Fluorescence in situ hybridization identifies high risk Barrett's patients likely to develop esophageal adenocarcinoma.

Barrett's esophagus (BE) with high-grade dysplasia (HGD) defines a group of individuals at high risk of progression to esophageal adenocarcinoma (EA). Fluorescence in situ hybridization (FISH) has been shown to be useful for the detection of dysplasia and EA in endoscopic brushing specimens from BE patients. The aim of this study was to determine whether FISH in combination with histological findings would further identify more rapid progressors to EA. This is a retrospective cohort study of high-risk patients, having a history of biopsy-confirmed HGD without EA, with an endoscopic brushing specimen analyzed by FISH while undergoing endoscopic surveillance and treatment between April 2003 and October 2010. Brushing specimens were assessed by FISH probes targeting 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) and evaluated for the presence of polysomy, defined as multiple chromosomal gains (displaying ≥ 3 signals for ≥ 2 probes). Specimens containing ≥ 4 cells exhibiting polysomy were considered polysomic. HGD was confirmed by at least two experienced gastrointestinal pathologists. Of 245 patients in this study, 93 (38.0%) had a polysomic FISH result and 152 (62.0%) had a non-polysomic FISH result. Median follow-up was 3.6 years (interquartile range [IQR] 2-5 years). Patients with a polysomic FISH result had a significantly higher risk of developing EA within 2 years (14.2%) compared with patients with a non-polysomic FISH result (1.4%, P < 0.001). These findings suggest that a polysomic FISH result in BE patients with simultaneous HGD identifies patients at a higher risk for developing EA compared with those with non-polysomy.

NSGC practice guideline: prenatal screening and diagnostic testing options for chromosome aneuploidy.

The BUN and FASTER studies, two prospective multicenter trials in the United States, validated the accuracy and detection rates of first and second trimester screening previously reported abroad. These studies, coupled with the 2007 release of the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin that endorsed first trimester screening as an alternative to traditional second trimester multiple marker screening, led to an explosion of screening options available to pregnant women. ACOG also recommended that invasive diagnostic testing for chromosome aneuploidy be made available to all women regardless of maternal age. More recently, another option known as Non-invasive Prenatal Testing (NIPT) became available to screen for chromosome aneuploidy. While screening and testing options may be limited due to a variety of factors, healthcare providers need to be aware of the options in their area in order to provide their patients with accurate and reliable information. If not presented clearly, patients may feel overwhelmed at the number of choices available. The following guideline includes recommendations for healthcare providers regarding which screening or diagnostic test should be offered based on availability, insurance coverage, and timing of a patient's entry into prenatal care, as well as a triage assessment so that a general process can be adapted to unique situations.

A line scanning confocal fluorescent microscope using a CMOS rolling shutter as an adjustable aperture.

Traditional confocal microscopy uses a physical aperture barrier to prevent out-of-focus light from reaching the detector. The physical nature of a conventional aperture limits control over the system confocality. We describe a new line scanning confocal microscope that eliminates a need for a physical aperture by employing a software-controllable rolling shutter on a CMOS camera. A confocal image is obtained by synchronizing motion of the rolling shutter and the laser line scanning over a sample. Confocal resolution of this microscope is adjustable in real time and independently established for each fluorescence channel by changing the rolling shutter width. This technology has been implemented in the IN Cell Analyzer 6000 system by GE Healthcare.

Accidental discharge of brodifacoum baits into a freshwater lake: a case study.

Approximately 700 kg of cereal bait containing 20 ppm of the anticoagulant rodenticide brodifacoum was spilled into a southern New Zealand lake in 2010 from a helicopter being used to transport containers of brodifacoum bait for an aerial baiting operation. In the month after the spill no residual brodifacoum was detected in samples of lake water, sediment, benthic invertebrates, eels, and two birds.

Clinical characteristics and outcomes of diabetic patients with Staphylococcus aureus bacteremia and endocarditis.

