תוצאת חיפוש

Use of Unlicensed and Off-Label Drugs in Hospitalized Children

M. Lifshitz, V. Gavrilov, R. Gorodischer

Toxicology Unit, Pediatrics Dept. A, Soroka Medical Center, and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Many drugs used in children are based on pharmacological data obtained in adults. Therefore, many drugs are either unlicensed for use in children or are prescribed outside the terms of the product license (off-label). This pilot study assessed use of unlicensed or off-label drugs in hospitalized children.

Drug orders of patients admitted to a general pediatric ward were reviewed retrospectively in a random sample. Assessment was based on the data of the Physicians' Desk Reference and the Israel Drug Compendium. 80 different drugs and 278 drug orders were written for 92 patients (0.5 months - 11 years old, mean 26.9 months) in 97 admissions. Of these 52.9% were either off-label or unlicensed. Patients received 1 or more unlicensed or off-label drugs in 64.9% of admissions. They were more often off-label than unlicensed. The main reasons for use of off-label drugs were unusual doses and inappropriate age. The main reason for unlicensed drugs was modification of a particular formulation of a licensed drug.

This pilot study indicates that use of drugs in an off-label or unlicensed manner in children is probably quite frequent in Israel. Our data emphasize the need for licensing a large number of drugs for use in children, based on the same scientific principles as in adults. Further collaborative studies in different pediatric centers in Israel, involving different types of pediatric settings (ambulatory and in-hospital), is required to evaluate comprehensively the magnitude of this preliminary finding.

Laser Treatment of Airway Obstruction in Infants and Children

Y. Efrati, S.M. Sarfaty, S. Kromholz, G. Eshel, M. Weinberg, I. Vinograd

Depts. of Pediatric Surgery, Otolaryngology, Anesthesia and Pediatric Intensive Care, Assaf Harofeh Medical Center, Zerifin (Affiliated with Sackler Faculty of Medicine, Tel Aviv University)

Airway obstruction during infancy and childhood requiring surgical ablation is rare, and surgical intervention poses a significant challenge. During recent decades, appropriate endoscopic instrumentation, together with advanced laser beam technology have provided new operative modalities for such patients.

From 1993 to 1995 we treated 40 infants and children, 26 males and 14 females, 13 days to 11 years old (mean 3.3 years) with Nd-YAG or CO² laser. Obstructing lesions included granulation tissue or polyps (16 cases), septa or webs (27), or benign tumors (4). 7 had more than a single lesion.

All were treated endoscopically under general anesthesia without any operative or postoperative deaths. Surgical intervention removed the obstruction and related symptoms in 34. In 6, laser treatment failed, necessitating additional surgical procedures. 3 had circumferential subglottic web. Operative complications included bleeding during removal of a hemangioma in 1 and recrudescence in another. Postoperative complications were transient respiratory failure and pneumonia in 6, all of which resolved with appropriate treatment.

This series proves that laser technology is feasible in the treatment of airway obstruction during infancy and childhood, and is safe and effective.

Alpha-Amino Adipic Aciduria: a Rare Psycho-Motor Syndrome

Ben-Ami Sela, Tamar Massos, Dov Fogel, Joseph Zlotnik

Pathological Chemistry and Child Development Institutes, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

A 3.5-year-old boy with developmental motor retardation, hypotonicity, and severe speech disturbance had alpha-amino adipic acid in his blood and very high levels in his urine. In only 20 cases has this catabolite of lysine and hydroxylysine been found in high concentrations in urine, due to enzymatic block.

The clinical features associated with alpha-amino adipic aciduria may include mental retardation, developmental and motor delay, learning difficulties, convulsions, speech problems and ataxia. 3 siblings had milder symptoms of psychomotor delay and intermediate degrees of alpha amino-adipic aciduria, suggesting that the described developmental deficits could be related to this metabolite or its derivatives.

Evaluation of Asthmatic Children Presenting at Emergency Rooms

Haim Bibi, Elena Shoychet, David Shoseyov, Michael Armoni, Emil Chai, Dorit Ater

Pediatric Pulmonary Clinic and Pediatric Dept., Barzilai Medical Center, Ashkelon; Pediatric Pulmonary Clinic, Bikur Cholim Hospital, Jerusalem; Emergency Room, Barzilai Medical Center, Ashkelon; and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Bronchial asthma in the pediatric age group has become prevalent recently. Many children who suffer from asthma arrive at the emergency room (ER) with exacerbations which did not respond to medical treatment at home.

