[Show abstract][Hide abstract] ABSTRACT: Background & aim:
Fermented foods have been proposed for the prevention of infectious diseases. We evaluated the efficacy of fermented foods in reducing common infectious diseases (CIDs) in children attending daycare.
Prospective randomized, double-blind, placebo-controlled trial (registered under Clinical Trials.gov identifier NCT01909128) on healthy children (aged 12-48 months) consuming daily cow's milk (group A) or rice (group B) fermented with Lactobacillus paracasei CBA L74, or placebo (group C) for three months during the winter season. The main study outcome was the proportion of children who experienced at least one CID. All CIDs were diagnosed by family pediatricians. Fecal concentrations of innate (α- and β-defensins and cathelicidin LL-37) and acquired immunity biomarkers (secretory IgA) were also evaluated.
377 children (193 males, 51%) with a mean (SD) age of 32 (10) months completed the study: 137 in group A, 118 in group B and 122 in group C. Intention-to-treat analysis showed that the proportion of children who experienced at least one CID was lower in group A (51.8%) and B (65.9%) compared to group C (80.3%). Per-protocol analysis showed that the proportion of children presenting upper respiratory tract infections was lower in group A (48.2%) and group B (58.5%) compared with group C (70.5%). The proportion of children presenting acute gastroenteritis was also lower in group A (13.1%) and group B (19.5%) compared with group C (31.1%). A net increase of all fecal biomarkers of innate and acquired immunity was observed for groups A and B compared to group C. Moreover, there was a negative association between fecal biomarkers and the occurrence of CID.
Dietary supplementation with cow's milk or rice fermented with L. paracasei CBA L74 prevents CIDs in children attending daycare possibly by means of a stimulation of innate and acquired immunity.
Full-text · Article · Dec 2015 · Clinical Nutrition
[Show abstract][Hide abstract] ABSTRACT: To assess the quality of guidelines, consensus statements and systematic reviews on flu and pneumococcal immunisations in HIV-infected children.
The authors screened PubMed and Embase databases until the year 2009 for guidelines, consensus statements and systematic reviews on flu and pneumococcal immunisations in HIV-infected patients. The authors also explored relevant websites of agencies/institutions involved with HIV infection, immunisation or guidelines. The Appraisal of Guidelines for Research and Evaluation instrument and the checklists of the Scottish Intercollegiate Guidelines Network were used to evaluate the scientific quality of guidelines and systematic reviews.
Eighteen articles were identified. Only one guideline was of good overall quality. Generally the weakest domains were 'Applicability' and 'Editorial Independence.' Although of poor methodological quality, the main recommendations on flu and pneumococcus vaccinations were similar. There were minor differences in the type of pneumococcal vaccines in relation to patient's age, namely based on the settings in which recommendations were produced.
Although guidelines and systematic reviews on flu and pneumococcal vaccination in HIV-infected children came from authoritative institutions, their overall quality is poor, with the weakest fields being the methodological domains.
No preview · Article · Feb 2011 · BMJ quality & safety
[Show abstract][Hide abstract] ABSTRACT: In a previous multicentre study including 129 HIV-infected children, non-adherence to antiretroviral therapy was detected in 16% of patients and was mainly related to psychosocial rather than clinical or demographic features. The aim of this study was to explore the evolving pattern of adherence and its determinants in the same population of children.
An observational, cross-sectional multicentre study was done through a structured interview to the caregivers of HIV-infected children. Adherence was quantitatively evaluated through a 4-day recall adherence instrument.
One hundred and twelve children were included. Nineteen (17%) omitted more than 5% of doses in the preceding 4 days and were considered non-adherent. Of these, 10 had been found non-adherent and nine adherent in the previous study. In parallel, nine of the originally non-adherent children had become adherent. Adherence rates were higher in children receiving therapy from foster parents than in children receiving therapy from biological parents. Dose number significantly correlated with adherence.
