Cone Beam-CT-Based Bone Volume Assessments of Alveolar Synthetic Bone Graft GlassBONE™ in Cleft Lip and Palate Patients: A Retrospective Study.

Background: Clefts of the lip and palate (CLP) are facial deformities that require multiple surgical procedures during childhood. One of these steps consists of filling the alveolar space with bone graft, traditionally removed from the iliac crest. However, this procedure could be invasive in children. Aim: Here, we aimed to evaluate the outcomes of GlassBONE™ graft, a bioactive glass used as a bone substitute, as an alternative to the deleterious autologous bone graft in children. Materials & methods: Retrospective monocentric study with 17 children aged 7.5 ± 2.2 yo [3.8-13.3 yo] carrying CLP. This technique has been established at La Timone Children hospital (Assistance Publique - Hôpitaux de Marseille) since 2011. Clinical (scar, graft rejection and periodontal status) and radiological (both panoramic radiographs and cone beam-CT) follow-up was conducted one year after the graft. The primary outcome was the reduction of the cleft volume, and secondary was the eruption of the adjacent tooth through the graft. Results: GlassBONE™ permitted a significant reduction in the cleft volume by 42.4 ± 27.7% [0.6-81.1%] (p < 0.0001), corresponding to a filling of 57.6 ± 27.7% of the alveolar cleft. GlassBONE™ is well tolerated, ensuring satifactory clinical results (improvement in both scar and periodontal coverage), as well as the physiological evolution of the germs through the biomaterial. GlassBONE™ appears particularly suitable for small volumes, and we were able to determine a minimum volume of approximtely 0.259 + / - 0.155 cc required for a successful bone fusion. Conclusion: The bioactive glass GlassBONE™ could be safely used in children with small CLP cases, providing satisfactory clinical and radiological results.

SARS-CoV-2 Genome Sequencing Methods Differ in Their Abilities To Detect Variants from Low-Viral-Load Samples.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic surveillance has been vital in understanding the spread of coronavirus disease 2019 (COVID-19), the emergence of viral escape mutants, and variants of concern. However, low viral loads in clinical specimens affect variant calling for phylogenetic analyses and detection of low-frequency variants, important in uncovering infection transmission chains. We systematically evaluated three widely adopted SARS-CoV-2 whole-genome sequencing methods for their sensitivity, specificity, and ability to reliably detect low-frequency variants. Our analyses reveal that the ARTIC v3 protocol consistently displays high sensitivity for generating complete genomes at low viral loads compared with the probe-based Illumina Respiratory Viral Oligo panel and a pooled long-amplicon method. We show substantial variability in the number and location of low-frequency variants detected using the three methods, highlighting the importance of selecting appropriate methods to obtain high-quality sequence data from low-viral-load samples for public health and genomic surveillance purposes.

A better route to ALPPS: minimally invasive vs open ALPPS.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has gained both interest and controversy, as an alternative to portal vein embolisation (PVE) by inducing future liver remnant hypertrophy in patients at risk of liver failure following major hepatectomy. Open ALPPS induces more extensive hypertrophy in a shorter timespan than PVE; however, it is also associated with higher complication rates and mortality. Minimally invasive surgery (MIS), with its known benefits, has been applied to ALPPS in the hope of reducing the surgical insult and improving functional recovery time while preserving the extensive FLR hypertrophy. METHODS: A search of the PubMed, Medline, EMBASE and Cochrane Library databases was conducted on 10 July 2019. 1231 studies were identified and screened. 19 open ALPPS studies, 3 MIS ALPPS and 1 study reporting on both were included in the analysis. RESULTS: 1088 open and 46 MIS-ALPPS cases were included in the analysis. There were significant differences in the baseline characteristic: open ALPPS patients had a more diverse profile of underlying pathologies (p = 0.028) and comparatively more right extended hepatectomies (p = 0.006) as compared to right hepatectomy and left extended hepatectomy performed. Operative parameters (time and blood loss) did not differ between the two groups. MIS ALPPS had a lower rate of severe Clavien-Dindo complications (≥ IIIa) following stage 1 (p = 0.063) and significantly lower median mortality (0.00% vs 8.45%) (p = 0.007) compared to open ALPPS. CONCLUSION: Although MIS ALPPS would seem to be better than open ALPPS with reduced morbidity and mortality rates, there is still limited evidence on MIS ALPPS. There is a need for a higher quality of evidence on MIS ALPPS vs. open ALPPS to answer whether MIS ALPPS can replace open ALPPS.

