48 research outputs found

    Work‐Related Outcomes After a Myocardial Infarction

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90385/1/phco.24.16.1515.50946.pd

    Six-month mortality rates are lower in patients with an acute coronary syndrome treated with the combination of clopidogrel and a statin than in patients treated with either therapy alone: An analysis from the global registry of acute coronary events

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    La remunta la podem data de l'any 1928, aproximadament.Primer pla d'un edifici d'habitages, inicialment de planta baixa i pis, en què es remunten tres plantes en la part de la parcel·la que forma xamfrà a tres carrers. La remunta forma un volum molt potent que revalora estèticament l'edifici

    Creatinine monitoring patterns in the setting of direct oral anticoagulant therapy for non-valvular atrial fibrillation

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    Guidelines and experts note that patients with atrial fibrillation require regular renal function monitoring to ensure safe use of direct oral anticoagulants (DOACs). Insufficient monitoring could lead to inappropriate dosing and adverse events. Our objective was to describe the frequency of insufficient creatinine monitoring among patients on DOACs, and to describe clinical factors associated with insufficient monitoring. We hypothesized that renal impairment would be associated with insufficient monitoring. A retrospective cohort study was performed with data from the Michigan Anticoagulant Quality Improvement Initiative. Patients were included if they initiated DOAC therapy for stroke prevention related to atrial fibrillation, remained on therapy for ≥ 1 year, and had baseline creatinine and weight measurements. Creatinine clearance (CrCl) was calculated via Cockcroft-Gault equation. Our outcome was the presence of insufficient creatinine monitoring, defined as: \u3c 1 creatinine level/year for patients with CrCl \u3e 50, or \u3c 2 creatinine levels/year for patients with CrCl ≤ 50. Multivariable analysis was done via logistic regression. Study population included 511 patients. In overall, 14.0% of patients received insufficient monitoring. Among patients with CrCl \u3e 50, 11.5% had \u3c 1 creatinine level/year. Among patients with CrCl ≤ 50, 27.1% received \u3c 2 creatinine levels/year. Baseline renal dysfunction was associated with a higher likelihood of insufficient creatinine monitoring (adjusted odds ratio 3.64, 95% confidence interval 1.81-7.29). This shows a significant gap in the monitoring of patients on DOACs-patients with renal impairment are already at higher risk for adverse events. Future studies are needed to describe the barriers in monitoring these patients and to identify how to optimally address them

    A Prior Myocardial Infarction: How Does it Affect Management and Outcomes in Recurrent Acute Coronary Syndromes?

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    Background Despite improved secondary prevention efforts, acute coronary syndrome (ACS) recurrence among patients with prior history of coronary events remains high. The differences in presentation, management, and subsequent clinical outcomes in patients with and without a prior myocardial infarction (MI) and presenting with another episode of ACS remain unexplored. Methods A total of 3,624 consecutive patients admitted to the University of Michigan with ACS from January 1999 to June 2006 were studied retrospectively. In-hospital management, outcomes, and postdischarge outcomes such as death, stroke, and reinfarction in patients with and without a prior MI were compared. Results Patients with a prior MI were more likely to be older and have a higher incidence of diabetes mellitus, hypertension, hyperlipidemia, and peripheral vascular disease. In-hospital outcomes were not significantly different in the 2 groups, except for a higher incidence of cardiac arrest (4.3% versus 2.5%, p < 0.01) and cardiogenic shock (5.7% versus 3.9%, p = 0.01) among patients without a prior MI. However, at 6 mo postdischarge, the incidences of death (8.0% versus 4.5%, p < 0.0001) and recurrent MI (10.0% versus 5.1%, p < 0.0001) were significantly higher in patients with a prior history of MI compared with those without. Conclusion Patients with prior MI with recurrent ACS remain at a higher risk of major adverse events on follow-up. This may be partly explained by the patients not being on optimal medications at presentation, as well as disease progression. Increased efforts must be directed at prevention of recurrent ACS, as well as further risk stratification of these patients to improve their overall outcomes. Copyright © 2008 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61452/1/20356_ftp.pd

    The Expanded Kinesin-13 Repertoire of Trypanosomes Contains Only One Mitotic Kinesin Indicating Multiple Extra-Nuclear Roles

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    BACKGROUND: Kinesin-13 proteins have a critical role in animal cell mitosis, during which they regulate spindle microtubule dynamics through their depolymerisation activity. Much of what is known about Kinesin-13 function emanates from a relatively small sub-family of proteins containing MCAK and Kif2A/B. However, recent work on kinesins from the much more widely distributed, ancestral Kinesin-13 family, which includes human Kif24, have identified a second function in flagellum length regulation that may exist either alongside or instead of the mitotic role. METHODOLOGY/PRINCIPAL FINDINGS: The African trypanosome Trypanosoma brucei encodes 7 distinct Kinesin-13 proteins, allowing scope for extensive specialisation of roles. Here, we show that of all the trypanosomal Kinesin-13 proteins, only one is nuclear. This protein, TbKIN13-1, is present in the nucleoplasm throughout the cell cycle, but associates with the spindle during mitosis, which in trypanosomes is closed. TbKIN13-1 is necessary for the segregation of both large and mini-chromosomes in this organism and reduction in TbKIN13-1 levels mediated by RNA interference causes deflects in spindle disassembly with spindle-like structures persisting in non-mitotic cells. A second Kinesin-13 is localised to the flagellum tip, but the majority of the Kinesin-13 family members are in neither of these cellular locations. CONCLUSIONS/SIGNIFICANCE: These data show that the expanded Kinesin-13 repertoire of trypanosomes is not associated with diversification of spindle-associated roles. TbKIN13-1 is required for correct spindle function, but the extra-nuclear localisation of the remaining paralogues suggests that the biological roles of the Kinesin-13 family is wider than previously thought

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    The relationship between patient satisfaction with hospitalization and outcomes up to 6 months post-discharge in cardiac patients

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    Little is known about the relationship between patient satisfaction with inpatient care and post-discharge outcomes. This study examined inpatient hospital satisfaction after a cardiac event and outcomes through 6 months post-discharge. We examined 327 cardiac patients from the Bridging the Discharge Gap Effectively database who completed a patient satisfaction survey about their hospital admission and had post-discharge outcomes data. Higher patient satisfaction with the discharge process correlated with fewer readmissions at 90 days post-discharge. Higher patient satisfaction with hospital staff management of personal issues correlated with fewer emergency department visits at 6 months post-discharge. Higher patient satisfaction with overall assessment of care and hospitalization correlated with lower mortality rate at 6 months post-discharge. Being nonwhite correlated with lower nursing care satisfaction. Associations between cardiac patient satisfaction and outcomes exist. In this population, higher patient satisfaction correlated with better outcomes. Patient satisfaction data may be able to inform areas for health system improvement
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