A single-arm pilot study of guided self-help treatment based cognitive behavioral therapy for bulimia nervosa in Japanese clinical settings.

PubMed

Setsu, R; Asano, K; Numata, N; Tanaka, M; Ibuki, H; Yamamoto, T; Uragami, R; Matsumoto, J; Hirano, Y; Iyo, M; Shimizu, E; Nakazato, M

2018-04-25

Guided self-help treatments based on cognitive behavioral therapy (CBT-GSH) are regarded as a first-line effective treatment for bulimia nervosa (BN). With limited application for CBT-GSH in Japanese clinical settings, we conducted a single arm pilot study in order to confirm the acceptability and availability of CBT-GSH in Japan. 25 women with BN received 16-20 sessions of face-to-face CBT-GSH. Primary outcomes were the completion rate of intervention and abstinence rates from objective bingeing and purging as assessed by the Eating Disorder Examination. Secondary outcomes were other self-report measurements of the frequency of bingeing and purging, and characteristic psychopathologies of eating disorders. Assessments were conducted before CBT as baseline as well as after CBT. 92% (23/25) of the participants completed the CBT sessions. After CBT-GSH, 40% (10/25) of the participants (intention-to-treat) achieved symptom abstinence. The mean binge and purge episodes during the previous 28 days improved from 21.88 to 10.96 (50% reduction) and from 22.44 to 10.88 (52% reduction), each (before CBT-GSH to after CBT-GSH), and the within-group effect sizes were medium (Cohen's d = 0.67, 0.65, each). Our study provided a preliminary evidence about the feasibility of CBT-GSH in Japanese clinical settings for the future. Trial registration This study was registered retrospectively in the national UMIN Clinical Trials Registry on July 10, 2013 (registration ID: UMIN000011120).

Run-up to participation in ATACH II in Japan

PubMed Central

Toyoda, K; Sato, S; Koga, M; Yamamoto, H; Nakagawara, J; Furui, E; Shiokawa, Y; Hasegawa, Y; Okuda, S; Sakai, N; Kimura, K; Okada, Y; Yoshimura, S; Hoshino, H; Uesaka, Y; Nakashima, T; Itoh, Y; Ueda, T; Nishi, T; Gotoh, J; Nagatsuka, K; Arihiro, S; Yamaguchi, T; Minematsu, K

2012-01-01

Intracerebral hemorrhage (ICH) is a major cause of morbidity and mortality in Japan. Seventeen Japanese institutions are participating in the Antihypertensive Treatment for Acute Cerebral Hemorrhage (ATACH) II Trial (ClinicalTrials.gov no. NCT01176565; UMIN 000006526). This phase III trial is designed to determine the therapeutic benefit of early intensive systolic blood pressure (BP) lowering for acute hypertension in ICH patients. This report explains the long run-up to reach the start of patient registration in ATACH II in Japan, including our preliminary study, a nationwide survey on antihypertensive treatment for acute ICH patients, a multicenter study for hyperacute BP lowering (the SAMURAI-ICH study), revision of the official Japanese label for intravenous nicardipine, and construction of the infrastructure for the trial. PMID:23230457

Coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone improves postprandial endothelial dysfunction in patients with borderline and stage 1 hypertension.

PubMed

Kajikawa, Masato; Maruhashi, Tatsuya; Hidaka, Takayuki; Nakano, Yukiko; Kurisu, Satoshi; Matsumoto, Takeshi; Iwamoto, Yumiko; Kishimoto, Shinji; Matsui, Shogo; Aibara, Yoshiki; Yusoff, Farina Mohamad; Kihara, Yasuki; Chayama, Kazuaki; Goto, Chikara; Noma, Kensuke; Nakashima, Ayumu; Watanabe, Takuya; Tone, Hiroshi; Hibi, Masanobu; Osaki, Noriko; Katsuragi, Yoshihisa; Higashi, Yukihito

2018-01-12

The purpose of this study was to evaluate acute effects of coffee with a high content of chlorogenic acids and different hydroxyhydroquinone contents on postprandial endothelial dysfunction. This was a single-blind, randomized, placebo-controlled, crossover-within-subject clinical trial. A total of 37 patients with borderline or stage 1 hypertension were randomized to two study groups. The participants consumed a test meal with a single intake of the test coffee. Subjects in the Study 1 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or coffee with a high content of chlorogenic acids and a high content of hydroxyhydroquinone with crossover. Subjects in the Study 2 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or placebo coffee with crossover. Endothelial function assessed by flow-mediated vasodilation and plasma concentration of 8-isoprostanes were measured at baseline and at 1 and 2 h after coffee intake. Compared with baseline values, single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone, but not coffee with a high content of chlorogenic acids and high content of hydroxyhydroquinone or placebo coffee, significantly improved postprandial flow-mediated vasodilation and decreased circulating 8-isoprostane levels. These findings suggest that a single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone is effective for improving postprandial endothelial dysfunction. URL for Clinical Trial: https://upload.umin.ac.jp ; Registration Number for Clinical Trial: UMIN000013283.

An exploratory study on the efficacy and safety of a BCAA preparation used in combination with cardiac rehabilitation for patients with chronic heart failure.

PubMed

Takata, Munenori; Amiya, Eisuke; Watanabe, Masafumi; Hosoya, Yumiko; Nakayama, Atsuko; Fujiwara, Takayuki; Taya, Masanobu; Oguri, Gaku; Hyodo, Kanako; Takayama, Naoko; Takano, Nami; Mashiko, Tomoe; Uemura, Yukari; Komuro, Issei

2017-07-27

Sarcopenia is generally complicated with patients with chronic heart failure (CHF) and its presence negatively affects the course of heart failure, however effective nutritional intervention had not been elucidated yet. The primary objective of this study is to explore whether the addition of a branched-chain amino acid (BCAA) preparation for cardiac rehabilitation (CR) of patients with CHF further improves cardiopulmonary functions, skeletal muscle functions, and metabolism in comparison with conventional CR. This is a randomized, parallel-group comparative study. The elderly patients that were participated in CR and complicated with left ventricular systolic or diastolic dysfunction are randomized into two groups, CR + BCAA and CR. 20 weeks later, the second randomization is performed, which divide subjects into two groups with and without BCAA intervention without CR. Primary outcome measure is the rate of change of the anaerobic threshold workload from baseline to post-intervention. Secondary outcome include parameters of exercise capacity, cardiac function and psychological status. In the current study the effect of a promising new intervention, BCAA, will be assessed to determine whether its addition to CR improve exercise capacity in patients with heart failure, who are generally complicated with sarcopenia. This clinical trial was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR; JPRN-UMIN R000022440 ).

The Effects of Physical Exercise with Music on Cognitive Function of Elderly People: Mihama-Kiho Project

PubMed Central

Satoh, Masayuki; Ogawa, Jun-ichi; Tokita, Tomoko; Nakaguchi, Noriko; Nakao, Koji; Kida, Hirotaka; Tomimoto, Hidekazu

2014-01-01

Background Physical exercise has positive effects on cognitive function in elderly people. It is unknown, however, if combinations of non-pharmaceutical interventions can produce more benefits than single ones. This study aimed to identify if physical exercise combined with music improves cognitive function in normal elderly people more than exercise alone. Methods We enrolled 119 subjects (age 65–84 years old). Forty subjects performed physical exercise (once a week for an hour with professional trainers) with musical accompaniment (ExM group), developed by YAMAHA Music Foundation; 40 subjects performed the same exercise without music (Ex group); 39 subjects were the control group (Cont group). Before and after the year-long intervention, each patient was assessed by neuropsychological batteries. MRIs were performed before and after intervention; the Voxel-based Specific Regional analysis system for Alzheimer's Disease (VSRAD) was used to assess medial temporal lobe atrophy. Results Analysis of variance (ANOVA) was significant only in visuospatial function. The multiple comparison (ExM vs. Ex, ExM vs. Cont, Ex vs. Cont) was significant between the ExM and Cont group. Intra-group analyses before and after intervention revealed significant improvement in visuospatial function in the ExM group, and significant improvements in other batteries in all three groups. The VSRAD score significantly worsened in the ExM and Ex groups. Conclusions Physical exercise combined with music produced more positive effects on cognitive function in elderly people than exercise alone. We attributed this improvement to the multifaceted nature of combining physical exercise with music, which can act simultaneously as both cognitive and physical training. Trial Registration UMIN Clinical Trials Registry (UMIN-CTR) UMIN000012148 PMID:24769624

A Randomized Controlled Trial for the Effectiveness of Aromatherapy in Decreasing Salivary Gland Damage following Radioactive Iodine Therapy for Differentiated Thyroid Cancer.

PubMed

Nakayama, Michihiro; Okizaki, Atsutaka; Takahashi, Koji

2016-01-01

Objective. The aim of this study was to investigate effects of aromatherapy in decreasing salivary gland damage for patients undergoing radioactive iodine (RAI) therapy with differentiated thyroid cancer (DTC). Materials and Methods. The subjects were 71 patients with DTC. They were divided into aromatherapy group (group A, n = 35) and a control group (group B, n = 36). We blended 1.0 mL of lemon and 0.5 mL of ginger essential oils. The patients in the inhalation aromatherapy group inhaled this blend oil and those in the control group inhaled distilled water as placebo for 10 min during admission. We statistically compared salivary gland function before and after treatment between groups A and B. Results. In comparison with group B, the rate of change of the accumulation rate was significantly higher in the parotid glands and submandibular glands of group A ( P < 0.05). In comparison with group B, a significant increase in rate of secretion change before and after treatment was noted in the bilateral parotid glands in group A ( P < 0.05). Conclusion. Because an amelioration of salivary gland function was observed in the present study, our results suggest the efficacy of aromatherapy in the prevention of treatment-related salivary gland disorder. This trial is registered with UMIN Clinical Trial Registry: UMIN000013968.

A Randomized Controlled Trial for the Effectiveness of Aromatherapy in Decreasing Salivary Gland Damage following Radioactive Iodine Therapy for Differentiated Thyroid Cancer

PubMed Central

Okizaki, Atsutaka; Takahashi, Koji

2016-01-01

Objective. The aim of this study was to investigate effects of aromatherapy in decreasing salivary gland damage for patients undergoing radioactive iodine (RAI) therapy with differentiated thyroid cancer (DTC). Materials and Methods. The subjects were 71 patients with DTC. They were divided into aromatherapy group (group A, n = 35) and a control group (group B, n = 36). We blended 1.0 mL of lemon and 0.5 mL of ginger essential oils. The patients in the inhalation aromatherapy group inhaled this blend oil and those in the control group inhaled distilled water as placebo for 10 min during admission. We statistically compared salivary gland function before and after treatment between groups A and B. Results. In comparison with group B, the rate of change of the accumulation rate was significantly higher in the parotid glands and submandibular glands of group A (P < 0.05). In comparison with group B, a significant increase in rate of secretion change before and after treatment was noted in the bilateral parotid glands in group A (P < 0.05). Conclusion. Because an amelioration of salivary gland function was observed in the present study, our results suggest the efficacy of aromatherapy in the prevention of treatment-related salivary gland disorder. This trial is registered with UMIN Clinical Trial Registry: UMIN000013968. PMID:28042578

Assessment of Safety and Effectiveness of the Extracorporeal Continuous-Flow Ventricular Assist Device (BR16010) Use as a Bridge-to-Decision Therapy for Severe Heart Failure or Refractory Cardiogenic Shock: Study Protocol for Single-Arm Non-randomized, Uncontrolled, and Investigator-Initiated Clinical Trial.

