Fecal carriage and molecular epidemiologic characteristics of carbapenemase-producing Enterobacterales in primary care hospital in a Japanese city.

BACKGROUND: The worldwide spread of organisms with antimicrobial resistance is of concern, especially the trend of significantly increasing carbapenemase-producing Enterobacterales (CPE). In this study, we investigated the annual trend of intestinal CPE carriage rates in inpatients and healthy adults in a primary care hospital in Tenri, Japan. METHODS: We collected 551 samples of feces from inpatients in our institution and 936 samples from healthy people living in Tenri city from December 2012 to April 2015. All samples were cultured on MacConkey agar plates containing 4 µg/mL ceftazidime for screening test. The colonies grown on the screening medium were detected for carbapenemase genes (blaIMP-1, blaIMP-2, blaVIM, blaKPC, blaGES, blaNDM, and blaOXA-48 groups) by multiplex PCR, and CPE were identified by MALDI-TOF MS. Plasmid replicon typing and pulsed-field gel electrophoresis (PFGE) were performed on PCR-positive strains. RESULTS: The CPE carriage rate was 1.6% (9/551) in the inpatient group and 0% (0/936) in the healthy adults group. The numbers of strains positive for the carbapenemase gene were 4 for Enterobacter cloacae, 2 for Klebsiella pneumoniae, 1 for Citrobacter freundii, 1 for Raoultella ornithinolytica and 1 for Escherichia coli. In all CPE strains, the carbapenemase gene was blaIMP-6 and the plasmid replicon type was IncN. The 4 E. cloacae strains showed a similar pattern in PFGE. CONCLUSION: In the same city in Japan, CPE intestinal carriers were detected only in the inpatient group in this study but not in a healthy adults, suggesting that the spread of asymptomatic CPE carriers was confined to inpatients.

[Education and Training in Disaster Medicine for Clinical Laboratory Staff].

The clinical laboratory is essential to medicine in general. Clinical laboratory staff with a core of medical technologists are asked to take part in disaster medicine, and their education and training are urgently neces- sary to markedly contribute to disaster medicine. Clinical laboratory staff who participate in disaster medicine should have the following: 1) understanding of disaster medicine and the skills to implement it, 2)warm spirits of togetherness with disaster victims and enthusiasm to help them, 3) physical strength and self-control, 4) the ability to communicate and connect with other staff, 5) the ability to devise clinical laboratory systems according to the situation. It is desirable for associations of clinical laboratory and those of disaster medicine to work together to de- velop education programs and certification systems, and for education programs to be developed into medical technologist-training schools. [Review].

[The Role of Clinical Laboratory Technicians at Bone Marrow Transplantation : Blood Test].

Transplantation therapy for hematopoietic diseases is conducted by a team led by an attending physician. After transplantation, various adverse effects occur, such as graft versus host disease (GVHD) and thrombotic microangiopathy (TMA), recurrence, and engraftment failure. Therefore, attending physicians are busy with the evaluation of laboratory data, monitoring of immunosuppressants, use of blood products, and management of infectious diseases. Under such circumstances, laboratory technicians play various roles. Our blood test technicians conduct tests to predict outcomes desired by attending physicians and report them quickly and accurately. For that purpose, they must develop skills to interpret test results and examine morphological findings. In this report, we introduce our efforts to improve post-transplantation medical care. [Review].

Analysis of molecular epidemiologic characteristics of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli colonizing feces in hospital patients and community dwellers in a Japanese city.

Infectious diseases caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli are prevalent because of nosocomial infection. In addition, colonization of ESBL-producing E. coli in the intestinal tract of community dwellers due to the contamination of meat or environmental water is assumed to be one of the sources, but the causes have not been clarified. To analyze these factors, we investigated the difference in clonal groups using a combination of phylogenetic groups and multilocus sequence typing of ESBL-producing E. coli, which were obtained from the feces of an inpatient group in our hospital and a community-dwelling group living in a Japanese city. The carriage rate of ESBL-producing E. coli in the inpatient group was 12.5% (32/257), similar to that of 8.5% (42/496) in the community dwellers (P = 0.082). Of the ESBL clonal groups detected from the community dwellers, 52% (22/42) were clonal groups, including D-ST1485, D-ST70, D-ST2847, B2-ST550, B2-ST3510, A-ST93, A-ST580, A-ST716 and B1-ST2787, that have not been detected from human pathogens, meat, companion animals and environmental water, whereas all clonal groups detected from the inpatients were those that had already been reported. The rate of fluoroquinolone-resistant ESBL clonal groups colonizing the intestinal tract of the inpatient group rose as the number of hospital days increased. These results indicated that different factors were related to colonization of ESBL-producing E. coli in the feces of the inpatient group and the community-dwelling group.

