What Information Do Clinicians Deem Important for Counseling Parents Facing Extremely Early Deliveries?: Results from an Online Survey.

OBJECTIVE: The study aimed to better understand how neonatology and maternal fetal medicine (MFM) physicians convey information during antenatal counseling that requires facilitating shared decision-making with parents facing options of resuscitation versus comfort care after extremely early delivery STUDY DESIGN: Attending physicians at US centers with both Neo and MFM fellowships were invited to answer an original online survey about antenatal counseling for extremely early newborns. The survey assessed information conveyed, processes for facilitating shared decision-making (reported separately), and clinical experiences. Neonatology and MFM responses were compared. Multivariable logistic regression analyzed topics often and seldom discussed by specialty groups with respect to respondents' clinical experience and resuscitation option preferences at different gestational weeks. RESULTS: In total, 74 MFM and 167 neonatologists representing 94% of the 81 centers surveyed responded. Grouped by specialty, respondents were similar in counseling experience and distribution of allowing choices between resuscitation and no resuscitation for delivery at specific weeks of gestational ages. MFM versus neonatology reported similar rates of discussing long-term health and developmental concerns and differed in all other categories of topics. Neonatologists were less likely than MFM to discuss caregiver impacts (odds ratio [OR]: 0.14, 95% confidence interval [CI]: 0.11-0.18, p < 0.001) and comfort care details (OR: 0.19, 95% CI: 0.15-0.25, p < 0.001). Conversely, neonatology versus MFM respondents more frequently reported "usually" discussing topics pertaining to parenting in the NICU (OR: 1.5, 95% CI: 1.2-1.8, p < 0.001) and those regarding stabilizing interventions in the delivery room (OR: 1.8, 95% CI: 1.4-2.2, p < 0.001). Compared with less-experienced respondents, those with 17 years' or more of clinical experience had greater likelihood in both specialties to say they "usually" discussed otherwise infrequently reported topics pertaining to caregiver impacts. CONCLUSION: Parents require information to make difficult decisions for their extremely early newborns. Our findings endorse the value of co-consultation by MFM and neonatology clinicians and of trainee education on antenatal consultation education to support these families. KEY POINTS: · Neonatology versus MFM counselors provide complementary information.. · More experience was linked to discussing some topics.. · Co-consultation and trainee education is supported.. · What information parents value requires study..

How do Clinicians View the Process of Shared Decision-Making with Parents Facing Extremely Early Deliveries? Results from an Online Survey.

OBJECTIVE: The objective of this study was to better understand how neonatology (Neo) and maternal-fetal medicine (MFM) physicians approach the process of shared decision-making (SDM) with parents facing extremely premature (<25 weeks estimated gestational age) delivery during antenatal counseling. STUDY DESIGN: Attending physicians at U.S. centers with both Neo and MFM fellowships were invited to answer an original online survey about antenatal counseling for extremely early newborns. Preferences for conveying information are reported elsewhere. Here, we report clinicians' self-assessments of their ability to engage in deliberations and decision-making and perceptions of what is important to parents in the SDM process. Multivariable logistic regression analyzed respondents' views with respect to individual characteristics, such as specialty, gender, and years of clinical experience. RESULTS: In total, 74 MFMs and 167 Neos representing 94% of the 81 centers surveyed responded. Neos versus MFMs reported repeat visits with parents less often (<0.001) and agreed that parents were more likely to have made delivery room decisions before they counseled them less often (p < 0.001). Respondents reported regularly achieving most goals of SDM, with the exception of providing spiritual support. Most respondents reported that spiritual and religious views, risk to an infant's survival, and the infant's quality of life were important to parental decision-making, while a physician's own personal choice and family political views were reported as less important. While many barriers to SDM exist, respondents rated language barriers and family views that differ from those of a provider as the most difficult barriers to overcome. CONCLUSION: This study provides insights into how consultants from different specialties and demographic groups facilitate SDM, thereby informing future efforts for improving counseling and engaging in SDM with parents facing extremely early deliveries and supporting evidence-based training for these complex communication skills. KEY POINTS: · Perceptions differed by specialty and demographics.. · Parents' spiritual needs were infrequently met.. · Barriers to shared decision-making exist..