PubMed

Fukushima, Norihide; Tatsumi, Eisuke; Seguchi, Osamu; Takewa, Yoshiaki; Hamasaki, Toshimitsu; Onda, Kaori; Yamamoto, Haruko; Hayashi, Teruyuki; Fujita, Tomoyuki; Kobayashi, Junjiro

2018-06-08

The management of heart failure patients presenting in a moribund state remains challenging, despite significant advances in the field of ventricular assist systems. Bridge to decision involves using temporary devices to stabilize the hemodynamic state of such patients while further assessment is performed and a decision can be made regarding patient management. The purpose of this study (NCVC-BTD_01, National Cerebral and Cardiovascular Center-Bridge to Dicision_01) is to assess the safety and effectiveness of the newly developed extracorporeal continuous-flow ventricular assist system employing a disposable centrifugal pump with a hydrodynamically levitated bearing (BR16010) use as a bridge-to-decision therapy for patients with severe heart failure or refractory cardiogenic shock. NCVC-BTD_01 is a single-center, single-arm, open-label, exploratory, medical device, investigator-initiated clinical study. It is conducted at the National Cerebral and Cardiovascular Center in Japan. A total of nine patients will be enrolled in the study. The study was planned using Simon's minimax two-stage phase design. The primary endpoint is a composite of survival free of device-related serious adverse events and complications during device support. For left ventricular assistance, withdrawal of a trial device due to cardiac function recovery or exchange to other ventricular assist devices (VADs) for the purpose of bridge to transplantation (BTT) during 30 days after implantation will be considered study successes. For right ventricular assistance, withdrawal of tal device due to right ventricular function recovery within 30 days after implantation will be considered a study success. Secondary objectives include changes in brain natriuretic peptide levels (7 days after implantation of a trial device and the day of withdrawal of a trial device), period of mechanical ventricular support, changes in left ventricular ejection fraction (7 days after implantation of a trial device and the day of withdrawal of a trial device), and changes in left ventricular diastolic dimension (7 days after implantation of a trial device and the day of withdrawal of a trial device). We will disseminate the findings through regional, national, and international conferences and through peer-reviewed journals. UMIN Clinical Trials Registry (UMIN-CTR; R000033243) registered on 8 September 2017.

New assessment of endothelial function measured by short time flow-mediated vasodilation: Comparison with conventional flow-mediated vasodilation measurement.

PubMed

Matsui, Shogo; Kajikawa, Masato; Maruhashi, Tatsuya; Hashimoto, Haruki; Kihara, Yasuki; Chayama, Kazuaki; Goto, Chikara; Aibara, Yoshiki; Yusoff, Farina Mohamad; Kishimoto, Shinji; Nakashima, Ayumu; Noma, Kensuke; Kawaguchi, Tomohiro; Matsumoto, Takeo; Higashi, Yukihito

2018-05-04

Measurement of flow-mediated vasodilation (FMD) is an established method for assessing endothelial function. Measurement of FMD is useful for showing the relationship between atherosclerosis and endothelial function, mechanisms of endothelial dysfunction, and clinical implications including effects of interventions and cardiovascular events. To shorten and simplify the measurement of FMD, we have developed a novel technique named short time FMD (stFMD). We investigated the validity of stFMD for assessment of endothelial function compared with conventional FMD. We evaluated stFMD and conventional FMD in 82 subjects including patients with atherosclerotic risk factors and cardiovascular disease (66 men and 16 women, 57 ± 16 years). Both stFMD and conventional FMD were significantly correlated with age, systolic blood pressure, diastolic blood pressure and baseline brachial artery diameter. In addition, stFMD was significantly correlated with conventional FMD (r = 0.76, P < 0.001). Bland-Altman plot analysis showed good agreement between stFMD and conventional FMD. Moreover, stFMD in the at risk group and that in the cardiovascular disease group were significantly lower than that in the no risk group (4.6 ± 2.3% and 4.4 ± 2.2% vs. 7.3 ± 1.9%, P < 0.001, respectively). Optimal cutoff value of stFMD for diagnosing atherosclerosis was 7.0% (sensitivity of 71.0% and specificity of 85.0%). These findings suggest that measurement of stFMD, a novel and simple method, is useful for assessing endothelial function. Measurement of stFMD may be suitable for screening of atherosclerosis when repeated measurements of vascular function are required and when performing a clinical trial using a large population. URL for Clinical Trial: http://UMIN; Registration Number for Clinical Trial: UMIN000025458. Copyright © 2017 Elsevier B.V. All rights reserved.

Traditional Japanese Medicine Daikenchuto Improves Functional Constipation in Poststroke Patients

PubMed Central

Numata, Takehiro; Takayama, Shin; Tobita, Muneshige; Ishida, Shuichi; Katayose, Dai; Shinkawa, Mitsutoshi; Oikawa, Takashi; Aonuma, Takanori; Kaneko, Soichiro; Tanaka, Junichi; Kanemura, Seiki; Iwasaki, Koh; Ishii, Tadashi; Yaegashi, Nobuo

2014-01-01

Poststroke patients with functional constipation, assessed by the Rome III criteria, from 6 hospitals were recruited in a study on the effects of the traditional Japanese medicine Daikenchuto (DKT) on constipation. Thirty-four patients (17 men and 17 women; mean age: 78.1 ± 11.6 years) were randomly assigned to 2 groups; all patients received conventional therapy for constipation, and patients in the DKT group received 15 g/day of DKT for 4 weeks. Constipation scoring system (CSS) points and the gas volume score (GVS) (the measure of the intestinal gas volume calculated from plain abdominal radiographs) were recorded before and after a 4-week observation period. The total score on the CSS improved significantly in the DKT group compared to the control (P < 0.01). In addition, scores for some CSS subcategories (frequency of bowel movements, feeling of incomplete evacuation, and need for enema/disimpaction) significantly improved in the DKT group (P < 0.01, P = 0.049, and P = 0.03, resp.). The GVS was also significantly reduced in the DKT group compared to the control (P = 0.03). DKT in addition to conventional therapy is effective in treating functional constipation in poststroke patients. This study was a randomized controlled trial and was registered in the UMIN Clinical Trial Registry (no. UMIN000007393). PMID:25089144

Traditional Japanese medicine daikenchuto improves functional constipation in poststroke patients.

PubMed

Numata, Takehiro; Takayama, Shin; Tobita, Muneshige; Ishida, Shuichi; Katayose, Dai; Shinkawa, Mitsutoshi; Oikawa, Takashi; Aonuma, Takanori; Kaneko, Soichiro; Tanaka, Junichi; Kanemura, Seiki; Iwasaki, Koh; Ishii, Tadashi; Yaegashi, Nobuo

2014-01-01

Poststroke patients with functional constipation, assessed by the Rome III criteria, from 6 hospitals were recruited in a study on the effects of the traditional Japanese medicine Daikenchuto (DKT) on constipation. Thirty-four patients (17 men and 17 women; mean age: 78.1 ± 11.6 years) were randomly assigned to 2 groups; all patients received conventional therapy for constipation, and patients in the DKT group received 15 g/day of DKT for 4 weeks. Constipation scoring system (CSS) points and the gas volume score (GVS) (the measure of the intestinal gas volume calculated from plain abdominal radiographs) were recorded before and after a 4-week observation period. The total score on the CSS improved significantly in the DKT group compared to the control (P < 0.01). In addition, scores for some CSS subcategories (frequency of bowel movements, feeling of incomplete evacuation, and need for enema/disimpaction) significantly improved in the DKT group (P < 0.01, P = 0.049, and P = 0.03, resp.). The GVS was also significantly reduced in the DKT group compared to the control (P = 0.03). DKT in addition to conventional therapy is effective in treating functional constipation in poststroke patients. This study was a randomized controlled trial and was registered in the UMIN Clinical Trial Registry (no. UMIN000007393).

A multicenter randomized trial comparing rabeprazole and itopride in patients with functional dyspepsia in Japan: the NAGOYA study

PubMed Central

Kamiya, Takeshi; Shikano, Michiko; Kubota, Eiji; Mizoshita, Tsutomu; Wada, Tsuneya; Tanida, Satoshi; Kataoka, Hiromi; Adachi, Hiroshi; Hirako, Makoto; Okuda, Noriaki; Joh, Takashi

2017-01-01

The aims of this study were to compare the therapeutic effects of a proton pump inhibitor (PPI), rabeprazole (RPZ), and a prokinetic agent, itopride (ITO), and to investigate the role of PPI in the treatment strategy for Japanese functional dyspepsia (FD) patients. We randomly assigned 134 patients diagnosed by Rome III criteria to 4 weeks treatment with RPZ 10 mg/day (n = 69) or ITO 150 mg/day (n = 65). Dyspeptic symptoms were evaluated using FD scores at baseline and after 1, 2 and 4 weeks of treatment. We also divided subjects into predominantly epigastric pain syndrome (EPS) or postprandial distress syndrome (PDS), and evaluated the efficacy of RPZ and ITO respectively. RPZ showed a significant decrease in the Rate of Change (RC) in FD score within 1 week, which was maintained until after 4 weeks, with RPZ a significant effect compared with ITO at all evaluation points. In addition, RPZ showed a significant decrease in FD score in subjects with both EPS and PDS, whereas a significant decrease in the RC with ITO was only shown in those with predominant PDS. Acid-suppressive therapy with RPZ is useful for PDS as well EPS in Japanese FD patients (UMIN Clinical Trials Registry number: UMIN 000013962). PMID:28366993

A multicenter randomized trial comparing rabeprazole and itopride in patients with functional dyspepsia in Japan: the NAGOYA study.

PubMed

Kamiya, Takeshi; Shikano, Michiko; Kubota, Eiji; Mizoshita, Tsutomu; Wada, Tsuneya; Tanida, Satoshi; Kataoka, Hiromi; Adachi, Hiroshi; Hirako, Makoto; Okuda, Noriaki; Joh, Takashi

2017-03-01

The aims of this study were to compare the therapeutic effects of a proton pump inhibitor (PPI), rabeprazole (RPZ), and a prokinetic agent, itopride (ITO), and to investigate the role of PPI in the treatment strategy for Japanese functional dyspepsia (FD) patients. We randomly assigned 134 patients diagnosed by Rome III criteria to 4 weeks treatment with RPZ 10 mg/day ( n  = 69) or ITO 150 mg/day ( n  = 65). Dyspeptic symptoms were evaluated using FD scores at baseline and after 1, 2 and 4 weeks of treatment. We also divided subjects into predominantly epigastric pain syndrome (EPS) or postprandial distress syndrome (PDS), and evaluated the efficacy of RPZ and ITO respectively. RPZ showed a significant decrease in the Rate of Change (RC) in FD score within 1 week, which was maintained until after 4 weeks, with RPZ a significant effect compared with ITO at all evaluation points. In addition, RPZ showed a significant decrease in FD score in subjects with both EPS and PDS, whereas a significant decrease in the RC with ITO was only shown in those with predominant PDS. Acid-suppressive therapy with RPZ is useful for PDS as well EPS in Japanese FD patients (UMIN Clinical Trials Registry number: UMIN 000013962).

Sugammadex facilitates early recovery after surgery even in the absence of neuromuscular monitoring in patients undergoing laryngeal microsurgery: a single-center retrospective study.

PubMed

Park, Eui-Seok; Lim, Byung Gun; Lee, Won-Joon; Lee, Il Ok

2016-08-02

In many countries, routine clinical anaesthesia does not always involve neuromuscular monitoring. In these clinical settings, the efficacy and safety of sugammadex use has not yet been confirmed. We investigated the efficacy and safety of sugammadex in the absence of neuromuscular monitoring. One hundred and forty patients who underwent laryngeal microsurgery with the use of rocuronium as a neuromuscular blocking agent, without the use of a neuromuscular monitoring device, were retrospectively investigated. The patients were randomly chosen among all the patients who met the inclusion criteria at a tertiary university hospital between July 2013 and February 2015 and were allocated to group S (sugammadex group) or group P (pyridostigmine group) according to the neuromuscular reversal agent administered. Five patients were excluded from analysis and 135 patients completed the study. Primary outcome was extubation time. Secondary outcomes were anaesthesia time, the correlation between anaesthesia time and extubation time, the total amount of rocuronium, and postoperative adverse events in the post-anaesthesia care unit (PACU). Extubation time was significantly shorter in group S (6.3 ± 3.9 min) than in group P (9.0 ± 5.4 min). Anaesthesia time was also significantly shorter in group S (30.7 ± 10.3 min) than in group P (35.8 ± 12.6 min). In the patients with an anaesthesia time of 30 min or less, there was a positive correlation between anaesthesia time and extubation time in group P (r = 0.453), but there was no significant relationship in group S. The total amount of rocuronium used was higher in group S (0.62 ± 0.11 mg kg(-1)) than in group P (0.38 ± 0.14 mg kg(-1)). Postoperative adverse events in the PACU were comparable between the groups, except for tachycardia events: the incidence of tachycardia was significantly lower in group S (8.0 %) than in group P (17.3 %). Sugammadex could shorten anaesthesia and extubation times as well as recovery time in the PACU and reduce postoperative hemodynamic complications in a clinical setting in the absence of neuromuscular monitoring. This may enhance the patients' recovery in the operating room and PACU while improving the postoperative condition of patients. The trial was registered in the UMIN clinical trials registry ( www.umin.ac.jp/ctr/index/htm ; unique trial number: UMIN000016602; registration number: R000019266 ; principal investigator's name: Byung Gun Lim; date of registration: February 22, 2015).

Evaluation of a Proton Pump Inhibitor for Sleep Bruxism: A Randomized Clinical Trial.