[View of Clinical Laboratory Physician on Pathophysiological Analysis by Close Cooperation of Clinical Laboratory and Ultrasonography.]

I want to give my opinion on what ultrasonography and the clinical laboratory should be to improve medical care. First, the close collaboration between ultrasonography and the clinical laboratory is the most im- portant. The development of technology and translation into the hands of medical technologists have been increasing the usefulness of ultrasonography to provide information for medical care. So, information should be used to interpret and report, respectively. The clinical research should be driven forward by collabora- tion and will result in improving medical care. Second, the system and culture of quality assurance should be established for ultrasonography as was done for clinical chemistry, hematology, etc. At that time, medical technologists who performed ultrasonography had to be aware that their abilities would be evaluated by oth- ers. Finally, it is important for medical technologists to educate young doctors not only on how to perform ultrasonography but also how to interpret images, because ultrasonography has been moving into the hands of medical technologists from doctors. Their sensitivity and view of life affect their works. I am sure of their importance in the clinical laboratory.

[Signs can be Found in "Clinical Laboratory Values" and "Ultrasonographic Findings" -Chairmen's Introductory Remarks.]

Many examinations have limitations, including specificity. Therefore, multiple examinations should be combined for practical diagnosis to facilitate treatment. In symposium 14 (ultrasound and clinical examina- tion), 5 speakers presented how to combine diagnostic methods in their clinical practice. This symposium highlighted the importance of the comprehensive management of multiple examinations for optimal patient care.

[Laboratory and Team-Based Medicine--From the Standpoint of JSLM].

The Japanese Society of Laboratory Medicine (JSLM) organized a working group to promote team-based medicine 2 years ago. The Japan Society for Clinical Laboratory Automation (JSCLA) formed a committee for team-based medicine and it was active for five years from 2006 to 2011. The author, an officer of the JSCLA, presents previous activities and policies for the future. The three main activities were as follows: Firstly, a seminar with a lecture and practice was held at meetings of the JSCLA. Secondly, Internet services were set up to introduce action programs and promote team-based medicine. Thirdly, the guidebook was edited, written from the point of view of laboratory medicine. The committee worked hard and produced favorable results. It is difficult with the present circumstances to organize a committee for team-based medicine in the JSCLA again. We expect cooperation in seminars and meetings.

[View of a Laboratory Physician on the Present and Future of Clinical Laboratories].

It is meaningful to discuss the "present and future of laboratories" for the development of laboratories and education of medical technologists. Laboratory staff must be able to perform urgent high-quality tests and take part in so-called team-based medicine and should be proud of devising systems that efficiently provide laboratory data for all medical staff. On the other hand, there may be staff with a poor sense of professionalism who work no more than is expected and too readily ask firms and commercial laboratories to solve problems. Overwork caused by providing team-based medicine and a decrease in numbers of clinical chemists are concerns. The following are hoped for in the future. Firstly, laboratory staff will become conscious of their own high-level abilities and expand their areas of work, for example, bioscience, proteomics, and reproductive medicine. Secondly, a consultation system for medical staff and patients will be established. Thirdly, clinical research will be advanced, such as investigating unknown pathophysiologies using laboratory data and samples, and developing new methods of measurement. Lastly, it is of overriding importance that staff of laboratory and educational facilities will cooperate with each other to train the next generation. In conclusion, each laboratory should be appreciated, attractive, positive regarding its contribution to society, and show individuality.

[Comments on routine laboratory data that are of practical use for physicians].