The complications from S. aureus bacteremia (SAB) and infective endocarditis (SAIE) are higher in patients with diabetes. We summarize the characteristics and outcome of diabetic patients enrolled in a multicenter trial of daptomycin vs. standard therapy for SAB and SAIE. Adult patients with SAB were randomized to daptomycin 6 mg/kg/day or standard therapy (vancomycin 1 g every 12 h or antistaphylococcal penicillin 2 g every 4 h, both with gentamicin 1 mg/kg every 8 h for 4 days). Clinical success was defined as survival, resolution of S. aureus infection, and clinical outcome of cure or improved 6 weeks after end of therapy. Diabetic patients (86/235) were older, more overweight, and were more likely to present with systemic inflammatory response syndrome (SIRS) and to have complicated SAB. Clinical success rates were similar (67.4% in diabetics and 70.5% in non-diabetics). The mortality rate was significantly higher among diabetic patients (22.1% vs. 11.4%, p = 0.038). In the diabetes subgroup, the clinical success and mortality rates were comparable between the daptomycin and the standard therapy arms. The presence of diabetes is associated with significantly higher mortality in patients with SAB and SAIE. Daptomycin is an alternative therapeutic option in diabetic patients with these serious staphylococcal infections.

Outcomes with daptomycin versus standard therapy for osteoarticular infections associated with Staphylococcus aureus bacteraemia.

OBJECTIVES: To evaluate the clinical characteristics, treatment and outcomes of patients with osteoarticular infections (OAIs) associated with Staphylococcus aureus bacteraemia (SAB). METHODS: The clinical characteristics and outcomes for patients with OAI were described using a post hoc analysis of an open label, randomized trial comparing daptomycin with standard therapy (vancomycin or anti-staphylococcal penicillin with initial gentamicin) for the treatment of SAB. RESULTS: OAI occurred in 32 of 121 patients (21 daptomycin and 11 standard therapy) with complicated SAB (18 septic arthritis, 9 vertebral osteomyelitis and 7 others). Two patients had osteomyelitis in more than one site. Success rates seen in two groups were as follows: vertebral osteomyelitis [3/5 (60%) daptomycin versus 0/2 (0%) comparator], septic arthritis [7/11 (64%) versus 3/5 (60%)], sternal osteomyelitis [3/3 (100%) versus 1/2 (50%)] and long bone osteomyelitis [0/1 (0%) versus 1/1 (100%)]. Success rates in both treatment groups improved with surgical therapy. Creatine phosphokinase elevations to >500 IU/L occurred in one patient on daptomycin who discontinued therapy, whereas renal impairment developed in three patients on standard therapy, two of whom discontinued therapy. Two patients treated with daptomycin and one patient on vancomycin had increases in S. aureus MICs to daptomycin and vancomycin, respectively. Three patients treated with daptomycin died following completion of therapy, with mortality attributed to multiple co-morbid conditions and inadequate debridement of OAIs in these patients. No deaths were reported in the standard therapy group. CONCLUSIONS: Daptomycin may be considered an alternative to standard therapy in the treatment of patients with complicated SAB and OAI.

Phase I trial of recombinant interleukin 3 before and after carboplatin/etoposide chemotherapy in patients with solid tumors: a southwest oncology group study.

