Application of the Weighted-Incidence Syndromic Combination Antibiogram (WISCA) to guide the empiric antibiotic treatment of febrile neutropenia in oncological paediatric patients: experience from two paediatric hospitals in Northern Italy.

BACKGROUND: Guidelines about febrile neutropenia in paediatric patients are not homogeneous; the best empiric treatment of this condition should be driven by local epidemiology. The Weighted-Incidence Syndromic Combination Antibiogram (WISCA) addresses the need for disease-specific local susceptibility evidence that could guide empiric antibiotic prescriptions based on outcome estimates of treatment regimens obtained as a weighted average of pathogen susceptibilities. This study developed a WISCA model to inform empirical antibiotic regimen selection for febrile neutropenia (FN) episodes in onco-haematological paediatric patients treated at two Italian paediatric tertiary centres. METHODS: We included blood cultures from patients with a bloodstream infection and neutropenia admitted to the Paediatric Haematology-Oncology wards in Padua and Genoa Hospitals from 2016 to 2021. WISCAs were developed by estimating the coverage of 20 antibiotics as monotherapy and of 21 combined regimens with a Bayesian probability distribution. RESULTS: We collected 350 blood cultures, including 196 g-negative and 154 g-positive bacteria. Considering the most used antibiotic combinations, such as piperacillin-tazobactam plus amikacin, the median coverage for the pool of bacteria collected in the study was 78%. When adding a glycopeptide, the median coverage increased to 89%, while the replacement of piperacillin-tazobactam with meropenem did not provide benefits. The developed WISCAs showed that no monotherapy offered an adequate coverage rate for the identified pathogens. CONCLUSIONS: The application of WISCA offers the possibility of maximizing the clinical utility of microbiological surveillance data derived from large hospitals to inform the choice of the best empiric treatment while contributing to spare broad-spectrum antibiotics.

Development of a Weighted-Incidence Syndromic Combination Antibiogram (WISCA) to guide the choice of the empiric antibiotic treatment for urinary tract infection in paediatric patients: a Bayesian approach.

BACKGROUND: To evaluate the ability of Weighted-Incidence Syndromic Combination Antibiograms (WISCA) to inform the selection of empirical antibiotic regimens for suspected paediatric community-acquired urinary tract infections. METHODS: Data were collected from outpatients (< 15 years) accessing the emergency rooms of Padua University-Hospital and Mestre Dell' Angelo-Hospital (Venice) between January 1st, 2016, and December 31st, 2018. WISCAs were developed by estimating the coverage of eight regimens using a Bayesian hierarchical model adjusted for age, sex, and previous antibiotic treatment or renal/urological comorbidities. RESULTS: 385 of 620 urine culture requests were included in the model analysis. The most frequently observed bacterium was E. coli (85% and 87%, Centre A and B). No centre effect on coverage estimates was found, and data were successfully pooled together. Coverage ranged from 77.8% (Co-trimoxazole) to 97.6% (Carbapenems). Complex cases and males had significantly lower odds of being covered by a regimen than non-complex cases and females (odds ratio (OR) 0.49 [95% HDI, 0.38-0.65], and OR: 0.73 [95% HDIs, 0.56-0.96] respectively). Children aged 3-5 years had lower odds of being covered by a regimen than other age groups, except for neonates. CONCLUSIONS: The developed WISCAs provide highly informative estimates on coverage patterns overcoming the limitation of combination antibiograms and expanding the framework of previous Bayesian WISCA algorithm.

A simple instrument to assess the risk of falling in postpartum women: the SLOPE scale (riSk of faLling in pOstPartum womEn).

