A case of distal limb arterial tortuosity and dilation: observations and potential clinical significance.

Arterial tortuosity describes variation via bending of the arterial wall and has been noted in several arteries throughout the body. Tortuous blood vessels can cause nerve compression, as well as present difficulties to surgeons and radiologists. Here we present an unusual case of multi-vessel arterial tortuosity discovered in 78-year-old Hispanic male cadaver, independent of systemic pathology. The left ulnar and right tibial arteries were dissected, and using calibrated digital callipers, their external and internal diameters were measured both at the origin site and at the site of greatest dilation. Both wall thickness and the number of inflection points were also measured. Six bends were noticed in the ulnar artery and its diameter measured 8.11 mm at its widest, with a wall thickness of 0.88 mm. On the lower extremity, the right tibial artery had three bends and its diameter measured 4.86 mm at its widest, with a wall thickness of 1.32 mm. This uncommon tortuosity is not only more prone to laceration during surgery, but the bending and thickening can be mistaken for tumours. Finally, fluid dynamics can be altered, resulting in an impact on blood pressure in the extremities. Thus, raising awareness is crucial to prevent both symptoms and iatrogenic complications.

Cardiovascular risk modification in participants with coronary disease screened by the Kidney Early Evaluation Program.

BACKGROUND: Coronary artery disease (CAD) identifies the need for intensive treatment of risk factors among individuals with chronic kidney disease (CKD), a high-risk, complex cardiovascular risk state. METHODS: An estimated glomerular filtration rate<60 mL/min/1.73 m2 or a urine albumin:creatinine ratio (ACR)≥30 mg/g (3.4 mg/mmol) defined CKD. RESULTS: Of 70,454 volunteers screened the mean age was 53.5±15.7 years and 68.3% were female. A total of 5410 (7.7%) had a self-reported history of CAD; 1295 (1.8%) had a history of prior percutaneous coronary intervention (PCI); and 1124 (1.6%) had a prior history of coronary artery bypass surgery (CABG). Multivariate analysis for the outcome of suboptimal CAD risk management (composite of systolic blood pressure≥130 mmHg, glucose≥125 mg/dL (6.9 mmol/L) for diabetics, total cholesterol≥200 mg/dL (5.2 mmol/L), or current smoking; n=38,746/53,403, 72.5%) revealed older age (per year) (odds ratio (OR)=1.04, 95% confidence interval (CI) 1.03-1.04, P<0.0001), male gender (OR=1.40, 95% CI 1.34-1.47, P<0.0001), ACR≥30 mg/g (3.4 mg/mmol) (OR=1.66, 95% CI 1.55-1.79, P<0.0001), body mass index (per kg/m2) (OR=1.06, 95% CI 1.06-1.06, P<0.0001), CAD without a history of revascularization (OR=1.14, 95% CI 1.02-1.28, P=0.02) and care received by a nephrologist (OR=1.49, 95% CI 1.22-1.83, P<0.0001) were associated with worse risk factor control. Prior coronary revascularization and being under the care of a cardiologist were not associated with either improved or suboptimal risk factor control. CONCLUSIONS: Chronic kidney disease is associated with overall poor rates of CAD risk factor control.

Insights Obtained by Culturing Saccharibacteria With Their Bacterial Hosts.

Oral microbiome research has moved from asking "Who's there?" to "What are they doing?" Understanding what microbes "do" involves multiple approaches, including obtaining genomic information and examining the interspecies interactions. Recently we isolated a human oral Saccharibacteria (TM7) bacterium, HMT-952, strain TM7x, which is an ultrasmall parasite of the oral bacterium Actinomyces odontolyticus. The host-parasite interactions, such as phage-bacterium or Saccharibacteria-host bacterium, are understudied areas with large potential for insight. The Saccharibacteria phylum is a member of Candidate Phyla Radiation, a large lineage previously devoid of cultivated members. However, expanding our understanding of Saccharibacteria-host interactions requires examining multiple phylogenetically distinct Saccharibacteria-host pairs. Here we report the isolation of 3 additional Saccharibacteria species from the human oral cavity in binary coculture with their bacterial hosts. They were obtained by filtering ultrasmall Saccharibacteria cells free of other larger bacteria and inoculating them into cultures of potential host bacteria. The binary cocultures obtained could be stably passaged and studied. Complete closed genomes were obtained and allowed full genome analyses. All have small genomes (<1 Mb) characteristic of parasitic species and dramatically limited de novo synthetic pathway capabilities but include either restriction modification or CRISPR-Cas systems as part of an innate defense against foreign DNA. High levels of gene synteny exist among Saccharibacteria species. Having isolates growing in coculture with their hosts allowed time course studies of growth and parasite-host interactions by phase contrast, fluorescence in situ hybridization, and scanning electron microscopy. The cells of the 4 oral Saccharibacteria species are ultrasmall and could be seen attached to their larger Actinobacteria hosts. Parasite attachment appears to lead to host cell death and lysis. The successful cultivation of Saccharibacteria species has significantly expanded our understanding of these ultrasmall Candidate Phyla Radiation bacteria.

