Long-neglected stent in a transplanted kidney.
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Biomedical subjects
Publications and source records attributed to M Lam.
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Knowledge of toxins, virulence factors and antibiotic resistance genes is essential for bio-defense applications aimed at identifying 'functional' signatures for characterizing emerging or engineered pathogens. Whereas genetic signatures identify a pathogen, functional signatures identify what a pathogen is capable of. To facilitate rapid identification of sequences and characterization of genes for signature discovery, we have collected all publicly available (as of this writing), organized sequences representing known toxins, virulence factors, and antibiotic resistance genes in one convenient database, which we believe will be of use to the bio-defense research community. MvirDB integrates DNA and protein sequence information from Tox-Prot, SCORPION, the PRINTS virulence factors, VFDB, TVFac, Islander, ARGO and a subset of VIDA. Entries in MvirDB are hyperlinked back to their original sources. A blast tool allows the user to blast against all DNA or protein sequences in MvirDB, and a browser tool allows the user to search the database to retrieve virulence factor descriptions, sequences, and classifications, and to download sequences of interest. MvirDB has an automated weekly update mechanism. Each protein sequence in MvirDB is annotated using our fully automated protein annotation system and is linked to that system's browser tool. MvirDB can be accessed at http://mvirdb.llnl.gov/.
SETTING: Canada receives more than 200000 immigrants annually. Immigrants account for 92% of tuberculosis (TB) cases in Toronto, Ontario. Epidemiological profiling of recent immigrants is needed to provide more effective TB programs. DESIGN: A population-based, retrospective cohort study of recent immigrants to Ontario, 1990-1997. We generated adjusted rates, risk ratios (RRs), hazard rates since arrival, and a complementary log-log model to describe TB risk, compare the survival distributions between different sexes, age groups and world regions of birth, and determine predictors of disease. RESULTS: TB in recent immigrants was 23 times (95%CI 20.9-25.5) higher than in Canadian-born, non-aboriginal people. Those aged 16-30 and >65 years experienced the highest rates. Sub-Saharan Africa had the highest rates for both sexes (RR 95.5, 95%CI 84.3-108.2), followed by India and Asia. Hazard rates decreased after arrival, but remained elevated. The highest risk was associated with arrival in 1990 and living in Canada <1 year. CONCLUSION: Risk for TB varied by region of birth, age at landing and time since arrival. Sex was not significant. Persons from sub-Saharan Africa and age >65 years were the highest risk groups. Risk decreased significantly in the first 1-2 years after arrival, after which it plateaued.
An understanding of genetic variation and structure of pest populations has the potential to improve the efficiency of measures to control them. Genetic analysis was undertaken at five microsatellite loci in four native Australian and 14 introduced New Zealand populations of the common brushtail possum Trichosurus vulpecula in order to document these parameters. Genetic variation in New Zealand populations, and phylogenetic relationships among Australian and New Zealand populations, were largely predicted by the recorded introduction history. Populations on the two main islands of New Zealand had only slightly lower genetic diversity than did Australian populations, except that allelic richness on the South Is. was significantly lower. Diversity was higher in North Is. than in South Is. populations (although not significantly so) and mainland New Zealand populations as a group were significantly more diverse than offshore islands that represented secondary population size bottlenecks. In phylogenetic analyses South Is. and offshore island populations grouped with Tasmania, while North Is. populations grouped either with mainland Australia or were intermediate between the two Australian sources. This scheme was supported by admixture coefficients showing that North and South Is./offshore island populations were largely mainland Australian and Tasmanian in origin, respectively. Population structure differed markedly between the North and South Islands: populations were typically more genetically differentiated on the former than the latter, which also showed significant isolation-by-distance. Substantial linkage disequilibrium in most sampled New Zealand but no Australian population between microsatellite loci Tv16 and Tv27 suggests they may be physically linked.
