Predictors of Recurrent Hospitalizations and the Importance of These Hospitalizations for Subsequent Mortality After Incident Transient Ischemic Attack.

BACKGROUND: We examined predictors of recurrent hospitalizations and the importance of these hospitalizations for subsequent mortality after incident transient ischemic attacks (TIA) that have not yet been investigated. METHODS: Adults hospitalized for TIA from 2000 through 2017 were examined for recurrent hospitalizations, days, and percentage of time spent hospitalized and long-term mortality. RESULTS: Of 266 patients hospitalized for TIA, 122 died, 212 had 826 anycondition hospitalization (59 from TIA-related conditions) corresponding to 3384 inpatient days during 1693 person-years of follow-up. Of 42 patient-level characteristics, age greater than or equal to 65 years (Incidence rate ratio [IRR] 1.75, 95% confidence interval [CI] 1.19-2.55), current smoking (IRR 2.15, 95% CI 1.39-3.33), concurrent heart failure (IRR 1.81, 95% CI 1.17-2.80) or anemia (IRR 1.90, 95% CI 1.40-2.48), and no prescription statin (IRR 1.45, 95% CI 1.04-2.03, P = .0289) emerged as significant predictors of anycondition rehospitalization. All these variables except heart failure remained significant predictors of TIA-related rehospitalizations. All-cause mortality was significantly increased after each hospitalization from anycondition (hazard ratio [HR] 1.32, 95% CI 1.26-1.39), TIA-related condition (HR 1.72; 95% CI 1.28-2.30), and per each day (HR 1.05, 95% CI 1.04-1.05) and per 1% of follow-up time spent hospitalized from anycondition (HR 1.45, 95% CI 1.34-1.58). CONCLUSIONS: Older age, current tobacco smoking, concurrent heart failure or anemia, and no prescription statin, easily measured patient-level characteristics, identifies patients with TIA at high risk for recurrent hospitalizations and the burden of these hospitalizations predicts subsequent mortality.

Five-Year Mortality After Transient Ischemic Attack: Focus on Cardiometabolic Comorbidity and Hospital Readmission.

BACKGROUND AND PURPOSE: We aimed at providing estimates of mortality associated with cardiometabolic comorbidity and incident readmission from cardiometabolic as compared with noncardiometabolic conditions after a first transient ischemic attack. METHODS: Between 2000 and 2015, patients hospitalized for a first transient ischemic attack were examined for cardiometabolic comorbidities (diabetes mellitus, coronary artery disease, heart failure, and atrial fibrillation), 5-year incident hospitalization, and time to death. RESULTS: Of 251 patients with transient ischemic attack, 134 (53%) had at least 1 and 55 (22%) had at least 2 cardiometabolic conditions. By 5 years, 491 readmissions (134 [27%] cardiometabolic and 357 [73%] noncardiometabolic) and 75 deaths (27 [36%] cardiometabolic and 47 [64%] noncardiometabolic) were observed. Mortality was increased with any concurrent cardiometabolic comorbidity (hazard ratio, 1.89; 95% confidence interval, 1.17-3.03; P=0.0089) with multiplicative mortality risk from a combination of coronary artery disease and heart failure. Each hospitalization was associated with a 1.5-fold risk of death (95% confidence interval, 1.37-1.64; P<0.0001). Risk of cardiometabolic and noncardiometabolic mortality was correlated with the corresponding category-specific readmission. CONCLUSIONS: Among patients hospitalized for first transient ischemic attack, 5-year mortality is associated with concurrent cardiometabolic comorbidity and rates of subsequent hospitalization.

The Effects of Caffeine on Arousal, Response Time, Accuracy, and Performance in Division I Collegiate Fencers.

Doyle, TP, Lutz, RS, Pellegrino, JK, Sanders, DJ, and Arent, SM. The effects of caffeine on arousal, response time, accuracy, and performance in Division I collegiate fencers. J Strength Cond Res 30(11): 3228-3235, 2016-Caffeine has displayed ergogenic effects on aerobic performance. However, sports requiring precision and quick reaction may also be impacted by central nervous system arousal because of caffeine consumption. The purpose of this study was to assess the effects of caffeine on arousal, response time (RT), and accuracy during a simulated fencing practice. Using a randomized, within-subjects, placebo-controlled, double-blind design, Division I male and female college fencers (N = 13; 69.1 ± 3.5 kg) were administered caffeine doses of 0, 1.5, 3.0, 4.5, 6.0, or 7.5 mg·kg during separate testing days. Performance was assessed via RT and accuracy to a 4-choice reaction task. A total of 25 trials were performed each day using a random 2- to 8-s delay between trials. Arousal was assessed using the activation-deactivation adjective check list. Results of repeated-measures multivariate analysis of variance revealed a significant dose effect (p = 0.02) on performance. Follow-up analyses indicated this was due to a significant effect for RT (p = 0.03), with the dose-response curve exhibiting a quadratic relationship. Response time was significantly faster (p < 0.01) for the 1.5, 3.0, and 6.0 mg·kg conditions than for the placebo condition. Results also indicated a significant dose effect for composite RT + accuracy performance (p < 0.01). The dose-response curve was again quadratic, with performance beginning to deteriorate at 7.5 mg·kg. Energetic arousal, tiredness, tension, and calmness all significantly changed as a function of caffeine dose (p ≤ 0.05). Based on these results, caffeine improves RT and overall performance in fencers, particularly as doses increase up to 4.5-6.0 mg·kg. Above this level, performance begins to deteriorate, consistent with an "inverted-U" model of arousal and performance.

