Focused ultrasound examination of the chest on patients admitted with acute signs of respiratory problems:a study protocol for a pragmatic randomised controlled multicentre trial

INTRODUCTION: Patients with acute respiratory problems poses a diagnostic challenge because similar symptoms can be caused by various pathological conditions. Focused ultrasound examination (f-US) of the heart and lungs has proven to increase the diagnostic accuracy in these patients. In this protocol of a randomised multicentre trial, we study the effect of f-US of the heart and lungs in patients with respiratory problems performed by emergency physicians (EP) as soon as the patient arrives to the emergency department (ED). The primary outcome is the number of patients with a correct presumptive diagnosis at 4 hours from admission. METHODS AND ANALYSIS: This is a semiblinded randomised prospective study. 288 patients will be included and randomised into the control or intervention group. All patients receive a standard diagnostic evaluation by the EP to assess the primary presumptive diagnosis. Investigators are EP, with varying degrees of experience in f-US, who perform an f-US of the heart and lungs in patients in both treatment arms. f-US results in the intervention group are non-blinded to the treating EP to be included in the assessment of the 4-hour presumptive diagnosis. As standard for correct diagnosis, we perform a blinded journal audit after discharge. As primary analysis, we use the intention-to-treat analysis. CONCLUSIONS: This study is the first multicentre trial in EDs to investigate whether f-US, in the hands of the EP, increases the proportion of correct diagnosis at 4 hours after arrival when performed on patients with respiratory problems. ETHICS AND DISSEMINATION: This trial is conducted in accordance with the Helsinki II Declaration and approved by the Danish Data Protection Agency and the Committee on Biomedical Research Ethics for the Region of Southern Denmark. Results will be published in accordance with the CONSORT statement in a peer-reviewed scientific journal regardless of the outcome. TRIAL REGISTRATION NUMBER: NCT02550184; Pre-results

Screening for pre-eclampsia using pregnancy-associated plasma protein-A or placental growth factor measurements in blood samples collected at 8–14 weeks' gestation

Objectives: To assess the value of pregnancy-associated plasma protein-A (PAPP-A) in screening for preterm pre-eclampsia (PE) (delivery &lt; 37 weeks' gestation) measured in maternal blood samples collected before 11 weeks, and to compare the screening performance of PAPP-A with that of placental growth factor (PlGF) from blood samples collected at 8–14 weeks. Methods: This study analyzed data from women who participated in the PRESIDE (Pre-eclampsia Screening in Denmark) study, a prospective, non-interventional multicenter study investigating the predictive performance of the Fetal Medicine Foundation first-trimester screening algorithm for PE in a Danish population. As part of combined first-trimester screening, a routine blood sample was collected at 8–14 weeks' gestation and PAPP-A was measured. Excess serum was stored at −80°C and analyzed for PlGF in batches after delivery. Most women in the PRESIDE study had an extra blood sample collected at the time of the first-trimester scan at 11–14 weeks, which was also analyzed for PlGF and PAPP-A in batches after all the participants had delivered. Screening performance was assessed in terms of the detection rate at a 10% screen-positive rate (SPR) for a combination of PAPP-A or PlGF with maternal factors alone and for a combination of each of these biomarkers with maternal factors, mean arterial pressure (MAP) and uterine artery pulsatility index (UtA-PI). Results: The study population comprised 8386 women who had a routine combined first-trimester aneuploidy screening blood sample collected at 8–14 weeks' gestation. In pregnancies that developed preterm PE, the median PAPP-A multiples of the median from routine blood samples were 0.78 (95% CI, 0.67–0.90) before 10 weeks, 0.80 (95% CI, 0.58–1.10) at 10 weeks and 0.64 (95% CI, 0.53–0.78) at 11–14 weeks. In women with samples collected before 10 weeks, there was no significant improvement in the detection rate of preterm PE when PAPP-A or PlGF was combined with maternal factors alone or when combined with maternal factors, MAP and UtA-PI. In routine samples collected at or after 10 weeks, PAPP-A only increased the detection rate of preterm PE slightly. However, PlGF in samples collected at or after 10 weeks increased the detection rate from 31.3% (95% CI, 16.1–50.0%) to 56.3% (95% CI, 37.7–73.6%) at a 10% SPR, i.e. an increase in the detection rate of 25.0% (95% CI, 4.3–44.4%), when combined with maternal factors alone. When PlGF collected from the PRESIDE sample at 11–14 weeks was combined with maternal factors, MAP and UtA-PI, there was an increase in the detection rate from 50.9% (95% CI, 37.1–64.6%) to 67.3% (95% CI, 53.3–79.3%), i.e. an increase of 16.4% (95% CI, 5.6–29.0%) at a 10% SPR. Conclusions: PAPP-A has limited value in first-trimester screening for PE, whereas PlGF adds significantly to the detection rate of preterm PE at 10–14 weeks' gestation.</p

