Aim
To compare the efficacy and safety of once‐weekly (OW) semaglutide versus thrice‐daily (TID) insulin aspart (IAsp) in participants with inadequately controlled type 2 diabetes (T2D) treated with ...insulin glargine (IGlar) and metformin.
Materials and Methods
SUSTAIN 11 (NCT03689374) was a randomized (1:1), parallel, open‐label, multinational, phase 3b trial. After a 12‐week run‐in to optimize once‐daily IGlar U100, 1748 adults with T2D (HbA1c >7.5% to ≤10.0%) were randomized to OW semaglutide or TID IAsp as add‐on to optimized IGlar and metformin for 52 weeks. The primary outcome was change in HbA1c from randomization to week 52. Confirmatory secondary endpoints included the occurrence of severe hypoglycaemic episodes and change in body weight (BW). Safety was assessed.
Results
HbA1c (randomization: 8.6% 70.0 mmol/mol) decreased by 1.5% points (16.6 mmol/mol) and 1.2% points (13.4 mmol/mol) with semaglutide (n = 874) and IAsp (n = 874), respectively (estimated treatment difference ETD −0.29% points 95% confidence interval {CI} −0.38; −0.20; P < .0001 for non‐inferiority). Few severe hypoglycaemic episodes were recorded in either group, with no statistically significant difference between the groups. Change in BW from randomization (87.9 kg) to week 52 was in favour of semaglutide (−4.1 kg) versus IAsp (+2.8 kg) (ETD −6.99 kg 95% CI −7.41; −6.57). A higher proportion of participants experienced adverse events with semaglutide (58.5%) versus IAsp (52.1%); most were mild to moderate.
Conclusions
In this basal insulin‐treated population, OW semaglutide improved glycaemic control to a greater extent than TID IAsp and provided numerically greater weight loss.
Full text
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Several major invasive bacterial pathogens are encapsulated. Expression of a polysaccharide capsule is essential for survival in the blood, and thus for virulence, but also is a target for host ...antibodies and the basis for effective vaccines. Encapsulated species typically exhibit antigenic variation and express one of a number of immunochemically distinct capsular polysaccharides that define serotypes. We provide the sequences of the capsular biosynthetic genes of all 90 serotypes of Streptococcus pneumoniae and relate these to the known polysaccharide structures and patterns of immunological reactivity of typing sera, thereby providing the most complete understanding of the genetics and origins of bacterial polysaccharide diversity, laying the foundations for molecular serotyping. This is the first time, to our knowledge, that a complete repertoire of capsular biosynthetic genes has been available, enabling a holistic analysis of a bacterial polysaccharide biosynthesis system. Remarkably, the total size of alternative coding DNA at this one locus exceeds 1.8 Mbp, almost equivalent to the entire S. pneumoniae chromosomal complement.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Active surveillance of invasive group A streptococcal (GAS) infections was conducted in Denmark during 2003 and 2004 as a part of the Strep-EURO initiative. The main objective was to improve ...understanding of the epidemiology of invasive GAS disease in Denmark. During the 2 years, 278 cases were reported, corresponding to a mean annual incidence of 2.6 cases per 100,000 inhabitants. The vast majority of isolates, 253 (91%), were from blood, with the remaining 25 (9%) being from cerebrospinal fluid, joints, or other normally sterile sites. The mean case fatality rate (CFR) was 20%, with the rate being higher in patients more than 70 years of age (36.5%). For streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis the CFRs were 53% and 25%, respectively. Out of 16 T types recorded, three predominated: T28 (23%), T1 (22%), and the cluster T3/13/B3264 (14%). Among 29 different emm types, emm28 and emm1 accounted for 51% of strains, followed by emm3 (11%), emm89 (7%), and emm12 (5.5%). Low resistance rates were detected for macrolide-lincosamide-streptogramin B (MLSB) antibiotics (3%) and tetracycline (8%); two isolates exhibited coresistance to tetracycline and macrolides. Of nine pyrogenic exotoxin (superantigen) genes examined, speA and speC were identified in 58% and 40% of the strains, respectively; either of the genes was present in all strains causing STSS. Most strains harbored speG (99%). ssa was present in 14% of the isolates only. In Denmark, as in comparable countries, GAS invasive disease shows a sustained, high endemicity, with involvement of both established and emerging streptococcal emm and T types.
