversity and function remains rudimentary because studies have been limited to 16S and metagenomic surveys and experiments using a single type strain. Here, we describe the genomic diversity of 83 P. copri isolates from 11 human donors. We demonstrate that genomically distinct isolates, which can be categorized into different P. copri complex clades, utilize defined sets of polysaccharides. These differences are exemplified by variations in susC genes involved in polysaccharide transport as well as polysaccharide utilization loci (PULs) that were predicted in part from genomic and metagenomic data. Functional validation of these PULs showed that P. copri isolates utilize distinct sets of polysaccharides from dietary plant, but not animal, sources. These findings reveal both genomic and functional differences in polysaccharide utilization across human intestinal P. copri strains.

A Listeria monocytogenes Bacteriocin Can Target the Commensal Prevotella copri and Modulate Intestinal Infection.

Understanding the role of the microbiota components in either preventing or favoring enteric infections is critical. Here, we report the discovery of a Listeria bacteriocin, Lmo2776, which limits Listeria intestinal colonization. Oral infection of conventional mice with a Δlmo2776 mutant leads to a thinner intestinal mucus layer and higher Listeria loads both in the intestinal content and deeper tissues compared to WT Listeria. This latter difference is microbiota dependent, as it is not observed in germ-free mice. Strikingly, it is phenocopied by pre-colonization of germ-free mice before Listeria infection with Prevotella copri, an abundant gut-commensal bacteria, but not with the other commensals tested. We further show that Lmo2776 targets P. copri and reduces its abundance. Together, these data unveil a role for P.copri in exacerbating intestinal infection, highlighting that pathogens such as Listeria may selectively deplete microbiota bacterial species to avoid excessive inflammation.

The Prevotella copri Complex Comprises Four Distinct Clades Underrepresented in Westernized Populations.

Prevotella copri is a common human gut microbe that has been both positively and negatively associated with host health. In a cross-continent meta-analysis exploiting >6,500 metagenomes, we obtained >1,000 genomes and explored the genetic and population structure of P. copri. P. copri encompasses four distinct clades (>10% inter-clade genetic divergence) that we propose constitute the P. copri complex, and all clades were confirmed by isolate sequencing. These clades are nearly ubiquitous and co-present in non-Westernized populations. Genomic analysis showed substantial functional diversity in the complex with notable differences in carbohydrate metabolism, suggesting that multi-generational dietary modifications may be driving reduced prevalence in Westernized populations. Analysis of ancient metagenomes highlighted patterns of P. copri presence consistent with modern non-Westernized populations and a clade delineation time pre-dating human migratory waves out of Africa. These findings reveal that P. copri exhibits a high diversity that is underrepresented in Western-lifestyle populations.

Association of sleep attitudes with sleep hygiene, duration, and quality: a survey exploration of the moderating effect of age, gender, race, and perceived socioeconomic status.

OBJECTIVES: Sleep health is becoming more widely accepted as a possible preventative strategy against chronic disease and negative psychosocial outcomes. It is important to understand whether attitudes towards sleep vary by demographic characteristics and how potential differences in sleep attitudes could impact sleep outcomes. The present study examined whether there were demographic differences in sleep attitudes and whether the interaction between demographic characteristics and sleep attitudes impacted sleep outcomes (e.g. sleep hygiene, duration, and quality). METHODS: One hundred seventy-two adults from across the United States completed an anonymous survey on sleep and health. RESULTS: Sleep attitudes varied according to age, gender, and race, with more positive sleep attitudes reported by older adults, women, and those who identified as White. Although positive sleep attitudes predicted more sleep and better quality sleep, this association varied as a function of several demographic characteristics. A more complex picture arose for the interaction between demographics and sleep attitudes predicting sleep outcomes. CONCLUSIONS: Future research should continue to discover for whom favorable sleep attitudes are beneficial and explore when and how sleep attitudes may be altered.

