Clinical, pharmacokinetic and economic analysis of the first switch to an extended half-life factor IX (albutrepenonacog alfa, rFIX-FP) in Spain.

Extended half-life of factor IX (FIX) demonstrated clinical benefit and lower treatment burden than standard half-life FIX products in clinical trials. We analysed the impact in efficacy, pharmacokinetics (PKs) and costs of the switch from nonacog alfa (rFIX) to albutrepenonacog alfa (rFIX-FP) in the first patient with haemophilia B (HB) treated in Spain outside clinical trials. A 7-year-old boy presented with HB with poor venous access and repetition infections using rFIX, which was switched to rFIX-FP. Prophylaxis was adjusted by PKs using WAPPS-Hemo tailoring from 100 IU/kg/week of rFIX to 80 IU/kg/3 weeks of rFIX-FP. Comparing 6 months before, rFIX-FP reduced 68.5% FIX consumption/kg and 58.3% infusion frequency, but total costs/weight showed a slight increase. Ratio of half-life between rFIX and rFIX-FP was 3.4-3.7. This case report revealed that switch to rFIX-FP decreased frequency and FIX consumption, without adverse events and bleeds.

Can didactic continuing education improve clinical decision making and reduce cost of quality? Evidence from a case study.

INTRODUCTION: Administration of human serum albumin (HSA) solutions for the resuscitation of critically ill patients remains controversial. The objective of this study was to assess the effect of continuing medical education (CME) on health care professionals' clinical decision making with regard to HSA administration and the costs of quality (COQ). A quasi-experimental study of time series association of CME intervention with COQ and use of HSA solution was conducted at the Surgery Department of the Hospital Valjevo, Serbia. The CME contained evidence-based criteria for HSA solution administration in surgical patients. The preintervention period was defined as January 2009 to May 2011. CME was provided in June 2011, with the postintervention period June 2011 to May 2012. METHODS: Total mortality rate, the rate of nonsurgical mortality, the rate of surgical mortality, the rate of sepsis patient mortality, index of irrational use of HSA solutions, and number of hospital days per hospitalized patient were collected for each month as quality indicators. Statistical analysis was performed by multivariate autoregressive integrated moving average (MARIMA) modeling. The specification of the COQ was performed according to a traditional COQ model. RESULTS: The CME intervention resulted in an average monthly reduction of the hospital days per hospitalized patient, the rate of sepsis patient mortality, index of irrational use of HSA solutions, and COQ for $593,890.77 per year. DISCUSSION: Didactic CME presenting evidence-based criteria for HSA administration was associated with improvements in clinical decisions and COQ. In addition, this study demonstrates that models combining MARIMA and traditional COQ models can be useful in the evaluation of CME interventions aimed at reducing COQ.

Different injection techniques in the assessment of central haemodynamics in patients with cirrhosis.

OBJECTIVE: Patients with cirrhosis often present with an abnormal distribution of blood volume with a reduced central blood volume (CBV) and central circulation time (CCT). In this group of patients it is important to determine the central haemodynamics as accurately as possible. The purpose of the present study was to compare an alternative injection technique by injecting technetium-labelled human serum albumin ((99m)Tc-HSA) from a deposit within the catheter lumen with the conventional injection technique by injecting iodine-labelled human serum albumin ((125)I-HSA) directly from a syringe. MATERIALS AND METHODS: In 192 patients with cirrhosis, CCT, CBV, and cardiac output (CO) were determined according to kinetic principles. Injection of the two radiolabelled HSA were performed simultaneously and followed by arterial blood sampling every second for the first minute. RESULTS: CCT was significantly shorter, and CO and CBV were significantly lower when determined by the alternative catheter deposit injection technique compared to determination by the traditional syringe deposit injection technique. The mean difference (bias) between CCT measured with the two methods was 0.38 s with limits of agreement ranging from - 0.83 s to 1.59 s. CONCLUSION: This study demonstrates that different injection techniques result in a minor but significant difference of the measured haemodynamics. When highly accurate measurements of the central haemodynamics are needed, we recommend using the alternative injection technique by injection of the indicator from a deposit within the catheter in order to reduce overestimation of CCT.

Long-term tissue coverage of a biodegradable polylactide polymer-coated biolimus-eluting stent: comparative sequential assessment with optical coherence tomography until complete resorption of the polymer.