Simulating a Mott Insulator Using Attractive Interaction.

We study the particle-hole symmetry in the Hubbard model using ultracold fermionic atoms in an optical lattice. We demonstrate the mapping between charge and spin degrees of freedom and, in particular, show the occurrence of a state with "incompressible" magnetization for attractive interactions. Our results present a novel approach to quantum simulation by giving access to strongly correlated phases of matter through an experimental mapping to easier detectable observables.

Relation between feeding behaviour and energy metabolism in pigs fed diets enriched in dietary fibre and wheat aleurone.

Feed intake and its daily pattern are regulated both at a short and a long term by several control pathways, including energy balance regulation. This trial aimed to determine the effect of dietary fibre (DB) (mix of wheat, soy and sugar beet pulp fibres) and aleurone supplementation and their interaction on energy and nitrogen balances in growing pigs with ad libitum access to feed. Forty pigs (BW: 35 kg) were fed diets differing by fibre concentration (NDF concentration: 10% or 14% DM) and aleurone supplementation (0, 2 or 4 g/kg) during 3 weeks. Pigs were housed individually in a respiration chamber during the last week to record feeding behaviour and measure energy and nitrogen balances (n = 36). Glucose oxidation was studied on the 6th day with an injection of [U-13C] glucose and measurement of 13CO2 production. There was no significant interaction between DB inclusion and aleurone supplementation on any variables characterizing feeding behaviour. Pigs had less but longer meals with high level of DB, with an increased interval between two meals without effect on daily feed intake. The meal frequency significantly decreased when aleurone supplementation increased. Total tract apparent digestibility coefficient of DM, organic matter, ash, nitrogen and gross energy decreased when pigs received high DB level. Dietary fibre level increased significantly faecal excreted nitrogen. Aleurone supplementation decreased nitrogen retention. Free access to the feed induced a great individual variability not only in feed intake level (from 784 to 2290 g/day) but also in feeding behaviour (from 5.5 to 21.5 meals per day). This variability can be linked with the importance of underlying feed intake regulation pathways and difference in energy balance and metabolism efficiency. Several profiles of metabolism efficiency can be discriminate, thanks to a clustering based on feeding behaviour and pre-prandial concentrations of metabolites and hormones. In conclusion, DB inclusion decreased meal frequency, increased average meal size, decreased total tract apparent faecal digestibility coefficient of nitrogen and gross energy. Supplementation of aleurone decreased average daily feed intake with a reduction of the meal number per day, without modification of average meal size. Aleurone supplementation decreased nitrogen retention and nutrient deposition. Independently of experimental diets, the high individual variability permitted discriminating different profiles with different metabolic strategies. Efficient pigs with a high energy retention as protein and lipid seem to be able to adapt their metabolism according to energy sources.

RSK2 is a new Pim2 target with pro-survival functions in FLT3-ITD-positive acute myeloid leukemia.

Acute myeloid leukemia (AML) with the FLT3 internal tandem duplication (FLT3-ITD AML) accounts for 20-30% of AML cases. This subtype usually responds poorly to conventional therapies, and might become resistant to FLT3 tyrosine kinase inhibitors (TKIs) due to molecular bypass mechanisms. New therapeutic strategies focusing on resistance mechanisms are therefore urgently needed. Pim kinases are FLT3-ITD oncogenic targets that have been implicated in FLT3 TKI resistance. However, their precise biological function downstream of FLT3-ITD requires further investigation. We performed high-throughput transcriptomic and proteomic analyses in Pim2-depleted FLT3-ITD AML cells and found that Pim2 predominantly controlled apoptosis through Bax expression and mitochondria disruption. We identified ribosomal protein S6 kinase A3 (RSK2), a 90 kDa serine/threonine kinase involved in the mitogen-activated protein kinase cascade encoded by the RPS6KA3 gene, as a novel Pim2 target. Ectopic expression of an RPS6KA3 allele rescued the viability of Pim2-depleted cells, supporting the involvement of RSK2 in AML cell survival downstream of Pim2. Finally, we showed that RPS6KA3 knockdown reduced the propagation of human AML cells in vivo in mice. Our results point to RSK2 as a novel Pim2 target with translational therapeutic potential in FLT3-ITD AML.

