Assessment of an ICU-specific, electronic medical summary tool against traditional dictation to reduce communication gaps during ICU-to-inpatient transitions-in-care

  Background: Transition from the intensive care unit (ICU) to an inpatient unit is a vulnerable period where communication gaps between medical teams may be associated with preventable adverse events. The transition-in-care (TIC) summary encompasses essential clinical information and facilitates seamless continuity of patient care between sending and receiving healthcare teams. Yet, current dictation practices often produce summaries of suboptimal quality that result in delayed or incomplete information. An electronic TIC summary tool, an alternative method to dictation, standardizes information, which may ensure more timely and complete communication to reduce information breakdowns and delays. Objective: In order to standardize information communicated during ICU-to-inpatient transitions, an ICU-specific, electronic TIC summary tool was implemented in four adult ICUs in the Calgary zone. It is hypothesized that implementation of the electronic summary will improve completeness and timelines of TIC summaries.  Methods: A multiple baseline study design was used to evaluate the implementation of the electronic TIC summary. ICUs continued dictation practices for a baseline period, until the electronic tool was implemented sequentially (in a randomized order) to each ICU and evaluated for six months following implementation. Post-implementation, providers had the option to dictate or use the electronic summary. The primary outcome was a binary measure of both completeness of four critical elements and availability of the TIC summary at ICU release. Results: Preliminary results were obtained for two months of baseline (n=48) and post-implementation (n=48) from one ICU. Post-implementation summaries contained four critical elements and were more frequently available at ICU transfer than pre-implementation dictations (73% versus 2%, p<0.001). More post implementation summaries contained completion of essential information (median 88% versus 63%, p<0.001) and had greater availability during transition (90% versus 73%, p=0.04) than pre-implementation dictations. With data collection scheduled to end in June 2019, we anticipate full study results to be available fall 2019. Conclusions: Preliminary results post-implementation suggest greater completion and faster availability for the receiving clinicians. It is anticipated that full study findings will add to the current literature on the effect of computerized tools for reducing communication gaps between ICU and inpatient units during transitions-in-care to ultimately improve patient safety

Tmem26 Is Dynamically Expressed during Palate and Limb Development but Is Not Required for Embryonic Survival

The Tmem26 gene encodes a novel protein that we have previously shown to be regulated by hedgehog signalling in the mouse limb. We now report that Tmem26 expression is spatially and temporally restricted in other regions of the mouse embryo, most notably the facial primordia. In particular, Tmem26 expression in the mesenchyme of the maxillary and nasal prominences is coincident with fusion of the primary palate. In the secondary palate, Tmem26 is expressed in the palatal shelves during their growth and fusion but is downregulated once fusion is complete. Expression was also detected at the midline of the expanding mandible and at the tips of the eyelids as they migrate across the cornea. Given the spatio-temporally restricted expression of Tmem26, we sought to uncover a functional role in embryonic development through targeted gene inactivation in the mouse. However, ubiquitous inactivation of Tmem26 led to no overt phenotype in the resulting embryos or adult mice, suggesting that TMEM26 function is dispensable for embryonic survival

Azetidines Kill Multidrug-Resistant <i>Mycobacterium tuberculosis</i> without Detectable Resistance by Blocking Mycolate Assembly

Tuberculosis (TB) is the leading cause of global morbidity and mortality resulting from infectious disease, with over 10.6 million new cases and 1.4 million deaths in 2021. This global emergency is exacerbated by the emergence of multidrug-resistant MDR-TB and extensively drug-resistant XDR-TB; therefore, new drugs and new drug targets are urgently required. From a whole cell phenotypic screen, a series of azetidines derivatives termed BGAz, which elicit potent bactericidal activity with MIC99 values &lt;10 μM against drug-sensitive Mycobacterium tuberculosis and MDR-TB, were identified. These compounds demonstrate no detectable drug resistance. The mode of action and target deconvolution studies suggest that these compounds inhibit mycobacterial growth by interfering with cell envelope biogenesis, specifically late-stage mycolic acid biosynthesis. Transcriptomic analysis demonstrates that the BGAz compounds tested display a mode of action distinct from the existing mycobacterial cell wall inhibitors. In addition, the compounds tested exhibit toxicological and PK/PD profiles that pave the way for their development as antitubercular chemotherapies. </p

Community Violence Exposure and Conduct Problems in Children and Adolescents with Conduct Disorder and Healthy Controls

