Pediatric ocular rosacea, a misdiagnosed disease with high morbidity: Proposed diagnostic criteria

Ocular rosacea is an important and underdiagnosed chronic inflammatory disorder observed in children. A clinical spectrum ranging from chronic eyelid inflammation, recurrent ocular redness, photophobia and/or hordeola/chalazions and conjunctival/corneal phlyctenules evolving to neovascularization and scarring may occur. Visual impairment and consequent amblyopia are frequent and corneal perforation although rare is the most feared complication. Ocular manifestations usually precede cutaneous lesions. Although few cases of pediatric ocular rosacea (POR) have been reported in the literature, many cases must have been underdiagnosed or misdiagnosed. The delay in diagnosis is greater than one year in the large majority of cases and may lead to serious ocular sequelae. This review aims to highlight the clinical features of POR, its epidemiology, easy diagnosis and effective treatment. We also propose new diagnostic criteria, in which at least three of the five clinical criteria must be present: (1) Chronic or recurrent keratoconjunctivitis and/or red eye and/or photophobia; (2) Chronic or recurrent blepharitis and/or chalazia/ hordeola; (3) Eyelid telangiectasia documented by an ophthalmologist; (4) Primary periorificial dermatitis and/ or primary features of rosacea; and (5) Positive familial history of cutaneous and/or ocular rosacea.

An investigation of the molecular pharmacology of G protein-coupled receptor 35

G protein-coupled receptors (GPCRs) are seven-pass integral membrane proteins that act as transducers of extracellular signals across the lipid bilayer. Their location and involvement in basic and pathological physiological processes has secured their role as key targets for pharmaceutical intervention. GPCRs are targeted by many of the best-selling drugs on the market and there are a substantial number of GPCRs that are yet to be characterised; these could offer interest for therapeutic targeting. GPR35 is one such receptor that, as a result of gene knockout and genome wide association studies, has attracted interest through its association with cardiovascular and gastrointestinal disease. Elucidation of the basic physiological function of GPR35 has, however, been difficult due a paucity of potent and selective ligands in addition to a lack of consensus on the endogenous ligand. Herein, a focussed drug discovery effort was carried out to identify agonists of GPR35. Various in vitro cellular assays were employed in conjunction with N- or C-terminally manipulated forms of the receptor to investigate GPR35’s signalling profile and to provide an assay format suitable for the characterisation of newly identified ligands. Although GPR35 associates with both Gαi/o and Gα13 families of small heterotrimeric G proteins, the G protein-independent β-arrestin-2 recruitment format was found to be the most suited to drug screening efforts. Small molecule compound screening, carried out in conjunction with the Medical Research Council Technology, identified compound 1 as the most potent ligand of human GPR35 reported at that time. However, the lower efficacy and potency of compound 1 at the rodent species orthologues of GPR35 prevented its use in in vivo studies. A subsequent effort, carried out with Novartis, focused on mast cell stabilisers as putative agonists of GPR35, revealed lodoxamide and bufrolin as highly potent agonists that activated human and rat GPR35 with equal potency. This finding offered–for the first time–the opportunity to employ the same GPR35 ligand between species at a similar concentration, an important factor to consider when translating rodent in vivo functional studies to those in man. Additionally, using molecular modelling and site directed mutagenesis studies, these newly identified compounds were used to aid characterisation of the ligand binding pockets of human and rat GPR35 to reveal the molecular basis of species selectivity at this receptor. In summary, this research effort presents GPR35 tool compounds that can now be used to dissect the basic biology of GPR35 and investigate its contribution to disease.

Improving the use of G-CSF during chemotherapy using physiological mathematical modelling : a quantitative systems pharmacology approach