Long-term outcomes in nondiabetic chronic kidney disease.

The Modification of Diet in Renal Disease (MDRD) Study examined the effects of strict blood pressure control and dietary protein restriction on the progression of kidney disease. Here, we retrospectively evaluated outcomes of nondiabetic participants with stages 2-4 chronic kidney disease (CKD) from randomized and nonrandomized cohorts of the MDRD Study. Kidney failure and survival status through December of 2000, were obtained from the US Renal Data System and the National Death Index. Event rates were calculated for kidney failure, death, and a composite outcome of death and kidney failure. In the 1666 patients, rates for kidney failure were four times higher than that for death. Kidney failure was a more likely event than death in subgroups based on baseline glomerular filtration rate, proteinuria, kidney disease etiology, gender, and race. It was only among those older than 65 that the rate for death approximated that for kidney failure. In contrast to other populations with CKD, our study of relatively young subjects with nondiabetic disease has found that the majority of the participants advanced to kidney failure with a low competing risk of death. In such patients, the primary emphasis should be on delaying progression of kidney disease.

Low birth weight is associated with chronic kidney disease only in men.

The association of low birth weight and chronic kidney disease was examined in a screened volunteer population by the National Kidney Foundation's Kidney Early Evaluation Program. This is a free, community-based health program enrolling individuals aged 18 years or older with diabetes, hypertension, or a family history of kidney disease, diabetes, or hypertension. Self-reported birth weight was categorized and chronic kidney disease defined as an estimated glomerular filtration rate less than 60 ml per min per 1.73 m(2) or a urine albumin/creatinine ratio >or=30 mg/g. Among 12 364 participants, 15% reported a birth weight less than 2500 g. In men, significant corresponding odds ratios were found after adjustment for demographic characteristics and health conditions to this low birth weight and chronic kidney disease, but there was no association among women. There was no significant interaction between birth weight and race for either gender. Efforts to clinically understand the etiology of this association and potential means of prevention are essential to improving public health.

Mortality studies comparing peritoneal dialysis and hemodialysis: what do they tell us?

Several recent large-scale epidemiological studies comparing mortality among end-stage renal disease (ESRD) patients receiving hemodialysis (HD) versus peritoneal dialysis (PD) show conflicting results. In this paper, we undertake a critical review of these studies. Our goal is to determine if there are any consistent trends in outcomes between HD and PD within select subgroups of patients once methodological differences have been accounted for. A total of six large-scale registry studies and three prospective cohort studies conducted in the United States (US), Canada, Denmark, and the Netherlands were reviewed. Summary findings from these studies are presented for comparative purposes. Additional summary analyses based on previously reported data on 398 940 incident US Medicare patients are included for the purpose of comparing results from this population of patients to those of the other select studies when similar methods of analysis are applied. Results are summarized in terms of the relative risk of death for PD versus HD (RR[PD:HD]). Differences in results between the nine studies can be attributed to the degree of case-mix adjustment carried out and to the use of different subgroups when comparing mortality between HD and PD. When these differences are accounted for, we found a remarkable degree of synergism in results between the registry studies and, to a lesser degree, the prospective cohort studies. PD was generally found to be associated with equal or better survival among non-diabetic patients and younger diabetic patients in all four countries. However, among older diabetic patients, results varied by country. The Canadian and Danish registries showed no difference in survival between PD and HD among older diabetics while in the US, HD was associated with better survival for diabetics aged 45 and older. All studies show a time-dependent trend in the RR of death with PD generally associated with equivalent or better survival during the first year or two of dialysis. However, results on longer-term survival varied according to study and to different subgroups within studies. Subgroup analyses in the prospective cohort studies were limited by small numbers of patients resulting in highly varied and somewhat controversial results when compared to the larger registry-based studies. Based on our review of recent publications and additional analyses of US Medicare data, we conclude that overall patient survival is similar for PD and HD but that important differences do exist within select subgroups of patients, particularly those subgroups defined by age and the presence or absence of diabetes.

