Impact of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on renal and mortality outcomes in people with Type 2 diabetes and proteinuria.

AIM: To assess the impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on renal and mortality outcomes in people with Type 2 diabetes and proteinuria. METHODS: A literature search up to 6 June 2019 was performed. We included randomized trials of ≥100 participants with Type 2 diabetes and micro- or macroalbuminuria comparing an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker with placebo ± background anti-hypertensives or non-angiotensin-converting enzyme inhibitor or angiotensin receptor blocker-containing anti-hypertensives, which included follow-up of ≥12 months. Endpoints included doubling of serum creatinine, end-stage renal disease, all-cause and cardiovascular mortality and progression and regression of proteinuria. A Hartung-Knapp random-effects model (between-study variance calculated using the Paule-Mandel estimator) producing a risk ratio with 95% confidence interval was employed. RESULTS: The use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker was not associated with a significant reduction in the risk of a doubling in serum creatinine (n = 7 trials, RR = 0.77, 95% CI = 0.50-1.21). Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers reduced the risk of progressing to end-stage renal disease (n = 8, RR = 0.79, 95% CI = 0.75-0.83). No difference in all-cause (n = 11, RR = 0.98, 95% CI = 0.89-1.08) or cardiovascular mortality (n = 6 trials, RR = 1.08, 95% CI = 0.92-1.28), nor the composite outcome of doubling in serum creatinine, end-stage renal disease or mortality (n = 3 trials, RR = 0.87, 95% CI = 0.72-1.06), was observed. Progression of proteinuria was decreased with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use vs. control (n = 10, RR = 0.49, 95% CI = 0.33-0.74). Regression of proteinuria was not improved with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (n = 11, RR = 1.55, 95% CI = 0.93-2.58). CONCLUSION: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may reduce the risk of end-stage renal disease and slow the progression of nephropathy, but they do not appear to decrease all-cause or cardiovascular mortality in people with Type 2 diabetes and proteinuria.

Economic evaluations of fluticasone-propionate/salmeterol combination therapy for chronic obstructive pulmonary disease: a review of published studies.

This review identifies and evaluates the comprehensive reporting of peer-reviewed economic evaluations of the effectiveness of fluticasone-propionate/salmeterol combination (FSC) therapy for maintenance treatment of chronic obstructive pulmonary disease (COPD). Economic evaluations were included if published in English since 2003. Evaluation categories included in the review were cost-effectiveness, cost-utility, and cost-consequence analyses. FSC is cost-effective in comparison to short-acting bronchodilators (SABDs). Cost and outcome differences between FSC and other long-acting therapies were modest. Studies exhibited large variations in populations, designs and environment, limiting the ability to draw conclusions. Many new maintenance treatments for COPD have been approved since 2010. Most have yet to be compared to older treatments like FSC. Evaluations are needed that consider costs and outcomes from a societal perspective (e.g., patients' ability to keep working) and evaluations that include subgroup analyses to investigate differential impacts according to clusters of patient characteristics.

[Diagnostic instruments of delirium]. / Outils diagnostiques de l'état confusionnel aigu.

Delirium is a frequent medical problem in hospitalized patients and is often underdiagnosed in spite its high morbidity and mortality. Early diagnosis and treatment are mandatory. Amongst diagnostic instruments currently available, the Confusion Assessment Method (CAM) appears to be the best bedside tool due to its performance and rapidity of use. An adaptation for intensive care patients, CAM-ICU, has also been validated.

Essential role of choline for pneumococcal virulence in an experimental model of meningitis.

OBJECTIVES: The goal of the present study was to elucidate the contribution of the newly recognized virulence factor choline to the pathogenesis of Streptococcus pneumoniae in an animal model of meningitis. RESULTS: The choline containing strain D39Cho(-) and its isogenic choline-free derivative D39Cho(-)licA64--each expressing the capsule polysaccharide 2--were introduced intracisternally at an inoculum size of 10(3) CFU into 11 days old Wistar rats. During the first 8 h post infection both strains multiplied and stimulated a similar immune response that involved expression of high levels of proinflammatory cytokines, the matrix metalloproteinase 9 (MMP-9), IL-10, and the influx of white blood cells into the CSF. Virtually identical immune response was also elicited by intracisternal inoculation of 10(7) CFU equivalents of either choline-containing or choline-free cell walls. At sampling times past 8 h strain D39Cho(-) continued to replicate accompanied by an intense inflammatory response and strong granulocytic pleiocytosis. Animals infected with D39Cho(-) died within 20 h and histopathology revealed brain damage in the cerebral cortex and hippocampus. In contrast, the initial immune response generated by the choline-free strain D39Cho(-)licA64 began to decline after the first 8 h accompanied by elimination of the bacteria from the CSF in parallel with a strong WBC response peaking at 8 h after infection. All animals survived and there was no evidence for brain damage. CONCLUSION: Choline in the cell wall is essential for pneumococci to remain highly virulent and survive within the host and establish pneumococcal meningitis.

Phenotypic variability of beta-glucoside utilization and its correlation to pathogenesis process in a few enteric bacteria.

Utilization of beta-glucosides is markedly variable in the members of the family Enterobacteriaceae. The results presented here provide molecular clues for evolutionary events that resulted in the phenotypic variability seen amongst the members of these species. The genomic hybridization of selected Enterobacteriaceae members with the Escherichia coli bgl and cel genes resulted in detection of a complete homolog of the bgl and cel operons in Shigella sonnei, a member that is evolutionarily closest to E. coli. However, the Salmonella group of organisms have been shown to carry only a homolog of bglR and bglG regions and the deletions of the bglF and bglB genes. Similarly, Proteus mirabilis, Enterobacter aerogenes and a non-enteric Gram-negative bacterium Pseudomonas aeruginosa have been shown to carry a homolog of the bglR and bglG regions and deletions of the bglF and bglB genes. The homolog of the cel operon could be identified in S. sonnei and Salmonella groups of organisms. Possible implications of these observations, in connection with the phenotypic variability seen in beta-glucoside utilization amongst these members, are discussed.

Plasmid-mediated suppression of the mutational activation of the bgl operon in Shigella sonnei.

SSOR, a clinical isolate of Shigella sonnei which exhibits a Salicin-negative phenotype, is unable to mutate to give rise to Sal+ derivatives although a homolog of the Escherichia coli bgl operon is retained by the strain. This was correlated to the presence of an endogenous plasmid in the strain. A plasmid-cured derivative, AK711, could give rise to Sal+ mutants in two steps. Introduction of the plasmid DNA, extracted from SSOR, into various strains of E. coli and S. sonnei, resulted in ampicillin resistant transformants. Interestingly, the presence of the plasmid suppressed the mutational activation of the bgl operon in the transformants. This was further substantiated by the observation that, transformants that have lost the plasmid regained the ability for mutational activation of the bgl operon. Preliminary characterisation of the plasmid indicated a size of 3.8 kb with an origin of replication resembling that of ColE1 replicons and the bla gene homolog of Tn3. Observations of the mutation frequency at the srl and lac loci in the presence of the plasmid indicate that there is a reduction in the mutation frequency, suggesting an antimutator activity associated with the plasmid.