Safety of sildenafil in premature infants with severe bronchopulmonary dysplasia (SILDI-SAFE): a multicenter, randomized, placebo-controlled, sequential dose-escalating, double-masked, safety study.

BACKGROUND: Pulmonary hypertension is a deadly complication of bronchopulmonary dysplasia, the most common pulmonary morbidity of prematurity. Despite these catastrophic consequences, no evidence-based therapies are available for the prevention of pulmonary hypertension in this population. Sildenafil is a potent pulmonary vasodilator approved by the US Food and Drug Administration for the treatment of pulmonary hypertension in adults. Preclinical models suggest a beneficial effect of sildenafil on premature lungs through improved alveolarization and preserved vascular development. Sildenafil may therefore prevent the development of pulmonary hypertension associated with lung disease of prematurity by reducing pulmonary vascular remodeling and lowering pulmonary vascular resistance; however, clinical trial evidence is needed. The present study, supported by the National Institutes of Health's National Heart Lung and Blood Institute, will generate safety, pharmacokinetics, and preliminary effectiveness data on sildenafil in a population of premature infants with severe bronchopulmonary dysplasia at risk for pulmonary hypertension. METHODS: We have designed a multicenter, randomized, placebo-controlled, sequential dose-escalating, double-masked, safety trial of sildenafil in premature infants with severe bronchopulmonary dysplasia. We will randomize 120 premature infants < 29 weeks gestational age with severe bronchopulmonary dysplasia at 32-40 weeks postmenstrual age in a dose-escalating approach 3:1 (sildenafil: placebo) sequentially into each of 3 cohorts at ~ 30 clinical sites. Participants will receive up to 34 days of study drug, followed by 28 days of safety monitoring. The primary outcome will be safety as determined by incidence of hypotension. Secondary outcomes will include pharmacokinetics and preliminary effectiveness of sildenafil based on presence or absence of pulmonary hypertension diagnosed by echocardiography at the end of treatment period. DISCUSSION: Sildenafil is a promising intervention to prevent the development of pulmonary hypertension in premature infants with bronchopulmonary dysplasia. Clinical trials of sildenafil specifically designed for premature infants are urgently needed. The current study will make substantial contributions to scientific knowledge of the safety of sildenafil in premature infants at risk for pulmonary hypertension. Results from the study will be used by investigators to inform the design of a pivotal efficacy trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04447989 . Registered 25 June 2020.

Serological survey of feline viral pathogens in free-living European wildcats (Felis s. silvestris) from Luxembourg.

European populations of free-living wildcats have been shown to be exposed to cat viruses. Luxembourg has a high degree of habitat fragmentation, and hybridisation rates between domestic cats and wildcats are high. We therefore assessed the seroprevalence of six viruses in 34 serum samples collected between 2001 and 2016 from wildcats in Luxembourg. The values for feline leukemia virus (FeLV; 52.9%) and feline coronavirus (FCoV; 47.1%) were amongst the highest reported for wildcats. We found evidence for the cumulative likelihood of exposure to FCoV affecting its seroprevalence. Routine monitoring of viral agents in this strictly protected species should be considered.

Preventing the Return of Fear Using Reconsolidation Update Mechanisms Depends on the Met-Allele of the Brain Derived Neurotrophic Factor Val66Met Polymorphism.