BACKGROUND: Biolimus-eluting stents (BESs) with a biodegradable polymer in abluminal coating achieve more complete coverage at 9 months compared with sirolimus-eluting stents (SESs) with a durable polymer, as assessed by optical coherence tomography (OCT). Whether this advantage persists or augments after complete resorption of the polymer (>12 months) is unknown. METHODS: The LEADERS trial compared the performance of BES with that of SES. Patients were randomly allocated to a sequential angiographic follow-up, including OCT in selected sites, at 9 and 24 months. Struts coverage was compared using Bayesian hierarchical models as the primary outcome for the OCT substudy. RESULTS: Fifty-six patients (26 BES, 30 SES) were enrolled in the OCT substudy. Twenty-one patients (10 BES, 11 SES) agreed to perform a second OCT follow-up at 24 months. Eleven lesions and 12 stents were analyzed sequentially in the BES group (2,455 struts at 9 months, 2,131 struts at 24 months) and 11 lesions and 18 stents in the SES group (3,421 struts at 9 months, 4,170 struts at 24 months). The previously reported advantage of BES over SES in terms of better strut coverage at 9 months was followed by improvement in coverage of the SES, resulting in identical coverage in both BES and SES at 24 months: 1.5% versus 1.8% uncovered struts, difference -0.2%, 95% credibility interval, -3.2% to 2.6%, P = .84. CONCLUSIONS: More complete strut coverage of BES as compared with SES at 9 months was followed by improvement of coverage in SES between 9 and 24 months and a similar long-term coverage in both stent types at 24 months.

Human albumin use at hospitals in the Metropolitan Region of Rio de Janeiro, Brazil.

The study analyzes the use of human albumin in hospitals in Rio de Janeiro, Brazil, using inpatient data from the information system of Brazil's health system between 1999 and 2001. Death was the main outcome as patients died in 32% of admissions in which human albumin was used as compared with 4% of all admissions in the same period and region. The Charlson Comorbidity Index was included for risk adjustment. Human albumin was used in 10,111 in-patients more than 1 year old. 87,774 50-ml bottles of 20% human albumin were consumed at a cost of US$ 1,755. The main diagnoses were neoplasms (29.1%), diseases of the digestive system (17.5%) and circulatory system (16%). Death rate increased with age, public ownership of the hospital, clinical services (as opposed to surgical services), length of stay and use of intensive care. Death was associated with use of more than four bottles of human albumin (PR: 1.30; 99%CI: 1.23-1.37), adjusted for severity and speciality. The results are cause for concern as they may be related to poor compliance with guidelines, excess of risk to patients and unnecessary expenses for the public health system.

Human albumin use at hospitals in the Metropolitan Region of Rio de Janeiro, Brazil / Uso de albumina humana nos hospitais da Região Metropolitana do Estado do Rio de Janeiro, Brasil

The study analyzes the use of human albumin in hospitals in Rio de Janeiro, Brazil, using inpatient data from the information system of Brazil's health system between 1999 and 2001. Death was the main outcome as patients died in 32 percent of admissions in which human albumin was used as compared with 4 percent of all admissions in the same period and region. The Charlson Comorbidity Index was included for risk adjustment. Human albumin was used in 10,111 in-patients more than 1 year old. 87,774 50-ml bottles of 20 percent human albumin were consumed at a cost of US$ 1,755. The main diagnoses were neoplasms (29.1 percent), diseases of the digestive system (17.5 percent) and circulatory system (16 percent). Death rate increased with age, public ownership of the hospital, clinical services (as opposed to surgical services), length of stay and use of intensive care. Death was associated with use of more than four bottles of human albumin (PR: 1.30; 99 percentCI: 1.23-1.37), adjusted for severity and speciality. The results are cause for concern as they may be related to poor compliance with guidelines, excess of risk to patients and unnecessary expenses for the public health system.