The preparation and physical characterization are reported for the single-molecule magnet salts [M(Cp')(2)](n)()[Mn(12)O(12)(O(2)CC(6)F(5))(16)(H(2)O)(4)] (M = Fe, n = 1, Cp' = C(5)Me(5) (2a), C(5)H(5) (2b); M = Co, n = 1, Cp' = C(5)Me(5) (2c), C(5)H(5) (2d); M = Fe, n = 2, Cp' = C(5)Me(5) (2e), C(5)H(5) (2f)) to investigate the effects of paramagnetic cations on the magnetization relaxation behavior of [Mn(12)]- anionic single-molecule magnets. Complex 2a.2H(2)O crystallizes in the orthorhombic space group Aba2, with cell dimensions at 173 K of a = 25.6292(2) A, b = 25.4201(3) A, c = 29.1915(2) A, and Z = 4. Complex 2c.2CH(2)Cl(2).C(6)H(14) crystallizes in the monoclinic space group P2(1)/c, with cell dimensions at 173 K of a = 17.8332(6) A, b = 26.2661(9) A, c = 36.0781(11) A, beta = 92.8907(3) degrees, and Z = 4. These two salts consist of either paramagnetic [Fe(C(5)Me(5))(2)]+ cations or diamagnetic [Co(C(5)Me(5))(2)]+ cations, and [Mn(12)O(12)(O(2)CC(6)F(5))(16)(H(2)O)(4)]- anions. The structures of the anions in the two salts are similar, consisting of a central Mn(4)O(4) cubane moiety, surrounded by a nonplanar ring of eight Mn atoms that are bridged by and connected to the cube via mu(3)-O(2)- ions. The oxidation states of four Mn sites out of eight outer Mn ions in complex 2a were assigned to be +2.75 from the valence bond sum analysis although the disordering of bridging carboxylates prevents more precise determination. On the other hand in complex 2c, one Mn site out of eight outer Mn ions was identified as a Mn(II) ion, accommodating the "extra" electron; this was deduced by a valence bond sum analysis. Thus, the anion in complex 2c has a Mn(II)(1)Mn(III)(7)Mn(IV)(4) oxidation state description. The Jahn-Teller axes of the Mn(III) ions in both anions are roughly aligned in one direction. All complexes studied exhibit a single out-of-phase ac magnetic susceptibility (chi"(M)) signal in the 4.6-4.8 K range for complexes 2a-2d and in the 2.8-2.9 K range for complexes 2e and 2f at 1 kHz ac frequency. The temperature of the chi"(M) peaks is frequency dependent, as expected for single-molecule magnets. From Arrhenius plots of the frequency dependence of the temperature of the chi"(M) maxima, the effective energy barriers U(eff) for changing spin from "up" to spin "down" were estimated to be 50-54 K for complexes 2a-2d and 27-28 K for complexes 2e and 2f. The least-squares fits of the reduced magnetization data indicate that both complexes 2a and 2d have ground states of S = (21)/(2). High-frequency EPR spectra were recorded for complex 2a at frequencies of 217, 327, and 434 GHz in the 4.5-30 K range. The observed transition fields were least-squares fit to give g = 1.91, D = -0.35 cm(-1), and B(4)(0) = -3.6 x 10(-7) cm(-1) for the S = (21)/(2) ground state. The effective energy barrier U(eff) is slightly lower than U estimated from D, which is consistent with the thermally assisted tunneling model. Magnetization hysteresis loops were observed for complexes 2a and 2c. Although 2a was oriented in a different manner as expected by strong magnetic field, both complexes show clear hysteresis loops with some steps on them, indicating that the effect of the magnetic cation on the magnetization relaxation of the anionic [Mn(12)]- complex is rather small. An 11% (57)Fe enriched complex 2b was studied by means of Mössbauer spectroscopy down to as low as 1.7 K. Slow paramagnetic relaxation broadening and magnetic hyperfine splitting were evident in the low-temperature spectra, indicating that the iron atoms feel a growing magnetic field owing to slow magnetization reversal in the [Mn(12)]- anions.
Photodynamic therapy (PDT), a novel and promising cancer treatment that employs a combination of a photosensitizing chemical and visible light, induces apoptosis in human epidermoid carcinoma A431 cells. However, the precise mechanism of PDT-induced apoptosis is not well characterized. To dissect the pathways of PDT-induced apoptosis, we investigated the involvement of mitochondrial damage by examining a second generation photosensitizer, the silicon phthalocyanine 4 (Pc 4). By using laser-scanning confocal microscopy, we found that Pc 4 localized to cytosolic membranes primarily, but not exclusively, in mitochondria. Formation of mitochondrial reactive oxygen species (ROS) was detected within minutes when cells were exposed to Pc 4 and 670-675 nm light. This was followed by mitochondrial inner membrane permeabilization, depolarization and swelling, cytochrome c release, and apoptotic death. Desferrioxamine prevented mitochondrial ROS production and the events thereafter. Cyclosporin A plus trifluoperazine, blockers of the mitochondrial permeability transition, inhibited mitochondrial inner membrane permeabilization and depolarization without affecting mitochondrial ROS generation. These data indicate that the mitochondrial ROS are critical in initiating mitochondrial inner membrane permeabilization, which leads to mitochondrial swelling, cytochrome c release to the cytosol, and apoptotic death during PDT with Pc 4.
