Accuracy of a portable pulse oximeter in monitoring hypoxemic infants with cyanotic heart disease.

OBJECTIVE: Infants with single ventricle physiology have arterial oxygen saturations between 75 and 85%. Home monitoring with daily pulse oximetry is associated with improved interstage survival. They are typically sent home with expensive, bulky, hospital-grade pulse oximeters. This study evaluates the accuracy of both the currently used Masimo LNCS and a relatively inexpensive, portable, and equipped with Bluetooth technology study device, by comparing with the gold standard co-oximeter. DESIGN: Prospective, observational study. SETTING: Single institution, paediatric cardiac critical care unit, and neonatal ICU. INTERVENTIONS: none. PATIENTS: Twenty-four infants under 12 months of age with baseline oxygen saturation less than 90% due to cyanotic CHD. MEASUREMENTS AND RESULTS: Pulse oximetry with WristOx2 3150 with infant sensors 8008 J (study device) and Masimo LCNS saturation sensor connected to a Philips monitor (hospital device) were measured simultaneously and compared to arterial oxy-haemoglobin saturation measured by co-oximetry. Statistical analysis evaluated the performances of each and compared to co-oximetry with Schuirmann's TOST equivalence tests, with equivalence defined as an absolute difference of 5% saturation or less. Neither the study nor the hospital device met the predefined standard for equivalence when compared with co-oximetry. The study device reading was on average 4.0% higher than the co-oximeter, failing to show statistical equivalence (p = 0.16). The hospital device was 7.4% higher than the co-oximeter and also did not meet the predefined standard for equivalence (p = 0.97). CONCLUSION: Both devices tended to overestimate oxygen saturation in this patient population when compared to the gold standard, co-oximetry. The study device is at least as accurate as the hospital device and offers the advantage of being more portable with Bluetooth technology that allows reliable, efficient data transmission. Currently FDA-approved, smaller portable pulse oximeters can be considered for use in home monitoring programmes.

Comparison of local reactions to oxaliplatin infusions by peripheral versus central venous administration.

PURPOSE: Oxaliplatin, a platinum-type alkylator, is not classified as a vesicant but can cause local reactions when infused by peripheral vein. Providence Cancer Center, like other institutions, deferred the venous administration method to clinical judgment incorporating patient preference. Patient experience was evaluated for oxaliplatin-related local reactions by peripheral or central venous administration. METHODS: A retrospective review of the electronic medical record was performed of the period of January 2011 to March 2013 to identify patients who received oxaliplatin. Included were 59 patients who were given the option of either peripheral or central venous drug administration. The two patient groups (peripheral vein vs. central vein administration) were compared in terms of frequency and type of local reactions (redness/discoloration, swelling, numbness/cold, or pain/discomfort). RESULTS: Nineteen (63.3%) of the patients in the peripheral vein group experienced some type of local reaction compared to none in the central vein group (p < .0001). Pain was the most common local reaction, occurring in 17 (56.7%) patients in the peripheral group. Despite the occurrence of a local reaction, the majority of patients did not alter their initial choice of infusion method. CONCLUSION: This is the first published report to characterize and quantify a single institution's experience with oxaliplatin-related local reactions. A significantly greater number of local reactions, particularly pain, occurred with the administration of oxaliplatin peripherally vs. centrally. This analysis impacted our institution's best practice for oxaliplatin infusions.

Total pancreatectomy for pancreatic ductal adenocarcinoma: review of the National Cancer Data Base.

BACKGROUND: Total pancreatectomy is infrequently performed for pancreatic cancer. Perceived operative mortality and questionable survival benefit deter many surgeons. Clinical outcomes, described in single-center series, remain largely unknown. METHODS: The National Cancer Database was queried for cases of pancreatic ductal adenocarcinoma undergoing total pancreatectomy (1998-2011). Univariate survival analyses were performed for 21 variables: demographic (8), tumor characteristics (5), surgery outcomes (6), and adjuvant therapy (2). The Log-rank test of differences in Kaplan-Meier survival curves was used for categorical variables. Variables with p < 0.05 were included in a multivariate analysis. Cox proportional hazards regression was used to analyze continuous variables and multivariate models. RESULTS: 2582 patients with staging and survival data made up the study population. 30-day mortality was 5.5%. Median overall survival was 15 months, with 1, 3, and 5-year survival rates of 60%, 22%, and 13%, respectively. Age, facility type, tumor size and grade, lymph node positivity, margin positivity, and adjuvant therapy significantly impacted survival in multivariate analysis. CONCLUSION: Although total pancreatectomy is a reasonable option for selected patients with pancreatic ductal adenocarcinoma, survival of the entire group is limited. Operative mortality is improved from prior reports. Greater survival benefits were seen in younger patients with smaller, node negative tumors resected with negative margins in academic research centers.

