Age-related High-frequency Hearing Loss Is Not Associated With Horizontal Semicircular Canal Function.

OBJECTIVE: Investigate the association between age-related hearing loss and reduced peripheral vestibular function using paired assessments of high-frequency hearing and horizontal semicircular canal (HSC) function. We hypothesized that age-related high-frequency hearing loss would be correlated with reduced HSC function and, therefore, useful to predict age-related vestibular hypofunction. DESIGN: We conducted a single center, retrospective cross-sectional study in a tertiary/academic referral hospital. This study included 185 patients who were diagnosed with a cerebellopontine angle (CPA) tumor and referred to the academic hospital to evaluate treatment options. Data collected included pure-tone audiometry, caloric reflex test, video head-impulse test (vHIT), and medical history. High-frequency hearing loss was quantified by the high Fletcher index (hFI), and horizontal semicircular canal (HSC) function were quantified by the caloric reflex test and vHIT. RESULTS: We observed a significant association between age and high-frequency hearing loss that was significantly worse in men compared with women. In contrast, we observed no significant association between age and HSC function assessed by either the caloric reflex test or vHIT. We observed associations between HSC function and sex, with male sex predicting reduced HSC function by caloric reflex testing but enhanced HSC function by vHIT. High-frequency hearing loss did not predict HSC hypofunction. CONCLUSIONS: We found no evidence indicating age-related decline in HSC function or an association between age-related high-frequency hearing loss and age-related decline in HSC function. We did observe sex-specific differences in HSC function. Our study highlights the need for sex-specific normative values for identifying age-related reduced peripheral vestibular function and for future work linking comprehensive assessments of inner ear function with tests of balance and stability to understand the complex interactions underlying hearing loss and imbalance, especially in the elderly.

Family screening in patients with isolated bicuspid aortic valve : Restriction to those with aortic dilatation is not justified.

AIM: To determine the prevalence of undiagnosed bicuspid aortic valve (BAV) and isolated aortic dilatation in first-degree relatives (FDRs) of patients with isolated BAV and to explore the recurrence risk of BAV in different subgroups of probands with BAV. Recent American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines recommend family screening in patients with associated aortopathy only. METHODS: During follow-up visits, patients with isolated BAV received a printed invitation for their FDRs advising cardiac screening. RESULTS: From 2012-2019, 257 FDRs of 118 adult BAV patients were screened, among whom 63 (53%) index patients had undergone aortic valve surgery (AVS), including concomitant aortic replacement in 25 (21%). Of the non-operated index patients, 31 (26%) had aortic dilatation (> 40 mm). Mean age of the FDRs was 48 years (range 4-83) and 42% were male. The FDR group comprised 20 parents, 103 siblings and 134 offspring. Among these FDRs, 12 (4.7%) had a previously undiagnosed BAV and 23 (8.9%) had an isolated aortic dilatation. FDRs of the probands with previous AVS (n = 147) had a risk ratio for BAV of 2.25 (95% confidence interval (CI) 0.62-8.10). FDRs of the probands with BAV and repaired or unrepaired aortic dilatation (n = 127) had a risk ratio for BAV of 0.51 (95% CI 0.16-1.66). CONCLUSION: Screening FDRs of patients with isolated BAV resulted in a reasonable yield of 14% new cases of BAV or isolated aortic dilatation. A trend towards an increased risk of BAV in FDRs was observed in the probands with previous AVS, whereas this risk seemed to be diminished in the probands with associated aortic dilatation. This latter finding does not support the restrictive ACC/AHA recommendation.

Objective determination of peripheral edema in heart failure patients using short-wave infrared molecular chemical imaging.