Routine laboratory data are not adequately used to follow a patient because medical students are not educated to comprehend them with time series analysis. The Department of Laboratory Medicine can support physicians by adding comments to laboratory data that are of practical use for following a patient. At Shinshu University School of Medicine, routine laboratory data are discussed by time series analysis in a reversed clinicopathological conference(R-CPC). The general status is checked and then the state of each organ is examined using routine laboratory data, and we can obtain much more information about the patient than from physical examinations. In this R-CPC, several specialists in laboratory medicine discussed routine laboratory data of a patient with severe inflammation. It was difficult to diagnose him with a bacterial infection. Elevation of white blood cell count and high C-reactive protein suggested bacterial infection, and decreased platelets showed the possibility of bacteremia. However, he was clinically diagnosed as having multiple trauma without bacterial infection after falling down a mountainside. If routine laboratory data are finely analyzed by specialists in laboratory medicine, physicians can obtain useful information for patient treatment from the Department of Laboratory Medicine.

[Antimicrobial susceptibilityof clinical isolates of aerobic gram-negative bacteria in 2008].

We determined MICs of antibacterial agents against 1145 clinical strains of aerobic Gram-negative bacteria (22 species) isolated at 16 Japanese facilities in 2008. MICs were determined using mostly broth microdilution method and antibacterial activity was assessed. Strains producing extended-spectrum beta-lactamases (ESBL) accounted for 3.8% of Escherichia coli, 2.6% of Klebsiella pneumoniae, 6.8% of Klebsiella oxytoca, 5.5% of Proteus mirabilis and 1.8% of Proteus vulgaris. ESBL produced strains were 6.8% at K. oxytoca that increased compared with 3.2% and 5.5% at P. mirabilis that decreased compared with 18.8% in 2006. Among Haemophilus influenzae, 61.7% that decreased compared with 67.7% in 2006, equaled 58.7% in 2004, were strains when classified by penicillin-binding protein 3 mutation. Against Pseudomonas aeruginosa, the activity of most antibacterial agents was similar to that in 2006. Although two antibacterial agents that tobramycin showed an MIC90 of 1 microg/mL and doripenem showed an MIC90 of 4 microg/mL against P. aeruginosa have potent activity. Of all P. aeruginosa strains, 4.3% were resistant to six agents of nine antipseudomonal agents, that decreased compared to 12.2% in 2004 and 5.7% in 2006. Against other glucose-non-fermentative Gram-negative rods, the activity of most antibacterial agents was similar to that in 2006.

[Antimicrobial susceptibility of clinical isolates of aerobic gram-positive cocci and anaerobic bacteria in 2008].

The activity of antibacterial agents against aerobic Gram-positive cocci (25 genus or species, 1029 strains) and anaerobic bacteria (21 genus or species, 187 strains) isolated from clinical specimens in 2008 at 16 clinical facilities in Japan were studied using either broth microdilution or agar dilution method. The ratio of methicillin-resistant strains among Staphylococcus aureus and Staphylococcus epidermidis was 59.6% and 81.2%, suggesting that resistant strains were isolated at high frequency. Vancomycin (VCM), linezolid (LZD) and quinupristin/dalfopristin (QPR/DPR) had good antibacterial activity against methicillin-resistant S. aureus and methicillin-resistant S. epidermidis, with MIC90s of < or = 2 microg/mL. The ratio of penicillin (PC) intermediate and resistant strains classified by mutations of PC-binding proteins among Streptococcus pneumoniae was 92.0% that was highest among our previous reports. Cefpirome, carbapenems, VCM, teicoplanin (TEIC), LZD and QPR/DPR had MIC90s of < or = 1 microg/mL against PC-intermediate and resistant S. pneumoniae strains. Against all strains of Enterococcus faecalis and Enterococcus faecium, the MICs of VCM and TEIC were under 2 microg/mL, and no resistant strain was detected, suggesting that these agents had excellent activities against these species. 15.9% of E. faecalis strains and 1.2% of E. faecium strains showed intermediate to LZD. 17.1% of E. faecium strains showed intermediate or resistant to QPR/DPR. Against all strains of Clostridium difficile, the MIC of VCM was under 1 microg/mL, suggesting that VCM had excellent activity. Carbapenems showed good activity against Clostridiales, Bacteroides spp., and Prevotella spp., but one strain of Bacteroides fragilis showed resistant to carbapenems. And so, the susceptibility of this species should be well-focused in the future at detecting continuously.

[Nationwide surveillance of parenteral antibiotics containing meropenem activities against clinically isolated strains in 2009].