Impact of lymph node status in patients with intrahepatic cholangiocarcinoma treated by major hepatectomy: a review of the National Cancer Database.

INTRODUCTION: Routine lymphadenectomy in the surgical treatment of intrahepatic cholangiocarcinoma (ICC) is not routinely performed. We aim to define predictive indicators of survival in patients with positive lymph nodes. METHODS: The National Cancer Data Base (NCDB) was queried for patients who underwent major hepatectomy for ICC between 1998 and 2011. Clinical and pathologic data were assessed using uni- and multi-variate analyses. A sub-analysis was performed on the 160 patients with positive lymph nodes. RESULTS: Of 849 patients with lymph node data, 57% had at least one lymph node examined. Median survival for lymph node negative patients was 37 months versus 15 months for lymph node positive patients. In lymph node positive patients, poorer survival was associated with not receiving chemotherapy (HR 1.83, p = 0.003), tumor size > 5 cm (p = 0.029), and older age (p < 0.0001). Lymph node positive patients age less than 45 had a median survival of 27 months. CONCLUSIONS: Overall survival in patients with lymph node metastases from ICC is poor. Adjuvant therapy was associated with a longer survival in lymph node positive patients, although prospective data are needed. Routine lymphadenectomy should be strongly considered to provide prognostic information and guidance for adjuvant therapy.

Multimodal treatment of unresectable hepatocellular carcinoma to achieve complete response results in improved survival.

INTRODUCTION: With technological advances, questions arise regarding how to best fit newer treatment modalities, such as transarterial therapies, into the treatment algorithm for patients with hepatocellular carcinoma (HCC). METHODS: Between 2005 and 2011, 128 patients initially treated with transarterial radioembolization or chemoembolization using drug-eluting beads were identified. The response was graded retrospectively. Toxicity was measured 1, 3, and 6 months after the first and last treatments. RESULTS: Sixty-five patients (53%) were advanced stage. Twenty patients (16%) had an initial complete response, but with additional treatments, this was increased to 46 (36%). Patients with a complete response as their best response to treatment had a median survival [95% confidence interval (CI)] of 5.77 (2.58, upper limit not yet reached) years, significantly longer than those whose best response was a partial response, 1.22 (0.84, 2.06) years and those with stable disease as their best response, 0.34 (0.29, 0.67) years. Repeated treatments did not increase toxicity. DISCUSSION: This retrospective review of patients treated for intermediate and advanced stage HCC revealed a significant survival advantage in patients who achieved a complete response. These data support use of a multi-modality approach to intermediate and advanced stage HCC, combining liver-directed treatments as necessary to achieve a complete response.

Health care utilization among veterans with pain and posttraumatic stress symptoms.

OBJECTIVE: To examine health care utilization among veterans with both chronic pain and posttraumatic stress symptoms. METHODS: Retrospective cohort study of 40,716 veterans in a VA regional network from January 1, 2002 to January 1, 2007. Veterans were categorized into pain-only, posttraumatic stress disorder symptoms (PTSD)-only, and pain plus PTSD (pain+PTSD) comparison groups. Negative binomial models were used to compare adjusted rates of primary care, mental health, and specialty pain service use, as well as opioids, benzodiazepines, nonopioid analgesics, and antidepressant prescriptions. Rates of clinic visits were calculated by days per year, and rates of medication use were calculated by prescription months per year. Participants were followed for a mean duration of 47 months. RESULTS: Participants were 94.7% men and had a mean age of 58.9 years. Nearly all used primary care (99.2%), 37.1% used pain-related specialty care, and 33.8% used mental health services. Nonopioid and opioid analgesics were the most commonly used medications (63.7% and 53.8%, respectively). Except for mental health visits, which did not differ between PTSD-only and pain+PTSD groups, the pain+PTSD group used significantly more of all categories of health care services than the pain-only and PTSD-only groups. For example, the pain+PTSD group had 7% more primary care visits (rate ratio [RR]=1.07; 95% confidence interval [CI]: 1.05, 1.09) than the pain-only group and 46% more primary care visits than the PTSD-only group (RR=1.46; 95% CI: 1.40, 1.52). Adjusted rates of opioid, benzodiazepine, nonopioid analgesic, and antidepressant prescriptions were higher for the pain+PTSD group than either of the comparison groups. CONCLUSIONS: Our findings support our expectation that veterans with both pain and PTSD symptoms use more health care services than those with pain or PTSD symptoms alone. Research is needed to assess the health care costs associated with increases in health care utilization among these veterans.