SIGNIFICANCE: Peripheral pitting edema is a clinician-administered measure for grading edema. Peripheral edema is graded 0, 1 + , 2 + , 3 + , or 4 + , but subjectivity is a major limitation of this technique. A pilot clinical study for short-wave infrared (SWIR) molecular chemical imaging (MCI) effectiveness as an objective, non-contact quantitative peripheral edema measure is underway. AIM: We explore if SWIR MCI can differentiate populations with and without peripheral edema. Further, we evaluate the technology for correctly stratifying subjects with peripheral edema. APPROACH: SWIR MCI of shins from healthy subjects and heart failure (HF) patients was performed. Partial least squares discriminant analysis (PLS-DA) was used to discriminate the two populations. PLS regression (PLSR) was applied to assess the ability of MCI to grade edema. RESULTS: Average spectra from edema exhibited higher water absorption than non-edema spectra. SWIR MCI differentiated healthy volunteers from a population representing all pitting edema grades with 97.1% accuracy (N = 103 shins). Additionally, SWIR MCI correctly classified shin pitting edema levels in patients with 81.6% accuracy. CONCLUSIONS: Our study successfully achieved the two primary endpoints. Application of SWIR MCI to monitor patients while actively receiving HF treatment is necessary to validate SWIR MCI as an HF monitoring technology.

Investigation of the association between gall bladder wall thickness and hypoalbuminaemia in dogs.

OBJECTIVES: To assess the correlation between gallbladder wall thickness and serum/plasma albumin concentrations in dogs. MATERIALS AND METHODS: Retrospective searches of digital medical record databases were conducted to identify dogs that had either severely low serum/plasma albumin concentration (<1.5 g/dL) or ultrasonographic evidence of gallbladder wall thickening (>2 mm). Analysis of covariance models were used to analyze gallbladder wall thickness with sample type (serum vs plasma), age, etiology, albumin, and albumin ' etiology as the covariates. RESULTS: A total of 216 dogs met inclusion criteria. One-hundred and forty-six dogs had a thickened gallbladder wall (Group 1). Median serum/plasma albumin concentration for dogs in this group was 2.2 g/dL (1 to 5 g/dL), and 84 dogs (57.5%) had hypoalbuminemia (<2.5 g/dL). The search for dogs with severe hypoalbuminemia (< 1.5 g/dL) identified 70 dogs (Group 2). In this group, median gallbladder wall thickness was 1.3 mm (0.2 to 6.1 mm) and 17 dogs (24.3%) had a thickened gallbladder wall. Serum/plasma albumin concentration and gallbladder wall thickness were not significantly correlated for Group 1 (r = 0.0044, p = 0.9580) or Group 2 (r = -0.1137, p = 0.3487). A moderate negative correlation (-0.64) was identified between gallbladder wall thickness and albumin concentration in dogs with immune-mediated diseases (p = 0.03). CLINICAL SIGNIFICANCE: Gallbladder wall thickness and serum/plasma albumin concentration are independent variables in dogs.

Ethical review of COVID-19 research in the Netherlands; a mixed-method evaluation among medical research ethics committees and investigators.

BACKGROUND: During the beginning of the COVID-19 pandemic there was an urgent need for accelerated review of COVID-19 research by Medical Research Ethics Committees (MRECs). In the Netherlands this led to the implementation of so-called 'fast-track-review-procedures' (FTRPs) to enable a swift start of urgent and relevant research. The objective of this study is to evaluate FTRPs of MRECs in the Netherlands during the COVID-19 pandemic and to compare them with the regular review procedures (RRPs). METHODS AND FINDINGS: An explanatory sequential mixed method study was conducted. Online questionnaires and four group interviews were conducted among MREC representatives and investigators of COVID-19 research. In addition, data from a national research registration system was requested. Main outcome measures are differences in timelines, quality of the review and satisfaction between FTRPs and RRPs. The total number of review days was shorter in FTRP (median 10.5) compared to RRPs (median 98.0). Review days attributable to the MRECs also declined in FTRPs (median 8.0 versus 50.0). This shortening can be explained by installing ad hoc (sub)committees, full priority given to COVID-19 research, regular research put on hold, online review meetings and administrative leniency. The shorter timelines did not affect the perceived quality of the review and ethical and legal aspects were not weighted differently. Both MREC representatives and investigators were generally satisfied with the review of COVID-19 research. Weaknesses identified were the lack of overview of COVID-19 research and central collaboration and coordination, the delay of review of regular research, and limited reachability of secretariats. CONCLUSIONS: This study shows that accelerated review is feasible during emergency situations. We did not find evidence that review quality was compromised and both investigators and MRECs were content with the FTRP. To improve future medical ethical review during pandemic situations and beyond, distinguishing main and side issues, working digitally, and (inter)national collaboration and coordination are important.

