The effect of probiotics on prevention of upper respiratory tract infections in the paediatric community - a systematic review.

Prevention of acute upper respiratory tract infections (URTIs) is becoming an increasingly important concept in public health application due to the increase in antibiotic resistance. Probiotics have been shown to have some effect on prevention in various reviews. In this study we aimed to re-asses the effect of probiotics as there has been a substantial increase in literature regarding the effects and safety of probiotics in the paediatric population. Two major databases were systematically searched to identify clinical trials eligible for inclusion. Study selection, data extraction and quality assessment were carried out by two reviewers. This review comprises 33 randomised controlled trials (RCTs) applied to a paediatric population with high-quality methodology. The primary outcome for this review was the incidence of respiratory tract infections. Secondary outcomes were severity of symptoms, missed days of school, incidence of antibiotic use and safety of prebiotic use. This review showed that probiotics have an impact on decreasing the incidence of URTIs and the severity of symptoms. The use of probiotics is extremely safe and as studies increase in evaluation of the effect of probiotics more and more show a significant beneficiary effect. Although still a long way from becoming a unanimous treatment modality, the small positive changes that probiotics have on URTIs is important to consider and the use of probiotics should be encouraged more.

Human milk mycobiota composition: relationship with gestational age, delivery mode, and birth weight.

Intestinal and human milk microbiota studies during infancy have shown variations according to geographical location, delivery mode, gestational age, and mother-related factors during pregnancy. In this study, we performed metagenomic mycobiota analyses of 44 transient and mature human milk among five different groups: mothers of normal spontaneous delivery-term (NS-T), caesarean delivery-term (CS-T), premature (PT), small for gestational age (SGA), and large for gestational age (LGA) infants. Fungi were detected in 80 out of the 88 samples. Regarding the number of observed fungal species, the NS-T group was more homogeneous (less variable) comparing the other groups (P<0.05). In the transient human milk samples, the most abundant species were Saccharomyces cerevisiae (33.3%) and Aspergillus glaucus (27.4%). While A. glaucus (33.7%) was second most abundant species in mature milk, S. cerevisiae disappeared (P<0.01) and Penicillium rubens became the most abundant species (35.5%) (P<0.05). Among the NS-T group, the most abundant species was Malassezia globosa in both transient and mature milk. In contrast, S. cerevisiae was the most abundant species in transient human milk (45.0%) in the CS-T group, but it disappeared in mature milk (P<0.01). In transient milk, M. globosa was only represented 6.0-9.0% of taxa in the PT, SGA, and LGA groups (P<0.05). In transient and mature milk in the PT, SGA and LGA groups, the most abundant species were A. glaucus and P. rubens. In mature milk samples, P. rubens is more abundant in CS-T group, PT group and LGA group, than the NS-T groups (P<0.05 for all). Although fungi constitute only a very small part of the human milk microbiome, we observed some changes that the human milk mycobiota composition varies in caesarean delivery, premature, SGA and LGA groups, comparing the normal spontaneous delivery, as well as differences between transient and mature human milk.

EVALUATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN A PAEDIATRIC INTENSIVE CARE UNIT.

BACKGROUND: Relative adrenal insufficiency (RAI) is the inadequate production of cortisol due to dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis during a severe illness. We evaluated the HPA axis and RAI in a tertiary pediatric intensive care unit (PICU). METHODS: A total of 100 PICU patients were included in this prospective cohort study. Basal serum levels of adrenocorticotropic hormone (ACTH), cortisol values were compared with those in the control group. A low-dose ACTH stimulation test was performed in patients with basal cortisol levels below 18 µg/dL. RESULTS: The basal cortisol levels of the PICU patients were significantly higher than those of the control group (P < 0.05). All tested patients (n= 24) had delta cortisol levels > 9 µg/dL and a peak cortisol response > 18 µg/dL. Basal cortisol levels were positively correlated with Pediatric Risk of Mortality (PRISM) III scores (P < 0.05; r = 0.363). The basal or stimulated cortisol levels of the patients who received glucocorticoid treatment were higher than the cut-off levels. CONCLUSIONS: High basal or stimulated cortisol levels are indicative of disease severity in the acute phase of stress. Patients with very high cortisol levels should be particularly carefully monitored because of the high mortality risk.

