Clinical and Economic Outcomes Associated With the Timing of Initiation of Basal Insulin in Patients With Type 2 Diabetes Mellitus Previously Treated With Oral Antidiabetes Drugs

AbstractPurposeIn patients with type 2 diabetes mellitus (T2DM) not achieving glycemic targets using oral antidiabetes drugs (OADs), studies suggest that timely insulin initiation has clinical benefits. Insulin initiation at the early versus late stage of disease progression has not been explored in detail. This retrospective database analysis investigated clinical and economic outcomes associated with the timing of insulin initiation in patients with T2DM treated with ≥1 OAD in a real-world US setting.MethodsThis study linked data from the Truven Health MarketScan® Commercial database, Medicare Supplemental database, and Quintiles Electronic Medical Records database. A total of 1830 patients with T2DM were included. Patients were grouped according to their OAD use before basal insulin initiation (1, 2, or ≥3 OADs) as a proxy for the timing of insulin initiation. Clinical and economic outcomes were evaluated over 1 year of follow-up.FindingsDuring follow-up the 1 OAD group, compared with the 2 and ≥3 OADs groups, had a greater reduction in glycosylated hemoglobin A1c (−1.7% vs −1.0% vs −0.9%, respectively; P < 0.0001), greater achievement of glycemic target (38.2% vs 26.7% vs 19.6%, respectively; P < 0.0001), and a lower incidence of hypoglycemia (2.7% vs 6.6% vs 5.0%, respectively; P = 0.0002), with no difference in total health care costs ($21,167 vs$21,060 vs $20,133, respectively).ImplicationsThis study shows that early insulin initiation (represented by the 1 OAD group) may be clinically beneficial to patients with T2DM not controlled with OADs, without adding to costs. This supports the call for timely initiation of individualized insulin therapy in this population

Association of neighborhood-level factors with hospitalization for community-associated methicillin-resistant Staphylococcus aureus, New York City, 2006: a multilevel observational study

Background: Hospitalizations with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection have increased in New York City, with substantial geographic variation across neighborhoods. While individual-level risk factors, such as age, sex, HIV infection, and diabetes have been described, the role of neighborhood-level factors (e.g., neighborhood HIV prevalence or income) has not been examined. Methods: To explore plausible neighborhood-level factors associated with CA-MRSA-related hospitalizations, a retrospective analysis was conducted using New York City hospital discharges from 2006 and New York City-specific survey and health department surveillance data. CA-MRSA-related hospitalizations were identified using diagnosis codes and admission information. Associations were determined by using sex-specific multilevel logistic regression. Results: The CA-MRSA hospitalization rate varied by more than six-fold across New York City neighborhoods. Females hospitalized with CA-MRSA had more than twice the odds of residing in neighborhoods in the highest quintile of HIV prevalence (adjusted odds ratio [AOR]Q5 vs. Q1 2.3, 95% CI: 1.2, 2.7). Both males and females hospitalized with CA-MRSA had nearly twice the odds of residing in neighborhoods with moderately high proportion of men who have sex with men (MSM) residing in the neighborhood (males: AORQ4 vs. Q1 1.7, 95% CI: 1.1, 2.7; females: AORQ4 vs. Q1 2.0, 95% CI: 1.1, 3.6); but this association did not hold for neighborhoods in the highest quintile (males: AORQ5 vs. Q1 1.2, 95% CI: 0.76, 1.8; females: AORQ5 vs. Q1 1.5, 95% CI: 0.82, 2.7). Conclusions: Neighborhood-level characteristics were associated with CA-MRSA hospitalization odds, independent of individual-level risk factors, and may contribute to the population-level burden of CA-MRSA infection

Smoking Patterns and Receipt of Cessation Services Among Pregnant Women in Argentina and Uruguay

Introduction: The 5A’s (Ask, Advise, Assess, Assist, and Arrange) strategy, a best-practice approach for cessation counseling, has been widely implemented in high-income countries for pregnant women; however, no studies have evaluated implementation in middle-income countries. The study objectives were to assess smoking patterns and receipt of 5A’s among pregnant women in Buenos Aires, Argentina and Montevideo, Uruguay. Methods: Data were collected through administered questionnaires to women at delivery hospitalizations during October 2011–May 2012. Eligible women attended one of 12 maternity hospitals or 21 associated prenatal care clinics. The questionnaire included demographic data, tobacco use/cessation behaviors, and receipt of the 5A’s. Self-reported cessation was verified with saliva cotinine. Results: Overall, of 3400 pregnant women, 32.8% smoked at the beginning of pregnancy; 11.9% quit upon learning they were pregnant or later during pregnancy, and 20.9% smoked throughout pregnancy. Smoking prevalence varied by country with 16.1% and 26.7% who smoked throughout pregnancy in Argentina and Uruguay, respectively. Among pregnant smokers in Argentina, 23.8% reported that a provider asked them about smoking at more than one prenatal care visit; 18.5% were advised to quit; 5.3% were assessed for readiness to quit, 4.7% were provided assistance, and 0.7% reported follow-up was arranged. In Uruguay, those percentages were 36.3%, 27.9%, 5.4%, 5.6%, and 0.2%, respectively. Conclusions: Approximately, one in six pregnant women smoked throughout pregnancy in Buenos Aires and one in four in Montevideo. However, a low percentage of smokers received any cessation assistance in both countries. Healthcare providers are not fully implementing the recommended 5A’s intervention to help pregnant women quit smoking.Fil: Berrueta, Amanda Mabel. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Morello, Paola. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Alemán, Alicia. Unidad de Investigación Clínica y Epidemiológica Montevideo; UruguayFil: Tong, Van T.. Centers for Disease Control and Prevention; Estados UnidosFil: Johnson, Carolyn. Tulane School of Public Health and Tropical Medicine; Estados UnidosFil: Dietz, Patricia M.. Centers for Disease Control and Prevention; Estados UnidosFil: Farr, Sherry L.. Centers for Disease Control and Prevention; Estados UnidosFil: Mazzoni, Agustina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Colomar, Mercedes. Unidad de Investigación Clínica y Epidemiológica Montevideo; UruguayFil: Ciganda, Alvaro. Unidad de Investigación Clínica y Epidemiológica Montevideo; UruguayFil: Llambi, Laura. Unidad de Investigación Clínica y Epidemiológica Montevideo; UruguayFil: Becú, Ana. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Gibbons, Luz. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Smith, Ruben A.. Centers for Disease Control and Prevention; Estados UnidosFil: Buekens, Pierre. Tulane School of Public Health and Tropical Medicine; Estados UnidosFil: Belizan, Jose. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Althabe, Fernando. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Structure of the γ-D-glutamyl-L-diamino acid endopeptidase YkfC from Bacillus cereus in complex with L-Ala-γ-D-Glu: insights into substrate recognition by NlpC/P60 cysteine peptidases.

