Simultaneous evaluation of abstinence and relapse using a Markov chain model in smokers enrolled in a two-year randomized trial

Abstract Background GEE and mixed models are powerful tools to compare treatment effects in longitudinal smoking cessation trials. However, they are not capable of assessing the relapse (from abstinent back to smoking) simultaneously with cessation, which can be studied by transition models. Methods We apply a first-order Markov chain model to analyze the transition of smoking status measured every 6 months in a 2-year randomized smoking cessation trial, and to identify what factors are associated with the transition from smoking to abstinent and from abstinent to smoking. Missing values due to non-response are assumed non-ignorable and handled by the selection modeling approach. Results Smokers receiving high-intensity disease management (HDM), of male gender, lower daily cigarette consumption, higher motivation and confidence to quit, and having serious attempts to quit were more likely to become abstinent (OR = 1.48, 1.66, 1.03, 1.15, 1.09 and 1.34, respectively) in the next 6 months. Among those who were abstinent, lower income and stronger nicotine dependence (OR = 1.72 for ≤ vs. > 40 K and OR = 1.75 for first cigarette ≤ vs. > 5 min) were more likely to have relapse in the next 6 months. Conclusions Markov chain models allow investigation of dynamic smoking-abstinence behavior and suggest that relapse is influenced by different factors than cessation. The knowledge of treatments and covariates in transitions in both directions may provide guidance for designing more effective interventions on smoking cessation and relapse prevention. Trial Registration clinicaltrials.gov identifier: NCT00440115Peer Reviewe

Impact of admission blood glucose level on outcomes in community-acquired pneumonia in older adults

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background: Community-acquired pneumonia (CAP) is a common cause of morbidity and mortality in older adults. Although diabetes mellitus is a risk factor for pneumonia, the clinical impact of blood glucose level at the time of admission is not clear. Our goal was to examine the association between admission hyperglycemia and subsequent mortality, length of stay, and readmission outcomes in older adults with CAP. Methods: A retrospective observational study was conducted using hospital data for community-acquired pneumonia admissions in 857 persons from January 1, 2008 to December 31, 2010. We examined the effects of admission glucose level on mortality, length of stay, and 30 day readmission, adjusted for demographic factors and comorbidity. Results: The mean age of the sample was 64 years, and 51% of the subjects were female. Inpatient mortality occurred in 4.6% and the median length of stay was 5 days (interquartile range 3–9 days). Readmission within 30 days occurred in 17%. We found little impact of first glucose measures on in-hospital mortality (P = 0.94), length of stay (P = 0.95), and 30-day readmission (P = 0.56). Subjects 65 years and older trended towards higher in-hospital mortality. Older age, cancer, heart failure, and cirrhosis were associated with adverse outcomes. Conclusion: Glucose level upon admission for community-acquired pneumonia was not associated with adverse outcomes within 30 days in older adults. Keywords: community-acquired pneumonia, hyperglycemia, readmission rates, hospital mortalit

Impact of a modified data capture period on Liu comorbidity index scores in Medicare enrollees initiating chronic dialysis

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background: The Liu Comorbidity Index uses the United States Renal Data System (USRDS) to quantify comorbidity in chronic dialysis patients, capturing baseline comorbidities from days 91 through 270 after dialysis initiation. The 270 day survival requirement results in sample size reductions and potential survivor bias. An earlier and shorter time-frame for data capture could be beneficial, if sufficiently similar comorbidity information could be ascertained. Methods: USRDS data were used in a retrospective observational study of 70,114 Medicare- and Medicaid-eligible persons who initiated chronic dialysis during the years 2000–2005. The Liu index was modified by changing the baseline comorbidity capture period to days 1–90 after dialysis initiation for persons continuously enrolled in Medicare. The scores resulting from the original and the modified comorbidity indices were compared, and the impact on sample size was calculated. Results: The original Liu comorbidity index could be calculated for 75% of the sample, but the remaining 25% did not survive to 270 days. Among 52,937 individuals for whom both scores could be calculated, the mean scores for the original and the modified index were 7.4 ± 4.0 and 6.4 ± 3.6 points, respectively, on a 24-point scale. The most commonly calculated difference between scores was zero, occurring in 44% of patients. Greater comorbidity was found in those who died before 270 days. Conclusions: A modified version of the Liu comorbidity index captures the majority of comorbidity in persons who are Medicare-enrolled at the time of chronic dialysis initiation. This modification reduces sample size losses and facilitates inclusion of a sicker portion of the population in whom early mortality is common. Keywords: Comorbidity, Kidney failure, Chronic, Renal dialysis, Epidemiologic research desig