O estudo analisou o uso da albumina humana em hospitais do Rio de Janeiro, Brasil, utilizando os registros do Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH/SUS), 1999 e 2001. Como 32 por cento das internações resultaram em óbito, em comparação com 4 por cento de óbito para todas as internações no mesmo período e região, este foi o desfecho principal do estudo. A albumina humana foi usada em 10.111 internações de maiores de um ano, que consumiram 87.774 frascos - 50mL a 20 por cento, com gasto de US$ 1.755,00. Os principais diagnósticos foram neoplasias (29,1 por cento), doenças do aparelho digestivo (17,5 por cento) e do aparelho circulatório (16 por cento). Houve maior proporção de óbitos de pacientes mais idosos, que receberam mais doses de albumina humana, internados por mais tempo, em especialidades clínicas, em UTI, em hospitais públicos. O óbito esteve associado ao uso de mais de quatro frascos de albumina humana (RP: 1,30; IC99 por cento: 1,23-1,37), ajustado por gravidade e especialidade. Os resultados evidenciam a baixa adesão aos protocolos, o excesso de risco para os pacientes e os gastos desnecessários para o sistema público de saúde.

Experience of using human albumin solution 4.5% in 1195 therapeutic plasma exchange procedures.

The aim of the study was to document the incidence of adverse reactions (ADRs) in subjects undergoing therapeutic plasma exchange with human albumin 4.5% solution (Zenalb 4.5) and to explore whether there were any differences in tolerability with a change from UK to US plasma and a subsequent manufacturing modification. Zenalb 4.5 was initially manufactured from recovered plasma from UK blood donations and later from source plasma from US donors. The modification was a salt diafiltration step. A prospective survey was conducted at three UK aphaeresis units; data from 154 subjects undergoing 1195 plasma exchanges using Zenalb 4.5 were collected. Adverse events with at least a possible relationship to treatment were recorded. There were 20 ADRs per 1195 exchanges (1.7%), experienced by 14 subjects (9.1%). The most common reaction was rigours in 17 exchanges (1.4%) and 12 subjects (7.8%). ADRs occurred in 0.8% (2/250) of plasma exchanges with UK plasma, 0.2% (1/539) using US plasma/original manufacturing method, 4.3% (16/370) using US plasma/modified method and 12.5% (1/8) using US plasma/mixed original and modified methods. Data were incomplete for the remaining 28 exchanges, but no ADRs were reported. Moreover, 17 ADRs occurred over a 14-month period and involved 10 batches manufactured from US plasma (1 original, 9 by modified method). The incidence then returned to the previously lower level. There was no explanation for this cluster of events. Overall, there was no evidence that plasma source or manufacturing method affected tolerability and it was concluded that human albumin 4.5% solution (Zenalb 4.5) is well tolerated during plasma exchange therapy.

The COASST study: cost-effectiveness of albumin in severe sepsis and septic shock.

INTRODUCTION: The cost-effectiveness of albumin-based fluid support in patients with severe sepsis is not known. METHODS: We compared standard medical practice and systematic albumin infusion. The study population consisted of patients with severe sepsis and/or septic shock admitted to one of the 35 intensive care units belonging to the Cub-Réa regional database between 1 January 1998 and 31 December 2002. Only stays longer than 24 hours and only patients with a minimum of circulatory, renal, or respiratory failure were considered. Cost estimates were based on French diagnosis-related groups and fixed daily prices. A 4.6% reduction in mortality was expected in the albumin arm, as observed in the Saline vs Albumin Fluid Evaluation (SAFE) Study. Life expectancy was estimated with the declining exponential approximation of life expectancy method, based on age, sex, Simplified Acute Physiology Score II, and McCabe score. RESULTS: The number of lives saved among the 11137 patients was 513. The average life expectancy of the 5156 patients who left the hospital alive was estimated to be 9.78 years. The costs per life saved and per year life saved were 6037 euro and 617 euro, respectively. Sensitivity analyses confirmed the robustness of the results. CONCLUSION: The application of the SAFE Study results to CUB-Réa data shows that albumin infusion is cost-effective in severe sepsis.

Contrast-enhanced triggered harmonic sonography for assessment of periarticular hemodynamic changes in experimental arthritis.