The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics against clinical isolates of 2655 strains including 810 strains of Gram-positive bacteria, 1635 strains of Gram-negative bacteria, and 210 strains of anaerobic bacteria obtained from 30 medical institutions during 2009 was examined. The results were as follows; (1) MEPM was more active than the other carbapenem antibiotics tested against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MEPM was also active against most of the species tested in Gram-positive and anaerobic bacteria, except for multidrug resistant strains including methicillin-resistant Staphylococcus aureus (MRSA). (2) MEPM maintained potent and stable antibacterial activity against Pseudomonas aeruginosa. The proportion of MEPM-resistant strains to ciprofloxacin-resistant strains or imipenem-resistant strains were 53.1% and 58.0% respectively. (3) The proportion of extended-spectrum beta-lactamase (ESBL) strains was 3.1% (26 strains) in enterobacteriaceae. And the proportion of metallo-beta-lactamase strains was 2.0% (6 strains) in P. aeruginosa. (4) Of all species tested, there were no species except for Bacteroides fragilis group, which MIC90 of MEPM was more than 4-fold higher than those in our previous study. Therefore, there is almost no significant decrease in susceptibility of clinical isolates to meropenem. In conclusion, the results from this surveillance study suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem for serious infections treatment at present, 14 years passed after available for commercial use in Japan.

Measuring serum prothrombin in patients treated with warfarin or direct oral anticoagulants.

BACKGROUND: Warfarin therapy influences generation of γ-carboxyglutamyl (Gla) residues in prothrombin, causing reduced coagulation activity. It will leave such inactive prothrombin in serum after clot formation, resulting in serum prothrombin constituting total inactive prothrombin in these patients. METHODS: An ELISA was developed to measure biologically inactive prothrombin in serum, and applied to serum from warfarin therapy causing a decrease in Gla residues or direct oral anticoagulant (DOAC) therapy as its contrast. RESULTS: The concentrations of serum prothrombin in both the warfarin and DOAC groups were higher than those in the healthy group (p < 0.01 and p < 0.001, respectively). When serum in the previous three groups was treated with barium carbonate to exclude prothrombin, which lost several Gla residues, the prothrombin concentration in the DOAC group decreased to the same level as that in the healthy group, indicating that prothrombin was obtained at a high level only in the warfarin group (p < 0.01). CONCLUSIONS: Warfarin and DOAC led to increase in serum prothrombin concentration. The reason is that DOAC decreases prothrombin recruitment during fibrin clot formation, while warfarin leads to the accumulation of inactive prothrombin, which have a decreased number of Gla residues.

[Evaluation of target attainment rate of pazufloxacin mesilate using Monte Carlo simulation method].

We calculated achievement rates of target attainment of AUC/MIC using Monte Carlo simulation (MCS). Two doses of pazufloxacin mesilate (PZFX) between q.d. and b.i.d. were compared for each species of bacterium. Concentrations for AUC of PZFX of 8 patients were measured at this hospital, and those from a phase I clinical study (phase I, 6 healthy volunteers) were used. MICs of PZFX were determined for each species of bacterium of respiratory organ origin (Pseudomonas aeruginosa, Haemophilus influenzae, Streptococcus pneumoniae, and Klebsiella pneumoniae). AUC per day of 500 mg b.i.d. used twice AUC (PZFX 500 mg x 2/day by patient, PZFX 500 mg x 2/day by phase I). Target attainment of AUC/MIC was AUC/MIC > or = 30 in S. pneumoniae and AUC/MIC > or = 125 in the other species of bacteria (P. aeruginosa, H. influenzae, and K. pneumoniae). As a result, patients showed an about 3 times higher AUC than the phase I subjects (67.9/21.9 microg/mL). In addition, the target attainment of AUC/MIC showed the highest rate in PZFX 500 mg x 2/day in patients with each type of bacteria: H. influenzae (98%), K. pneumoniae (89%), S. pneumoniae (66%), and P aeruginosa (41%). Target attainment of AUC/MIC was H. influenzae (91%), K. pneumoniae (81%), P. aeruginosa (5%), and S. pneumoniae (0%) in phase I. Therefore, the effectiveness of PZFX was estimated to be low using the MCS method with the phase I data.

[Antimicrobial susceptibility of clinical isolates of aerobic Gram-positive cocci and anaerobic bacteria in 2006].