BACKGROUND: Memory reconsolidation is the direct effect of memory reactivation followed by stabilization of newly synthesized proteins. It has been well proven that neural encoding of both newly and reactivated memories requires synaptic plasticity. Brain derived neurotrophic factor (BDNF) has been extensively investigated regarding its role in the formation of synaptic plasticity and in the alteration of fear memories. However, its role in fear reconsolidation is still unclear; hence, the current study has been designed to investigate the role of the BDNF val66met polymorphism (rs6265) in fear memory reconsolidation in humans. METHODS: An auditory fear-conditioning paradigm was conducted, which comprised of three stages (acquisition, reactivation, and spontaneous recovery). One day after fear acquisition, the experimental group underwent reactivation of fear memory followed by the extinction training (reminder group), whereas the control group (non-reminder group) underwent only extinction training. On day 3, both groups were subjected to spontaneous recovery of earlier learned fearful memories. The treat-elicited defensive response due to conditioned threat was measured by assessing the skin conductance response to the conditioned stimulus. All participants were genotyped for rs6265. RESULTS: The results indicate a diminishing effect of reminder on the persistence of fear memory only in the Met-allele carriers, suggesting a moderating effect of the BDNF polymorphism in fear memory reconsolidation. CONCLUSIONS: Our findings suggest a new role for BDNF gene variation in fear memory reconsolidation in humans.

Comparison between live and photographed slit lamp grading of corneal staining.

PURPOSE: To compare live and photographic (still) grades of corneal staining of the same eyes and the repeatability of grading between two investigators. METHODS: Thirty patients were recruited to participate in a contact lens study, and their level of corneal staining was graded by two investigators in situ (live images), using slit lamp biomicroscopy. Digital still images of the corneal staining were also captured during the study visits. An independent observer selected 105 of the still images graded by investigator 1 and another 105 images graded by investigator 2 and presented them to the original investigator in a random order, on three separate occasions. Grading was performed at the time of the live grading and the three still image sessions, using the Centre for Contact Lens Research corneal staining scale that combines grades of both extent and type to provide an overall "global staining score" from 0 to 10,000 for corneal staining. A comparison was made between live and still grades as well as the intrainvestigator repeatability for the multiple grading of the still images. RESULTS: The mean (±SD) of corneal staining grades recorded for the same eyes examined live and then later on three occasions was 1795 (±1083) and 714 (±974), respectively, for participants examined by investigator 1 (p < 0.001) and 1854 (±1075) and 461 (±411) for those examined by investigator 2 (p < 0.001). There was a significant difference over the three repeated still grading sessions for each investigator (p < 0.001), although there was a high degree of consistency among the three still grading sessions for each of the investigators: the intraclass correlation for investigator 1 was 0.91 (confidence interval, 0.87 to 0.93) and that for investigator 2 was 0.82 (confidence interval, 0.77 to 0.87). DISCUSSION: Digital still image grading of corneal staining significantly underrepresented the amount of corneal staining observed through a slit lamp. Clinical investigators graded corneal staining with a high degree of consistency.

Prevalence of vitamin D deficiency in pre-type 1 diabetes and its association with disease progression.

AIMS/HYPOTHESIS: Vitamin D deficiency is common in people with type 1 diabetes, but its role in disease progression is unclear. Our aim was to assess the prevalence of vitamin D deficiency in prediabetes (defined as the presence of multiple islet autoantibodies), and investigate whether or not progression to type 1 diabetes is faster in children with vitamin D deficiency and multiple islet autoantibodies. METHODS: Levels of 25-hydroxyvitamin D [25(OH)D] were measured in 108 children with multiple islet autoantibodies within 2 years of islet autoantibody seroconversion, in 406 children who remained islet autoantibody-negative and in 244 patients with newly diagnosed type 1 diabetes. Children with multiple islet autoantibodies were prospectively followed for a median of 5.8 years (interquartile range 3.4-8.6 years) to monitor progression to type 1 diabetes. RESULTS: In the cross-sectional analysis, 25(OH)D levels were lower and the prevalence of vitamin D deficiency (<50 nmol/l) was higher in children with prevalent multiple islet autoantibodies than in islet autoantibody-negative children (59.9 ± 3.0 vs 71.9 ± 1.5 nmol/l; p < 0.001; 39.8% vs 28.3%; p = 0.021). The differences in vitamin D levels between the groups were greatest in summer. The cumulative incidence of type 1 diabetes at 10 years after seroconversion was similar between children with vitamin D deficiency and those with sufficient vitamin D levels (51.8% [95% CI 29.3, 74.3] vs 55.4% [95% CI 35.5, 72.3], p = 0.8). CONCLUSIONS/INTERPRETATION: Vitamin D levels were lower in children with multiple islet autoantibodies and in children with type 1 diabetes than in autoantibody-negative children. However, vitamin D deficiency was not associated with faster progression to type 1 diabetes in children with multiple islet autoantibodies.

eDNA-based monitoring of Batrachochytrium dendrobatidis and Batrachochytrium salamandrivorans with ddPCR in Luxembourg ponds: taking signals below the Limit of Detection (LOD) into account.