The purpose of this study was to introduce a novel instrument aimed at stratifying the risk of falling in postpartum patients. The research was a survey of a sample of 460 midwives working at different hospitals, mainly in Northern Italy, except for a hospital in Rome (Italy). The survey, consisting of 70 items, was conducted among midwives and asked them to express their opinion regarding the increased risk of falling in puerperal women on a Likert scale according to the characteristics listed in the questionnaire. Items were derived from the synthesis of scales available in the literature from settings other than the postpartum period, and interviews were conducted with midwives with great experience in this area. A shortened version was obtained using principal component analysis. A 30-item final scale was obtained, the SLOPE (riSk of faLling in pOst-Partum womEn), ranging from 0 to 100. The scale allows stratification of postpartum women at low (0-10), intermediate (10-20) and high risk (>20) of falling. The development of the SLOPE scale is the first step towards more rational evidence-based management of the risk of falling in postpartum women in current clinical practice.Impact statementWhat is already known on this subject? Falls occurring in the postnatal period are not limited to women because infants are often involved in this adverse event, with several significant consequences. There is a lack of information on this issue due to the absence of both registries and scales for the prevention of falls.What do the results of this study add? The main result of this study is the development of a novel scale to assess the falling risk in postpartum women.What are the implications of these findings for clinical practice and/or further research? The development of this novel scale, even if based on midwives' experience and not on patients' data, is a first step towards a more rational evidence-based management of the risk of falling in postpartum women.

Effect of Protein-Fortified Diet on Nitrogen Balance in Critically Ill Patients: Results from the OPINiB Trial.

Nitrogen balance (NB) is considered a good marker of adequate protein intake and it has been suggested to be a good predictor of patients' health outcomes. However, in literature, there is a lack of large randomized trials examining NB-guided protein intake in patients in intensive care units (ICUs). A randomized controlled trial enrolling patients admitted to ICU was done to compare changes in NB. Participants were randomized to a standard or protein-fortified diet (protein intake of 1.8 g/kg/day according to the guidelines of the Society of Critical Care Medicine and the American Society for Parenteral and Enteral Nutrition). The primary endpoint was represented by the NB on Day 1, 3, and study exit. Forty patients were enrolled in the study (19 in the protein-fortified group). The longitudinal analysis showed that, on Day 3, patients randomized to the protein-fortified diet were more likely (p < 0.001) to present better NB (at 3 days, patients in the protein-fortified diet were estimated to have a nitrate value of 5.22 g more than patients in the standard diet, 95% CI 3.86-6.58). The protein-fortified diet was found to be significantly and directly associated with changes in NB in critically ill patients admitted to ICU.

An Epistemological View on Risk Exposure Assessment: A Case Study.

BACKGROUND: Research in Health Risk Assessment is increasingly covering a preeminent role in health care studies. However, risk assessment faces the issue of properly measuring risk exposure. OBJECTIVE: The aim of the study has been to tackle some methodological issues regarding the risk assessment analysis in the health field, giving more emphasis to a philosophical and epistemological approach in order to show the difficulties in adopting suitable exposure assessment techniques. METHOD: Here, we present a methodological review and a critical discussion of foreign body injuries articles in child population as a case study. A Medline, Econlite and CIS bibliographic search was conducted considering the term "foreign bodies" only in "children" and "risk". Only English papers are considered. Further research on CDC, CPSC, DGSANCO databases has been performed. Different approaches in risk assessment are reviewed using four case-study papers with the purpose of pointing out their limitations. RESULT: Ten papers are retrieved though literature review reporting risk estimate of foreign bodies injuries in children. CONCLUSION: Considering that different variables affecting the risk of choking injuries, like intrinsic characteristic of a product or the intensity levels at which children are exposed, and then it seems very difficult to correctly evaluate risk of injuries. For this reason, we have argued for an epistemological and holistic approach toward risk assessment.

Definition of a tolerable upper intake level of niacin: a systematic review and meta-analysis of the dose-dependent effects of nicotinamide and nicotinic acid supplementation.