The relationship between eDNA particle concentration and organism abundance in nature is strengthened by allometric scaling.

Organism abundance is a critical parameter in ecology, but its estimation is often challenging. Approaches utilizing eDNA to indirectly estimate abundance have recently generated substantial interest. However, preliminary correlations observed between eDNA concentration and abundance in nature are typically moderate in strength with significant unexplained variation. Here, we apply a novel approach to integrate allometric scaling coefficients into models of eDNA concentration and organism abundance. We hypothesize that eDNA particle production scales nonlinearly with mass, with scaling coefficients < 1. Wild populations often exhibit substantial variation in individual body size distributions; we therefore predict that the distribution of mass across individuals within a population will influence population-level eDNA production rates. To test our hypothesis, we collected standardized body size distribution and mark-recapture abundance data using whole-lake experiments involving nine populations of brook trout. We correlated eDNA concentration with three metrics of abundance: density (individuals/ha), biomass (kg/ha) and allometrically scaled mass (ASM) (∑(individual mass0.73 )/ha). Density and biomass were both significantly positively correlated with eDNA concentration (adj. r2  = 0.59 and 0.63, respectively), but ASM exhibited improved model fit (adj. r2  = 0.78). We also demonstrate how estimates of ASM derived from eDNA samples in "unknown" systems can be converted to biomass or density estimates with additional size-structure data. Future experiments should empirically validate allometric scaling coefficients for eDNA production, particularly where substantial intraspecific size distribution variation exists. Incorporating allometric scaling may improve predictive models to the extent that eDNA concentration may become a reliable indicator of abundance in nature.

What women want and why. Women's preferences for induction of labour or expectant management in late-term pregnancy.

BACKGROUND: Both induction of labour at 41 weeks and expectant management until 42 weeks are common management strategies in low-risk pregnancy since there is no consensus on the optimal timing of induction in late-term pregnancy for the prevention of adverse outcomes. Our aim was to explore maternal preference for either strategy and the influence on quality of life and maternal anxiety on this preference. METHODS: Obstetrical low-risk women with an uncomplicated pregnancy were eligible when they reached a gestational age of 41 weeks. They were asked to fill in questionnaires on quality of life (EQ6D) and anxiety (STAI-state). Reasons of women's preferences for either induction or expectant management were explored in a semi-structured questionnaire containing open ended questions. RESULTS: Of 782 invited women 604 (77.2%) responded. Induction at 41 weeks was preferred by 44.7% (270/604) women, 42.1% (254/604) preferred expectant management until 42 weeks, while 12.2% (74/604) of women did not have a preference. Women preferring induction reported significantly more problems regarding quality of life and were more anxious than women preferring expectant management (p<0.001). Main reasons for preferring induction of labour were: "safe feeling" (41.2%), "pregnancy taking too long" (35.4%) and "knowing what to expect" (18.6%). For women preferring expectant management, the main reason was "wish to give birth as natural as possible" (80.3%). CONCLUSION: Women's preference for induction of labour or a policy of expectant management in late-term pregnancy is influenced by anxiety, quality of life problems (induction), the presence of a wish for natural birth (expectant management), and a variety of additional reasons. This variation in preferences and motivations suggests that there is room for shared decision making in the management of late-term pregnancy.

