Safety and immunogenicity of the epicutaneous reactivation of pertussis toxin immunity in healthy adults: a phase I, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Protection induced by acellular vaccines can be short, requiring novel immunization strategies. Objectives of this study were to evaluate safety and capacity of a recombinant pertussis toxin (PTgen) -coated Viaskin® epicutaneous patch to recall memory responses in healthy adults. METHODS: This double-blind, placebo-controlled randomized trial (Phase I) assessed the safety and immunogenicity of PTgen administered on days 0 and 14 to healthy adults using Viaskin® patches applied directly or after epidermal laser-based skin preparation. Patch administration was followed by Boostrix®dTpa on day 42. Antibodies were assessed at days 0, 14, 28, 42 and 70. RESULTS: Among 102 volunteers enrolled, 80 received Viaskin-PT (Viaskin-PT 25 µg (n = 25), Viaskin-PT 50 µg (n = 25), laser + Viaskin-PT 25 µg (n = 5), laser + Viaskin-PT 50 µg (n = 25)), Viaskin-placebo (n = 10) or laser + Viaskin-placebo (n = 2). Incidence of adverse events was similar across groups (any local event: 21/25 (84.0%), 24/25 (96.0%), 4/5 (80.0%), 24/25 (96.0%), 8/10 (80.0%), 10/12 (83.0%), respectively). Direct application induced no detectable response. On day 42, PT-IgG geometric mean concentrations were significantly higher following laser + Viaskin-PT 25 µg and 50 µg (139.87 (95% CI 87.30-224.10) and 121.76 (95% CI 95.04-156.00), respectively), than laser + Viaskin-placebo (59.49, 95% CI 39.37-89.90). Seroresponse rates were higher following laser + Viaskin-PT 25 µg (4/5 (80.0%), 95% CI 28.4-99.5) and 50 µg (22/25 (88.0%), 95% CI 68.8-97.5) than laser + Viaskin-placebo (0/12 (0.0%), 95% CI 0.0-26.5). CONCLUSIONS: Viaskin-PT applied after laser-based epidermal skin preparation showed encouraging safety and immunogenicity results: anti-PT booster responses were not inferior to those elicited by Boostrix®dTpa. This study is registered at ClinicalTrials.gov (NCT03035370) and was funded by DBV Technologies.

Pain after tonsillectomy: effectiveness of current guidelines?

BACKGROUND: Tonsillectomy is one of the most common major surgical procedures performed in children. In 2013, the use of codeine in children was severely restricted. French guidelines for treating tonsillectomy's postoperative pain at home have been reconsidered OBJECTIVE: The aim of our study was to measure effectiveness and safety of two schedules: acetaminophen + ibuprofen (A + I) and acetaminophen + tramadol (A + T) in children who underwent tonsillectomy. SETTING AND PATIENTS: We undertook a 1 year prospective and observational single-center study. All children who underwent tonsillectomy were eligible. The choice of the regimen, A + I group or A + T group, was left for the anesthesiologist in charge, done during the pre-anesthetic assessment. After hospital discharge, parents had to give systematically A + I or A + T, 4 times a day during 5 days and then acetaminophen alone for the next 5 days The primary endpoint was the home pain assessed using Parents' Postoperative Pain Measurement Short Form (PPPM-SF) scale. Secondary endpoints were the rate of further hospitalization and/or surgery due to tonsillectomy-related adverse events. RESULTS: Over the study period, 342 tonsillectomies were performed. The return rate of PPPM-SF scales was 58%. Two hundred patients were analyzed. The median age was 4 [3; 5.2] years and was lower in group A + I (4 [3; 5]; 5 [4; 7]; p < 0.0001). PPPM-SF scores were greater than or equal to 3 in both groups during the first 6 postoperative days. The mean decrease of PPPM-SF score over time was higher in group A + I than in group A + T (p = 0.007). Readmission rate was significantly higher in group A + T (A + I: 0; A + T: 7; p = 0.002) as the rate of reoperation for bleeding (A + I: 0; A + T: 3; p = 0.049). CONCLUSION: Home pain management after tonsillectomy should be improved. In clinical practice, A + I seems at least as effective as the combination A + T, without increasing readmission and/or additional surgery for bleeding.