Antiferromagnetic Correlations in Two-Dimensional Fermionic Mott-Insulating and Metallic Phases.

We experimentally study the emergence of antiferromagnetic correlations between ultracold fermionic atoms in a two-dimensional optical lattice with decreasing temperature. We determine the uniform magnetic susceptibility of the two-dimensional Hubbard model from simultaneous measurements of the in situ density distribution of both spin components. At half filling and strong interactions our data approach the Heisenberg model of localized spins with antiferromagnetic correlations. Moreover, we observe a fast decay of magnetic correlations when doping the system away from half filling.

Formation of Defence Primary Healthcare: a new way of delivering firm base primary healthcare.

Following the Strategic Defence and Security Review of 2010, the UK Surgeon General was directed to merge the delivery of primary healthcare from the three single Service organisations to a unified Defence Primary Healthcare. Although front line clinical staff were to be preserved, considerable savings were to be made in headquarters staff. This was one of the largest UK military medicine changes in delivery for a generation. The changes were completed on time with the transfer of UK and overseas general practice, specialist community services and dentistry, with a later requirement to add healthcare for the Reserves. The first years of this initiative have been remarkably successful, and Defence Primary Healthcare (DPHC) has progressively increased performance in all the QOF criteria measured by Defence Statistics.

Insulin degludec results in lower rates of nocturnal hypoglycaemia and fasting plasma glucose vs. insulin glargine: A meta-analysis of seven clinical trials.

BACKGROUND AND AIMS: Basal insulin analogues have a reduced risk of hypoglycaemia compared with NPH insulin, but hypoglycaemia still remains a major impediment to achieving recommended fasting plasma glucose (FPG) targets in patients with diabetes. Insulin degludec (IDeg) is a new basal insulin that forms soluble multihexamers after subcutaneous injection resulting in an ultra-long duration of action and stable glucose-lowering effect. The aim of this analysis was to compare the effect of IDeg on FPG and nocturnal confirmed hypoglycaemia as compared to insulin glargine (IGlar). METHODS AND RESULTS: Data were included from seven phase 3a, randomised, open-label, treat-to-target clinical trials in which once-daily IDeg was compared with once-daily IGlar. Two trials included a total of 957 patients with type 1 diabetes (T1D) and five trials included a total of 3360 patients with type 2 diabetes (T2D); all trials were 26 or 52 weeks in duration. Confirmed hypoglycaemia was defined as plasma glucose <3.1 mmol/L or severe episodes requiring assistance, and nocturnal hypoglycaemia occurred between 00:01 and 05:59. In all trials, the mean end-of-trial FPG was lower for IDeg than IGlar, reaching statistical significance in three trials. Similarly, IDeg was associated with a lower rate of nocturnal confirmed hypoglycaemia vs. IGlar, which was statistically significant in three trials, regardless of type of diabetes or background therapy. CONCLUSION: This analysis shows that the lower rate of nocturnal confirmed hypoglycaemia seen with IDeg relative to IGlar is accompanied by a reduced mean FPG, in particular in patients with T2D.

Efficacy and safety of insulin degludec given as part of basal-bolus treatment with mealtime insulin aspart in type 1 diabetes: a 26-week randomized, open-label, treat-to-target non-inferiority trial.