Recombinant human interleukin 3 (rhIL-3, expressed in Escherichia coli) is a hematopoietic growth factor with protean biological effects on bone marrow in animal models, including enhanced granulocyte and platelet production and the capacity to ameliorate chemotherapy-induced bone marrow toxicity. We, therefore, undertook a Phase I trial in patients with advanced solid tumors and normal bone marrow function. Cohorts of four to six patients each received daily s.c. doses of rhIL-3 (SDZ-ILE-964; Sandoz) at dose levels of 1. 0, 2.5, 5.0, and 10.0 microgram/kg according to the following schedule: cycle 1, rhIL-3 days 1-14; cycle 2, carboplatin (350 mg/m2) on day 1 and etoposide (100 mg/m2) on days 1-3; and cycle 3, carboplatin (350 mg/m2) on day 1, etoposide (100 mg/m2) on days 1-3, and rhIL-3 on days 4-17. Each cycle was a total of 28 days. An analysis of 20 patients entered into all four escalating dose levels revealed that, during cycle 1, absolute neutrophil count (ANC) increased from a median baseline of 6,643/mm3 to a median of 12,692/mm3, and platelets increased from a median baseline of 314,000/mm3 to a median of 465,000/mm3. When cycle 2 was compared with cycle 3, the median ANC nadir increased from 192/mm3 to 988/mm3, and the mean ANC nadir increased from 458/mm3 to 1,297/mm3. Median platelet count nadirs increased from 29,000/mm3 to 84,000/mm3, and the mean nadir platelet counts increased from 72,000/mm3 to 129,000/mm3. Total days on which platelets were <50,000/mm3 was 52 for cycle 2 and 19 for cycle 3. The maximum tolerated dose of rhIL-3 was 5.0 microgram/kg/day; dose-limiting toxicities included fatigue, chills, fever, and headache. These data suggest a clear but variable biological activity observed with IL-3, as measured by the reduction in the depth and duration of thrombocytopenia and/or neutropenia when cycle 2 was compared with cycle 3. rhIL-3 is a promising cytokine that may help to ameliorate the bone marrow toxicity observed with the use of chemotherapeutic agents.

Interferon-alpha 2a in the treatment of acquired immunodeficiency syndrome-related Kaposi's sarcoma.

In a series of studies, recombinant interferon-alpha 2a (rIFN alpha 2a, Roferon-A) was administered alone (273 men) or combined with vinblastine (91 men) to patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma (KS). Patients were treated with daily doses of rIFN alpha 2a ranging from 3 to 54 million international units (I.U.) administered intramuscularly. A dose of 36 million I.U. daily for approximately 10 weeks followed by a three times weekly maintenance schedule with the same dose resulted in the best overall therapeutic benefit. An escalating-dose regimen of 3, 9, and 18 million I.U. daily, each for 3 days, followed by 36 million I.U. daily, produced equivalent therapeutic benefit with amelioration of acute toxicity in some patients. Response was more likely in patients without a history of opportunistic infection or B symptoms (fever, night sweats, or weight loss). Response rate increased with increasing baseline CD4 lymphocyte count and was 45.5% in patients with a CD4 count of greater than 400/mm3. Responding patients with a CD4 count of greater than 200/mm3 had a distinct survival advantage over patients who had similar CD4 counts but whose tumors did not regress with therapy. The addition of vinblastine increased toxicity and did not improve the response rate or prolong survival. Side effects included fatigue, fever, chills, myalgias, headaches, anorexia, nausea, diarrhea, and dizziness. Mild abnormalities in hematologic and liver function tests occurred in some patients. Most adverse effects diminished or resolved with continued therapy. We conclude that rIFN alpha 2a offers important therapeutic benefit in a select group of patients with AIDS-related KS.

Health care utilization in multiple sclerosis: a population-based study in Olmsted County, MN.

OBJECTIVE: The authors sought to determine acute ambulatory- and hospital-billed charges for the Olmsted County, Minnesota Multiple Sclerosis (MS) Disability Prevalence Cohort and compare them to those incurred by the general population. METHODS: Billed charges for 155 people with clinically definite or laboratory-supported MS were compared with those of age- and gender-matched non-MS controls. Billing data, including all inpatient and outpatient acute and rehabilitative medical care charges over a 5-year period surrounding a December 1, 1991 prevalence date, were analyzed. Data were correlated with level of disability using the Minimal Record of Disability for MS. RESULTS: Median total annual billed charges for most individuals with MS, including those with less severe ($1,277) and relapsing-remitting illness ($1,348), did not differ from those for controls ($1,327, p=0.075). Only those with severe MS (22.6%) had median annual medical charges higher than controls ($5,440, p < 0.001). Male patients with MS had higher median annual total charges ($2,353) than male controls ($762, p=0.003). Total charges for female patients with MS ($1,440) were not different from those for female controls ($1469). Median annual outpatient charges were 15% more for the MS group ($1,418) than for controls ($1,231). Patients with MS had a mean of 0.2 hospital admissions annually compared with 0.1 annual admissions per control patient. Among variables collected on persons with MS, the Expanded Disability Status Scale was the strongest predictor of level of charges (p < 0.001). CONCLUSION: Acute ambulatory- and hospital-billed charges for most patients with MS do not differ from those of the general population.