The activity of antibacterial agents against aerobic Gram-positive cocci (26 species, 1022 strains) and anaerobic bacteria (23 species, 184 strains) isolated from clinical specimens in 2006 at 16 clinical facilities in Japan were studied using either broth microdilution or agar dilution method. The ratio of methicillin-resistant strains among Staphylococcus aureus and Staphylococcus epidermidis was 53.0% and 65.8%, suggesting that resistant strains were isolated at high frequency. Vancomycin (VCM) and quinupristin/dalfopristin (QPR/DPR) had good antibacterial activity against methicillin-resistant S. aureus and methicillin-resistant S. epidermidis, with MIC90s of < or = 2 micrcog/mL. The ratio of penicillin (PC) intermediate and resistant strains classified by mutations of PC-binding proteins among Streptococcus pneumoniae was 87.6%. Ceftriaxone, cefpirome, cefepime, carbapenem antibiotics, VCM, teicoplanin, linezolid(LZD) and QPR/DPR had MIC90s of < or = 1 microg/mL against PC-intermediate and resistant S. pneumoniae strains. Against all strains of Enterococcus faecalis and Enterococcus faecium, the MICs of VCM and TEIC were under 2 microg/mL, and no resistant strain was detected, suggesting that these agents had excellent activities against these species. 10.9% of E. faecalis strains or 3.5% of E. faecium strains showed intermediate or resistant to LZD. 24.4% of E. faecium strains showed intermediate or resistant to QPR/DPR. Against all strains of Clostridium difficile, the MIC of VCM were under 1 microg/mL, suggesting that VCM had excellent activity against C. difficile. Carbapenems showed good activity against Peptococcaceae, Bacteroides spp., and Prevotella spp. However since several strains of Bacteroides fragilis showed resistant to carbapenems and the susceptibility of this species should be well-focused in the future.

[Antimicrobial susceptibility of clinical isolates of aerobic Gram-negative bacteria in 2006].

We determined MICs of antibacterial agents against 1280 clinical strains of aerobic Gram-negative bacteria (19 genus or species) isolated at 16 Japanese facilities in 2006. MICs were determined using mostly broth microdilution method and antibacterial activity was assessed. Strains producing extended-spectrum beta-lactamases (ESBL) accounted for 3.7% of Escherichia coli, 2.7% of Klebsiella spp., and 11.4% of Proteus spp. Notably, 18.8% of Proteus mirabilis was found to produce ESBL higher than 16.7% in 2004. This result was higher extremely than other species. Among Haemophilus influenzae, only 1.2% produced beta-lactamase and 62.8% that increased compared with 57.7% in 2004, were beta-lactamase-negative ampicillin-resistant strains when classified by penicillin-binding protein 3 mutation. Although few antibacterial agents against Pseudomonas aeruginosa have potent activity, only three agents--doripenem, ciprofloxacin, and tobramycin-showed an MIC90 of 4 microg/mL. Of all P aeruginosa strains, 5.7% were resistant to six or more agents of nine antipseudomonal agents, a decrease compared to 8.7% in 2004. Against other glucose-non-fermentative Gram-negative bacteria, the activity of most antibacterial agents was similar to that in 2004.

[Evaluation of diagnostic performance of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) for HCV related hepatocellular carcinoma developed after long-term follow up].

PURPOSE: This study evaluated the diagnostic performance of two tumor markers, alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP), a combination of these tests and other common tests for patients developing hepatocellular carcinoma (HCC) during long-term follow-up for HCV-related liver disease. METHODS: We reviewed the medical records of 144 patients who developed HCC after at least one-year follow up for HCV-related liver disease in Yamaguchi University Hospital or Tenri Hospital and demographic, clinical and laboratory data were collected retrospectively. To evaluate diagnostic test performance, we defined the oldest data collected from each patient at least one year before the diagnosis of HCC as negative control data. RESULTS: Sensitivity and specificity were 0.52, 0.61 for AFP with a cut-off of 20 ng/ml compared to 0.47 and 1.00 for DCP with a cut-off of 40 mAU/ml, respectively. Combination tests for AFP at 100 ng/ml and DCP at 40 mAU/ml yielded the best sensitivity at 0.84 with a specificity of 0.50. Multivariate logistic regression model using AFP, AST, LD, hemoglobin, prothrombin time and male ratio as variables showed significantly better diagnostic performance, i.e. sensitivity 0.85, specificity 0.74, than single test or combination test using AFP and DCP alone. CONCLUSIONS: AFP and DCP alone were not sufficient for detection of HCC developing during long-term follow-up of HCV-related cirrhosis. Logistic regression including AFP and commonly used laboratory tests showed superior diagnostic accuracy compared to that of tumor marker tests alone.