Association of hyperlipidaemia with 5-year survival after hospitalisation for acute myocardial infarction: a propensity score matched analysis.

Objectives: The primary objective was to examine the association between hyperlipidaemia (HLP) and 5-year survival after incident acute myocardial infarction (AMI). The secondary objectives were to assess the effect of HLP on survival to discharge across patient subgroups, and the impact of statin prescription, intensity and long-term statin adherence on 5-year survival. Methods: Retrospective cohort study of 7071 patients hospitalised for AMI at Mayo Clinic from 2001 through 2011. Of these, 2091 patients with HLP (age (mean±SD) 69.7±13.5) were propensity score matched to 2091 patients without HLP (age 70.6±14.2). Results: In matched patients, HLP was associated with higher rate of survival to discharge than no HLP (95% vs 91%; log-rank <0.0001). At year 5, the adjusted HR for all-cause mortality in patients with HLP versus no HLP was 0.66 (95% CI 0.58-0.74), and patients with prescription statin versus no statin was 0.24 (95% CI 0.21 to 0.28). The mean survival was 0.35 year greater in patients with HLP than in those with no HLP (95% CI 0.25 to 0.46). Patients with HLP gained on an average 0.17 life year and those treated with statin 0.67 life year at 5 years after AMI. The benefit of concurrent HLP was consistent across study subgroups. Conclusions: In patients with AMI, concomitant HLP was associated with increased survival and a net gain in life years, independent of survival benefit from statin therapy. The results also reaffirm the role of statin prescription, intensity and adherence in reducing the mortality after incident AMI.

Initial and subsequent 3-year cost after hospitalization for first acute ischemic stroke and intracerebral hemorrhage.

AIMS: To examine 1) the major drivers of index hospitalization and 3-year post-acute follow-up care, 2) cost for rehabilitation and homecare, and 3) indirect cost from lost productivity after acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH). METHODS: Retrospective study of adults hospitalized with AIS (n = 811) and ICH (N = 145) between 2003 and 2014. Direct costs standardized to Medicare reimbursement rates were captured for hospitalization and 3-year follow-up or death. Adjusted cost estimates were assessed using generalized linear modeling with gamma distribution. Costs for rehabilitation, home healthcare, and lost productivity were assessed using sets of cost captured through literature review. RESULTS: Calculated as mean cost per person: hospitalization $18,154 for AIS and $24,077 for ICH; monthly 3-year aggregate $5138 for AIS and $8172 for ICH; 3-year inpatient rehabilitation $4185 for AIS and $4196 for ICH; homecare $19,728 for AIS and $14,487 for ICH; indirect cost from lost productivity $77,078 for AIS and $56,601 for ICH. Age < 55 years, being non-white, and stroke severity were strongly associated with greater hospitalization cost for AIS and ICH. Hyperlipidemia incurred lower while cancer, coronary artery disease, asthma/chronic obstructive pulmonary disease, heart failure, and anemia incurred higher 3-year aggregate cost for AIS. Cancer and diabetes mellitus incurred higher 3-year aggregate cost for ICH. CONCLUSIONS: We provide estimates of direct and indirect costs incurred for acute and continuing post-acute care through a 3-year follow-up period after first-ever AIS and ICH with important comparisons for predictors between index hospitalization and 3-year post-stroke costs.

Association between hyperlipidemia and mortality after incident acute myocardial infarction or acute decompensated heart failure: a propensity score matched cohort study and a meta-analysis.

OBJECTIVE: To examine the effect of HLP, defined as having a pre-existing or a new in-hospital diagnosis based on low density lipoprotein cholesterol (LDL-C) level ≥100 mg/dL during index hospitalisation or within the preceding 6 months, on all-cause mortality after hospitalisation for acute myocardial infarction (AMI) or acute decompensated heart failure (ADHF) and to determine whether HLP modifies mortality associations of other competing comorbidities. A systematic review and meta-analysis to place the current findings in the context of published literature. DESIGN: Retrospective study, 1:1 propensity-score matching cohorts; a meta-analysis. SETTING: Large academic centre, 1996-2015. PARTICIPANTS: Hospitalised patients with AMI or ADHF. MAIN OUTCOMES AND MEASURES: All-cause mortality and meta-analysis of relative risks (RR). RESULTS: Unmatched cohorts: 13 680 patients with AMI (age (mean) 68.5 ± (SD) 13.7 years; 7894 (58%) with HLP) and 9717 patients with ADHF (age, 73.1±13.7 years; 3668 (38%) with HLP). In matched cohorts, the mortality was lower in AMI patients (n=4348 pairs) with HLP versus no HLP, 5.9 versus 8.6/100 person-years of follow-up, respectively (HR 0.76, 95% CI 0.72 to 0.80). A similar mortality reduction occurred in matched ADHF patients (n=2879 pairs) with or without HLP (12.4 vs 16.3 deaths/100 person-years; HR 0.80, 95% CI 0.75 to 0.86). HRs showed modest reductions when HLP occurred concurrently with other comorbidities. Meta-analyses of nine observational studies showed that HLP was associated with a lower mortality at ≥2 years after incident AMI or ADHF (AMI: RR 0.72, 95% CI 0.69 to 0.76; heart failure (HF): RR 0.67, 95% CI 0.55 to 0.81). CONCLUSIONS: Among matched AMI and ADHF cohorts, concurrent HLP, compared with no HLP, was associated with a lower mortality and attenuation of mortality associations with other competing comorbidities. These findings were supported by a systematic review and meta-analysis.

