Impact of a network system for providing proper inhalation technique by community pharmacists.

OBJECTIVE: The availability of many types of inhalers in the treatment of asthma has resulted in a wide range of prescription choices for clinicians. With so many devices available, however, there is some confusion regarding their proper use among both medical staff and patients. Since 2007, Kitano Hospital and Kita-ku Pharmaceutical Association, Osaka, Japan, have provided a network system for delivering instruction on correct inhalation technique through community pharmacists. We examined the clinical effects of this network system. METHODS: Our measurements included the manner in which community pharmacists instruct patients with asthma, the frequency of asthma exacerbations, patients' adherence to inhalation therapy using a 5-point Likert scale questionnaire, and patients' health status both prior to this system and at 4 years after. RESULTS: Usable information was obtained from 53 community pharmacists and 146 patients with asthma at baseline and from 60 community pharmacists and 148 patients at 4 years. When compared with baseline values, significant improvement was found in pharmacists' instruction and significant decreases were observed in the frequency of asthma exacerbations (1.4 ± 1.6 vs. 1.0 ± 1.4 times/yr, p = .042) and emergency room visits (0.5 ± 1.0 vs. 0.2 ± 0.5 times/yr, p = .004). Adherence to the inhalation regimen significantly increased (4.0 ± 0.7 vs. 4.2 ± 0.8, p = .041), but health status was unchanged. CONCLUSIONS: Our network system may improve asthma control and adherence to inhalation regimens.

Repeated instruction on inhalation technique improves adherence to the therapeutic regimen in asthma.

BACKGROUND: Adherence to inhalation therapy is a critical determinant of the success of asthma management. Reasons for nonadherence have been well studied, but reasons for good adherence are poorly understood. Understanding the mechanisms of adherence to inhalation therapy is important in developing strategies to promote adherence. The objective of this study was to assess the factors and mechanisms that contribute to and the clinical outcomes relating to adherence to inhalation therapy. METHODS: The factors and outcomes related to adherence to inhalation therapy were examined cross-sectionally in 176 adults with asthma using a self-reported adherence questionnaire that consisted of four items dealing with the use of inhaled controller medications. A 5-point Likert scale was used for the responses to each item. Adherence was assessed based on the overall mean adherence score. RESULTS: Of the 176 patients who were potential participants, 146 (83%) responded with usable information. Significant factors associated with the overall mean adherence score were older age (r = .18, p = .032) and receiving repeated instruction on inhalation techniques (p = .0016). Of the 146 respondents, 25 (17.1%) patients were given repeated verbal instruction or demonstrations of inhalation technique by a respiratory physician. On logistic regression analysis, good adherence to inhalation therapy was significantly related to the receiving of repeated instruction on inhalation technique, with an odds ratio of 2.90 (95% confidence interval 1.07-7.88; p = .037). Furthermore, less intentional nonadherent behavior was reported in patients with repeated instruction on inhalation technique compared to those without it. A significant correlation was found between the overall mean adherence score and the frequency of asthma exacerbations (r = -.19, p = .021), emergency room visits (r = -.19, p = .042), and the health-related quality of life score (St. George's Respiratory Questionnaire: Total, r = -.22, p = .024; Symptoms, r = -.21, p = .022; Impacts, r = -.20, p = .035). CONCLUSIONS: Repeated instruction on inhalation techniques may contribute to adherence to inhalation therapy through decreasing intentional nonadherence. Furthermore, good adherence to the therapeutic regimen may offer good asthma-related outcomes.

[Influence of black vinegar on itraconazole absorption].

