Merja Möttönen

An open randomized controlled trial of infection prevention in child day-care centers.

OBJECTIVE Child care outside the home increases childrens infections substantially. We have to evaluate the possibilities for reducing the transmission of infections by an infection prevention program. DESIGN AND METHODS A 15-month randomized controlled trial involving 20 day-care centers was conducted to evaluate the efficacy of an infection prevention program. The program was introduced in 10 centers and the other matched 10 centers served as controls. Records were made of the occurrence of infections and absences from care or work because of infections among the children, their parents and the personnel of the day-care centers. RESULTS Both the children and the personnel in the program centers had significantly fewer infections than those in the control centers, the reduction being 9% [95% confidence interval (95% CI), 4 to 16%, P < 0.002] among 3-year-old children and 8% (95% CI 0 to 14%, P = 0.049) among the older children. The children at the program centers received 24% fewer prescriptions of antimicrobials (95% CI 22 to 27%, P < 0.001). Likewise there were 2.5 man-year fewer absences from work on the part of parents because of a childs illness during 1 year in the program centers, a 24% difference (95% CI 18 to 29%, P < 0.001). CONCLUSIONS Effective prevention of infections is possible in child day-care centers, and this can benefit both the families and the personnel. Such a program is cost-effective even if a specialist nurse implements it.

High Body Mass Index Increases the Risk for Osteonecrosis in Children With Acute Lymphoblastic Leukemia

PURPOSE The aim of the study was to determine the incidence of and clinical risk factors for radiographic osteonecrosis (ON) in children treated for acute lymphoblastic leukemia (ALL) using the Nordic ALL protocols. PATIENTS AND METHODS Ninety-seven consecutive patients with childhood ALL were studied prospectively by magnetic resonance imaging (MRI) of the lower extremities at the end of the treatment. RESULTS Twenty-three (24%) of the 97 patients had ON. Seven of the patients (30%) were symptomatic, and three patients (13%) required surgical interventions. Multiple logistic regression analysis showed that high body mass index (BMI; P = .04), female sex (P = .01), older age at diagnosis (P < .001), and higher cumulative dexamethasone dose (P = .03) were independent risk factors for radiographic ON. The cumulative prednisone dose did not differ significantly between the patients with and without ON. The incidence of radiographic ON decreased significantly, from 36% to 7%, when the duration of dexamethasone exposure during the delayed-intensification phase was shortened from 3 to 4 weeks to 2 weeks with a taper (P = .001). CONCLUSION ON as determined by MRI was found to be a common complication in children and adolescents after treatment with the Nordic ALL protocols. Revision of the ALL protocols by shortening the single exposure to dexamethasone has diminished the risk for ON remarkably. High BMI was identified as a new significant risk factor for ON.

Treatment-related death in childhood acute lymphoblastic leukaemia in the Nordic countries: 1992-2001.

Despite continuously more successful treatment of childhood acute lymphoblastic leukaemia (ALL), 2–5% of children still die of other causes than relapse. The Nordic Society of Paediatric Haematology and Oncology‐ALL92 protocol included 1652 patients ≤15 years of age with precursor B‐ and T‐cell ALL diagnosed between 1992 and 2001. Induction deaths and deaths in first complete remission (CR1) were included in the study. A total of 56 deaths (3%) were identified: 19 died during induction (1%) and 37 in CR1 (2%). Infection was the major cause of death in 38 cases. Five patients died of early death before initiation of cytotoxic therapy. Five patients died because of toxicity of inner organs and one of accidental procedure failures. Seven patients died of complications following allogenic haematopoietic stem cell transplantation (HSCT) in CR1. Girls were at higher risk of treatment‐related death (TRD) [relative risk (RR) = 2·2; 95% confidence interval (CI95%): 1·2–4·0, P < 0·01], mostly because of infections. Risk of TRD was also higher in children with Down syndrome (RR = 4·5; CI95%: 2·0–10·2, P < 0·00). In conclusion, 3% of children with ALL died of TRD, with bacterial infections as the most common cause of death. Girls and Down syndrome patients had a higher risk of TRD. Infections still remain a major challenge in childhood ALL.

Use of micronutrients and alternative drugs by children with acute lymphoblastic leukemia

The use of alternative therapies is thought to be common among cancer patients. To clarify the popularity of micronutrients among children with cancer, we performed a controlled follow-up survey. The use of micronutrients and alternative drugs by 15 families of children with acute lymphoblastic leukemia (ALL) receiving chemotherapy (62 members) and 26 control families (106 members) was monitored by means of daily diaries from November 1987 to December 1989. Forty percent of children with ALL (6 of 15) and 7.7% of their controls (2 of 26) took alternative medicines, the usage among the children with ALL being statistically significantly more common (difference, 32.3%; 95% confidence interval for difference [CI] 7.1, 57.5%; P < 0.04). All children with ALL and 50.0% of the control children (13 of 26) took vitamins (difference, 50.0%; 95% CI, 20.4-79.6%; P < 0.01). A total of 27.7% of the other members of the ALL families (13 of 47) and 11.1% of their counterparts in the control families (10 of 90) took alternative medicines, the usage in the index families being statistically significantly more common (difference, 16.6%; 95% CI, 3.4-29.7%; P < 0.03). The malignancy increased the use of alternative medicines among all members of the family and of vitamins and trace elements among the affected children.

Respiratory viral infections in children with leukemia.