La diminution des doses administrées ou même la cessation complète d'un traitement chimiothérapeutique est souvent la conséquence de la réduction du nombre de neutrophiles, qui sont les globules blancs les plus fréquents dans le sang. Cette réduction dans le nombre absolu des neutrophiles, aussi connue sous le nom de myélosuppression, est précipitée par les effets létaux non spécifiques des médicaments anti-cancéreux, qui, parallèlement à leur effet thérapeutique, produisent aussi des effets toxiques sur les cellules saines. Dans le but d'atténuer cet impact myélosuppresseur, on administre aux patients un facteur de stimulation des colonies de granulocytes recombinant humain (rhG-CSF), une forme exogène du G-CSF, l'hormone responsable de la stimulation de la production des neutrophiles et de leurs libération dans la circulation sanguine. Bien que les bienfaits d'un traitement prophylactique avec le G-CSF pendant la chimiothérapie soient bien établis, les protocoles d'administration demeurent mal définis et sont fréquemment déterminés ad libitum par les cliniciens. Avec l'optique d'améliorer le dosage thérapeutique et rationaliser l'utilisation du rhG-CSF pendant le traitement chimiothérapeutique, nous avons développé un modèle physiologique du processus de granulopoïèse, qui incorpore les connaissances actuelles de pointe relatives à la production des neutrophiles des cellules souches hématopoïétiques dans la moelle osseuse. À ce modèle physiologique, nous avons intégré des modèles pharmacocinétiques/pharmacodynamiques (PK/PD) de deux médicaments: le PM00104 (Zalypsis®), un médicament anti-cancéreux, et le rhG-CSF (filgrastim). En se servant des principes fondamentaux sous-jacents à la physiologie, nous avons estimé les paramètres de manière exhaustive sans devoir recourir à l'ajustement des données, ce qui nous a permis de prédire des données cliniques provenant de 172 patients soumis au protocol CHOP14 (6 cycles de chimiothérapie avec une période de 14 jours où l'administration du rhG-CSF se fait du jour 4 au jour 13 post-chimiothérapie). En utilisant ce modèle physio-PK/PD, nous avons démontré que le nombre d'administrations du rhG-CSF pourrait être réduit de dix (pratique actuelle) à quatre ou même trois administrations, à condition de retarder le début du traitement prophylactique par le rhG-CSF. Dans un souci d'applicabilité clinique de notre approche de modélisation, nous avons investigué l'impact de la variabilité PK présente dans une population de patients, sur les prédictions du modèle, en intégrant des modèles PK de population (Pop-PK) des deux médicaments. En considérant des cohortes de 500 patients in silico pour chacun des cinq scénarios de variabilité plausibles et en utilisant trois marqueurs cliniques, soient le temps au nadir des neutrophiles, la valeur du nadir, ainsi que l'aire sous la courbe concentration-effet, nous avons établi qu'il n'y avait aucune différence significative dans les prédictions du modèle entre le patient-type et la population. Ceci démontre la robustesse de l'approche que nous avons développée et qui s'apparente à une approche de pharmacologie quantitative des systèmes (QSP). Motivés par l'utilisation du rhG-CSF dans le traitement d'autres maladies, comme des pathologies périodiques telles que la neutropénie cyclique, nous avons ensuite soumis l'étude du modèle au contexte des maladies dynamiques. En mettant en évidence la non validité du paradigme de la rétroaction des cytokines pour l'administration exogène des mimétiques du G-CSF, nous avons développé un modèle physiologique PK/PD novateur comprenant les concentrations libres et liées du G-CSF. Ce nouveau modèle PK a aussi nécessité des changements dans le modèle PD puisqu’il nous a permis de retracer les concentrations du G-CSF lié aux neutrophiles. Nous avons démontré que l'hypothèse sous-jacente de l'équilibre entre la concentration libre et liée, selon la loi d'action de masse, n'est plus valide pour le G-CSF aux concentrations endogènes et mènerait en fait à la surestimation de la clairance rénale du médicament. En procédant ainsi, nous avons réussi à reproduire des données cliniques obtenues dans diverses conditions (l'administration exogène du G-CSF, l'administration du PM00104, CHOP14). Nous avons aussi fourni une explication logique des mécanismes responsables de la réponse physiologique aux deux médicaments. Finalement, afin de mettre en exergue l’approche intégrative en pharmacologie adoptée dans cette thèse, nous avons démontré sa valeur inestimable pour la mise en lumière et la reconstruction des systèmes vivants complexes, en faisant le parallèle avec d’autres disciplines scientifiques telles que la paléontologie et la forensique, où une approche semblable a largement fait ses preuves. Nous avons aussi discuté du potentiel de la pharmacologie quantitative des systèmes appliquées au développement du médicament et à la médecine translationnelle, en se servant du modèle physio-PK/PD que nous avons mis au point.

Flexible bronchoscopy contribution in the approach of diagnosis and treatment of children’s respiratory diseases: the experience of a unique pediatric unit in Tunisia.