BACKGROUND: Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal) are two pathogenic fungi that are a significant threat to amphibian communities worldwide. European populations are strongly impacted and the monitoring of the presence and spread of these pathogens is crucial for efficient decision-making in conservation management. RESULTS: Here we proposed an environmental DNA (eDNA) monitoring of these two pathogenic agents through droplet digital PCR (ddPCR) based on water samples from 24 ponds in Luxembourg. In addition, amphibians were swabbed in eight of the targeted ponds in order to compare the two approaches at site-level detection. This study allowed the development of a new method taking below-Limit of Detection (LOD) results into account thanks to the statistical comparison of the frequencies of false positives in no template controls (NTC) and below-LOD results in technical replicates. In the eDNA-based approach, the use of this method led to an increase in Bd and Bsal detection of 28 and 50% respectively. In swabbing, this resulted in 8% more positive results for Bd. In some samples, the use of technical replicates allowed to recover above-LOD signals and increase Bd detection by 35 and 33% respectively for eDNA and swabbing, and Bsal detection by 25% for eDNA. CONCLUSIONS: These results confirmed the usefulness of technical replicates to overcome high levels of stochasticity in very low concentration samples even for a highly sensitive technique such as ddPCR. In addition, it showed that below-LOD signals could be consistently recovered and the corresponding amplification events assigned either to positive or negative detection via the method developed here. This methodology might be particularly worth pursuing in pathogenic agents' detection as false negatives could have important adverse consequences. In total, 15 ponds were found positive for Bd and four for Bsal. This study reports the first record of Bsal in Luxembourg.

Use of a photographic manipulation tool to assess corneal vascular response.

PURPOSE: Corneal vasculature change in contact lens wearers has been linked to the level of hypoxia within the cornea.To assess the impact a treatment has on limbal vessels, a sensitive method of measurement and quantification is required. METHODS: A group of 21 highly myopic, hydrogel wearers, with preexisting signs of corneal hypoxia, were enrolled into a study where they wore sifilcon A penetrated hydrogel lenses (Dk/t ± 117), on a daily wear basis for 9 months. At all scheduled visits, photographs were taken of the superior, inferior, temporal, and nasal limbal regions which were then imported into Adobe Photoshop. A red-free filter was applied to enhance the contrast of the blood columns. In each quadrant, the length of the longest visible blood column was measured and the blood columns that penetrated 0.5 mm into the cornea were counted. A control group of 11 non-lens wearers was recruited. Their photographs were taken at the beginning of the study and 9 months later. An independent, masked observer assessed the photographs. RESULTS: There was a significant decrease in the maximum penetration of the blood column in all quadrants (p = 0.001) from baseline to the 9-month visit (e.g., superior: baseline 0.84 ± 0.39 mm; 9 months 0.63 ± 0.20 mm). There was also significant reduction in the number of visible blood columns longer than 0.5 mm in each quadrant (p = 0.001) from baseline to 9 months in all quadrants (e.g., superior: baseline 14.0 ± 8.2; 9 months 6.5 ± 6.0). The control group showed no change over time for the maximum blood column length (p = 0.638) or the number of columns 0.5 mm (p = 0.341). CONCLUSIONS: A group of highly myopic subjects exhibited reduction in the maximum length and number of blood columns in the cornea when ref it with a highly permeable silicone hydrogel material. The use of photography, along with Adobe Photoshop software, provides a reliable way of measuring corneal vascular responses over time.

Reduced pancreatic volume and beta-cell area in patients with chronic pancreatitis.