Effects of feed composition on the fouling on cation-exchange membranes desalinating polymer-flooding produced water.

HYPOTHESIS: Cation exchange membranes (CEMs) are subject to fouling when utilized to desalinate wastewater from the oil and gas industry, hampering their performance. The kind and extent of the fouling are most likely dependent on the composition of the stream, which in practical applications can vary significantly. EXPERIMENTS: Fouling experiments were performed on commercial cation exchange membranes, which were used in electrodialysis runs to desalinate solutions of varying composition. The variations included ionic strength, type of ions, amount of viscosifying polyelectrolyte (partially hydrolyzed polyacrylamide), presence of crude oil, and surfactants. Performance parameters, like electric potential and pH, were monitored during the runs, after which the membranes were recovered and analyzed. FINDINGS: Fouling was detected on most CEMs and occurred mainly in the presence of the viscosifying polyelectrolyte. Under normal pH conditions (pH ~ 8), the polyelectrolyte fouled the concentrate side of the CEMs, as expected due to electrophoresis. However, by applying a current in the opposite direction, the polyelectrolyte layer could be removed. Precipitation occurred mostly on the opposite side of the membrane, with different morphology depending on the feed composition.

Ketonuria is not associated with hyperemesis gravidarum disease severity.

OBJECTIVE: To assess the association between ketonuria and hyperemesis gravidarum (HG) disease severity. STUDY DESIGN: We included pregnant women hospitalised for HG who participated in the Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding (MOTHER) trial and women who were eligible, chose not to be randomised and agreed to participate in the observational cohort. Between October 2013 and March 2016, in 19 hospitals in the Netherlands, women hospitalised for HG were approached for study participation. The presence of ketonuria was not required for study entry. Ketonuria was measured at hospital admission with a dipstick, which distinguishes 5 categories: negative and 1+ through 4 + . The outcome measures were multiple measures of HG disease severity at different time points: 1) At hospital admission (study entry): severity of nausea and vomiting, quality of life and weight change compared to pre-pregnancy weight, 2) One week after hospital admission: severity of nausea and vomiting, quality of life and weight change compared to admission, 3) Duration of index hospital admission and readmission for HG at any time point RESULTS: 215 women where included. Ketonuria was not associated with severity of nausea and vomiting, quality of life or weight loss at hospital admission, nor was the degree of ketonuria at admission associated with any of the outcomes 1 week after hospital admission. The degree of ketonuria was also not associated with the number of readmissions. However, women with a higher degree of ketonuria had a statistically significant longer duration of hospital stay (per 1+ ketonuria, difference: 0.27 days, 95 % CI: 0.05 to 0.48). CONCLUSIONS: There was no association between the degree of ketonuria at admission and severity of symptoms, quality of life, maternal weight loss, or number of readmissions, suggesting that ketonuria provides no information about disease severity or disease course. Despite this, women with a higher degree of ketonuria at admission were hospitalised for longer. This could suggest that health care professionals base length of hospital stay on the degree of ketonuria. Based on the lack of association between ketonuria and disease severity, we suggest it has no additional value in the clinical management of HG.

Tumour biomarkers: association with heart failure outcomes.

