Dominique Turck

Critical systematic review of the level of evidence for routine use of probiotics for reduction of mortality and prevention of necrotizing enterocolitis and sepsis in preterm infants

BACKGROUND & AIMS Probiotics have been suggested to prevent severe necrotizing enterocolitis (NEC) and decrease mortality in preterm infants. The aim of this paper was to systematically analyze the level of evidence (LoE) of published controlled randomized trials (RCTs) on probiotics in preterm infants. METHODS Literature searches were made up to November 2010. LoE of recommendations based on single trials or meta-analyses were scored following the Oxford Center for Evidence based Medicine approach (1a - meta-analyses of 1b LoE studies; 1b - well designed RCT; 2a - meta-analyses which include 2b LoE studies; 2b - lesser quality RCT). RESULTS Fifteen trials were included (Two 1b LoE trials and thirteen 2b LoE trials). Methodological assessment revealed considerable heterogeneity. Some probiotics may be beneficial in relation to reduction of severe NEC (2b LoE) and reduction of mortality (2b LoE). Probiotics do not accelerate feeding advancement (1b and 2b LoE). There was no convincing benefit with regard to prevention of sepsis (1b and 2b LoE). CONCLUSION There is insufficient evidence to recommend routine probiotics. However, there is encouraging data (2b LoE) which justifies the further investigation regarding the efficacy and safety of specific probiotics in circumstances of high local incidence of severe NEC.

Efficacy, tolerance, and pharmacokinetics of once daily tobramycin for pseudomonas exacerbations in cystic fibrosis

OBJECTIVE To compare once daily with thrice daily tobramycin for treatment of Pseudomonas aeruginosainfection in patients with cystic fibrosis. DESIGN 22 patients with cystic fibrosis, mean (SD) age 11 (3.4) years (range 5.6–19.3), with pulmonary pseudomonas exacerbations were randomly assigned to receive a 14 day course of tobramycin (15 mg/kg/day) either in three infusions (group A) (n = 10) or a single daily infusion (group B) (n = 12), combined with ceftazidime (200 mg/kg/day as three intravenous injections). Efficacy was assessed by comparison of pulmonary, nutritional, and inflammatory indices on days 1 and 14. Cochlear and renal tolerance were assessed on days 1 and 14. Tobramycin concentration was measured in serum and sputum 1, 2, 3, 4, 8, and 24 hours after the start of the infusion. Analysis was by non-parametric Wilcoxon test. RESULTS Variables improving (p < 0.05) in both groups A and B were, respectively: weight/height (+4% and +3.1%), plasma prealbumin (+66 and +63 mg/l), forced vital capacity (FVC) (+14% and +11%), forced expiratory volume in one second (+15% and +14%), and forced expiratory flow between 25% and 75% of FVC (+13% and +21%). Improvement was not significantly different between groups. Renal and cochlear indices remained within the normal range. Serum peak concentration of tobramycin on day 1 was 13.2 (7.1) mg/l in group A and 42.5 (11.2) mg/l in group B (p < 0.001); serum trough was 1.1 (0.8) mg/l in group A and 0.3 (0.2) mg/l in group B (p < 0.01). Tobramycin concentrations in sputum were two to three times higher in group B than group A. CONCLUSIONS Once daily tobramycin combined with three injections of ceftazidime is safe and effective for the treatment of pseudomonas exacerbations in cystic fibrosis patients.

Efficacy of methotrexate in pediatric Crohn's disease: A French multicenter study

Background: Immunosuppressors play a major role in maintaining remission in Crohns disease (CD). In patients who do not tolerate or escape therapy with azathioprine (AZA)/6‐mercaptopurine, there is a marked need for other immunosuppressive drugs. The aim of the present study was to evaluate the efficacy and safety of methotrexate (MTX) in children with active CD. Methods: In a retrospective multicenter (n = 3) study, the efficacy of MTX to induce complete remission or a clinical improvement was analyzed in 61 children with active CD. Results: CD was diagnosed at a mean age of 11.1 ± 2.3 years, and MTX was introduced 3.1 ± 2.2 years after diagnosis. Indications to use MTX were a nonresponse to or relapse under AZA (n = 42) or AZA intolerance/toxicity (n = 19). MTX improved or induced complete remission in 49 patients (80%), of whom 18 (29.5%) relapsed after 13 ± 10 months of treatment. Under MTX medication, complete remission was observed in 39%, 49%, and 45% at 3, 6, and 12 months, respectively. Follow‐up over at least 24 months in 11 children confirmed a sustained remission on MTX monotherapy up to 40 months. Adverse reactions were observed in 14 patients (24%), requiring discontinuation of MTX in 6 children (10%) (liver enzyme elevation, n = 2; varicella‐zoster, n = 1; nausea, n = 3). MTX allowed corticosteroid discontinuation in 36 patients. Conclusions: MTX improved the clinical course in most pediatric CD patients who escaped or did not tolerate AZA. Short‐time toxicity of MTX resulted in drug discontinuation in <10%. These data point to a beneficial and safe use of MTX in the treatment of pediatric CD.