BACKGROUND: Objective quantification is critical for assessment of functional sonography in inflammatory arthritis. To create a microbubble contrast-enhanced image of vessels that lie below the resolution of a standard US system, a technique is required that detects preferentially the contrast agent echo, rejecting that from background tissue: harmonic imaging. OBJECTIVES: To investigate the ability of contrast-enhanced triggered harmonic sonography (CETHS) to evaluate periarticular hemodynamic changes over the course of experimental arthritis and to discriminate presence and absence of arthritis based on measurement values obtained at specific time-points. MATERIALS AND METHODS: Arthritis was induced in rabbits knees by intra-articular injection of serum bovine albumin, which acted as an antigen. A total of 11 rabbits (8 with unilateral arthritis and 3 control animals) were imaged at 0, 1, 7, 14, 21 and 28 days of antigen-induced arthritis and euthanized at 28 days. A continuous infusion protocol was performed (triggering times 30.0, 20.0, 10.0, 5.0, 2.0, 1.0, and 0.5 s). Hemodynamic indices of synovial microvasculature (vascular volume, mean velocity and flow rate) were obtained and compared with clinical, laboratory, and histological surrogate markers. RESULTS: Although interval CETHS changes were noted for flow rate (P=0.007) and vascular volume (P=0.003) ratios in albumin-injected knees, no significant differences in ratios were identified over time between albumin-injected and non-injected knees for flow rate (P=0.52), vascular volume (P=0.23) and mean velocity (P=0.19). Flow rate most accurately differentiated between presence and absence of arthritis according to clinical measurements in early (day 1) arthritis, and mean velocity in mid-term arthritis (day 14; both P=0.02). CONCLUSION: Although the measurement properties of CETHS indices were poor in the evaluation of hemodynamic differences over time in albumin-injected knees compared with non-injected knees, they enabled discrimination between presence and absence of arthritis at specific time-points in different stages.

Histogram analysis of pharmacokinetic parameters by bootstrap resampling from one-point sampling data in animal experiments.

A bootstrap method is proposed for assessing statistical histograms of pharmacokinetic parameters (AUC, MRT, CL and V(ss)) from one-point sampling data in animal experiments. A computer program, MOMENT(BS), written in Visual Basic on Microsoft Excel, was developed for the bootstrap calculation and the construction of histograms. MOMENT(BS) was applied to one-point sampling data of the blood concentration of three physiologically active proteins ((111)In labeled Hsp70, Suc(20)-BSA and Suc(40)-BSA) administered in different doses to mice. The histograms of AUC, MRT, CL and V(ss) were close to a normal (Gaussian) distribution with the bootstrap resampling number (200), or more, considering the skewness and kurtosis of the histograms. A good agreement of means and SD was obtained between the bootstrap and Bailer's approaches. The hypothesis test based on the normal distribution clearly demonstrated that the disposition of (111)In-Hsp70 and Suc(20)-BSA was almost independent of dose, whereas that of (111)In-Suc(40)-BSA was definitely dose-dependent. In conclusion, the bootstrap method was found to be an efficient method for assessing the histogram of pharmacokinetic parameters of blood or tissue disposition data by one-point sampling.

The use of albumin in patients with decompensated cirrhosis: the case in favor.

In conclusion, in the course of patients with advanced liver disease there are several indications for institution of intravenous albumin. These include: a) enhancement of diuretic effect on mobilization of ascites fluid, b) prevention of post-paracentesis circulatory dysfunction after total/large volume paracentesis, c) prevention of hepatorenal syndrome in patients affected with SBP, and d) administration of albumin in combination with vasoconstrictor drugs as the only effective therapy for hepatorenal syndrome. Albumin is relatively inexpensive and can be given in an outpatient setting.

Evaluation of serum albumin utilization in inpatient at a private hospital in Bangkok.

Serum albumin is widely used for the treatment of hypovolemia, shock, hyperbilirubinemia or acute liver failure. However, serum albumin itself may have a significant effect on the action, elimination or distribution of other medications in blood which may affect the outcome of the treatment. Besides, it is also expensive and, most important, can be a carrier for many life-threatening diseases such as AIDS. The objective of this study is to evaluate the serum albumin utilization in inpatient at a private hospital in Bangkok, Thailand. Descriptive, retrospective study was designed to monitor the 25% w/v serum albumin orders over a four-month period. The background information, doses and rational of serum albumin orders, other medication orders, side effects, the interaction between serum albumin and other medications, the laboratory results and also clinical outcome of the patients were recorded. From the medication orders of 74 inpatients, there were 104 orders of serum albumin for 9 indications. The most common indications were hypoalbuminemia (48%) and cirrhosis (9%). From the total number of serum albumin orders, there were only 67 orders (64.4%) prescribed with rational dose and duration under appropriate indications. Totally about 35.6% of serum albumin orders were prescribed with improper indications such as edema, anemia or coronary artery bypass grafting. Out of 35.6%, 14% of the orders were prescribed to contraindicated patients. No side effect of serum albumin infusion was found during this study. The result indicates the over-utilization of serum albumin and specific guideline for using this agent should be set in every hospital.