Adherence to antiretroviral therapy is a dynamic phenomenon that changes with time. The evolving pattern shows a fairly constant distribution of adherence because a similar number of patients gain and lose adherence. Psychosocial rather than clinical features are major determinants of adherence.
No preview · Article · Dec 2009 · Expert Opinion on Pharmacotherapy
[Show abstract][Hide abstract] ABSTRACT: To evaluate the applicability and efficacy of guidelines for the management of acute gastroenteritis (AGE) as used by pediatricians.
This was a national, open, randomized, controlled intervention trial. The intervention consisted of a 2-hour course based on the guidelines for management of AGE. Seventy-five randomly selected primary care pediatricians underwent training in AGE management (group A), and 75 pediatricians who were not specifically trained served as controls (group B). Each pediatrician enrolled 10 children age 1-36 months with acute-onset diarrhea. Outcome measures were guidelines applicability, duration of diarrhea, and difference in body weight between the first visit and 5-7 days later.
The baseline features of the children were similar in groups A (n = 617) and B (n = 692). A total of 404 of the 617 children in group A (65.5%) were fully treated according to the guidelines, compared with 20 of the 692 children in group B (3%). Most violations involved administration of unnecessary drugs or diets. The duration of diarrhea was shorter in group A (intention-to-treat: 83.3 vs 90.9 hours; P < .001). Weight gain was marginally, but statistically significantly, higher in the children treated according to the guidelines (per-protocol analysis: +16.5 gr vs -13.5 gr; P < .05).
Guidelines for AGE have good applicability and excellent efficacy. Adjunctive medical interventions are associated with a longer duration of diarrhea.
No preview · Article · Oct 2009 · The Journal of pediatrics
[Show abstract][Hide abstract] ABSTRACT: These guidelines update and extend evidence-based indications for the management of children with acute gastroenteritis in Europe.
The guideline development group formulated questions, identified data, and formulated recommendations. The latter were graded with the Muir-Gray system and, in parallel, with the GRADE system.
Gastroenteritis severity is linked to etiology, and rotavirus is the most severe infectious agent and is frequently associated with dehydration. Dehydration reflects severity and should be monitored by established score systems. Investigations are generally not needed. Oral rehydration with hypo-osmolar solution is the major treatment and should start as soon as possible. Breastfeeding should not be interrupted. Regular feeding should continue with no dietary changes including milk. Recent data suggest that in the hospital setting, in non-breast-fed infants and young children, lactose-free feeds can be considered in the management of gastroenteritis. Active therapy may reduce the duration and severity of diarrhea. Effective interventions include administration of specific probiotics such as Lactobacillus GG or Saccharomyces boulardii, diosmectite or racecadotril. Anti-infectious drugs should be given in exceptional cases. Ondansetron is effective against vomiting, but its routine use requires safety clearance given the warning about severe cardiac effects. Hospitalization should generally be reserved for children requiring enteral/parenteral rehydration; most cases may be managed in an out-patients setting. Enteral rehydration is superior to intravenous rehydration. Ultrarapid schemes of intravenous rehydration are not superior to standard schemes and may be associated with higher readmission rates.
Acute gastroenteritis is best managed using a few simple, well defined medical interventions.
Full-text · Article · Jun 2008 · Journal of pediatric gastroenterology and nutrition
[Show abstract][Hide abstract] ABSTRACT: To compare the efficacy of five probiotic preparations recommended to parents in the treatment of acute diarrhoea in children. Design Randomised controlled clinical trial in collaboration with family paediatricians over 12 months.
Children aged 3-36 months visiting a family paediatrician for acute diarrhoea.
Children's parents were randomly assigned to receive written instructions to purchase a specific probiotic product: oral rehydration solution (control group); Lactobacillus rhamnosus strain GG; Saccharomyces boulardii; Bacillus clausii; mix of L delbrueckii var bulgaricus, Streptococcus thermophilus, L acidophilus, and Bifidobacterium bifidum; or Enterococcus faecium SF68.