A longitudinal study of T1 hypointense lesions in relapsing MS: MSCRG trial of interferon beta-1a. Multiple Sclerosis Collaborative Research Group.

BACKGROUND: T1 hypointense lesions (T1 black holes) are focal areas of relatively severe CNS tissue damage detected by MRI in patients with MS. OBJECTIVE: To determine the natural history of T1 hypointense lesions in relapsing MS and the utility of T1 hypointense lesions as outcome measures in MS clinical trials. METHODS: MR studies were from the Multiple Sclerosis Collaborative Research Group trial. Longitudinal results are reported in 80 placebo- and 80 interferon beta-1a (IFNbeta-1a)-treated patients with mild to moderate disability relapsing-remitting MS. RESULTS: There was a small but significant correlation between T1 hypointense lesion volume and disability at baseline and on trial (r = 0.22, r = 0.28). In placebo patients there was a 29.2% increase in the mean volume of T1 hypointense lesions (median 124.5 mm3) over 2 years (p < 0.001 for change from baseline), as compared to an 11.8% increase (median 40 mm3) in the IFNbeta-1a-treated patients (change from baseline not significant). These treatment group comparisons did not quite reach significance. The most significant contributor to change in T1 hypointense lesions was the baseline number of enhancing lesions (model r2 = 0.554). Placebo patients with more active disease, defined by enhancing lesions at baseline, were the only group to show a significant increase in T1 hypointense lesion volume from baseline. CONCLUSION: The development of T1 hypointense lesions is strongly influenced by prior inflammatory disease activity, as indicated by enhancing lesions. These results suggest that treatment with once weekly IM IFNbeta-1a (30 mcg) slows the 2-year accumulation of these lesions in the brain.

A longitudinal study of brain atrophy in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG).

OBJECTIVE: To determine if progressive brain atrophy could be detected over 1- and 2-year intervals in relapsing MS, based on annual MR studies from the Multiple Sclerosis Collaborative Research Group (MSCRG) trial of interferon beta-1a (Avonex). METHODS: All subjects had mild to moderate disability, with baseline expanded disability status scores ranging from 1.0 to 3.5, and at least two relapses in the 3 years before study entry. Atrophy measures included third and lateral ventricle width, brain width, and corpus callosum area. RESULTS: Significant increases were detected in third ventricle width at year 2 and lateral ventricle width at 1 and 2 years. Significant decreases in corpus callosum area and brain width were also observed at 1 and 2 years. Multiple regression analyses suggested that the number of gadolinium-enhancing lesions at baseline was the single significant contributor to change in third ventricle width. Atrophy over 1 and 2 years as indicated by enlargement of the third and lateral ventricle and shrinkage of the corpus callosum was greater for patients entering the trial with enhancing lesions. Greater disability increments over 1 and 2 years were associated with more severe third ventricle enlargement. CONCLUSION: In patients with relapsing MS and only mild to moderate disability, significant cerebral atrophy is already developing that can be measured over periods of only 1 to 2 years. The course of cerebral atrophy in MS appears to be influenced by prior inflammatory disease activity as indicated by the presence of enhancing lesions. Brain atrophy measures are important markers of MS disease progression because they likely reflect destructive and irreversible pathologic processes.