AIMS: The efficacy and safety of insulin degludec (IDeg) was compared with insulin detemir (IDet), both administered once daily (OD) as basal treatment in participants with type 1 diabetes mellitus (T1DM). The primary outcome was non-inferiority of IDeg to IDet in glycated haemoglobin (HbA1c) reduction after 26 weeks. METHODS: This multinational, 26-week, controlled, open-label, parallel-group trial randomized adults with T1DM to IDeg or IDet as OD basal insulin treatment combined with mealtime bolus insulin aspart (IAsp). Participants with T1DM treated with any basal-bolus insulin regimen for ≥ 12 months prior to the trial, a mean HbA1c ≤ 10.0% (85.8 mmol/mol) and body mass index (BMI) ≤ 35.0 kg/m(2) at screening participated in the trial (IDeg: N = 302; IDet: N = 153). RESULTS: After 26 weeks, HbA1c decreased 0.73% (8.0 mmol/mol) (IDeg) and 0.65% (7.1 mmol/mol) (IDet) [estimated treatment difference (ETD) IDeg-IDet: -0.09% (-0.23; 0.05)95% CI (-10.0 mmol/mol [-2.6; 0.6]95% CI ); confirming non-inferiority]. Mean fasting plasma glucose improved in both groups, and was lower with IDeg than IDet [ETD IDeg-IDet: -1.66 mmol/l (-2.37; -0.95)95% CI , p < 0.0001]. The rate of confirmed hypoglycaemia was similar with IDeg and IDet [45.83 vs. 45.69 episodes per patient-year of exposure (PYE); estimated rate ratio (RR) IDeg/IDet: 0.98 (0.80; 1.20)95% CI , p = 0.86]. The rate of nocturnal confirmed hypoglycaemia was lower with IDeg than IDet [4.14 vs. 5.93 episodes per PYE; RR IDeg/IDet: 0.66 (0.49; 0.88)95% CI , p = 0.0049]. Adverse event profiles were similar between groups. CONCLUSION: IDeg administered OD in basal-bolus therapy effectively improved long-term glycaemic control in participants with T1DM with a lower risk of nocturnal confirmed hypoglycaemia than IDet.

Difference in short-term responses to a high-fiber diet in pigs divergently selected for residual feed intake.

Residual feed intake (RFI), defined as the difference between observed and predicted feed intakes, has been explored as a relevant selection criterion to improve feed efficiency in growing pigs. Previous studies exploring the genetic and physiological bases of RFI have been focused on pigs fed a regular diet. The aim of this study was to evaluate the effects of RFI selection on pigs' ability to digest and metabolize a diet enriched in fiber. After 11 wk of age, pigs of 2 lines divergently selected for RFI (low or high; n = 7 pairs of littermates in each line) were fed either a control diet (133 g NDF and 9.69 MJ NE/kg) or a high-fiber diet (244 g NDF and 8.36 MJ NE/kg) for 3 wk. Irrespective of diet, ADFI and water consumption were lower (P < 0.001) in the low RFI line, whereas G:F over the test period was 16% greater (P < 0.001) in that line compared with the high RFI line. There was no line-associated difference in the digestibility of nutrients and energy, despite a lighter digestive tract (-6.4%, P = 0.04) and a lower colon weight (-8.6%, P = 0.03) in the low RFI pigs than in the high RFI pigs. As compared with the control diet, ADFI was reduced (-7.5%, P < 0.001) in both lines when fed a high-fiber diet, but ADG and G:F were lowered for the high RFI line only (P < 0.05). The high-fiber diet decreased (P < 0.01) the digestibility values of nutrients and energy similarly in both lines. However, it increased the ratio of acetate to propionate concentrations in the distal part of the gastrointestinal tract for the high RFI line only (P < 0.07). The pattern of response of plasma metabolites and hormones to a meal test was altered by RFI selection, but it was not affected by the diet. The increase in glucose concentration after meal ingestion was more pronounced (P < 0.05) in the low RFI line, and long-lasting plasma concentrations of lactate tended to be lower (P < 0.10) in the low RFI line than in high RFI line. Plasma NEFA concentrations were greater in that line compared with the high RFI line. The activity levels of catabolic enzymes in muscle and the liver did not differ between lines and diets. In conclusion, the low RFI pigs seem to better utilize a high-fiber diet than high RFI pigs. This was not associated with marked changes in digestion, and the underlying metabolic mechanisms remain to be clarified.

Overexpression of gastric leptin precedes adipocyte leptin during high-fat diet and is linked to 5HT-containing enterochromaffin cells.