Primary outcomes were duration of diarrhoea and daily number and consistency of stools. Secondary outcomes were duration of vomiting and fever and rate of admission to hospital. Safety and tolerance were also recorded.
571 children were allocated to intervention. Median duration of diarrhoea was significantly shorter (P<0.001) in children who received L rhamnosus strain GG (78.5 hours) and the mix of four bacterial strains (70.0 hours) than in children who received oral rehydration solution alone (115.0 hours). One day after the first probiotic administration, the daily number of stools was significantly lower (P<0.001) in children who received L rhamnosus strain GG and in those who received the probiotic mix than in the other groups. The remaining preparations did not affect primary outcomes. Secondary outcomes were similar in all groups.
Not all commercially available probiotic preparations are effective in children with acute diarrhoea. Paediatricians should choose bacterial preparations based on effectiveness data.
Current Controlled Trials ISRCTN56067537 [controlled-trials.com].
[Show abstract][Hide abstract] ABSTRACT: Adherence to antiretroviral (ART) therapy, as reported by children caregivers, was investigated and compared with physicians' estimates of adherence. Two parallel structured questionnaires were administered to caregivers of 129 HIV-infected children and to their physicians in seven different Italian reference centers. Doses omitted in the last four days were recorded. Perfect adherence (>95% of prescribed doses taken in the last four days before interview) was reported by caregivers of 103 (79%) children. Five children (5%) omitted one dose of any ART drug in four days and were considered adherent. Low (<95 but >80% of doses) and poor (<80% of doses) adherence were reported by 15 (12%) and six (5%) caregivers, respectively. Forty-eight children (37%) were judged to be non-adherent by their physicians, including 35 children who were receiving all the prescribed doses according to caregivers. The physicians identified eight out of the 21 non-adherent children as adherent. Non-adherence estimates by physicians closely correlated with poor clinical conditions. These data indicate that adherence is a major problem but there is a clear discrepancy between caregiver reports and physician judgement. The results underline the need of close surveillance of adherence in HIV-positive children in order to evaluate the effectiveness of ART therapy.
[Show abstract][Hide abstract] ABSTRACT: The severity of childhood gastroenteritis is generally believed to be age-related rather than aetiology-related. Rotavirus-induced gastroenteritis is more severe than gastroenteritis caused by other enteric pathogens and is also age-related. We thus addressed the question of whether the increased severity of rotavirus-induced gastroenteritis is related to age or to features intrinsic to the agent.
In this multicentre, hospital-based, prospective survey, we evaluated the severity of diarrhoea in rotavirus-positive and rotavirus-negative children up to 4 years of age. Severity was assessed with a score in four groups of age-matched children.
Rotavirus was detected in 381 of 911 children. Disease severity was evaluated in 589 cases for which clinical data were complete. The rotavirus-positive and rotavirus-negative groups differed with regards to diarrhoea duration, hospital stay, degree of dehydration and the number of episodes of vomiting. Gastroenteritis was more severe in rotavirus-positive than in rotavirus-negative children. In contrast, none of the main severity parameters differed in the four age groups, irrespective of the presence of rotavirus.
These data provide the evidence that aetiology and not age determines diarrhoeal severity. The demonstration that diarrhoea was more severe in rotavirus-positive children supports the need for a rotavirus vaccine and for studies that address the duration of vaccine protection.
No preview · Article · Apr 2007 · European Journal of Pediatrics
[Show abstract][Hide abstract] ABSTRACT: Antiemetics are not included for treatment of vomiting associated with acute gastroenteritis (AGE) in children by standard guidelines. We performed a survey to determine antiemetic prescribing rates by Italian pediatricians. A structured questionnaire was distributed at a pediatric national conference. The majority of responders reported prescribing antiemetics for pediatric gastroenteritis. Although there is insufficient evidence to justify their use, the use of antiemetics is widely present among pediatricians.