Hyperbaric oxygen improves engraftment of ex-vivo expanded and gene transduced human CD34+ cells in a murine model of umbilical cord blood transplantation

Delayed engraftment and graft failure represent major obstacles to successful umbilical cord blood (UCB) transplantation. Herein, we evaluated the use of hyperbaric oxygen (HBO) therapy as an intervention to improve human UCB stem/progenitor cell engraftment in an immune deficient mouse model. Six-to eight-week old NSG mice were sublethally irradiated 24 hours prior to CD34+ UCB cell transplant. Irradiated mice were separated into a non-HBO group (where mice remained under normoxic conditions) and the HBO group (where mice received two hours of HBO therapy; 100% oxygen at 2.5 atmospheres absolute). Four hours after completing HBO therapy, both groups intravenously received CD34+ UCB cells that were transduced with a lentivirus carrying luciferase gene and expanded for in vivo imaging. Mice were imaged and then sacrificed at one of 10 times up to 4.5 months post-transplant. HBO treated mice demonstrated significantly improved bone marrow, peripheral blood , and spleen (p=0.0293) retention and subsequent engraftment. In addition, HBO significantly improved peripheral, spleen and bone marrow engraftment of human myeloid and B-cell subsets. In vivo imaging demonstrated that HBO mice had significantly higher ventral and dorsal bioluminescence values. These studies suggest that HBO treatment of NSG mice prior to UCB CD34+ cell infusion significantly improves engraftment

Incidence and Clinical Predictors of Ocular Candidiasis in Patients with Candida

Purpose. The aim of this study is to determine the incidence and the predictors of ocular candidiasis among patient with Candida fungemia. Methods. We retrospectively reviewed the charts of all patients diagnosed with candidemia at the University of Kansas Medical Center during February 2000–March 2010. Data regarding patients’ demographics, clinical characteristics, laboratory results, and ophthalmology examination findings were collected. Results. A total of 283 patients with candidemia were enrolled. The mean age (± standard deviation) was 55 ± 18 years; 66% were male. The most commonly isolated Candida species were C. albicans (54%), C. parapsilosis (20%), C. glabrata (13%), and C. tropicalis (8%). Only 144 (51%) patients were evaluated by ophthalmology; however, the proportion of patients who were formally evaluated by an ophthalmologist increased during the study period (9%in 2000 up to 73%in 2010; P<0.0001). Evidence of ocular candidiasis was present in 18 (12.5%) patients. Visual symptoms were reported by 5 of 18 (28%) patients. In multivariable analysis, no predictors of ocular candidiasis were identified. Conclusions. The incidence of ocular candidiasis among patients with fungemia remains elevated. Most patients are asymptomatic and therefore all patients with candidemia should undergo fundoscopic examination to rule out ocular involvement