BACKGROUND & AIMS: Chronic pancreatitis (CP) often leads to the development of diabetes. To understand better this pathogenic mechanism, we investigated whether islet cell area and pancreatic volume are reduced in CP patients, islet cell turnover increases in CP patients, and islet cells are less vulnerable to apoptosis than acinar cells. METHODS: Pancreatic tissues from 43 patients with CP and 27 controls were examined by immunohistochemistry and quantitative morphometry. Pancreas volume was determined using abdominal computed tomography data. RESULTS: The pancreatic volumes were 64.9 +/- 4.3 cm(3) in CP patients and 82.3 +/- 6.7 cm(3) in controls (P = .035). beta-cell areas were 0.69% +/- 0.08% in CP patients and 0.97% +/- 0.08% in controls (P = .017), whereas alpha-cell areas did not differ between the groups (P = .47). There were no differences in the frequencies of replication among groups of alpha-cells, beta-cells, duct cells, or acinar cells nor were there differences in numbers of apoptotic alpha-cells or beta-cells between CP patients and controls. However, CP patients had an approximately 10-fold increase in numbers of apoptotic acinar cells compared with controls (P < .0001). CONCLUSIONS: Pancreatic volume was reduced by 21%, and the area comprising beta-cells was reduced by 29% in patients with CP. The lack of increased beta-cells turnover in CP patients, despite an approximately 10-fold increase in the number of apoptotic acinar cells, suggests that the damage to the pancreas is highly specific for the exocrine compartment and affects the endocrine islets to a lesser extent.

Beyond endogeneity in analyses of public opinion: Evaluations of healthcare by the foreign born across 24 European countries.

To address the problem of endogeneity in public opinion research, this study examines the opinions of healthcare held by the foreign born, i.e. those not socialized in the system they are asked to evaluate. It (a) explores the degree to which the healthcare ratings of the foreign born depend on the country's institutional healthcare setting; (b) stresses the importance of referential standards and the significance of knowledge and previous experiences of healthcare services in the country of origin; and (c) investigates differences in healthcare ratings with the length of time foreign born spent in the destination country. This study uses data from the seven rounds of the European Social Survey (2002-2014) and applies multilevel modelling techniques. Results show the institutional characteristics of healthcare services in the country of residence are associated with healthcare evaluations of the foreign born, in particular if these services are compared to those in the country of origin: the better healthcare institutions perform relative to those in the country of origin, the higher the healthcare ratings. Although comparisons with the country of origin seem relevant to all foreign born, they are sometimes more important to recent arrivals. This study suggests knowledge and experience of different healthcare institutions change perspectives and evaluations of healthcare. This finding enriches the discussion of the effects of socialisation and adaptation processes in the formation of public opinion.

Is it unfair for the affluent to be able to purchase "better" healthcare? Existential standards and institutional norms in healthcare attitudes across 28 countries.

Existing research has found that individuals often perceive healthcare inequalities as unfair; yet, there is high variation in unfairness perceptions between countries. This raises the question of whether the institutional context of the healthcare system is associated with what people perceive as unfair. Using data from the ISSP study and OECD health expenditure data from 2011/13, we explore whether individual attitudes about the unfairness of healthcare inequality - the ability to purchase "better" healthcare for the affluent - vary systematically with a country's institutional environment: namely, with the prevalence of cost barriers to healthcare access, and with the degree and type of public healthcare financing. Three general findings emerge from the analysis: (1) Higher cost barriers correlate with lower levels of perceived unfairness in healthcare inequality, suggesting those exposed to greater levels of inequality tend to be more accepting of inequality. This finding is consistent with empirical justice theory and the expected relevance of an 'existential' standard of justice, stemming from individuals' proclivities to accept the status quo as just. (2) Further, greater public financing of healthcare correlates with higher perceived unfairness. Drawing on neo-institutionalist theory, this may suggest that greater public financing enshrines access to healthcare as a universal right, and hence provides an ideational framing that delegitimizes unequal opportunities for purchasing better healthcare. (3) Further, higher unfairness perceptions of lower income and educational groups are more strongly associated with greater public financing than those of their respective comparison groups. This may indicate that the normative right to healthcare is of particular importance to the disadvantaged, which could potentially explain the political quiescence on healthcare of lower income and educated persons in societies that lack universal health systems. In sum, this study contributes to the larger debate on the interrelatedness of healthcare institutions and public opinion, and specifically on perceptions of unfairness.