Full-text · Article · Oct 2006 · Journal of pediatric gastroenterology and nutrition
[Show abstract][Hide abstract] ABSTRACT: We previously detected specific binding activity of Escherichia coli heat-stable enterotoxin (ST), the guanylin exogenous ligand, in rat colonic basolateral membranes. Because guanylin circulates in the bloodstream, we tested the hypothesis that it modulates intestinal ion transport by acting on the serosal side of intestinal cells. The effects of the mucosal and serosal addition of ST and guanylin on ion transport were investigated in the rat proximal colon and in Caco-2 cells in Ussing chambers, by monitoring short-circuit current (Isc). cGMP concentration was measured in Caco-2 cells by RIA. Mucosal ST addition induced an increase in Isc in rat proximal colon consistent with anion secretion. Serosal addition induced the same effects but to a lesser extent. The electrical effects observed in Caco-2 cells paralleled those observed in rat proximal colon. A pattern similar to the electrical response was observed with cGMP concentration. Guanylin addition to either side of Caco-2 cells induced the same effects as ST, although to a lesser extent. In all conditions, the electrical effect disappeared in the absence of chloride. ST directly interacts with basolateral receptors in the large intestine inducing chloride secretion through an increase of cGMP. However, the serosal effects are less pronounced compared with those observed with mucosal addition. Guanylin shows the same pattern, suggesting that it plays a role in the regulation of ion transport in the colon, but the relative importance of serosally mediated secretion remains to be determined.
Full-text · Article · Aug 2005 · Pediatric Research
[Show abstract][Hide abstract] ABSTRACT: To investigate rates and determinants of adherence to antiretroviral therapy in Italian children infected with the human immunodeficiency virus (HIV).
An observational, cross-sectional multicentre study was performed through a structured interview with the caregivers of HIV-infected children. The interview included quantitative information on adherence in the 4 d before interview. Sociodemographic, clinical and psychosocial characteristics of children were recorded.
129 children (median age 96 mo) were enrolled, of whom 94 were on highly active antiretroviral therapy (HAART). Twenty-one (16%) omitted more than 5% of total doses in 4 d and were considered non-adherent. However, only 11% of caregivers reported that therapy had been administered at the correct times. No significant difference was found between age and the stage of HIV infection. Children aware of their HIV status were less adherent. Individual drugs showed a broad adherence pattern and children who received HAART were more adherent. Children receiving therapy from foster parents were more adherent than those receiving drugs from biological parents or relatives.
Adherence is a major problem in children. Psychological rather than clinical or sociodemographic features and types of drug are major determinants of adherence.
[Show abstract][Hide abstract] ABSTRACT: Inappropriate infant feeding including a lack of breastfeeding and the early introduction of cow's milk are the most common forms of infant feeding malpractice. To evaluate the hypothesis that infant feeding malpractices are associated with mothers' low level of education, questionnaires were administered to 400 mothers of infants below 12 mo of age divided into 3 groups according to their various educational levels. Items included the type of milk given at birth and at 1, 3 and 6 mo of age. To investigate the efficacy of paediatricians in orienting infant feeding, the same questionnaire was given to 30 paediatricians in primary paediatric healthcare, in hospitals or in private practices. Initiation of breastfeeding was similar in the three groups. An analysis of the data showed that an increasing number of infants born to mothers of low and intermediate educational level did not receive exclusive breastfeeding compared with those with a higher level of education, a difference that was significant as early as 1 mo of age. In infants aged 3 mo, the prevalence of exclusive breastfeeding was 37%, 40% and 65% in the three groups, respectively, in relation to progressively increasing levels of education. In infants of 6 mo, the respective prevalence rates were 13%, 15% and 48%. Early introduction of cow's milk showed a similar correlation with educational level. A greater number of infants born to mothers with a low level of education received cow's milk at 3 mo of age compared with those born to mothers with an intermediate education (12% vs 5%). A similar difference was observed between the latter group and infants born to mothers with a high educational level (0%). This pattern was supported by data for infants at 6 mo of age with prevalence rates for cow's milk feeding of 39%, 20% and 0% in the three groups in association with progressively increasing level of educational (p < 0.05). The analysis of the paediatricians' response to the questionnaire showed that while physicians know and correctly prescribe age-related infant nutrition regimens, they are unaware that a substantial number of mothers do not comply with what they prescribe. Overall, these data support the relationship between a low educational level and infant feeding malpractice and suggest that a more effective role should be played by paediatricians in supporting an adequate duration of breastfeeding and the use of formula rather than cow's milk protein.