PubMed

Ohmure, H; Kanematsu-Hashimoto, K; Nagayama, K; Taguchi, H; Ido, A; Tominaga, K; Arakawa, T; Miyawaki, S

2016-12-01

Bruxism is a repetitive jaw-muscle activity characterized by clenching or grinding of the teeth and/or bracing or thrusting of the mandible. Recent advances have clarified the relationship between gastroesophageal reflux and sleep bruxism (SB). However, the influence of pharmacological elimination of gastric acid secretion on SB has not been confirmed. The authors aimed to assess the efficacy of a proton pump inhibitor (PPI) on SB and to examine the gastrointestinal (GI) symptoms and endoscopic findings of the upper GI tract in SB patients. The authors performed a randomized double-blind placebo-controlled crossover study at Kagoshima University Hospital. Twelve patients with polysomnography (PSG)-diagnosed SB underwent an assessment of GI symptoms using the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) and esophagogastroduodenoscopy. At baseline (i.e., before interventions), the mean frequencies of electromyography (EMG) bursts and rhythmic masticatory muscle activity (RMMA) episodes were 65.4 ± 49.0 bursts/h and 7.0 ± 4.8 episodes/h, respectively, and at least 1 RMMA episode with grinding noise was confirmed in all participants. The mean FSSG score was 8.4 ± 5.6, and 41.7% of patients were diagnosed with gastroesophageal reflux disease. Mild reflux esophagitis was confirmed in 6 patients. PSG, including EMG of the left masseter muscle and audio-video recording, was performed on days 4 and 5 of administration of 10 mg of the PPI (rabeprazole) or placebo. PPI administration yielded a significant reduction in the frequency of EMG bursts, RMMA episodes, and grinding noise. No significant differences were observed regarding the swallowing events and sleep variables. Since the clinical application of PPI for SB treatment should remain on hold at present, the results of this trial highlight the potential application of pharmacological gastroesophageal reflux disease treatment for SB patients. Larger scale studies are warranted to corroborate these findings. (UMIN Clinical Trials Registry: UMIN000004577). © International & American Associations for Dental Research 2016.

Limited accessibility to designs and results of Japanese large-scale clinical trials for cardiovascular diseases.

PubMed

Sawata, Hiroshi; Ueshima, Kenji; Tsutani, Kiichiro

2011-04-14

Clinical evidence is important for improving the treatment of patients by health care providers. In the study of cardiovascular diseases, large-scale clinical trials involving thousands of participants are required to evaluate the risks of cardiac events and/or death. The problems encountered in conducting the Japanese Acute Myocardial Infarction Prospective (JAMP) study highlighted the difficulties involved in obtaining the financial and infrastructural resources necessary for conducting large-scale clinical trials. The objectives of the current study were: 1) to clarify the current funding and infrastructural environment surrounding large-scale clinical trials in cardiovascular and metabolic diseases in Japan, and 2) to find ways to improve the environment surrounding clinical trials in Japan more generally. We examined clinical trials examining cardiovascular diseases that evaluated true endpoints and involved 300 or more participants using Pub-Med, Ichushi (by the Japan Medical Abstracts Society, a non-profit organization), websites of related medical societies, the University Hospital Medical Information Network (UMIN) Clinical Trials Registry, and clinicaltrials.gov at three points in time: 30 November, 2004, 25 February, 2007 and 25 July, 2009. We found a total of 152 trials that met our criteria for 'large-scale clinical trials' examining cardiovascular diseases in Japan. Of these, 72.4% were randomized controlled trials (RCTs). Of 152 trials, 9.2% of the trials examined more than 10,000 participants, and 42.8% examined between 1,000 and 10,000 participants. The number of large-scale clinical trials markedly increased from 2001 to 2004, but suddenly decreased in 2007, then began to increase again. Ischemic heart disease (39.5%) was the most common target disease. Most of the larger-scale trials were funded by private organizations such as pharmaceutical companies. The designs and results of 13 trials were not disclosed. To improve the quality of clinical trials, all sponsors should register trials and disclose the funding sources before the enrolment of participants, and publish their results after the completion of each study.

Effect of Interpersonal Interaction on Festinating Gait Rehabilitation in Patients with Parkinson’s Disease

PubMed Central

Uchitomi, Hirotaka; Ogawa, Ken-ichiro; Orimo, Satoshi; Wada, Yoshiaki; Miyake, Yoshihiro

2016-01-01

Although human walking gait rhythms are generated by native individual gait dynamics, these gait dynamics change during interactions between humans. A typical phenomenon is synchronization of gait rhythms during cooperative walking. Our previous research revealed that fluctuation characteristics in stride interval of subjects with Parkinson’s disease changed from random to 1/f fluctuation as fractal characteristics during cooperative walking with the gait assist system Walk-Mate, which emulates a human interaction using interactive rhythmic cues. Moreover, gait dynamics were relearned through Walk-Mate gait training. However, the system’s clinical efficacy was unclear because the previous studies did not focus on specific gait rhythm disorder symptoms. Therefore, this study aimed to evaluate the effect of Walk-Mate on festinating gait among subjects with Parkinson’s disease. Three within-subject experimental conditions were used: (1) preinteraction condition, (2) interaction condition, and (3) postinteraction condition. The only difference between conditions was the interactive rhythmic cues generated by Walk-Mate. Because subjects with festinating gait gradually and involuntarily decreased their stride interval, the regression slope of stride interval as an index of severity of preinteraction festinating gait was elevated. The regression slope in the interaction condition was more gradual than during the preinteraction condition, indicating that the interactive rhythmic cues contributed to relieving festinating gait and stabilizing gait dynamics. Moreover, the gradual regression slope was carried over to the postinteraction condition, indicating that subjects with festinating gait have the potential to relearn stable gait dynamics. These results suggest that disordered gait dynamics are clinically restored through interactive rhythmic cues and that Walk-Mate may have the potential to assist therapists in more effective rehabilitation. Trial Registration: UMIN Clinical Trials Registry UMIN000012591 PMID:27253376

Prognostic Impact of Primary Tumor Location on Clinical Outcomes of Metastatic Colorectal Cancer Treated With Cetuximab Plus Oxaliplatin-Based Chemotherapy: A Subgroup Analysis of the JACCRO CC-05/06 Trials.

PubMed

Sunakawa, Yu; Ichikawa, Wataru; Tsuji, Akihito; Denda, Tadamichi; Segawa, Yoshihiko; Negoro, Yuji; Shimada, Ken; Kochi, Mitsugu; Nakamura, Masato; Kotaka, Masahito; Tanioka, Hiroaki; Takagane, Akinori; Tani, Satoshi; Yamaguchi, Tatsuro; Watanabe, Takanori; Takeuchi, Masahiro; Fujii, Masashi; Nakajima, Toshifusa

2017-09-01

Primary tumor location is a critical prognostic factor in metastatic colorectal cancer (mCRC); however, it remains unclear whether tumor location is a predictor of the response to cetuximab treatment. It is also uncertain if BRAF mutation contributes to the impact of tumor location on survival. We assessed the prognostic impact of tumor location on clinical outcomes in mCRC patients treated with first-line cetuximab chemotherapy. The associations of tumor location with overall survival and progression-free survival were evaluated in mCRC patients with KRAS exon 2 wild-type tumors who were enrolled onto 2 clinical trials: JACCRO CC-05 of cetuximab plus FOLFOX (n = 57, UMIN000004197) and CC-06 of cetuximab plus SOX (n = 61, UMIN000007022). Tumors proximal or from splenic flexure to rectum were defined as right-sided or left-sided, respectively. In addition, exploratory RAS and BRAF mutation analyses were performed. A total of 110 patients were assessable for tumor location; 90 had left-sided tumors. Left-sided tumors were significantly associated with longer overall survival (36.2 vs. 12.6 months, hazard ratio = 0.28, P < .0001) and progression-free survival (11.1 vs. 5.6 months, hazard ratio = 0.47, P = .0041) than right-sided tumors; similar results were obtained in multivariate analysis. A subanalysis showed that the association was evident in the FOLFOX group and that tumor location was an independent prognostic factor irrespective of BRAF status in RAS wild-type patients. Primary tumor location might be a predictor of survival independent of BRAF status in mCRC patients who receive first-line cetuximab combined with oxaliplatin-based chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of High-Dose Rebamipide Treatment for Low-Dose Aspirin-Induced Moderate-to-Severe Small Intestinal Damage

PubMed Central

Watanabe, Toshio; Takeuchi, Toshihisa; Handa, Osamu; Sakata, Yasuhisa; Tanigawa, Tetsuya; Shiba, Masatsugu; Naito, Yuji; Higuchi, Kazuhide; Fujimoto, Kazuma; Yoshikawa, Toshikazu; Arakawa, Tetsuo

2015-01-01

Background Low-dose aspirin (LDA) frequently causes small bowel injury. While some drugs have been reported to be effective in treating LDA-induced small intestinal damage, most studies did not exclude patients with mild damage thought to be clinically insignificant. Aim We conducted a multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy of a high dose of rebamipide, a gastroprotective drug, for LDA-induced moderate-to-severe enteropathy. Methods We enrolled patients who received 100 mg of enteric-coated aspirin daily for more than 3 months and were found to have more than 3 mucosal breaks (i.e., erosions or ulcers) in the small intestine by capsule endoscopy. Eligible patients were assigned to receive either rebamipide 300 mg (triple dose) 3 times daily or placebo for 8 weeks in a 2:1 ratio. Capsule endoscopy was then repeated. The primary endpoint was the change in the number of mucosal breaks from baseline to 8 weeks. Secondary endpoints included the complete healing of mucosal breaks at 8 weeks and the change in Lewis score (an endoscopic score assessing damage severity) from baseline to 8 weeks. Results The study was completed by 38 patients (rebamipide group: n = 25, placebo group: n = 13). After 8 weeks of treatment, rebamipide, but not placebo, significantly decreased the number of mucosal breaks (p = 0.046). While the difference was not significant (p = 0.13), the rate of complete mucosal break healing in the rebamipide group (32%, 8 of 25) tended to be higher than that in the placebo group (7.7%, 1 of 13). Rebamipide treatment significantly improved intestinal damage severity as assessed by the Lewis score (p = 0.02), whereas placebo did not. The triple dose of rebamipide was well tolerated. Conclusions High-dose rebamipide is effective for the treatment of LDA-induced moderate-to-severe enteropathy. Trial Registration UMIN Clinical Trials Registry UMIN000003463 PMID:25874951

Effects of Anma massage therapy (Japanese massage) for gynecological cancer survivors: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Cancer patients and survivors regularly feel anxious about cancer recurrence or death, even after the conclusion of medical treatment, and they are often highly physiologically and psychologically stressed. Massage therapy is one of the most widely used complementary and alternative therapies used in the hope of alleviating such stress and physical and psychological complaints and to improve health-related quality of life. This randomized phase III, two-armed, parallel group, clinical trial was designed after obtaining positive findings in a preliminary study. The primary objective is to verify the effects of continuous Japanese massage therapy, referred to as Anma therapy, for cancer survivors. The secondary objective is to confirm the immediate effects of a single Anma massage session for cancer survivors. Methods/Design Sixty cancer survivors older than 20 years of age who have had histologically confirmed uterine cervical, endometrial, ovarian, fallopian tube or peritoneal cancer in the past, but with no recurrence for more than 3 years since receiving standard medical treatment, are being recruited by gynecologists in medical facilities. In the coordinating office, they are randomly allocated to two groups (n = 30 each): an Anma massage group receiving a 40-min Anma massage session once weekly over a 2-month intervention period (total of eight Anma massage sessions) and a control group being followed by medical doctors and receiving no Anma massage sessions. The primary end point is the severity of physical subjective symptoms that cancer survivors report in daily life, assessed using a Visual Analogue Scale. Secondary end points are urine and saliva analyses, psychological condition and health-related quality-of-life scores as determined on the basis of a self-report questionnaire. Discussion Using the evidence-based findings of this trial, medical professionals should be able to explain the benefits conferred by Anma massage to cancer survivors and provide higher-quality information to better inform patients regarding their decisions about whether to receive such therapy. Trial registration This trial is registered with the UMIN Clinical Trials Registry as UMIN000009097. PMID:23883162

New dedicated bifurcated silicone stent placement for stenosis around the primary right carina.