Verbal short-term memory development and spoken language outcomes in deaf children with cochlear implants.

OBJECTIVES: Cochlear implants (CIs) help many deaf children achieve near-normal speech and language (S/L) milestones. Nevertheless, high levels of unexplained variability in S/L outcomes are limiting factors in improving the effectiveness of CIs in deaf children. The objective of this study was to longitudinally assess the role of verbal short-term memory (STM) and working memory (WM) capacity as a progress-limiting source of variability in S/L outcomes after CI in children. DESIGN: Longitudinal study of 66 children with CIs for prelingual severe-to-profound hearing loss. Outcome measures included performance on digit span forward (DSF), digit span backward (DSB), and four conventional S/L measures that examined spoken-word recognition (Phonetically Balanced Kindergarten word test), receptive vocabulary (Peabody Picture Vocabulary Test ), sentence-recognition skills (Hearing in Noise Test), and receptive and expressive language functioning (Clinical Evaluation of Language Fundamentals Fourth Edition Core Language Score; CELF). RESULTS: Growth curves for DSF and DSB in the CI sample over time were comparable in slope, but consistently lagged in magnitude relative to norms for normal-hearing peers of the same age. For DSF and DSB, 50.5% and 44.0%, respectively, of the CI sample scored more than 1 SD below the normative mean for raw scores across all ages. The first (baseline) DSF score significantly predicted all endpoint scores for the four S/L measures, and DSF slope (growth) over time predicted CELF scores. DSF baseline and slope accounted for an additional 13 to 31% of variance in S/L scores after controlling for conventional predictor variables such as: chronological age at time of testing, age at time of implantation, communication mode (auditory-oral communication versus total communication), and maternal education. Only DSB baseline scores predicted endpoint language scores on Peabody Picture Vocabulary Test and CELF. DSB slopes were not significantly related to any endpoint S/L measures. DSB baseline scores and slopes taken together accounted for an additional 4 to 19% of variance in S/L endpoint measures after controlling for the conventional predictor variables. CONCLUSIONS: Verbal STM/WM scores, process measures of information capacity, develop at an average rate in the years after cochlear implantation, but were found to consistently lag in absolute magnitude behind those reported for normal-hearing peers. Baseline verbal STM/WM predicted long-term endpoint S/L outcomes, but verbal STM slopes predicted only endpoint language outcomes. Verbal STM/WM processing skills reflect important underlying core elementary neurocognitive functions and represent potential intervention targets for improving endpoint S/L outcomes in pediatric CI users.

Development and validation of a major adverse transplant event (MATE) score to predict late graft loss in pediatric heart transplantation.

BACKGROUND: There is inadequate power to perform a valid clinical trial in pediatric heart transplantation (HT) using a conventional end-point, because the disease is rare and hard end-points, such as death or graft loss, are infrequent. We sought to develop and validate a surrogate end-point involving the cumulative burden of post-transplant complications to predict death/graft loss to power a randomized clinical trial of maintenance immunosuppression in pediatric HT. METHODS: Pediatric Heart Transplant Study (PHTS) data were used to identify all children who underwent an isolated orthotopic HT between 2005 and 2014 who survived to 6 months post-HT. A time-varying Cox model was used to develop and evaluate a surrogate end-point comprised of 6 major adverse transplant events (MATEs) (acute cellular rejection [ACR], antibody-mediated rejection [AMR], infection, cardiac allograft vasculopathy [CAV], post-transplant lymphoproliferative disease [PTLD] and chronic kidney disease [CKD]) occurring between 6 and 36 months, where individual events were defined according to international guidelines. Two thirds of the study cohort was used for score development, and one third of the cohort was used to test the score. RESULTS: Among 2,118 children, 6.4% underwent graft loss between 6 and 36 months post-HT, whereas 39% developed CKD, 34% ACR, 34% infection, 9% AMR, 4% CAV and 2% PTLD. The best predictive score involved a simple MATE score sum, yielding a concordance probability estimate (CPE) statistic of 0.74. Whereas the power to detect non-inferiority (NI), assuming the NI hazard ratio of 1.45 in graft survival was 10% (assuming 200 subjects and 6% graft loss rate), the power to detect NI assuming a 2-point non-inferiority margin was >85% using the MATE score. CONCLUSION: The MATE score reflects the cumulative burden of MATEs and has acceptable prediction characteristics for death/graft loss post-HT. The MATE score may be useful as a surrogate end-point to power a clinical trial in pediatric HT.