Background: Respiratory viruses occur frequently in the community and are a common cause of fever in children. Data on respiratory viral infections in children with cancer are limited. Methods: A long-term, prospective, multicenter study was carried out in Finland searching for respiratory viruses in febrile children with leukemia. For this purpose, 138 febrile episodes in 51 children with leukemia were analyzed. Twelve types of respiratory viruses were searched for by viral culture, antigen detection, and polymerase chain reaction tests. Results: Evidence of a respiratory viral infection was found in 61 of 138 febrile episodes (44%), accounting for an incidence of 0.8 (range, 0–2.4) per person year at risk during the treatment of leukemia. The most common viruses detected were rhinovirus (22%), respiratory syncytial virus (11%), human bocavirus (5%), and influenza A virus (4%). Dual viral infections were detected in 12 cases (9%). Half of the children had respiratory symptoms with cough being the most common symptom. Two children developed pneumonia. The mean duration of fever was 2.6 (SD 1.7) days in children with respiratory viral infection and 2.1 (SD 1.3) days in children without evidence of viral infection (P = 0.44). Conclusions: Respiratory viruses are found commonly during febrile episodes in children with leukemia. The detection of viruses permits the use of available antiviral agents, may explain a poor response to antimicrobial agents, and minimizes the proportion of febrile episodes without possible etiologic agents in children with leukemia.

OVARIAN GRANULOSA CELL TUMORS IN CHILDHOOD

Granulosa cell tumors (GCT) of the ovary are prepubertal in 5% of the patients. In girls less than 20 years old, 80% of GCTs differ from those among adults. These juvenile granulosa cell tumors (JGCTs) are usually benign. GCTs belong to ovarian sex cord-stromal tumors, the more common ovarian tumors being epidermal and germinal. The etiology of GCT remains unknown. Most young children with GCT present with precocious pseudopuberty. Among adolescents GCT often causes menstrual irregularities, virilization, abdominal swelling, and pain. When JGCT is limited to the ovaries the outcome is excellent with only salpingo-oophorectomy. However, more widely spread tumors are difficult to treat and cause mortality. Cisplatin-containing chemotherapy can induce remissions in adult GCTs. Estrogens and peptide hormones, i.e., inhibin, are useful in the follow-up of the patients. The authors describe 3 children with GCT and review current data on this rare tumor from molecular biology to clinical aspects.

Human bocavirus in children with acute lymphoblastic leukemia

A new human parvovirus, human bocavirus, has recently been identified in respiratory secretions, feces and serum. It is associated with lower and most likely also upper respiratory tract infections. Most commonly reported symptoms are cough, rhinorrhea, expiratory wheezing and fever, and the virus is preferentially detected in young children. We report three children with acute lymphoblastic leukemia who had acute febrile episodes with concomitant detection of human bocavirus in their respiratory secretions. One of them had five consecutive febrile episodes during 6 months, all associated with the presence of human bocavirus at varying viral loads, suggesting prolonged shedding or reactivation of the virus.

Early and treatment‐related deaths in childhood acute myeloid leukaemia in the Nordic countries: 1984–2003

Despite major improvements in the cure rate of childhood acute myeloid leukaemia (AML), 5–15% of patients still die from treatment‐related complications. In a historical prospective cohort study, we analysed the frequency, clinical features and risk factors for early deaths (ED) and treatment‐related deaths (TRD) in 525 children included in the Nordic Society of Paediatric Haematology and Oncology (NOPHO)‐AML‐84, ‐88 and ‐93 trials. Seventy patients (13%) died before starting treatment or from treatment‐related complications. The death rate rose from 11% in NOPHO‐AML‐84 to 29% in ‐88, but then fell to 8% in ‐93. Sixteen patients (3%) died within the first 2 weeks, mainly from bleeding or leucostasis. Hyperleucocytosis, age <2 or ≥10 years were risk factors. After day 15, 10% of patients died from treatment‐related complications with infection as the main cause of death. Risk factors were age <2 or ≥10 years and treatment according to the NOPHO‐AML‐88 protocol. The number of EDs and TRDs in AML is high. Therefore optimal antifungal prophylaxis is essential, and studies on the benefit of antibacterial prophylaxis and individual risk factors for ED and TRD are needed.

Prospective controlled survey of viral infections in children with acute lymphoblastic leukemia during chemotherapy

Background. Infections cause significant morbidity in children with acute lymphoblastic leukemia (ALL). The incidence of viral infections commonly occurring in children with ALL receiving chemotherapy was compared with viral infections in control children and the spread of infections in families was traced.

Absences for sickness among children in day care.

The number of days of absence because of sickness, recorded for all children in one city in Finland, cared for in municipal day care over a period of 2.5 years, was collected from the monthly figures kept by the city council office for accounting purposes. The average number of days of absence per child was 24 per year at child‐care centers and 9 in family care (p < 0.01) at age less than 3 years, 13 and 7, respectively (p < 0.05) at age 3–5 years, and 10 and 5, respectively (p < 0.05) among those aged 6 years. The average duration of absence in all age groups was 3.6 days in child‐care centers and 2.5 days in family‐care centers. The number of days absent at each child‐care center in 1986 correlated significantly with that for 1987 (r=0.58, p < 0.001), indicating consistency in the absence figures. A bivariate analysis showed the number of children in the child‐care centers (r= 0.32, p < 0.05) to explain the number of absences for sickness, and after this factor had been controlled in a multivariate analysis, the number of nurses serving out food while looking after the children (r= 0.27, p < 0.01) and the number of families to whom the children belonged (r=0.27, p < 0.01).