Screening for pre-eclampsia with competing-risks model using placental growth factor measurement in blood samples collected before 11 weeks' gestation

OBJECTIVES: To describe the distributional properties and assess the performance of placental growth factor (PlGF) measured in blood samples collected before 11 weeks' gestation in the prediction of pre-eclampsia (PE).METHODS: The study population consisted of pregnant women included in the Pre-eclampsia Screening in Denmark (PRESIDE) study with a PlGF measurement from the routine combined first-trimester screening (cFTS) blood sample collected at 8-14 weeks' gestation. PRESIDE was a prospective multicenter study investigating the predictive performance of the Fetal Medicine Foundation (FMF) first-trimester screening algorithm for PE in a Danish population. In the current study, serum concentration of PlGF in the cFTS blood samples was analyzed in batches between January and June 2021.RESULTS: A total of 8386 pregnant women were included. The incidence of PE was 0.7% at &lt; 37 weeks' gestation and 3.0% at ≥ 37 weeks. In blood samples collected at 10 weeks' gestation, PlGF multiples of the median (MoM) were significantly lower in pregnancies with preterm PE &lt; 37 weeks compared to unaffected pregnancies. However, PlGF MoM did not differ significantly between pregnancies with PE and unaffected pregnancies in samples collected before 10 weeks' gestation.CONCLUSIONS: The gestational-age range for PlGF sampling may be expanded from 11-14 to 10-14 weeks when assessing the risk for PE using the FMF first-trimester screening model. There is little evidence to support the use of PlGF in blood samples collected before 10 weeks' gestation. © 2023 The Authors. Ultrasound in Obstetrics &amp; Gynecology published by John Wiley &amp; Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.</p

Diagnostic value of whole-body-focused ultrasonography in high-acuity patients in the emergency department:a prospective single-center cross-sectional study

Background: A fast and diagnostic accurate tool to assess the unselected category of high-acuity patients, in whom the underlying pathology is not always obvious, is needed in the emergency departments (ED). We aim to describe the feasibility, validity and diagnostic yield of a routine whole-body-focused ultrasonography (wbf-us) in an unselected group of high-acuity ED patients. Methods: In a prospective observational study, a convenience sample of ED patients (≥ 18 years) with a high-acuity score or systolic blood pressure &lt; 100 mmHg received a routine wbf-us of the heart, lungs, abdomen and deep veins by two non-expert sonographers. Final diagnosis was established by experienced auditors. Investigators were blinded to the patients’ medical history and emergency physicians and auditors were blinded to the investigators assessments. Diagnostic accuracy was assessed by comparing the investigators’ ultrasonography findings to a structured double-blinded clinical audit of patient files. Results: We included 171 patients, initiated a whole-body-focused ultrasonography examination (wbf-us) in 160 and completed it in 128 patients with an average time of a full examination of 28 min. We found pathology in 65/171 (38%) of the patients whose most frequent symptoms upon arrival were cardiopulmonary. Among the patients who received wbf-us, we found the majority of pathology by wbf-us of the lungs (n = 50, 31%), the heart (n = 26, 16%), few in the abdomen (n = 5, 3%) and none in the deep veins. The overall sensitivity was 50–100%, specificity 84–94%, positive predictive value 11–44% and negative predictive value 94–100%. Conclusion: Focused cardiopulmonary ultrasonography might be considered for routine use in high-acuity ED patients with cardiopulmonary symptoms whereas focused ultrasonography of the abdomen and deep veins performed by non-expert sonographers only seems indicated in selected patients. Trial registration Danish Data Protection Agency (ID 13/12076). Committee on Biomedical Research Ethics for the Region of Southern Denmark (ID S-20130047).</p