Regional Metastatic Behavior of Nonfunctional Pancreatic Neuroendocrine Tumors: Impact of Lymph Node Positivity on Survival.

OBJECTIVES: Literature addressing the significance of lymph node positivity in the management of nonfunctional pancreatic neuroendocrine tumors (PNETs) is conflicting. METHODS: The National Cancer Data Base was queried for patients who underwent surgical resection of nonfunctional PNETs between 1998 and 2011. Clinical data and overall survival were analyzed using χ and Cox proportional hazards regression. Multiple imputation was used as a comparative analysis because of the high number of patients missing data on tumor grade. RESULTS: Two thousand seven hundred thirty-five patients were identified. The overall incidence of lymph node metastasis was 51%. In the subset of patients with grade 1 tumors less than 1 cm, 24% had positive lymph nodes. Overall median survival for patients with negative lymph nodes was 11 years compared with 8 years for lymph node-positive patients (P < 0.001). On multivariate survival analysis, tumor grade, distant metastases, regional lymph node involvement, positive surgical margins, male sex, and older age were predictive of decreased overall survival. CONCLUSIONS: Lymph node positivity was associated with decreased overall survival. The incidence of lymph node involvement in resected low-grade tumors less than 1 cm is higher than previously reported. Patients selected for resection of PNETs should be offered lymphadenectomy for staging.

Does comorbid chronic pain affect posttraumatic stress disorder diagnosis and treatment? Outcomes of posttraumatic stress disorder screening in Department of Veterans Affairs primary care.

Because posttraumatic stress disorder (PTSD) is both prevalent and underrecognized, routine primary care-based screening for PTSD has been implemented across the Veterans Health Administration. PTSD is frequently complicated by the presence of comorbid chronic pain, and patients with both conditions have increased symptom severity and poorer prognosis. Our objective was to determine whether the presence of pain affects diagnosis and treatment of PTSD among Department of Veterans Affairs (VA) patients who have a positive PTSD screening test. This retrospective cohort study used clinical and administrative data from six Midwestern VA medical centers. We identified 4,244 VA primary care patients with a positive PTSD screen and compared outcomes for those with and without a coexisting pain diagnosis. Outcomes were three clinically appropriate responses to positive PTSD screening: (1) mental health visit, (2) PTSD diagnosis, and (3) new selective serotonin reuptake inhibitor (SSRI) prescription. We found that patients with coexisting pain had a lower rate of mental health visits than those without pain (hazard ratio: 0.889, 95% confidence interval: 0.821-0.962). There were no significant differences in the rate of PTSD diagnosis or new SSRI prescription between patients with and without coexisting pain.

OX40, PD-1 and CTLA-4 are selectively expressed on tumor-infiltrating T cells in head and neck cancer.

The tumor microenvironment of squamous cell carcinoma of the head and neck (SCCHN) has been shown to be immune suppressive. Therefore, strategies aimed at overcoming this issue could have a positive therapeutic impact. Hence, we investigated the expression of the known immune-modulatory proteins OX40, programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in SCCHN on different T-cell subsets of tumor-infiltrating lymphocytes (TIL) to ascertain whether these proteins could potentially be targeted alone or in combination for future clinical trials. T cells from peripheral blood (PBL) and tumor were analyzed for the expression of OX40, PD-1 and CTLA-4 in 29 patients undergoing surgery. These proteins were all expressed significantly higher in T-cell subsets isolated from tumors compared with PBL of the same patient. OX40 expression was significantly greater in the TIL regulatory T-cell (Treg) population relative to conventional CD4 and CD8 TIL or the Treg isolated from PBL. PD-1 expression was increased in all T-cell subsets relative to PBL. CTLA-4 was also increased in all TIL subsets relative to blood, and similar to OX40, its highest level of expression was observed in the Treg TIL. The highest frequency of PD-1, CTLA-4 and OX40 triple-positive cells were found in the Treg population isolated from the tumor. We analyzed both human papilloma virus-positive and -negative patients and found similar levels and expression patterns of these two patient populations for all three proteins. These data suggest that there may be therapeutic advantages of targeting these pathways independently or in combination for patients with this disease.

