Co-inhalation of roflumilast, rather than formoterol, with fluticasone more effectively improves asthma in asthmatic mice.

Roflumilast is approved as an add-on therapy for chronic obstructive pulmonary disease. The inflammation in chronic obstructive pulmonary disease is mainly neutrophilic, while in asthma it is mainly eosinophilic, studies addressing role of roflumilast in eosinophilic inflammation are recommended. Also in severe asthma, the dominant inflammatory cells are neutrophils. Thus, roflumilast has a potential off-label use in the treatment of asthma. This study was designed to evaluate the effects of co-inhalation of roflumilast and fluticasone compared to that of formoterol and fluticasone in ovalbumin-sensitized and-challenged BALB/c mice. Besides normal control group, the ovalbumin-asthmatic mice were randomly divided into seven groups (n = 8): positive control, vehicle-treated, and five drug-treated groups. Treatments (µg/kg) were given as 15 min-inhalation once/day for five days as follows: roflumilast (500), formoterol (50), fluticasone (1000), roflumilast + fluticasone (500 + 1000), and formoterol + fluticasone (50 + 1000). Penh values were measured in conscious unrestrained mice using the single-chamber whole-body plethysmography. Airway hyperreactivity to inhaled methacholine was evaluated. Bronchoalveolar lavage fluid was used for the measurements of levels of IL-4, IL-5, TNF-α, OVA-specific IgE, and total and differential white cells. Lung sections were stained with hematoxylin and eosin and periodic acid-Schiff. The asthmatic mice showed significant increases in airway hyperreactivity which were significantly reversed by the combination treatments. The asthmatic mice showed significant increases in levels of IL-4, IL-5, TNF-α, ovalbumin-specific IgE, and total and differential white cells in bronchoalveolar lavage fluid. All treatments (except formoterol) significantly reversed these changes mainly with roflumilast + fluticasone. The asthmatic mice showed severe inflammatory infiltration and goblet cell hyperplasia which were maximally reversed by roflumilast + fluticasone, while minimally reversed by formoterol. In conclusion, co-inhalation of roflumilast + fluticasone more significantly improved inflammation and histopathological changes than co-inhalation of formoterol + fluticasone in ovalumin-asthmatic mice. Further studies are needed to help confirm the potential off-label add-on use of roflumilast in typical and atypical asthma and asthma-chronic obstructive pulmonary disease overlap syndrome. Impact statement Roflumilast, a selective phosphodiesterase-4 inhibitor, was approved for the treatment of chronic obstructive pulmonary disease (COPD). This study showed that co-inhalation of roflumilast and fluticasone significantly decreased airway hyperresponsiveness in ovalumin-asthmatic mice. Also, it more significantly improved inflammation and histopathological changes than co-inhalation of formoterol and fluticasone. The current results showed that inhaled roflumilast reduced counts of eosinophils, neutrophils, and macrophages in bronchoalveolar lavage fluid. Consequently, inhaled roflumilast might be of potential off-label benefit in treatment of eosinophilic and neutrophilic asthma and asthma-COPD overlap syndrome (ACOS). These results could also support other experimental and clinical studies addressing the same issue.

Pediatrician knowledge, perception, and experience on child abuse and neglect in Saudi Arabia.

BACKGROUND AND OBJECTIVES: The objective of this study was to assess the knowledge, perception, and professional experience of pediatricians in Saudi Arabia regarding child abuse and neglect. DESIGN AND SETTING: Descriptive study during a one day pediatric conference held on King King Abdulaziz University Hospital , a tertiary care teaching hospital in western Saudi Arabia. PATIENTS AND METHODS: The study targeted 198 attendees who were invited from different healthcare sectors in the country. RESULTS: The overall knowledge of participants about some important aspects of child abuse and negligence was adequate, ranging between 82% and 91%. However, their knowledge about reporting cases of child abuse and neglect was quite deficient, ranging between 66% and 79%. As for professional experience about child abuse and negligence it showed considerable variation between participants ranging between 43% and 82%, in which pediatricians who received their medical education in Saudi Arabia scored statistically significantly higher, while pediatricians who received their medical education in Western countries scored higher in all other aspects of the study. CONCLUSIONS: Currently, the knowledge and clinical experience on the subject of child abuse and neglect in Saudi Arabia is enough to adopt a comprehensive strategy for the prevention and interventions of child maltreatment at all levels. Pediatricians are expected to play a key role by leading and facilitating this process.

Transcatheter closure of patent ductus arteriosus: Evaluating the effect of the learning curve on the outcome.

BACKGROUND AND OBJECTIVES: Initial experience with transcatheter closure of patent ductus arteriosus (PDA) using detachable coils and Amplatzer duct occluder devices is reported. We evaluated the outcome, complications, and influence of the learning curve, and also assessed the need of surgical backup for such interventional procedures. METHODS: From January 2000 to December 2004, 121 patients underwent transcatheter closure of PDA. Aortic angiogram was performed to evaluate the size, position, and shape of the duct for appropriately choosing the occluder device type and size. A second aortic angiogram was performed 10 minutes after device deployment. Echocardiography was repeated at intervals of 24 hours, then at 1, 3, and 6 months after the procedure to assess complications. Stepwise multiple regression analysis was used to assess the role of experience in improving the outcome of the procedure. RESULTS: Of 121 cases, four patients had pulmonary artery embolization of the occluder device which was successfully retrieved in the catheterization laboratory, while two others had embolization that required surgical intervention. Four patients had temporary residual leak, nine had protrusion of the device into the aorta without significant Doppler pressure gradient or hemolysis on follow-up, and five had partial hemodynamically insignificant obstruction to the left pulmonary artery. Statistical analysis showed that the effect of the learning curve and experience was responsible for 93% improvement in the procedural outcome over the five-year study period. CONCLUSION: Transcatheter occlusion of PDA is safe and effective alternative to surgery. Complications occurred in those with unfavorable duct anatomy and with the use of multiple coils. Surgical backup was important for such interventional procedures. Experience played a major role in the proper choice of device type and size which greatly influenced the outcome of the procedure.

