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PubMed2001

Analysis of heart rate variability with correlation dimension method in a normal population and in heart transplant patients.

INTRODUCTION: The correlation dimension (CD) method is related to chaos theory and is used to quantify heart rate variability (HRV). The CD is a measure for the amount of correlations present in the signal. METHODS: The algorithm used to calculate the CD is based on the method of Grassberger and Proccacia. The method was first validated on signals with known CD and then applied to HRV-signals of heart transplants and an age-matched control group of healthy subjects. The CD of the corresponding surrogate time series was calculated to investigate non-linear correlations in the HRV-signal. Circadian variations of the CD were studied in 20 healthy subjects, including men and women. RESULTS: The value of the CD for healthy subjects ranged from 2.12 to 5.53 with a mean value of 4.32. For heart transplants, only a few time series showed a finite value of the CD that varied between 2.10 and 5.60. Also, a significant difference was found between the CD of the original and the surrogate time series in healthy subjects. The CD of women is higher than the CD of men, and this difference was more pronounced during the night than during the day. CONCLUSIONS: This limited study shows that the CD alone cannot be used to make a distinction between HRV-signals of healthy subjects and of heart transplants. However, there is evidence that there are non-linear correlations present in the HRV-signal and that there are significant gender and circadian differences in the CD.

Algorithms↗

PubMed1994

Use of surrogate information time for monitoring the effect of treatment on the change in a response variable in clinical trials.

We discuss the monitoring of clinical trials data and propose two surrogates for total information for use with the spending function approach where there are repeated measurements and we wish to compare the rates of change in a response variable under different treatments. These surrogates are applied to a setting similar to the Lung Health Study. Although the surrogates do not require estimation of the variance parameters, they do require some knowledge of the ratio R of the within- to the between-individual variances. The effects of overestimating and underestimating R are illustrated. In situations of uncertainty we recommend overestimating R, to provide a conservative estimate of information time at each interim analysis.

Adult↗

PubMed1998

Demonstration of nonlinear components in heart rate variability of healthy persons.

We present a systematic approach for detecting nonlinear components in heart rate variability (HRV). The analysis is based on twenty-three 48-h Holter recordings in healthy persons during sinus rhythm. Although many segments of 1,024 R-R intervals are stationary, only few stationary segments of 8,192-32,768 R-R intervals can be found using a test of Isliker and Kurths (Int. J. Bifurcation Chaos 3:1573-1579, 1993.). By comparing the correlation integrals from these segments and corresponding surrogate data sets, we reject the null hypothesis that these time series are realization of linear processes. On the basis of a test statistic exploring the differences of consecutive R-R intervals, we reject the hypothesis that the R-R intervals represent a static transformation of a linear process using optimized surrogate data. Furthermore, time irreversibility of the heartbeat data is demonstrated. We interpret these results as a strong evidence for nonlinear components in HRV. Thus R-R intervals from healthy persons contain more information than can be extracted by linear analysis in the time and frequency domain.

Adult↗

PubMed2005

Effectiveness of whole brain radiotherapy in the treatment of brain metastases: a systematic review.

BACKGROUND: Brain metastases are the most common intracranial tumour in adults, estimated to occur in up to 40% of patients with cancer. Despite being used in clinical practice for 50 years, the effectiveness of whole brain radiotherapy for the treatment of brain metastases remains uncertain. OBJECTIVES: To assess the effectiveness of whole brain radiotherapy (WBRT) on survival and quality of life. To identify whether patient performance status, number of brain metastases, extent of extracranial disease and primary site of cancer are important effect modifiers. DESIGN: Systematic literature review. METHODS: Electronic searches of four databases, augmented by hand searches of the most frequently encountered journal and assessment of the reference lists of consensus statements and all retrieved papers. Included papers underwent structured data extraction, assessment and qualitative synthesis. RESULTS: Thirty-two primary studies were included, with a range of study designs, methodological quality, pre-treatment variables, interventions and outcome measures. From the limited evidence available, survival appeared to increase when patients were selected by performance status (survival increasing from approximately three to seven months in high performance status groups, as defined by Karnofsky performance status or Recursive Partitioning Analysis classification). The evidence suggests no survival benefit when patients with poor performance status were treated with whole brain radiotherapy. No studies undertook direct measurement of patients' quality of life. Surrogate measures of patients' quality of life, such as improvement in neurological function or improvement/maintenance of KPS > or =70, produced response rates ranging from 7 to 90%. CONCLUSION: The heterogeneity of study designs, quality and outcomes necessitates caution in interpreting the review findings. WBRT appears to be of benefit in higher performance status patients but not in low performance status patients. This suggests a basis for current practice, however further robust trial evidence is required.

