Effect of intensive versus standard blood pressure control on major adverse cardiac events and serious adverse events: A bivariate analysis of randomized controlled trials

Background: Intensive blood pressure (BP) lowering may offer protective effects against major adverse cardiac event (MACE) but is also associated with a greater risk of a serious adverse event (SAE). The risk-benefit profile of intensive versus standard BP control has not been comprehensively assessed. Methods: Four studies were identified from a systematic literature search for randomized controlled trials comparing intensive versus standard BP lowering that reported both MACE and SAE endpoints. A previously described statistical approach was applied to characterize the efficacy-safety tradeoff of BP control. The bivariate outcome was computed to quantitatively assess the net clinical benefit (NCB) of intensive BP lowering as compared to standard treatment, with positive values indicating increased risks and negative values indicating decreased risks. Results: Data from the SPRINT trial demonstrated that intensive strategy was superior in MACE but inferior in SAE, thereby eroding the NCB (bivariate outcome: 0.33% [?0.50% to 1.21%]). Intensive strategy from the SPS3 trial fulfilled non-inferiority in both MACE and SAE but did not reach a favorable NCB (?1.31% [?2.25% to 0.01%]). The ACCORD trial suggested that intensive strategy was non-inferior in MACE but inferior in SAE (?0.19% [?0.79% to 1.37%]). Results from the VALISH trial were inconclusive for SAE but suggested non-inferiority in MACE (?1.19% [?3.24% to 0.68%]). Conclusions: Compared to the standard blood pressure target, pooled data from randomized controlled trials suggest that intensive strategy did not achieve a net clinical benefit when weighing the benefit of MACE reduction against the risk of SAE under the bivariate framework.Abbreviations: Blood pressure (BP), diastolic blood pressure (DBP), major adverse cardiac event (MACE), net clinical benefit (NCB), serious adverse event (SAE), systolic blood pressure (SBP).     

Antimycobacterial action of a new glycolipid‐peptide complex obtained from extracellular metabolites of Raoultella ornithinolytica

In this paper, an antimycobacterial component of extracellular metabolites of a gut bacterium Raoultella ornithinolytica from D. veneta earthworms was isolated and its antimycobacterial action was tested using Mycobacterium smegmatis. After incubation with the complex obtained, formation of pores and furrows in cell walls was observed using microscopic techniques. The cells lost their shape, stuck together and formed clusters. Surface‐enhanced Raman spectroscopy analysis showed that, after incubation, the complex was attached to the cell walls of the Mycobacterium. Analyses of the component performed with Fourier transform infrared spectroscopy demonstrated high similarity to a bacteriocin nisin, but energy dispersive X‐ray spectroscopy analysis revealed differences in the elemental composition of this antimicrobial peptide. The component with antimycobacterial activity was identified using mass spectrometry techniques as a glycolipid–peptide complex. As it exhibits no cytotoxicity on normal human fibroblasts, the glycolipid–peptide complex appears to be a promising compound for investigations of its activity against pathogenic mycobacteria.     

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in children 6–59 months of age: A phase 3, randomized,noninferiority study

Background

In the Southern Hemisphere 2010 influenza season, Seqirus’ split-virion, trivalent inactivated influenza vaccine was associated with increased reports of fevers and febrile reactions in young children. A staged clinical development program of a quadrivalent vaccine (Seqirus IIV4 [S-IIV4]; Afluria® Quadrivalent/Afluria Quad?/Afluria Tetra?), wherein each vaccine strain is split using a higher detergent concentration to reduce lipid content (considered the cause of the increased fevers and febrile reactions), is now complete.

Dietary and oral hygiene habits in children with type I diabetes mellitus related to dental caries

The aims of the study were to evaluate differences in dietary, oral hygiene habits and social class in children with Type I diabetes mellitus (DM), compared to non-diabetics, and to investigate relationship between selected caries-risk factors and caries experience in diabetics. MATERIAL AND METHODS: 70 children with Type I DM and 70 age- and sex-matched non-diabetic controls were included in the study. Metabolic control of diabetes was categorized into well- to- moderately-controlled and poorly-controlled groups based on glycosylated haemoglobin HbA1c. The study was based on the data obtained from the questionnaire including information about dietary and oral hygiene habits, pattern of dental visits and social class. Results showed that the diabetic children had more frequent main meals and less snacking than their controls: the mean number of main meals/day was 4.33 (SD = 0.93) in the diabetics, and 2.53 (SD = 0.85) in the controls. Significantly less diabetics (43%) used sweet drinks than their controls (79%). There were no differences according to the frequency of toothbrushing as well as frequency of dental visits between the diabetics and controls, however, significantly more diabetics reported that they never used dental floss than non-diabetics. There were no significant differences in the diet, toothbrushing frequency between the diabetics with different metabolic control. Multiple logistic regression analysis showed that among caries risk associated variables only age of children (OR = 1.98; CI = 1.23-3.19) and level of metabolic control of diabetes (OR = 4.65; CI = 1.28-16.89) were statistically significantly associated with high caries experience in the diabetics. CONCLUSIONS: Frequent consumption of sweet drinks and snacks can influence caries development in children. Amongst the diabetics, the differences in caries prevalence can be explained by combination of biological and behavioral factors rather than single dietary or oral hygiene elements.     

The complement system in primary Sjögren’s syndrome: the expression of certain cascade and regulatory proteins in labial salivary glands – observational study

IntroductionThe complement cascade and regulatory proteins are involved in the pathogenesis of the Sjögren’s syndrome and other autoimmune diseases. The complement activation via the alternative pathway was recognized as a major pathogenic mechanism in autoimmune conditions. The aim of this study was to assess expression of complement cascade components and regulatory proteins in minor salivary glands in patients with primary Sjögren’s syndrome (pSS).Materials and methodsThe expression of C1q and C5b-9 – membrane attack complex and regulatory proteins such as: membrane cofactor protein (MCP), decay-accelerating factor (DAF) and protectin were examined using immunochemistry method in specimens from biopsy of minor salivary glands in pSS patients. The biopsy material was obtained from 20 pSS patients, 5 patients with non-specific sialadenitis and from 5 patients with suspicion of dryness syndrome without sialadenitis confirmation.ResultsNone of the examined samples showed the expression of C1q or the effector C5b-9. Membrane cofactor protein expression was lower in pSS group than in both non-specific sialadenitis and noninflamed salivary glands. The inflammatory cells in pSS samples partially expressed MCP. There were differences in the sites and intensity of membrane protectin expression exclusively on the luminal surfaces in pSS; on the luminal and, partially, antiluminal surface in non-specific inflammation, and on the entire cell surface in unaffected salivary glands. There were no DAF expression in salivary gland tissue in biopsy specimens in all studied subjects.ConclusionsThe study demonstrated the absence of complement-cascade proteins (C1q, MAC) in the salivary glands of pSS patients, which may indicated a lack of local complement activation via the classical pathway and the observed gland tissue damage being due to a mechanism other than MAC-induced cytolysis. The differences in the expression of complement regulatory proteins between pSS, non-specific sialadenitis, and normal salivary glands may indicate that alternative functions of these regulatory proteins may be of greater significance in pSS. Low MCP expression in pSS in comparison with non-specific sialadenitis and normal salivary glands, may suggest altered modulation of cell-mediated immunity in pSS. The differences in the location and intensity of protectin (CD59) expression indicates a possibility of reducing the proinflammatory effect of protectin in pSS.