Interstitial fibrosis quantification in renal transplant recipients randomized to continue cyclosporine or convert to sirolimus.

Conversion from cyclosporine (CsA) to sirolimus at week 12 after kidney transplantation is associated with a significant improvement in renal function. The aim of this analysis was to investigate the effect of this conversion on interstitial fibrosis (IF), a hallmark of chronic allograft injury, in patients taking part in the CONCEPT trial. This multicenter, prospective, trial included 193 renal recipients randomized at week 12 to switch from CsA to sirolimus or to continue CsA, with mycophenolate mofetil. Routine biopsy with automated, quantified assessment of IF by a program of color segmentation was performed at 1 year in 121 patients. At 1 year, renal function was significantly improved in the conversion group as assessed by estimated GFR (MDRD) and measured GFR. Biopsy results, however, showed no between-group difference in percentage of IF. Calculated GFR at 1 year was significantly associated with the percentage of IF (p = 0.004, R(2)= 0.07). By multivariate analysis diabetic patients had more fibrosis than non-diabetic patients. In conclusion, although kidney transplant patients converted from CsA to sirolimus showed significant improvement in renal function, we found no difference of IF on 1-year biopsies.

Laparoscopic appendectomy in children: sense or nonsense?

The authors present a retrospective analysis of their first 1.500 paediatric laparoscopic appendectomies. Three types of techniques (OUT, MIXED, IN) are described. The average age of the patients was 8 years (range: 2 to 16 years). In case of acute appendicitis the postoperative complication rate was 0.6%. In case of peritonitis the postoperative complication rate raised to 13.3%. Conversion rate was 3.3%. There were no death. Mean hospital stay was 1.8 days for acute appendicitis and 6.5 days for peritonitis. Laparoscopic appendectomy in children has an unquestionable diagnostic interest, decreases the parietal complications and has a better cosmetic result in case of peritonitis or ectopic appendicitis. Benefits are highest in case of peritonitis by decreasing postoperative pain and length of hospital stay. The teaching value for learning laparoscopic surgeons is obvious. Increase of intraperitoneal residual abscesses, as well as increasing cost, remain controversial. This series is a plea for laparoscopic appendectomy in children.

[Hemorrhagic surgery in two Jehova's witness children refusing programmed autotransfusion: a place for erythropoietin]. / Chirurgie hémorragique chez deux enfants de témoins de Jéhovah refusant l'autotransfusion programmée: place de l'érythropoïétine.

We report two cases of haemorrhagic surgery in a 6-year-old and 16-year-old girl, respectively, whose parents were Jehovah's witnesses and therefore opposed to preoperative blood donation, but accepting intraoperative blood salvage. Erythropoietin and intravenous iron were administered preoperatively to increase red cell mass. Intraoperative blood salvage, including normovolaemic haemodilution and intraoperative autologous transfusion, avoided homologous blood transfusion.

[Bronchial endoscopy under local anesthesia and pain in children. The value of a nitrous oxide-oxygen combination]. / Endoscopie bronchique sous anesthésie locale et douleur chez l'enfant. Intérêt du mélange protoxyde d'azote-oxygène.

