Long-term follow-up of patients with extensive segmental infantile hemangioma of the cervical or facial region: A French single-center prospective study.

BACKGROUND: Infantile hemangiomas (IHs) can be part of PHACE (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, eye anomalies) syndrome when they are segmental, extensive, and located on the face or neck. The initial assessment is codified and well known, but there are no recommendations for the follow-up of these patients. The aim of this study was to assess the long-term prevalence of different associated abnormalities. METHODS: Patients with a history of large segmental IHs of the face or neck. diagnosed between 2011 and 2016 were included in the study. Each patient underwent an ophthalmological, dental, ENT (ear, nose, and throat), dermatological, neuro-pediatric, and radiological assessment at inclusion. Eight patients including five with PHACE syndrome were prospectively evaluated. RESULTS: After a mean follow-up of 8.5 years, three patients presented with an angiomatous aspect of the oral mucosa, two with hearing loss, and two with otoscopic abnormalities. No patients developed ophthalmological abnormalities. The neurological examination was altered in three cases. Brain magnetic resonance imaging follow-up was unchanged in three out four patients and revealed atrophy of the cerebellar vermis in 1 patient. Neurodevelopmental disorders were found in five of the patients and learning difficulties were observed in five patients. The S1 location appears to be associated with a higher risk of neurodevelopmental disorders and cerebellar malformations, while the S3 location was associated with more progressive complications, including neurovascular, cardiovascular, and ENT abnormalities. CONCLUSION: Our study reported late complications in patients with a large segmental IH of the face or neck, whether associated with PHACE syndrome or not, and we proposed an algorithm to optimize the long-term follow-up.

Aerobic exercise capacity is normal in obesity with or without metabolic syndrome.

BACKGROUND: Obesity might be a cause of limited aerobic exercise capacity. It is often associated with metabolic syndrome (MS) that includes cardiovascular comorbidities as arterial hypertension. Cardiopulmonary exercise testing (CPET) is the gold-standard to assess aerobic capacity and discriminate causes of dyspnea. AIM: To evaluate aerobic capacity in obesity and if MS or hypertensive treatment impacts on the CPET profile. METHODS: CPET of 146 obese patients, whom 33 and 31 were matched for MS and antihypertensive medication, were analyzed. VO2peak (mL/min/Kg) was reported in percentage of predicted value, or, divided by body weight, fat free mass (FFM) or body weight expected for a body mass index of 24 (BMI24). RESULTS: VO2peak (20,8 ± 4,4 mL/min/Kg) was normal when expressed in percentage predicted for obesity (111 ± 22%pred) or divided by FFM and weightBMI24 (33,6 ± 5,6 and 30,6 ± 6,2 respectively). The latter correlated better with maximal work rate (r = 0,7168, p < 0,001). Obese patients showed normal ventilatory efficiency (ventilation to carbon dioxide production slope: 28 ± 4), VO2 to work rate (10,2 ± 1,6 mLO2/Watt) and, slightly elevated heart rate to VO2 slope (4,0 ± 1,1 bpm/mL/min/Kg). Compared to normotensives, hypertensive medicated patients had higher blood pressure at anaerobic threshold (142 ± 23 vs 158 ± 26 mmHg, p = 0,001) but not at maximal exercise (189 ± 31 vs 201 ± 23 mmHg, p = NS), and, had lower actual maximal heart rate (155 ± 23 vs 143 ± 25 bpm, p = 0,03). There was no difference between obese patients with or without MS. CONCLUSION: Obese people with or without MS present with similar and normal aerobic profile related to the excessive body weight. VO2peak divided by weightBMI24 is an easy and clinical meaningful index for obese patients.

Tritium in precipitation on 5 sites in North-West France during the 2017-2019 period.