Objective: Our study aimed at assessing the role of flexible bronchoscopy (FB) in improving diagnosis and management of children’s respiratory conditions in the pediatric unit of FB, newly created and unique in Tunisia. Methods: Retrospective study including all the FB achieved in our pediatric unit from 2009 to 2014. Results: We performed 365 FB in 333 patients aged 46 months on average (1 month - 15 years), often under conscious anesthesia (81.6%). FB was performed for diagnostic purposes in 341 cases and for therapeutic purposes in 24 cases. Eight anatomical abnormalities were revealed in 22 patients. An intraluminal bronchial obstruction was found in 71 FB, mainly due to a foreign body (n=36). A vascular anomaly was responsible for nine cases out of 17 extraluminal obstructions. Airways malacia was observed in 60 FB. Bronchoalveolar lavage was performed in 196 cases. It was determinant in 43.9% of the cases. FB was of great diagnostic value in 74.8% of the cases. It influenced the management of the patients in 58% of the cases. The FB for therapeutic purposes was beneficial in all cases. Few complications occurred (5.5%). Conclusion: FB is a safe tool providing precious diagnostic and/or therapeutic help for the clinician. Keywords:

Objective Structured Clinical Examinations (OSCE) improved communication skills of student of Pharmacology in Medicine and Podiatry degree.

Objective Structured Clinical Examinations (OSCE) improved communication skills of student of Pharmacology in Medicine and Podiatry degree. Bellido I, Blanco E, Gomez-Luque A. D. Pharmacology and Clinical Therapeutic. Medicine School. University of Malaga. IBIMA. Malaga, Spain. Objective Structured Clinical Examinations (OSCEs) are versatile multipurpose evaluative tools that can be utilized to assess health care professionals in a clinical setting including communication skills and ability to handle unpredictable patient behavior, which usually are not included in the traditional clinical exam. To designee and perform OSCEs by student is a novelty that really like to the students and may improve their arguing and planning capacities and their communication skills. Aim: To evaluate the impact of designing, developing and presenting Objective Structured Clinical Examinations (OSCE) by student in the communication skills development and in the learning of medicines in Medicine and Podiatry undergraduate students. Methods: A one-year study in which students were invited to voluntarily form groups (4 students maximum). Each group has to design and perform an OSCE (10 min maximum) showing a clinical situation/problem in which medicines’ use was needed. A clinical history, camera, a mobile-phone's video editor, photos, actors, dolls, simulators or whatever they may use was allowed. The job of each group was supervised and helped by a teacher. The students were invited to present their work to the rest of the class. After each OSCE performance the students were encouraged to ask questions if they wanted to do it. After all the OSCEs performances the students voluntarily answered a satisfaction survey. Results: Students of Pharmacology of Medicine degree and Podiatry degree, N=80, 53.75% female, 21±2.3 years old were enrolled. 26 OSCEs showing a clinical situation or clinical problem were made. The average time spent by students in making the OSCE was 21.5±9 h. The percentage of students which were satisfied with this way of presentation of the OSCE was 89.7%. Conclusion: Objective Structured Clinical Examinations (OSCE) designed and performed by student of Pharmacology of the Medicine and Podiatry Degree improved their communication skills.

Hábitos de fotoprotección en los niños que concurren a Dermatología Pediátrica del Centro Hospitalario Pereira Rosell: Photoprotective habits in children seen at the Pediatric Dermatology Unit of CHPR

Introducción: la exposición a la radiación ultravioleta durante la infancia y la adolescencia juega un papel trascendente en el desarrollo futuro del cáncer de piel. Los niños se exponen al sol tres veces más que los adultos y antes de los 21 años se ha recibido entre el 50 y el 80 % de la radiación solar total. Objetivo: conocer qué saben los padres de la población objetivo sobre los efectos del sol en la piel y los ojos, y cuáles son sus hábitos de fotoprotección, los de sus hijos y los factores relacionados con ello. Métodos: estudio transversal a padres de niños que concurrieron a la policlínica de Dermatología Pediátrica del Centro Hospitalario Pereira Rossell durante los meses de octubre 2013 a enero 2014. Resultados: se entrevistó a un total de 100 padres, la media de edad de los hijos fue de 7,85 años, el 62% de los niños eran provenientes de familias de bajo nivel socioeconómico y educacional. El 43% de los encuestados respondió que le gusta estar bronceados, en comparación con un 28% que no le gusta. La medida de fotoprotección más utilizada tanto por padres (73%) como por hijos (86%) fue el protector solar, seguida de los lentes de sol en los adultos y del uso rutinario de sombrero en los niños. Conclusiones: los métodos utilizados se basan en gran medida en el uso de protectores solares con un uso inadecuado de los mismos en gran parte de los encuestados.