Galactose inhibits lactase expression by mouse jejunal enterocytes.

Present work uses a combination of quantitative cytochemistry and measurements of cell migration rates to describe galactose effects on lactase expression by mouse enterocytes. Mice fed galactose were found to eat less, weigh less and drink more than mice maintained on a low-carbohydrate isocalorific diet. The enterocyte migration rate in these mice was also only one third of that determined in low-carbohydrate-fed animals. The rate at which lactase activity increased in the brush border membrane of migrating enterocytes was 3-times greater in low-carbohydrate- compared with galactose-fed mice. The time during which this increase persisted was, however, 3-times less in low-carbohydrate-fed animals. The maximum rate of sucrase-maltase appearance, measured as control in these experiments, remained unaffected by galactose feeding. Galactose effects on lactase expression might in part result from mice being unable to metabolise this substrate. Previously it has been stated that galactose increases lactase biosynthesis in rat intestine (Koldovsky, O., Bustamonte, S. and Yamada (1981) In Mechanisms of intestinal adaptation (Robinson, J.W.L., Dowling, R.H. and Ricken, E.O., eds.), pp. 153-156, MTP Press, Lancaster). This result is discussed in relation to the opposite finding reported in the present work for mouse jejunal enterocytes. The need to relate enzyme appearance to age and developmental state of enterocytes in this type of study is also emphasized.

Acute promyelocytic leukemia. Management of the coagulopathy during daunorubicin-prednisone remission induction.

Seven adults with acute promyelocytic leukemia (APL) and disseminated intravascular coagulation were treated for remission induction with daunorubicin hydrochloride and prednisone. In all patients the coagulopathy was managed with continuous-infusion heparin sodium and vigorous transfusion with platelets, cryoprecipitate, and fresh frozen plasma. Five patients survived induction; they all achieved complete remission (CR). Median duration of CR was 27 + months; two patients presently survive in their initial CR at 28 and 48 months. Recognition of APL as a distinct type of acute leukemia and prompt initiation of treatment aimed at rapid cytoreduction and control of the coagulopathy has resulted in a prolonged disease-free survival for the majority of patients.

Modelling molecular mechanisms controlling sequential gene expression in differentiating mammalian enterocytes.

The gut epithelium represents a continuous developmental system in which cell proliferation in intestinal crypts is followed by the sequential expression of digestive and absorptive functions as enterocytes migrate out of crypts to the tips of intestinal villi. We have developed a mathematical model in the present work to mimic these sequential aspects of enterocyte differentiation. Using this model allows the characteristics of lactase expression to be ascribed to transcriptional control. In the case of a glucose transporter, however, it became necessary to assume an additional translational control that decreased exponentially as enterocytes migrated along villi. The suggestion that this type of modelling is useful in predicting which set of enterocytes is likely to use translation or transcription to control gene expression is also discussed.

Disposition of vancomycin during hemofiltration.

The disposition of vancomycin was assessed in five patients receiving hemofiltration after intravenous dosing with an 18 mg/kg dose after a hemofiltration procedure. The serum concentration-time profile was characterized before, during, and after the next hemofiltration procedure. The t 1/2 of vancomycin was 136.0 +/- 27.2 hours (mean +/- SD) before hemofiltration and 4.1 +/- 1.2 during hemofiltration. Approximately 400 mg of vancomycin was recovered in the filtrate and the hemofiltration clearance was 152.6 +/- 21.5 ml/min. A significant relationship was observed between vancomycin clearance and ultrafiltration flow rate (r = 0.9914). A marked rebound in vancomycin serum concentration (52.4% +/- 15.6%) was observed in all patients. Hemofiltration has a significant effect on the disposition of vancomycin. Because of the marked interpatient variability in elimination t 1/2 and the degree and time course of the rebound, an individualized approach to vancomycin therapy in this patient population is recommended.