BACKGROUND: There is increasing recognition that heart failure (HF) and cancer are conditions with a number of shared characteristics. OBJECTIVES: To explore the association between tumour biomarkers and HF outcomes. METHODS: In 2,079 patients of BIOSTAT-CHF cohort, we measured six established tumour biomarkers: CA125, CA15-3, CA19-9, CEA, CYFRA 21-1 and AFP. RESULTS: During a median follow-up of 21 months, 555 (27%) patients reached the primary end-point of all-cause mortality. CA125, CYFRA 21-1, CEA and CA19-9 levels were positively correlated with NT-proBNP quartiles (all P < 0.001, P for trend < 0.001) and were, respectively, associated with a hazard ratio of 1.17 (95% CI 1.12-1.23; P < 0.0001), 1.45 (95% CI 1.30-1.61; P < 0.0001), 1.19 (95% CI 1.09-1.30; P = 0.006) and 1.10 (95% CI 1.05-1.16; P < 0.001) for all-cause mortality after correction for BIOSTAT risk model (age, BUN, NT-proBNP, haemoglobin and beta blocker). All tumour biomarkers (except AFP) had significant associations with secondary end-points (composite of all-cause mortality and HF hospitalization, HF hospitalization, cardiovascular (CV) mortality and non-CV mortality). ROC curves showed the AUC of CYFRA 21-1 (0.64) had a noninferior AUC compared with NT-proBNP (0.68) for all-cause mortality (P = 0.08). A combination of CYFRA 21-1 and NT-proBNP (AUC = 0.71) improved the predictive value of the model for all-cause mortality (P = 0.0002 compared with NT-proBNP). CONCLUSIONS: Several established tumour biomarkers showed independent associations with indices of severity of HF and independent prognostic value for HF outcomes. This demonstrates that pathophysiological pathways sensed by these tumour biomarkers are also dysregulated in HF.

Infectious diseases and antimicrobial prescribing: Online spaced education for junior doctors.

BACKGROUND: Inappropriate antimicrobial prescribing may harm patients and drive antimicrobial resistance. Junior doctors' knowledge of infectious diseases and antimicrobial prescribing is inadequate. Online spaced case-based learning can improve knowledge. OBJECTIVE: To develop infectious diseases and antimicrobial prescribing course content for online spaced education and assess its effectiveness and feasibility for junior doctors. METHODS: Infectious diseases and antimicrobial course content was developed for an online spaced education platform (Qstream Inc., Burlington, MA). Junior doctors (postgraduate years 1-3) at two tertiary teaching hospitals in Sydney participated in the study. Course content was provided with Qstream at one hospital and at the other hospital via two face-to-face (FTF) tutorials from August to October 2017. Knowledge and self-confidence were compared before and after training within and between both cohorts. RESULTS: Participation in the course was higher in the Qstream cohort with 48/127 (37.8%) completing the course compared with 44/110 (40%) attending one or both FTF sessions, of whom 22/110 (20%) attended both. Improvement in mean knowledge score from 69.7% to 81.5% in the Qstream cohort was significantly greater than the FTF cohort's minimal improvement from 67.6% to 67.9% (95% CI 2.79-20.33; P=0.01). In the Qstream cohort mean confidence rating (0-10) improvement from 5.14 to 6.55 was greater than the FTF group improvement from 5.37 to 5.85 (95% CI 0.132-1.171; P=0.02). Qstream feedback was very positive. CONCLUSIONS: Online spaced education in infectious diseases and antimicrobial prescribing was feasible, acceptable and effective for junior doctors. It has potential to reduce inappropriate antimicrobial prescribing and warrants further investigation.

Influence of solution composition on fouling of anion exchange membranes desalinating polymer-flooding produced water.

HYPOTHESIS: Anion exchange membranes (AEMS) are particularly prone to fouling when employed to desalinate polymer flooding produced water (PFPW), an abundant sub-product from the oil and gas industry. The formation of fouling on an AEM will be affected by the composition of the solution, which includes various dissolved salts, partially hydrolyzed polyacrylamide (HPAM), crude oil, and surfactants. EXPERIMENTS: Electrodialysis experiments were performed to desalinate feed solutions with different compositions, aiming to distinguish between their individual and combined effects. The solutions contained diverse mono- and divalent ions. The analysis included data collected during the desalination and characterization of the fouled AEMs by diverse analytical techniques. FINDINGS: HPAM produced the most severe effects in terms of visible fouling and increase of resistance. This polyelectrolyte fouls the AEM by adsorbing on its surface and by forming a viscous gel layer that hampers the replenishment of ions from the bulk solution. Ca and Mg have a large influence on the formation of thick HPAM gel layers, while the oily compounds have only a minimal influence acting mainly as a destabilizing agent. The membranes also presented scaling consisting of calcium precipitates. The effects of the gel layer were minimized by applying current reversal and foulant-free solution.

