Initial Sulfonylurea Use and Subsequent Insulin Therapy in Older Subjects with Type 2 Diabetes Mellitus

BACKGROUND: In type 2 diabetes mellitus (T2DM), progressive loss of beta cell function over time requires treatment intensification and eventually initiation of insulin for many patients. Relative to metformin, a greater rate of decline in beta cell function over time has been observed with sulfonylurea treatment. The present study examined the association between initial monotherapy with metformin or sulfonylurea and subsequent initiation of insulin in older subjects with T2DM. METHODS: In a retrospective cohort study using the GE electronic medical record database, eligible subjects with T2DM included those ≥65 years who received their first prescription of sulfonylurea or metformin as initial monotherapy between January 1, 2003 to December 31, 2008. The follow-up period lasted to the end of 2009 or the subject’s latest data available. Insulin initiation was determined by prescription records. Logistic regression analysis evaluated the likelihood of insulin addition. A Cox regression model estimated time to initiation of insulin. Differences in baseline characteristics were controlled for using propensity score matching. RESULTS: Overall, 12,036 subjects were included in the analysis. Mean age was 75 years and 50% were male. Subjects who initiated with sulfonylurea had a significantly (P < 0.001) higher incidence of insulin addition (2.8% vs. 1.4%) compared to those initiated with metformin within 1 year of follow-up. The likelihood of initiating insulin was higher in subjects initiated with sulfonylurea than with metformin (adjusted odds ratio 1.82, 95% confidence interval [CI] 1.40–2.38; P < 0.001). Sulfonylurea use was also significantly associated with a shorter time to insulin use compared to metformin (adjusted hazards ratio 2.10, 95% CI 1.83–2.39; P < 0.001). CONCLUSION: In a cohort of older subjects with T2DM initiating antihyperglycemic therapy, new users of sulfonylurea monotherapy were more likely to receive insulin therapy and received it earlier than those starting with metformin

Pre-existing cardiovascular diseases and glycemic control in patients with type 2 diabetes mellitus in Europe: a matched cohort study

<p>Abstract</p> <p>Background</p> <p>Although there is a growing body of evidence showing that patients with type 2 diabetes mellitus (T2DM) have poor glycemic control in general, it is not clear whether T2DM patients with pre-existing cardiovascular diseases (CVD) are more or less likely to have good glycemic control than patients without pre-existing CVD. Our aim was to examine the degree of glycemic control among T2DM patients in Europe with and without pre-existing CVD.</p> <p>Methods</p> <p>This is a matched cohort study based on a multi-center, observational study with retrospective medical chart reviews of T2DM patients in Spain, France, United Kingdom, Norway, Finland, Germany, and Poland. Included patients were aged >= 30 years at time of diagnosis of T2DM, had added a SU or a PPARγ agonist to failing metformin monotherapy (index date) and had pre-existing CVD (cases). A control cohort with T2DM without pre-existing CVD was identified using 1:1 propensity score matching. With difference-in-difference approach, logistic and linear regression analyses were applied to identify differences in glycemic control by CVD during the follow up period, after controlling for baseline demographics, clinical information, and concurrent anti-hyperglycemic medication use.</p> <p>Results</p> <p>The percentage of case patients with adequate glycemic control relative to control patients during the 1st, 2nd, 3rd, and 4th years after the index date was 19.9 vs. 26.5, 16.8 vs. 26.5, 18.8 vs. 28.3, and 16.8 vs. 23.5 respectively. Cases were significantly less likely to have adequate glycemic control (odds ratio: 0.62; 95% confidence interval: 0.46-0.82) than controls after adjusting for baseline differences, secular trend, and other potential confounding covariates.</p> <p>Conclusions</p> <p>T2DM patients with pre-existing CVD tended to have poorer glycemic control than those without pre-existing CVD, all other factors being equal. It suggests that clinicians may need to pay more attention to glycemic control among T2DM patients with CVD.</p

Disease burden of urinary tract infections among type 2 diabetes mellitus patients in the U.S.