Clinical characteristics and responsiveness to treatment in Lennox-Gastaut syndrome. A retrospective hospital audit.

OBJECTIVE: To describe the clinical profile of Lennox-Gastaut syndrome (LGS) patients and to assess the best antiepileptic drug combination. METHODS: Patient files of all children diagnosed with LGS at King Abdul-Aziz University (KAUH), Jeddah, Kingdom of Saudi Arabia between January 2000 to January 2005 were retrieved and analyzed. Details on clinical data, and disease related variables were collected. Treatment trial, last drug combination, maintenance dosage, seizure frequency, and duration before and after treatment, and the overall effect in reducing seizures were recorded. RESULTS: Fifty-four patients were identified with a male:female ratio of 2.4:1 with age range of 10 months to 14 years. A history of febrile convulsion was found in 11 (20%) patients, history of infantile spasm was found in 14 patients (26%), mental retardation in 52 patients (96%), and hypotonia in 13 patients (24%). All patients had abnormal EEG that meets the diagnostic criteria. Brain CT scan was abnormal in 32 (65%) patients. Brain MRI was abnormal in 17 (23%) patients. Neuroradiological abnormalities varied from non-specific atrophy to hippocampal sclerosis and calcification. Metabolic screening carried out for 11 patients (20%) was normal. All patients were on a 3-drug combination at some stage of their disease. The most frequent combination was sodium valproate and lamotrigine. Intravenous immunoglobulin was used in 2 patients with temporary improvement; ketogenic diet was tried in one patient, which did not add much to fit control. CONCLUSION: The severe nature and intractability of LGS emphasize the need for active and efficacious treatment, which can improve the prognosis as a whole. Different combinations of new anticonvulsants could achieve significant seizure control and could modify the quality of life for these patients. Each patient needs to be considered individually, taking into account the potential benefit of each therapy weighed against the risk of adverse effects.

Frequency and clinical characteristics of ketoacidosis at onset of childhood type 1 diabetes mellitus in Northwest Saudi Arabia.

OBJECTIVE: To determine the frequency, and to describe the clinical characteristics of ketoacidosis at initial diagnosis of childhood type 1 diabetes mellitus (T1DM) in Al-Madina region of the Northwest province of Saudi Arabia. METHODS: We retrospectively analyzed the hospital records of 311 (152 males and 159 females) children diagnosed with childhood T1DM in Al-Madina region, Saudi Arabia between January 1992 and December 2004. RESULTS: At diagnosis 172 (55.3%) children presented with diabetic ketoacidosis at the onset of their illness, 101 (58.7%) were females and 71 (41.3%) males. We found females to have more ketoacidosis at the onset of their illness with 1.4:1 female to male ratio. The mean age at presentation with ketoacidosis was 6.7 years (95% CI=5.6-7.8) ranging from 4 months to 14 years. Most of the ketoacidosis was mild to moderate (84.9%), while only 26 (15.1%) children had the severe type. Sixty-one (35.5%) children were in the younger age group, 54 (31.4%) were in the middle age group, and 57 (33.1%) were in older age group, there was no significant difference (p=0.5) between the 3 age groups in the frequency of ketoacidosis. The duration of symptoms before presentation with ketoacidosis was 15.8 days (95% CI=13.5-18.1). Altered consciousness was present in 21 (12.2%) children; all of them were from the severe type of ketoacidosis. There was a strong correlation between the severity of the central nervous system depression and the degree of acidosis (r=0.826, p<0.0001), but no correlation with age, gender, duration of symptoms, and blood glucose level. CONCLUSION: The frequency of ketoacidosis at onset of childhood diabetes mellitus in our region is significant. Prevention of diabetic ketoacidosis and reduction of its frequency should be a goal in managing children with diabetes. Rising standards of medical information and general awareness can contribute to this.

Normal values of pulse oximetry in newborns at high altitude.

The aim of the study was to establish normal values of pulse oximetry saturation, respiratory rate, heart rate, and blood pressure in healthy newborns at high altitude. Vital signs and oximetry saturation readings were collected from healthy term newborns at birth, at 1 h, and at 24 h of life. These were analyzed and compared with reference ranges at sea level. This study was carried out at altitudes of 1640 m above sea level in Taif city, Saudi Arabia. A total of 6011 term newborns were examined at birth and 1 h and 4274 were examined at 24 h of life. At birth, the mean SpO(2) was 68.6 per cent and 60.3 per cent from the right upper and lower limbs, respectively. Mean SpO(2) was 94.3 per cent and 95.4 per cent at the age of 1 and 24 h, respectively. These values were significantly lower than those reported at sea level. The mean respiratory rate, heart rate, and mean blood pressure at 24 h were 45.7/min, 149.7/min, and 46.9 mmHg, respectively. It is concluded that pulse oximetry saturation for newborn babies is lower at higher altitudes than at sea level. This effect is observable at altitudes of 1600 m above sea level. Cut-off levels lower than those used at sea level should be adopted when dealing with newborns living at high altitudes.