Incidence and significance of neutralizing antibodies to interferon beta-1a in multiple sclerosis. Multiple Sclerosis Collaborative Research Group (MSCRG)

BACKGROUND: Interferon beta is an effective treatment for relapsing multiple sclerosis (MS). As with other protein drugs, neutralizing antibodies (NAB) can develop that reduce the effectiveness of treatment. OBJECTIVES: To determine the incidence and biological significance of NAB to interferon beta-la (IFN-beta-1a; Avonex; Biogen, Cambridge, MA) in MS patients. METHODS: A two-step assay for NAB to IFN-beta-1a was developed and used to assay serum samples from participants in the phase III clinical trial of IFN-beta-1a, and from patients in an ongoing open-label study of IFN-beta-1a. The biological significance of NAB to IFN-beta-1a was determined by relating the NAB assay result to in vivo induction of the IFN-inducible molecules neopterin and beta-2 microglobulin, and the clinical significance was determined by comparing clinical and MRI measures of disease activity after 2 years of IFN-beta-1a therapy in patients who were NAB+ and NAB-. The incidence of NAB was compared in MS patients who had used only IFN-beta-1a with the incidence in MS patients who had used only IFN-beta-1b. RESULTS: In patients in the open-label study, development of NAB to IFN-beta-1a resulted in a titer-dependent reduction in neopterin induction after interferon injections. In patients in the phase III study, development of NAB was associated with a reduction in beta-2 microglobulin induction. In the phase III study, a trend toward reduced benefit of IFN-beta-1a on MRI activity in NAB+ versus NAB- patients was observed. The incidence of NAB to IFN-beta-1a in the open-label study was approximately 5% over 24 months of treatment of IFN-beta-1a therapy, but was four- to sixfold higher using the same assay for patients exposed only to IFN-beta-1b for a similar duration. There were no clinical, MRI, or CSF characteristics that were predictive of which patients would develop NAB. CONCLUSIONS: NAB directed against IFN-beta have in vivo biological consequences in patients with MS. The frequency with which MS patients develop NAB against IFN-beta is significantly greater with IFN-beta-1b therapy compared with IFN-beta-1a therapy. Treatment decisions in MS patients treated with IFN-beta should take into account development of NAB.

Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG).

BACKGROUND AND OBJECTIVE: A phase III double-blind, placebo-controlled clinical trial demonstrated that interferon beta-1a (IFN beta-1a) (Avonex, Biogen) significantly delayed progression of disability in relapsing MS patients. The primary clinical outcome was time from study entry until disability progression, defined as > or = 1.0 point worsening from baseline Kurtzke Expanded Disability Status Scale (EDSS) score persisting for at least two consecutive scheduled visits separated by 6 months. The objective of this study was to examine the magnitude of benefit on EDSS and its clinical significance. METHODS: Post hoc analyses related to disability outcomes using data collected during the double-blind, placebo-controlled phase III clinical trial. RESULTS: (1) Clinical efficacy related to disability did not depend on the definition of disability progression. A significant benefit in favor of IFN beta-1a was observed when > or = 2.0 point worsening from baseline EDSS was required or when worsening was required to persist for > or = 1.0 year. (2) Placebo recipients who reached the primary clinical outcome worsened by a larger amount from baseline EDSS than did IFN beta-1a recipients who reached the primary study outcome. (3) Significantly fewer IFN beta-1a recipients progressed to EDSS milestones of 4.0 (relatively severe impairment) or 6.0 (unilateral assistance needed to walk). (4) Cox proportional hazards models demonstrated that the only baseline characteristic strongly correlated with longer time to disability progression was IFN beta-1a treatment. CONCLUSIONS: The primary clinical outcome for the IFN beta-1a clinical trial underestimated clinical benefits of treatment. Results in this report demonstrate that IFN beta-1a treatment is associated with robust, clinically important beneficial effects on disability progression in relapsing MS patients.

The Olmsted County Benchmark Project: primary study findings and potential implications for corporate America.

Since 1965, expenditures for medical care in the United States have increased 10-fold. As a result, corporate outlays for health benefits have skyrocketed. Employers have instituted various cost-containment measures based in part on reports of wide variations in rates of utilization and the assumption that unnecessary or inappropriate utilization of medical care contributes to increasing costs. Frequently, however, employers lack adequate means for identifying sources of variation or for evaluating its appropriateness. In this article, we report on a project in which hospital utilization among several US corporate populations was compared with that for a geographically defined benchmark population to assist employers in the assessment of their rates of utilization and expenditures and to identify specific areas that merit further investigation. Our findings illuminate the difficulties in constructing valid rates from medical-care claims data and emphasize potential biases due to problems of comparability between populations. We also address the potential value of such comparison for helping corporations identify areas in which cost-containment efforts may be most effective and yet not jeopardize the quality of medical care.