AbstractAimsType 2 diabetes is a reported risk factor for more frequent and severe urinary tract infections (UTI). We sought to quantify the annual healthcare cost burden of UTI in type 2 diabetic patients.MethodsAdult patients diagnosed with type 2 diabetes were identified in MarketScan administrative claims data. UTI occurrence and costs were assessed during a 1-year period. We examined UTI-related visit and antibiotic costs among patients diagnosed with UTI, comparing those with versus without a history of UTI in the previous year (prevalent vs. incident UTI cases). We estimated the total incremental cost of UTI by comparing all-cause healthcare costs in patients with versus without UTI, using propensity score-matched samples.ResultsWithin the year, 8.2% (6,014/73,151) of subjects had ≥1 UTI, of whom 33.8% had a history of UTI. UTI-related costs among prevalent versus incident cases were, respectively, $603 versus$447 (p=0.033) for outpatient services, $1,607 versus$1,819 (p=NS) for hospitalizations, and $61 versus$35 (p<0.0001) for antibiotics. UTI was associated with a total all-cause incremental cost of $7,045 (95% CI: 4,130, 13,051) per patient with UTI per year.ConclusionsUTI is common and may impose a substantial direct medical cost burden among patients with type 2 diabetes

Lower 30-day readmission rates with roflumilast treatment among patients hospitalized for chronic obstructive pulmonary disease

BACKGROUND: Few data exist related to the impact of roflumilast on health care utilization. This retrospective study estimated 30-day hospital readmission rates between patients who did and did not use roflumilast among those with COPD hospitalizations. METHODS: Data were from MarketScan, a large US commercial health insurance claims database. Patients aged ≥40 years with at least one hospitalization for COPD between 2010 and 2011 were included. The roflumilast group included patients who used roflumilast within 14 days after the first hospitalization (index), while the comparison group (non-roflumilast) included patients who did not use roflumilast during the study period. Continuous enrollment for at least 6 months before and 30 days after the index date was required. The 30-day hospitalization rate was calculated after the index hospitalization. Conditional logistic regression with propensity score 1:3 matching was employed to assess the difference in 30-day hospital readmission rates between the roflumilast and non-roflumilast groups, adjusting for baseline characteristics, comorbidity, health care utilization, and COPD medication use within 14 days after the index date. RESULTS: A total of 15,755 COPD patients met the selection criteria, ie, 366 (2.3%) in the roflumilast group and 15,389 (97.7%) in the non-roflumilast group. The mean (± standard deviation) age was 71±12.5 years and 52% were female. After propensity score matching, all-cause 30-day hospitalization rates were 6.9% and 11.1% in the roflumilast and non-roflumilast groups, respectively. COPD-related 30-day hospitalization rates were 6.3% and 9.2% in the roflumilast and non-roflumilast groups, respectively. Conditional logistic regression identified a significantly lower likelihood of all-cause 30-day readmission (odds ratio 0.59, 95% confidence interval 0.37–0.93, P=0.023) for roflumilast patients relative to non-roflumilast patients. CONCLUSION: This study showed, in a real-world setting, that use of roflumilast was associated with a lower rate of hospital readmission within 30 days among patients hospitalized for COPD

A Disorder-to-Order Transition Activates an ATP-Independent Membrane Protein Chaperone

The 43 kDa subunit of the chloroplast signal recognition particle, cpSRP43, is an ATP-independent chaperone essential for the biogenesis of the light harvesting chlorophyll-binding proteins (LHCP), the most abundant membrane protein family on earth. cpSRP43 is activated by a stromal factor, cpSRP54, to more effectively capture and solubilize LHCPs. The molecular mechanism underlying this chaperone activation is unclear. Here, a combination of hydrogen–deuterium exchange, electron paramagnetic resonance, and NMR spectroscopy experiments reveal that a disorder-to-order transition of the ankyrin repeat motifs in the substrate binding domain of cpSRP43 drives its activation. An analogous coil-to-helix transition in the bridging helix, which connects the ankyrin repeat motifs to the cpSRP54 binding site in the second chromodomain, mediates long-range allosteric communication of cpSRP43 with its activating binding partner. Our results provide a molecular model to explain how the conformational dynamics of cpSRP43 enables regulation of its chaperone activity and suggest a general mechanism by which ATP-independent chaperones with cooperatively folding domains can be regulated

Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering DrugsClinical Perspective: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors)

Reduction in cardiovascular death and hospitalization for heart failure (HHF) was recently reported with the sodium-glucose cotransporter-2 inhibitor (SGLT-2i) empagliflozin in patients with type 2 diabetes mellitus who have atherosclerotic cardiovascular disease. We compared HHF and death in patients newly initiated on any SGLT-2i versus other glucose-lowering drugs in 6 countries to determine if these benefits are seen in real-world practice and across SGLT-2i class

Study of the production of Λb0\Lambda_b^0 and B‾0\overline{B}^0 hadrons in pppp collisions and first measurement of the Λb0→J/ψpK−\Lambda_b^0\rightarrow J/\psi pK^- branching fraction