Salivary cortisol level and uncooperative behavior in pediatric dental practice

Aim: To investigate the relation between uncooperative behavior and salivary cortisol level in children who underwent preventive dental care. Methods: The sample was composed by 10 children of both sexes aged 40 to 52 months, presenting uncooperative behavior during dental preventive treatments. The saliva collection was performed using a cotton wheel and an Eppendorf tube (Sarstedt Salivete®) in 3 different moments: a) at home, on a day without dental treatment and at the same time on the day of the sessions treatment; b) 30 min after the end of the session, when there was manifestation of uncooperative behavior; c) 30 min after the end of the session, when there was a cooperative behavior of the child. A sample of saliva was centrifuged for 5 minutes at 2400 rpm, 1 of mL of saliva was pipetted in an Eppendorf tube and stored in a freezer at -20 ° C. For the determination of the levels of salivary cortisol was used an Active® kit for cortisol enzyme immunoassay (EIA) DSL-10-67100, composed of specific rabbit antibody anti-cortisol. Data were analyzed statistically for the uncooperative behavior issued in the beginning and at the end of sessions, using the paired t test (p<0.05) and for cortisol levels in saliva samples at home, after the beginning and at the end of sessions, using repeated-measures ANOVA and Tukey’s test (p<0.05). Results: During expression of uncooperative behavior in preventive dental care sessions the salivary cortisol level was significantly higher (0.65 ± 0.25 μg/dL) compared with expression of collaborative behavior (0.24 ± 0.10 μg/dL). Conclusions: It is possible to conclude that, even under preventive intervention, the stress must be controlled in order to reduce dental anxiety and fear.

Pediatric Nurses’ Information and Applications Related To Ethical Codes

Background: Ethics is defined as the entirety of moral principles that form the basis of individuals’ behavior; it can also be defined as “moral theory” or “theoretical ethics”. Objectives: To determinate information and applications related to ethical codes of pediatric nurses. Patients and Methods: Participants were nurses attending the Neonatal Intensive Care Unit Nursing Course and the Pediatric Nursing Course conducted in Istanbul between September 2011 and December 2012. A total of nurses attending the courses at the specified dates and who agreed to participate in the study were included in the analysis. Data were collected through a questionnaire that we developed in accordance with current literature on nursing ethics. Results: 140 nurses participated in this study. Information and applications were related to ethical codes of nurses including four categories; autonomy, beneficence, nonmaleficence, justice. The principle of confidentiality/keeping secrets. Exactly 64.3% of nurses reported having heard of nursing ethical codes. The best-known ethical code was the principle of justice. Furthermore, while the rates were generally low, some nurses engaged in unethical practices such as patient discrimination and prioritizing acquaintances. Conclusions: We conclude that most nurses working in pediatric clinics act in compliance with ethical codes. We also found that the majority of nurses wanted to learn about ethical codes. For this reason, we recommended that nurses working in clinics and future nurses in training be informed of the appropriate ethical behavior and codes.

Analysis of Outcome of Intraplueral Streptokinase in Pediatric Empyema Thoracis even in Advanced Stages: A Prospective Study

Background: Empyema thoracis in children causes significant morbidity. Standard treatment of Empyema thoracis includes tube drainage and antibiotics. But the tube drainage often fails. Intrapleural Streptokinase has been used in empyema thoracis with good success rate. Objectives: We evaluated the efficacy of intra-pleural Streptokinase in management of empyema thoracis even in advanced stages. Patients and Methods: A total of 28 patients with empyema thoracis requiring intercostal tube drainage aged zero to twelve years were included in the study who were admitted in Pediatric intensive care unit. 15,000 units/kg of Streptokinase was instilled into the pleural cavity. Response was assessed by clinical outcome, after unclamping and subsequent chest radiography and serial chest ultrasounds. Results: Streptokinase enhanced drainage in all patients with complete resolution of empyema thoracis in 26 patients. Two patients were referred for surgery. Only 7.2% required surgery. Streptokinase was equally effective if started before or after seven days. Conclusions: Intrapleural Streptokinase is the preferred treatment for treating pediatric empyema thoracis even in advanced stages and can avoid surgery.