Altering residency curriculum in response to a changing practice environment: use of the Mayo internal medicine residency alumni survey.

To elicit the opinions of practicing internists who had graduated from a single internal medicine residency program about the adequacy of their training and its relevance to their medical practice, we mailed a survey to 1,342 physicians who had spent at least 1 year in the Mayo internal medicine residency training program. Of this group, 703 alumni (52%) responded to the survey, 532 of whom were currently practicing internal medicine. Our detailed analysis was based on responses from these 532 and, for some aspects of evaluation, on the 121 general internists who had completed residency training after 1970. Of the respondents, 42% spent more than 80% of their time in general medicine, and 53% had at least some subspecialty practice; 55% were involved in teaching, 20% in some research, and 37% in various administrative duties. In 27%, all patient-care activities involved primary care, an increase from 18% in a 1979 survey and 9% in 1972. Of those who were subspecialists, 67% spent more than half their time in subspecialty practice. Of those who were trained after 1970, 90% were board certified. Most respondents thought that their training in the internal medicine subspecialties was adequate, that additional procedure training was needed in joint aspiration, line placement, and flexible sigmoidoscopy, and that many allied medical areas were important to their practice and necessitated additional training. Although virtually all respondents assessed their inpatient training as adequate, only 42% were fully satisfied with their outpatient training. Alumni surveys can be useful in restructuring a residency program to meet the needs of the trainees.

Potential effect of authorization bias on medical record research.

OBJECTIVE: To analyze the influence of recent changes in Minnesota statutes that generally require prior authorization for use of medical records for research from patients who received medical care after Jan. 1, 1997. MATERIAL AND METHODS: In this Mayo Clinic Institutional Review Board-approved study, we obtained a stratified random sample of patients encountered at Mayo Clinic Rochester during the period 1994 through 1996 and estimated the proportion willing to provide the general authorization. On the basis of data from administrative files, we then compared demographic, diagnostic, and utilization characteristics for patients who provided authorization and those who did not. RESULTS: Overall, 3.2% (95% confidence interval, 2.4 to 4.0%) of the study subjects declined authorization. If patients not responding to requests for authorization were also considered to have refused, the overall refusal rate would be 20.7% (95% confidence interval, 18.5 to 22.9%). Women were somewhat more likely to refuse authorization than were men (4.0% versus 2.4%; P = 0.067), and patients younger than 60 years were more likely to refuse than were older patients (5.4% versus 1.2%; P<0.001). Patients residing more than 120 miles from Rochester were much less likely to decline authorization than were local residents (2.1% versus 5.8%; P = 0.001). Patients with prior diagnoses that might be considered more sensitive such as mental disorders, infectious diseases, and reproductive problems also were more likely to refuse authorization. CONCLUSION: These data demonstrate that laws requiring written authorization for research use of the medical record could result in substantial biases in etiologic and outcome studies, the direction and magnitude of which may vary from topic to topic. Clinicians should be prepared to enter the discussion to help inform patients and legislators of the potential hazards of laws that restrict access to medical records for research purposes.

Assessment of prediction of mortality by using the APACHE II scoring system in intensive-care units;.

Some investigators have suggested that information on quality of care in intensive-care units (ICUs) may be inferred from mortality rates. Specifically, the ratio of actual to predicted hospital mortality (A/P) has been proposed as a valid measure for comparing ICU outcomes when predicted mortality has been derived from data collected during the first 24 hours of ICU therapy with use of a severity scoring tool, APACHE II (acute physiology and chronic health evaluation). We present a comparison of mortality ratios (A/P) in four ICUs under common management, in two hospitals within a single institution. Significant differences in A/P were detected for nonoperative patients (0.99 versus 0.67;P = 0.014) between the two hospitals. This variation was traced to uneven representation of a subset of patients who had chronic health problems related to diseases that necessitated admission to the hematology-oncology or hepatology service. No differences in A/P were seen between the two hospitals for operative patients or for nonoperative patients on services other than hematology-oncology or hepatology. Thus, differences in A/P detected by using the APACHE II system not only may reside in operational factors within the ICU organization but also may be related to weaknesses in the APACHE II model to measure factors intrinsic to the disease process in some patients. We suggest that case-mix must be examined in detail before concluding that differences in A/P are caused by differences in quality of care.