Incremental risk of long-term mortality with increased burden of comorbidity in hospitalized patients with pneumonia.

BACKGROUND: Patients hospitalized for pneumonia often have concurrent comorbid conditions (CCs). The influence of CCs on the risk of subsequent death is not fully understood. METHODS: We examined adults hospitalized for pneumonia between 1996 through 2015 at Mayo Clinic for the presence of 20 priori selected CCs. We estimated cumulative all-cause mortality by number of CCs using multivariable Cox regression model. RESULTS: Study comprised of 9580 adults (age 70 ±â€¯17.0 years, men 53%, whites 88%) with median number of CCs 3 (interquartile 1-4), and overall deaths 6032 (62.9%) during 50,934 person-years of follow up (118.5 deaths/1000 person-years). After adjustment, any single comorbid condition was associated with 9% greater risk of death (95% confidence interval 1.08-1.11, P < 0.0001). When study cohort was stratified according to number of comorbidities (none, 1, 2, 3, 4, 5, and ≥6 CCs), the risk of death increased as the number of CCs increased (33 for no CCs vs 252 deaths for ≥6 CCs per 1000 person-years). CONCLUSIONS: Long-term mortality after hospitalization for pneumonia increases as the burden of comorbidities increases. Therefore, a simple comorbidity count help improve prognostic accuracy in identifying patients at increased risk of death following an episode of pneumonia.

Effect of early hospital readmission and comorbid conditions on subsequent long-term mortality after transient ischemic attack.

Background: The implications of early readmission on long-term mortality after transient ischemic attack (TIA) are not known. We aimed at examining the effect of 180-day readmission on subsequent long-term mortality after index hospitalization for TIA. Methods: A retrospective study of patients hospitalized for first-ever TIA at Mayo Clinic from 2000 through 2017. Patients readmitted within 180 days postdischarge were compared with those not readmitted in long-term risk of death. Results: Of 251 TIA patients aged 73 ± 15 years with 1509 person-years of follow-up, 65 (26%) were readmitted within 180 days of discharge and 125 died during a median follow-up of 5.7 years. The mortality was 10 vs. 7 deaths per 100 person-years in patients who were readmitted compared to those who were not readmitted with hazard ratio (HR) 1.73 (95% confidence interval [CI] 1.13-2.66). Other competing predictors of mortality were age ≥65 years (HR 5.70, 95% CI 2.72-11.96), cancer (HR 1.65, 95% CI 1.03-3.38), chronic obstructive pulmonary disease (HR 1.90, 95% CI 1.07-3.38), heart failure (HR 3.03, 95% CI 1.82-5.06), dementia (HR 5.87, 95% CI 3.27-10.52), creatinine ≥1.4 mg/dl (HR 1.89, 95% CI 1.17-3.06), and hemoglobin level <10 g/dl (HR 2.80, 95% CI 1.20-6.66). Conclusions: Hospital readmission within 180 days of discharge from index TIA was associated with increased risk of death several years after initial readmission. Older age and several comorbidities identified during index hospitalization also confer increased risk for long-term mortality.

Carboxamide SIRT1 inhibitors block DBC1 binding via an acetylation-independent mechanism.

SIRT1 is an NAD (+) -dependent deacetylase that counteracts multiple disease states associated with aging and may underlie some of the health benefits of calorie restriction. Understanding how SIRT1 is regulated in vivo could therefore lead to new strategies to treat age-related diseases. SIRT1 forms a stable complex with DBC1, an endogenous inhibitor. Little is known regarding the biochemical nature of SIRT1-DBC1 complex formation, how it is regulated and whether or not it is possible to block this interaction pharmacologically. In this study, we show that critical residues within the catalytic core of SIRT1 mediate binding to DBC1 via its N-terminal region, and that several carboxamide SIRT1 inhibitors, including EX-527, can completely block this interaction. We identify two acetylation sites on DBC1 that regulate its ability to bind SIRT1 and suppress its activity. Furthermore, we show that DBC1 itself is a substrate for SIRT1. Surprisingly, the effect of EX-527 on SIRT1-DBC1 binding is independent of DBC1 acetylation. Together, these data show that protein acetylation serves as an endogenous regulatory mechanism for SIRT1-DBC1 binding and illuminate a new path to developing small-molecule modulators of SIRT1.