Pharmacoeconomic evaluation of micafungin versus caspofungin as definitive therapy for candidaemia and invasive candidiasis (IC) in Turkey.

Micafungin was shown to be as efficacious as caspofungin in treating patients with candidaemia and invasive candidiasis (IC). However, it remains unknown if micafungin or caspofungin is a cost-effective definitive therapy for candidaemia and IC in Turkey. The present study aimed to determine the economic impact of using micafungin versus caspofungin for treatment of candidaemia and IC in the Turkish setting. A decision analytic model was constructed and was populated with data (i.e. transition probabilities, duration of initial antifungal treatment, reasons for treatment failure, percentage of patients who stepped down to oral fluconazole, and duration on oral fluconazole) obtained from a published randomised clinical trial. Cost inputs were derived from the latest Turkish resources while data that were not readily available in the literature were estimated by expert panels. One-way sensitivity analyses, threshold analyses, scenario analyses and probabilistic sensitivity analyses were conducted. Caspofungin (€2693) incurred a lower total cost than micafungin (€4422), with a net cost saving of €1729 per treated patient. Drug acquisition cost was the main cost driver for both study arms. The model outcome was robust over wide variations (of ±100.0% from the base case value) for all input parameters except for micafungin drug cost and the duration of initial treatment with micafungin. Caspofungin appears to be a cost-saving option in treating candidaemia and IC from the Turkish hospital perspective.

Effects of synbiotic on anthropometry, lipid profile and oxidative stress in obese children.

Recent studies have suggested some beneficial effects of probiotics and/or prebiotics on obesity in adults; such experience is limited in children and adolescents. This study was an open-label, randomised, controlled study including children with primary obesity. The first group was treated with a standard method with a reduced calorie intake and increased physical activity. The second group received add-on daily synbiotic supplementation during one month. The aim of this study was to evaluate potential effects of a synbiotic on anthropometric measurements, lipid profile and oxidative stress parameters. One month of supplementation of the synbiotic resulted in a significant reduction of weight (P<0.001) and body mass index (P<0.01). Changes (% reduction comparing to baseline) in anthropometric measurements, were significantly higher in the children receiving the additional synbiotic supplement (P<0.05). The percentage of children with weight loss was higher in the synbiotic group, but not statistically significant (71.4 vs 64.2%, P>0.05). At the 30(th) day of synbiotic intervention, serum total cholesterol, low density lipoprotein cholesterol and total oxidative stress levels significantly declined (P<0.05). Changes in serum lipid levels were significantly higher in the synbiotic group (P<0.05). Changes in serum total oxidative stress levels before and after the intervention period, were significant in synbiotic group (P<0.01). In our study, changes in weight, body mass index, and triceps skinfold thickness were higher in the group receiving the one month synbiotic supplement thin in the standard method group. The supplement tested also had a beneficial effect on lipid profile and total oxidative stress. To the best of our knowledge, this is the first study showing the effects of synbiotics on oxidative stress in obese patients with an additional effect on weight loss regarding to previous studies.

Saccharomyces boulardii CNCM I-745 reduces the duration of diarrhoea, length of emergency care and hospital stay in children with acute diarrhoea.