In vitro effects of non-steroidal anti-inflammatory drugs on human polymorphonuclear cells and lymphocyte migration.

1. The action of the non-steroidal anti-inflammatory drugs (NSAID), sodium salicylate, aspirin, phenylbutazone and indomethacin was investigated on the migration of human polymorphonuclear cells (PMNs) and lymphocytes, using the system of migration of leucocytes from glass capillary tubes. 2. All NSAID produced a dose-dependent inhibition of cell migration, and were more effective on the migration of the PMN than on lymphocytes. 3. Drugs optimally suppressed PMN migration after 20 to 24 h incubation, and lymphocytes after 3 to 6 h. 4. Prolonged incubation of cells with several concentrations of NSAID demonstrated an 'escape' from inhibition in PMNs prepared from one subject.

A sequential screning test based on the running component of audiogenic seizures in mice, including reference compound PD50 values.

1. The running component of audiogenic seizures in mice has been used as the basis of a sequential screening test for the detection of a variety of centrally acting drugs.2. For acceptance by the test, an active compound must completely suppress the running component in a total of sixteen mice at a dose of 1/5 LD50 intraperitoneally.3. Considerable economies in the numbers of animals required for screening have been achieved, the mean number of mice required to reject an inactive compound being 2.0.4. The running component is highly sensitive to anticonvulsants and general central depressants, and insensitive to phenothiazine tranquillizers and morphine. Reserpine caused an increase in the severity of the running component.5. The statistical model used in this test is of general application to screening test situations which use quantal data.

Measurement of inflammation in man and animals by radiometry.

1. A radiometer is described, which is sensitive to infrared radiation in the range 0-25 mum, and which, after calibration with a black body standard can be used as a non-contact, fast reading thermometer.2. An example of acute joint inflammation in a patient with rheumatoid arthritis is described. The temperatures over the joint measured by radiometry, followed inflammatory changes in the joint effusion.3. Using rats, the method of measuring inflammation by radiometry was compared with measurements of increase in joint size. Changes measured by radiometry preceded changes shown by increase in joint size.4. The radiometer method was able to demonstrate the effect of an anti-inflammatory drug, given orally, against carrageenin inflammation.5. The procedure was found to be an accurate means of measuring inflammation and the anti-inflammatory effects of drugs. It was faster and less tedious than the other methods for the quantitative measurement of inflammation in man and animals.

Long-term survival of renal transplant recipients in the United States after acute myocardial infarction.

Cardiac disease is a major cause of death in renal transplant recipients. One third of the cardiac deaths are attributed to acute myocardial infarction (AMI). Few data exist on predictors of long-term survival of renal transplant recipients after AMI. The purpose of this study is to determine predictors of survival (including treatment era) for renal transplant recipients in the United States after AMI. The US Renal Data System database of 783, 171 patients was used to retrospectively examine outcomes of renal transplant recipients hospitalized during 1977 to 1996 for a first AMI after initiation of renal replacement therapy. Long-term survival was estimated by life-table method, and independent predictors of survival were examined in a comorbidity-adjusted Cox model. There were 4,250 renal transplant recipients with AMI. The in-hospital death rate was 12.8%. Overall 2-year cardiac and all-cause mortality rates were 11.8% +/- 0.6% (SE) and 33.6% +/- 0. 8%, respectively. The poorest survival after AMI occurred in patients with diabetic end-stage renal disease (ESRD), with 2-year cardiac and all-cause mortality rates of 14.9% +/- 1.1% and 40.5% +/- 1.4%, respectively. In the Cox model, the risks for cardiac and all-cause death from AMI were 51% (P = 0.0003) and 45% less (P < 0. 0001) in 1990 to 1996 compared with 1977 to 1984, respectively. The long-term survival of renal transplant recipients in the United States after AMI has markedly improved in the modern treatment era. Patients with diabetic ESRD experience the worst outcome.

Cardiovascular disease in end-stage renal disease patients.