Context: Nicotinic acid and nicotinamide are soluble compounds of the vitamin B group, widely used to regulate the lipid profile in hyperlipidemic individuals. Higher doses of nicotinic acid are associated with adverse effects, especially flushing. A unique tolerable upper intake level (UL) of nicotinic acid has not been defined. Objective: This meta-analysis aims to evaluate adverse effects and their incidence after supplementation with different doses of nicotinic acid and nicotinamide, comparing results with current ULs in Europe and the United States. Data Sources: PubMed was searched for articles providing detailed information about nicotinic acid or nicotinamide supplementation and related outcomes. Study Selection: A total of 2670 citations were selected for screening. Two primary outcomes were considered: occurrence of adverse effects following nicotinic acid or nicotinamide supplementation, and dose at which adverse effects occurred. Data extraction: Details on study population, type and duration of treatment, dosage of vitamins, association with lipid-influencing drugs, length of follow-up, and incidence and type of adverse events were extracted. Results: After screening, 47 articles involving 11 741 individuals were included. Meta-analysis was based on estimation of benchmark doses for the probability of adverse effects after supplementation. In individuals with dyslipidemia or cardiovascular disease, nicotinic acid monotherapy seems to be protective against any adverse effects considered, as adverse events occurred at doses above those used with other treatments. In healthy individuals treated with nicotinic acid alone, major adverse effects occurred at doses below 1000 mg/d. Conclusions: Results may indicate a high degree of conservativeness in the UL of nicotinic acid, fixed at 35 mg/d in United States and 10 mg/d in Europe. Reconsideration of the UL of nicotinic acid for nutritional supplements, possibly differentiating between ULs in healthy and unhealthy individuals, may be warranted.

Prebiotic effect of an infant formula supplemented with galacto-oligosaccharides: randomized multicenter trial.

OBJECTIVE: The objective of the study was to investigate the effects of a galacto-oligosaccharides (GOS)-supplemented formula on the intestinal microbiota in healthy term infants, with a specific consideration for gastrointestinal symptoms as colic, stool frequency and consistency, regurgitation. METHODS: This was a randomized, double-blind, controlled, parallel-group clinical trial performed simultaneously by 6 centers in Italy. Three groups were considered: breastfed, formula-fed, and GOS-supplemented formula-fed infants. Formula-fed infants were randomized to receive either the control or the study formula and consume the assigned formula exclusively until the introduction of complementary feeding. The nutritional composition of the 2 formulas were identical, apart from the supplemented GOS (0.4 g/100 mL) in the study formula. Four different types of bacteria were evaluated in order to assess the efficacy of GOS-supplemented formula on infants: Bifidobacterium, Lactobacillus, and Clostridium, Escherichia coli. RESULTS: A total of 199 breastfed infants and 163 formula-fed infants were recruited. When considering stool frequency and consistency, GOS-supplemented formula presented normal and soft stools in the majority of episodes (89%). In the supplemented group the incidence of colic was lower with respect to the control group. A significantly lower count of Clostridium and a higher count of Bifidobacterium were found when comparing study formula and control formula in infants with colic. In children with colic the ratio between Clostridium count and Bifidobacterium and Lactobacillus count was in favor of the latter two when considering the GOS-supplemented formula group with respect to the control one. CONCLUSIONS: The prebiotic-supplemented formula mimicked the effect of human milk in promoting Bifidobacterium and Lactobacillus growth and in inhibiting Clostridium growth, resulting in a significantly lower presence of colic.

The burden of inappropriate emergency department pediatric visits: why Italy needs an urgent reform.

OBJECTIVE: To better understand the issue of inappropriate pediatric Emergency Department (ED) visits in Italy, including the impact of the last National Health System reform. STUDY DESIGN: A retrospective cohort study was conducted with five health care providers in the Veneto region (Italy) in a 2-year period (2010-2011). ED visits were considered "inappropriate" by evaluating both nursing triage and resource utilization, as addressed by the Italian Ministry of Health in 2007. Factors associated with inappropriate ED visits were identified. The cost of each visit was calculated. PRINCIPAL FINDINGS: In total, 134,358 ED visits with 455,650 performed procedures were recorded in the 2-year period; of these, 76,680 (57.1 percent) were considered inappropriate ED visits. Patients likely to make inappropriate ED visits were younger, female, visiting the ED during night or holiday, when the primary care provider (PCP) is not available. CONCLUSION: The National Health System reform aims to improve efficiency, effectiveness, and costs by opening PCP offices 24 hours a day and 7 days a week. This study highlights the need for a deep reorganization of the Italian Primary Care System not only providing a larger time availability but also treating the parents' lack of education on children's health.

An encapsulated juice powder concentrate improves markers of pulmonary function and cardiovascular risk factors in heavy smokers.

