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Michael J Flanigan

Publications and source records attributed to Michael J Flanigan.

11 recordsLinked to original sources
PubMed2006

Effect of dialysis center profit-status on patient survival: a comparison of risk-adjustment and instrumental variable approaches.

OBJECTIVE: To compare the estimated effects of dialysis center profit status on patient survival using alternative estimation strategies with retrospective data. DATA SOURCES/STUDY SETTING: Patient and provider-level retrospective data from the United States Renal Data System (USRDS), 1996-1999. STUDY DESIGN: Observational risk adjustment and instrumental variable methods. DATA COLLECTION/EXTRACTION METHODS: Study collected measures from various USRDS files describing clinical characteristics, survival, and the profit status of the initial dialysis center for incident end-stage renal disease (ESRD) patients aged 67+. USRDS facility files were used to assess dialysis center profit status and measure patient distances to dialysis centers. PRINCIPAL FINDINGS: Found survival effect related to profit status in the range of previous research using risk-adjusting covariates similar to those used in previous models. Adding further risk-adjusting covariates halved this effect. The relative proximity of for-profit and nonprofit dialysis centers to the patient residence was the strongest determinant of the profit status of the patient's initial dialysis center. The effect of profit status on survival was eliminated using the two-stage least squares variant of instrumental variable estimation with the relative proximity of for-profit and nonprofit dialysis centers to the patient's residence as the instrument. CONCLUSIONS: Using only the variation in initial dialysis center profit status that was related to the relative proximity of for-profit and nonprofit dialysis centers to the patient, we found no relationship between dialysis center profit status and patient survival. These results are in contrast to results obtained using risk-adjustment methods with a limited set of risk-adjusting covariates.

Aged↗
PubMed2005

Does hemodialysis increase protein breakdown? Dissociation between whole-body amino acid turnover and regional muscle kinetics.

Hemodialysis (HD) is a protein catabolic procedure. Whole-body amino acid turnover studies identify dialysate amino acid loss and reduced protein synthesis as the catabolic events; proteolysis is not increased. Regional amino acid kinetics, however, document enhanced muscle protein breakdown as the cause of the catabolism; muscle protein synthesis also increased but to a lesser magnitude than the increment in protein breakdown. This discordance between whole-body and regional kinetics is best explained by the contrasting physiology between the muscle and the liver. During HD, muscle releases amino acids, which then are taken up by the liver for de novo protein synthesis. There seems to be a somatic to visceral recycling of amino acids. Evidence supporting this concept includes the increased fractional synthesis of albumin and fibrinogen during HD. It should be emphasized that region- or organ-specific kinetics vary, and whole-body turnover is a composite of all of the visceral and somatic compartments taken together. Reduced whole-body protein synthesis may be a compensatory adaptation to dialysate amino acid loss with a consequent reduction in plasma amino acid concentration. Notwithstanding the protein catabolic nature of HD, evidence is accumulating that intradialytic nutritional supplementation may blunt its catabolic effect.

Amino Acids↗
PubMed2004

Hormonal responses to fasting and refeeding in chronic renal failure patients.

To study anorexia in chronic renal failure (CRF) patients, we measured appetite-related hormones in seven CRF patients and four controls. Plasma concentrations and fractional changes from baseline (values from day 1, 0800) are listed as control vs. CRF (means +/- SE). Leptin, although higher in CRF (5.6 +/- 1.7 and 34 +/- 17 ng/ml), was suppressed after fasting; decrements were -51 +/- 9 and -55 +/- 8%. Nocturnal surge present during feeding was abolished upon fasting in both groups. Neuropeptide Y (NPY) was elevated in CRF (72 +/- 12 vs. 304 +/- 28 pg/ml, P = 0.0002). NPY rhythm, reciprocal to that of leptin, was muted in CRF. Basal cortisol was similar in both groups (17 +/- 3 and 17 +/- 2 microg/dl). In the controls, cortisol peaked in the morning and declined in the evening. CRF showed blunted cortisol suppression. Decrements were -61 +/- 3 and -20 +/- 9% at 1800 on day 1 (P = 0.008) and -61 +/- 8 and -26 +/- 8% at 2000 on day 2 (P = 0.02). Basal ACTH (25 +/- 5 and 54 +/- 16 pg/ml) as well as diurnal pattern was not statistically different between the groups. Baseline insulin was 6 +/- 1 and 20 +/- 9 microU/ml. During fasting, insulin was suppressed to -64 +/- 10 and -51 +/- 9%, respectively. Upon refeeding, increments were 277 +/- 96 and 397 +/- 75%. Thus, in our CRF patients, anorexia was not due to excess leptin or deficient NPY. Impaired cortisol suppression should favor eating. Insulin suppression during fasting and secretion after feeding should enhance both eating and anabolism. The constant high NPY suggests increased tonic hypersecretion.