Safety of human albumin--serious adverse events reported worldwide in 1998-2000.

BACKGROUND: Previous pharmacovigilance studies have indicated a low rate of adverse events in patients receiving human albumin. However, the incidence of adverse events is likely to have been underestimated because of under-reporting. A more accurate estimate may be possible during a period such as 1998-2000, when awareness regarding albumin safety was heightened by publication of a meta-analysis. METHODS: All serious adverse event reports received, and total doses of albumin distributed worldwide from the beginning of 1998 to the end of 2000 by 10 major suppliers of therapeutic human albumin were compiled. RESULTS: Distributed albumin doses totalled 1.62 x 10(7). The total numbers of non-fatal and fatal serious adverse events reported were 198 and 13, respectively. The incidence of all reported serious non-fatal and fatal adverse events was 5.28 per 10(6) doses (CI 1.60-17.4 per 10(6) doses). For non-fatal serious adverse events only, the observed incidence was 4.65 per 10(6) doses (CI 1.34-16.2 per 10(6) doses). No patient death was classified as probably related to albumin administration. The observed incidence of fatal serious adverse events possibly related to albumin was 0.185 per 10(6) doses (CI 0.0597-0.574 per 10(6) doses). The observed incidence of all non-fatal and fatal serious adverse events was significantly higher during the 1998-2000 period as compared with 1990-1997 (incidence rate ratio 4.98; CI 3.94-6.29), probably chiefly as a result of reduced under-reporting. CONCLUSIONS: Although the observed incidence of adverse events is likely to be an underestimate, nevertheless both non-fatal and fatal serious adverse events in albumin recipients appear to be rare. These results add further support to the excellent safety record of human albumin.

Assessment of left atrial appendage filling pattern by using intravenous administration of microbubbles: comparison between mitral stenosis and mitral regurgitation.

Mitral stenosis (MS) and mitral regurgitation (MR) are the most frequent conditions that cause a dilation and dysfunction of the left atrial appendage (LAA). Despite similarly dilated LAA in patients with MS and MR, the incidence of LAA thrombi and the risk of thromboembolism is different between these patients. The purpose of this study was to characterize the filling pattern of LAA by using intravenous administration of perfluorocarbon-exposed dextrose albumin (PESDA) during transesophageal echocardiographic examination in patients with MS and MR. Twenty-four patients with moderate to severe MS, 12 patients with severe MR, and a control group including 30 patients with conditions other than mitral valve disease underwent transesophageal echocardiographic examination with an intravenous bolus injection of PESDA. LAA emptying and filling velocities and maximal and minimal areas of LAA and LAA ejection fraction were measured. Digital gray-scale intensity (GSI) of the left atrial (LA) and LAA cavity after PESDA injection was measured by off-line analysis. Compared with control patients, patients with MS or MR had larger maximal and minimal areas of LAA and reduced LAA ejection fraction. LAA peak emptying flow velocity was significantly lower in patients with MS compared with those of MR or control patients. LAA peak filling velocity was significantly lower in patients with MS compared with that of control patients. However, there was no significant difference of LAA peak filling velocity between the patients with MS and MR. There was no significant difference of GSI ratio of LAA and LA between patients with MR and control patients; however, GSI ratio of LAA and LA was significantly lower in patients with MS compared with that of MR. The incidence of LAA spontaneous echo contrast and LAA thrombi in patients with MS was significantly higher than that of the patients with MR and control subjects (P <.005). Despite similarly dilated LAA area and depressed contractile function of LAA in patients with MS and MR compared with control patients, profoundly impaired LAA filling with resultant flow stasis was demonstrated by contrast echocardiography in patients with MS. These findings may explain the higher incidence of LAA spontaneous echo contrast and thrombus in patients with MS.

Prospective study comparing human albumin vs. reinfusion of ultrafiltrate-ascitic fluid after total paracentesis in cirrhotic patients with tense ascites.