Dementia risk and dynamic response to exercise: A non-randomized clinical trial

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background Physical exercise may support brain health and cognition over the course of typical aging. The goal of this nonrandomized clinical trial was to examine the effect of an acute bout of aerobic exercise on brain blood flow and blood neurotrophic factors associated with exercise response and brain function in older adults with and without possession of the Apolipoprotein epsilon 4 (APOE4) allele, a genetic risk factor for developing Alzheimer’s. We hypothesized that older adult APOE4 carriers would have lower cerebral blood flow regulation and would demonstrate blunted neurotrophic response to exercise compared to noncarriers. Methods Sixty-two older adults (73±5 years old, 41 female [67%]) consented to this prospectively enrolling clinical trial, utilizing a single arm, single visit, experimental design, with post-hoc assessment of difference in outcomes based on APOE4 carriership. All participants completed a single 15-minute bout of moderate-intensity aerobic exercise. The primary outcome measure was change in cortical gray matter cerebral blood flow in cortical gray matter measured by magnetic resonance imaging (MRI) arterial spin labeling (ASL), defined as the total perfusion (area under the curve, AUC) following exercise. Secondary outcomes were changes in blood neurotrophin concentrations of insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and brain derived neurotrophic factor (BDNF). Results Genotyping failed in one individual (n = 23 APOE4 carriers and n = 38 APOE4 non-carriers) and two participants could not complete primary outcome testing. Cerebral blood flow AUC increased immediately following exercise, regardless of APOE4 carrier status. In an exploratory regional analyses, we found that cerebral blood flow increased in hippocampal brain regions, while showing no change in cerebellum across both groups. Among high inter-individual variability, there were no significant changes in any of the 3 neurotrophic factors for either group immediately following exercise. Conclusions Our findings show that both APOE4 carriers and non-carriers show similar effects of exercise-induced increases in cerebral blood flow and neurotrophic response to acute aerobic exercise. Our results provide further evidence that acute exercise-induced increases in cerebral blood flow may be regional specific, and that exercise-induced neurotrophin release may show a differential effect in the aging cardiovascular system. Results from this study provide an initial characterization of the acute brain blood flow and neurotrophin responses to a bout of exercise in older adults with and without this known risk allele for cardiovascular disease and Alzheimer’s disease

Effect of aerobic exercise on amyloid accumulation in preclinical Alzheimer’s: A 1-year randomized controlled trial

Background Our goal was to investigate the role of physical exercise to protect brain health as we age, including the potential to mitigate Alzheimer’s-related pathology. We assessed the effect of 52 weeks of a supervised aerobic exercise program on amyloid accumulation, cognitive performance, and brain volume in cognitively normal older adults with elevated and sub-threshold levels of cerebral amyloid as measured by amyloid PET imaging. Methods and findings This 52-week randomized controlled trial compared the effects of 150 minutes per week of aerobic exercise vs. education control intervention. A total of 117 underactive older adults (mean age 72.9 [7.7]) without evidence of cognitive impairment, with elevated (n = 79) or subthreshold (n = 38) levels of cerebral amyloid were randomized, and 110 participants completed the study. Exercise was conducted with supervision and monitoring by trained exercise specialists. We conducted 18F-AV45 PET imaging of cerebral amyloid and anatomical MRI for whole brain and hippocampal volume at baseline and Week 52 follow-up to index brain health. Neuropsychological tests were conducted at baseline, Week 26, and Week 52 to assess executive function, verbal memory, and visuospatial cognitive domains. Cardiorespiratory fitness testing was performed at baseline and Week 52 to assess response to exercise. The aerobic exercise group significantly improved cardiorespiratory fitness (11% vs. 1% in the control group) but there were no differences in change measures of amyloid, brain volume, or cognitive performance compared to control. Conclusions Aerobic exercise was not associated with reduced amyloid accumulation in cognitively normal older adults with cerebral amyloid. In spite of strong systemic cardiorespiratory effects of the intervention, the observed lack of cognitive or brain structure benefits suggests brain benefits of exercise reported in other studies are likely to be related to non-amyloid effects

Improving quality indicator report cards through Bayesian modeling

<p>Abstract</p> <p>Background</p> <p>The National Database for Nursing Quality Indicators^®(NDNQI^®) was established in 1998 to assist hospitals in monitoring indicators of nursing quality (eg, falls and pressure ulcers). Hospitals participating in NDNQI transmit data from nursing units to an NDNQI data repository. Data are summarized and published in reports that allow participating facilities to compare the results for their units with those from other units across the nation. A disadvantage of this reporting scheme is that the sampling variability is not explicit. For example, suppose a small nursing unit that has 2 out of 10 (rate of 20%) patients with pressure ulcers. Should the nursing unit immediately undertake a quality improvement plan because of the rate difference from the national average (7%)?</p> <p>Methods</p> <p>In this paper, we propose approximating 95% credible intervals (CrIs) for unit-level data using statistical models that account for the variability in unit rates for report cards.</p> <p>Results</p> <p>Bayesian CrIs communicate the level of uncertainty of estimates more clearly to decision makers than other significance tests.</p> <p>Conclusion</p> <p>A benefit of this approach is that nursing units would be better able to distinguish problematic or beneficial trends from fluctuations likely due to chance.</p