Photodynamic therapy (PDT) activates the mitochondrial pathway of apoptosis, for which the release of cytochrome c into the cytosol is considered critical. To further elucidate the role of cytochrome c release in PDT-induced apoptosis, we monitored cytochrome c localization immunocytochemically and related it to nuclear apoptosis of the same cells. When mouse L5178Y-R cells were treated with 300 nM phthalocyanine (Pc) 4 and 0-75 mJ/cm(2) red light, cytochrome c release had a dose response similar to that of clonogenic cell killing, with nearly identical threshold doses. Within individual cells, the release of cytochrome c appeared to be an all-or-none phenomenon. Moreover, it was tightly associated with activation of a caspase-3-like protease and changes in nuclear morphology. Thus, in response to Pc 4-PDT, the release of cytochrome c from mitochondria is a key determinant of apoptotic cell death.
The complexes [Fe[HC(3,5-Me2pz)3]2](BF4)2 (1), [Fe[HC(pz)3]2](BF4)2 (2), and [Fe[PhC(pz)2(py)]2](BF4)2 (3) (pz = 1-pyrazolyl ring, py = pyridyl ring) have been synthesized by the reaction of the appropriate ligand with Fe(BF4)2.6H2O. Complex 1 is high-spin in the solid state and in solution at 298 K. In the solid phase, it undergoes a decrease in magnetic moment at lower temperatures, changing at ca. 206 K to a mixture of high-spin and low-spin forms, a spin-state mixture that does not change upon subsequent cooling to 5 K. Crystallographically, there is only one iron(II) site in the ambient-temperature solid-state structure, a structure that clearly shows the complex is high-spin. Mössbauer spectral studies show conclusively that the magnetic moment change observed at lower temperatures arises from the complex changing from a high-spin state at higher temperatures to a 50:50 mixture of high-spin and low-spin states at lower temperatures. Complexes 2 and 3 are low-spin in the solid phase at room temperature. Complex 2 in the solid phase gradually changes over to the high-spin state upon heating above 295 K and is completely high-spin at ca. 470 K. In solution, variable-temperature 1H NMR spectra of 2 show both high-spin and low-spin forms are present, with the percentage of the paramagnetic form increasing as the temperature increases. Complex 3 is low-spin at all temperatures studied in both the solid phase and solution. An X-ray absorption spectral study has been undertaken to investigate the electronic spin states of [Fe[HC(3,5-Me2pz)3]2](BF4)2 and [Fe[HC(pz)3]2](BF4)2. Crystallographic information: 2 is monoclinic, P2(1)/n, a = 10.1891(2) A, b = 7.6223(2) A, c = 17.2411(4) A, beta = 100.7733(12) degrees, Z = 2; 3 is triclinic, P1, a = 12.4769(2) A, b = 12.7449(2) A, c = 13.0215(2) A, alpha = 83.0105(8) degrees, beta = 84.5554(7) degrees, gamma = 62.5797(2) degrees, Z = 2.
BACKGROUND: Studies in medical fields other than ophthalmology have given conflicting results regarding the reliability of the time trade-off technique of utility assessment. We performed a study to determine the test-retest reliability of the time trade-off technique for assessing utilities in patients with ocular diseases of the retina and to investigate possible factors associated with differences in utility over time. METHODS: Patients referred to the retina service of a tertiary care hospital in eastern Canada were eligible for the initial interview if they had best corrected vision of 20/30 or worse in at least one eye and were deemed competent to answer the required questions. Patients were interviewed prospectively between December 1999 and March 2000 during a normal 30-minute period needed for pharmacologic mydriasis to occur. Demographic, clinical (including Snellen visual acuity) and time trade-off utility information was collected through chart review and standardized interview. Patients who completed the interview successfully were called back 28 days later for follow-up. RESULTS: Of the 138 eligible patients 112 (81.2%) completed the initial interview. Of the 112, 96 (85.7%) completed the second interview. Half of the respondents were women, and all but one respondent were white. The mean age was 65.3 years. The primary reasons for visual loss included diabetic retinopathy (59 patients [61.4%]) and age-related macular degeneration (14 patients [14.6%]). The intraclass correlation coefficient between the initial and follow-up visual utilities was 0.7634 (95% confidence interval 0.6655-0.8355). INTERPRETATION: Our results show excellent reliability of the time trade-off technique of utility assessment in patients with ocular diseases of the retina.