Immersive Virtual Reality in Basic Point-of-Care Ultrasound Training:A Randomized Controlled Trial

This study was aimed at comparing the learning efficacy of a traditional instructor-led lesson with that of a completely virtual, self-directed lesson in immersive virtual reality (IVR) in teaching basic point-of-care ultrasonography (PoCUS) skills. We conducted a blinded, non-inferiority, parallel-group, randomized controlled trial in which final-year medical students were randomized to an instructor-led (n = 53) or IVR (n = 51) lesson. Participants' learning efficacy was evaluated by blinded assessors, who rated each participant's performance using the Objective Structured Assessment of Ultrasound Skills (OSAUS) assessment tool.The mean total scores for participants were 11.0 points (95% confidence interval: 9.8-12.2) for the instructor-led lesson and 10.3 points (95% confidence interval: 9.0-11.5) for the IVR lesson. No significant differences were observed between the groups with respect to total score (p = 0.36) or subgroup objectives of the OSAUS score (p = 0.34 for familiarity, p = 0.45 for image optimization, p = 0.96 for systematic approach and p = 0.07 for interpretation). Maintenance costs for both courses were estimated at 400 euros each. Startup costs for the instructor-led course were estimated 16 times higher than those for the IVR course. The learning efficacy of an instructor-led lesson on basic US did not differ significantly from that of a self-directed lesson in IVR, as assessed using the OSAUS. The results suggest that IVR could be an equivalent alternative to instructor-led lessons in future basic ultrasonography courses, but further research is warranted to clarify the role of IVR in PoCUS courses.</p