This study evaluates risk factor monitoring in end-stage renal disease (ESRD) patients with cardiovascular disease. Death rates from cardiovascular disease in ESRD patients are 20 to 40 times higher than in the general population, and 72% of ESRD patients with an acute myocardial infarction (AMI) are dead within 2 years of follow-up. Patients who have sustained an AMI rarely receive definitive testing to assess coronary circulation, and cardiac catheterization rates and revascularization rates are low, even after the high-risk event of an AMI. Risk factor intervention to treat lipid disorders in the ESRD population has received little attention, with the USRDS reporting that in 1998, 58% of dialysis and 64% of transplant patients had no lipid monitoring performed within a year. Of those tested, only 33% of dialysis and 27% of transplant patients had two or more tests within 1 year. Glycemic control monitoring in the form of HbA1c, recommended for diabetes management, is also underutilized in ESRD patients, with fewer than half receiving a single test within 1 year and only 10% receiving three or more tests. This raises concerns that diabetic glycemic control monitoring may be suboptimal in the ESRD population. The use of diabetic eye examinations and diabetic glucose monitoring is also low, as are influenza vaccination rates. These data suggest that the clinical care of cardiovascular disease in the ESRD patients needs more attention.

Hematocrit levels and associated Medicare expenditures.

Clinical studies and the National Kidney Foundation-Dialysis Outcomes Quality Initiative guidelines suggest that a target hematocrit of 33% to less than 36% is appropriate for patient benefit. Previous studies have shown an association of lower risks for death and hospitalization when hematocrits were 33% to less than 36%. In this study, we assessed the relationship between hematocrit value and associated Medicare expenditures, analyzing incident Medicare hemodialysis patients from January 1, 1991, through June 30, 1995. All patients survived at least 90 days to normalize eligibility and an additional 6-month entry period to assess comorbidity and hematocrit values. All patients were followed up from July 1, 1991, through December 31, 1996. We assessed the association between hematocrit values in the 6-month entry period and the Medicare-allowable Part A and Part B per-member-per-month (PMPM) expenditures in the follow-up period, controlling for other variables, including patient demographic characteristics, comorbid conditions, and severity of disease. We found that hematocrits of 33% to less than 36% and 36% and higher were associated with lower Medicare-allowable payments in the follow-up period. Compared with reference patients with hematocrits of 30% to less than 33%, the Medicare-allowable PMPM expenditures were significantly greater for patients with hematocrits less than 27% and 27% to less than 30% (12. 7% and 5.3%, respectively), and the Medicare-allowable PMPMs were significantly less for patients with hematocrits of 33% to less than 36% and 36% and higher (6.0% and 8.2%, respectively). Although these findings suggest that the treatment of anemia may be associated with significant savings in total patient Medicare expenditures, caution should be considered because these findings are associations and should not be deemed as showing causality.

Prevalence and characteristics of individuals with chronic kidney disease in a large health maintenance organization.

This study is designed to estimate the prevalence of and gain further insight into the characteristics of the chronic kidney disease (CKD) population in a large US health maintenance organization (HMO) to better understand the CKD population in the United States overall. Analyses were performed using data from a staff and network model HMO in the southwestern United States with more than 150,000 members per year during 1994 to 1997. The estimated prevalence of CKD in the HMO population varied from 0.4% to 7.1%, depending on the definition of CKD used. Regardless of the definition, CKD was more common in men compared with women and in patients with diabetes mellitus and/or hypertension. Applying the age- and sex-specific prevalence rates in the HMO to the US population in 1990, we estimate there were approximately 9.1 million Americans with at least one elevated sex-specific creatinine (Cr) value and approximately 4.2 million Americans with at least two elevated Cr values separated by 90 days or greater, a more rigorous definition of CKD. From these results, it is apparent that there are a large number of patients in the United States with CKD. Most have not been identified because screening for CKD generally is not performed. Considering the high prevalence of CKD and the high cost and clinical morbidity associated with end-stage renal disease (ESRD), it is clear that CKD is an important public health problem. Early identification of patients with CKD would allow treatment that could slow the progression to ESRD, improve clinical outcomes, and constrain the growth of costs in the ESRD program. The time has come for a structured public and professional educational program to address this serious condition.

Impact of disease severity and hematocrit level on reuse-associated mortality.