Between July and December 1997, 136 children 8 months to 14 years of age (61% below 3 years), were studied in our pediatric ER. Investigation included physical examination and pulse oximetry, which were used as guidelines for scoring the children on arrival and post-treatment. Spirometry was done in those who could cooperate. For each patient a detailed questionnaire about medical and sociodemographic factors was filled.

Primary pediatricians used mainly beta-agonist and corticosteroid inhalators, while pediatric pulmonologists used mainly inhaled steroids. There was no relationship between severity of attack on arrival at the ER, mode of treatment and speed of recovery in the ER. More children treated by a general pediatrician more were admitted to hospital. Low parental education and paternal smoking were risk factors for recurrent hospital admissions.

Our results indicate that parents must be educated to stop smoking, especially those with asthmatic children, and primary pediatricians should be updated with regard to proper treatment and follow-up of asthma.

One-Stage Surgery for Hirschsprung's Disease in Children

Mark Weinberg, Baruch Klin, Itzhak Vinograd

Dept. of Pediatric Surgery, Assaf Harofeh Medical Center, Zerifin, and Sackler School of Medicine, Tel Aviv University

Traditionally Hirschsprung's disease has been treated by 2-or 3-stage procedures. During the past 6 years a 1-stage Duhamel procedure without stoma has become our treatment of choice for Hirschsprung's disease in neonates and young infants. Over a 6-year period, 15 infants and children with colonic Hirschsprung's disease were treated with the 1-stage Duhamel retro-rectal pull-through procedure without a stoma, with the Lester-Martin modification. All patients had the usual short segment aganglionosis, but 1 had a long segment which included the splenic flexure.

Early complications included wound infection in 1 and minor rectal bleeding in 3. Late complications included constipation in 1 and enterocolitis in 4. Long-term functional results were very good in all those operated except for 1 with rectal achalasia.

We conclude that Hirschsprung's disease can be successfully treated with a 1-stage pull-through operation, the child usually benefitting from the shorter hospital stay and the avoidance of a colostomy.

Plication of Diaphragm for Postoperative, Phrenic Nerve Injury in Infants and Young Children

Yael Refaely, David A. Simansky, Michael Paley, Alon Yellin

Sheba Medical Center, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University

Paralysis of the diaphragm may cause life-threatening respiratory distress in infants and young children because of paradoxical motion of the affected diaphragm and contralateral shift of the mediastinum during expiration. Phrenic nerve injury (PNI) may follow chest operations.

10 children with diaphragmatic paralysis and severe respiratory distress underwent plication of the diaphragm. Ages ranged from 14 days to 5 years. 9 had PNI after operations for congenital heart disease and 1 after resection of an intraspinal cervical lipoma. The right side was affected in 7, the left in 3.

Indication for surgery was inability to wean from mechanical ventilation, which had ranged from 11 to 152 days (median 35). 8 underwent plication via a thoracic approach and 2 via an abdominal approach. There were no complications directly related to the operation.

The interval from plication to weaning from mechanical ventilation ranged from 2 to 140 days (median 4). 1 patient died 2 hours after plication due to severe heart failure and 2 after prolonged hospitalization due to sepsis and multi-organ failure. 6 were extubated 2-8 days (median 4) after plication and 1 only after 40 days.

Early diaphragmatic plication is simple and avoids more serious surgery. While effective in ventilator-dependent infants and young children, it should not be used in those with multi-organ failure. Early plication may prevent the complications of prolonged mechanical ventilation.

Burns in Children in Israel: Epidemiology, Prevention and Treatment

Arieh Eldad

Medical Corps, Israel Defense Forces and Burns Unit, Hadassah University Hospital, Ein Kerem, Jerusalem

45% of all hospitalized burn casualties in Israel are children younger than 16 years old. In various hospitals they make up 30-60% of all burn casualties, depending on the proportion of children in the area of hospital intake, social and economic factors and the type of hospital. Length of hospitalization of children is shorter than that of the general population (7.3 vs 9.0 days). Scalding is the main cause of thermal injuries among babies and infants (70%), while fire burns are the most common causes among adolescents (56.5%); 90% of babies are injured at home; only 40% of adolescents are burned in home accidents.