Itraconazole (ITCZ), a useful oral drug effective against Aspergillus, is reported to cause insufficient blood concentration through unstable enteral absorption. Hypoacidic gastic conditions have been reported to reduce absorption, whereas acidic drinks promote it. We present a case of pulmonary aspergillosis in a subject administered ITCZ with black vinegar, a popular health food in Japan. The 59-year-old man showed high blood concentrations of ITCZ, resulting in good Aspergillosis control. To confirm the efficacy in black vinegar on absorbing ITCZ, we administered ITCZ capsules with and without black vinegar to 10 healthy adults after preparation with a proton pump inhibitor to decrease gastric acidity, and measured blood concentrations of ITCZ and the metabolite OH-ITCZ. Administration of this combination increased ITCZ and OH-ITCZ Cmax significantly. For patients who produce too little gastric juice, black vinegar could thus serve to promote ITCZ capsule absorption.

Antimicrobial susceptibilities of Streptococcus pneumoniae isolated from adult patients with community-acquired pneumonia in Japan.

BACKGROUND AND OBJECTIVE: Streptococcus pneumoniae (S. pneumoniae) is the most common pathogen associated with community-acquired pneumonia and its resistance to antimicrobials is a worldwide problem. The aim of this study was to investigate the current drug susceptibilities of S. pneumoniae isolated from adult patients with community-acquired pneumonia in Japan. METHODS: S. pneumoniae strains isolated from adult patients with pneumococcal pneumonia from 10 institutions were collected prospectively between May 2003 and October 2004 and tested for drug susceptibilities. Clinical data were analysed and the risk factors for drug resistance investigated. RESULTS: A total of 141 isolates of S. pneumoniae were analysed. Of these S. pneumoniae isolates, 46.1% had intermediate penicillin resistance and the minimum inhibitory concentration (MIC) occurring in the greatest number of isolates and MIC90 value was 2 microg/mL. The prevalence of resistance to macrolides was 80%, with the MIC90 values being greater than or equal to 16 microg/mL. Approximately 40% of the strains were resistant to oral third-generation cephems. Penicillin and erythromycin resistance were both associated with the pre-existing chronic disease states. CONCLUSIONS: The cephem and macrolide resistance of S. pneumoniae was higher than penicillin resistance in adult patients with community-acquired pneumococcal pneumonia in Japan. We recommend that bacterial identification and sensitivities are determined in areas where the macrolide resistance to S. pneumoniae is high.

[Liaison-psychiatric service in palliative care].

In Japan, Palliative Care Teams became eligible for health insurance coverage in 2002. Cancer is the principal cause of death in Japan, and over 90% of cancer patients die at hospitals. However, health care professionals are not yet very accustomed to facing dying patients, but need to do so especially in palliative care. Three cases are introduced to show our practice as a palliative care team from a psychiatric point of view and make you reconsider the necessity of organized care for cancer patients and liaison-psychiatric service by means of palliative care.

[Case of bronchocentric granulomatosis that became recognized in the course of allergic bronchopulmonary aspergillosis].

A 56-year-old man with allergic bronchopulmonary aspergillosis (ABPA) was admitted due to the appearance of nodular opacities in the right upper lung field on chest radiography, after discontinuing itraconazole and clarithromycin on the suspicion of possible hepatic adverse effects. Chest CT scans on admission revealed nodular opacities in the right S3 and lingula bronchus, and bilateral bronchiectasis with mucoid impactions. A specimen obtained by transbronchial lung biopsy showed complete replacement of bronchioles by necrotizing granulomatous inflammation, containing the diagnosis of bronchocentric granulomatosis. Treatment with corticosteroids and micafungin sodium resulted in marked resolution of nodular opacities and mucoid impacts. This case suggests that abrupt cessation of antifungal agents and macrolides may provoke acute exacerbation of ABPA and development of bronchocentric granulomatosis.

[Diffuse expression of KIT in a pulmonary artery sarcoma].

