Coolsense® versus EMLA® for peripheral venous cannulation in adult volunteers: A randomised crossover trial

Peripheral venous cannulation (PVC) is a commonly performed invasive medical procedure. Topical treatments such as the eutectic mixture of local anaesthetics (EMLA®, Aspen Pharmacare Australia Pty Ltd, St Leonards, NSW) attenuate the associated pain, but are limited by requiring up to one hour of application before becoming effective. The Coolsense® (Coolsense Medical Ltd., Tel Aviv, Israel) pain numbing applicator is a new device using a cryoanalgesic means to anaesthetise skin within seconds. Coolsense is being increasingly used for cannulation, but comparative studies are lacking. We recruited 64 healthy adult volunteers to this open-label two sequence, two period randomised crossover trial. Participants had two 20 gauge venous cannulae inserted, one on the dorsum of each hand. Each cannulation attempt was preceded by treatment with Coolsense or an EMLA patch containing 2.5% lidocaine and 2.5% prilocaine. The primary outcome was participant pain using the 0–10 numerical pain rating scale. Secondary outcomes were participant satisfaction scores on a 0–10 scale, treatment preference, and failed cannulation attempts. Participants were randomly assigned to either the Coolsense EMLA ( n = 32) or EMLA Coolsense ( n = 32) sequence. All participants completed the trial. The pooled mean paired difference of the numerical pain rating scale was –1.84 (95% confidence intervals –1.28 to –2.41; P < 0.001) in favour of EMLA. The pooled mean paired difference for satisfaction score was 2.26 (95% confidence intervals 1.46 to 3.07; P < 0.001) higher with EMLA. Most participants preferred EMLA over Coolsense ( P < 0.001). There was no significant difference regarding failed cannulation between the two treatments ( P = 0.14). Among healthy individuals undergoing elective PVC, EMLA was associated with reduced pain, increased satisfaction, and was the preferred treatment compared to Coolsense.

Kidney length normative values in children aged 0–19 years — a multicenter study

Background Currently used pediatric kidney length normative values are based on small single-center studies, do not include kidney function assessment, and focus mostly on newborns and infants. We aimed to develop ultrasound-based kidney length normative values derived from a large group of European Caucasian children with normal kidney function. Methods Out of 1,782 children aged 0–19 years, 1,758 individuals with no present or past kidney disease and normal estimated glomerular filtration rate had sonographic assessment of kidney length. The results were correlated with anthropometric parameters and estimated glomerular filtration rate. Kidney length was correlated with age, height, body surface area, and body mass index. Height-related kidney length curves and table were generated using the LMS method. Multivariate regression analysis with collinearity checks was used to evaluate kidney length predictors. Results There was no significant difference in kidney size in relation to height between boys and girls. We found significant (p < 0.001), but clinically unimportant (Cohen’s D effect size = 0.04 and 0.06) differences between prone vs. supine position (mean paired difference = 0.64 mm, 95% CI = 0.49–0.77) and left vs. right kidneys (mean paired difference = 1.03 mm, 95% CI = 0.83–1.21), respectively. For kidney length prediction, the highest coefficient correlation was observed with height (adjusted R2 = 0.87, p < 0.0001). Conclusions We present height-related LMS-percentile curves and tables of kidney length which may serve as normative values for kidney length in children from birth to 19 years of age. The most significant predictor of kidney length was statural height. Graphic Abstract

Commencing one-handed chest compressions while activating emergency medical system using a handheld mobile device in lone-rescuer basic life support: a randomised cross-over simulation study

IntroductionIn conventional basic life support (c-BLS), a lone rescuer is recommended to start chest compressions (CCs) after activating the emergency medical system. To initiate earlier CCs in lone-rescuer BLS, we designed a modified BLS (m-BLS) sequence in which the lone rescuer commences one-handed CCs while calling for help using a handheld cellular phone with the other free hand. This study aimed to compare the quality of BLS between c-BLS and m-BLS.MethodsThis was a simulation study performed with a randomised cross-over controlled trial design. A total of 108 university students were finally enrolled. After training for both c-BLS and m-BLS, participants performed a 3-minute c-BLS or m-BLS on a manikin with a SkillReporter at random cross-over order. The paired mean difference with SE between c-BLS and m-BLS was assessed using paired t-test.ResultsThe m-BLS had reduced lag time before the initiation of CCs (with a mean estimated paired difference (SE) of −35.0 (90.4) s) (p<0.001). For CC, a significant increase in compression fraction and a higher number of CCs with correct depth were observed in m-BLS (with a mean estimated paired difference (SE) of 16.2% (0.6) and 26.9% (3.3), respectively) (all p<0.001). However, no significant paired difference was observed in the hand position, compression rate and interruption time. For ventilation, the mean tidal volumes did not differ. However, the number of breaths with correct tidal volume was higher in m-BLS than in c-BLS.ConclusionIn simulated lone-rescuer BLS, the m-BLS could deliver significantly earlier CCs than the c-BLS while maintaining high-quality cardiopulmonary resuscitation.

