Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial.

OBJECTIVES: Febrile urinary tract infections are common in children and associated with the risk for renal scarring and long-term complications. Antimicrobial prophylaxis has been used to reduce the risk for recurrence. We performed a study to determine whether no prophylaxis is similar to antimicrobial prophylaxis for 12 months in reducing the recurrence of febrile urinary tract infections in children after a first febrile urinary tract infection. METHODS: The study was a controlled, randomized, open-label, 2-armed, noninferiority trial comparing no prophylaxis with prophylaxis (co-trimoxazole 15 mg/kg per day or co-amoxiclav 15 mg/kg per day) for 12 months. A total of 338 children who were aged 2 months to <7 years and had a first episode of febrile urinary tract infection were enrolled: 309 with a confirmed pyelonephritis on a technetium 99m dimercaptosuccinic acid scan with or without reflux and 27 with a clinical pyelonephritis and reflux. The primary end point was recurrence rate of febrile urinary tract infections during 12 months. Secondary end point was the rate of renal scarring produced by recurrent urinary tract infections on technetium 99m dimercaptosuccinic acid scan after 12 months. RESULTS: Intention-to-treat analysis showed no significant differences in the primary outcome between no prophylaxis and prophylaxis: 12 (9.45%) of 127 vs 15 (7.11%) of 211. In the subgroup of children with reflux, the recurrence of febrile urinary tract infections was 9 (19.6%) of 46 on no prophylaxis and 10 (12.1%) of 82 on prophylaxis. No significant difference was found in the secondary outcome: 2 (1.9%) of 108 on no prophylaxis versus 2 (1.1%) of 187 on prophylaxis. Bivariate analysis and Cox proportional hazard model showed that grade III reflux was a risk factor for recurrent febrile urinary tract infections. Whereas increasing age was protective, use of no prophylaxis was not a risk factor. CONCLUSIONS: For children with or without primary nonsevere reflux, prophylaxis does not reduce the rate of recurrent febrile urinary tract infections after the first episode.

Antibiotic treatment for pyelonephritis in children: multicentre randomised controlled non-inferiority trial.

OBJECTIVE: To compare the efficacy of oral antibiotic treatment alone with treatment started parenterally and completed orally in children with a first episode of acute pyelonephritis. DESIGN: Multicentre, randomised controlled, open labelled, parallel group, non-inferiority trial. SETTING: 28 paediatric units in north east Italy. PARTICIPANTS: 502 children aged 1 month to <7 years with clinical pyelonephritis. INTERVENTION: Oral co-amoxiclav (50 mg/kg/day in three doses for 10 days) or parenteral ceftriaxone (50 mg/kg/day in a single parenteral dose) for three days, followed by oral co-amoxiclav (50 mg/kg/day in three divided doses for seven days). Main outcomes measures Primary outcome was the rate of renal scarring. Secondary measures of efficacy were time to defervescence (<37 degrees C), reduction in inflammatory indices, and percentage with sterile urine after 72 hours. An exploratory subgroup analysis was conducted in the children in whom pyelonephritis was confirmed by dimercaptosuccinic acid (DMSA) scintigraphy within 10 days after study entry. RESULTS: Intention to treat analysis showed no significant differences between oral (n=244) and parenteral (n=258) treatment, both in the primary outcome (scarring scintigraphy at 12 months 27/197 (13.7%) v 36/203 (17.7%), difference in risk -4%, 95% confidence interval -11.1% to 3.1%) and secondary outcomes (time to defervescence 36.9 hours (SD 19.7) v 34.3 hours (SD 20), mean difference 2.6 (-0.9 to 6.0); white cell count 9.8x10(9)/l (SD 3.5) v 9.5x10(9)/l (SD 3.1), mean difference 0.3 (-0.3 to 0.9); percentage with sterile urine 185/186 v 203/204, risk difference -0.05% (-1.5% to 1.4%)). Similar results were found in the subgroup of 278 children with confirmed acute pyelonephritis on scintigraphy at study entry. CONCLUSIONS: Treatment with oral antibiotics is as effective as parenteral then oral treatment in the management of the first episode of clinical pyelonephritis in children. TRIAL REGISTRATION: Clinical Trials NCT00161330 [ClinicalTrials.gov].

[Heart failure in Eastern Veneto: prevalence, hospitalization rate, adherence to guidelines and social costs]. / Lo scompenso cardiaco nel veneto orientale: prevalenza, ospedalizzazione, aderenza alle linee guida e costi sociali.

Heart failure is a prominent problem of public health, requiring innovating methods of health services organization. Nevertheless, data are still not available on prevalence, hospitalization rate, adherence to Guidelines and social costs in the general Italian population. The necessity to identifying patients with heart failure derives from the efficacy of new therapeutic interventions in reducing morbidity and mortality. In this study we aimed to identify, in a subset of the Eastern Veneto population, patients with heart failure through a pharmacologic-epidemiologic survey. The study was divided in 5 phases: (1) identification of patients on furosemide in the year 2000 in the ASL 10 of Eastern Veneto general population, through an analysis of a specific pharmaceutic service database; (2) definition of the actual prevalence of heart failure in a casual sample of these patients, through data base belonging to general practitioners, cardiologists, or others. Diagnosis was based on the following criteria: (a) previous diagnosis of heart failure; (b) previous hospitalization for heart failure; (c) clinical evidence, with echocardiographic control in unclear cases; (3) survey of hospitalizations; (4) evaluation of adhesion to guidelines, through both databases and questionnaires; (5) analysis of the social costs of the disease, with a retrospective "bottom up" approach. From a total population of 198,000 subjects, we identified 4502 patients on furosemide. In a casual sample of 10,661 subjects we defined a prevalence of heart failure in Eastern Veneto of 1.1%, that increased to 7.1% in octagenarians. The prescription of life saving drugs was satisfactory, while rather poor was the indication to echocardiography and to cardiologic consultation. Hospitalization rate for DRG 127 was low: 2.1/1000 inhabitants/year in the general population and 12.5 /1000 inhabitants/year in patients >70 years of age. Yearly mortality was 10.3%. Social costs were elevated (15.394 Euros/patient/year), due to a relevant sanitary component (hospital 53%, drugs 28%) and particularly a to an indirect cost component. In conclusion, the assumption of furosemide lends itself as a good marker for identifying patients with heart failure. Patient identification is simple, cheap and cost-efficient, and can be easily reproduced in other regional areas.