Prior studies on reuse-associated mortality have presented conflicting results and included few adjustments for disease severity or hematocrit levels. To evaluate the impact of patient and provider characteristics on reuse-associated mortality, we developed a period-prevalent model with a 6-month entry period. Five cohorts of Medicare hemodialysis patients surviving from July 1 through December 31 of the entry year (1991, 60,985 patients; 1992, 63,081 patients; 1993, 76,018 patients; 1994, 82,899 patients; 1995, 91,761 patients) were followed up for the next year. Using a basic Cox regression survival model (M-1) including age, sex, race, renal diagnosis, prior end-stage renal disease time, unit age, unit size, water treatment, dialysate, and germicide, results were compared with those using a more inclusive model (M-4) adding dialyzer type (conventional or high efficiency/high flux), unit designation (hospital based or freestanding), unit profit status, comorbidity, disease severity, and hematocrit. The previous association of for-profit units with increased mortality was not present after 1994. Whereas the M-1 analysis showed better survival in reuse units after 1991, the more complete M-4 analysis showed no difference in the risk for mortality between reuse and no-reuse units. We conclude that mortality rates in the United States from 1991 to 1995, when adjusted comprehensively for patient and unit characteristics, were not different in units that practiced reuse and those that did not.

Mortality risks of peritoneal dialysis and hemodialysis.

Studies of outcomes associated with dialysis therapies have yielded conflicting results. Bloembergen et al showed that prevalent patients on continuous ambulatory peritoneal dialysis (CAPD) or continuous cycling peritoneal dialysis (CCPD) had a 19% higher mortality risk than hemodialysis patients, and Fenton et al, analyzing Canadian incident patients, found a 27% lower risk. Attempting to reconcile these differences, we evaluated incident Medicare patients (99,048 on hemodialysis, 18,110 on CAPD/CCPD) from 1994 through 1996, following up to June 30, 1997. Patients were followed to transplantation, death, loss to follow-up, 60 days after modality change, or end of the study period. For each 3-month survival period, we used an interval Poisson regression to compare death rates, adjusting for age, gender, race, and primary renal diagnosis. A Cox regression was used to evaluate cause-specific mortality, and proportionality was addressed in both regressions by separating diabetic and nondiabetic patients. The Poisson regressions showed CAPD/CCPD to have outcomes comparable with or significantly better than hemodialysis, although results varied over time. The Cox regression found a lower mortality risk in nondiabetic CAPD/CCPD patients (women younger than 55 years: risk ratio [RR] = 0. 61; Cl, 0.59 to 0.66; women age 55 years or older: RR = 0.87; Cl, 0. 84 to 0.91; men younger than 55 years: RR = 0.72; Cl, 0.67 to 0.77; men age 55 years or older: RR = 0.87; Cl, 0.83 to 0.92) and in diabetic CAPD/CCPD patients younger than 55 (women: RR = 0.88; Cl, 0. 82 to 0.94; men: RR = 0.86; Cl, 0.81 to 0.92). The risk of all-cause death for female diabetics 55 years of age and older, in contrast, was 1.21 (Cl, 1.17 to 1.24) for CAPD/CCPD, and in cause-specific analyses, these patients had a significantly higher risk of infectious death. We conclude that, overall, within the first 2 years of therapy, short-term CAPD/CCPD appears to be associated with superior outcomes compared with hemodialysis. It also appears that patients on the two therapies have different mortality patterns over time, a nonproportionality that makes survival analyses vulnerable to the length of follow-up. Further investigation is needed to evaluate both the potential explanations for these findings and the use of more advanced statistical methods in the analysis of mortality rates associated with these dialytic therapies.

Evaluation of disease-state management of dialysis patients.

Dialysis patients are the only Medicare beneficiaries prohibited from joining managed care plans. Concerns have been raised about the ability of such plans to provide the comprehensive care required by patients with this complex condition. However, more than 20,000 dialysis patients belong to such plans because they were enrolled before developing end-stage renal disease (ESRD). Disease-state management, successfully applied to patients with diabetes mellitus and congestive heart failure, is now being used in patients with ESRD. Standardized mortality ratios (SMRs) and standardized hospitalization ratios (SHRs) were calculated for 1998 and 1999 in 1,541 patients enrolled in the RMS Disease Management program of renal disease-state management using US Renal Data System methods. SMRs were 0.643 and 0.806 for 1998 and 1999, respectively, significantly different from 1.0 for both years (P < 0.001). SHRs were 0.620 and 0.503 for 1998 and 1999, respectively, significantly different from 1.0 for both years (P < 0.001). Although additional studies are needed to define the aspects of care that are most important for the outcomes seen, this study shows that favorable outcomes are achievable for this vulnerable patient population within a managed care setting that applies coordinated approaches to care.