Brain Neoplasms↗

PubMed2006

Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients.

BACKGROUND: Target of rapamycin inhibitors (TOR-I) (sirolimus, everolimus) are immunosuppressive agents with a novel mode of action but an uncertain clinical role. OBJECTIVES: To investigate the benefits and harms of immunosuppressive regimens containing TOR-I when compared to other regimens as initial therapy for kidney transplant recipients. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (in The Cochrane Library, issue 2, 2005), MEDLINE (1966-June 2005), EMBASE (1980-June 2005), the specialised register of the Cochrane Renal Group (June 2005)., and contacted authors and pharmaceutical companies to identify relevant studies. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs where drug regimens containing TOR-I were compared to alternative drug regimens in the immediate post-transplant period were included, without age restriction, dosage or language of report. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for eligibility and quality, and extracted data. Results are expressed as relative risk (RR) or weight mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: Thirty three trials (142 reports) were included (sirolimus (27), everolimus (5), head-to-head (1)). When TOR-I replaced CNI there was no difference in acute rejection, but serum creatinine was lower (MD -18.31 micromol/L, -30.96 to -5.67), and bone marrow more suppressed (leucopenia: RR 2.02 1.12 to 3.66; thrombocytopenia: RR 6.97 2.97 to 16.36; anaemia: RR 1.67, 1.27 to 2.20). When TOR-I replaced antimetabolites, acute rejection (RR 0.84, 0.71 to 0.99) and cytomegalovirus infection (CMV) (RR 0.49; 0.37 to 0.65) were reduced, but hypercholesterolaemia was increased (RR 1.65, 1.32 to 2.06). For low versus high-dose TOR-I, with equal CNI dose, rejection was increased (RR 1.23, 1.06 to 1.43) but calculated GFR higher (MD 4.27 mL/min, 1.12 to 7.41), and for low-dose TOR-I/standard-dose CNI versus higher-dose TOR-I/reduced CNI, acute rejection (RR 0.67, 0.52 to 0.88) and calculated GFR (MD -9.46 mL/min, -12.16 to -6.76) were reduced. There was no significant difference in mortality, graft loss or malignancy risk for TOR-I in any comparison. AUTHORS' CONCLUSIONS: TOR-I have been evaluated in four different primary immunosuppressive algorithms; as replacement for CNI and for antimetabolites, in combination with CNI at low and high dose and with variable dose of CNI. Generally, surrogate endpoints for graft survival favour TOR-I (lower risk of acute rejection and higher GFR) and surrogate endpoints for patient outcomes are worsened by TOR-I (bone marrow suppression, lipid disturbance). Long-term hard-endpoint data from methodologically robust RCTs are still needed.

Everolimus↗

PubMed2004

Emergency room injury presentations as an indicator of alcohol-related problems in the community: a multilevel analysis of an international study.

OBJECTIVE: This study describes and examines the development of surrogate measures of acute alcohol-related injury for use in the evaluation of community-based prevention initiatives. METHOD: An international collaborative study of alcohol and injury, the Emergency Room Collaborative Alcohol Analysis Project (ERCAAP), provided a subset of data on 8580 emergency room (ER) presentations from five countries and 28 ER facilities. RESULTS: Presentations most likely to be alcohol related were those made between 12:00 AM and 4:59 AM (56%), on Fridays, Saturdays or Sundays (26%); and those among injured persons who were male (28%), who were aged between 18 and 45 years (24%) or who were unmarried (24%). Multilevel logistic regression models confirmed the significance of the above variables as predictors of alcohol involvement prior to the injury event. The strongest predictor variable was presentation between 12 midnight and 4:59 AM with an odds ratio of 4.92 (Wald Test chi2 = 397.6, p < .001). Being male had an odds ratio of 3.01 (Wald Test chi2 = 247.25, p < .001), and presenting on a Friday, Saturday or Sunday night had an odds ratio of 1.50 (Wald Test chi2 = 49.6, p < .001), whereas being under 45 (odds ratio [OR] = 1.20, p < .05) and being unmarried (OR = 1.2, p < .01) were less strong predictors. Combining all these values for variables raised the probability of prior alcohol involvement in such injury presentations to 0.65, although only 3.37% of all cases met these criteria, limiting applicability of this combined variable as a surrogate measure for intervention studies. Probabilities of prior alcohol involvement are presented with other combinations of values for the predictor variables. CONCLUSIONS: Frequency of nighttime injury presentations to ER facilities, particularly by men, can be used as a reliable surrogate measure of alcohol-related injuries for various epidemiological and evaluation purposes.