A Retrospective Case Series of Synovial Sarcoma of the Upper Extremity.

PURPOSE: Previous studies have grouped the treatment of axial and appendicular synovial sarcomas. The purpose of this study was to assess the prognostic variables of upper extremity synovial sarcomas (UESS) and compare the outcomes of those who underwent a nononcologic or inadvertent excision prior to definitive resection to those who underwent an initial oncologic resection. METHODS: We reviewed the records of 23 UESS treated with definitive surgery at our institution between 1990 and 2014. There were 13 women and 10 men with a median age of 30 years (6-60) and median follow-up of 63 months (15-248). Prognostic variables, recurrence-free survival (RFS), and overall survival (OS) were then assessed. RESULTS: Fifteen patients (65%) had a prior unplanned excision. Five patients required an amputation to obtain local control of disease. There were 3 observed local recurrences and 2 distant metastases at a median of 45 months from presentation. We found no difference in need for amputation, RFS, or OS between those who had undergone a planned excision and those who had an unplanned excision. CONCLUSION: While we were unable to find a significant difference in outcomes or amputation rates between those who underwent reexcision of a previously unplanned excision and those who underwent an initial planned resection, the high rate of unplanned excision is troubling and should remind practitioners to consider sarcoma in the differential of all upper extremity masses.

The barriers to linkage and retention in care for women living with HIV in an high income setting where they comprise a minority group.

Women comprise a minority population of individuals living with HIV in Australia, and are often poorly represented in research and clinical trials so their needs remain largely unknown. Data suggests that they are diagnosed later than men and start antiretroviral therapy at a lower CD4 cell count. This raises the question whether there are sex specific barriers to linkage and retention in care. This study analyzed 484 surveys received from clinicians collecting demographic, virological, and reproductive health data along with perceived barriers to linkage and retention in care. Most women (67%) were estimated to have been linked into care within 28 days of diagnosis. For women who were not linked into care for more than 28 days, the most commonly reason cited was fear of disclosure to others, followed by fear of disclosure to their partner. The main reasons given for non-retention in care were related to transport, carer responsibilities, financial pressure, health beliefs and concern about stigma or disclosure.

Validation of Reference Charts for Mid-Trimester Fetal Biometry.

OBJECTIVE: The aim of our study was to assess charts proposed for international use in the Intergrowth-21st Project. METHODS: Ultrasound data were collected from 43,923 healthy singleton pregnancies examined at 18-23 weeks of gestation in the Netherlands. Fetal measurements were converted into Z-scores using previous and current Dutch reference charts and Intergrowth charts. The distributions of the Z-scores were compared with the expected standard normal distribution. RESULTS: In the Dutch population, Intergrowth curves perform well for head circumference and biparietal diameter, but not for abdominal circumference (AC, Z- score = 0.43) and femur length (FL, Z-score = 0.26). Similar findings have been reported in other European countries. Compared with the population in the Intergrowth study, Dutch women are relatively tall (170 vs. 162 cm) and sturdy (67 vs. 61 kg) with a moderately high BMI. Maternal size, in particular maternal height, is positively correlated with birthweight. CONCLUSIONS: Whilst the establishment of the Intergrowth charts is an important step towards worldwide uniformity, for now locally derived charts still perform better, especially for AC and FL. Results from our validation study indicate that distinction between normal and pathologically small babies may be improved by taking maternal size into account.

Dickkopf-related protein 1 and gremlin 1 show different response than frizzled-related protein in human synovial fluid following knee injury and in patients with osteoarthritis.