Cognitive determinants of healthcare evaluations - A comparison of Eastern and Western European countries.

Knowing the public opinion of healthcare is essential when assessing healthcare system performance; but little research has focussed on the links between the public's general attitude to the healthcare system and its perceptions and expectations of specific healthcare-related aspects. Using data from the fourth round of the European Social Survey 2008/09, we explore the cognitive determinants of global evaluations of the healthcare system in 12 Eastern and 16 Western European countries. We find that healthcare evaluations follow a coherent cognitive reasoning. They are associated with (i) perceptions of the performance of healthcare systems (i.e. efficiency, equality of treatment, health outcomes), (ii) expectations of the government's role in providing healthcare, and (iii) reflections on demographic pressures (i.e. aging populations). Contrary to the general assumption that normative expectations are responsible for differences in healthcare evaluations between Eastern and Western Europe, our results suggest that regional differences are largely due to a more negative perception of the performance of healthcare systems within Eastern Europe. To enhance the public opinion of healthcare, policy makers should improve the efficiency of healthcare systems and take measures to assure equality in health treatment.

An update of Brachyspira hyodysenteriae serotyping.

Brachyspira (B.) hyodysenteriae the causative agent of swine dysentery (SD) has been divided into 9 serotypes on basis of its lipooligosaccharide (LOS). Knowledge on circulating serotypes in Europe, however, is rare. Regarding that immunity to SD is serotype specific an update of B. hyodysenteriae serotyping was undertaken. A LOS band of 10 to 25kDa was identified being appropriate for this purpose. Isolates from Germany, Spain, Denmark, USA and Japan were characterized in the immunoblot by sera raised to serotypes 1 through 7, serogroups H and I (reference strains) and to eight German strains. In total, 57 (51%) isolates responded to at least one of the antisera. Regarding German isolates (n=75) only 35 (46.7%) were identified but mainly by antisera to German strains. Positive Spanish isolates (12 of 17) yielded similar results. In contrast, positively reacting Danish isolates (9 of 12) were mainly identified by antisera to the reference strains as it was the case for recent U.S. (1 of 8) and Japanese isolates (3 of 5). Results indicate that B. hyodysenteriae has a high degree of serological heterogeneity that has probably differently developed in diverse geographical areas over time. This situation represents a challenge for vaccine development.

Confocal microscopy and optical coherence tomography imaging of hereditary granular dystrophy.

OBJECTIVES: This case report examines the clinical characteristics of hereditary granular dystrophy through the use of slit lamp digital photography, confocal microscopy (CM) and optical coherence tomography (OCT). A review of the literature describing the histopathological and genetic associations of stromal dystrophies, suggest it may be possible to differentiate dystrophies based on their clinical manifestations, and appearances of CM and OCT images, with or without the use of genetic testing. CASE REPORT: Two sisters, previously diagnosed with Granular (Groenouw I) Dystrophy, were examined. Examination included the use of digital slit lamp photography, CM and OCT imaging. RESULTS: "Breadcrumb" opacities were visualized in the anterior two-thirds of the stroma with all three imaging techniques. Opacities were demonstrated in the posterior third of the stroma with the digital photography and OCT techniques. CONCLUSIONS: The digital photography, CM and OCT images support the sister's diagnosis of Granular (Groenouw I) Dystrophy. Currently, genetic and histopathological testing are the only techniques available to determine exactly which corneal dystrophy and gene mutation are present. The results of this case report demonstrate that slit lamp digital photography, combined with CM and OCT may be capable of providing sufficient diagnostic information to diagnose corneal granular dystrophies in a clinical setting.