Randomized clinical trial of the efficacy and safety of preservative-free tafluprost and timolol in patients with open-angle glaucoma or ocular hypertension.

PURPOSE: To compare the efficacy and safety of tafluprost, a preservative-free (PF) prostaglandin analogue, with PF timolol in patients with open-angle glaucoma or ocular hypertension. DESIGN: Randomized, double-masked, multicenter clinical trial. METHODS: After discontinuation and washout of existing ocular hypotensive treatment, patients who had intraocular pressure (IOP) ≥23 and ≤36 mm Hg in at least 1 eye at the 08:00 hour time point were randomized 1:1 to 12 weeks of treatment with either PF tafluprost 0.0015% or PF timolol 0.5%. IOP was measured 3 times during the day (08:00, 10:00, 16:00 hours) at baseline and at weeks 2, 6, and 12. It was hypothesized that PF tafluprost would be noninferior to PF timolol over 12 weeks with regard to change from baseline IOP. The trial was powered for a noninferiority margin of 1.5 mm Hg at each of the 9 time points assessed. RESULTS: A total of 643 patients were randomized and 618 completed (PF tafluprost = 306, PF timolol = 312). IOPs at the 3 time points assessed during the baseline visit ranged from 23.8 to 26.1 mm Hg in the PF tafluprost group and 23.5 to 26.0 mm Hg in the PF timolol group. IOPs at the 3 time points assessed during the 12-week visit ranged from 17.4 to 18.6 mm Hg for PF tafluprost and 17.9 to 18.5 mm Hg for PF timolol. At all 9 time points, the upper limits of the 2-sided 95% confidence intervals for the difference between treatments in IOP lowering were less than the prespecified noninferiority margin. Similar percentages of PF tafluprost and PF timolol patients reported ocular pain/stinging/irritation (4.4% vs 4.6%) and pruritus (2.5% vs 1.5%). The percentages of PF tafluprost and PF timolol patients reporting conjunctival hyperemia were 4.4% vs 1.2% (nominal P = .016). CONCLUSIONS: The IOP-lowering effect of PF tafluprost was noninferior to that of PF timolol. PF tafluprost is an efficacious and generally well-tolerated ocular hypotensive agent.

Efficacy and safety of sitagliptin in the treatment of patients with type 2 diabetes in China, India, and Korea.

The efficacy and safety of sitagliptin as monotherapy were evaluated in Chinese, Indian, and Korean patients with type 2 diabetes inadequately controlled by diet and exercise. In a randomized, placebo-controlled, double-blind, 18-week trial, 530 patients with HbA(1c) >or=7.5% and

A novel Staphylococcus aureus vaccine: iron surface determinant B induces rapid antibody responses in rhesus macaques and specific increased survival in a murine S. aureus sepsis model.

Staphylococcus aureus is a major cause of nosocomial infections worldwide, and the rate of resistance to clinically relevant antibiotics, such as methicillin, is increasing; furthermore, there has been an increase in the number of methicillin-resistant S. aureus community-acquired infections. Effective treatment and prevention strategies are urgently needed. We investigated the potential of the S. aureus surface protein iron surface determinant B (IsdB) as a prophylactic vaccine against S. aureus infection. IsdB is an iron-sequestering protein that is conserved in diverse S. aureus clinical isolates, both methicillin resistant and methicillin sensitive, and it is expressed on the surface of all isolates tested. The vaccine was highly immunogenic in mice when it was formulated with amorphous aluminum hydroxyphosphate sulfate adjuvant, and the resulting antibody responses were associated with reproducible and significant protection in animal models of infection. The specificity of the protective immune responses in mice was demonstrated by using an S. aureus strain deficient for IsdB and HarA, a protein with a high level of identity to IsdB. We also demonstrated that IsdB is highly immunogenic in rhesus macaques, inducing a more-than-fivefold increase in antibody titers after a single immunization. Based on the data presented here, IsdB has excellent prospects for use as a vaccine against S. aureus disease in humans.

Evaluation of a multilocus sequence typing system for Staphylococcus epidermidis.

Staphylococcus epidermidis is a significant cause of nosocomial disease. However, the taxonomy of this pathogen, particularly at subspecies level, is unclear. A multilocus sequence typing (MLST) scheme has therefore been investigated as a tool to elucidate taxonomic relationships within this group, based on genetic relatedness. DNA sequences for internal fragments of seven housekeeping genes were compared in 47 geographically and temporally diverse S. epidermidis isolates that were obtained from clinical infections. Twenty-three different allelic profiles were detected; 17 of these were represented by single strains and the largest profile group contained 17 isolates. Diversity of the same collection of isolates was investigated by using PFGE of SmaI-digested genomic DNA to test the discrimination and validity of the MLST approach. Isolates within the largest profile group were resolved into four distinct PFGE clusters on the basis of their SmaI digest patterns. Isolates within other profile groups that contained multiple isolates had matching PFGE SmaI patterns within each group. It appears that MLST is an effective method for grouping S. epidermidis strains at the subspecies level; however, it is not as discriminatory as it has been for other species for which MLST schemes have been established and, used alone, would not be a useful method for epidemiological studies. In addition, it was demonstrated that this method was effective for confirming the identity of S. epidermidis CoNS (coagulase-negative) isolates.