Accidents↗

PubMed2003

Fractal properties of human muscle sympathetic nerve activity.

Muscle sympathetic nerve activity (MSNA) in resting humans is characterized by cardiac-related bursts of variable amplitude that occur sporadically or in clusters. The present study was designed to characterize the fluctuations in the number of MSNA bursts, interburst interval, and burst amplitude recorded from the peroneal nerve of 15 awake, healthy human subjects. For this purpose, we used the Allan and Fano factor analysis and dispersional analysis to test whether the fluctuations were time-scale invariant (i.e., fractal) or random in occurrence. Specifically, we measured the slopes of the power laws in the Allan factor, Fano factor, and dispersional analysis curves. In addition, the Hurst exponent was calculated from the slope of the power law in the Allan factor curve. Whether the original time series contained fractal fluctuations was decided on the basis of a comparison of the values of these parameters with those for surrogate data blocks. The results can be summarized as follows. Fluctuations in the number of MSNA bursts and interburst interval were fractal in each of the subjects, and fluctuations in burst amplitude were fractal in four of the subjects. We also found that fluctuations in the number of heartbeats and heart period (R-R interval) were fractal in each of the subjects. These results demonstrate for the first time that apparently random fluctuations in human MSNA are, in fact, dictated by a time-scale-invariant process that imparts "long-term memory" to the sequence of cardiac-related bursts. Whether sympathetic outflow to the heart also is fractal and contributes to the fractal component of heart rate variability remains an open question.

Adult↗

PubMed2002

Does preprocessing change nonlinear measures of heart rate variability?

This work investigated if methods used to produce a uniformly sampled heart rate variability (HRV) time series significantly change the deterministic signature underlying the dynamics of such signals and some nonlinear measures of HRV. Two methods of preprocessing were used: the convolution of inverse interval function values with a rectangular window and the cubic polynomial interpolation. The HRV time series were obtained from 33 Wistar rats submitted to autonomic blockade protocols and from 17 healthy adults. The analysis of determinism was carried out by the method of surrogate data sets and nonlinear autoregressive moving average modelling and prediction. The scaling exponents alpha, alpha(1) and alpha(2) derived from the detrended fluctuation analysis were calculated from raw HRV time series and respective preprocessed signals. It was shown that the technique of cubic interpolation of HRV time series did not significantly change any nonlinear characteristic studied in this work, while the method of convolution only affected the alpha(1) index. The results suggested that preprocessed time series may be used to study HRV in the field of nonlinear dynamics.

Adolescent↗

PubMed2003

Eutrophication risk assessment in coastal embayments using simple statistical models.

A statistical methodology is proposed for assessing the risk of eutrophication in marine coastal embayments. The procedure followed was the development of regression models relating the levels of chlorophyll a (Chl) with the concentration of the limiting nutrient--usually nitrogen--and the renewal rate of the systems. The method was applied in the Gulf of Gera, Island of Lesvos, Aegean Sea and a surrogate for renewal rate was created using the Canberra metric as a measure of the resemblance between the Gulf and the oligotrophic waters of the open sea in terms of their physical, chemical and biological properties. The Chl-total dissolved nitrogen-renewal rate regression model was the most significant, accounting for 60% of the variation observed in Chl. Predicted distributions of Chl for various combinations of the independent variables, based on Bayesian analysis of the models, enabled comparison of the outcomes of specific scenarios of interest as well as further analysis of the system dynamics. The present statistical approach can be used as a methodological tool for testing the resilience of coastal ecosystems under alternative managerial schemes and levels of exogenous nutrient loading.