Adrenocorticotropic Hormone↗
PubMed2004

Whole-genome shotgun assembly and comparison of human genome assemblies.

We report a whole-genome shotgun assembly (called WGSA) of the human genome generated at Celera in 2001. The Celera-generated shotgun data set consisted of 27 million sequencing reads organized in pairs by virtue of end-sequencing 2-kbp, 10-kbp, and 50-kbp inserts from shotgun clone libraries. The quality-trimmed reads covered the genome 5.3 times, and the inserts from which pairs of reads were obtained covered the genome 39 times. With the nearly complete human DNA sequence [National Center for Biotechnology Information (NCBI) Build 34] now available, it is possible to directly assess the quality, accuracy, and completeness of WGSA and of the first reconstructions of the human genome reported in two landmark papers in February 2001 [Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., Smith, H. O., Yandell, M., Evans, C. A., Holt, R. A., et al. (2001) Science 291, 1304-1351; International Human Genome Sequencing Consortium (2001) Nature 409, 860-921]. The analysis of WGSA shows 97% order and orientation agreement with NCBI Build 34, where most of the 3% of sequence out of order is due to scaffold placement problems as opposed to assembly errors within the scaffolds themselves. In addition, WGSA fills some of the remaining gaps in NCBI Build 34. The early genome sequences all covered about the same amount of the genome, but they did so in different ways. The Celera results provide more order and orientation, and the consortium sequence provides better coverage of exact and nearly exact repeats.

Computational Biology↗
PubMed2004

Online measurement of urea concentration in spent dialysate during hemodialysis.

BACKGROUND: We describe online optical measurements of urea in the effluent dialysate line during regular hemodialysis treatment of several patients. Monitoring urea removal can provide valuable information about dialysis efficiency. METHODS: Spectral measurements were performed with a Fourier-transform infrared spectrometer equipped with a flow-through cell. Spectra were recorded across the 5000-4000 cm(-1) (2.0-2.5 microm) wavelength range at 1-min intervals. Savitzky-Golay filtering was used to remove baseline variations attributable to the temperature dependence of the water absorption spectrum. Urea concentrations were extracted from the filtered spectra by use of partial least-squares regression and the net analyte signal of urea. RESULTS: Urea concentrations predicted by partial least-squares regression matched concentrations obtained from standard chemical assays with a root mean square error of 0.30 mmol/L (0.84 mg/dL urea nitrogen) over an observed concentration range of 0-11 mmol/L. The root mean square error obtained with the net analyte signal of urea was 0.43 mmol/L with a calibration based only on a set of pure-component spectra. The error decreased to 0.23 mmol/L when a slope and offset correction were used. CONCLUSIONS: Urea concentrations can be continuously monitored during hemodialysis by near-infrared spectroscopy. Calibrations based on the net analyte signal of urea are particularly appealing because they do not require a training step, as do statistical multivariate calibration procedures such as partial least-squares regression.

Calibration↗
PubMed2003

Response to inadequate dialysis in chronic peritoneal dialysis patients. Results from the 2000 Centers for Medicare and Medicaid (CMS) ESRD Peritoneal Dialysis Clinical Performance Measures (PD-CPM) Project.

BACKGROUND: It is not known if patient prescriptions are being changed if patients are receiving an inadequate dose of peritoneal dialysis. METHODS: Data from the 2000 Centers for Medicare and Medicaid were used to obtain data on dialysis adequacy and dialysis prescriptions. RESULTS: A total of 359 of 1,268 (28%) adult peritoneal dialysis patients had a total weekly Kt/V urea (twKt/V) less than 2.0 and 436 of 1,245 (35%) patients had a total weekly creatinine clearance (twCrCl) less than 60 L/wk/1.73 m2, defined as "inadequate dialysis." Among chronic ambulatory peritoneal dialysis (CAPD) patients, 81 of 188 (43%) patients had inadequate dialysis and a change in the peritoneal dialysis prescription within 6 months of the initial adequacy value. Among cycler patients, 106 of 197 (54%) patients had inadequate dialysis and a change in the prescription. Thirty-six of 46 (78%) CAPD patients and 48 of 56 (86%) cycler patients had an improvement in twKt/V after the prescription was revised. Thirty-two of 42 (76%) CAPD patients and 45 of 57 (79%) cycler patients had an improvement in twCrCl after the prescription was changed. For these patients, twKt/V increased from 1.6 +/- 0.3 to 2.1 +/- 0.5, with an increase in the peritoneal Kt/V urea from 1.5 +/- 0.3 to 1.9 +/- 0.4. Similarly, twCrCl increased from 46.3 +/- 7.5 to 59.1 +/- 10.6 L/wk/1.73 m2 with an increase in the peritoneal CrCl dose from 42.0 +/- 9.1 to 52.7 +/- 9.9 L/wk/1.73 m2. CONCLUSION: About half of peritoneal dialysis patients with inadequate dialysis did not have a prescription change and could benefit from modifications in their dialysis prescription.

