Comparison of TachoSil and TachoComb in patients undergoing liver resection-a randomized, double-blind, non-inferiority trial.

BACKGROUND: This study aimed to demonstrate the noninferior efficacy of TachoSil vs. TachoComb in Japanese patients undergoing liver resection and to assess the safety of TachoSil vs. TachoComb in these patients. METHODS: This randomized, double-blind, noninferiority study (JapicCTI-090684) involved participants scheduled for liver resection/living donors (age ≥ 20 years). TachoSil or TachoComb (1:1 allocation ratio) was applied to control persistent exudative bleeding after primary hemostasis during liver resection/removal for donation. The primary outcome was hemostasis 5 min after study treatment application. The 95% confidence interval (CI) for the difference in the proportion of participants with hemostasis 5 min after application of TachoSil/TachoComb was determined; noninferiority of TachoSil was indicated if the lower limit of the CI was ≥-14%. Adverse events (AEs) were recorded. RESULTS: All participants in the efficacy analysis (TachoSil: 54/54, 100%; TachoComb: 54/54, 100%) achieved hemostasis 5 min after study treatment application. Therefore, TachoSil was noninferior to TachoComb. All participants experienced ≥1 AE; however, none discontinued because of an AE. Most (≥97.8%) AEs were mild or moderate in severity. CONCLUSIONS: These findings confirm the safety profile and noninferior hemostatic efficacy of TachoSil compared with TachoComb.

Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials.

There remain liver-related safety concerns, regarding potential hepatotoxicity in humans, induced by green tea intake, despite being supposedly beneficial. Although many randomized controlled trials (RCTs) of green tea extracts have been reported in the literature, the systematic reviews published to date were only based on subjective assessment of case reports. To more objectively examine the liver-related safety of green tea intake, we conducted a systematic review of published RCTs. A systematic literature search was conducted using three databases (PubMed, EMBASE and Cochrane Central Register of Controlled Trials) in December 2013 to identify RCTs of green tea extracts. Data on liver-related adverse events, including laboratory test abnormalities, were abstracted from the identified articles. Methodological quality of RCTs was assessed. After excluding duplicates, 561 titles and abstracts and 119 full-text articles were screened, and finally 34 trials were identified. Of these, liver-related adverse events were reported in four trials; these adverse events involved seven subjects (eight events) in the green tea intervention group and one subject (one event) in the control group. The summary odds ratio, estimated using a meta-analysis method for sparse event data, for intervention compared with placebo was 2.1 (95% confidence interval: 0.5-9.8). The few events reported in both groups were elevations of liver enzymes. Most were mild, and no serious liver-related adverse events were reported. Results of this review, although not conclusive, suggest that liver-related adverse events after intake of green tea extracts are expected to be rare.

A randomized double blind placebo-controlled clinical trial of Hochuekkito, a traditional herbal medicine, in the treatment of elderly patients with weakness N of one and responder restricted design.

OBJECTIVE: To evaluate the effects of Hochuekkito, a traditional Japanese and Chinese medicine, in the treatment of elderly patients with general weakness. To devise a suitable study design for assessing the clinical effectiveness of traditional herbal medicines. METHODS: Fifteen elderly patients (mean +/- SD: age 78.4 +/- 7.8; m/f 3/12) participated in this study. A multicenter, prospective, randomized, double-blind, placebo-controlled study with N of one and responder restricted design was performed. After the run-in period, the patients were divided into responders and non-responders. Only responders were entered in the study, and were randomized into three groups: an active-placebo group, a placebo-active group and an active-active group. The study consisted of two 6-week terms with a 2-week washout period in between. We assessed the Short Form 36 Health Survey (SF-36) and Profile of Mood States (POMS) as an endpoint of quality of life (QOL). In addition, we assessed the biodefense status by measuring the natural killer cytolytic activity (NK activity), IL-2 producing activity of peripheral lymphocytes, lymphocyte proliferating activity and lymphocyte cell-surface antigens. RESULTS: The physical component summary of the SF-36 analysis significantly improved in the Hochuekkito-treated group. Four components (A-H: anger-hostility, F: fatigue, T-A: tension-anxiety, C: confusion) out of six improved in the Hochuekkito-treated group in the POMS analysis. Lymphocyte proliferating activity improved in the Hochuekkito-treated group but not significantly. Concerning the surface antigens of peripheral lymphocytes, the population of CD3 positive cells and CD3CD4 double positive cells increased in the Hochuekkito-treated group. CONCLUSION: We revealed that Hochuekkito improved the QOL and immunological status of elderly patients with weakness by randomized controlled trial. Our study design might be useful for assessing the efficacy of traditional herbal medicine in the future.