Serum Immunoregulatory Proteins as Predictors of Overall Survival of Metastatic Melanoma Patients Treated with Ipilimumab.

Treatment with ipilimumab improves overall survival (OS) in patients with metastatic melanoma. Because ipilimumab targets T lymphocytes and not the tumor itself, efficacy may be uniquely sensitive to immunomodulatory factors present at the time of treatment. We analyzed serum from patients with metastatic melanoma (247 of 273, 90.4%) randomly assigned to receive ipilimumab or gp100 peptide vaccine. We quantified candidate biomarkers at baseline and assessed the association of each using multivariate analyses. Results were confirmed in an independent cohort of similar patients (48 of 52, 92.3%) treated with ipilimumab. After controlling for baseline covariates, elevated chemokine (C-X-C motif) ligand 11 (CXCL11) and soluble MHC class I polypeptide-related chain A (sMICA) were associated with poor OS in ipilimumab-treated patients [log10 CXCL11: HR, 1.88; 95% confidence interval (CI), 1.14-3.12; P = 0.014; and log10 sMICA quadratic effect P = 0.066; sMICA (≥ 247 vs. 247): HR, 1.75; 95% CI, 1.02-3.01]. Multivariate analysis of an independent ipilimumab-treated cohort confirmed the association between log10 CXCL11 and OS (HR, 3.18; 95% CI, 1.13-8.95; P = 0.029), whereas sMICA was less strongly associated with OS [log10 sMICA quadratic effect P = 0.16; sMICA (≥ 247 vs. 247): HR, 1.48; 95% CI, 0.67-3.27]. High baseline CXCL11 and sMICA were associated with poor OS in patients with metastatic melanoma after ipilimumab treatment but not vaccine treatment. Thus, pretreatment CXCL11 and sMICA may represent predictors of survival benefit after ipilimumab treatment as well as therapeutic targets.

Rationale, design, and baseline characteristics of a community-based comparative effectiveness trial to prevent type 2 diabetes in economically disadvantaged adults: the RAPID Study.

Reaching Out and Preventing Increases in Diabetes (RAPID) is a community-based randomized trial evaluating the comparative costs and effectiveness of a group-based adaption of the DPP lifestyle intervention developed and implemented in partnership with the YMCA. RAPID enrolled adult primary care patients, with BMI 24 kg/m(2) or higher and abnormal glucose metabolism (HbA1c 5.7-6.9% or fasting plasma glucose 100-125 mg/dL). 509 participants were enrolled and randomized to one of two groups: standard clinical advice plus free-of-charge access to a group-based adaption of the DPP offered by the Y, versus standard clinical advice alone. Key outcomes for future analysis will include differences in body weight and other cardiovascular risk factors over a 24-month intervention period. At baseline, RAPID participants had a mean (SD) age of 51 ± 12.1 years, weight of 225.1 ± 56.2 lbs, and BMI of 36.9 ± 8.6 kg/m(2). 70.7% were women, 57.2% were African American, 35.4% were non-Hispanic White, and 3.2% were Hispanic. Mean HbA1c was 6.05 ± 0.34%. Additionally, 55.4% of participants had a baseline systolic blood pressure of ≥130 mmHg, 33.1% had a total blood cholesterol exceeding 200mg/dL, and 74% reported a household income of <$25,000. The RAPID Study successfully randomized a large cohort of participants with a wide distribution of age, body weight, and race who are at high risk for developing type 2 diabetes.

Durable responses and reversible toxicity of high-dose interleukin-2 treatment of melanoma and renal cancer in a Community Hospital Biotherapy Program.