The risk of invasive pneumococcal disease is increased among children with some chronic diseases. The objective of this study was to quantify the risk of invasive pneumococcal disease in a wide range ...of chronic diseases.
Cases of invasive pneumococcal disease among children (aged 0-17 years) were identified from 1977 through 2005 by using a national surveillance program in Denmark. Rate ratios were assessed in a case-control study by using 10 age- and gender-matched controls per case. Chronic diseases were defined a priori.
Among 1655 children with invasive pneumococcal disease, 19% had a history of chronic disease, according to our definition, versus 5% of controls. An increased risk of invasive pneumococcal disease was observed for children followed >30 days after initial hospital contact for a chronic disease, but it was also increased in children with >or=5 hospital contacts for any other reason. Children with a history of cancer, chronic renal disease, splenectomy, and transplantation were particularly susceptible to invasive pneumococcal disease. Adjusted for number of hospital contacts, the risk for children with other types of chronic disease was 1.4-fold more than for those with hospital contacts for any reason.
Cancer, chronic renal diseases, splenectomy, and transplantation were strongly associated with an increased risk of invasive pneumococcal disease in children. For children with other chronic diseases, their excess risk seemed to be attributable mostly to frail children having repeated hospital contact rather than their underlying condition.
Diabetes-related foot ulcers (DFUs) and their sequelae result in large patient and societal burdens. Long-term data determining the efficacy of individual glucose-lowering agents on DFUs are lacking. ...Using existing data from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, we conducted post hoc analyses assessing the impact of liraglutide versus placebo in people with type 2 diabetes and at high risk of cardiovascular (CV) events on the incidence of DFUs and their sequelae.
The LEADER trial (NCT01179048) was a randomized, double-blind, multicenter, CV outcomes trial assessing liraglutide (1.8 mg/day) versus placebo, in addition to standard of care, for up to 5 years. Information on DFUs was collected systematically during the trial, and DFU complications were assessed post hoc through reviewing case narratives.
During a median of 3.8 years' follow-up, similar proportions of patients reported at least one episode of DFU in the liraglutide and placebo groups (3.8% 176/4,668 versus 4.1% 191/4,672, respectively; hazard ratio HR 0.92 95% CI 0.75, 1.13;
= 0.41). Analysis of DFU-related complications demonstrated a significant reduction in amputations with liraglutide versus placebo (HR 0.65 95% CI 0.45, 0.95;
= 0.03). However, no differences were found for foot infections, involvement of underlying structures, or peripheral revascularization in the main analysis.
Treatment with liraglutide in patients with type 2 diabetes and at high risk of CV events in the LEADER trial did not increase the risk of DFU events and was associated with a significantly lower risk of DFU-related amputations compared with placebo. This association, possibly due to chance, needs further investigation.
Danish nationwide surveillance data on invasive pneumococcal disease from the 5-year period from 1995 to 1999, including 5,452 isolates, are presented and described. Annual overall incidence rates, ...serotype distribution, and antimicrobial susceptibility patterns of the isolates were monitored. Major changes in the total annual incidence rate from 27/100,000 in 1996 to 17/100,000 in 1999 and a significant change in the proportion of invasive isolates belonging to types 1 and 12F were observed. The serotype coverage rate by the 23-valent polysaccharide vaccine among the elderly was 92.9%, and the serotype coverage rate by the 7-, 9-, and 11-valent pneumococcal conjugate vaccines among children less than 2 years old were 71.7, 75.2, and 81.4%, respectively. Invasive isolates with reduced susceptibility to penicillin or erythromycin increased from 1995 to 1999, with a high proportion of the penicillin-nonsusceptible invasive isolates originating from people 60 years old or older (57.0%). These observations underline the importance of adequate surveillance systems of invasive pneumococcal disease to introduce and maintain national vaccine strategies and adequate antibiotic policy.
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