Influence of recombinant interferon alpha on nutritional status and growth pattern in children with chronic viral hepatitis

AbstractAnorexia and weight loss are frequently reported as adverse effects during recombinant interferon α (rIFN-α) treatment. The aim of the present study was to assess both nutritional status and growth of children and adolescents treated with rIFN-α for chronic viral hepatitis. Eleven patients aged 4–16 years with histologically proven chronic active hepatitis (hepatitis B,n=9; hepatitis C,n=2) receiving rIFN-α subcutaneously thrice a week for 6 months were studied. Weight and height increments were assessed during the 6 months before starting iIFN-α. Weight and height were measured every 3 months (M0, M3, M6) during the 6 months of rIFN-α treatment, then every 6 months during the follow up period (6–36 months). Weight decreased in every child during rIFN-α treatment (weight loss varies from 0.5 to 2.6 kg after 3 months of treatment). Weight/age Z-score decreased from 0.12 at M0 to −0.69 at M3 (P<0.01), then increased between M3 and M6 (−0.33) (P<0.01), but normalized (0.02) only 6 months after completion of treatment. Nutritional status was significantly impaired during treatment (Z-score for weight/height decreased from 0.18 at M0 to −0.74 at M3,P<0.01) and recovered progressively thereafter. Height and height velocity were not modified by rIFN-α treatment. A reduction of the caloric intake observed between M0 and M3 might explain these features.ConclusionSignificant but transient abnormalities of the nutritional status are encountered constantly at the beginning of rIFN-α therapy without any deleterious effect on growth. Information of the families and nutritional intervention during treatment should be required, in order to limit the importance of weight loss.

Local antibiotic lock for the treatment of infections related to central catheters in parenteral nutrition in children

BACKGROUND Central venous catheter-related (CVC) infections represent the most common complication of parenteral nutrition. These infections are usually treated by means of long-term systemic antibiotic treatment. The objective of this study was to determine the efficacy of combining a local antibiotic lock with a short systemic double antibiotic to treat CVC-related staphylococci infections. METHODS Any child with coagulase-negative staphylococci or Staphylococcus aureus septicemia, confirmed by a positive blood culture, was included in the study. A double antibiotic systemic treatment composed of amikacin and teicoplanin was started and continued for 5 days. The antibiotic treatment was combined from the first day (D0) with a local teicoplanin lock, which was left for 12 hours a day in the catheter for 15 days. Parenteral nutrition was continued on a nocturnal cyclic mode during antibiotic treatment. The efficacy of the treatment was evaluated by clinical (body temperature), biologic [C-reactive protein levels (CRP)], and bacteriologic (blood culture) measures. RESULTS Twenty CVC-related infection episodes in 13 patients were analyzed for the study. In the initial biologic test, CRP varied from 2 to 130 mg/L (mean 43 mg/L). After 3 days of treatment, CRP varied from 2 to 61 mg/L (mean 12 mg/L). The median time until normalization of temperature and CRP levels after the beginning of antibiotic treatment was 3.2 days (range 1 to 14 days) and 6.2 days (range 2 to 19 days), respectively. All blood cultures were negative for infection 48 hours after stopping the treatment. Only 1 therapeutic failure was observed during the treatment. The patient had persistent signs of clinical septicemia that required removal of the CVC. Two catheter-related infection recurrences were observed in the month after termination of the local antibiotic lock, which also required removal of the CVC. The central venous catheter was maintained in the other cases. CONCLUSIONS Teicoplanin antibiotic locks, combined with a short conventional systemic antibiotic treatment and continuation of cyclic parenteral nutrition, seem effective and well-tolerated treatments for CVC infections.

Nutritional impact of antipseudomonas intravenous antibiotic courses in cystic fibrosis.