OBJECTIVE: Cigarette smoking is associated with reduced pulmonary function and increased risk factors for cardiovascular disease. This randomized placebo-controlled double-blind study evaluated the effects of two different combinations of mixed fruit and vegetable juice powder concentrate (Juice Plus+, NSA, Collierville, TN) on heavy smokers. METHODS: At baseline (T 0) and after 3 months' supplementation (T 1), pulmonary function parameters and cardiovascular risk factors-that is, plasma total homocysteine (tHcy) with related B vitamins and cysteine (tCys) concentrations-were assessed in 75 apparently healthy smokers (aged 49.2 ± 10.6 years, >20 cigarettes/d, duration ≥10 years) randomized into 3 groups: placebo (P), fruit/vegetable (FV) and fruit/vegetable/berry (FVB). RESULTS: T 0: most smokers showed abnormalities in tHcy and tCys concentrations. T 1: respiratory function was unchanged in P and slightly, but not significantly, improved in FV, whereas FVB showed a significant improvement in forced expiratory flow at 25% (FEF25; p < 0.0001 vs P and FV) and significant improvement in CO diffusion lung/alveolar volume (DLCO/VA). FV and FVB (50%) showed significant reduction in tHcy and tCys compared to T 0 ( p < 0.0001) and P ( p < 0.0001). CONCLUSIONS: At T 1, both supplemented groups, but to a greater extent the FVB group, showed improvements in some pulmonary parameters, cardiovascular risk factors, and folate status. The beneficial effects of Juice Plus+ supplementation could potentially help smokers, even if smoking cessation is advisable.

Multifunctional food: medical evidence and methodological notes on substantiating health claims.

In nutritional research, a specific issue is about understanding how to provide a clear and solid proof of the health effects of each functional food. The problems range from regulatory perspectives down to very basic methodological issues. In addition, when multi-functionality comes into play, then several additional problems are posed in terms of the methodological appropriateness of research done. In this review, a focus is provided on some methodological issues related to (i) the general concepts of 'proving' effects in a methodological perspective and (ii) the difficulties of specifically proving functional effects of food. A specific attention is dedicated on the characteristic problems which, from a methodological perspective, arise when multi-functionality is the matter of the proof.

Effects of encapsulated fruit and vegetable juice powder concentrates on oxidative status in heavy smokers.

OBJECTIVE: Long-term cigarette smoking has negative effects on oxidative status, promoting low-density lipoprotein (LDL) oxidation and formation of lipid peroxides. We evaluated the effects of 2 different encapsulated formulas, consisting primarily of mixed juice powder concentrate, on oxidative status compared with placebo. METHODS: This randomized, double-blind, placebo-controlled study was performed on 101 apparently healthy heavy smokers (>20 cigarettes/d, duration >10 years; median age 47 years, range 41-57 years; 54 M) before and after 3 months' supplementation. Subjects were randomized into 3 groups, well matched for sex and age: (1) placebo; (2) fruit/vegetable (FV); and (3) fruit/vegetable/berry (FVB). Analysis of oxidative status was performed on 75 (46 M) compliant subjects (>95% of assigned capsules). Changes in lipid panel parameters, oxidative-INDEX (Oxy-I, calculated on the basis of serum hydroperoxides and total antioxidant capacity measured by spectrophotometric methods), oxidized-LDL (ox-LDL; enzyme-linked immunosorbent assay [ELISA] method), and malondialdehyde (MDA; gas chromatography-mass spectrometry method) in free (fMDA), bound (bMDA), and total (tMDA = fMDA + bMDA) forms are reported. Statistical analysis was performed with R statistical software. RESULTS: After supplementation, compared with placebo, both FV and FVB groups showed a significant decrease in total cholesterol (p < 0.05), ox-LDL (p = 0.03), and fMDA levels (p = 0.004) accompanied by a slight increase in bMDA concentrations, possibly as the result of fMDA conjugation. Moreover, a significant decrease in Oxy-I was found in both active groups compared with placebo (p < 0.001). CONCLUSION: Intervention with both nutraceutical formulations resulted in improvement in some oxidative alterations attributed to long-term cigarette smoking.