Bayes Theorem↗

PubMed2001

Molecular analysis of a hospital cafeteria-associated salmonellosis outbreak using modified repetitive element PCR fingerprinting.

A hospital cafeteria-associated outbreak of gastroenteritis due to Salmonella enterica serotype Infantis was retrospectively evaluated using modified repetitive element PCR (rep-PCR) fingerprinting with the ERIC2 and BOXA1R primers and computer-assisted gel analysis and dendrogram construction. Rep-PCR yielded objective between-cycler, same-strain similarity values of from 92% (composite fingerprints) to 96% (ERIC2 fingerprints). The 70 Salmonella isolates (which included 19 serotype Infantis isolates from the hospital outbreak, 10 other serotype Infantis isolates, and 41 isolates representing 14 other serotypes) were resolved well to the serotype level with each of the three fingerprint types (ERIC2, BOXA1R, and composite). Rep-PCR typing uncovered several historical serotyping errors and provided presumptive serotype assignments for other isolates with incomplete or undetermined serotypes. Analysis of replicate fingerprints for each isolate, as generated on two different thermal cyclers, indicated that most of the seeming subserotype discrimination noted in single-cycler dendrograms actually represented assay variability, since it was not reproducible in combined-cycler dendrograms. Rep-PCR typing, which would have been able to identify the presence of the hospital-associated serotype Infantis outbreak after the second outbreak isolate, could be used as a simple surrogate for serotyping by clinical microbiology laboratories that are equipped for diagnostic PCR.

Bacterial Typing Techniques↗

PubMed2000

Comparison of Cryptosporidium parvum viability and infectivity assays following ozone treatment of oocysts.

Several in vitro surrogates have been developed as convenient, user-friendly alternatives to mouse infectivity assays for determining the viability of Cryptosporidium parvum oocysts. Such viability assays have been used increasingly to determine oocyst inactivation following treatment with chemical, physical, or environmental stresses. Defining the relationship between in vitro viability assays and oocyst infectivity in susceptible hosts is critical for determining the significance of existing oocyst inactivation data for these in vitro assays and their suitability in future studies. In this study, four viability assays were compared with mouse infectivity assays, using neonatal CD-1 mice. Studies were conducted in the United States and United Kingdom using fresh (<1 month) or environmentally aged (3 months at 4 degrees C) oocysts, which were partially inactivated by ozonation before viability and/or infectivity analyses. High levels of variability were noted within and between the viability and infectivity assays in the U.S. and United Kingdom studies despite rigorous control over oocyst conditions and disinfection experiments. Based on the viability analysis of oocyst subsamples from each ozonation experiment, SYTO-59 assays demonstrated minimal change in oocyst viability, whereas 4',6'-diamidino-2-phenylindole-propidium iodide assays, in vitro excystation, and SYTO-9 assays showed a marginal reduction in oocyst viability. In contrast, the neonatal mouse infectivity assay demonstrated significantly higher levels of oocyst inactivation in the U.S. and United Kingdom experiments. These comparisons illustrate that four in vitro viability assays cannot be used to reliably predict oocyst inactivation following treatment with low levels of ozone. Neonatal mouse infectivity assays should continue to be regarded as a "gold standard" until suitable alternative viability surrogates are identified for disinfection studies.

Animals↗

PubMed2005

Characterization of particulate and gas exposures of sensitive subpopulations living in Baltimore and Boston.