OBJECTIVE To evaluate the short term effects on nutritional status of home intravenous anti-pseudomonas antibiotic courses in cystic fibrosis (CF) patients chronically colonised withPseudomonas aeruginosa. DESIGN A prospective study involving 38 CF patients, mean age 10.9 (SD 4.3) years (range 4.3 to 22.2 years), presenting with pulmonary exacerbations of P aeruginosainfection. The patients received a 14 day antibiotic course of intravenous ceftazidime (200 mg/kg/day) and either amikacin (35 mg/kg/day) or tobramycin (15 mg/kg/day). Nutritional evaluation on days 1 and 14 involved measurements of weight, weight/height ratio (per cent of predicted value), energy intake (per cent of recommended daily allowances), serum prealbumin, and body composition assessed by two methods: bioelectrical analysis (BIA) and skinfold anthropometry. The non-parametric Wilcoxon t test was used for statistical analysis, with a Bland-Altman plot to assess the degree of agreement between the two methods of evaluating body composition. RESULTS Weight increased by 1.0 (0.8) kg (p < 0.001); weight/height increased from 94.4(12.2)% to 98(12.7)% (p < 0.001), energy intake from 107(32)% to 119(41)% (p < 0.02), and prealbumin from 183 (63) to 276 (89) mg/l (p < 0.001). Fat mass increased by 0.8 (1.0) kg (p < 0.001), without any significant change in fat-free mass. The limits of agreement between BIA and anthropometry were –0.7 kg and +1.1 kg. CONCLUSIONS Antibiotic courses allow an improvement in nutritional status in CF patients, with a gain in fat mass.

Outcome of Functional Constipation in Childhood: A 10-Year Follow-Up Study

Objectives To assess the outcome of patients presenting with functional constipation in childhood during a 10-year period and to determine any risk factors for developing persistent constipation throughout adolescence and adulthood. Patients and Methods 72 children (mean age 4 years; 40 boys) referred for constipation were included in a longitudinal set of observations. Initial workup included segmental colonic transit time and anorectal manometry; 45 of the 72 patients could be reevaluated 10 to 12 years later. Results 21 of 45 patients (46%; 95% confidence interval 29% to 67%) remained constipated at follow-up. Encopresis and recurrent abdominal pain were present in 25% and 56% of patients, respectively. Patients with anorectal dyssynergia remained more frequently constipated at follow-up than the others: 61% versus 29% (P < .05). Conclusion Almost 50% of patients presenting with constipation during childhood remained constipated on long-term follow-up. Anorectal dyssynergia is associated with a worse prognosis.

Tolerance, pharmacokinetics and efficacy of once daily amikacin for treatment of Pseudomonas aeruginosa pulmonary exacerbations in cystic fibrosis patients

Twenty cystic fibrosis patients aged 1.8–22 years (mean ±SD: 9.6 ± 4.8 years) withPseudomonas aeruginosa pulmonary exacerbations were treated with amikacin (AM) (35 mg/kg/day in one daily 30 min infusion) associated with either ceftazidime (200 mg/kg/day in 3 i.v. injections) (n = 19) or imipenem (n = 1) at the same dose. Glomerular and tubular functions (creatinine clearance, 24-h proteinuria, β2 microglobulinuria, lysozymuria) and audiometry remained within normal ranges from day 0 to day 14. A peak concentration of AM of 83 ± 19 mg/l and a trough concentration of 0.8 ±0.5 mg/l were observed in blood while AM levels in sputum were above the minimal inhibitory concentration 50 from 30 min to 16 h. No serum accumulation of AM was observed during the treatment. From day 0 to day 14, the following changes were observed: weight/height ratio: 96%–100% (P < 0.001); daily energy intake: 111%–128% of RDA (P < 0.001); prealbumin: 195–290 mg/l (P < 0.001); forced vital capacity (FVC): 66%–81% (P < 0.01); forced expiratory volume in 1 s: 60%–75% (P < 0.01); forced expiratory flow between 25% and 75% of FVC: 42%–56% (P < 0.01); nocturnal SaO2 also improved significantly; cardiac rate decreased from 89 ±18/min to 76 ± 16/min (P < 0.001); respiratory rate decreased from 31 ±15/min to 26 ± 10/min (P < 0.05); inflammatory parameters (white blood cells, polymorphonuclear cells, erythrocyte sedimentation rate) also improved.

Later effects of breastfeeding practice: the evidence.

Breastfeeding plays a key role in the programming process during early life but, due to confounding factors, it is difficult to draw conclusions on long-term health benefits. The magnitude of the beneficial effect of breastfeeding on blood pressure (-2 mmHg) and total cholesterol (-0.2 mmol/l) is likely to have public health implications. However, it is unknot known whether breastfeeding reduces the risk of cardiovascular mortality. Breastfeeding may protect against the development of celiac disease. The protective role of breastfeeding against type 1 diabetes seems likely, but the mechanisms involved are still under discussion. There is no convincing evidence that breastfeeding reduces the risk of leukemia and cancer. Breastfeeding is associated with a better cognitive development (-3 points) that is present as early as at 6 months of age and sustained throughout childhood and adolescence. The benefits of breast milk may be related to its high content in docosahexaenoic acid which plays an important role in brain development. Increasing the duration of breastfeeding is correlated with an increase in cognitive development.

Severe selenium deficiency secondary to chylous loss

Selenium deficiency is observed in patients with poor intake. We report the first case of a child with lymphangiomatosis who presented a myopathy associated with severe cardiomyopathy secondary to selenium deficiency due to selenium loss in chylous fluid.