Although, total paracentesis associated with human albumin substitution has shown to be a rapid, effective and safe treatment of diuretic refractory ascites in advanced liver cirrhosis, it implies high costs and has a limited availability. Therefore an alternative procedure the reinfusion of concentrated ascites has gained popularity in recent years (Smart et al. 1990; Grazioto et al. 1997). It was the aim of the study to compare human albumin substitution vs. reinfusion of ascitic-ultrafiltrate after total paracentesis. 35 patients with cirrhosis and tense ascites received total paracentesis associated with either human albumin (5-8 g/l ascites) (= group A) or reinfusion of an ascitic-ultrafiltrate fluid by means of hemofiltration technique (= group B). The mean volume of ascites removed was 9.41 (2.1-20.0) in group A and 11.41 (6.5-21.0) in group B. No significant differences in serum electrolytes, liver and renal function, coagulation profiles and hormones of the renin-angiotensin-aldosterone system were observed during hospitalization. In both groups sodium excretion increased significantly. 43% of the patients in group B developed pyrexia and chill after reinfusion of the ascitic-ultrafiltrate fluid. In one patient an anaphylactic bronchospasm occurred requiring IUC-treatment. The treatment cost in case of human albumin were 326.-DM vs. 290.-DM for each patient treated with ascitic-ultrafiltrate fluid reinfusion. The probabilities of hospital readmission and survival were similar in both groups during follow-up. The results indicate that i.v. infusion of ascitic-ultrafiltrate fluid is as effective as total paracentesis and albumin infusion in case of diuretic refractory ascites. However, according to the costs of instruments and staff and due to the significant allergic reactions caused by ascitic fluid it cannot be considered as a real alternative to albumin substitution.

Current non-surgical usage of albumin preparations in clinic divisions.

New guidelines for the clinical use of blood preparations, intended to promote a more rational use, were issued by the Japanese Ministry of Health and Welfare in June 1999. The purpose of this article is to clarify the current situation in the non-surgical use of albumin (Alb) preparations in each clinic division and to design a plan to promote the rational use of these products at Yamaguchi University Hospital. Of the patients administered Alb preparations in the clinic divisions of our hospital over the six-month period from January 1 to June 30, 1999, 454 were selected based on prescription records of plasma component preparations. Most of the patients were 60 years of age or older (61.7%) and from the surgery division (65.2%). The total amount of Alb administered to the patients was 52.9 kg. Those patients whose serum Alb concentration was less than 2.5 g/dl before and more than 3.5 g/dl after the administration numbered 125 and 122, respectively. The total amount of Alb overdosed to the patients, whose Alb concentration after administration of the preparations was more than 2.5 g/dl, was 17.7 kg (33.5% of the administered amount). The overdosed patients belonged mainly to the surgery division. These results indicate that it is possible to cut back on Alb by reconsidering the criteria for its administration, and that we need to promote more intensively the need to monitor the level and predict the effect of Alb in surgical divisions.

A protocol-based treatment for intradialytic hypotension in hospitalized hemodialysis patients.

Human serum albumin is used in hemodialysis (HD) units as treatment for hypotension despite its high cost and undetermined efficacy. During a 4-month period in 1995, albumin was used in 22% of 1,296 consecutive HD treatments in the HD unit or intensive care units (ICUs) at our tertiary-care hospital. We evaluated the safety and efficacy of a protocol designed to minimize albumin use for treating HD-associated hypotension (HDAH). The protocol consisted of the stepwise use of saline, mannitol, and albumin for the purpose of achieving physician-determined ultrafiltration goals. Patients were exempted from receiving the protocol for age younger than 18 years, freshly declotted angioaccess, or cardiovascular instability. The protocol was evaluated prospectively in 2,559 consecutive dialysis sessions (15% in ICUs) in 442 patients. Hypotension occurred during 608 sessions (24%), and attending nephrologists elected to initiate the protocol in 71% of these cases. Of the 433 instances in which the protocol was begun, reversal of hypotension was achieved without the need for albumin in 91% and with the addition of albumin in an additional 2%. Protocol treatment was not completed because of nursing error in 1% or clotting of filter or angioaccess in 4%. Use of the protocol failed to reverse hypotension in only 2% of the cases in which it was completed. Albumin was administered in only 6% of the 2,559 HD treatments. In summary, our protocol-based approach to HDAH was effective, easy for nurses to use, albumin sparing, and cost reducing.