Examination of Risk for Sleep-Disordered Breathing Among College Football Players.

CONTEXT: Professional football linemen are at risk for sleep-disordered breathing (SDB) compared with other types of athletes. It is currently unknown whether college football linemen display a similar risk profile. OBJECTIVE: (1) To determine for the first time whether college football linemen show risk for SDB and (2) test the hypothesis that SDB risk is higher in college football linemen compared with an athletic comparison group. DESIGN: Descriptive laboratory study. SETTING: The Health Risk Assessment Laboratory. PARTICIPANTS: Male football linemen (n = 21) and track (n = 19) Division I athletes between the ages of 18 and 22 years. INTERVENTIONS: Participants completed the Multivariable Apnea Prediction Index and Epworth Sleepiness Scale surveys, validated measures of symptoms of sleep apnea and daytime sleepiness, respectively. Neck and waist circumferences, blood pressure, Modified Mallampati Index (MMPI), and tonsil size were determined, followed by body composition assessment using dual-energy X-ray absorptiometry. MAIN OUTCOME MEASURES: Scores from surveys, anthropometric data, MMPI, and body composition. RESULTS: Survey data demonstrated a deficiency in sleep quality and efficiency, coinciding with increased self-reported symptoms of apnea (Multivariable Apnea Prediction Index = 0.78) in college linemen relative to track athletes. Neck circumference (44.36 cm), waist circumference (107.07 cm), body mass index (35.87 kg/m2), and percent body fat (29.20%), all of which exceeded the clinical predictors of risk for obstructive sleep apnea, were significantly greater in linemen compared with track athletes. Multivariable Apnea Prediction variables were significantly correlated with MMPI, neck circumference, percent body fat, body mass index, and systolic blood pressure (r ≥ .31, P < .05), indicating that college football linemen are at increased risk for SDB. CONCLUSIONS: Risk factors for SDB recognized in professional football linemen are also present at the college level. Screening may minimize present or future risk for SDB, as well as the downstream risk of SDB-associated metabolic and cardiovascular disease.

Direct and Indirect Associations of Sleep Knowledge and Attitudes With Objective and Subjective Sleep Duration and Quality via Sleep Hygiene.

Although a few studies have examined sleep knowledge and attitudes as predictors of sleep behavior, the question of which better predicts actual sleep behavior is still open. Furthermore, the construct of sleep attitudes has been inconsistently defined and measured. We examined both sleep knowledge and attitudes to determine their unique associations with sleep hygiene behaviors, and direct and indirect associations with objective and subjective sleep outcomes. College students (N = 218) completed a series of questionnaires before and after wearing a FitBit Flex accelerometer for 7 days. We collected objective sleep duration and quality using this apparatus, while participants reported subjective sleep outcomes, hygiene behaviors, knowledge, and attitudes. Analyses controlled for self-reported depression, diagnosed sleep disorder, and sleep-related medications. For both objective and subjective measures, more positive sleep attitudes but not greater sleep knowledge was directly associated with longer sleep duration, and indirectly (through sleep hygiene) with better sleep quality. The role of sleep attitudes in sleep-related behaviors and outcomes deserves further investigation as a potentially modifiable factor in sleep intervention efforts.

Critical Role for the Microbiota in CX3CR1+ Intestinal Mononuclear Phagocyte Regulation of Intestinal T Cell Responses.

The intestinal barrier is vulnerable to damage by microbiota-induced inflammation that is normally restrained through mechanisms promoting homeostasis. Such disruptions contribute to autoimmune and inflammatory diseases including inflammatory bowel disease. We identified a regulatory loop whereby, in the presence of the normal microbiota, intestinal antigen-presenting cells (APCs) expressing the chemokine receptor CX3CR1 reduced expansion of intestinal microbe-specific T helper 1 (Th1) cells and promoted generation of regulatory T cells responsive to food antigens and the microbiota itself. We identified that disruption of the microbiota resulted in CX3CR1+ APC-dependent inflammatory Th1 cell responses with increased pathology after pathogen infection. Colonization with microbes that can adhere to the epithelium was able to compensate for intestinal microbiota loss, indicating that although microbial interactions with the epithelium can be pathogenic, they can also activate homeostatic regulatory mechanisms. Our results identify a cellular mechanism by which the microbiota limits intestinal inflammation and promotes tissue homeostasis.