RADI-11. Evaluating the Tissue Effects of Dose-escalated Pre-operative Stereotactic Radiotherapy for Resectable Brain Metastasis

Background Although the classic radiobiologic principles of radiotherapy are well understood, the unique effects of the large fractional does that characterize stereotactic radiotherapy (SRT), specifically in terms of antitumor immune cellular processes, vascular damage, tumor necrosis, and apoptosis on brain metastasis have yet to be adequately demonstrated. The objective of this study is to provide the first in-human evaluation of the biological effects of SRT in resected brain metastasis. Methods All paired primary tumors and metastases for patients who underwent dose-escalated preoperative SRT followed by resection were evaluated for tumor necrosis using hematoxylin-eosin staining. T cells (CD3+, CD4+, CD8+), natural killer cells (CD56+), vessel density (CD31+), and apoptotic factors (caspase-3) were determined by immunohistochemical analysis. Results Fifteen patients with brain metastases from solid tumors received a median preoperative SRT dose of 18 Gy (range: 15–18 Gy) in 1 fraction, with 2 patients receiving 27–30 Gy in 3–5 fractions, followed by resection within a median interval of 90 hours (Range: 17.1–260 hours). The rate of necrosis was found to be significantly higher in irradiated brain metastases than in non-irradiated primary tumor samples (mean paired difference: 30.47, SD: 29.28, p=0.001). A decrease in all immunomodulatory cell populations was found in irradiated metastasis: CD3 (mean paired difference -19.4, SD: 31.7, p=0.03), CD4 (-10.0, SD: 20, p=0.01), and CD8 (-17.4, SD: 22.1, p=0.008). While irradiated samples had numerically lower CD 31+, CD 56+, and caspase-3 scores, the difference was not statistically significant. Time interval from SRT to surgery had no effect on these parameters. Conclusions There is complex interplay between tumor-associated cells and the unique radiobiological effects of SRT on tumor tissue. Although time interval from SRT to surgery was associated with increased tumor necrosis, differences in immunomodulatory factors may be multifactorial, including concurrent corticosteroids or the immunosuppressive effect of SRT.

Use baseline axial length measurements in myopic patients to predict the control of myopia with and without atropine 0.01%

Purpose Identifying axial length growth rate as an indicator of fast progression before initiating atropine 0.01% for myopia progression in children. Method From baseline, axial length growth over six months was measured prospectively. Subjects were then initiated on atropine 0.01% if axial length growth was greater than 0.1mm per 6 months (fast progressors), axial length and spherical equivalent change measurements recorded every six months. The rate of change was compared to the baseline pre-treatment rate. If axial length change was below the threshold, subjects received monitoring only. Results 73 subjects were identified as fast progressors and commenced atropine 0.01%, (mean baseline refraction of OD -2.9±1.6, OS -2.9±1.8 and a mean baseline axial length OD 24.62 ± 1.00 mm, OS 24.53 ± 0.99 mm). At six months, the mean paired difference of axial length growth rate was significantly reduced by 50% of baseline (all 73 subjects, p<0.05). 53 subjects followed to 12 months, and 12 to 24 months maintained a reduced growth rate. Change in mean spherical equivalent was significantly reduced compared to pre-treatment refractive error (mean paired difference p<0.05) and at each subsequent visit. 91 children were slow progressors and remained untreated. Their axial length growth rate did not change significantly out to 24 months. Spherical equivalent changed less than -0.5D annually in this group. Conclusion Identifying fast progressors before treatment initiation demonstrated a strong treatment effect with atropine 0.01% reducing their individual rate of myopia progression by 50%. Another large group of myopic children, slow progressors, continued without medical intervention. A baseline axial length growth rate is proposed as a guideline to identify fast progressors who are more likely to benefit from atropine 0.01%.

Liquid Biopsies from Pleural Effusions and Plasma from Patients with Malignant Pleural Mesothelioma: A Feasibility Study

Background: Malignant pleural mesothelioma (MPM) is a fatal tumor with a poor prognosis. The recent developments of liquid biopsies could provide novel diagnostic and prognostic tools in oncology. However, there is limited information about the feasibility of this technique for MPMs. Here, we investigate whether cancer-specific DNA sequences can be detected in pleural fluids and plasma of MPM patients as free circulating tumor DNA (ctDNA). Methods: We performed whole-exome sequencing on 14 tumor biopsies from 14 patients, and we analyzed 20 patient-specific somatic mutations with digital droplet PCR (ddPCR) in pleural fluids and plasma, using them as cancer-specific tumor biomarkers. Results: Most of the selected mutations could be detected in pleural fluids (94%) and, noteworthy, in plasma (83%) with the use of ddPCR. Pleural fluids showed similar levels of somatically mutated ctDNA (median = 12.75%, average = 16.3%, standard deviation = 12.3) as those detected in solid biopsies (median = 21.95%; average = 22.21%; standard deviation = 9.57), and their paired difference was weakly statistically significant (p = 0.048). On the other hand, the paired difference between solid biopsies and ctDNA from plasma (median = 0.29%, average = 0.89%, standard deviation = 1.40) was highly statistically significant (p = 2.5 × 10−7), corresponding to the important drop of circulating somatically mutated DNA in the bloodstream. However, despite the tiny amount of ctDNA in plasma, varying from 5.57% down to 0.14%, the mutations were detectable at rates similar to those possible for other tumors. Conclusions: We found robust evidence that mutated DNA is spilled from MPMs, mostly into pleural fluids, proving the concept that liquid biopsies are feasible for MPM patients.