Pre-eclampsia screening in Denmark (PRESIDE):national validation study

Objectives: To investigate the predictive performance of the Fetal Medicine Foundation (FMF) first-trimester screening algorithm for pre-eclampsia in a Danish population and compare screening performance with that of the current Danish strategy, which is based on maternal risk factors. Methods: This was a prospective study of women with a singleton pregnancy attending for their first-trimester ultrasound scan and screening for aneuploidies at six Danish university hospitals between May 2019 and December 2020. Prenatal data on maternal characteristics and medical history were recorded, and measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum pregnancy-associated plasma protein-A (PAPP-A) and serum placental growth factor (PlGF) were collected without performing a risk assessment for pre-eclampsia. Information on acetylsalicylic acid use was recorded. After delivery, pregnancy outcome, including gestational age at delivery and pre-eclampsia diagnosis, was recorded. Pre-eclampsia risk assessment for each woman was calculated blinded to outcome using the FMF screening algorithm following adjustment to the Danish population. Detection rates (DRs) of the FMF algorithm were calculated for a fixed screen-positive rate (SPR) of 10% and for the SPR achieved in the current Danish screening. Results: A total of 8783 pregnant women were included, with a median age of 30.8 (interquartile range (IQR), 28.1–33.9) years. The majority were white (95%), naturally conceiving (90%), non-smokers (97%) and had no family history of pre-eclampsia (96%). The median body mass index was 23.4 (IQR, 21.2–26.6) kg/m2. A complete risk assessment including maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A was available for 8156 women (92.9%). In these women, UtA-PI was measured bilaterally with a median value of 1.58 (IQR, 1.27–1.94) and the median resting MAP of 80.5 (IQR, 76.1–85.4) mmHg in two consecutive measurements. Among these, 303 (3.7%) developed pre-eclampsia, including 55 (0.7%) cases of pre-eclampsia with delivery &lt; 37 weeks of gestation and 16 (0.2%) cases of pre-eclampsia with delivery &lt; 34 weeks. At a SPR of 10%, combined screening using the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A had a DR of 77.4% (95% CI, 57.6–97.2%) for pre-eclampsia with delivery &lt; 34 weeks, 66.8% (95% CI, 54.4–79.1%) for pre-eclampsia with delivery &lt; 37 weeks and 44.1% (95% CI, 38.5–49.7%) for pre-eclampsia with delivery at any gestational age. The current Danish screening strategy using maternal risk factors detected 25.0% of women with pre-eclampsia with delivery &lt; 34 weeks and 19.6% of women with pre-eclampsia with delivery &lt; 37 weeks at a SPR of 3.4%. When applying the FMF algorithm including maternal characteristics, MAP, UtA-PI and PlGF at the fixed SPR of 3.4%, the DRs were 60.5% (95% CI, 36.9–84.1%) for PE with delivery &lt; 34 weeks and 45.2% (95% CI, 32.0–58.5%) for PE with delivery &lt; 37 weeks. Conclusion: In this large Danish multicenter study, the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A predicted 77.4% of cases with pre-eclampsia with delivery &lt; 34 weeks and 66.8% of cases with pre-eclampsia with delivery &lt; 37 weeks of gestation at a SPR of 10%, suggesting that the performance of the algorithm in a Danish cohort matches that in other populations.</p

Outlook for inverse design in nanophotonics

Recent advancements in computational inverse design have begun to reshape the landscape of structures and techniques available to nanophotonics. Here, we outline a cross section of key developments at the intersection of these two fields: moving from a recap of foundational results to motivation of emerging applications in nonlinear, topological, near-field and on-chip optics.Comment: 13 pages, 6 figure

Codeine in post-operative pain. Study of the influence of sparteine phenotype and serum concentrations of morphine and morphine-6-glucuronide

Objective: Within the past decade, human experimental pain studies have supported the 50-year-old hypothesis that codeine is a prodrug, which has to be converted to morphine to exert an analgesic effect. This study aimed at evaluating the impact of sparteine phenotype and serum concentrations of morphine on the efficacy of codeine in post-operative pain. Methods: Eighty-one patients with a pain rating of 3 or more on a 0-10 numerical rating scale 0.5 h after surgery were included in the study. The patients were given an oral dose of 100 mg codeine and rated pain with the numerical rating scale 0.5 h and 1 h after medication. Blood for determination of serum concentration of codeine and its metabolites was collected 1 h after medication, and a 12-h urine sample after administration of 100 mg sparteine was used to determine the sparteine phenotype. Results: Eight patients were poor metabolizers and 66 were extensive metabolizers of sparteine, while the urine samples for the remaining seven patients were lost. In 22 patients, including the eight poor metabolizers, the serum concentrations of both morphine and morphine-6-glucuronide (M6G) were below the limit of determination of the assay, i.e. 1.5 nmol · l-1 and 2 nmol · l-1, respectively. A sum of the concentration of these two substances below 10 nmol · l-1 was found in an additional eight patients. The sum of differences between pre- and post-operative pain ratings did not differ between the two phenotypes (P = 0.60), whereas the 30 patients with serum concentrations of morphine plus M6G below 10 nmol · l-1 had a marginally significant lower sum than the 51 patients with higher levels of these substances (median 1.5 vs 2.5, P = 0.058). Conclusions: A low serum concentration of morphine and M6G seems to be common in patients treated with codeine for post-operative pain, and low concentrations of these active substances may be related to decreased efficacy of codeine.</p