Evidence from the literature has shown that Saccharomyces boulardii provides a clinically significant benefit in the treatment of acute infectious diarrhoea in children. In this multicentre, randomised, prospective, controlled, single blind clinical trial performed in children with acute watery diarrhoea, we aimed to evaluate the impact of S. boulardii CNCM I-745 in hospitalised children, in children requiring emergency care unit (ECU) stay and in outpatient settings. The primary endpoint was the duration of diarrhoea (in hours). Secondary outcome measures were duration of hospitalisation and diarrhoea at the 3(rd) day of intervention. In the whole study group (363 children), the duration of diarrhoea was approximately 24 h shorter in the S. boulardii group (75.4±33.1 vs 99.8±32.5 h, P<0.001). The effect of S. boulardii (diarrhoea-free children) was observed starting at 48 h. After 72 h, only 27.3% of the children receiving probiotic still had watery diarrhoea, in contrast to 48.5% in the control group (P<0.001). The duration of diarrhoea was significantly reduced in the probiotic group in hospital, ECU and outpatient settings (P<0.001, P<0.01 and P<0.001, respectively). The percentage of diarrhoea-free children was significantly larger after 48 and 72 h in all settings. The mean length of hospital stay was shorter with more than 36 h difference in the S. boulardii group (4.60±1.72 vs 6.12±1.71 days, P<0.001). The mean length of ECU stay was shorter with more than 19 h difference in the probiotic group (1.20±0.4 vs 2.0±0.3 days, P<0.001). No adverse effects related to the probiotic were noted. Because treatment can shorten the duration of diarrhoea and reduce the length of ECU and hospital stay, there is likely a social and economic benefit of S. boulardii CNCM I-745 in adjunction to oral rehydration solution in acute infectious gastroenteritis in children.

The history of probiotics: the untold story.

Probiotic, a word derived from Latin, means 'for life'. A long time before the awareness of probiotic microorganisms, fermented products, such as beer, bread, wine, kefir, kumis and cheese had been very frequently used for nutritional and therapeutic purposes. It is widely believed that fermented products were probably found, or better to say, discovered spontaneously. The legend tells that yoghurt is most likely resulted from a fermentation process within the animal skin bags used for transportation of water and milk in regions with low humidity and high temperatures (Middle Asia and Middle East). The history of probiotics goes paralel with the evolution of human race and, thanks to the sophisticated techniques at the moment, can be traced back to the ancient times, nearly 10,000 years ago. The aims of this review are to highlight the important events for probiotic history, to correct the widely available anonymous misinformation in the literature and to remind to the readers important characters in its history.

Cost effectiveness of caspofungin vs. voriconazole for empiric therapy in Turkey.

Invasive fungal infections from febrile neutropenia are associated with significant cost and mortality. The mainstay of treatment has been liposomal amphotericin B, however, echinocandins and azoles have shown promise as alternative treatments. Data on clinical efficacy exist, however, data incorporating pharmacoeconomic considerations are required in Turkey. The aim of this study was to investigate the cost effectiveness of caspofungin vs. voriconazole in empiric treatment of febrile neutropenia in Turkey. A decision analytic model was utilised, built upon two randomised-controlled trials and supplemented with expert panel input from clinicians in Turkey. A five-point composite outcome measure was utilised and sensitivity analyses were performed to demonstrate the robustness of the model. The base case scenario resulted in caspofungin being preferred by TL2,533, TL29,256 and TL2,536 per patient treated, successfully treated patient and patient survival, respectively (approx. USD1414, 16 328 and 1415); sensitivity analyses did not change the outcome. Monte Carlo simulation highlighted a 78.8% chance of favouring caspofungin. The result was moderately sensitive to treatment duration and acquisition cost of the antifungal agents compared. This is the first pharmacoeconomic study comparing caspofungin to voriconazole within Turkey, resulting in an advantage towards caspofungin. The study will aid in formulary decision-making based on the clinical and economic consequences of each agent in the Turkish health care setting.

Pharmacoeconomic evaluation of caspofungin versus liposomal amphotericin B in empirical treatment of invasive fungal infections in Turkey.

Invasive fungal infections (IFIs) are a major concern within healthcare systems. This pharmacoeconomic study evaluated the use of caspofungin (CAS) versus liposomal amphotericin B (L-AmB) in the empirical treatment of IFIs within the Turkish healthcare system. A decision-analytic model was adopted, utilising data from a randomised, non-inferiority clinical trial and a panel of clinical experts in Turkey. A five-point composite outcome measure was used to evaluate both agents. Sensitivity analyses were performed. In the base-case scenario, CAS was preferred over L-AmB by Turkish Lira (TL) 3961 per patient treated, TL 12 904 per successfully treated patient and TL 3972 per death averted. One-way sensitivity analysis did not change the study outcome. Monte Carlo simulation concluded a 71.0% chance of the outcome favouring CAS. The results were most sensitive to changes in length of stay. This is the first economic evaluation of the empirical treatment of IFIs in Turkey and suggests that CAS is more cost effective than L-AmB.