Exposure to community violence through witnessing or being directly victimized has been associated with conduct problems in a range of studies. However, the relationship between community violence exposure (CVE) and conduct problems has never been studied separately in healthy individuals and individuals with conduct disorder (CD). Therefore, it is not clear whether the association between CVE and conduct problems is due to confounding factors, because those with high conduct problems also tend to live in more violent neighborhoods, i.e., an ecological fallacy. Hence, the aim of the present study was: (1) to investigate whether the association between recent CVE and current conduct problems holds true for healthy controls as well as adolescents with a diagnosis of CD; (2) to examine whether the association is stable in both groups when including effects of aggression subtypes (proactive/reactive aggression), age, gender, site and socioeconomic status (SES); and (3) to test whether proactive or reactive aggression mediate the link between CVE and conduct problems. Data from 1178 children and adolescents (62% female; 44% CD) aged between 9 years and 18 years from seven European countries were analyzed. Conduct problems were assessed using the Kiddie-Schedule of Affective Disorders and Schizophrenia diagnostic interview. Information about CVE and aggression subtypes was obtained using self-report questionnaires (Social and Health Assessment and Reactive-Proactive aggression Questionnaire (RPQ), respectively). The association between witnessing community violence and conduct problems was significant in both groups (adolescents with CD and healthy controls). The association was also stable after examining the mediating effects of aggression subtypes while including moderating effects of age, gender and SES and controlling for effects of site in both groups. There were no clear differences between the groups in the strength of the association between witnessing violence and conduct problems. However, we found evidence for a ceiling effect, i.e., individuals with very high levels of conduct problems could not show a further increase if exposed to CVE and vice versa. Results indicate that there was no evidence for an ecological fallacy being the primary cause of the association, i.e., CVE must be considered a valid risk factor in the etiology of CD

Quality-of-life assessment in dementia: the use of DEMQOL and DEMQOL-Proxy total scores

Purpose There is a need to determine whether health-related quality-of-life (HRQL) assessments in dementia capture what is important, to form a coherent basis for guiding research and clinical and policy decisions. This study investigated structural validity of HRQL assessments made using the DEMQOL system, with particular interest in studying domains that might be central to HRQL, and the external validity of these HRQL measurements. Methods HRQL of people with dementia was evaluated by 868 self-reports (DEMQOL) and 909 proxy reports (DEMQOL-Proxy) at a community memory service. Exploratory and confirmatory factor analyses (EFA and CFA) were conducted using bifactor models to investigate domains that might be central to general HRQL. Reliability of the general and specific factors measured by the bifactor models was examined using omega (?) and omega hierarchical (? h) coefficients. Multiple-indicators multiple-causes models were used to explore the external validity of these HRQL measurements in terms of their associations with other clinical assessments. Results Bifactor models showed adequate goodness of fit, supporting HRQL in dementia as a general construct that underlies a diverse range of health indicators. At the same time, additional factors were necessary to explain residual covariation of items within specific health domains identified from the literature. Based on these models, DEMQOL and DEMQOL-Proxy overall total scores showed excellent reliability (? h > 0.8). After accounting for common variance due to a general factor, subscale scores were less reliable (? h < 0.7) for informing on individual differences in specific HRQL domains. Depression was more strongly associated with general HRQL based on DEMQOL than on DEMQOL-Proxy (?0.55 vs ?0.22). Cognitive impairment had no reliable association with general HRQL based on DEMQOL or DEMQOL-Proxy. Conclusions The tenability of a bifactor model of HRQL in dementia suggests that it is possible to retain theoretical focus on the assessment of a general phenomenon, while exploring variation in specific HRQL domains for insights on what may lie at the ‘heart’ of HRQL for people with dementia. These data suggest that DEMQOL and DEMQOL-Proxy total scores are likely to be accurate measures of individual differences in HRQL, but that subscale scores should not be used. No specific domain was solely responsible for general HRQL at dementia diagnosis. Better HRQL was moderately associated with less depressive symptoms, but this was less apparent based on informant reports. HRQL was not associated with severity of cognitive impairment

Dysregulation of CXC motif ligand 10 during aging and association with cognitive performance

Chronic low-grade inflammation during aging (inflammaging) is associated with cognitive decline and neurodegeneration, however, the mechanisms underlying inflammaging are unclear. We studied a population (n = 361) of healthy young and old adults from the MyoAge cohort. Peripheral levels of C-X-C motif chemokine 10 (CXCL10) was found to be higher in older adults, compared with young, and negatively associated with working memory performance. This coincided with an age-related reduction in blood DNA methylation at specific CpGs within the CXCL10 gene promoter. In vitro analysis supported the role of DNA methylation in regulating CXCL10 transcription. A polymorphism (rs56061981) that altered methylation at one of these CpG sites further associated with working memory performance in two independent aging cohorts. Studying prefrontal cortex samples, we found higher CXCL10 protein levels in those with Alzheimer’s disease, compared to aged controls. These findings support the association of peripheral inflammation, as demonstrated by CXCL10, in aging and cognitive decline. We reveal age-related epigenetic and genetic factors which contribute to the dysregulation of CXCL10