Between October 2017 and May 2019, measurements of tritium in rainwater were carried out at several sites in north-west France. Tritium is an important tracer for hydroclimatic studies and this work provided up-to-date data that we compared with Global Network for Isotopes in Precipitation (GNIP) measurements. Of the various sites studied, some could potentially be affected by atmospheric gaseous emissions from the nuclear industries in the region (reprocessing plant, nuclear power plant). On our reference site, the activities measured in rainwater are often below the decision threshold (<0.15 Bq.L-1). Two other sites with little impact from nuclear industries have mean activities of less than 0.7 Bq.L-1. At the two Cherbourg sites closer to the nuclear industries, the activities in rainwater are slightly higher on average, though still close to 1 Bq.L-1, but the activities are more variable when the rainfall accompanies an air mass from the Orano La Hague nuclear site. Using existing GNIP data and a simple model to simulate predicted data up to 2019, it is shown that all our measured data are comparable with the predicted activities for GNIP stations with a marine influence, in the case of the reference site and the sites with little impact from nuclear industries, and for GNIP stations with a continental influence, in the case of the other sites. Seasonal variation in activities was detected, with greater activities in the spring-summer period corresponding to the well known 'spring leak' phenomenon. This study also reveals significant differences between the activities measured on the western side of France (influenced by the Atlantic Ocean) and those measured in a continental zone. The mean levels of tritium in rainwater in France, excluding any nuclear influence, can be estimated on average at less than 0.3 Bq.L-1 in the western marine zone, and at around 1 Bq.L-1 in the continental zones.

Insulin glargine compared to neutral protamine Hagedorn (NPH) insulin in patients with type-2 diabetes uncontrolled with oral anti-diabetic agents alone in Hong Kong: a cost-effectiveness analysis.

BACKGROUND: International guidelines recommend using basal insulin in patients with type-2 diabetes mellitus if glycaemic target cannot be attained on non-insulin anti-diabetic drugs. Available choices of basal insulin include intermediate-acting neutral protamine Hagedorn (NPH) insulin and long-acting insulin analogues like insulin glargine U100. Despite clear advantages of glargine U100, the existing practice in Hong Kong still favours NPH insulin due to lower immediate drug costs. OBJECTIVES: The objective of this study was to assess the cost-effectiveness of insulin glargine U100 compared to NPH insulin in patients with type-2 diabetes uncontrolled with non-insulin anti-diabetic agents alone in Hong Kong. METHODS: The IQVIA™ Core Diabetes Model (CDM) v9.0 was used to conduct the cost-effectiveness analysis of glargine U100 versus NPH. Baseline characteristics were collected from the Hong Kong Diabetes Registry. Efficacy rates were extracted from a published study comparing glargine U100 and NPH in Asia, utilities from published literature, and costs constructed using the Hong Kong Hospital Authority (HA) Gazette (public healthcare setting). The primary outcome was an incremental cost-effectiveness ratio (ICER). RESULTS: Insulin glargine U100 resulted in an ICER of HKD 98,663 per Quality Adjusted Life Year (QALY) gained. The incremental gains in QALY and costs were 0.217 years and HKD 21,360 respectively. Results from scenario and probabilistic sensitivity analyses were consistent with that from base case analysis. CONCLUSION: Insulin glargine U100 is a cost-effective treatment for patients with type 2 diabetes compared to NPH insulin in setting in Hong Kong. This was mainly driven by the significantly lower rates of hypoglycaemia of insulin glargine U100 than NPH insulin.

The epigenetic control of transposable elements and imprinted genes in newborns is affected by the mode of conception: ART versus spontaneous conception without underlying infertility.