Association of pontine small infarction (lacuna) with disturbance of postural stability.

Neuronal degeneration within the brainstem has been reported in patients with impaired postural stability. However, the functional significance of these abnormalities is unknown at present. In the present study, we evaluated the relationship between the presence of pontine lacunae and postural stability measured by stabilometry. A total of 209 consecutive patients without neurological signs were divided into three groups according to the territory of lacunae on magnetic resonance imaging: (1) non-lacunar group, (2) pontine lacunar group, and (3) non-pontine lacunar group. Stabilometry was performed and statokinesigram measures including each Romberg quotient were compared among the three groups. Using multivariate analysis, postural stability was found to be disturbed in the pontine lacunar group compared with the other groups. The data of stabilometry in this group were compatible with disturbance of the central controlling system for keeping postural stability. Pontine lacuna is associated with patients with postural instability. This result may be related to the deterioration of the central coordination system for posture and locomotion.

Gemcitabine and vinorelbine followed by docetaxel in patients with advanced non-small-cell lung cancer: a multi-institutional phase II trial of nonplatinum sequential triplet combination chemotherapy (JMTO LC00-02).

To evaluate the efficacy and toxicity of the sequential nonplatinum combination chemotherapy consisting of gemcitabine (GEM) and vinorelbine (VNR) followed by docetaxel (DOC) in patients with advanced non-small-cell lung cancer (NSCLC), we conducted the multiinstitutional phase II study. A total of 44 chemotherapy-naive patients with advanced NSCLC were treated with GEM 1000 mg m(-2) and VNR 25 mg m(-2) intravenously on days 1 and 8 every 3 weeks for three cycles. DOC 60 mg m(-2) was then administrated intravenously at 3-week intervals for three cycles. Patients were evaluated for response and toxicity with each cycle of the treatment. The major objective response rate was 47.7% (95% confidence interval (CI), 33.8-62.1%). Median survival time (MST) was 15.7 months and 1-year survival rate was 59%. In the GEM/VNR cycle, grade 3/4 neutropenia occurred in 36.3%, grade 3/4 anaemia in two patients (4.5%) and grade 3 thrombocytopenia in one patient (2.3%). Grade 3 pneumonitis occurred in two patients (4.5%) in GEM/VNR cycles. In the DOC cycles, grade 3/4 neutropenia occurred in 39.4% but no patient experienced grade 3/4 anaemia or thrombocytopenia. Of the 44 eligible patients, 33 patients completed three cycles of GEM/VNR and 22 patients completed six cycles of planned chemotherapy (three cycles of GEM/VNR followed by three cycles of DOC). The sequential triplet nonplatinum chemotherapy consisted of GEM/VNR followed by DOC, and was very active and well tolerated. This study forms the basis for an ongoing phase III trial that compares this nonplatinum triplet and standard platinum doublet combination (carboplatin/paclitaxel).

Right sylvian fissure subarachnoid hemorrhage has electrocardiographic consequences.