Personal exposures to particulate and gaseous pollutants and corresponding ambient concentrations were measured for 56 subjects living in Baltimore, Maryland, and 43 subjects living in Boston, Massachusetts. The 3 Baltimore cohorts consisted of 20 healthy older adults (seniors), 21 children, and 15 individuals with physician-diagnosed chronic obstructive pulmonary disease (COPD*). The 2 Boston cohorts were 20 healthy seniors and 23 children. All children were 9 to 13 years of age; seniors were 65 years of age or older; and the COPD participants had moderate to severe physician-diagnosed COPD. Personal exposures to particulate matter with aerodynamic diameters less than 2.5 microm (PM2.5), sulfate (SO(4)2-), elemental carbon (EC), ozone (03), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were measured simultaneously for 24 hours/day. All subjects were monitored for 8 to 12 consecutive days. The primary objectives of this study were (1) to characterize the personal particulate and gaseous exposures for individuals sensitive to PM health effects and (2) to assess the appropriateness of exposure assessment strategies for use in PM epidemiologic studies. Personal exposures to multiple pollutants and ambient concentrations were measured for subjects from each cohort from each location. Pollutant data were analyzed using correlation and mixed-model regression analyses. In Baltimore, personal PM2.5 exposures tended to be comparable to (and frequently lower than) corresponding ambient concentrations; in Boston, the personal exposures were frequently higher. Overall, personal exposures to the gaseous pollutants, especially O3 and SO2, were considerably lower than corresponding ambient concentrations because of the lack of indoor sources for these gases and their high removal rate on indoor surfaces. Further, the impact of ambient particles on personal exposure (the infiltration factor) and differences in infiltration factor by city, season, and cohort were investigated. No difference in infiltration factor was found among the cohorts, which suggests that all subjects were exposed to the same fraction of ambient PM2.5 for a given ambient concentration. In addition, the results show significant correlations between ambient PM2.5 concentrations and corresponding personal exposures over time and provide further indication that ambient gaseous pollutant concentrations may be better surrogates for personal PM2.5 exposures, especially personal exposures to PM2.5 of ambient origin, than their respective personal exposures. These results have important implications for PM health effects studies that use regression models including both ambient PM2.5 and gaseous pollutant concentrations as independent variables, because both parameters may be serving as surrogates for PM2.5 exposures.

Adolescent↗

PubMed2004

Quantification of variability and uncertainty for air toxic emission inventories with censored emission factor data.

Probabilistic emission inventories were developed for urban air toxic emissions of benzene, formaldehyde, chromium, and arsenic for the example of Houston. Variability and uncertainty in emission factors were quantified for 71-97% of total emissions, depending upon the pollutant and data availability. Parametric distributions for interunit variability were fit using maximum likelihood estimation (MLE), and uncertainty in mean emission factors was estimated using parametric bootstrap simulation. For data sets containing one or more nondetected values, empirical bootstrap simulation was used to randomly sample detection limits for nondetected values and observations for sample values, and parametric distributions for variability were fit using MLE estimators for censored data. The goodness-of-fit for censored data was evaluated by comparison of cumulative distributions of bootstrap confidence intervals and empirical data. The emission inventory 95% uncertainty ranges are as small as -25% to +42% for chromium to as large as -75% to +224% for arsenic with correlated surrogates. Uncertainty was dominated by only a few source categories. Recommendations are made for future improvements to the analysis.

Air Pollutants↗

PubMed2004

Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial.

BACKGROUND: Rheumatoid arthritis is characterised by inflammatory synovitis, articular destruction, and accelerated atherogenesis. HMG-CoA (3-hydroxy-3-methylglutarylcoenzyme A) reductase inhibitors (statins) mediate clinically significant vascular risk reduction in patients without inflammatory disease and might have immunomodulatory function. We postulated that statins might reduce inflammatory factors in rheumatoid arthritis and modify surrogates for vascular risk. METHODS: 116 patients with rheumatoid arthritis were randomised in a double-blind placebo-controlled trial to receive 40 mg atorvastatin or placebo as an adjunct to existing disease-modifying antirheumatic drug therapy. Patients were followed up over 6 months and disease activity variables and circulating vascular risk factors were measured. Coprimary outcomes were change in disease activity score (DAS28) and proportion meeting EULAR (European League Against Rheumatism) response criteria. Analysis was by intention to treat. FINDINGS: At 6 months, DAS28 improved significantly on atorvastatin (-0.5, 95% CI -0.75 to -0.25) compared with placebo (0.03, -0.23 to 0.28; difference between groups -0.52, 95% CI -0.87 to -0.17, p=0.004). DAS28 EULAR response was achieved in 18 of 58 (31%) patients allocated atorvastatin compared with six of 58 (10%) allocated placebo (odds ratio 3.9, 95% CI 1.42-10.72, p=0.006). C-reactive protein and erythrocyte sedimentation rate declined by 50% and 28%, respectively, relative to placebo (p<0.0001, p=0.005, respectively). Swollen joint count also fell (-2.69 vs -0.53; mean difference -2.16, 95% CI -3.67 to -0.64, p=0.0058). Adverse events occurred with similar frequency in patients allocated atorvastatin and placebo. INTERPRETATION: These data show that statins can mediate modest but clinically apparent anti-inflammatory effects with modification of vascular risk factors in the context of high-grade autoimmune inflammation.