Evaluation of Educational Environment for Medical Students of a Tertiary Pediatric Hospital in Tehran, Using DREEM Questionnaire

Background: Tertiary pediatric hospitals usually provide excellent clinical services, but such centers have a lot to do for educational perfection. Objectives: This study was performed to address under-graduate educational deficits and find feasible solutions. Patients and Methods: This cross-sectional study was done in a target population of 77 sixth year undergraduate medical students (response rate = 78%) who spent their 3-month pediatric rotation in the Children’s Medical Center, the Pediatrics Center of Excellence in Tehran, Iran. The Dundee ready educational environment measure (DREEM) instrument was used for assessing educational environment of this subspecialized pediatric hospital. Results: Among 60 students who answered the questionnaires, 24 were male (40%). Participants’ age ranged from 23 to 24 years. The mean total score was 95.8 (48%). Comparison of scores based on students’ knowledge showed no significant difference. Problematic areas were learning, academic self-perception, and social self-perception. Conclusions: Having an accurate schedule to train general practitioner, using new teaching methods, and providing a non-stressful atmosphere were suggested solutions.

Tracheostomy in Pediatric Intensive Care Unit: When and Where?

Background: Tracheostomy was first observed in Egyptian drawings in 3600 BC and performed frequently during the 1800’s diphtheria epidemic. Objectives: The aim of this study was to elucidate the indications, complications, mortality rate, and the effect of pediatric tracheostomy on length of PICU or hospital stay. Materials and Methods: Demographic characteristics, diagnosis at admission, duration of ventilation of 152 patients were analyzed retrospectively. Results: The most common tracheostomy indication was prolonged intubation. The mean duration of mechanical ventilation before tracheostomy was 23.8 days. Forty five percent of the tracheostomy procedures were performed at bedside. Neither the place nor the age had any effect on the development of complications (P = 0.701, P = 0.622). The procedure enabled 62% of the patients to be discharged from hospital. Conclusions: Tracheostomy facilitates discharge and weaning of mechanical ventilation. Although the timing of tracheostomy has to be determined for each individual patient, three weeks of ventilation seems to be a suitable period for tracheostomy. Tracheostomy can be performed at bedside safely but patient selection should be made carefully.

Pediatric Coronary Artery Revascularization Surgery: Development and Effects on Survival, Cardiac Events and Graft Patency for Children With Kawasaki Disease Coronary Involvements

Pediatric coronary artery bypass surgery gained wide acceptance with the introduction of internal thoracic arteries (ITAs) for bypass operations for post Kawasaki disease (KD) lesions. The technique is now established as the standard surgical choice, and its safety even in infancy, graft patency, growth potential, graft longevity and clinical efficacy have been well documented. In this article the author reviews the development of pediatric coronary bypass as the main indication for the treatment of coronary lesions due to KD. I believe that coronary revascularization surgery in pediatric population utilizing uni- or bilateral ITAs is the current gold-standard as the most reliable treatment, although percutaneous coronary intervention with or without a stent has been tried with vague long-term results in children.

Different Aspects of General Anesthesia in Pediatric Dentistry: A Review

Context:Most child population is able to undergo dental treatment in the conventional setting. However, some children fail to cope with in-office conscious state and cannot respond to usual management modalities. This review aims to discuss the topic further. Evidence Acquisition: A computerized search in databases PubMed, MEDLINE, EMBASE, Google Scholar and Google were performed using dental general anesthesia related keywords. Original and review English-written articles that were limited to child population were retrieved without any limitation of publication date. The suitable papers were selected and carefully studied. A data form designed by author was used to write relevant findings. Results: Preoperative oral examination and comprehensive evaluation of treatment needs is only possible after clinical and radiographic oral examination. Effective collaboration in dental GA team should be made to minimize psychological trauma of children who undergo dental GA. Before conducting comprehensive dental treatment under GA, the general health of the child and the success rate of procedures provided needs to be accurately evaluated. It is noteworthy that determination of the optimal timing for GA dental operation is of great importance. Providing safety with pediatric dental rehabilitation under GA is critical. Conclusions: Besides criteria for case selection of dental GA, some degree of dental practitioner’s judgment is required to make decision. Pre- and post-operative instructions to parents or caregiver decrease the risk of complications. However, trained resuscitation providers, careful monitoring and advanced equipment minimize adverse outcomes.