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Obesity in adults: a 2022 adapted clinical practice guideline for Ireland

This Clinical Practice Guideline (CPG) for the management of obesity in adults in Ireland, adapted from the Canadian CPG, defines obesity as a complex chronic disease characterised by excess or dysfunctional adiposity that impairs health. The guideline reflects substantial advances in the understanding of the determinants, pathophysiology, assessment, and treatment of obesity. It shifts the focus of obesity management toward improving patient-centred health outcomes, functional outcomes, and social and economic participation, rather than weight loss alone. It gives recommendations for care that are underpinned by evidence-based principles of chronic disease management; validate patients' lived experiences; move beyond simplistic approaches of "eat less, move more" and address the root drivers of obesity. People living with obesity face substantial bias and stigma, which contribute to increased morbidity and mortality independent of body weight. Education is needed for all healthcare professionals in Ireland to address the gap in skills, increase knowledge of evidence-based practice, and eliminate bias and stigma in healthcare settings. We call for people living with obesity in Ireland to have access to evidence-informed care, including medical, medical nutrition therapy, physical activity and physical rehabilitation interventions, psychological interventions, pharmacotherapy, and bariatric surgery. This can be best achieved by resourcing and fully implementing the Model of Care for the Management of Adult Overweight and Obesity. To address health inequalities, we also call for the inclusion of obesity in the Structured Chronic Disease Management Programme and for pharmacotherapy reimbursement, to ensure equal access to treatment based on health-need rather than ability to pay

Drug binding sites on Nat1.8 sodium channels

The voltage-gated sodium channel, Nav 1.8, is known to play an important role in pain signalling. In this thesis, the functional properties and drug binding sites of wild type and mutant Nav 1.8 sodium channel currents were studied in mammalian sensory neuron-derived ND7/23 cells using whole-cell patch clamp. While the voltage-dependence of activation was similar for wild type human and rat Nay 1.8 channels, the voltage-dependence of steady-state inactivation was more hyperpolarised for hNav 1.8 compared to rNav 1.8. Furthermore, as a consequence of the different time course for inactivation between human and rat channels, inhibition during frequent stimulation was less pronounced for hNav 1.8 than for rNav 1.8. Thus, this would imply that the human channel is more inactivated at normal resting potentials, and can support higher firing frequencies than the rat channel. The action of tetracaine, ralfmamide, 227c89, Vl02862, and Nav1. 8-selective compound A-803467 on wild type hNav 1.8 and rNav 1.8 channels was studied. All compounds showed preferential block of inactivated channels rather than resting channels. Compound A-803467 showed greater affinity for inactivated hNav 1.8 channels than for inactivated rNav 1.8 channels. Unexpectedly, an increase in current was observed for V102862 and A-803467 during recovery from inactivation, likely due to "disinhibition" of resting block. For A-803467, rather than usedependent inhibition, this disinhibition increased the current during frequent stimulation, while for VI 02862 it led to the absence of inhibition during low frequency stimulation. Thus while both V 102862 and A-803467 are potent inhibitors ofNav 1.8, V102862, rather than A-803467 might be a more useful blocker where physiological firing frequencies are higher. Alanine mutations at residues 1381, N390, L14l0, V14l4, Il706, F1710 and Y1717 were made in the pore-lining S6 segments of the hN av 1. 8 channel, and at the corresponding positions in the rNav 1.8 channel. Many of the mutations caused shifts in voltage-dependence of activation and inactivation, and gave a faster time course of inactivation, indicating that the native residues at these positions are important for both activation and inactivation in Nav 1.8 sodium channels. The affinity of tetracaine for the resting and inactivated channels was reduced by hNav1.8 mutations 138lA, F1710A and Y1717A (only inactivated state affinity was measured for the latter), and by mutation F17l0A for A-803467. For mutation L1410A both compounds caused complete resting block at very low concentrations; this block was removed by further stimulation. While tetracaine did not show disinhibition for wild type channels during recovery from inactivation, it was seen particularly for mutants L1410 and F1710A. All mutations increased the extent of disinhibition of A-803467. These results suggest that the Nav 1.8-selective compound A-803467 acts within the pore S6 segments with a differing but partially overlapping site to that of the local anaesthetic tetracaine