OBJECTIVE: To explore the involvement of the wingless-type MMTV integration site (WNT) and bone morphogenetic protein (BMP) antagonists dickkopf-related protein 1 (DKK1), frizzled-related protein (FRZB) and gremlin 1 (GREM1) in knee injury and osteoarthritis (OA). DESIGN: The antagonists were immunoassayed in synovial fluid from a cross-sectional cohort of nine knee healthy reference subjects, patients with recent (0-77 days, n = 158) or old (1-37 years, n = 50) knee injuries, and OA (n = 22). Cartilage (ARGS-aggrecan, cartilage oligomeric matrix protein and C2C type II collagen) and other biomarkers were assessed in synovial fluid in a subset of samples. Statistical analysis was by Kendall's tau (τ) correlation, Mann-Whitney U test, and linear regression analysis. RESULTS: Compared to references, median concentration of GREM1 (but not DKK1 and FRZB) was elevated 1.5-fold immediately after injury, and FRZB was reduced 1000-folds in OA. All three antagonists decreased with increasing time after injury as well as with increasing age, but the temporal change after injury was less accentuated for FRZB (peaked 8-22 days after injury) compared to that of DKK1 and GREM1 (peaked immediately after injury). In the recent injury group, there was a correlation between GREM1 and DKK1 (τ = 0.172); FRZB concentrations correlated with concentrations of cartilage biomarkers (τ between 0.257 and 0.369), while DKK1 and GREM1 were inversely correlated (τ between -0.177 and -0.217) with these markers. CONCLUSIONS: Our results indicate separate roles for the antagonists, where DKK1 and GREM1 had similarities in response to injury and in OA, with a different response for FRZB.

Cost-effectiveness of diagnostic testing strategies including cervical-length measurement and fibronectin testing in women with symptoms of preterm labor.

OBJECTIVE: To evaluate the cost-effectiveness of combining cervical-length (CL) measurement and fetal fibronectin (fFN) testing in women with symptoms of preterm labor between 24 and 34 weeks' gestation. METHODS: This was a model-based cost-effectiveness analysis evaluating seven test-treatment strategies based on CL measurement and/or fFN testing in women with symptoms of preterm labor from a societal perspective, in which neonatal outcomes and costs were weighted. Estimates of disease prevalence, test accuracy and costs were based on two recently performed nationwide cohort studies in The Netherlands. RESULTS: Strategies using fFN testing and CL measurement separately to predict preterm delivery are associated with higher costs and incidence of adverse neonatal outcomes compared with strategies that combine both tests. Additional fFN testing when CL is 15-30 mm was considered cost effective, leading to a cost saving of €3919 per woman when compared with a treat-all strategy, with a small deterioration in neonatal health outcomes, namely one additional perinatal death and 21 adverse outcomes per 10 000 women with signs of preterm labor (incremental cost-effectiveness ratios €39 million and €1.9 million, respectively). Implementing this strategy in The Netherlands, a country with about 180 000 deliveries annually, could lead to an annual cost saving of between €2.4 million and €7.6 million, with only a small deterioration in neonatal health outcomes. CONCLUSION: In women with symptoms of preterm labor at 24-34 weeks' gestation, performing additional fFN testing when CL is between 15 and 30 mm is a viable and cost-saving strategy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

How do hospital respiratory clinicians perceive antimicrobial stewardship (AMS)? A qualitative study highlighting barriers to AMS in respiratory medicine.

BACKGROUND: Suboptimal antibiotic use in respiratory infections is widespread in hospital medicine and primary care. Antimicrobial stewardship (AMS) teams within hospitals, commonly led by infectious diseases physicians, are frequently charged with optimizing the use of respiratory antibiotics, but there is limited information on what drives antibiotic use in this area of clinical medicine, or on how AMS is perceived. AIM: To explore the perceptions of hospital respiratory clinicians on AMS in respiratory medicine. METHODS: In-depth interviews were conducted with 28 clinicians (13 doctors and 15 nurses) from two hospitals in Australia. Data were analysed thematically using the framework approach. FINDINGS: Four key barriers to the integration of AMS processes within respiratory medicine, from the participants' perspectives, were identified: CONCLUSIONS: AMS processes are introduced in hospitals with established social structures and knowledge bases. This study found that AMS in respiratory medicine challenges and conflicts with many of these dynamics. If the influence of these dynamics is not considered, AMS processes may not be effective in containing antibiotic use in hospital respiratory medicine.