OBJECTIVES: In obesity, while hyperleptinemia highly correlates with excess fat mass, the status of gastric leptin remains unknown. Here, we investigated the expression of leptin in stomach biopsies of obese humans and analyzed the temporal changes of gastric leptin expression in response to diet-induced obesity and its impact on 5-hydroxytryptamine (5HT)-producing cells. METHODS: Enterochromaffin (EC) cells and expression of leptin, PAX4 (critical factor for EC specification), tryptophane hydroxylase-1 (TPH1, the peripheral rate-limiting enzyme for 5HT) and 5HT were examined by immunofluorescence, quantitative real-time PCR, radioimmunoassay, respectively, in stomach and duodenum biopsies from 19 obese and 14 normo-weighed individuals, and in mucosa scrapings from C57Bl6/J diet-induced obese mice, leptin-deficient ob/ob mice and intestine-specific leptin receptor isoform B-deficient mice. RESULTS: Gastric mucosa of obese subjects displays an increased expression of leptin (LEP mRNA by fivefold and protein by twofold, P<0.01), TPH1 ((1.75-2.73, 95% confidence interval (CI)) vs (0.38-0.67, 95% CI); P<0.01) and PAX4 ((1.33-2.11, 95%CI) vs (0.62-0.81, 95% CI); P<0.01) as compared with normo-weighed individuals. In diet-induced obese mice, the overexpressions of gastric leptin, antral Pax4, Tph1 and increased EC cell number occurred before the onset of obesity and hyperleptinemia (reflect of adipocyte leptin production). In addition, leptin deficiency was associated with reduced Pax4 mRNA, whereas oral leptin treatment enhanced both Tph1 and Pax4 mRNA. Finally, mice with an intestine-specific deletion of leptin signaling exhibit significant decrease in duodenal mucosa 5HT content. CONCLUSIONS: These data demonstrate that gastric leptin is upregulated in obese individuals. RESULTS from high-fat diet mice showed that overexpression of gastric leptin that is linked to gut '5HT pathway' occurred before the onset of obesity and expansion of fat mass. This may be relevant in the pathophysiology of obesity.

[Intracranial hemorrhage in adults: place of antithrombotic treatment]. / Hémorragies intracrâniennes de l'adulte : implication de plus en plus importante des traitements antithrombotiques ?

BACKGROUND AND PURPOSE: Antithrombotic (anticoagulants and antiplatelets) are responsible for iatrogenic accidents, with a specific impact in neurosurgery. Bleeding complications are the most common and best-known. But the link to antiplatelet or to dual association of antithrombotic treatment with intracranial haemorrhage is not complete yet. We studied the proportion of patients under antithrombotic treatment, when an intracranial hemorrhage occurred, as well as the morbi-mortality of each group of patients (with or without antithrombotic treatment). Finally, we studied the proportion of off-label prescriptions. METHODS: We conducted a monocentric and comprehensive prospective study on a group of patients. All patients that had been admitted for intracranial hemorrhage to our hospital, in a 5-month period were included in the study. RESULTS: One hundred and sixty patients admitted for an intracranial hemorrhage were included during 70days of call. Seventy-four of these patients (46.25%) were under antithrombotic treatment: 40 under antiplatelet treatment (54%), 29 under anticoagulant treatment (39.2%), four under dual antithrombotic treatment (5.4%), and one under Arixtra(®). Half of the patients under antithrombotic treatment had poor prognosis as compared to 40% of patients without antithrombotic treatment. Off-label antithrombotic therapy was estimated at 27.3% of all prescriptions. CONCLUSIONS: The prevalence of antithrombotic therapy in patients is high when intracranial hemorrhage occurs. Some complications could be avoided by decreasing the number of off-label prescriptions and by better controlling their use (using standardized INR). Antiplatelet treatments and new antithrombotic therapies require better drug monitoring which could be part of the establishment of a specific register.

Comparative effects of level of dietary fiber and sanitary conditions on the growth and health of weanling pigs.