A 77-year-old woman presented with hoarseness and hemoptysis. Chest CT scan revealed a mediastinal tumor in the lumen of the left pulmonary artery. A definitive diagnosis could not be made based on mediastinoscopy and thoracotomy. Eight months later, multiple nodular shadows appeared in both lung fields.Video-assisted lung biopsy showed that these nodules were lung metastases of a spindle cell sarcoma. Based on the pathological and radiological findings, a pulmonary artery sarcoma was eventually diagnosed. Interestingly, on immunohistological staining, the tumor cells were diffusely positive for KIT, which is an immunohistochemical marker of gastrointestinal stromal tumors. The patient was treated with imatinib, a KIT tyrosine kinase inhibitor; however, the tumors progressed. The relationship between pulmonary artery sarcoma and KIT requires further study.

[Relationship between time taken from collection of blood to incubation and measurement in whole-blood interferon gamma assay for diagnosis of Mycobacterium tuberculosis infection].

BACKGROUND: The introduction of second-generation QuantiFERON-TB (QFT) enables the diagnosis of Mycobacterium tuberculosis (TB) infection with high specificity and sensitivity. This in vitro diagnostic test uses 2 TB-specific proteins (ESAT-6 and CFP-10) to stimulate cells in heparinized whole blood and detects interferon-gamma (IFN-gamma) produced from blood cells. When QFT is done in laboratories outside of the hospital, several hours may be required to transport blood samples. We studied the relationship between QFT results and the time taken from collection of blood to incubation (preincubation time). METHODS: Heparinized whole blood drawn from TB suspects was immediately transported to a laboratory. We started to incubate 4 aliquots of blood with ESAT-6, CFP-10, mitogen (phytohemagglutinin), and nil control, at 1, 3, 6, 9, and 12 h after blood was drawn. After incubation, the concentration of IFN-gamma in each plasma sample was determined by ELISA, and values E and C were expressed as the concentration of IFN-gamma with ESAT-6 or CFP-10, minus the concentration of IFN-gamma in the nil control. Value E or C > or =0.35IU/mL was considered positive, > or =0.10 and<0.35IU/mL as equivocal (gray zone), and<0.10IU/mL as negative. We analyzed 8 patients with value E or C > or =0.10IU/mL at a preincubation time of 1 h. RESULTS: Value E and C decreased especially for preincubation time >6 h. As a result, the interpretation of value E changed from "positive" to "equivocal" in 2 cases and from "equivocal" to "negative" in 2 cases. Interpretation of value C also changed from "positive" to "equivocal" or "negative" in 2 cases and from "equivocal "to "negative" in 1 case. Even if the higher of value E or C were used for analysis, QFT results changed in half of patients when preincubation time was>6 h. CONCLUSION: Since QFT results in half of patients changed when preincubation time was>6 h, incubation of whole blood should start < or =6 h after blood drawing.

Phase II study of carboplatin and weekly paclitaxel combination chemotherapy in advanced non-small cell lung cancer: a Kansai Clinical Oncology Group study.

The objective of this phase II study was to evaluate the efficacy and toxicity of carboplatin and weekly paclitaxel combination chemotherapy in previously untreated, advanced non-small cell lung cancer (NSCLC). Patients received paclitaxel at a dose of 70 mg/m(2) on days 1, 8, 15, and carboplatin with the target dose of area under the curve (AUC) of 6 on day 1 every 28 days. Forty-six patients were enrolled. A median of four cycles (range, 1-13) were administered. Complete response was observed in one patient (2.2%) and partial response in 23 patients (50%), yielding an overall intent-to-treat response rate of 52.2% (95% confidence interval, 37.8-66.6%). The median survival time was 395 days and 1-year survival rate was 51.4%. Toxicities were mild. Twelve patients (26%) had grade 3 and three patients (7%) had grade 4 neutropenia. Grade 3 thrombocytopenia was seen in four patients (8%). Massive hematoemesis due to duodenal ulcer was observed in one patient, but no other patients experienced grade 3 or more non-hematological toxicities. There was no treatment-related death. Carboplatin and weekly paclitaxel combination chemotherapy is an efficacious and feasible regimen in patients with advanced NSCLC, and this treatment will be a reasonable alternative to the conventional triweekly regimen of paclitaxel and carboplatin.