A novel immuno-gold labeling protocol for nanobody-based detection of HER2 in breast cancer cells using immuno-electron microscopy.

Immuno-electron microscopy is commonly performed with the use of antibodies. In the last decade the antibody fragment indicated as nanobody (VHH or single domain antibody) has found its way to different applications previously done with conventional antibodies. Nanobodies can be selected to bind with high affinity and specificity to different antigens. They are small (molecular weight ca. 15kDa) and are usually easy to produce in microorganisms. Here we have evaluated the feasibility of a nanobody binding to HER2 for application in immuno-electron microscopy. To obtain highest labeling efficiency combined with optimal specificity, different labeling conditions were analysed, which included nanobody concentration, fixation and blocking conditions. The obtained optimal protocol was applied for post-embedment labeling of Tokuyasu cryosections and for pre-embedment labeling of HER2 for fluorescence microscopy and both transmission and scanning electron microscopy. We show that formaldehyde fixation after incubation with the anti-HER2 nanobody, improves labeling intensity. Among all tested blocking agents the best results were obtained with a mixture of cold water fish gelatine and acetylated bovine serum albumin, which prevented a-specific interactions causing background labeling while preserving specific interactions at the same time. In conclusion, we have developed a nanobody-based protocol for immuno-gold labeling of HER2 for Tokuyasu cryosections in TEM as well as for pre-embedment gold labeling of cells for both TEM and SEM.

Complications of pregnancy and labour in women with Klippel-Trénaunay syndrome: a nationwide cross-sectional study.

OBJECTIVE: To evaluate complications of pregnancy, including thromboembolism, in women with extensive vascular malformations associated with Klippel-Trénaunay syndrome (KTS). DESIGN: Nationwide cross-sectional study. SETTING: Two tertiary expert centres and the Dutch Klippel-Trénaunay patient organisation. SAMPLE: Adult women with KTS. METHODS: Patients with KTS were invited to participate in a comprehensive online survey about their obstetric history. Reference data on pregnancy outcomes and complications of non-diseased women were collected from population-based cohorts from the literature. MAIN OUTCOME MEASURES: Prevalence of complications, specifically venous thromboembolism and postpartum haemorrhage. RESULTS: Sixty women completed the survey. Seventeen patients did not conceive, of whom three refrained from pregnancy because of KTS. A total of 97 pregnancies and 86 deliveries were reported in 43 patients. KTS-related symptoms were aggravated during pregnancy in 43% of patients. Deep vein thrombosis was present in 5.8% and pulmonary embolism was present in 2.3% of pregnancies, which was extremely high compared with the reference population (P < 0.0001), with a relative risk of 108.9 (95% confidence interval, 95% CI 46.48-255.03) and 106.2 (95% CI 26.97-418.10), respectively. Severe postpartum haemorrhage (PPH) occurred in 11% of KTS pregnancies, compared with 5.8% of pregnancies in the reference population (relative risk, RR 1.81, 95% CI 0.97-3.37, P = 0.06). CONCLUSIONS: Our data suggest that women with KTS have a significant risk of venous thromboembolic events, severe postpartum haemorrhage, and aggravation of KTS symptoms during pregnancy, and in early postpartum period. Obstetricians should counsel patients about these risks in the preconception phase. Antithrombotic prophylaxis should be considered in the obstetric management of patients with KTS. TWEETABLE ABSTRACT: High risk of complications during pregnancy and labour in women with Klippel-Trénaunay syndrome.