An additional child case of an aldosterone-producing adenoma with an atypical presentation of peripheral paralysis due to hypokalemia.

Aldosterone-producing adenoma, which is characterized by hypertension, hypokalemia, and elevated aldosterone levels with suppressed plasma renin activity, is a rare condition during childhood and is also potentially curable. To the best of our knowledge, nearly 25 cases of childhood aldosterone-secreting adenoma have been reported in the literature to date. Here we describe a 13-yr-old girl with primary hyperaldosteronism secondary to aldosterone-secreting adenoma. The patient was admitted to our hospital with the neuromuscular complaints of muscle weakness and inability to walk due to hypokalemia. She had been misdiagnosed as having hypokalemic periodic paralysis 2 months before admission and her symptoms had radically improved with potassium supplementation. However, her blood pressure levels had increased and her symptoms reappeared 2 days prior to being observed during hospitalization in our institution. Laboratory examinations revealed hypokalemia (2.1 mEq/l), and increased serum aldosterone levels with suppressed plasma renin activity. Abdominal ultrasonography and abdominal magnetic resonance imaging revealed left adrenal mass. Laparoscopic adrenalectomy was performed and histopathological examinations showed benign adrenal adenoma. Serum aldosterone levels and blood pressure levels returned to normal after surgical intervention. This case demonstrates the importance of a systemic evaluation including blood pressure monitorization of children with hypokalemia as intermittent hypertension episodes may be seen; cases without hypertension may be misdiagnosed as rheumatological or neurological disorders such as hypokalemic periodic paralysis, as in our case.

Plasma total homocysteine levels in children with type 1 diabetes: relationship with vitamin status, methylene tetrahydrofolate reductase genotype, disease parameters and coronary risk factors.

The objectives of this study were: to determine plasma total homocysteine tHcy levels and the prevalence of hyperhomocysteinemia in children with type 1 diabetes, to determine correlates of plasma tHcy levels with nutritional factor such as serum folic acid and vitamin B12 levels, genetic factors as methylenetetrahydrofolate reductase MTHFR gene polymorphism (C677T and A1298C), to attempt to identify possible dependencies between tHcy and the degree of metabolic control, the duration of the disease and presence of complications, and also to determine the relationship between other coronary risk factors. Plasma tHcy levels and other related parameters performed in 32 children with type 1 diabetes and 23 age-sex matched healthy children. Median tHcy level was higher in the patient group (11.38, 3.28 to 66.01 micromol/l) than the control group (8.78, 1.06 to 13.66 mol/l) (p < 0.05). A 28.1 per cent (n = 9) of the diabetic patients had hyperhomocysteinemia, four case with mild and five case with moderate. Plasma tHcy levels were positively correlated with disease duration and C-reactive protein CRP levels and negatively correlated with disease onset age. The hyperhomocysteinemic group had higher CRP levels, longer disease duration and early onset of disease than non-hyperhomocysteinemic group (p < 0.05 in both), respectively. The hyperhomocysteinemic group had significantly higher CRP, total cholesterol, triglyceride, apolipoprotein B, systolic blood pressure, blood urea nitrogen and creatinine levels and lower folate, apolipoprotein A1 levels and glomerular filtration rate values than the control group. Plasma tHcy levels were higher in diabetic children with poor metabolic control. Because of hyperhomocysteinemia is common in diabetic children and plasma tHcy levels correlated with early onset of the disease and disease duration, we recommend the usage of plasma tHcy levels as a risk indicator parameter with other coronary risk factor for detecting and preventing cardiovascular disease in diabetic children.