Aged↗

PubMed2003

Designing 'balanced' crystalloids.

OBJECTIVE: To present a rationale for the design of balanced resuscitation and renal replacement crystalloids based on Stewart's physical chemical approach to acid-base. DATA SOURCES: Articles and published abstracts on acid-base physiology, crystalloid infusions and renal replacement therapy. SUMMARY OF REVIEW: Although it is uncertain that crystalloid-induced metabolic acidosis causes significant harm, Stewart's approach assists in designing balanced fluids without this side effect. In his analysis, the three independent variables determining acid-base balance are PCO2, the total concentration of non-volatile weak acid (A(TOT)) and the strong ion difference (SID). Raising and lowering A(TOT) while holding SID constant cause a metabolic acidosis and alkalosis respectively. Lowering and raising plasma SID while clamping A(TOT) cause a metabolic acidosis and alkalosis respectively. The SID of a crystalloid is its [HCO3-], or that part of an organic bicarbonate surrogate which is metabolised on infusion. Rapid infusion alters plasma SID towards crystalloid SID, but also lowers A(TOT) by haemodilution. We have shown that the SID of a balanced infusion crystalloid is 24 mEq/L. This generates a fall in plasma SID precisely counteracting the A(TOT) dilutional alkalosis. In contrast, a balanced renal replacement crystalloid must generate a higher plasma SID appropriate for the existing A(TOT), since there is no dilution. If A(TOT) is low, as in hypoalbuminaemia, the balanced dialysis SID falls correspondingly. A further SID reduction is needed to counteract Donnan effects within the filter. CONCLUSIONS: A crystalloid SID of 24 mEq/L is 'balanced' for rapid intravenous administration. The 'balanced' SID of renal replacement fluids is likely to be significantly higher, although less than the normal plasma SID of 42 mEq/L.

Journal Article↗

PubMed2006

Target of rapamycin inhibitors (sirolimus and everolimus) for primary immunosuppression of kidney transplant recipients: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Target of rapamycin inhibitors (TOR-I) have a novel mode of action but uncertain clinical role. We performed a systematic review of randomized trials where immunosuppressive regimens containing TOR-I were compared with other regimens as initial therapy for kidney transplant recipients. METHODS: Databases (inception, June 2005) and conference proceedings (1996-2005) were searched. Two independent reviewers assessed trials for eligibility and quality. Results at 1 year, are expressed as relative risk (RR), where values<1 favor TOR-I, or lower dose of TOR-I, and for continuous outcomes are expressed as weighted mean difference (WMD), both expressed with 95% confidence intervals (CI). RESULTS: Thirty-three trials (142 reports) were included (27 trials of sirolimus, 5 of everolimus, and 1 of head-to-head comparison). When TOR-I replaced calcineurin inhibitors (CNI) (8 trials with 750 participants), there was no difference in acute rejection (RR, 1.03; 95% CI, 0.74-1.44), but serum creatinine was lower (WMD, -18.31 micromol/L; 95% CI, -30.96 to -5.67) and bone marrow more suppressed (leukopenia: RR 2.02; 95% CI, 1.12-3.66; thrombocytopenia: RR, 6.97; 95% CI, 2.97-16.36; and anaemia: RR, 1.67; 95% CI, 1.27-2.20). When TOR-I replaced antimetabolites (11 trials with 3966 participants), acute rejection and cytomegalovirus infection (CMV) were reduced (RR, 0.84; 95% CI, 0.71-0.99; RR, 0.49; 95% CI, 0.37-0.65, respectively), but hypercholesterolemia was increased (RR, 1.65; 95% CI, 1.32-2.06). When low- was compared with high-dose TOR-I, with equal CNI dose (10 trials with 3,175 participants), rejection was increased (RR, 1.23; 95% CI, 1.06-1.43) but calculated glomerular filtration rate (GFR) higher (WMD, 4.27 mL/min; 95% CI, 1.12-7.41), and when lower-dose TOR-I and standard-dose CNI were compared with higher-dose TOR-I and reduced CNI, acute rejection was reduced (RR, 0.67; 95% CI, 0.52-0.88), but calculated GFR was also reduced (WMD, -9.46 mL/min; 95% CI, -12.16 to -6.76). There was no significant difference in mortality, graft loss, or malignancy risk for TOR-I in any comparison. CONCLUSIONS: TOR-I have been evaluated in four different primary immunosuppressive algorithms: as replacement for CNI and antimetabolites, in combination with CNI at low and high doses, and with a variable dose of CNI. Generally, surrogate endpoints for graft survival favor TOR-I (lower risk of acute rejection and higher GFR), and surrogate endpoints for patient outcomes are worsened by TOR-I (bone marrow suppression and lipid disturbance). Long-term hard-endpoint data from methodologically robust randomized trials are still required.