The First-Derivative Curve of the Coagulation Waveform Reveals the Cause of aPTT Prolongation.

Clot waveform analysis based on activated partial thromboplastin time (aPTT) is reported to be a useful assay. We attempted to find beneficial parameters with the first-derivative curve. We examined 106 plasma samples with prolonged aPTT and analyzed the first-derivative curve statistically by dividing it into 6 groups (Lupus anticoagulant, Heparin, Direct oral anticoagulants, Factor VIII inhibitor, Hepatic dysfunctions and Factor deficiency). We obtained 7 coordinates for parameter measurement by analyzing the first-derivative curve and set 20 parameters including the velocity axis, the time axis, and area parameters. The distribution was checked by extracting each parameter that showed the most significant difference in the 6 groups. As a result, it was revealed that we could classify aPTT prolongation by using a combination of 3 parameters, the initial-to-peak gradient, the ratio initial-to-intermediate velocity/intermediate-to-peak velocity, and the initial-to-peak area size. We constructed a flowchart combining these 3 parameters and were able to discriminate 75% of the specimens. These parameters derived from the first-derivative curve of clot waveform analysis are useful tools to discriminate aPTT prolongation.

Influence of Warfarin Therapy on Prothrombin Production and Its Posttranslational Modifications.

BACKGROUND: Protein induced by vitamin K absence-II (PIVKA-II) is produced by the liver during hepatoma and upon warfarin administration. Those patients have disturbed protein synthesis and glycosylation in the liver. This decreases the number of γ-carboxyglutamyl (Gla) residues on prothrombin, converting prothrombin into PIVKA-II. The mechanism of this conversion, however, is not clearly understood. METHODS: Prothrombin was isolated from healthy and warfarin-treated individuals whose liver function of protein production was quantitatively normal. Glycan structures in the purified prothrombin containing PIVKA-II were qualitatively analyzed by high performance liquid chromatography after labeling the glycan with fluorophore 2-aminobenzamide. RESULTS: The concentration of PIVKA-II was significantly higher in the warfarin-treated individuals than in the healthy individuals (P< 0.001). Although protein production in the liver was normal in both groups, the concentration of prothrombin was lower in the warfarin-treated individuals than in the healthy individuals (P < 0.001). The main glycan was A2 in the healthy and warfarin-treated individuals (86.6 ± 4.4% and 85.6 ± 3.4%, respectively). Eight types of glycan were characterized in both groups, although generation of PIVKA-II in the warfarin-treated individuals did not lead to variation in glycosylation of prothrombin. CONCLUSIONS: Warfarin therapy leads to lower amounts of prothrombin and Gla residues within prothrombin without exerting qualitative and quantitative change in glycan profile and protein synthetic function in the liver.

[Effects of real-time analysis of brain natriuretic peptide (BNP) on physicians' decision making in outpatient settings].

Brain natriuretic peptide (BNP) is a strong diagnostic indicator of heart failure. Currently, automated plasma BNP measurement is possible, allowing physicians to ascertain each outpatient's BNP level on the day of consultation. We investigated whether providing a real-time analysis of BNP would lead to a superior outcome in the outpatient setting. The subjects were 111 outpatients who consulted the cardiovascular internal medicine with a BNP value of 200 pg/ml or more. Of these patients, 53 were assessed before the introduction of the real-time analysis of BNP (Pre group), and 58 were assessed after its introduction (Post group). We compared the courses taken based on physicians' direction between the Pre and Post groups. Three patients were admitted to the hospital on the consultation day, and 55 patients were followed up on an outpatient basis, including 27 patients requiring an adjustment of medication, in the Post group. However, 11 patients were hospitalized and 42 were followed up as outpatients, including 16 patients requiring an adjustment of medication, in the Pre group. The number of patients hospitalized on the consultation day in the Post group was less than half of that in the Pre group. Furthermore, fewer outpatients visited the emergency department before their next scheduled appointment due to heart failure aggravation in the Post than in the Pre group (2 out of 55 vs. 10 out of 42 outpatients; difference, 0.202; 95% CI, 0.069 to 0.334; p=0.003). The provision of BNP analysis at the time of consultation reduced the rate of hospitalization and cardiovascular events in heart-failure outpatients.