Charlotte Attitudes Towards Sleep (CATS) Scale: A validated measurement tool for college students.

OBJECTIVE: Using a 4-phase study design, the present study developed and tested the Charlotte Attitudes Towards Sleep (CATS) Scale, a measurement tool for assessing sleep attitudes in college students. PARTICIPANTS: Participants were 706 undergraduate students recruited at a southeastern university and on a national recruitment Web site between October 2013 and April 2015. METHODS: All participants completed the CATS Scale. Participants then completed either a measure of social desirability, faulty sleep beliefs, or measures of sleep and sleep hygiene. Phase 3 participants (N = 168) completed the CATS Scale 2 weeks later to examine test-retest reliability. RESULTS: Analyses indicated that the scale was content valid, internally consistent, and independent of social desirability, yielded acceptable temporal stability, and demonstrated concurrent validity in relation to sleep behaviors and outcomes. CONCLUSIONS: The CATS Scale is a theoretically driven instrument with promising psychometric properties that may prove beneficial for future research and application efforts among college students.

Interleukin-15 promotes intestinal dysbiosis with butyrate deficiency associated with increased susceptibility to colitis.

Dysbiosis resulting in gut-microbiome alterations with reduced butyrate production are thought to disrupt intestinal immune homeostasis and promote complex immune disorders. However, whether and how dysbiosis develops before the onset of overt pathology remains poorly defined. Interleukin-15 (IL-15) is upregulated in distressed tissue and its overexpression is thought to predispose susceptible individuals to and have a role in the pathogenesis of celiac disease and inflammatory bowel disease (IBD). Although the immunological roles of IL-15 have been largely studied, its potential impact on the microbiota remains unexplored. Analysis of 16S ribosomal RNA-based inventories of bacterial communities in mice overexpressing IL-15 in the intestinal epithelium (villin-IL-15 transgenic (v-IL-15tg) mice) shows distinct changes in the composition of the intestinal bacteria. Although some alterations are specific to individual intestinal compartments, others are found across the ileum, cecum and feces. In particular, IL-15 overexpression restructures the composition of the microbiota with a decrease in butyrate-producing bacteria that is associated with a reduction in luminal butyrate levels across all intestinal compartments. Fecal microbiota transplant experiments of wild-type and v-IL-15tg microbiota into germ-free mice further indicate that diminishing butyrate concentration observed in the intestinal lumen of v-IL-15tg mice is the result of intrinsic alterations in the microbiota induced by IL-15. This reconfiguration of the microbiota is associated with increased susceptibility to dextran sodium sulfate-induced colitis. Altogether, this study reveals that IL-15 impacts butyrate-producing bacteria and lowers butyrate levels in the absence of overt pathology, which represent events that precede and promote intestinal inflammatory diseases.

Sleep characteristics, body mass index, and risk for hypertension in young adolescents.

Inadequate sleep has been identified as a risk factor for a variety of health consequences. For example, short sleep durations and daytime sleepiness, an indicator of insufficient sleep and/or poor sleep quality, have been identified as risk factors for hypertension in the adult population. However, less evidence exists regarding whether these relationships hold within child and early adolescent samples and what factors mediate the relationship between sleep and risk for hypertension. Using data from the Study of Early Child Care and Youth Development, the present study examined body mass index (BMI) as a possible mediator for the effects of school-night sleep duration, weekend night sleep duration, and daytime sleepiness on risk for hypertension in a sample of sixth graders. The results demonstrated gender-specific patterns. Among boys, all three sleep characteristics predicted BMI and yielded significant indirect effects on risk for hypertension. Oppositely, only daytime sleepiness predicted BMI among girls and yielded a significant indirect effect on risk for hypertension. The findings provide clarification for the influence of sleep on the risk for hypertension during early adolescence and suggest a potential need for gender-specific designs in future research and application endeavors.