Adult↗
PubMed2002

A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome.

The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart.

Animals↗
PubMedDate not supplied

Technology in clinical practice.

Salt and water are the major components of extracellular fluid, and each patient on dialysis has a unique serum sodium activity that is defended to ensure homeostasis. Dialysate use that does not restore extracellular composition to its equilibrium value results in disequilibrium and affects dialysis discomfort, blood pressure, thirst, and weight gain. When dialysate sodium activity exceeds the dialyzable plasma sodium activity, sodium diffuses from the dialysate into the patient. This results in hypertonicity, cellular dehydration, plasma volume expansion, and hypertension. A dialysate sodium activity below the patient's dialyzable plasma sodium reverses this process. Neither of these situations is desirable. Rather, dialysis should restore homeostasis by reconstituting the extracellular fluid to its desired salt and water content. Because each patient has a unique serum sodium activity, this goal can only be realized by using individualized dialysate sodium prescriptions. Further, because a patient's dialyzable sodium is dynamic and determined by serum chemistry plus dialyzer membrane behavior, the dialysate sodium needed to achieve isonatemic dialysis can only be defined by measuring the dialyzable serum sodium activity during dialysis. Achieving balanced salt and water removal to preserve homeostasis and intracellular tonicity requires automated sensors and feed-back control of dialysate conductivity.

Biotechnology↗
PubMedDate not supplied

Risk factors for early mortality in U.S. peritoneal dialysis patients: impact of residual renal function.

BACKGROUND: Potential risk factors for 1-year mortality, including the peritoneal component of dialysis dose, residual renal function, demographic data, hematocrit, serum albumin, dialysate-to-plasma creatinine ratio, and blood pressure, were examined in a national cohort of peritoneal dialysis patients randomly selected for the Centers for Medicare and Medicaid Services End-Stage Renal Disease (ESRD) Core Indicators Project. METHODS: The study involved retrospective analysis of a cohort of 1,219 patients receiving chronic peritoneal dialysis who were alive on December 31, 1996. RESULTS: During the 1-year follow-up period, 275 patients were censored and 200 non censored patients died. Among the 763 patients who had at least one calculable adequacy measure, the mean [+/- standard deviation (SD)] weekly Kt/V urea was 2.16 +/- 0.61 and the mean weekly creatinine clearance was 66.1 +/- 24.4 L/1.73 m2. Excluding the 365 patients who were anuric, the mean (+/- SD) urinary weekly Kt/V urea was 0.64 +/- 0.52 (median: 0.51) and the mean (+/- SD) urinary weekly creatinine clearance was 31.0 +/- 23.3 L/1.73 m2 (median: 26.3 L/1.73 m2). By Cox proportional hazard modeling, lower quartiles of renal Kt/V urea were predictive of 1-year mortality; lower quartiles of renal creatinine clearance were of borderline significance for predicting 1-year mortality. The dialysate component of neither the weekly creatinine clearance nor the weekly Kt/V urea were predictive of 1-year mortality. Other predictors of 1-year mortality (p < 0.01) included lower serum albumin level, older age, and the presence of diabetes mellitus as the cause of ESRD, and, for the creatinine clearance model only, lower diastolic blood pressure. CONCLUSION: Residual renal function is an important predictor of 1-year mortality in chronic peritoneal dialysis patients.

Adult↗
PubMedDate not supplied

Sources of Staphylococcus aureus for patients on continuous ambulatory peritoneal dialysis.

OBJECTIVE: This study was designed to determine whether family members and health care workers are a source of Staphylococcus aureus for patients on peritoneal dialysis. DESIGN: Over 36 months, cultures were obtained from the nares of patients, family members that cared for the patients' catheters, and health care workers in a dialysis unit. Pulsed-field gel electrophoresis was performed on all S. aureus isolates. SETTING: A university-based peritoneal dialysis program. PARTICIPANTS: 74 patients, 32 family members, and 17 health care workers. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The number of patients that acquired S. aureus strains during the study period. RESULTS: Of the 48 patients whose initial nares cultures were negative, 7 (15%) acquired S. aureus strains. Overall, 24 of 53 (45%) patients that had 2 or more cultures obtained during the study gained strains. Potential sources were not identified for strains gained by 11 (46%) patients. Five patients appeared to acquire their strains from family members; however, other patients also shared related strains; 8 patients acquired strains shared by other patients. CONCLUSIONS: Family members and other patients appeared to be important sources of S. aureus for patients on peritoneal dialysis. Health care workers that carry S. aureus transiently may be important intermediaries. Good hand hygiene is essential to prevent transmission of S. aureus to these susceptible patients.

Caregivers↗