PubMed

Oki, Masahide; Saka, Hideo

2013-08-01

Silicone stenting has been widely used to palliate respiratory symptoms in patients suffering from airway stenosis. Although many types and shapes of stents have been developed, there is no ideal stent for stenosis around the carina between the bronchus to the right upper lobe and the bronchus intermedius (primary right carina). The purpose of this study was to evaluate the feasibility, efficacy, and safety of a new silicone stent designed for treating airway stenosis around the primary right carina. We recruited 16 patients with suspected stenosis around the primary right carina. Ten of the patients met the inclusion criteria for inserting the study stent. All stenting procedures were performed with a rigid and flexible bronchoscope under general anesthesia. The study stent could be mounted successfully on the primary right carina in all 10 patients. Five patients underwent stenting using only the new stent, and the other five underwent stenting with it on the primary right carina and a silicone Y stent on the main carina. The dyspnea index improved in eight of the 10 patients, including one who was mechanically ventilated. Early complications developed in three patients (temporary pneumonia in two and retention of secretions in one), and late complications occurred in two patients (granuloma formation in one and hemoptysis in one). Stent placement with the new silicone stent designed to fit on the primary right carina is feasible, effective, and acceptably safe. UMIN-Clinical Trials Registry; No.: UMIN000001776; URL: www.umin.ac.jp/ctr.

Evaluation of a novel immunochromatographic device for rapid and accurate clinical detection of Porphyromonas gingivalis in subgingival plaque.

PubMed

Imamura, K; Takayama, S; Saito, A; Inoue, E; Nakayama, Y; Ogata, Y; Shirakawa, S; Nagano, T; Gomi, K; Morozumi, T; Akiishi, K; Watanabe, K; Yoshie, H

2015-10-01

An important goal for the improved diagnosis and management of infectious and inflammatory diseases, such as periodontitis, is the development of rapid and accurate technologies for the decentralized detection of bacterial pathogens. The aim of this prospective multicenter study was to evaluate the clinical use of a novel immunochromatographic device with monoclonal antibodies for the rapid point-of-care detection and semi-quantification of Porphyromonas gingivalis in subgingival plaque. Sixty-three patients with chronic periodontitis and 28 periodontally healthy volunteers were subjected to clinical and microbiological examinations. Subgingival plaque samples were analyzed for the presence of P. gingivalis using a novel immunochromatography based device DK13-PG-001, designed to detect the 40k-outer membrane protein of P. gingivalis, and compared with a PCR-Invader method. In the periodontitis group, a significant strong positive correlation in detection results was found between the test device score and the PCR-Invader method (Spearman rank correlation, r=0.737, p<0.0001). The sensitivity, specificity, and positive and negative predictive values of the test device were 96.2%, 91.8%, 90.4% and 96.7%, respectively. The detection threshold of the test device was determined to be approximately 10(4) (per two paper points). There were significant differences in the bacterial counts by the PCR-Invader method among groups with different ranges of device scores. With a cut-off value of ≥0.25 in device score, none of periodontally healthy volunteers were tested positive for the subgingival presence of P. gingivalis, whereas 76% (n=48) of periodontitis subjects were tested positive. There was a significant positive correlation between device scores for P. gingivalis and periodontal parameters including probing pocket depth and clinical attachment level (r=0.317 and 0.281, respectively, p<0.01). The results suggested that the DK13-PG-001 device kit can be effectively used for rapid, chair-side detection and semi-quantification of P. gingivalis in subgingival plaque. UMIN Clinical Trials Registry (UMIN-CTR) UMIN000011943. Copyright © 2015 Elsevier B.V. All rights reserved.

Trichuris suis ova therapy for allergic rhinitis does not affect allergen-specific cytokine responses despite a parasite-specific cytokine response.

PubMed

Bourke, C D; Mutapi, F; Nausch, N; Photiou, D M F; Poulsen, L K; Kristensen, B; Arnved, J; Rønborg, S; Roepstorff, A; Thamsborg, S; Kapel, C; Melbye, M; Bager, P

2012-11-01

Parasitic helminths have been shown to reduce inflammation in most experimental models of allergic disease, and this effect is mediated via cytokine responses. However, in humans, the effects of controlled helminth infection on cytokine responses during allergy have not been studied. The aim was to investigate whether infection with the nematode parasite Trichuris suis alters systemic cytokine levels, cellular cytokine responses to parasite antigens and pollen allergens and/or the cytokine profile of allergic individuals. In a randomized double-blinded placebo-controlled clinical trial (UMIN trial registry, Registration no. R000001298, Trial ID UMIN000001070, URL: http://www.umin.ac.jp/map/english), adults with grass pollen-induced allergic rhinitis received three weekly doses of 2500 Trichuris suis ova (n = 45) or placebo (n = 44) over 6 months. IFN-γ, TNF-α, IL-4, IL-5, IL-10 and IL-13 were quantified via cytometric bead array in plasma. Cytokines, including active TGF-β, were also quantified in supernatants from peripheral blood mononuclear cells cultured with parasite antigens or pollen allergens before, during and after the grass pollen season for a sub-cohort of randomized participants (T. suis ova-treated, n = 12, Placebo-treated, n = 10). Helminth infection induced a Th2-polarized cytokine response comprising elevated plasma IL-5 and parasite-specific IL-4, IL-5 and IL-13, and a global shift in the profile of systemic cytokine responses. Infection also elicited high levels of the regulatory cytokine IL-10 in response to T. suis antigens. Despite increased production of T. suis-specific cytokines in T. suis ova-treated participants, allergen-specific cytokine responses during the grass pollen season and the global profile of PBMC cytokine responses were not affected by T. suis ova treatment. This study suggests that cytokines induced by Trichuris suis ova treatment do not alter allergic reactivity to pollen during the peak of allergic rhinitis symptoms. © 2012 Blackwell Publishing Ltd.

The effect of a behavioral activation program on improving mental and physical health complaints associated with radiation stress among mothers in Fukushima: a randomized controlled trial.

PubMed

Imamura, Kotaro; Sekiya, Yuki; Asai, Yumi; Umeda, Maki; Horikoshi, Naoko; Yasumura, Seiji; Yabe, Hirooki; Akiyama, Tsuyoshi; Kawakami, Norito

2016-11-08

Mothers living with small children in Fukushima prefecture may experience radiation anxiety and related symptoms after the Fukushima Dai'ich Nuclear Power Plant Accident. A behavioral activation (BA) program was developed to improve their psychosomatic symptoms. The purpose of this randomized controlled trial was to examine the effectiveness of a BA program for improving psychological distress and physical symptoms among mothers with preschool children in Fukushima-prefecture 3 years after the Fukushima Daiichi Nuclear Power Plant accident. Participants were recruited from mothers living with a preschool child(ren) in Fukushima city and surrounding areas though a newspaper advertisement, posters, and flyers. Participants allocated to the intervention group received a newly developed group-based BA program, which consisted of two 90- min lessons with a 1-week interval. Psychological distress and physical symptoms as a primary outcome, and radiation anxiety and positive well-being (liveliness and life satisfaction) as a secondary outcome, were measured at baseline, 1- and 3-month follow-ups. Participants were randomly allocated to either an intervention or a control group (18 and 19, respectively). The BA program showed a marginally significant intervention effect on psychological distress (p = 0.051) and physical symptoms (p = 0.07) at 1-month follow-up, while the effect became smaller at 3-month follow-up. The effect sizes at 1-month were medium to large (-0.72 and -0.56, respectively). There was a significant intervention effect on increasing liveliness at 3-month follow-up (p = 0.02); and there were marginally significant effects on life satisfaction at 1- and 3-month follow-ups (both p = 0.09). This BA program may be effective for improving psychological distress, physical symptoms, and well-being, at least for a short duration, among mothers with preschool children after the nuclear power plant accident in Fukushima, while a further large-scale study is needed. The UMIN Clinical Trials Registry (UMIN-CTR; ID =  UMIN000014081 ). Registered 27 May 2014.

Mitigation of sociocommunicational deficits of autism through oxytocin-induced recovery of medial prefrontal activity: a randomized trial.

PubMed

Watanabe, Takamitsu; Abe, Osamu; Kuwabara, Hitoshi; Yahata, Noriaki; Takano, Yosuke; Iwashiro, Norichika; Natsubori, Tatsunobu; Aoki, Yuta; Takao, Hidemasa; Kawakubo, Yuki; Kamio, Yoko; Kato, Nobumasa; Miyashita, Yasushi; Kasai, Kiyoto; Yamasue, Hidenori

2014-02-01

Sociocommunicational deficits make it difficult for individuals with autism spectrum disorders (ASD) to understand communication content with conflicting verbal and nonverbal information. Despite growing prospects for oxytocin as a therapeutic agent for ASD, no direct neurobiological evidence exists for oxytocin's beneficial effects on this core symptom of ASD. This is slowing clinical application of the neuropeptide. To directly examine whether oxytocin has beneficial effects on the sociocommunicational deficits of ASD using both behavioral and neural measures. At the University of Tokyo Hospital, we conducted a randomized, double-blind, placebo-controlled, within-subject-crossover, single-site experimental trial in which intranasal oxytocin and placebo were administered. A total of 40 highly functioning men with ASD participated and were randomized in the trial. Single-dose intranasal administration of oxytocin (24 IU) and placebo. Using functional magnetic resonance imaging, we examined effects of oxytocin on behavioral neural responses of the participants to a social psychological task. In our previous case-control study using the same psychological task, when making decisions about social information with conflicting verbal and nonverbal contents, participants with ASD made judgments based on nonverbal contents less frequently with longer time and could not induce enough activation in the medial prefrontal cortex. Therefore, our main outcomes and measures were the frequency of the nonverbal information-based judgments (NVJs), the response time for NVJs, and brain activity of the medial prefrontal cortex during NVJs. Intranasal oxytocin enabled the participants to make NVJs more frequently (P = .03) with shorter response time (P = .02). During the mitigated behavior, oxytocin increased the originally diminished brain activity in the medial prefrontal cortex (P < .001). Moreover, oxytocin enhanced functional coordination in the area (P < .001), and the magnitude of these neural effects was predictive of the behavioral effects (P ≤ .01). These findings provide the first neurobiological evidence for oxytocin's beneficial effects on sociocommunicational deficits of ASD and give us the initial account for neurobiological mechanisms underlying any beneficial effects of the neuropeptide. umin.ac.jp/ctr Identifier: UMIN000002241 and UMIN000004393.

Randomized study of low-dose versus standard-dose chemoradiotherapy for unresectable esophageal squamous cell carcinoma (JCOG0303)

PubMed Central

Shinoda, Masayuki; Ando, Nobutoshi; Kato, Ken; Ishikura, Satoshi; Kato, Hoichi; Tsubosa, Yasuhiro; Minashi, Keiko; Okabe, Hiroshi; Kimura, Yusuke; Kawano, Tatsuyuki; Kosugi, Shin-Ichi; Toh, Yasushi; Nakamura, Kenichi; Fukuda, Haruhiko

2015-01-01

Low-dose cisplatin and 5-fluorouracil (LDPF) chemotherapy with daily radiotherapy (RT) is used as an alternative chemoradiotherapy regimen for locally advanced esophageal carcinoma. We evaluated whether RT plus LDPF chemotherapy had an advantage in terms of survival and/or toxicity over RT plus standard-dose cisplatin and 5-fluorouracil (SDPF) chemotherapy in this study. This multicenter trial included esophageal cancer patients with clinical T4 disease and/or unresectable regional lymph node metastasis. Patients were randomly assigned to receive RT (2 Gy/fraction, total dose of 60 Gy) with SDPF (arm A) or LDPF (arm B) chemotherapy. The primary endpoint was overall survival (OS). A total of 142 patients (arm A/B, 71/71) from 41 institutions were enrolled between April 2004 and September 2009. The OS hazard ratio in arm B versus arm A was 1.05 (80% confidence interval, 0.78–1.41). There were no differences in toxicities in either arm. Arm B was judged as not promising for further evaluation in the phase III setting. Thus, the Data and Safety Monitoring Committee recommended that the study be terminated. In the updated analyses, median OS and 3-year OS were 13.1 months and 25.9%, respectively, for arm A and 14.4 months and 25.7%, respectively, for arm B. Daily RT plus LDPF chemotherapy did not qualify for further evaluation as a new treatment option for patients with locally advanced unresectable esophageal cancer. This study was registered at the UMIN Clinical Trials Registry as UMIN000000861. PMID:25640628

New tapered metallic stent for unresectable malignant hilar bile duct obstruction.