No preview · Article · Oct 2003 · Acta paediatrica (Oslo, Norway: 1992). Supplement
[Show abstract][Hide abstract] ABSTRACT: Severe diarrhea and enteropathy of unknown origin are frequent in patients infected with human immunodeficiency type 1 virus (HIV-1). The HIV-1 transactivating factor protein (Tat) is a key factor in the pathogenesis of acquired immunodeficiency syndrome. We investigated whether Tat could directly induce ion secretion and cell damage in enterocytes.
Electrical parameters (ion transport studies) were measured in Caco-2 cell monolayers and in human colonic mucosa specimens mounted in Ussing chambers. The effect of Tat on intestinal mucosa integrity was determined by monitoring the transepithelial electrical resistance of Caco-2 cell monolayers. (3)H-thymidine incorporation and cell count were used to evaluate the effect of Tat on cell growth. Intracellular calcium concentrations were measured at the single-cell level using microfluorometry technique.
Tat protein induced ion secretion in Caco-2 cells and in human colonic mucosa similar to that induced by bacterial enterotoxins. It also significantly prevented enterocyte proliferation. In both instances, the effect of Tat was maximum at concentrations within the range detected in the sera of HIV-1-infected patients. Anti-Tat antibodies inhibited both effects. Ion secretion and the antiproliferative effects were mediated by L-type Ca(2+) channels. An increase in intracellular calcium concentration in Caco-2 cells was found after addition of Tat.
These results indicate that Tat may be involved in HIV-1-related intestinal disease through direct interaction with enterocytes.
No preview · Article · Feb 2003 · Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: 1 report that, although neither the frequency nor the severity of rotavirus infection were increased in HIV-infected Malawian children, the number of deaths was higher in HIV- positive than in HIV-negative children in the short-term follow-up. However, if children lost to follow-up or those who died in the early phase of the disease are included in the analysis, the number of deaths is 19 of 102 HIV- infected compared with eight of 91 HIV-negative children (p>0·05). We were surprised by such a high number of deaths in immunocompromised and immunocompetent children. Cunliffe and colleagues rightly ask for urgent specific intervention, including studies on the safety and immunogenicity of vaccines against rotavirus. However, while awaiting for pre- ventive strategies, we believe that an effective treatment is already available as oral administration of human serum immunoglobulin, in one 300 mg/kg bodyweight dose. We have initially used human immunoglobulin to treat children with life-threatening rotavirus diarrhoea. In a subsequent double- blind, placebo-controlled study, passive immunotherapy resulted in faster recovery and early discharge of immunocompetent children admitted to hospital with severe rotavirus diarrhoea, without adverse effects. 2 The same treatment was given to three children who had AIDS and severe rotavirus infection, and led to quick remission of diarrhoea and permanent clearance of the virus. 3 Similar results were obtained by others with immuno- globulin from immunised bovine colostrum. 4 We currently give human immunoglobulin to children with severe rotavirus infection and to patients at risk of a poor outcome. Human immunoglobulin, although expensive, is widely available. Its effectiveness seems to be related to high titres of specific neutralising anti- bodies to rotavirus. Specific titres are consistently detected in preparations commercially available for intravenous use, because of the high frequency of rotavirus infection and the consequent widespread immune response. The mechanism of immunoglobulin efficacy is probably related to a dose and time- related direct neutralisation of rotavirus, which prevents enterocyte infection and cell death. 5 Thus, immunoglobulin should be administered orally in the early phase for maximum efficacy. This information may be of practical relevance, while awaiting the develop- ment of safer vaccines that will hopefully be effective, for normal or compromised immune function.