BACKGROUND AND PURPOSE: Abnormal ECG changes are frequently observed in patients with subarachnoid hemorrhage (SAH). Recently, evidence has been obtained that right insular cortex mediates sympathetic cardiovascular effects. We therefore assessed the laterality and location of SAH dominance in inducing cardiovascular changes as measured by ECG, blood pressure, and heart rate. METHODS: After exclusion of 11 SAH patients who died within 1 month after onset, we studied 118 consecutive patients. Data were obtained from records of blood pressure and pulse on admission. Abnormal ECG changes were determined from ECGs on admission and almost 1 month later. From brain CT scans performed immediately after admission, the amount of SAH in each of the 8 cisterns and fissures was measured semiquantitatively. RESULTS: Twenty-six patients had abnormal changes on admission ECG, while 92 patients did not. Systolic blood pressure, diastolic blood pressure, and the amounts of blood in the left ambient cistern, left suprasellar cistern, quadrigeminal cistern, right ambient cistern, right suprasellar cistern, right sylvian fissure, and the set of all cisterns were significantly greater in the group with ECG change than in the group without ECG change. Multivariate logistic regression analysis with stepwise method indicated that systolic blood pressure >160 mm Hg (P=0.0006) and the amounts of SAH in the quadrigeminal cistern (P=0.022) and right sylvian fissure (P=0.0019) were independently associated with abnormal ECG change. CONCLUSIONS: Cardiac consequences are possible in patients with massive right sylvian fissure SAH or when systolic blood pressure is >160 mm Hg.

Early small cell lung cancer with extensive inflammation and scar formation.

A 56-year-old man, at one year before his first visit to our hospital, had presented cough, stridor and chest pain, and expectorated a mass, resulting in prompt disappearance of the symptoms. He was afflicted with recurrent symptoms, and the bronchoscopy showed a polypoid tumor occluding the right lower bronchus. The tumor was resected via bronchoscopy, which revealed histologically small cell carcinoma with significant inflammation and scar formation. The tumor was macroscopically the same as the one that had been expectorated by the patient at one year previously. A right lower lobectomy was conducted, but the specimen demonstrated no residual tumor. Tumor invasion into the bronchial wall was therefore limited within the submucosal layer for more than a year. Finally, the present tumor was diagnosed as an early small cell lung cancer with a characteristic of self involution. With no adjuvant treatment, the patient is well without tumor recurrence at 3 years to date after the surgery.

Prognostic significance of magnetic resonance imaging of femoral marrow in patients with myelodysplastic syndromes.

PURPOSE: To investigate whether the abnormalities observed on femoral marrow magnetic resonance images are related to the development of leukemia and survival of patients with myelodysplastic syndromes (MDS). PATIENTS AND METHODS: The findings on magnetic resonance images of the femoral marrow were evaluated over periods of 1 to 92 months (median, 18 months) in 42 consecutive adult patients with newly diagnosed MDS. Magnetic resonance images were obtained by the T1-weighted spin echo method and the short T1 inversion recovery technique. RESULTS: Magnetic resonance images showed that the femoral marrow patterns changed from fatty, faint, or nodular to scattered or uniform as the disease progressed. Development of acute myeloid leukemia was observed in only 13 patients whose marrow exhibited a scattered or uniform pattern. The overall survival of the 29 patients with a scattered or uniform marrow pattern was significantly shorter than that of the 13 patients with a fatty, faint, or nodular marrow pattern (10.7% v 73.3% at 7 years; P < .01). The period of leukemia-free survival was also significantly shorter in the patients with a scattered or uniform marrow pattern versus a fatty, faint, or nodular pattern (37.7% v 100% at 7 years; P < .01). CONCLUSION: Magnetic resonance images of the femoral marrow can provide valuable information for assessing the prognosis and determining the most appropriate management of patients with MDS.

An application of meta-analysis techniques in the evaluation of adverse experiences with antihypertensive agents.

PURPOSE: To investigate the profiles of adverse events (AEs) in randomized controlled trials of antihypertensive agents therapy with the technique of meta-analysis. METHODS: A total of 620 articles were selected from MEDLINE, EMBASE, JAPIC-DOC, JMEDICINE and manual searching. Two independent reviewers examined the 620 selected articles according to the following criteria: (1) the methods of randomization, (2) making for allocating treatments, (3) therapeutic class of drugs, (4) sample sizes, (5) duration of the treatment, (6) primary endpoint, (7) reporting method for all adverse events, (8) method of monitoring AEs, and (9) incidence rates of all reported AEs. To combine the risk difference and risk ratios of incidence between CCBs and beta blockers or diuretics, the method of DerSimonian and Laird based on random effect model was applied. RESULTS: A total of 3073 patients were included in this meta-analysis of serious adverse events (SAEs). There was no significant difference in the total incidence of SAEs between CCBs and diuretics or between CCBs and beta blockers. We found that patients treated with CCBS had 0.14% fewer SAEs compared with the patients treated with diuretics. Contrarily, the patients treated with CCBs had 0.29% more SAEs compared with the patients treated with beta blockers. There was a significant difference between the patients treated with CCBs and those treated with diuretics in the symptoms with headache and oedema. With respect to the comparison between CCBs and beta blockers, flushing occurred 8.75% more frequently in the CCBs group than in the beta blockers group. CONCLUSION: A meta-analysis can be applied to safety analyses of data obtained in clinical trials if all of the RCT articles used include a complete description of adverse experiences.