There are conflicting results on the growth and health of weanling pigs (Sus scrofa) fed high-fiber diets, and responses may differ according to sanitary conditions. This study was conducted to explore the growth, health, and fecal microbiota of weanling pigs fed either low- or high-fiber diets in 2 different sanitary conditions. Forty-eight pigs weaned at 28 d of age were individually housed in "good" (clean) or "poor" (unclean) sanitary conditions. During 2 consecutive phases, pigs were fed 2 diets containing a low (control) or high level of fiber: 121 or 169 g/kg total dietary fiber (TDF) for Phase I and 146 or 217 g/kg for Phase II, which lasted 15 and 20 d, respectively. This led to 4 experimental treatments in Phase I in a 2 × 2 factorial arrangement (2 sanitary conditions × 2 diets) and 8 experimental treatments in Phase II in a 2 × 2 × 2 factorial arrangement (2 sanitary conditions × 2 diets in Phase I × 2 diets in Phase II). The poor sanitary conditions led to a reduced G:F (0.617 vs. 0.680 for poor and good sanitary conditions, respectively; P = 0.01) over the entire experimental period. The number of pigs with diarrhea in Phase I tended to be greater in the poor sanitary conditions with the high-fiber diet than the control diet (7 vs. 3 pigs, P = 0.07). Enterococcus was prominent in feces of these diarrheic pigs. At 5 wk after weaning, compared with good sanitary conditions, the fecal microbiota of pigs housed in poor sanitary conditions was characterized by more Lactobacillus (9.24 vs. 8.34 log cfu/g, P < 0.001), more Enterobacteria (6.69 vs. 5.58 log cfu/g, P < 0.001), and less anaerobic sulfite bacteria (3.72 vs. 5.87 log cfu/g; P < 0.001). The feces of pigs in poor sanitary conditions contained more total VFA and proportionally more butyrate (9.7 vs. 5.7% for poor and good conditions, respectively, independently of dietary treatment, P < 0.001). At 5 wk after weaning, feces of pigs fed the high-fiber diet during Phase II contained less Enterococcus bacteria than pigs fed the control diet (4.06 vs. 4.56 log cfu/g; P = 0.05), and more total VFA with a decreased proportion of branched-chain fatty acids (5.0 vs. 6.1%; P = 0.006). To conclude, feeding pigs a high-fiber diet in the immediate period after weaning is probably an additional risk factor for slower BW gain, especially in poor sanitary conditions.

Changes in basophil activation during grass-pollen sublingual immunotherapy do not correlate with clinical efficacy.

BACKGROUND: Biomarkers predicting the safety and efficacy of sublingual immunotherapy (SLIT) remain to be established. METHODS: Eighty-nine patients with allergic rhinoconjunctivitis to grass pollen received either a placebo or five-grass-pollen daily tablet sublingually for 4 months. Following exposure in an allergen challenge chamber, clinical responders and nonresponders were identified individually by evaluating their rhinoconjunctivitis total symptom score (RTSS). Activation of peripheral blood basophils was measured by cytofluorometry before and after 2 or 4 months of immunotherapy, based on CD203c surface expression following allergen stimulation. RESULTS: Patients receiving the grass-pollen tablet had a relative mean improvement of 29.3% vs placebo in the average RTSS after 4 months of SLIT (P < 0.0003). No significant changes in basophil activation were noticed after 2 or 4 months of SLIT despite induction of specific IgGs. Among individual clinical responders, basophil activation was either decreased, increased, or unmodified during SLIT. Levels of basophil activation prior to immunotherapy were not predictive of local adverse reactions associated with immunotherapy. A moderate association was found between basophil activation and allergen-specific IgE levels, skin reactivity, or RTSS, suggesting that the former is, to some extent, indicative of disease severity. As such, patients with the highest level of basophil activation before treatment were more likely to benefit clinically from SLIT. CONCLUSIONS: Allergen reactivity of peripheral blood basophils is not a biomarker for adverse events or early onset of clinical responses to SLIT.

[Exogenous tooth discoloration in children: black stains]. / Les colorations dentaires noires exogènes chez l'enfant : Black-stains.

Black-stains are a coloring frequently met in pediatric dentistry. They can be medically diagnosed as 1-mm borders or unfinished lines formed by a dark exogenous substance which follows the gingival festoon of bet coronary (in cervical third of the crown) temporary teeth and permanent, or they can appear in like points or dark spots. They are caused by bacteria anaerobic chromogenous. The dominant responsible species are actinomyces. Blacks-stains are ferrous depots, formed following a chemical interaction on the surface of the tooth between sulphide of hydrogen (under the effect of the anaerobic bacteria which are producing hydrogen) and the iron contained in the saliva (by a healthy diet) or that released by red blood corpuscles (in case of bloody gums). Black-stains are a shape of characteristic dental plaque by its flora with trend to calcify. It contains an insoluble iron salt with a content raised in calcium and in inorganic phosphor. The coloring Black-stain is a mild pathology and has no incidence on the vitality of the tooth. Certainly these spots are unsightly. The dental surgeon in current practice can deprive them. The pediatrician plays a leading role in the diagnosis and advice to parents and patients affected by these stains.