BACKGROUND: High-dose interleukin-2 (IL-2) has been FDA-approved for over 20 years, but it is offered only at a small number of centers with expertise in its administration. We analyzed the outcomes of patients receiving high-dose IL-2 in relation to the severity of toxicity to ascertain if response or survival were adversely affected. METHODS: A retrospective analysis of the outcomes of 500 patients with metastatic renal cell carcinoma (RCC) (n = 186) or melanoma (n = 314) treated with high-dose IL-2 between 1997 and 2012 at Providence Cancer Center was performed. IL-2 was administered at a dose of 600,000 international units per kg by IV bolus every 8 hours for up to 14 doses. A second cycle was administered 16 days after the first and patients with tumor regression could receive additional cycles. Survival and anti-tumor response were analyzed by diagnosis, severity of toxicity, number of IL-2 cycles and subsequent therapy. RESULTS: The objective response rate in melanoma was 28% (complete 12% and partial 16%), and in RCC was 24% (complete 7% and partial 17%). The 1-, 2- and 3-year survivals were 59%, 41% and 31%, for melanoma and 75%, 56% and 44%, for RCC, respectively. The proportion of patients with complete or partial response in both melanoma and RCC was higher in patients who a) required higher phenylephrine doses to treat hypotension (p < 0.003), b) developed acidosis (bicarbonate < 19 mmol (p < 0.01)), or c) thrombocytopenia (<50, 50-100, >100,000 platelets; p < 0.025). The proportion achieving a complete or partial response was greater in patients with melanoma who received 5 or more compared with 4 or fewer IL-2 cycles (p < 0.0001). The incidence of death from IL-2 was less than 1% and was not higher in patients who required phenylephrine. CONCLUSIONS: High-dose IL-2 can be administered safely; severe toxicity including hypotension is reversible and can be managed in a community hospital. The tumor response and survival reported here are superior to the published literature and support treating patients to their individualized maximum tolerated dose. IL-2 should remain part of the treatment paradigm in selected patients with melanoma and RCC.

Profiles of verbal working memory growth predict speech and language development in children with cochlear implants.

PURPOSE: Verbal short-term memory (STM) and working memory (WM) skills predict speech and language outcomes in children with cochlear implants (CIs) even after conventional demographic, device, and medical factors are taken into account. However, prior research has focused on single end point outcomes as opposed to the longitudinal process of development of verbal STM/WM and speech-language skills. In this study, the authors investigated relations between profiles of verbal STM/WM development and speech-language development over time. METHOD: Profiles of verbal STM/WM development were identified through the use of group-based trajectory analysis of repeated digit span measures over at least a 2-year time period in a sample of 66 children (ages 6-16 years) with CIs. Subjects also completed repeated assessments of speech and language skills during the same time period. RESULTS: Clusters representing different patterns of development of verbal STM (digit span forward scores) were related to the growth rate of vocabulary and language comprehension skills over time. Clusters representing different patterns of development of verbal WM (digit span backward scores) were related to the growth rate of vocabulary and spoken word recognition skills over time. CONCLUSION: Different patterns of development of verbal STM/WM capacity predict the dynamic process of development of speech and language skills in this clinical population.

Effects of albumin/furosemide mixtures on responses to furosemide in hypoalbuminemic patients.

Hypoalbuminemic patients often have sufficient fluid accumulation to mandate diuretic therapy but are often resistant to diuresis. Studies have suggested that hypoalbuminemia itself impairs delivery of effective amounts of diuretic agent into the urine, the site of action. Therefore, administration of mixtures of albumin and loop diuretics may enhance responses. Thirteen patients with biopsy-proven cirrhosis and ascites (age, 51.2 +/- 8.1 yr; Child-Pugh score, 8.5 +/- 1.0; serum albumin concentration, 3.0 +/- 0.6 g/dl) were studied in this randomized crossover study. Sodium balance was maintained throughout the study with a metabolic diet. All patients received spironolactone, but administration of all other diuretic agents was discontinued. Each patient received all of the following four treatments intravenously: (1) 40 mg of furosemide, (2) 25 g of albumin, (3) 40 mg of furosemide and 25 g of albumin premixed ex vivo, and (4) 40 mg of furosemide and 25 g of albumin infused simultaneously into different arms. Responses were assessed by measuring urinary sodium excretion and relating the urinary furosemide excretion rate to the sodium excretion rate. Additionally, the pharmacokinetics of furosemide were assessed. Furosemide pharmacokinetics were similar for all treatment arms. Albumin alone had negligible diuretic effects. Neither albumin regimen increased the response to furosemide. Moreover, the relationship between the urinary furosemide excretion rate and the sodium excretion rate was unaffected by albumin. In conclusion, albumin failed to enhance the diuretic effects of furosemide in cirrhotic patients with ascites. Therefore, the coadministration of albumin and furosemide for the treatment of cirrhosis, and likely other hypoalbuminemic conditions, should not be used clinically.