Creatinine↗

PubMed2001

High short-term mortality in hospitalized patients with advanced dementia: lack of benefit of tube feeding.

BACKGROUND: The influence of tube feeding on survival in hospitalized patients with advanced dementia is controversial. OBJECTIVE: To assess long-term survival in an inception cohort, incident tube feeding placement during the index hospitalization, and the influence of tube feeding on survival in this group of patients. SUBJECTS AND METHODS: Ninety-nine hospitalized patients with advanced dementia and an available surrogate decision maker were followed up through and after the index hospitalization for mortality and placement of a feeding tube. Other variables measured included advance directive status, presence of a long-term primary care physician, level of involvement of the surrogate decision maker, admitting diagnosis, prior hospitalizations, comorbidities, and diagnosis related group diagnostic category. RESULTS: A new feeding tube was placed in 50% (51/99) of the study patients during the index hospitalization, 31% (31/99) left the hospital without a feeding tube, and 17% (17/99) were admitted with a feeding tube already in place. By stepwise logistic regression analysis, predictors of new feeding tube placement included African American ethnicity (odds ratio, 9.43; 95% confidence interval, 2.1-43.2) and residence in a nursing home (odds ratio, 4.9; 95% confidence interval, 1.02-2.5). Median survival of the 99 patients was 175 days. Eighty-five (85%) survived the index hospitalization, and 28 (28%) were still alive at last follow-up, a range of 1.3 to 4.2 years after enrollment in the study. Tube feeding was not associated with survival (P =.90). An admitting diagnosis of infection was associated with higher mortality (odds ratio, 1.9; 95% confidence interval, 1.01-3.6). CONCLUSIONS: In this cohort of hospitalized patients with advanced dementia, risk of receiving a new feeding tube is high, associated with African American ethnicity, and prior residence in a nursing home, and has no measurable influence on survival. With or without a feeding tube, these patients have a 50% six-month median mortality.

Aged↗

PubMed2000

Nonlinear analysis of continuous ECG during sleep II. Dynamical measures.

The hypothesis that cardiac rhythms are associated with chaotic dynamics implicating a healthy flexibility has motivated the investigation of continuous ECG with methods of nonlinear system theory. Sleep is known to be associated with modulations of the sympathetic and parasympathetic control of cardiac dynamics. Thus, the differentiation of ECG signals recorded during different sleep stages can serve to determine the usefulness of nonlinear measures in discriminating ECG states in general. For this purpose the following six nonlinear measures were implemented: correlation dimension D2, Lyapunov exponent L1. Kolmogorov entropy K2, as well as three measures derived from the analysis of unstable periodic orbits. Results of this study show that continuous ECG signals can be differentiated from linear stochastic surrogates by each of the nonlinear measures. The most significant finding with respect to the sleep-related differentiation of ECG signals is an increase in dominant chaoticity assessed by L1 and a reduction in the degrees of freedom estimated by D2 during REM sleep compared to slow wave sleep. Our findings suggest that the increase in dominant chaoticity during REM sleep with regard to time-continuous nonlinear analysis is comparable to an increased heart rate variability. The reduction in the correlation dimension may be interpreted as an expression of the withdrawal of respiratory influences during REM sleep.

Adult↗