The average Adjusted Symptom Score, a new primary efficacy end-point for specific allergen immunotherapy trials.

BACKGROUND: In clinical trials, the efficacy of immunotherapy for allergic rhinoconjunctivitis symptoms is often evaluated with the average Rhinoconjunctivitis Total Symptom Score (ARTSS). Effective treatment is associated with a lower ARTSS vs. placebo but use of rescue medication to alleviate symptoms reduces the RTSS and decreases the mean difference between active treatment and placebo groups. OBJECTIVE: To develop and describe the average Adjusted Symptom Score (AdSS), a new end-point reflecting symptom severity and rescue medication use in allergic rhinoconjunctivitis trials. METHODS: To calculate the AdSS, the RTSS is adjusted as follows: if a patient takes rescue medication on day d, the day's AdSS (AdSS(d)) is defined as the value of RTSS(d) or AdSS(d-1), whichever is higher. The AdSS on the following day (AdSS(d+1)) is defined as the value of RTSS(d+1) or AdSS(d), whichever is higher. The average of the daily AdSSs (during the season) was calculated post hoc for two trials investigating the efficacy of five-grass pollen sublingual immunotherapy tablets in adult and paediatric patients and compared with the ARTSS and three other outcome measures (the average Rescue Medication Score (ARMS), the ARTSS and the average Combined Score). RESULTS: The average AdSS clearly discriminated between active and placebo treatments and confirmed the original ARTSS results. Adjustment for rescue medication use decreased the observed placebo effect. CONCLUSION AND CLINICAL RELEVANCE: The average AdSS can be a valuable alternative to the ARTSS as a primary efficacy end-point in grass pollen allergic rhinoconjunctivitis trials. By adjusting the RTSS for rescue medication use, the AdSS can estimate symptom severity and the treatment effect more accurately. The AdSS is now being tested prospectively in large clinical trials.

The allergen challenge chamber: a valuable tool for optimizing the clinical development of pollen immunotherapy.

The clinical development of allergen immunotherapy for allergic rhinoconjunctivitis because of pollen is complicated by seasonal, geographical and subject-related variability in allergen exposure. Using an allergen challenge chamber (ACC), a room that enables reproducible challenges with controlled levels of inhalant allergens for several hours, these factors can be controlled. The ACC has often been used to evaluate symptomatic medications but is underexploited in the field of allergen immunotherapy. When used in conjunction with a programme of natural-exposure trials, the ACC enables researchers to (i) facilitate the allergen immunotherapy dose-finding process, (ii) accelerate the transition from Phase I/II to Phase III trials, (iii) characterize the onset and maintenance of action, (iv) avoid the confounding effects of rescue medication, (v) better characterize the baseline or pretreatment characteristics of trial subjects, (vi) perform better-standardized physical and laboratory measurements during an acute challenge, (vii) simplify trial logistics and use smaller numbers of subjects than would be required in equivalent natural-exposure studies and (viii) support (but not replace) Phase III natural-exposure trials for the investigation into long-term and disease-modifying effects. ACC studies can further increase levels of evidence for allergen immunotherapy--the only current therapy potentially capable of modifying the underlying allergic disease.

[Travelling families: a nurses' consultation]. / La famille en voyage: une consultation infirmière sur mesure.

In support of the general practitioners and paediatricians of both the private and public sectors, a team of three nurses specialised in Travel Health Medicine offers first line consultations to families about to travel. The team updates basic vaccinations and determines the vaccinations specific to each destination, particularly the yellow fever vaccine, following the recommendations of the Swiss Group of Travel Health Medicine and the Federal Office of Public Health. The nurses inform and prescribe the adequate medication against malaria for parents and children. The consultation is also a place for counselling, where parents can ask questions about various subjects related to their travel. Tact, receptiveness, and reassurance are essential assets of the nurses, allowing for an efficient and useful consultation for the travellers.