Effect of a network system for providing proper inhalation technique by community pharmacists on clinical outcomes in COPD patients.

INTRODUCTION: Nonadherence to inhalation therapy is very common in patients with chronic obstructive pulmonary disease (COPD). Few data are available to support the role of community pharmacists in optimizing inhalation therapy in COPD patients. Since 2007, the Kitano Hospital and the Kita-ku Pharmaceutical Association have provided a network system for delivering correct inhalation techniques through certified community pharmacists. The effects of this network system on clinical outcomes in COPD patients were examined. METHODS: A total of 88 consecutive outpatients with COPD at baseline and 82 of those 4 years later were recruited from the respiratory clinic of Kitano Hospital Medical Research Institute. Measurements included the frequency of COPD exacerbations, patients' adherence to inhalation therapy using a five-point Likert scale questionnaire, and patients' health status both prior to this system and 4 years later. RESULTS: Usable information was obtained from 55 patients with COPD at baseline, and from 51 patients 4 years later. Compared with baseline values, a significant decrease was observed in the frequency of COPD exacerbations (1.5 ± 1.6 versus 0.8 ± 1.4 times/year, P = 0.017). Adherence to the inhalation regimen increased significantly (4.1 ± 0.7 versus 4.4 ± 0.8, P = 0.024), but health status was unchanged. At 4 years, of 51 COPD patients, 39 (76%) patients who visited the certified pharmacies showed significantly higher medication adherence than those who did not (4.6 ± 0.6 versus 3.9 ± 1.0, P = 0.022). CONCLUSION: The network system may improve COPD control and adherence to inhalation regimens.

A randomized, placebo-controlled trial of acupuncture in patients with chronic obstructive pulmonary disease (COPD): the COPD-acupuncture trial (CAT).

BACKGROUND: Dyspnea on exertion (DOE) is a major symptom of chronic obstructive pulmonary disease (COPD) and is difficult to control. This study was performed to determine whether acupuncture is superior to placebo needling in improving DOE in patients with COPD who are receiving standard medication. METHODS: Sixty-eight of 111 patients from the Kansai region of Japan who were diagnosed as having COPD and were receiving standard medication participated in a randomized, parallel-group, placebo-controlled trial (July 1, 2006, through March 31, 2009) in which the patients, evaluators, and statistician were unaware of the random allocation. Participants were randomly assigned to traditional acupuncture (real acupuncture group, n=34) or placebo needling (placebo acupuncture group, n=34). Both groups received real or placebo needling at the same acupoints once a week for 12 weeks. The primary end point was the modified Borg scale score evaluated immediately after the 6-minute walk test. Measurements were obtained at baseline and after 12 weeks of treatment. RESULT: After 12 weeks, the Borg scale score after the 6-minute walk test was significantly better in the real acupuncture group compared with the placebo acupuncture group (mean [SD] difference from baseline by analysis of covariance, -3.6 [1.9] vs 0.4 [1.2]; mean difference between groups by analysis of covariance, -3.58; 95% CI, -4.27 to -2.90). Patients with COPD who received real acupuncture also experienced improvement in the 6-minute walk distance during exercise, indicating better exercise tolerance and reduced DOE. CONCLUSION: This study clearly demonstrates that acupuncture is a useful adjunctive therapy in reducing DOE in patients with COPD. TRIAL REGISTRATION: umin.ac.jp/ctr Identifier: UMIN000001277.

Relationships between repeated instruction on inhalation therapy, medication adherence, and health status in chronic obstructive pulmonary disease.