OBJECTIVE: Although earlier research has suggested that baseline prealbumin level is an independent predictor of outcome among dialysis patients, the prognostic importance of serial prealbumin levels is less clear. The present study had 3 objectives: first, to determine if prealbumin (a marker of visceral protein stores with a relatively short half-life) predicts subsequent albumin levels taken at least 1 month later; second, to examine the association between serial prealbumin levels and clinical outcome; and third, to examine the association between changes in prealbumin level and outcome. DESIGN: The prognostic value of serial prealbumin levels was examined by linear regression analysis and Cox hazard models in an observational cohort study using a repeated measures design and time-dependent covariates. SETTING: Patients were followed by a tertiary care center, receiving hemodialysis (HD; at either an in-center dialysis unit or one of several satellite units operated by the hospital) or home peritoneal dialysis (PD). PATIENTS: A retrospective cohort was identified consisting of 268 incident and prevalent chronic HD and PD patients receiving dialysis from June 1998 to September 1999. MAIN OUTCOME: The study examined the association between serial prealbumin measurements and future laboratory and clinical outcomes (albumin, hospitalization, and death). RESULTS: Serial prealbumin values were independent predictors of future albumin levels among HD patients (P =.04), but not PD patients. Independent predictors of hospitalization included diabetes for PD patients (P =.0012) and advanced age for HD patients (P =.0008). Advanced age and diabetes were independent predictors of death for both HD (P =.0001 and P =.0368) and PD patients (P =.0014 and P =.0164). Serial prealbumin values, measured as time-dependent covariates, did not predict hospitalization or death. Further analyses examined the prognostic value of changes in prealbumin and albumin values as time-dependent covariates. The final multivariate analysis identified low baseline albumin level as an independent predictor of hospitalization among HD patients (P =.0282), whereas low baseline prealbumin was an independent predictor of death for HD patients (P =.0001). Interestingly, negative changes in serial prealbumin measurements were also independent predictors of death among HD patients (P =.0025). CONCLUSION: Serial prealbumin measurements predict subsequent albumin values among HD patients. As well, low baseline prealbumin level is an independent predictor of adverse outcome among HD patients. Although repeated prealbumin measurements in and of themselves were of no added prognostic value, falling prealbumin values identified by repeated measurements were additional independent predictors of death. These results support the clinical utility of regular prealbumin monitoring among HD patients.
BACKGROUND: The Cardiac Anesthesia Risk Evaluation (CARE) score is a simple risk classification for cardiac surgical patients. It is based on clinical judgment and three clinical variables: comorbid conditions categorized as controlled or uncontrolled, surgical complexity, and urgency of the procedure. This study compared the CARE score with the Parsonnet, Tuman, and Tu multifactorial risk indexes for prediction of mortality and morbidity after cardiac surgery. METHODS: In this prospective study, 3,548 cardiac surgical patients from one institution were risk stratified by two investigators using the CARE score and the three tested multifactorial risk indexes. All patients were also given a CARE score by their attending cardiac anesthesiologist. The first 2,000 patients served as a reference group to determine discrimination of each classification with receiver operating characteristic curves. The following 1,548 patients were used to evaluate calibration using the Pearson chi-square goodness-of-fit test. RESULTS: The areas under the receiver operating characteristic curves for mortality and morbidity were 0.801 and 0.721, respectively, with the CARE score rating by the investigators; 0.786 and 0.710, respectively, with the CARE score rating by the attending anesthesiologists (n = 8); 0.808 and 0.726, respectively, with the Parsonnet index; 0.782 and 0.697, respectively, with the Tuman index; 0.770 and 0.724 with the Tu index, respectively. All risk models had acceptable calibration in predicting mortality and morbidity, except for the Parsonnet classification, which failed calibration for morbidity (P = 0.026). CONCLUSIONS: The CARE score performs as well as multifactorial risk indexes for outcome prediction in cardiac surgery. Cardiac anesthesiologists can integrate this score in their practice and predict patient outcome with acceptable accuracy.