To evaluate the efficacy of continuous administration of 50% nitrous oxide in oxygen for reducing pain during flexible fiberoptic bronchoscopy 32 children aged 3-60 months were randomly assigned to an experimental or a control group. Indications for endoscopy included persistent atelectasis (6), wheezing (10) cystic fibrosis (2) pneumonia (11) persistent cough (3). All patients received Midazolam (0.3 mg/kg) atropine (20 mcg/kg) intra rectaly 20 minutes before the procedure. The flexible fiberoptic bronchoscope (Olympus BF3C4) was inserted transnasally through a face mask. Topical anesthesia with 1% lidocaine hydrochloride (3 mg/kg) was applied to the nose, larynx, trachea and bronchial tree over 15 minutes through the suction chanel of the bronchoscope. All patients were monitored with a pulse oximeter and a cardiac monitor. The experimental group (n = 16) received 50% nitrous oxide in oxygen prior (3 minutes) and during flexible fiberoptic bronchoscopy, the control group (n = 16) received only oxygen. We measured pain of the children by a behavioral observation scale (Children's Hospital of Eastern Ontario Pain Scale: CHEOPS) at each phase of topical anesthesia during bronchoscopy in the two groups. At the end of bronchoscopy physician's satisfaction was scored by a visual analogue scale (VAS 0-100) in which 0 corresponded to absence of satisfaction. Nitrous oxide was associated with lesser pain scores than those with oxygen. Physician significantly preferred these procedure compared with oxygen. No complication occurred during procedure. Combined with local anesthesia midazolam and atropin the administration of 50% nitrous oxide in oxygen seems a better choice for flexible fiberoptic bronchoscopy in children and should be used routinely.

[Activity of pediatric emergency departments in 1991]. / Activité d'un service d'accueil des urgences pédiatriques en 1991.

The authors report the results of a prospective survey concerning the children examined in the pediatric emergency ward of the Lenval's hospital in Nice. The study was conducted over a period of 124 days, one month of each season, and included 3,611 children. There was a majority of boys (60.8%) and children older than 7 years (56.8%). The representation of foreign children was 11.2%. Most of the consultations were decided by the parents (86%); 6.2% were sent by a general practitioner and 1.1% by a pediatrician; 6.5% were conveyed through a professional public health service transport. Traumatology was the main surgical etiology and supplied the large majority of benign cases and 23% of the emergencies. Upper respiratory and bronchopulmonary tract infections and gastroenteritis represented 70% of medical etiologies. A complementary investigation, essentially a radiological examination, was carried out in 53.6% of cases. A wound suture was performed in 13% and a plaster immobilization in 9.2% of cases. The hospitalisation's rate was 22%. Emergencies represented 1.8% of cases. A surgical intervention with general anesthesia was performed in 4.4% of cases within 12 hours following the admission. A recent law (ministerial circular: 14.05, 1991) defines the organisation and working principles of the public emergency departments in France as requiring an uninterrupted activity, a continuous medical presence and an area for very short hospitalization. This should improve the quality of the pediatric emergency wards, providing that the financial means will be available.

[Radiographic study of the rheumatoid hand and etiopathogenic mechanisms of deformities. Apropos of 100 cases]. / Etude radiographic de la main rhumatoïde et des mécanismes étiopathogéniques des déformations. A propos de 100 cas.

X-rays of the hands and wrists of 100 patients suffering from rheumatoid arthritis (RA) were compared to those of 65 control subjects matched for age and sex. Osteoarticular destruction was assessed using Larsen's index and by carpal bone deformities; ulnar deviation of the fingers (UDF) and radial deviation of carpal bones (RDC). No significant asymmetry of lesions in the right or left hands can be demonstrated, whatever the subsets of patients and osteoarticular manifestations studied. After a one year course, there is no significant difference between patients and control subjects. Only the index of carpal deformity is significantly high and the clinical course progresses between 1 and 5 years (p = 0.02). The difference becomes significant for UDF (p less than 0.01) after the disease evolves for 5 to 10 yrs. UDF is correlated with carpal osteoarticular lesions (p = 0.01) and metacarpophalangeal lesions (MCP). Different osteoarticular lesions of the hand are correlated with each other. The close correlation between UDF and RDC and MCP involvement has been confirmed by various statistical tests. Comparison of seropositive and seronegative patients with RA only reveals a more marked disturbance of MCP in the seropositive patients. Various methods of assessing osteoarticular deformities and joint destruction are discussed. Finally, the etiopathogenic mechanisms causing deformities of the hand in RA were studied, and the authors reviewed the importance of the initial involvement of soft tissues and therapeutic implications whereby prevention of disease extension using prompt local therapy is recommended.