STUDY QUESTION: Do assisted reproductive technologies alter DNA methylation and/or transcription of transposable elements and imprinted genes in cord blood and placenta? SUMMARY ANSWER: After ART, DNA methylation and/or transcription changes of some transposable elements and imprinted genes were found in placenta samples while transcription modifications for some transposable elements were also discovered in cord blood. WHAT IS KNOWN ALREADY: Recent studies have confirmed the increased risk of placenta-related adverse pregnancy outcomes and the excess of imprinted disorders with abnormal methylation patterns after ART, which raises the issue of a potential ART-induced epigenetic risk. STUDY DESIGN, SIZE, DURATION: A total of 51 IVF/ICSI (15 conventional and 36 ICSI) singleton pregnancies were prospectively included from January 2013 to April 2015 and compared to 48 spontaneously conceived singleton pregnancies. PARTICIPANTS/MATERIALS, SETTING, METHODS: The DNA methylation and transcription of three imprinted loci (H19/IGF2, KCNQ1OT1 and SNURF DMRs) and four transposon families (LINE-1, ERVFRD, AluYa5 and ERVW) in cord blood and placenta obtained at birth were assessed by pyrosequencing and quantitative RT-PCR, respectively. All data were adjusted for gestational age at delivery, sex of the newborn, parity and maternal age. MAIN RESULTS AND THE ROLE OF CHANCE: DNA methylation levels of H19/IGF2, KCNQ1OT1, LINE-1Hs and ERVFRD-1 were significantly lower in IVF/ICSI placentas than in control placentas, while there was no difference for cord blood. Moreover, the expression of ERVFRD-1 and LINE-1 ORF2 in cord blood and ERVFRD-1 in placenta was lower in the IVF/ICSI group than in controls. The expression of ERVFRD-1 in placenta correlated positively with birth weight and placenta weight, but only in the control group, thus pointing to the potential deregulation of syncytin function after ART. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The control group of fertile couples having conceived within 1 year prevented us from deciphering the distinct roles of ART and infertility. WIDER IMPLICATIONS OF THE FINDINGS: These novel findings of ERVFRD (syncytin-2) expression correlating with birth weight and placenta weight suggest that more research on syncytins and pregnancy-associated diseases could lead to them being used as biomarkers or even as therapeutic targets. The epigenetic modifications in placenta for sequences involved in foetal development raise the question of their potential effects on pregnancy and future life. These results should encourage us to analyse the exact causes and consequences of epigenetic changes and strive to minimize these variations in the interests of epigenetic safety after ART. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by a grant from Besançon and Dijon University Hospitals. The authors have no conflicts of interest to declare.

Atmospheric tritium concentrations under influence of AREVA NC La Hague reprocessing plant (France) and background levels.

In-air tritium measurements were conducted around the AREVA NC La Hague reprocessing plant, as well as on other sites that are not impacted by the nuclear industry in northwest of France. The results indicate that the dominant tritium form around the AREVA site is HT (86%). HT and HTO levels are lower than 5 and 1 Bq. m-3 for hourly samples taken in the plume. No tritiated organic molecules (TOM) were detected. 26 measurement campaigns were performed and links were established between near-field 85Kr, HT and HTO activities. Environmental measurements are in line with those taken at the discharge stack, and tend to demonstrate that there are no rapid changes in the tritium forms released. Out of the influence of any nuclear activities, the levels measured were below 13 mBq.m-3 for HT and 5 mBq.m-3 for HTO (<0.5 Bq. L-1). HTO level in air seems to be influenced by HTO activities in surrounding seawater.

Assessment of Public Health and Economic Impact of Intranasal Live-Attenuated Influenza Vaccination of Children in France Using a Dynamic Transmission Model.