OBJECTIVE: To determine the extent to which postpyloric feeding reduces gastroesophageal regurgitation and pulmonary microaspiration in critically ill patients. DESIGN: Randomized trial. SETTING: A medical/surgical intensive care unit at a tertiary care hospital. PARTICIPANTS: Intensive care unit patients were expected to remain ventilated >72 hrs. We excluded patients with esophageal, gastric, or small bowel surgery in the last week and patients with overt or clinically significant gastrointestinal bleeding. We studied 33 patients; 42.4% were female, mean age (sd) was 59.2 (+/- 16.8) yrs, and mean Acute Physiology and Chronic Health Evaluation II score was 22.5 (7.8). INTERVENTIONS: Patients were randomized to gastric or postpyloric enteral feeds. Technetium 99-sulphur colloid was added to the feeds for 6 hrs of each of the first 3 days on study. MEASUREMENTS AND RESULTS: We sampled the oropharynx and trachea hourly for the 6 hrs per day that patients received radioisotope-labeled enteral feeds, and the level of radioactivity in these specimens was measured. We defined an episode of gastroesophageal regurgitation and microaspiration as an increase in radioactivity >100 counts per minute/g. Patients fed into the stomach had more episodes of gastroesophageal regurgitation (39.8% vs. 24.9%, p =.04) and trended toward more microaspiration (7.5% vs. 3.9%, p =.22) compared with patients fed beyond the pylorus. When the logarithmic mean of the radioactivity count was compared across groups, there was a trend toward an increase in gastroesophageal regurgitation (3.7 vs. 2.9 counts/g, p =.22) and a trend toward increased microaspiration (1.9 vs. 1.4 counts/g, p =.09) in patients fed into the stomach. Patients who had gastroesophageal regurgitation were much more likely to aspirate than patients who did not have gastroesophageal regurgitation (odds ratio: 3.2; 95% confidence interval: 1.36, 7.77). CONCLUSIONS: Feeding beyond the pylorus is associated with a significant reduction in gastroesophageal regurgitation and a trend toward less microaspiration.
The neonatal Fc receptor, FcRn, transports immunoglobulin G (IgG) across intestinal epithelial cells of suckling rats and mice from the lumenal surface to the serosal surface. In cell culture models FcRn transports IgG bidirectionally, but there are differences in the mechanisms of transport in the two directions. We investigated the effects of mutations in the cytoplasmic domain of FcRn on apical to basolateral and basolateral to apical transport of Fc across rat inner medullary collecting duct (IMCD) cells. Basolateral to apical transport did not depend upon determinants in the cytoplasmic domain. In contrast, an essentially tailless FcRn was markedly impaired in apical to basolateral transport. Using truncation and substitution mutants, we identified serine-313 and serine-319 as phosphorylation sites in the cytoplasmic domain of FcRn expressed in Rat1 fibroblasts. Mutations at Ser-319 did not affect transcytosis across IMCD cells. FcRn-S313A was impaired in apical to basolateral transcytosis to the same extent as tailless FcRn, whereas FcRn-S313D transported at wild-type levels. FcRn-S313A recycled more Fc to the apical medium than the wild-type receptor, suggesting that Ser-313 is required to allow FcRn to be diverted from an apical recycling pathway to a transcytotic pathway.