Mid-term development of the right ventricle in competitive athletes

Background Long-term intensive training induces physiological, morphological, and functional adaption of the athlete’s heart. Purpose To evaluate the development of athlete’s heart during a mid-term follow-up of competitive athletes using cardiac magnetic resonance (CMR). Material and Methods Eighteen competitive long-distance runners and triathletes (age 43 ± 13 years, 3 women) were prospectively examined in a longitudinal follow-up study 5.05 ± 0.6 years after baseline. CMR at 1.5-T was performed for functional and late gadolinium enhancement (LGE) imaging. Left ventricular (LV) and right ventricular (RV) end-diastolic volume (LVEDV, RVEDV) as well as ejection fraction (LVEF, RVEF), LV myocardial mass (LVMM), and atrial sizes were determined and compared to baseline in matched pairs statistics for paired difference. Results LVEDV (197 ± 38 mL vs. 196 ± 38 mL, paired difference −0.9 mL, P = 0.7) and LVEF (62 ± 7% vs. 62 ± 5%, paired difference 0.1%, P = 0.9) did not change during the follow-up period, whereas LVMM increased significantly (149 ± 31 g vs.164 ± 32 g, paired difference 14 g, P < 0.0001). RVEDV significantly increased from 221 ± 47 mL at baseline to 230 ± 52 mL (paired difference 10 mL, P = 0.0033). RVEF decreased from baseline 57 ± 8% to 53 ± 7% (paired difference −3%, P = 0.0234). Left atrial size showed no significant changes (24 ± 5 cm2 vs. 25 ± 6 cm2, paired difference 0.5 cm2, P = 0.17) and right atrial size increased significantly (30 ± 5 cm2 vs. 32 ± 4 cm2, paired difference 2 cm2, P = 0.0054). Conclusion This study supports the theory of ongoing remodeling in an athlete’s heart. Predominantly the right heart can further enlarge in a mid-term period. This response seems not linearly dependent on a steady, decreased, or increased training volume.

Hylaeus communis (Hymenoptera: Colletidae), a new exotic bee for North America with generalist foraging and habitat preferences

We document a novel exotic bee for North America, Hylaeus (Hylaeus) communis Nylander, 1852 (Hymenoptera: Colletidae), and determine whether it is likely to spread widely across the continent. To evaluate the extent to which H. communis behaves as a generalist and would be able to adapt to novel North American environments, we compare the breadth of its climatic, floral, habitat, and nesting preferences between its native European range and sites where it was first discovered in southern Québec, Canada. Specifically, we calculate the paired difference index, which approximates species generalism, from a set of bipartite networks linking Hylaeus Fabricius, 1793 species to their respective floral hosts and habitats. Results indicate that H. communis is the most adaptable bee of the European Hylaeus fauna and will likely acclimate to its new environment, being a greater generalist than an already widely established exotic bee, H. hyalinatus Smith, 1842. In southern Québec, we find that, despite visiting a wide variety of flowering species, it exhibits a strong association with non-native plants and resides almost exclusively in urban settings. We hypothesise that H. communis will be able to spread widely throughout North America via multiple human-mediated but accidental dispersal events and by following the distribution of European weeds and horticultural plants.

Perceptions on the Impact of a Just-in-Time Room on Trainees and Supervising Physicians in a Pediatric Emergency Department

ABSTRACT Background Just-in-time (JIT) training refers to education occurring immediately prior to clinical encounters. An in situ JIT room in a pediatric emergency department (ED) was created for procedural education. Objective We examined trainee self-reported JIT room use, its impact on trainee self-perception of procedural competence/confidence, and the effect its usage has on the need for intervention by supervising physicians during procedures. Methods Cross-sectional survey study of a convenience sample of residents rotating through the ED and supervising pediatric emergency medicine physicians. Outcomes included JIT room use, trainee procedural confidence, and frequency of supervisor intervention during procedures. Results Thirty-one of 32 supervising physicians (97%) and 122 of 186 residents (66%) completed the survey, with 71% of trainees reporting improved confidence, and 68% reporting improved procedural skills (P &lt; .05, +1.4-point average skills improvement on a 5-point Likert scale). Trainees perceived no difference among supervising physicians intervening in procedures with or without JIT room use (P = .30, paired difference −0.0 points). Nearly all supervisors reported improved trainee procedural confidence, and 77% reported improved trainee procedural skills after JIT room use (P &lt; .05, paired difference +1.8 points); 58% of supervisors stated they intervene in procedures without trainee JIT room use, compared with 42% with JIT room use (P &lt; .05, paired difference −0.4 points). Conclusions Use of the JIT room led to improved trainee confidence and supervisor reports of less procedural intervention. Although it carries financial and time costs, an in situ JIT room may be important for convenient JIT training.