[Meta-analysis of clinical trials for chemotherapy in cancer].

Meta-analysis has attracted great interest among clinical practitioners in recent years, leading to a steady output of related publications. Meta-analytic articles are easily found in the MEDLINE database using the publication-type option. This paper reviews how to use and understand meta-analysis with a special reference to chemotherapy applied to cancer patients. It is described in relationship to evidence-based medicine (EBM) and clinical practice guidelines. Cochrane collaboration is also referred to as an active voluntary organization conducting meta-analysis. In the technical sections, statistical issues and graphic representations are clearly illustrated using the example of hepatic arterial infusion for colorectal cancer patients. The difference between fixed and random effects models is briefly explained. Finally, an example from Cochrane Library, namely progestagen therapy for endometrial cancer, is illustrated to show the implications of meta-analysis for clinical practice.

Predictive validity of the Braunwald classification of unstable angina for angiographic findings, short-term prognoses, and treatment selection.

The authors tested the Braunwald classification for its predictive validity for underlying coronary conditions, clinical courses, and responses to treatment. A reliable definition and classification of unstable angina is needed to help physicians make correct diagnoses of patients' conditions and to appraise findings from clinical trials critically. Many clinical trials have been conducted, but it is difficult to compare the results because of different entry criteria. Of 113 consecutive patients admitted with unstable angina, 89 who had primary angina were studied. Braunwald's classification was applied at admission. The outcomes of interest during hospitalization were coronary angiographic findings, short-term prognoses, and the treatment selected. Multivariate analysis showed that the severity class expressed significant positive predictivity for coronary thrombi (adjusted odds ratio [OR], 6.53; 95% confidence interval [CI], 2.82 to 15.1) and progress to impending infarction (OR, 10.43; CI, 3.35 to 32.49). The treatment (OR, 0.02; CI, 0.004 to 0.08) and electrocardiographic (OR, 0.22; CI 0.10 to 0.49) classes showed independent negative predictivity for coronary vasospasm. The treatment (OR, 3.50; CI, 1.94 to 6.33) and electrocardiographic (odds ratio, 3.27; CI, 1.87 to 5.71) classes showed positive predictivity for the necessity for recanalization treatment with coronary angioplasty or bypass grafting. The Braunwald classification used at admission is highly predictive of underlying coronary conditions, progression to impending infarction, and the final selection of treatment. This classification should be considered in determining patient eligibility in clinical trials and studies.

Accumulating scientific evidence in cardiology with special reference to the Japanese contribution.

Clinical practice guidelines have been released as a current summary of the most recent scientific evidence in various areas. The paradigm by which evidence is regarded important is called evidence-based medicine (EBM). Sources of EBM are valid randomized controlled trials (RCT) and meta-analyses (MA). Only well-qualified studies should be used for the EBM. The characteristics for both RCTs and MAs are considered. controversial issues are also discussed, such as the safety of calcium channel blockers and the efficacy of magnesium for acute myocardial infarction. Finally, Japanese RCTs, either finished or ongoing, are summarized. International collaboration will become more important for registering and evaluating evidence followed by summarizing and updating the evidence.

[Relationship between insulin resistance and blood pressure].