AIM: Previous studies report a high prevalence of proteinuria in patients with obstructive sleep apnea syndrome (OSAS). This common syndrome may therefore be an important cause ofproteinuria and renal failure in the general population. This study was undertaken to assess the prevalence of proteinuria among OSAS patients, and to identify the factors associated with urine protein excretion in these patients. METHODS: Overnight polysomnography, urine protein to creatinine ratio (PTCR), body mass index (BMI), mean arterial pressure (MAP), and hematocrit were assessed prospectively in 224 patients referred for evaluation of suspected OSAS. Sleep apnea was defined as apnea-hypopnea score (AHS) > or = 5 events/hour. Proteinuria was defined as PTCR > 0.2 mg/mg. RESULTS: Sleep apnea was present in 143 subjects (63.8%), and proteinuria in 10 (4.5%). The highest PTCR was 0.677 mg/mg. PTCR and AHS were weakly correlated (r = 0.12, p = 0.08). PTCR correlated (alpha = 0.05) with lowest oxygen saturation (r = -0.18, p = < 0.01), time spent with oxygen saturation below 90% (r = 0.19, p = < 0.01), and BMI (r= 0. 17, p = < 0.01). The mean PTCR was similar in subjects with and without sleep apnea. Proteinuria was present in 7 of 143 (4.9%) subjects with AHS > or = 5 and 3 of 81 (3.7%) subjects with AHS < 5, a relative risk of 1.34, 95% CI (0.34, 5.32). Predictors of LogPTCR in multiple linear regression (model R2 - 0.104) were: AHS (< 5 or > or = 5), baseline oxygen saturation, sex, and MAP. CONCLUSIONS: Clinically significant proteinuria is uncommon in OSAS. The prevalence and severity of proteinuria are similar in both OSAS patients and patients without sleep-disordered breathing. Sleep apnea severity is weakly associated with urine protein excretion, related more to hypoxemia than to frequency of apneic events.
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UNLABELLED: Daily consumption of xylitol (5-10 g/day) added to chewing gum and confectionary foods has been previously shown to prevent dental caries in children. METHODS: Snack foods containing xylitol were developed and tested for acceptability in a convenience sample of 31 children ages 3 to 6 years. In order to mimic an after-meal snack, all children were tested during mid-morning, approximately 1 h after eating. Preference testing was based on the methodology of Birch et al. (J Nutr Educ, 1979; 11: 77-80). In the first phase, each child was presented with a tray of six xylitol-based foods (popsicles, pudding, gum drops, gelatin dessert, cookies, popcorn) and asked to taste each item in any desired order. Immediately after tasting a food, the child was asked to place it in front of one of three cartoon faces (smile, frown or neutral) representing the child's response to the taste of that particular food. In the second phase, the child was asked to rank order the foods in each face category (smile, frown or neutral). Ranks within categories were then combined to obtain a rank ordering for all of the foods. RESULTS: Non-parametric data analysis indicated significant differences in ranking between the foods when they were compared to each other (Friedman ANOVA by ranks, P<0.01). Pudding was significantly less preferred than the other foods (sign tests, P<0.04). At least 84% of the children found five of the six foods very good or satisfactory, when considered individually. CONCLUSIONS: These results suggest that snack foods developed with xylitol are generally well accepted by children.
A case of mesangioproliferative glomerulonephritis in a 55-year-old woman with selective IgA deficiency and serum antinuclear antibodies who presented with nephrotic syndrome is described. The patient did not have clinical or laboratory features of systemic lupus erythematosus (SLE) other than antinuclear antibodies. Histology of the patient's renal biopsy revealed a mesangioproliferative glomerulonephritis and direct immunofluorescence showed that paramesangial deposits contained predominant IgM with lesser IgG, C3 and C1q. These findings are identical to those previously described in a form of glomerulonephritis associated with IgA deficiency and would be atypical for lupus nephritis. Glomerulonephritis is not a well recognized complication of IgA deficiency, though it has been rarely reported in the literature. This case provides further evidence that IgA deficiency is associated with a unique immune complex-mediated glomerulopathy with characteristic immunopathological and ultrastructural features. It is the first reported case to present with nephrotic syndrome.
OBJECTIVE: Previous investigations using univariate study designs have reported that delayed referral to predialysis clinics is associated with adverse outcomes at the time of dialysis initiation. However, the independent effect of delayed referral is poorly defined. Moreover, the optimal time at which to refer patients to predialysis programs remains unclear. The aim of this study was to identify independent predictors of dialysis initiation requiring hospitalization. MATERIALS AND METHODS: A retrospective cohort of 201 predialysis patients was investigated using multivariate logistic regression analysis. RESULTS: Multivariate analysis selected advanced age (odds ratio (OR) 1.038,95% confidence interval (CI) 1.011-1.065), history of congestive heart failure (OR 2.877, 95% CI 1.205-6.871), and shorter predialysis follow-up time (OR 0.945, 95% CI 0.920-0.971) as independent predictors of in-hospital dialysis initiation. The risk of in-hospital dialysis initiation increased by 5.5% for every month lost due to late referral. CONCLUSION: Patients should be referred to predialysis programs as early as 24 months before anticipated dialysis initiation in order to minimize the risk of future adverse outcomes.