Dipeptidyl-peptidase VI from Bacillus sphaericus and YkfC from Bacillus subtilis have both previously been characterized as highly specific γ-D-glutamyl-L-diamino acid endopeptidases. The crystal structure of a YkfC ortholog from Bacillus cereus (BcYkfC) at 1.8 Å resolution revealed that it contains two N-terminal bacterial SH3 (SH3b) domains in addition to the C-terminal catalytic NlpC/P60 domain that is ubiquitous in the very large family of cell-wall-related cysteine peptidases. A bound reaction product (L-Ala-γ-D-Glu) enabled the identification of conserved sequence and structural signatures for recognition of L-Ala and γ-D-Glu and, therefore, provides a clear framework for understanding the substrate specificity observed in dipeptidyl-peptidase VI, YkfC and other NlpC/P60 domains in general. The first SH3b domain plays an important role in defining substrate specificity by contributing to the formation of the active site, such that only murein peptides with a free N-terminal alanine are allowed. A conserved tyrosine in the SH3b domain of the YkfC subfamily is correlated with the presence of a conserved acidic residue in the NlpC/P60 domain and both residues interact with the free amine group of the alanine. This structural feature allows the definition of a subfamily of NlpC/P60 enzymes with the same N-terminal substrate requirements, including a previously characterized cyanobacterial L-alanine-γ-D-glutamate endopeptidase that contains the two key components (an NlpC/P60 domain attached to an SH3b domain) for assembly of a YkfC-like active site

The structure of BVU2987 from Bacteroides vulgatus reveals a superfamily of bacterial periplasmic proteins with possible inhibitory function.

Proteins that contain the DUF2874 domain constitute a new Pfam family PF11396. Members of this family have predominantly been identified in microbes found in the human gut and oral cavity. The crystal structure of one member of this family, BVU2987 from Bacteroides vulgatus, has been determined, revealing a β-lactamase inhibitor protein-like structure with a tandem repeat of domains. Sequence analysis and structural comparisons reveal that BVU2987 and other DUF2874 proteins are related to β-lactamase inhibitor protein, PepSY and SmpA_OmlA proteins and hence are likely to function as inhibitory proteins

Identification of CD4+ T Cell Epitopes in C. burnetii Antigens Targeted by Antibody Responses

Coxiella burnetii is an obligate intracellular Gram-negative bacterium that causes acute Q fever and chronic infections in humans. A killed, whole cell vaccine is efficacious, but vaccination can result in severe local or systemic adverse reactions. Although T cell responses are considered pivotal for vaccine derived protective immunity, the epitope targets of CD4+ T cell responses in C. burnetii vaccination have not been elucidated. Since mapping CD4+ epitopes in a genome with over 2,000 ORFs is resource intensive, we focused on 7 antigens that were known to be targeted by antibody responses. 117 candidate peptides were selected from these antigens based on bioinformatics predictions of binding to the murine MHC class II molecule H-2 IAb. We screened these peptides for recognition by IFN-γ producing CD4+ T cell in phase I C. burnetii whole cell vaccine (PI-WCV) vaccinated C57BL/6 mice and identified 8 distinct epitopes from four different proteins. The identified epitope targets account for 8% of the total vaccination induced IFN-γ producing CD4+ T cells. Given that less than 0.4% of the antigens contained in C. burnetii were screened, this suggests that prioritizing antigens targeted by antibody responses is an efficient strategy to identify at least a subset of CD4+ targets in large pathogens. Finally, we examined the nature of linkage between CD4+ T cell and antibody responses in PI-WCV vaccinated mice. We found a surprisingly non-uniform pattern in the help provided by epitope specific CD4+ T cells for antibody production, which can be specific for the epitope source antigen as well as non-specific. This suggests that a complete map of CD4+ response targets in PI-WCV vaccinated mice will likely include antigens against which no antibody responses are made

Structures of three members of Pfam PF02663 (FmdE) implicated in microbial methanogenesis reveal a conserved α+β core domain and an auxiliary C-terminal treble-clef zinc finger

The first structures from the FmdE Pfam family (PF02663) reveal that some members of this family form tightly intertwined dimers consisting of two domains (N-terminal α+β core and C-terminal zinc-finger domains), whereas others contain only the core domain. The presence of the zinc-finger domain suggests that some members of this family may perform functions associated with transcriptional regulation, protein–protein interaction, RNA binding or metal-ion sensing

Structure of BT_3984, a member of the SusD/RagB family of nutrient-binding molecules

The crystal structure of BT_3984, a SusD-family protein, reveals a TPR N-terminal region providing support for a loop-rich C-terminal subdomain and suggests possible interfaces involved in sus complex formation