The ProPrems trial: investigating the effects of probiotics on late onset sepsis in very preterm infants

BACKGROUND: Late onset sepsis is a frequent complication of prematurity associated with increased mortality and morbidity. The commensal bacteria of the gastrointestinal tract play a key role in the development of healthy immune responses. Healthy term infants acquire these commensal organisms rapidly after birth. However, colonisation in preterm infants is adversely affected by delivery mode, antibiotic treatment and the intensive care environment. Altered microbiota composition may lead to increased colonisation with pathogenic bacteria, poor immune development and susceptibility to sepsis in the preterm infant.Probiotics are live microorganisms, which when administered in adequate amounts confer health benefits on the host. Amongst numerous bacteriocidal and nutritional roles, they may also favourably modulate host immune responses in local and remote tissues. Meta-analyses of probiotic supplementation in preterm infants report a reduction in mortality and necrotising enterocolitis. Studies with sepsis as an outcome have reported mixed results to date.Allergic diseases are increasing in incidence in "westernised" countries. There is evidence that probiotics may reduce the incidence of these diseases by altering the intestinal microbiota to influence immune function. METHODS/DESIGN: This is a multi-centre, randomised, double blinded, placebo controlled trial investigating supplementing preterm infants born at < 32 weeks' gestation weighing < 1500 g, with a probiotic combination (Bifidobacterium infantis, Streptococcus thermophilus and Bifidobacterium lactis). A total of 1,100 subjects are being recruited in Australia and New Zealand. Infants commence the allocated intervention from soon after the start of feeds until discharge home or term corrected age. The primary outcome is the incidence of at least one episode of definite (blood culture positive) late onset sepsis before 40 weeks corrected age or discharge home. Secondary outcomes include: Necrotising enterocolitis, mortality, antibiotic usage, time to establish full enteral feeds, duration of hospital stay, growth measurements at 6 and 12 months' corrected age and evidence of atopic conditions at 12 months' corrected age. DISCUSSION: Results from previous studies on the use of probiotics to prevent diseases in preterm infants are promising. However, a large clinical trial is required to address outstanding issues regarding safety and efficacy in this vulnerable population. This study will address these important issues. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN012607000144415The product "ABC Dophilus Probiotic Powder for Infants®", Solgar, USA has its 3 probiotics strains registered with the Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ--German Collection of Microorganisms and Cell Cultures) as BB-12 15954, B-02 96579, Th-4 15957

Individual-level predictors of inpatient childhood burn injuries: a case–control study

Abstract Background Burn injuries are considered one of the most preventable public health issue among children; however, are a cause of significant morbidity and mortality in Iran. The aim of this study was to assess individual-level predictors of severe burn injuries among children leading to hospitalization, in East Azerbaijan Province, in North-West of Iran. Methods The study was conducted through a hospital based case–control design involving 281 burn victims and 273 hospital-based controls who were frequency matched on age, gender and urbanity. Both bivariate and multivariate methods were used to analyze the data. Results Mean age of the participants was 40.5 months (95 % CI: 37–44) with the majority of burns occurring at ages between 2 months-13.9 years. It was demonstrated that with increase in the caregiver’s age there was a decrease in the odds of burn injuries (OR = 0.94, 95 % CI: 0.92-0.97). According to the multivariate logistic regression there were independent factors associated with burn injuries including childhood ADHD (OR = 2.82, 95 % CI: 1.68 - 4.76), child’s age (OR = 0.73, 95%CI: 0.67 - 0.80), flammability of clothing (OR = 1.60, 95 % CI: 1.12 - 2.28), daily length of watching television (OR = 1.31, 95 % CI: 1.06 - 1.61), playing outdoors (OR = 1.32, 95 % CI: 1.16 - 1.50) and increment in the economic status (OR = 1.37, 95 % CI: 1.18 - 1.60). Conclusion Major risk predictors of burn injuries among the Iranian population included childhood ADHD, child’s age, watching television, playing outdoors, high economic status and flammable clothing

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Quantitative Spectrophotometric Determination of Propranolol Hydrochloride in Pharmaceuticals Using Cerium(IV) Sulphate as Oxidimetric Reagent

Two simple, selective and economic spectrophotometric methods have been developed and validated for the analysis of the propranolol hydrochloride (PPH) in bulk drug and pharmaceuticals. The methods are based on the oxidation of PPH with cerium(IV) in acid medium and subsequent measurement of the excess cerium(IV) either by its reaction with p-dimethylamino benzaldehyde (pDMAB) and measuring the resulting color at 460 nm (method A) or by its reaction with sulphanilic acid (SAA) to give a pink colored product peaking at 540 nm (method B). The decrease in the absorption intensity of the colored products, due to the presence of the drug has been correlated with its concentration in the sample solution. Different experimental variables affecting the reaction are carefully studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients are found in the concentration ranges of 0.4-7.0 μg ml -1 for method A and 10-200 μg ml -1 for method B, respectively. The calculated molar absorptivity values are 3.72 � 10 4 for method A and 1.43 � 10 3 for method B. The methods have been validated for accuracy, precision, ruggedness and robustness and the results are found to be satisfactory. The proposed methods are successfully applied to the determination of PPH in pure and pharmaceutical dosage forms without any interference from the common excipients. The results obtained by the proposed methods are comparable with those obtained by the official methods

hVMAT2: A Target of Individualized Medication for Parkinson’s Disease

Vesicular monoamine transporter 2 (VMAT2) is responsible for sequestering cytosolically toxic dopamine into intracellular secretory vesicles. Animal genetic studies have suggested that reduced VMAT2 activity contributes to the genetic etiology of Parkinson’s disease (PD), but this role has not been established in humans. Based on human genetic association and meta-analysis, we first confirm the human VMAT2 (hVMAT2 or SLC18A2) promoter as a risk factor for PD in both family and unrelated US white people: marker rs363324 at –11.5 kb in the hVMAT2 promoter is reproducibly associated with PD in a cohort of nuclear families (p = 0.04506 in early-onset PD) and 3 unrelated US white people (meta-analysis p = 0.01879). In SH-SY5Y cells, low activity-associated hVMAT2 promoter confers high methylpiperidinopyrazole iodide cytotoxicity, which is likely attributed to functional polymorphisms bound by nuclear proteins. Interestingly, treatments with the dopamine neuron-protecting agent puerarin upregulates the promoter activity in a haplotype- and cell line-dependent manner. These pharmacogenetic findings suggest that hVMAT2 could be a risk factor and imply it as a target of genetic medications for PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13311-016-0435-5) contains supplementary material, which is available to authorized users