PubMed

Sakai, Yuji; Tsuyuguchi, Toshio; Nishikawa, Takao; Sugiyama, Harutoshi; Sasaki, Reina; Sakamoto, Dai; Watanabe, Yuto; Nakamura, Masato; Yasui, Shin; Mikata, Rintaro; Yokosuka, Osamu

2015-10-16

To examine the usefulness of a new tapered metallic stent (MS) in patients with unresectable malignant hilar bile duct obstruction. This new tapered MS was placed in 11 patients with Bismuth II or severer unresectable malignant hilar bile duct obstruction, as a prospective study. The subjects were six patients with bile duct carcinoma, three with gallbladder cancer, and two with metastatic bile duct obstruction. Stenosis morphology was Bismuth II: 7, IIIa: 3, and IV: 1. UMIN Clinical Trial Registry (UMIN000004758). MS placement was 100% (11/11) successful. There were no procedural accidents. The mean patency period was 208.401 d, the median survival period was 142.000 d, and the mean survival period was 193.273 d. Occlusion rate was 36.4% (4/11); the causes of occlusion were ingrowth and overgrowth in 2 patients each, 18.2%, respectively. Patients with occlusion underwent endoscopic treatment one more time and all were treatable. The tapered MS proved useful in patients with unresectable malignant hilar bile duct obstruction because it provided a long patency period, enabled re-treatment by re-intervention, and no procedural accidents occurred.

Effects of Oral L-Carnitine Administration in Narcolepsy Patients: A Randomized, Double-Blind, Cross-Over and Placebo-Controlled Trial

PubMed Central

Miyagawa, Taku; Kawamura, Hiromi; Obuchi, Mariko; Ikesaki, Asuka; Ozaki, Akiko; Tokunaga, Katsushi; Inoue, Yuichi; Honda, Makoto

2013-01-01

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement (REM) sleep abnormalities. A genome-wide association study (GWAS) identified a novel narcolepsy-related single nucleotide polymorphism (SNP), which is located adjacent to the carnitine palmitoyltransferase 1B (CPT1B) gene encoding an enzyme involved in β-oxidation of long-chain fatty acids. The mRNA expression levels of CPT1B were associated with this SNP. In addition, we recently reported that acylcarnitine levels were abnormally low in narcolepsy patients. To assess the efficacy of oral l-carnitine for the treatment of narcolepsy, we performed a clinical trial administering l-carnitine (510 mg/day) to patients with the disease. The study design was a randomized, double-blind, cross-over and placebo-controlled trial. Thirty narcolepsy patients were enrolled in our study. Two patients were withdrawn and 28 patients were included in the statistical analysis (15 males and 13 females, all with HLA-DQB1*06:02). l-carnitine treatment significantly improved the total time for dozing off during the daytime, calculated from the sleep logs, compared with that of placebo-treated periods. l-carnitine efficiently increased serum acylcarnitine levels, and reduced serum triglycerides concentration. Differences in the Japanese version of the Epworth Sleepiness Scale (ESS) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) vitality and mental health subscales did not reach statistical significance between l-carnitine and placebo. This study suggests that oral l-carnitine can be effective in reducing excessive daytime sleepiness in narcolepsy patients. Trial Registration University hospital Medical Information Network (UMIN) UMIN000003760 PMID:23349733

A New Mother-Child Play Activity Program to Decrease Parenting Stress and Improve Child Cognitive Abilities: A Cluster Randomized Controlled Trial

PubMed Central

Tachibana, Yoshiyuki; Fukushima, Ai; Saito, Hitomi; Yoneyama, Satoshi; Ushida, Kazuo; Yoneyama, Susumu; Kawashima, Ryuta

2012-01-01

Background We propose a new play activity intervention program for mothers and children. Our interdisciplinary program integrates four fields of child-related sciences: neuroscience, preschool pedagogy, developmental psychology, and child and maternal psychiatry. To determine the effect of this intervention on child and mother psychosocial problems related to parenting stress and on the children's cognitive abilities, we performed a cluster randomized controlled trial. Methodology/Principal Findings Participants were 238 pairs of mothers and typically developing preschool children (ages 4–6 years old) from Wakakusa kindergarten in Japan. The pairs were asked to play at home for about 10 min a day, 5 days a week for 3 months. Participants were randomly assigned to the intervention or control group by class unit. The Parenting Stress Index (PSI) (for mothers), the Goodenough Draw-a-Man intelligence test (DAM), and the new S-S intelligence test (NS-SIT) (for children) were administered prior to and 3 months after the intervention period. Pre–post changes in test scores were compared between the groups using a linear mixed-effects model analysis. The primary outcomes were the Total score on the child domain of the PSI (for child psychosocial problems related to parenting stress), Total score on the parent domain of the PSI (for maternal psychosocial problems related to parenting stress), and the score on the DAM (for child cognitive abilities). The results of the PSI suggested that the program may reduce parenting stress. The results of the cognitive tests suggested that the program may improve the children's fluid intelligence, working memory, and processing speed. Conclusions/Significance Our intervention program may ameliorate the children's psychosocial problems related to parenting stress and increase their cognitive abilities. Trial Registration UMIN Clinical Trials Registry UMIN000002265 PMID:22848340

The effect of blue-blocking intraocular lenses on circadian biological rhythm: protocol for a randomised controlled trial (CLOCK-IOL colour study).

PubMed

Nishi, Tomo; Saeki, Keigo; Obayashi, Kenji; Miyata, Kimie; Tone, Nobuhiro; Tsujinaka, Hiroki; Yamashita, Mariko; Masuda, Naonori; Mizusawa, Yutarou; Okamoto, Masahiro; Hasegawa, Taiji; Maruoka, Shinji; Ueda, Tetsuo; Kojima, Masashi; Matsuura, Toyoaki; Kurumatani, Norio; Ogata, Nahoko

2015-05-12

Blue light information plays an important role in synchronising internal biological rhythm within the external environment. Circadian misalignment is associated with the increased risk of sleep disturbance, obesity, diabetes mellitus, depression, ischaemic heart disease, stroke and cancer. Meanwhile, blue light causes photochemical damage to the retina, and may be associated with age-related macular degeneration (AMD). At present, clear intraocular lenses (IOLs) and blue-blocking IOLs are both widely used for cataract surgery; there is currently a lack of randomised controlled trials to determine whether clear or blue-blocking IOLs should be used. This randomised controlled trial will recruit 1000 cataract patients and randomly allocate them to receive clear IOLs or blue-blocking IOLs in a ratio of 1:1. The primary outcomes are mortality and the incidence of cardiovascular disease, cancer and AMD. Secondary outcomes are fasting plasma glucose, triglycerides, cholesterol, glycated haemoglobin, sleep quality, daytime sleepiness depressive symptoms, light sensitivity, the circadian rhythm of physical activity, wrist skin temperature and urinary melatonin metabolite. Primary outcomes will be followed until 20 years after surgery, and secondary outcomes will be assessed at baseline and 1 year after surgery. Ethical approval has been obtained from the Institutional Review Board of Nara Medical University (No. 13-032). The findings of this study will be communicated to healthcare professionals, participants and the public through peer-reviewed publications, scientific conferences and the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) home page. UMIN000014680. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy.

PubMed

Nakamura, Kazuhiko; Ihara, Eikichi; Akiho, Hirotada; Akahoshi, Kazuya; Harada, Naohiko; Ochiai, Toshiaki; Nakamura, Norimoto; Ogino, Haruei; Iwasa, Tsutomu; Aso, Akira; Iboshi, Yoichiro; Takayanagi, Ryoichi

2016-11-15

The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses. The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing. Combination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435).

Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy

PubMed Central

Nakamura, Kazuhiko; Ihara, Eikichi; Akiho, Hirotada; Akahoshi, Kazuya; Harada, Naohiko; Ochiai, Toshiaki; Nakamura, Norimoto; Ogino, Haruei; Iwasa, Tsutomu; Aso, Akira; Iboshi, Yoichiro; Takayanagi, Ryoichi

2016-01-01

Background/Aims The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. Methods In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses. Results The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing. Conclusions Combination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435). PMID:27282261

Influence of experimental oesophageal acidification on masseter muscle activity, cervicofacial behaviour and autonomic nervous activity in wakefulness.

PubMed

Ohmure, H; Sakoguchi, Y; Nagayama, K; Numata, M; Tsubouchi, H; Miyawaki, S

2014-06-01

Recent studies have been revealing the relationship between the stomatognathic system and the gastrointestinal tract. However, the effect of oesophageal acid stimulation on masticatory muscle activity during wakefulness has not been fully elucidated. To examine whether intra-oesophageal acidification induces masticatory muscle activity, a randomised trial was conducted investigating the effect of oesophageal acid infusion on masseter muscle activity, autonomic nervous system (ANS) activity and subjective symptoms. Polygraphic monitoring consisting of electromyography of the masseter muscle, electrocardiography and audio-video recording was performed in 15 healthy adult men, using three different 30-min interventions: (i) no infusion, (ii) intra-oesophageal saline infusion and (iii) intra-oesophageal infusion of acidic solution (0·1 N HCl; pH 1·2). This study was registered with the UMIN Clinical Trials Registry, UMIN000005350. Oesophageal acid stimulation significantly increased masseter muscle activity during wakefulness, especially when no behaviour was performed in the oro-facial region. Chest discomfort, including heartburn, also increased significantly after oesophageal acid stimulation; however, no significant correlation was observed between increased subjective symptoms and masseter muscle activity. Oesophageal acid infusion also altered ANS activity; a significant correlation was observed between masticatory muscle changes and parasympathetic nervous system activity. These findings suggest that oesophageal-derived ANS modulation induces masseter muscle activity, irrespective of the presence or absence of subjective gastrointestinal symptoms. © 2014 John Wiley & Sons Ltd.

Does cognitive behavioral therapy alter mental defeat and cognitive flexibility in patients with panic disorder?

PubMed

Nagata, Shinobu; Seki, Yoichi; Shibuya, Takayuki; Yokoo, Mizue; Murata, Tomokazu; Hiramatsu, Yoichi; Yamada, Fuminori; Ibuki, Hanae; Minamitani, Noriko; Yoshinaga, Naoki; Kusunoki, Muga; Inada, Yasushi; Kawasoe, Nobuko; Adachi, Soichiro; Oshiro, Keiko; Matsuzawa, Daisuke; Hirano, Yoshiyuki; Yoshimura, Kensuke; Nakazato, Michiko; Iyo, Masaomi; Nakagawa, Akiko; Shimizu, Eiji

2018-01-12

Mental defeat and cognitive flexibility have been studied as explanatory factors for depression and posttraumatic stress disorder. This study examined mental defeat and cognitive flexibility scores in patients with panic disorder (PD) before and after cognitive behavioral therapy (CBT), and compared them to those of a gender- and age-matched healthy control group. Patients with PD (n = 15) received 16 weekly individual CBT sessions, and the control group (n = 35) received no treatment. Patients completed the Mental Defeat Scale and the Cognitive Flexibility Scale before the intervention, following eight CBT sessions, and following 16 CBT sessions, while the control group did so only prior to receiving CBT (baseline). The patients' pre-CBT Mental Defeat and Cognitive Flexibility Scale scores were significantly higher on the Mental Defeat Scale and lower on the Cognitive Flexibility Scale than those of the control group participants were. In addition, the average Mental Defeat Scale scores of the patients decreased significantly, from 22.2 to 12.4, while their average Cognitive Flexibility Scale scores increased significantly, from 42.8 to 49.5. These results suggest that CBT can reduce mental defeat and increase cognitive flexibility in patients with PD Trial registration The study was registered retrospectively in the national UMIN Clinical Trials Registry on June 10, 2016 (registration ID: UMIN000022693).

Effects of Daikenchuto on Abdominal Bloating Accompanied by Chronic Constipation: A Prospective, Single-Center Randomized Open Trial.

PubMed

Yuki, Mika; Komazawa, Yoshinori; Kobayashi, Yoshiya; Kusunoki, Maho; Takahashi, Yoshiko; Nakashima, Sayaka; Uno, Goichi; Ikuma, Isao; Shizuku, Toshihiro; Kinoshita, Yoshikazu

2015-12-01

Daikenchuto (DKT), a traditional Japanese herbal medicine, is widely used for treatment of gastrointestinal disorders. We evaluated the efficacy and safety of DKT for abdominal bloating in patients with chronic constipation. To evaluate the efficacy and safety of DKT for the treatment of abdominal bloating. After discontinuing as-needed use of laxatives, 10 patients received oral DKT for 14 days (15 g/d). To evaluate small intestinal bacteria overgrowth (SIBO), a glucose breath test was performed before and after treatment with DKT. Before beginning the treatment, 4 patients (40%) had a diagnosis of SIBO based on a positive glucose breath test result. In both the SIBO and non-SIBO groups, bowel movement frequency and stool form remained unchanged after DKT treatment. For all patients, median total Gastrointestinal Symptoms Rating Scale score and the median Gastrointestinal Symptoms Rating Scale indigestion and constipation subscales were significantly decreased, whereas the median visual analog score for decreased abdominal bloating was significantly increased. Improvements of those symptoms were the same in both the SIBO and non-SIBO groups, indicating that DKT does not have effects on small intestine bacteria. No serious side effects were reported. DKT treatment improved quality of life for patients with chronic constipation regardless of the presence of SIBO and showed no effects on small intestine bacteria. UMIN Clinical Trial Registry identifier: UMIN000008070.