The product of the $\Lambda_b^0$ ($\overline{B}^0$) differential production cross-section and the branching fraction of the decay $\Lambda_b^0\rightarrow J/\psi pK^-$ ($\overline{B}^0\rightarrow J/\psi\overline{K}^*(892)^0$) is measured as a function of the beauty hadron transverse momentum, $p_{\rm T}$, and rapidity, $y$. The kinematic region of the measurements is $p_{\rm T}<20~{\rm GeV}/c$ and $2.0<y<4.5$. The measurements use a data sample corresponding to an integrated luminosity of $3~{\rm fb}^{-1}$ collected by the LHCb detector in $pp$ collisions at centre-of-mass energies $\sqrt{s}=7~{\rm TeV}$ in 2011 and $\sqrt{s}=8~{\rm TeV}$ in 2012. Based on previous LHCb results of the fragmentation fraction ratio, $f_{\Lambda_B^0}/f_d$, the branching fraction of the decay $\Lambda_b^0\rightarrow J/\psi pK^-$ is measured to be \begin{equation*} \mathcal{B}(\Lambda_b^0\rightarrow J/\psi pK^-)= (3.17\pm0.04\pm0.07\pm0.34^{+0.45}_{-0.28})\times10^{-4}, \end{equation*} where the first uncertainty is statistical, the second is systematic, the third is due to the uncertainty on the branching fraction of the decay $\overline{B}^0\rightarrow J/\psi\overline{K}^*(892)^0$, and the fourth is due to the knowledge of $f_{\Lambda_b^0}/f_d$. The sum of the asymmetries in the production and decay between $\Lambda_b^0$ and $\overline{\Lambda}_b^0$ is also measured as a function of $p_{\rm T}$ and $y$. The previously published branching fraction of $\Lambda_b^0\rightarrow J/\psi p\pi^-$, relative to that of $\Lambda_b^0\rightarrow J/\psi pK^-$, is updated. The branching fractions of $\Lambda_b^0\rightarrow P_c^+(\rightarrow J/\psi p)K^-$ are determined.Comment: 29 pages, 19figures. All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-032.htm

Evidence for the strangeness-changing weak decay Ξb−→Λb0π−\Xi_b^-\to\Lambda_b^0\pi^-

Using a $pp$ collision data sample corresponding to an integrated luminosity of 3.0~fb$^{-1}$, collected by the LHCb detector, we present the first search for the strangeness-changing weak decay $\Xi_b^-\to\Lambda_b^0\pi^-$. No $b$ hadron decay of this type has been seen before. A signal for this decay, corresponding to a significance of 3.2 standard deviations, is reported. The relative rate is measured to be ${{f_{\Xi_b^-}}\over{f_{\Lambda_b^0}}}{\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-) = (5.7\pm1.8^{+0.8}_{-0.9})\times10^{-4}$, where $f_{\Xi_b^-}$ and $f_{\Lambda_b^0}$ are the $b\to\Xi_b^-$ and $b\to\Lambda_b^0$ fragmentation fractions, and ${\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-)$ is the branching fraction. Assuming $f_{\Xi_b^-}/f_{\Lambda_b^0}$ is bounded between 0.1 and 0.3, the branching fraction ${\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-)$ would lie in the range from $(0.57\pm0.21)\%$ to $(0.19\pm0.07)\%$.Comment: 7 pages, 2 figures, All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-047.htm

Measurements of long-range near-side angular correlations in sNN=5\sqrt{s_{\text{NN}}}=5TeV proton-lead collisions in the forward region

Two-particle angular correlations are studied in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of $\sqrt{s_{\text{NN}}}=5$TeV, collected with the LHCb detector at the LHC. The analysis is based on data recorded in two beam configurations, in which either the direction of the proton or that of the lead ion is analysed. The correlations are measured in the laboratory system as a function of relative pseudorapidity, $\Delta\eta$, and relative azimuthal angle, $\Delta\phi$, for events in different classes of event activity and for different bins of particle transverse momentum. In high-activity events a long-range correlation on the near side, $\Delta\phi \approx 0$, is observed in the pseudorapidity range $2.0<\eta<4.9$. This measurement of long-range correlations on the near side in proton-lead collisions extends previous observations into the forward region up to $\eta=4.9$. The correlation increases with growing event activity and is found to be more pronounced in the direction of the lead beam. However, the correlation in the direction of the lead and proton beams are found to be compatible when comparing events with similar absolute activity in the direction analysed.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-040.htm