In Israel, burned children are treated in 25 different hospitals and in departments of pediatric surgery, plastic surgery, general surgery, pediatrics or burn departments. There is no pediatric burn unit in Israel.

Severe Transient Neutropenia due to Parvovirus B19

D. Heldenberg

Dept. of Pediatrics, Hillel Yaffe Medical Center, Hadera

A 10-year-old girl was admitted with a 3-day history of fever, cough, abdominal pain and vomiting. Severe neutropenia (total neutrophil count 186/mm³), a mild increase in ALT and AST, and a positive titer of IgM antibodies against parvovirus B19 were found. The neutropenia resolved and liver enzymes became normal as she recovered. We conclude that parvovirus B19 infection should be considered in the evaluation of an acute illness accompanied by severe neutropenia.

Familial Hemiplegic Migraine of Childhood

A. Livne, E. Lahat

Pediatric Division and Pediatric Neurology Unit, Assaf Harofeh Medical Center, and Sackler Faculty of Medicine, Tel Aviv University

Familial hemiplegic migraine is a rare autosomal, dominant, migraine subtype. It is characterized by acute episodes of hemiplegia and hemisensory deficits, and other neurological abnormalities occurring either before or together with severe headache, nausea and vomiting; episodes last several hours and then spontaneously subside. Intervals between episodes are relatively prolonged. Unless there is a relevant family history suggesting this syndrome, the diagnosis is usually delayed. Recently the gene for the syndrome was identified on chromosome 19. We report 3 boys and 1 girl, 11-15 years old with hemiplegic migraine.

Limited Percutaneous Surgical Drainage in Severe Neonatal Necrotizing Enterocolitis in Low Birth Weight Prematures

Robert Finaly, Zahavi Cohen, Vadim Kapuller, Agneta Golan, Edna Kurtzbart, Abraham Mares

Depts. of Pediatric Surgery and Neonatology, Soroka Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

The usual treatment of complicated neonatal necrotizing enterocolitis (NEC) is resection of the necrotic bowel, lavage of the peritoneal cavity and diversion enterostomy. Low-birth-weight premature neonates with this condition are in special danger if general anesthesia and full exploratory surgery is contemplated.

A relatively simple alternate procedure is percutaneous insertion under local anesthesia of a soft abdominal drain, most often in the right lower quadrant. The procedure is done in the neonatal intensive care unit without moving the whole set-up to the operating room.

4 such cases have been treated within the past year. 3 were discharged home as they did not require additional surgical treatment, not having developed intestinal stenosis or obstruction. 1 recovered from the acute episode, but succumbed to a severe intraventricular hemorrhage and respiratory failure 7 days after the procedure.

Our limited but most gratifying experience, in addition to similar experience of others, encourages us to recommend this simple surgical approach in the very sick low-birth-weight premature with fulminant NEC.

EBV-Related Post-Transplantation Lymphoproliferative Disorder

D. Doron, O. Papo, O. Portnoy, E. Granot

Depts. of Pediatrics, Pathology, and Radiology, Hadassah University Hospital, Jerusalem

We describe a 4.5-year-old girl in whom post transplantation lymphoproliferative disorder was diagnosed 1 year after liver transplantation. She ran a complicated course with multiple organ involvement: respiratory failure which required mechanical ventilation, renal failure, bone marrow depression and severe protein-losing enteropathy.

Rehospitalization of Children

U. Brook, Y. Buyanover

Pediatrics Dept., Wolfson Medical Center, Holon, and Sackler Medical School, Tel Aviv University

The aims of the study were to determine the rate of rehospitalization in 1997 a month after the end of initial hospitalization. 72 of 1174 children (6.1%) were rehospitalized. The mean age was 4.6±3.6 years (range 1 month-16 years). The average duration of the initial hospitalization of the 72 children was 8.3±6.0 (range 1-50) days, but only 3.6 days for all hospitalized children. The duration of the rehospitalization was 4.1±2.1 days (range 1-10 days). the interval between the 2 hospitalizations was 11.1±9.6 days (range 1-30 days). Among the diseases of the rehospitalized children in decreasing order were: respiratory diseases (including ORL) (40.9%), gastrointestinal diseases (27.7%), nervous system diseases, and bacteremia and septicemia (5.6%). Second hospitalizations in connection with these conditions were: gastrointestinal disease (34.7%); respiratory disease (29%); and bacteremia and septicemia (11.1%). Our recommendations are for attending physicians to follow-up regularly and periodically children who suffer from chronic diseases and are prone to develop exacerbations. This should be done in cooperation with hospital specialists so that the cooperation may reduce the rehospitalization of these children.