PURPOSE: Adherence to inhalation therapy is a critical determinant of the success of chronic obstructive pulmonary disease (COPD) management. However, in practice, nonadherence to inhalation therapy is very common in COPD patients. The effects of adherence to inhalation therapy in COPD have not been fully studied, and less is known about the relationship between medication adherence and quality of life in COPD. Our aim is to assess the factors that contribute to adherence to inhalation therapy and examine their correlation with quality of life. PATIENTS AND METHODS: A cross-sectional analysis of 88 COPD patients was performed using a self-reported adherence questionnaire with responses on a 5-point Likert scale. RESULTS: Of the 88 patients who were potential participants, 55 (63%) responded with usable information. The only significant factor associated with the overall mean adherence score was receiving repeated instruction about inhalation techniques (P = 0.032). Of the 55 respondents, 22 (40.0%) were given repeated verbal instruction and/or demonstrations of inhalation technique by a respiratory physician. Significant correlations were found between the overall mean adherence score and the health-related quality of life score (St George's Respiratory Questionnaire: total, r = -0.35, P = 0.023; symptoms, r = -0.43, P = 0.002; impacts, r = -0.35, P = 0.011). Furthermore, patients with repeated instruction showed better quality of life scores than those who did not receive instruction (total, P = 0.030; symptoms, P = 0.038; impacts, P = 0.019). CONCLUSIONS: Repeated instruction for inhalation techniques may contribute to adherence to therapeutic regimens, which relates to better health status in COPD.

Molecular characteristics of serotype 3 Streptococcus pneumoniae isolates among community-acquired pneumonia patients in Japan.

In order to understand the spread of the erythromycin-resistant serotype 3 Streptococcus pneumoniae clone in Japan, we have assessed the molecular characteristics of this clone. Among 156 S. pneumoniae isolates recovered from adults with community-acquired pneumonia between 2003 and 2005, 42 were serotype 3 and 40 were sequence type (ST) 180/Netherlands(3)-31 by multilocus sequence typing. Thirty-eight of the 40 ST 180 isolates had acquired resistance to erythromycin via the ermB gene. Although the ermB-positive ST180 clone isolates were more susceptible to penicillin and trimethoprim-sulfamethoxazole than ermB-positive non-ST180 isolates and contained a less mutated pbp1a or pbp2b gene, without a mefA gene, the ST180 clone was highly prevalent among ermB-positive isolates. Routine surveillance for the ST180 S. pneumoniae clone may soon become necessary.

Genotypes and related factors reflecting macrolide resistance in pneumococcal pneumonia infections in Japan.

Although macrolide-resistant Streptococcus pneumoniae strains possessing either the ermB or mefA gene are very common in Japan, clinical and microbial factors in community-acquired pneumonia (CAP) caused by different macrolide resistance genotypes have not been evaluated. A multicenter study of CAP caused by S. pneumoniae was performed in Japan from 2003 to 2005. A total of 156 isolates were tested for susceptibility to antibiotics correlated with ermB and mefA genotyping. Independent relationships between tested variables and possession of either the ermB or the mefA gene were identified. Of 156 isolates, 127 (81.4%) were resistant to erythromycin, with the following distribution of resistance genotypes: ermB alone (50.0%), mefA alone (23.7%), and both ermB and mefA (7.1%). All isolates were susceptible to telithromycin. By multivariate analysis, oxygen saturation of <90% on admission increased the risk for ermB-positive pneumococcal pneumonia (odds ratio [OR]=11.1; 95% confidence interval [CI]=1.30 to 95.0; P=0.03), but there were no associations with mefA or with ermB mefA positivity. Penicillin nonsusceptibility was associated with mefA-positive and with ermB- and mefA-positive isolates (OR=14.2; 95% CI=4.27 to 46.9; P<0.0001 and P<0.0001, respectively) but not with ermB-positive isolates. The overall patient mortality was 5.1%. Mortality, the duration of hospitalization, and the resolution of several clinical markers were not associated with the different erythromycin resistance genotypes. In Japan, S. pneumoniae with erythromycin resistance or possession of ermB, mefA, or both genes was highly prevalent in patients with CAP. The risk factors for ermB-positive, mefA-positive, and double ermB-mefA-positive pneumococcal pneumonia were different, but the clinical outcomes did not differ.