Liver elasticity measurement before and after biliary drainage in patients with obstructive jaundice: a prospective cohort studya prospective cohort study.

PubMed

Kubo, Kimitoshi; Kawakami, Hiroshi; Kuwatani, Masaki; Nishida, Mutsumi; Kawakubo, Kazumichi; Kawahata, Shuhei; Taya, Yoko; Kubota, Yoshimasa; Amano, Toraji; Shirato, Hiroki; Sakamoto, Naoya

2016-07-08

Obstructive jaundice has been reported to influence liver elasticity, independent of liver fibrosis. The aim of our prospective study was to evaluate the changes in liver elasticity, before and after biliary drainage, in patients with obstructive jaundice, and to evaluate the correlation between elasticity measures and serum markers of liver fibrosis. This is a prospective cohort study of 20 patients with obstructive jaundice. Liver elasticity was assessed by Transient Elastography (TE) and Virtual Touch™ Quantification (VTQ). Serum total bilirubin (T-Bil) level was measured before biliary drainage (Day 0), with measures repeated at 2 days (Day 2) and 7 days (Day 7) after biliary drainage. Serum levels of the following markers of liver fibrosis were also obtained on Day 0 and Day 7: hyaluronic acid (HA), procollagen-III-peptide (P-III-P). T-Bil, TE, and VTQ for the left (VTQ-L) and right (VTQ-R) lobes of the liver were all elevated before biliary drainage, with respective levels, measured at Day 0, of 11.9 ± 1.5 mg/dl, 12.1 ± 0.9 kPa, 2.23 ± 0.10 m/s, and 1.85 ± 0.10 m/s. All values decreased on Day 7 after drainage: T-Bil, 4.7 ± 1.0 mg/dl (P < 0.001); TE, 7.6 ± 0.6 kPa (P < 0.001); VTQ-L, 1.53 ± 0.08 m/s (P < 0.001); and VTQ-R, 1.30 ± 0.05 m/s (P < 0.001). Similar changes were observed in serum markers of liver fibrosis. Liver elasticity measures correlated with serum levels of T-Bil, P-III-P, and HA (r = 0.35-0.67, P < 0.001). This study confirmed decreases in liver elasticity, measured by TE and VTQ, after biliary drainage. Measures of liver elasticity correlated to levels of T-Bil and serum markers of liver fibrosis. (UMIN ID: UMIN00001284313). University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: UMIN00001284313 ); Registration date: 2014-01-14.

Lactic-fermented egg white improves visceral fat obesity in Japanese subjects-double-blind, placebo-controlled study.

PubMed

Matsuoka, Ryosuke; Kamachi, Keiko; Usuda, Mika; Wang, Wei; Masuda, Yasunobu; Kunou, Masaaki; Tanaka, Akira; Utsunomiya, Kazunori

2017-12-08

It was reported that egg white protein (EWP) reduced body fat in rats. We developed a lactic-fermented egg white (LE) that facilitates the consumption of egg whites by fermenting them with lactobacillus, and were able to study their intake in humans. In this double-blind, placebo-controlled design, we evaluated the effect of LE on visceral fat area (VFA). Participants included 37 adult males and females aged ≥40 years (VFA at navel ≥100 cm 2 ). They were divided into two groups: the control group and the LE group. The control and LE groups consumed drinks containing whey and LE, respectively, for 12 weeks (providing 8 g protein/day). VFA was measured at baseline and at week 12 of intake. Abdominal girth was measured at baseline and at weeks 6 and 12. LE intake decreased VFA significantly compared with baseline (-8.89 cm 2 , p < 0.05), and VFA was significantly lower than that in the control group (+1.71 cm 2 , p < 0.05). The LE group showed significant improvement in the ratio of visceral to subcutaneous fat area compared with baseline and the control group (p < 0.05). The results demonstrated that LE reduces VFA and improves the ratio of visceral to subcutaneous fat area. As other measurement items were not influenced, we concluded that LE improves visceral fat obesity. This clinical trial was retrospectively registered with the University hospital Medical Information Network (UMIN) Center, ( UMIN000026949 ; registered on 11/04/2017; http://www.umin.ac.jp /).

A multicenter, randomized, double-blind, placebo-controlled trial of high-dose rebamipide treatment for low-dose aspirin-induced moderate-to-severe small intestinal damage.

PubMed

Watanabe, Toshio; Takeuchi, Toshihisa; Handa, Osamu; Sakata, Yasuhisa; Tanigawa, Tetsuya; Shiba, Masatsugu; Naito, Yuji; Higuchi, Kazuhide; Fujimoto, Kazuma; Yoshikawa, Toshikazu; Arakawa, Tetsuo

2015-01-01

Low-dose aspirin (LDA) frequently causes small bowel injury. While some drugs have been reported to be effective in treating LDA-induced small intestinal damage, most studies did not exclude patients with mild damage thought to be clinically insignificant. We conducted a multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy of a high dose of rebamipide, a gastroprotective drug, for LDA-induced moderate-to-severe enteropathy. We enrolled patients who received 100 mg of enteric-coated aspirin daily for more than 3 months and were found to have more than 3 mucosal breaks (i.e., erosions or ulcers) in the small intestine by capsule endoscopy. Eligible patients were assigned to receive either rebamipide 300 mg (triple dose) 3 times daily or placebo for 8 weeks in a 2:1 ratio. Capsule endoscopy was then repeated. The primary endpoint was the change in the number of mucosal breaks from baseline to 8 weeks. Secondary endpoints included the complete healing of mucosal breaks at 8 weeks and the change in Lewis score (an endoscopic score assessing damage severity) from baseline to 8 weeks. The study was completed by 38 patients (rebamipide group: n = 25, placebo group: n = 13). After 8 weeks of treatment, rebamipide, but not placebo, significantly decreased the number of mucosal breaks (p = 0.046). While the difference was not significant (p = 0.13), the rate of complete mucosal break healing in the rebamipide group (32%, 8 of 25) tended to be higher than that in the placebo group (7.7%, 1 of 13). Rebamipide treatment significantly improved intestinal damage severity as assessed by the Lewis score (p = 0.02), whereas placebo did not. The triple dose of rebamipide was well tolerated. High-dose rebamipide is effective for the treatment of LDA-induced moderate-to-severe enteropathy. UMIN Clinical Trials Registry UMIN000003463.

Phase I/II trial of 2-weekly docetaxel combined with cisplatin plus fluorouracil in metastatic esophageal cancer (JCOG0807)

PubMed Central

Hironaka, Shuichi; Tsubosa, Yasuhiro; Mizusawa, Junki; Kii, Takayuki; Kato, Ken; Tsushima, Takahiro; Chin, Keisho; Tomori, Akihisa; Okuno, Tatsuya; Taniki, Toshikatsu; Ura, Takashi; Matsushita, Hisayuki; Kojima, Takashi; Doki, Yuichiro; Kusaba, Hitoshi; Fujitani, Kazumasa; Taira, Koichi; Seki, Shiko; Nakamura, Tsutomu; Kitagawa, Yuko

2014-01-01

We carried out a phase I/II trial of adding 2-weekly docetaxel to cisplatin plus fluorouracil (CF) therapy (2-weekly DCF regimen) in esophageal cancer patients to investigate its safety and antimetastatic activity. Patients received 2-weekly docetaxel (30 mg/m2 [dose level (DL)1] or 40 mg/m2 [DL2] with a 3 + 3 design in phase I, on days 1 and 15) in combination with fixed-dose CF (80 mg/m2 cisplatin, day 1; 800 mg/m2 fluorouracil, days 1–5) repeated every 4 weeks. The primary endpoint was dose-limiting toxicity (DLT) in phase I and central peer review-based response rate in phase II. At least 22 responders among 50 patients were required to satisfy the primary endpoint with a threshold of 35%. Sixty-two patients were enrolled in phase I and II. In phase I, 10 patients were enrolled with DLT of 0/3 at DL1 and 2/7 in DL2. Considering DLT and treatment compliance, the recommended phase II dose was determined as DL1. In phase II, the response rate was 62% (P < 0.0001; 95% confidence interval, 48–75%); median overall survival and progression-free survival were 11.1 and 5.8 months, respectively. Common grade 3/4 adverse events were neutropenia (25%), anemia (36%), hyponatremia (29%), anorexia (24%), and nausea (11%). No febrile neutropenia was observed. Pneumonitis caused treatment-related death in one patient. The 2-weekly DCF regimen showed promising antimetastatic activity and tolerability. A phase III study comparing this regimen with CF therapy is planned by the Japan Clinical Oncology Group. This study was registered at the UMIN Clinical Trials Registry as UMIN 000001737. PMID:25041052

Decreased frequency and duration of tooth brushing is a risk factor for endothelial dysfunction.

PubMed

Matsui, Shogo; Kajikawa, Masato; Maruhashi, Tatsuya; Iwamoto, Yumiko; Iwamoto, Akimichi; Oda, Nozomu; Kishimoto, Shinji; Hidaka, Takayuki; Kihara, Yasuki; Chayama, Kazuaki; Goto, Chikara; Aibara, Yoshiki; Nakashima, Ayumu; Noma, Kensuke; Taguchi, Akira; Higashi, Yukihito

2017-08-15

Periodontal disease is associated with endothelial dysfunction, leading to cardiovascular disease. The effect of detailed tooth brushing behavior, not only frequency but also duration of tooth brushing, on endothelial function is unclear. The purpose of this study was to evaluate the relationships of detailed methods of tooth brushing with vascular function. We evaluated flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation, and frequency and duration of tooth brushing in 896 subjects. We divided the subjects into three groups according to the frequency and duration of tooth brushing: low frequency and short duration group (

The synchronized trial on expectant mothers with depressive symptoms by omega-3 PUFAs (SYNCHRO): Study protocol for a randomized controlled trial.

PubMed

Nishi, Daisuke; Su, Kuan-Pin; Usuda, Kentaro; Chiang, Yi-Ju Jill; Guu, Tai-Wei; Hamazaki, Kei; Nakaya, Naoki; Sone, Toshimasa; Sano, Yo; Tachibana, Yoshiyuki; Ito, Hiroe; Isaka, Keiich; Hashimoto, Kenji; Hamazaki, Tomohito; Matsuoka, Yutaka J

2016-09-15

Maternal depression can be harmful to both mothers and their children. Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been investigated as an alternative intervention for pregnant women with depressive symptoms because of the supporting evidence from clinical trials in major depression, the safety advantage, and its anti-inflammatory and neuroplasticity effects. This study examines the efficacy of omega-3 PUFA supplementation for pregnant women with depressive symptoms in Taiwan and Japan, to provide evidence available for Asia. The rationale and protocol of this trial are reported here. The Synchronized Trial on Expectant Mothers with Depressive Symptoms by Omega-3 PUFAs (SYNCHRO) is a multicenter, double-blind, parallel group, randomized controlled trial. Participants will be randomized to either the omega-3 PUFAs arm (1,200 mg eicosapentaenoic acid and 600 mg docosahexaenoic acid daily) or placebo arm. Primary outcome is total score on the Hamilton Rating Scale for Depression (HAMD) at 12 weeks after the start of the intervention. We will randomize 56 participants to have 90 % power to detect a 4.7-point difference in mean HAMD scores with omega-3 PUFAs compared with placebo. Because seafood consumption varies across countries and this may have a major effect on the efficacy of omega-3 PUFA supplementation, 56 participants will be recruited at each site in Taiwan and Japan, for a total number of 112 participants. Secondary outcomes include depressive symptoms at 1 month after childbirth, diagnosis of major depressive disorder, changes in omega-3 PUFAs concentrations and levels of biomarkers at baseline and at 12 weeks' follow-up, and standard obstetric outcomes. Data analyses will be by intention to treat. The trial was started in June 2014 and is scheduled to end in February 2018. The trial is expected to provide evidence that can contribute to promoting mental health among mothers and children in Asian populations. Clinicaltrials.gov: NCT02166424 . Registered 15 June 2014; University Hospital Medical Information Network (UMIN) Center: UMIN000017979. Registered 20 May 2015.