Phase I multicenter trial of interleukin 6 therapy after autologous bone marrow transplantation in advanced breast cancer.

Our purpose was to determine the maximum tolerated dosage of rhIL-6 after high-dose cytotoxic chemotherapy and autologous BMT in patients with advanced breast cancer. Twenty patients (median age 43.5 years) received either CY and thiotepa (n = 3) or CY, thiotepa and carboplatin (n = 17) for 4 days. Unpurged autologous BM was reinfused 72 h later. Daily rhIL-6 therapy began the day of marrow infusion and continued until recovery of neutrophils (> or = 1.5 x 10(9)/l) and platelets (> or = 50 x 10(9)/l) or for a maximum of 28 days at a dosage of 0.3 microgram/kg/day (n = 7), 1 microgram/kg/day (n = 6) or 3 micrograms/kg/day (n = 7). Two of the initial 4 patients given rhIL-6 at 0.3 mu/kg i.v. experienced grade 4 hyperbilirubinemia, so subsequent patients received s.c. rhIL-6. Most toxicities attributable to rhIL-6 were reversible or mild constitutional symptoms, but dose-limiting grade 4 hyperbilirubinemia also occurred in 3 of the 7 patients receiving the 3 micrograms/kg dose. At the 0.3 and 1 microgram/kg/day doses, 8 of 13 patients completed the study vs. only 2 of 7 at the 3 micrograms/kg/day dose. During rhIL-6 treatment, neutrophil recovery (> or = 500 x 10(6)/l) occurred in 12 patients and platelet recovery (> or = 20 x 10(9)/l) occurred in 6 patients, 5 of whom received the 0.3 or 1 microgram/kg/day s.c. dose. The maximal tolerated dose of rhIL-6 after autologous BMT appeared to be 1 microgram/kg/day s.c., a dose appreciably lower than the maximal tolerated dose after conventional cytotoxic therapy.

Trends in elderly hospitalization and readmission rates for a geographically defined population: pre- and post-prospective payment.

To address the paucity of patient-level data regarding the effectiveness of Medicare's prospective payment system (PPS), we conducted a population-based study of inpatient hospitalizations among individually identified elderly residents of Olmsted County, Minnesota, 1970-1987. A 4.3% increase in total days of care/1000 population from 2,652/1,000 in 1970 to 2,766/1,000 in 1980 was followed by a 9.8% decline from 1980 to 1987 (2,495/1,000). The decline was due primarily to a 13.4% decrease in mean length stay (9.7 days in 1980 to 8.4 days in 1987). The number of hospitalizations/1,000 Olmsted County elderly in 1980 was already below 1987 U.S. figures and did not exhibit the decline evidenced nationally between 1980 and 1987. A 4.6% decline in the proportion of county residents age 65-74 years who were hospitalized (174/1,000 in 1980 to 166/1,000 in 1987) was offset by an 8.3% increase for persons age greater than or equal to 75 (252/1,000 to 273/1,000) and by a 5.7% increase in the number of hospitalizations per individual hospitalized for persons age 65-74 years (1.34 to 1.42). Using a time-dependent Cox model, which adjusted for differences in patients characteristics between years, there was a significantly higher risk of readmission within 14 days in 1987 vs 1980 (hazard ratio (HR) = 1.33, 95% confidence interval (CI) = 1.05-1.70). The difference between years was no longer evident at 30 or 60 days (HR = 0.84, 95% CI = 0.63-1.11 between 15 and 30 days; HR = 1.12, 95% CI = 0.84-1.49 between 31 and 60 days). This study suggests that initial effects of PPS on utilization may be temporary and that more research is needed to appreciate the impact of cost-containment on patient outcome.