Pediatric Research in an Office-Setting Network

Zahi Grossman, Ernesto Kahan, Samuel Gross, Shai Ashkenazi, Itamar Shalit

Kupat Holim Maccabi, Tel Aviv; Israel Ambulatory Pediatric Association; Dept. of Family Medicine, Tel Aviv University; and Schneider Children's Medical Center, Petah Tikva

Pediatric care in the community is gradually replacing traditional care in hospitals. Despite that, research activity in the community setting is minimal due to objective difficulties. These are mainly constraints of time, office work and lack of research-supporting logistics. In the past decade, throughout the world, primary physicians interested in research have grouped together and formed research networks. The aim of such networks is to support and promote research in the community.

An Israel Pediatric Research in Office-Setting network (IPROS) was established 2 years ago by the Israel Ambulatory Pediatric Association (IAPA). Today, there are over 140 pediatricians listed in IPROS, representing the heterogeneous composition of pediatricians in Israel. The network's policy is defined by a joint steering committee. The committee is composed of IAPA representatives, senior network members and Schneider Hospital senior investigators. The research subjects are diverse, and represent common practical issues.

Effective intra-net communication is vital to the existence of the network, and is accomplished by 3 modalities: 1) semiannual updates by mail, 2) e-mail, using an electronic mailing list to facilitate connection between members, 3) semi-annual meetings. Research budgets are derived from public sources like the Ministry of Health and IAPA, and private sources such as pharmaceutical companies. The administration of the network is supported by Schneider Children's Medical Center, and financed by IAPA.

Prognostic Implications in Pediatric Head Injuries

Gideon Paret, Ron Ben Abraham, Susana Berman, Amir Vardi, Rami Harel, Yossi Manisterski, Zohar Barzilay

Depts. of Pediatric Intensive Care and of Anesthesiology and Intensive Care, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

An unselected series of 200 consecutive cases of major head trauma in children aged 6 months to 16 years, seen during 4 years, was studied. Injuries were due to road accidents (40%), falls (30.5%) and other causes (29.5%), and were assessed clinically and by cranial CT.

On admission the Glasgow Coma Score ranged from 4.72-11.65 and in addition to pupillary responses and brain stem reflexes, was a significant predictor of outcome. Brain edema, midline shift, intracranial hemorrhage and also hyperglycemia, hypokalemia and coagulopathy, were associated with poor outcome. While 17% died, 53% were discharged in good functional condition.

Early identification of clinical features related to prognosis can help the caring team provide maximal support for patient and family.

Conservative Approach in Abdominal Trauma in Childhood

Nir Shoham, Yechiel Sweed

Dept. of Ophthalmology, HaEmek Medical Center, Afula and Dept. of Pediatric Surgery, Nahariya Medical Center

To determine the results of the conservative approach in the treatment of pediatric abdominal trauma, we retrospectively analyzed data from the files of 95 cases of abdominal trauma in children during a 5-year period.

51 patients (54%) had isolated abdominal injury, while 44 (46%) had multiple trauma. The most common causes of injury were road accidents and falls from heights (74%). CT scans were performed in 61 (64%) with positive results in 90%. Ultrasonography was done in 22 (23%) and was positive in 55%.

The spleen was the most vulnerable intra-abdominal organ (33 patients, 35%), as well as the organ most severely damaged. Other injured organs were: liver (30 cases), kidney (16), stomach (2), large blood vessels (2), and pancreas, duodenum and diaphragm (1 case each).

83 patients (87%) were treated conservatively, while 11 were operated on for penetrating abdominal trauma (3 cases), hemodynamic instability (3), positive DPL (3), and Scale 4 splenic injury and free intra-abdominal air on CT scan (1 case each). Early and late complications were mild.

It is concluded that CT is an efficient and reliable imaging method for diagnosis and staging of severity of injury in blunt abdominal trauma. Nonoperative management of solid organ injuries under careful observation in a pediatric trauma center is safe and appropriate. Most Scale 4 splenic injuries can be treated successfully without surgical intervention. Using this conservative approach there were no late complications.