A study designed to analyze the relationship between blood pressure and insulin resistance was conducted on 353 subjects who received medical health examinations, and who did not have obvious diabetes. Fasting plasma insulin (IRI), fasting plasma glucose (FPG), body mass index (BMI), waist hip ratio (WHR), body fat percentage, total cholesterol (TC), triglyceride, and urine sodium concentrations were measured or calculated. After analysis of the correlation's between each value, multiple regression analyses were performed. The results were as follows: 1) hypertensive subjects were significantly higher than non-hypertensives in with age, value of IRI, FPG, WHR, TC and BMI. 2) The values of IRI, WHR, and BMI were correlated each other. 3) After adjusted for age and sex by multiple regression analyses, IRI, WHR, and BMI were shown to have significant relationship to mean blood pressure. From this study, it is concluded that IRI is an indicator for insulin resistance and is related to blood pressure.

Effect of social factors on metabolic improvement in type II diabetic patients.

Psychological and social factors can profoundly influence a patient's success in adhering to a prescribed self-care regimen. A total of 34 inpatients with type II diabetes who attended the diabetes education program at a single clinic were studied as a retrospective cohort, beginning between 6 and 12 months after discharge. At the start of the study, the patients were classified into two groups, those with good control and those with poor control of diabetes, based on the rate of change of the glycosylated hemoglobin (HbAlc) value relative to the value at admission. Data for each patient were collected retrospectively from their medical records. Patients' family function was assessed by the adaptability, partnership, growth, affection, and resolve (APGAR) scoring system. Multiple regression analysis was used to determine the effect of demographic, medical, and social factors on metabolic improvement. The family APGAR score was higher in the good control group than in the group with poor control.

Characteristics of maternal employment during pregnancy: effects on low birthweight.

BACKGROUND: Although maternal employment is considered a risk factor for low birthweight (LBW), the manner in which employment might affect birthweight is poorly understood. In this analysis, selected characteristics of employment during pregnancy were examined for effects on pregnancy outcomes. METHODS: Work characteristics included the number of hours per week, physical activities, and environmental conditions. The outcomes of interest were fetal growth retardation (less than 2500 grams at term) and preterm delivery (less than 37 weeks). The study population consisted of 2711 non-Black, married mothers who participated in the 1980 National Natality Survey (NNS). The NNS data were merged with data from the 1977 revision of The Dictionary of Occupational Titles (DOT) from which measures of occupational physical activities and environmental exposures were obtained. Logistic regression was used in the analysis. RESULTS: Those who worked 40 or more hours per week were more likely than women who worked fewer hours to have a low birthweight delivery at greater than or equal to 37 weeks. No physical or environmental characterics of work were associated with low birthweight or preterm delivery. CONCLUSIONS: Non-Black married American women may face a risk of delivering low-birthweight babies at or near term only if they work 40 or more hours each week. However, the lack of risk associated with other characteristics of work may be a function of measurement error in the DOT data source or of low levels of exposure in the analysis population.

A comparative study of two statistical models for the analysis of binary data from longitudinal studies.

This study extensively compares two statistical models for the analysis of binary data from longitudinal studies. The first model was proposed by Zeger, Liang, and Self, which was abbreviated as ZLS model and another model was proposed by Origasa. The comparison focuses on both analytical and statistical view-points. The first discusses a type of the models and the second evaluates the effect from model misspecification by stimulation, assuming that the ZLS model is true.

[Subrenal capsule assay as a chemosensitivity test (III)--Comparison of host reaction, experimental chemotherapy and use of nude mice].

We studied fundamentally subrenal capsule assay, using human tumor specimens (gastric, breast and pancreas cancers) serially transplanted in nude mice. Any prominent difference of host reaction was not found between the host of BALB/c-nu/+, BALB/c-+/+ and CDF1 mice. Using immunocompetent BALB/c-nu/+ mice, experimental chemotherapy with mitomycin C (MMC) and 5-fluorouracil (5-FU) was carried out. On day 6, macroscopic and histological findings corresponded relatively well with 5-FU effect but not with MMC. Using BALB/c-nu/nu mice, we tried 15-day SRC assay. When the sensitivity of anti-cancer drugs was compared between early and intermediate phase after inoculation, no obvious difference was found macroscopically and histologically. BALB/c-nu/nu mouse will be useful as a host of SRC assay, and could be applicable to clinical fresh cases.