OBJECTIVES: We estimated the epidemiological and economic impact of extending the French influenza vaccination programme from at-risk/elderly (≥65 years) only to healthy children (2-17 years). METHODS: A deterministic, age-structured, dynamic transmission model was used to simulate the transmission of influenza in the French population, using the current vaccination coverage with trivalent inactivated vaccine (TIV) in at-risk/elderly individuals (current strategy) or gradually extending the vaccination to healthy children (aged 2-17 years) with intranasal, quadrivalent live-attenuated influenza vaccine (QLAIV) from current uptake up to 50% (evaluated strategy). Epidemiological, medical resource use and cost data were taken from international literature and country-specific information. The model was calibrated to the observed numbers of influenza-like illness visits/year. The 10-year number of symptomatic cases of confirmed influenza and direct medical costs ('all-payer') were calculated for the 0-17- (direct and indirect effects) and ≥18-year-old (indirect effect). The incremental cost-effectiveness ratio (ICER) was calculated for the total population, using a 4% discount rate/year. RESULTS: Assuming 2.3 million visits/year and 1960 deaths/year, the model calibration yielded an all-year average basic reproduction number (R 0) of 1.27. In the population aged 0-17 years, QLAIV prevented 865,000 influenza cases/year (58.4%), preventing 10-year direct medical expenses of €374 million. In those aged ≥18 years with unchanged TIV coverage, 1.2 million cases/year were averted (27.6%) via indirect effects (additionally prevented expenses, €457 million). On average, 613 influenza-related deaths were averted annually overall. The ICER was €18,001/life-year gained. The evaluated strategy had a 98% probability of being cost-effective at a €31,000/life-year gained threshold. CONCLUSIONS: The model demonstrated strong direct and indirect benefits of protecting healthy children against influenza with QLAIV on public health and economic outcomes in France.

The VATO project: An original methodology to study the transfer of tritium as HT and HTO in grassland ecosystem.

Tritium (3H) is mainly released into the environment by nuclear power plants, military nuclear facilities and nuclear reprocessing plants. The construction of new nuclear facilities in the world as well as the evolution of nuclear fuel management might lead to an increase of 3H discharges from the nuclear industry. The VATO project was set up by IRSN (Institut de Radioprotection et de Sûreté Nucléaire) and EDF (Electricité de France) to reduce the uncertainties in the knowledge about transfers of 3H from an atmospheric source (currently releasing HT and HTO) to a grassland ecosystem. A fully instrumented technical platform with specifically designed materials was set up downwind of the AREVA NC La Hague reprocessing plant (Northwest of the France). This study, started in 2013, was conducted in four main steps to provide an hourly data set of 3H concentrations in the environment, adequate to develop and/or validate transfer models. It consisted first in characterizing the physico-chemical forms of 3H present in the air around the plant. Then, 3H transfer kinetics to grass were quantified regarding contributions from various compartments of the environment. For this purpose, an original experimental procedure was provided to take account for biases due to rehydration of freeze-dried samples for the determination of OBT activity concentrations in biological samples. In a third step, the 3H concentrations measured in the air and in rainwater were reconstructed at hourly intervals. Finally, a data processing technique was used to determine the biological half-lives of OBT in grass.

Cost and co-morbidities associated with hypoglycemic inpatients in Belgium.

BACKGROUND AND OBJECTIVES: Little is known about the economic burden of hypoglycemia in Belgium, or its related co-morbidities. This study aimed at estimating the cost and length of stay associated with hypoglycemia-related hospitalizations in diabetic patients in Belgium and the association between hypoglycemia and in-hospital all-cause mortality, incidence of traumatic fractures, depression, and cardiovascular diseases (myocardial infarction or unstable angina), using retrospective data from 2011. METHODS: Patient data were retrieved from the IMS Hospital Disease Database, including longitudinal (per calendar year) information on diagnoses, procedures, and drugs prescribed in ∼20% of all Belgian hospital beds. The eligible population included all adult (<19 year) diabetic (both types) patients, further split between those with/without a history of hypoglycemia-related hospitalizations. Diabetes, hypoglycemia, and co-morbidities of interest were identified based on International Classification of Diseases and Related Health Problems Version 9 (ICD-9) diagnosis codes. All costs were extrapolated to 2014 using progression in hospitalization costs since 2001. RESULTS: A total of 43,410 diabetes-related hospitalizations were retrieved, corresponding to 30,710 distinct patients. The average hospitalization cost was €10,258 when hypoglycemia was documented (n = 2625), vs €7173 in other diabetic hospitalized patients (n = 40,785). When controlling for age and sex, a higher mortality risk (OR = 1.59; p-value <0.001), a higher incidence of traumatic fractures (OR = 1.25; p-value = 0.009), and a higher probability of depression-related hospitalizations (OR = 1.90; p-value <0.001) were observed in hypoglycemic patients. A similar risk of cardiovascular event was observed in both groups, but hypoglycemic patients were more at risk of experiencing multiple events. CONCLUSION: Hospitalizations for hypoglycemia are expensive and associated with an increased risk of depression and traumatic fractures as well as increased in-hospital mortality. Interventions that can help reduce the risk of hypoglycemia, and consequently the burden on hospitals and society, without compromising glycemic control, will help to further improve diabetes management.