Participants' understanding of a randomized controlled trial (RCT) through informed consent procedures in the RCT for breast cancer screening, J-START.

PubMed

Shiono, Yoko Narikawa; Zheng, Ying-Fang; Kikuya, Masahiro; Kawai, Masaaki; Ishida, Takanori; Kuriyama, Shinichi; Ohuchi, Noriaki

2014-09-25

It is often difficult to enrol healthy volunteers into a randomized controlled trial (RCT) as there are barriers to participants' proper understanding of a trial. This study aimed to evaluate degrees of understanding of the informed consent (IC) process among healthy volunteers who participated in an RCT. Additionally, factors associated with degree of understanding were investigated. The J-START (the Japan STrategic Anti-cancer Randomized controlled Trial) is an RCT investigating the effectiveness of ultrasonography screening for breast cancer in women aged 40 to 49 years. To evaluate participants' understanding of the J-START, we administered questionnaires to 376 Japanese women on the day of enrolment at five study sites across Japan. The respondents were asked to complete the anonymous questionnaire within 2 weeks. We assessed objective understanding and perceived subjective understanding of IC using a Japanese version of the Quality of Informed Consent scale (QuIC). Then we analyzed the characteristics of women whose understanding was poor, and clarified the association between providing information and their understanding of the study protocol. The average QuIC scores were 78.2 and 82.2 (out of 100 each) for objective and subjective understanding, respectively. These are generally acceptable scores for participants' understanding of an RCT. However, there were four domains with low scores, indicating poor understanding: (1) experimental nature of the study, (2) potential risks or discomfort, (3) benefit to self, and (4) compensation. Healthy volunteers generally well understood the J-START. Nevertheless, there were some domains in need of improvement. In order to facilitate participants' understanding, it is necessary to provide training to reduce differences in information-providing procedures between medical centres and to endeavour to provide consistent information and conditions. The J-START was registered with the University Hospital Medical Information Network Clinical Trial Registration (UMIN-CTR), Japan (registration number: UMIN000000757), on July 1, 2007.

Efficacy of Indigo Naturalis in a Multicenter Randomized Controlled Trial of Patients With Ulcerative Colitis.

PubMed

Naganuma, Makoto; Sugimoto, Shinya; Mitsuyama, Keiichi; Kobayashi, Taku; Yoshimura, Naoki; Ohi, Hidehisa; Tanaka, Shinji; Andoh, Akira; Ohmiya, Naoki; Saigusa, Keiichiro; Yamamoto, Takayuki; Morohoshi, Yuichi; Ichikawa, Hitoshi; Matsuoka, Katsuyoshi; Hisamatsu, Tadakazu; Watanabe, Kenji; Mizuno, Shinta; Suda, Wataru; Hattori, Masahira; Fukuda, Shinji; Hirayama, Akiyoshi; Abe, Takayuki; Watanabe, Mamoru; Hibi, Toshifumi; Suzuki, Yasuo; Kanai, Takanori

2018-03-01

Indigo naturalis (IN) is a traditional Chinese medicine that contains ligands for the aryl hydrocarbon receptor and promotes regeneration of the mucosa by inducing production of interleukin 22. IN might induce mucosal healing in patients with ulcerative colitis (UC). We performed a randomized controlled trial to investigate the safety and efficacy of IN in patients with UC. We performed a multicenter, double-blind trial evaluating the safety of 86 patients in Japan with active UC (Mayo scores of 6 or more), enrolled from March 30 through December 27, 2016. Patients were randomly assigned to groups and given a daily dose of 0.5, 1.0, or 2.0 g IN or placebo (1:1:1:1 ratio) for 8 weeks. The primary endpoint was the rate of clinical response at week 8, defined as a 3-point decrease in the Mayo score and a decrease of at least 30% from baseline, with a decrease of at least 1 point for the rectal bleeding subscore or absolute rectal bleeding score of 0-1. The main secondary endpoint was the rate of clinical remission at week 8, defined as a Mayo score or ≤2 and no subscores with a value >1. Mucosal healing was also assessed at week 8. The trial was terminated because of an external reason: a report of pulmonary arterial hypertension in a patient who used self-purchased IN for 6 months. In the intent-to-treat analysis, we observed a significant, dose-dependent linear trend in proportions of patients with clinical responses (13.6% with a clinical response to placebo; 69.6% to 0.5 g IN; 75.0% to 1.0 g IN; and 81.0% to 2.0 g IN) (Cochran-Armitage trend test P < .0001 compared with placebo). Proportions of patients in clinical remission at week 8 were significantly higher in the 1.0 g IN group (55.0%, P = .0004) and the 2.0 g IN group (38.1%, (P = .0093) than in the placebo group (4.5%). Proportions of patients with mucosal healing were 13.6% in the placebo group, 56.5% in the 0.5 g IN group, 60.0% in the 1.0 g IN group, and 47.6% in the 2.0 g IN group (P = .0278 compared with placebo). Although mild liver dysfunction was observed in 10 patients who received IN, no serious adverse events were observed. In a randomized, placebo-controlled trial, we found 8 weeks of IN (0.5-2.0 g per day) to be effective in inducing a clinical response in patients with UC. However, IN should not yet be used because of the potential for adverse effects, including pulmonary arterial hypertension. Clinical Trials Registry no: UMIN000021439 (http://www.umin.ac.jp/ctr/). Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Effects of a Gentle, Self-Administered Stimulation of Perineal Skin for Nocturia in Elderly Women: A Randomized, Placebo-Controlled, Double-Blind Crossover Trial

PubMed Central

Iimura, Kaori; Watanabe, Nobuhiro; Masunaga, Koichi; Miyazaki, Shogo; Hotta, Harumi; Kim, Hunkyung; Hisajima, Tatsuya; Takahashi, Hidenori; Kasuya, Yutaka

2016-01-01

Background Somatic afferent nerve stimuli are used for treating an overactive bladder (OAB), a major cause of nocturia in the elderly. Clinical evidence for this treatment is insufficient because of the lack of appropriate control stimuli. Recent studies on anesthetized animals show that gentle stimuli applied to perineal skin with a roller could inhibit micturition contractions depending on the roller’s surface material. We examined the efficacy of gentle skin stimuli for treating nocturia. Methods The study was a cross-over, placebo-controlled, double-blind randomized clinical study using two rollers with different effects on micturition contractions. Participants were elderly women (79–89 years) with nocturia. Active (soft elastomer roller) or placebo (hard polystyrene roller) stimuli were applied to perineal skin by participants for 1 min at bedtime. A 3-day baseline assessment period was followed by 3-day stimulation and 4-day resting periods, after which the participants were subjected to other stimuli for another 3 days. The primary outcome was change in the frequency of nighttime urination, for which charts were maintained during each 3-day period. Results Twenty-four participants were randomized, of which 22 completed all study protocols. One participant discontinued treatment because of an adverse event (abdominal discomfort). In participants with OAB (n = 9), change from baseline in the mean frequency of urination per night during the active stimuli period (mean ± standard deviation, −0.74 ± 0.7 times) was significantly greater than that during placebo stimuli periods (−0.15 ± 0.8 times [p < 0.05]). In contrast, this difference was not observed in participants without OAB (n = 13). Conclusions These results suggest that gentle perineal stimulation with an elastomer roller is effective for treating OAB-associated nocturia in elderly women. Here the limitation was a study period too short to assess changes in the quality of sleep and life. Trial Registration UMIN Clinical Trial Registry (CTR) UMIN000015809 PMID:27003163

The neuromuscular effects of rocuronium under sevoflurane-remifentanil or propofol-remifentanil anesthesia: a randomized clinical comparative study in an Asian population.

PubMed

Lee, Sangseok; Ro, Young Jin; Koh, Won Uk; Nishiyama, Tomoki; Yang, Hong-Seuk

2016-08-22

We conducted a prospective, randomized, multicenter study to evaluate the differences in the blocking effect of different doses of rocuronium between sevoflurane- or propofol-remifentanil anesthesia in an Asian population. A total of 368 ASA I-II patients was enrolled. Anesthesia was induced with 2.0 mg/kg propofol and 0.1 μg/kg/min remifentanil (TIVA) or 5.0 vol.% sevoflurane with 0.1 μg/kg/min remifentanil (SEVO). Tracheal intubation was facilitated at 180 s after the administration of rocuronium at 0.3, 0.6, or 0.9 mg/kg and then intubation condition was evaluated. The time to maximum block and recovery profile were monitored by TOF stimulation of the ulnar nerve and by recording the adductor pollicis response using acceleromyography. The numbers of patients with clinically acceptable intubation conditions were 41, 82, and 97 % (TIVA) and 34, 85, and 90 % (SEVO) at each dose of rocuronium, respectively. There were no significant differences in the time to maximum block between groups at each rocuronium dose. There were significant differences in the recovery to a train-of-four ratio of 90 % between the groups: 42.7 (19.5), 74.8 (29.9), and 118.4 (35.1) min (TIVA) and 66.5 (39.3), 110.2 (43.5), and 144.4 (57.5) min (SEVO) at 0.3, 0.6, and 0.9 mg/kg, respectively (P < 0.001). There are no significant differences in intubation conditions between propofol-remifentanil and sevoflurane-remifentanil anesthesia at the same dose of rocuronium. The type of anesthetic does not significantly influence the time to maximum block by rocuronium. Rocuronium at a dose of 0.9 mg/kg should be used for better intubation conditions with both anesthesia regimens in an Asian population. UMIN-CTR Clinical Trial ( http://www.umin.ac.jp/ctr/index.htm ; UMIN#000007289 ; date of registration 14(th) February 2012).

A new mother-child play activity program to decrease parenting stress and improve child cognitive abilities: a cluster randomized controlled trial.

PubMed

Tachibana, Yoshiyuki; Fukushima, Ai; Saito, Hitomi; Yoneyama, Satoshi; Ushida, Kazuo; Yoneyama, Susumu; Kawashima, Ryuta

2012-01-01

We propose a new play activity intervention program for mothers and children. Our interdisciplinary program integrates four fields of child-related sciences: neuroscience, preschool pedagogy, developmental psychology, and child and maternal psychiatry. To determine the effect of this intervention on child and mother psychosocial problems related to parenting stress and on the children's cognitive abilities, we performed a cluster randomized controlled trial. Participants were 238 pairs of mothers and typically developing preschool children (ages 4-6 years old) from Wakakusa kindergarten in Japan. The pairs were asked to play at home for about 10 min a day, 5 days a week for 3 months. Participants were randomly assigned to the intervention or control group by class unit. The Parenting Stress Index (PSI) (for mothers), the Goodenough Draw-a-Man intelligence test (DAM), and the new S-S intelligence test (NS-SIT) (for children) were administered prior to and 3 months after the intervention period. Pre-post changes in test scores were compared between the groups using a linear mixed-effects model analysis. The primary outcomes were the Total score on the child domain of the PSI (for child psychosocial problems related to parenting stress), Total score on the parent domain of the PSI (for maternal psychosocial problems related to parenting stress), and the score on the DAM (for child cognitive abilities). The results of the PSI suggested that the program may reduce parenting stress. The results of the cognitive tests suggested that the program may improve the children's fluid intelligence, working memory, and processing speed. Our intervention program may ameliorate the children's psychosocial problems related to parenting stress and increase their cognitive abilities. UMIN Clinical Trials Registry UMIN000002265.

Effects of an Internet-based cognitive behavioral therapy (iCBT) program in Manga format on improving subthreshold depressive symptoms among healthy workers: a randomized controlled trial.

PubMed

Imamura, Kotaro; Kawakami, Norito; Furukawa, Toshi A; Matsuyama, Yutaka; Shimazu, Akihito; Umanodan, Rino; Kawakami, Sonoko; Kasai, Kiyoto

2014-01-01

The purpose of this study was to develop a new Internet-based computerized cognitive behavior therapy (iCBT) program in Manga format, the Japanese cartoon, for workers and to examine the effects of the iCBT program on improving subthreshold depression using a randomized controlled trial (RCT) design among workers employed in private companies in Japan. All workers in a company (n = 290) and all workers in three departments (n = 1,500) at the headquarters of another large company were recruited by an invitation e-mail. Participants who fulfilled the inclusion criteria were randomly allocated to intervention or control groups (N = 381 for each group). A six-week, six-lesson iCBT program using Manga (Japanese comic) story was developed. The program included several CBT skills: self-monitoring, cognitive restructuring, assertiveness, problem solving, and relaxation. The intervention group studied the iCBT program at a frequency of one lesson per week. Depression (Beck Depression Inventory II; BDI-II) was assessed as a primary outcome at baseline, and three- and six-month follow-ups for both intervention and control groups were performed. The iCBT program showed a significant intervention effect on BDI-II (t = -1.99, p<0.05) with small effect sizes (Cohen's d: -0.16, 95% Confidence Interval: -0.32 to 0.00, at six-month follow-up). The present study first demonstrated that a computerized cognitive behavior therapy delivered via the Internet was effective in improving depression in the general working population. It seems critical to improve program involvement of participants in order to enhance the effect size of an iCBT program. UMIN Clinical Trials Registry UMIN000006210.