Sleep, impulse control, and sensation-seeking predict delinquent behavior in adolescents, emerging adults, and adults.

PURPOSE: The present study examined delinquent behavior from adolescence into adulthood within the dual systems model of adolescent risk-taking, which identifies maturational patterns of socioemotional and cognitive control systems as predictors of risk-taking. The role of sleep was also investigated within the relationship. METHODS: Hierarchical regression and path analysis examined delinquency at three waves (1996, 2001, and 2008) of the National Longitudinal Study of Adolescent Health. RESULTS: Impulse control and sensation-seeking predicted concurrent delinquent behavior at all three waves, demonstrating the developmental shift as described within the dual systems model in which the relative contribution of sensation-seeking decreases from adolescence into adulthood, whereas the relative contribution of impulse control improves. Data also revealed that sleep duration and delayed bedtimes had both direct and indirect associations with delinquent behavior during adolescence; sleep duration did not directly predict such activity during later waves. CONCLUSION: The dual systems model of adolescent risk-taking appears to be predictive of delinquent behavior during adolescence and the transition into adulthood. Preliminary findings suggest the importance of considering both adolescent sleep and cognitive and socioemotional development during research and prevention efforts of delinquent behavior.

Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice.

The composite human microbiome of Western populations has probably changed over the past century, brought on by new environmental triggers that often have a negative impact on human health. Here we show that consumption of a diet high in saturated (milk-derived) fat, but not polyunsaturated (safflower oil) fat, changes the conditions for microbial assemblage and promotes the expansion of a low-abundance, sulphite-reducing pathobiont, Bilophila wadsworthia. This was associated with a pro-inflammatory T helper type 1 (T(H)1) immune response and increased incidence of colitis in genetically susceptible Il10(−/−), but not wild-type mice. These effects are mediated by milk-derived-fat-promoted taurine conjugation of hepatic bile acids, which increases the availability of organic sulphur used by sulphite-reducing microorganisms like B. wadsworthia. When mice were fed a low-fat diet supplemented with taurocholic acid, but not with glycocholic acid, for example, a bloom of B. wadsworthia and development of colitis were observed in Il10(−/−) mice. Together these data show that dietary fats, by promoting changes in host bile acid composition, can markedly alter conditions for gut microbial assemblage, resulting in dysbiosis that can perturb immune homeostasis. The data provide a plausible mechanistic basis by which Western-type diets high in certain saturated fats might increase the prevalence of complex immune-mediated diseases like inflammatory bowel disease in genetically susceptible hosts.

Decreased Cognitive/CNS Function in Young Adults at Risk for Hypertension: Effects of Sleep Deprivation.

Hypertension has been linked to impaired cognitive/CNS function, and some of these changes may precede development of frank essential hypertension. The stress and fatigue of sleep deprivation may exacerbate these cognitive changes in young adults at risk. We hypothesize that individuals at risk for hypertension will show significant declines in cognitive function during a night of sleep deprivation. Fifty-one young adults were recruited for 28-hour total sleep deprivation studies. Hypertension risk was assessed by mildly elevated resting blood pressure and by family history of hypertension. A series of cognitive memory tasks was given at four test sessions across the sleep deprivation period. Although initially comparable in cognitive performance, persons at risk showed larger declines across the night for several indices of working memory, including code substitution, category, and order recall. These results suggest that cognitive/CNS changes may parallel or precede blood pressure dysregulation in the early stages of hypertension development. The role of CNS changes in the etiology of essential hypertension is discussed.