The conscious awareness of time distortions regulates the effect of emotion on the perception of time.

This study examined how the awareness of emotion-related time distortions modifies the effect of emotion on time perception. Before performing a temporal bisection task with stimulus durations presented in the form of neutral or emotional facial expressions (angry, disgusted and ashamed faces), some of the participants read a scientific text providing either correct or incorrect information on the emotion-time relationship. Other participants did not receive any information. The results showed that the declarative knowledge allowed the participants to regulate (decrease) the intensity of emotional effects on the perception of time, but did not trigger temporal effects when the emotional stimuli did not automatically induce emotional reactions that distorted time.

Near-field krypton-85 measurements in stable meteorological conditions around the AREVA NC La Hague reprocessing plant: estimation of atmospheric transfer coefficients.

The aim of this work was to study the near-field dispersion of (85)Kr around the nuclear fuel reprocessing plant at La Hague (AREVA NC La Hague - France) under stable meteorological conditions. Twenty-two (85)Kr night-time experimental campaigns were carried out at distances of up to 4 km from the release source. Although the operational Gaussian models predict for these meteorological conditions a distance to plume touchdown of several kilometers, we almost systematically observed a marked ground signal at distances of 0.5-4 km. The calculated atmospheric transfer coefficients (ATC) show values (1) higher than those observed under neutral conditions, (2) much higher than those proposed by the operational models, and (3) higher than those used in the impact assessments.

In-hospital costs associated with chronic constipation in Belgium: a retrospective database study.

BACKGROUND: Real-life data on the economic burden of chronic idiopathic constipation are scarce. The objectives of this study were to assess hospitalization resource use and costs associated with chronic constipation and its complications in Belgium. METHODS: This was a single country, retrospective study using the IMS Hospital Disease Database (2008), which comprises data on 34% of acute hospital beds in Belgium and contains information on patient demographics, length of stay (LOS), billed costs, drug use, diagnoses, and procedures. Stays with a primary diagnosis of constipation, or a secondary diagnosis of constipation and a concomitant diagnosis of a constipation-related complication, were selected. Patients with diagnoses of colorectal cancer, ulcerative colitis or Crohn's disease, or who had stays involving potentially constipation-inducing procedures, were excluded as having secondary constipation. Patients receiving opioids, calcium-antagonists, antipsychotics or antidepressants were excluded as having drug-induced constipation. KEY RESULTS: In total, 1541 eligible patients were identified. The average unadjusted cost per day in hospital for idiopathic constipation was €441 (€311 ± 1.4 in day clinic visits without overnight stays; €711 ± 14.0 in full hospitalizations with complications). The average LOS in a full hospitalization setting was 7.0 and 4.0 days in stays with and without complications, respectively. The most frequent drug and procedural treatments were osmotically acting laxatives (with complications: 42.61%; without complications: 35.69%), and transanal enema (2.32% and 2.03%), respectively. CONCLUSIONS & INFERENCES: The burden of constipation is often underestimated; it is a condition reflected by hospital-related costs comparable to such indications as migraine, which increase when associated with complications.