Effects of a Gentle, Self-Administered Stimulation of Perineal Skin for Nocturia in Elderly Women: A Randomized, Placebo-Controlled, Double-Blind Crossover Trial.

PubMed

Iimura, Kaori; Watanabe, Nobuhiro; Masunaga, Koichi; Miyazaki, Shogo; Hotta, Harumi; Kim, Hunkyung; Hisajima, Tatsuya; Takahashi, Hidenori; Kasuya, Yutaka

2016-01-01

Somatic afferent nerve stimuli are used for treating an overactive bladder (OAB), a major cause of nocturia in the elderly. Clinical evidence for this treatment is insufficient because of the lack of appropriate control stimuli. Recent studies on anesthetized animals show that gentle stimuli applied to perineal skin with a roller could inhibit micturition contractions depending on the roller's surface material. We examined the efficacy of gentle skin stimuli for treating nocturia. The study was a cross-over, placebo-controlled, double-blind randomized clinical study using two rollers with different effects on micturition contractions. Participants were elderly women (79-89 years) with nocturia. Active (soft elastomer roller) or placebo (hard polystyrene roller) stimuli were applied to perineal skin by participants for 1 min at bedtime. A 3-day baseline assessment period was followed by 3-day stimulation and 4-day resting periods, after which the participants were subjected to other stimuli for another 3 days. The primary outcome was change in the frequency of nighttime urination, for which charts were maintained during each 3-day period. Twenty-four participants were randomized, of which 22 completed all study protocols. One participant discontinued treatment because of an adverse event (abdominal discomfort). In participants with OAB (n = 9), change from baseline in the mean frequency of urination per night during the active stimuli period (mean ± standard deviation, -0.74 ± 0.7 times) was significantly greater than that during placebo stimuli periods (-0.15 ± 0.8 times [p < 0.05]). In contrast, this difference was not observed in participants without OAB (n = 13). These results suggest that gentle perineal stimulation with an elastomer roller is effective for treating OAB-associated nocturia in elderly women. Here the limitation was a study period too short to assess changes in the quality of sleep and life. UMIN Clinical Trial Registry (CTR) UMIN000015809.

The effects of physical exercise with music on cognitive function of elderly people: Mihama-Kiho project.

PubMed

Satoh, Masayuki; Ogawa, Jun-ichi; Tokita, Tomoko; Nakaguchi, Noriko; Nakao, Koji; Kida, Hirotaka; Tomimoto, Hidekazu

2014-01-01

Physical exercise has positive effects on cognitive function in elderly people. It is unknown, however, if combinations of non-pharmaceutical interventions can produce more benefits than single ones. This study aimed to identify if physical exercise combined with music improves cognitive function in normal elderly people more than exercise alone. We enrolled 119 subjects (age 65-84 years old). Forty subjects performed physical exercise (once a week for an hour with professional trainers) with musical accompaniment (ExM group), developed by YAMAHA Music Foundation; 40 subjects performed the same exercise without music (Ex group); 39 subjects were the control group (Cont group). Before and after the year-long intervention, each patient was assessed by neuropsychological batteries. MRIs were performed before and after intervention; the Voxel-based Specific Regional analysis system for Alzheimer's Disease (VSRAD) was used to assess medial temporal lobe atrophy. Analysis of variance (ANOVA) was significant only in visuospatial function. The multiple comparison (ExM vs. Ex, ExM vs. Cont, Ex vs. Cont) was significant between the ExM and Cont group. Intra-group analyses before and after intervention revealed significant improvement in visuospatial function in the ExM group, and significant improvements in other batteries in all three groups. The VSRAD score significantly worsened in the ExM and Ex groups. Physical exercise combined with music produced more positive effects on cognitive function in elderly people than exercise alone. We attributed this improvement to the multifaceted nature of combining physical exercise with music, which can act simultaneously as both cognitive and physical training. UMIN Clinical Trials Registry (UMIN-CTR) UMIN000012148.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roy, Sumit; Laerum, Frode; Brosstad, Frank

Purpose: To develop an animal model of acute deep vein thrombosis (DVT). Methods: In part I of the study nine juvenile domestic pigs were used. Each external iliac vein was transluminally occluded with a balloon catheter. Thrombin was infused through a microcatheter in one leg according to one of the following protocols: (1) intraarterial (IA): 1250 U at 25 U/min in the common femoral artery (n= 3); (2) intravenous (IV): 5000 U in the popliteal vein at 500 U/min (n= 3), or at 100 U/min (n= 3). Saline was administered in the opposite leg. After the animals were killed, themore » mass of thrombus in the iliofemoral veins was measured. The pudendoepiploic (PEV), profunda femoris (PF), and popliteal veins (PV) were examined. Thrombosis in the tributaries of the superficial femoral vein (SFVt) was graded according to a three-point scale (0, +, ++). In part II of the study IV administration was further investigated in nine pigs using the following three regimens with 1000 U at 25 U/min serving as the control: (1) 1000 U at 100 U/min, (2) 250 U at 25 U/min, (3) 250 U at 6.25 U/min. Results: All animals survived. In part I median thrombus mass in the test limbs was 1.40 g as compared with 0.25 g in the controls (p= 0.01). PEV, PFV and PV were thrombosed in all limbs infused with thrombin. IV infusion was more effective in inducing thrombosis in both the parent veins (mass 1.32-1.78 g) and SVFt (++ in 4 of 6 legs), as compared with IA infusion (mass 0.0-1.16 g; SFVt ++ in 1 of 3 legs). In part II thrombus mass in axial veins ranged from 1.23 to 2.86 g, and showed no relationship with the dose of thrombin or the rate of infusion. Tributary thrombosis was less extensive with 250 U at 25 U/min than with the other regimens. Conclusion: Slow distal intravenous thrombin infusion in the hind legs of pigs combined with proximal venous occlusion induces thrombosis in the leg veins that closely resembles clinical DVT in distribution.« less

Transdiagnostic and Transcultural: Pilot Study of Unified Protocol for Depressive and Anxiety Disorders in Japan.

PubMed

Ito, Masaya; Horikoshi, Masaru; Kato, Noriko; Oe, Yuki; Fujisato, Hiroko; Nakajima, Shun; Kanie, Ayako; Miyamae, Mitsuhiro; Takebayashi, Yoshitake; Horita, Ryo; Usuki, Masato; Nakagawa, Atsuo; Ono, Yutaka

2016-05-01

Unified protocol (UP) is a transdiagnostic cognitive behavior therapy for emotional disorders. It remains unknown whether UP is applicable for use in non-Western countries and for depressive disorders. We therefore examined its feasibility for a Japanese clinical population using this clinical trial design, which is multicentered, open-labeled, and single-armed (Clinical registry: UMIN000008322). The primary outcome was severity of anxiety symptoms, as assessed using Structured Interview Guide for the Hamilton Anxiety Rating Scale. Secondary outcomes were depressive symptoms, clinical global impression, functioning, quality of life, affectivity, emotion regulation, and adverse events. Of the 28 prospective participants, 17 were eligible and enrolled (depressive disorders=9, anxiety disorders=8). Severity of anxiety symptoms, which decreased significantly after the intervention, remained low for 3months (Hedges' g=1.29, 95% CI=0.56-2.06). Similar tendencies were observed for secondary outcome measures. No severe adverse event occurred. Two participants dropped out of the intervention. High treatment adherence and interrater reliability were confirmed. Results suggest the feasibility of UP in the Japanese context sufficient to warrant a larger clinical trial. Copyright © 2016. Published by Elsevier Ltd.

Effects of 6-month eicosapentaenoic acid treatment on postprandial hyperglycemia, hyperlipidemia, insulin secretion ability, and concomitant endothelial dysfunction among newly-diagnosed impaired glucose metabolism patients with coronary artery disease. An open label, single blinded, prospective randomized controlled trial.

PubMed

Sawada, Takahiro; Tsubata, Hideo; Hashimoto, Naoko; Takabe, Michinori; Miyata, Taishi; Aoki, Kosuke; Yamashita, Soichiro; Oishi, Shogo; Osue, Tsuyoshi; Yokoi, Kiminobu; Tsukishiro, Yasue; Onishi, Tetsuari; Shimane, Akira; Taniguchi, Yasuyo; Yasaka, Yoshinori; Ohara, Takeshi; Kawai, Hiroya; Yokoyama, Mitsuhiro

2016-08-26

Recent experimental studies have revealed that n-3 fatty acids, such as eicosapentaenoic acid (EPA) regulate postprandial insulin secretion, and correct postprandial glucose and lipid abnormalities. However, the effects of 6-month EPA treatment on postprandial hyperglycemia and hyperlipidemia, insulin secretion, and concomitant endothelial dysfunction remain unknown in patients with impaired glucose metabolism (IGM) and coronary artery disease (CAD). We randomized 107 newly diagnosed IGM patients with CAD to receive either 1800 mg/day of EPA (EPA group, n = 53) or no EPA (n = 54). Cookie meal testing (carbohydrates: 75 g, fat: 28.5 g) and endothelial function testing using fasting-state flow-mediated dilatation (FMD) were performed before and after 6 months of treatment. The primary outcome of this study was changes in postprandial glycemic and triglyceridemic control and secondary outcomes were improvement of insulin secretion and endothelial dysfunction. After 6 months, the EPA group exhibited significant improvements in EPA/arachidonic acid, fasting triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). The EPA group also exhibited significant decreases in the incremental TG peak, area under the curve (AUC) for postprandial TG, incremental glucose peak, AUC for postprandial glucose, and improvements in glycometabolism categorization. No significant changes were observed for hemoglobin A1c and fasting plasma glucose levels. The EPA group exhibited a significant increase in AUC-immune reactive insulin/AUC-plasma glucose ratio (which indicates postprandial insulin secretory ability) and significant improvements in FMD. Multiple regression analysis revealed that decreases in the TG/HDL-C ratio and incremental TG peak were independent predictors of FMD improvement in the EPA group. EPA corrected postprandial hypertriglyceridemia, hyperglycemia and insulin secretion ability. This amelioration of several metabolic abnormalities was accompanied by recovery of concomitant endothelial dysfunction in newly diagnosed IGM patients with CAD. Clinical Trial Registration UMIN Registry number: UMIN000011265 ( https://www.upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000013200&language=E ).

The patient general satisfaction of mandibular single-implant overdentures and conventional complete dentures: Study protocol for a randomized crossover trial.

PubMed

Kanazawa, Manabu; Tanoue, Mariko; Miyayasu, Anna; Takeshita, Shin; Sato, Daisuke; Asami, Mari; Lam, Thuy Vo; Thu, Khaing Myat; Oda, Ken; Komagamine, Yuriko; Minakuchi, Shunsuke; Feine, Jocelyne

2018-05-01

Mandibular overdentures retained by a single implant placed in the midline of edentulous mandible have been reported to be more comfortable and function better than complete dentures. Although single-implant overdentures are still more costly than conventional complete dentures, there are a few studies which investigated whether mandibular single-implant overdentures are superior to complete dentures when patient general satisfaction is compared. The aim of this study is to assess patient general satisfaction with mandibular single-implant overdentures and complete dentures. This study is a randomized crossover trial to compare mandibular single-implant overdentures and complete dentures in edentulous individuals. Participant recruitment is ongoing at the time of this submission. Twenty-two participants will be recruited. New mandibular complete dentures will be fabricated. A single implant will be placed in the midline of the edentulous mandible. The mucosal surface of the complete denture around the implant will be relieved for 3 months. The participants will then be randomly allocated into 2 groups according to the order of the interventions; group 1 will receive single-implant overdentures first and will wear them for 2 months, followed by complete dentures for 2 months. Group 2 will receive the same treatments in a reverse order. After experiencing the 2 interventions, the participants will choose one of the mandibular prostheses, and yearly follow-up visits are planned for 5 years. The primary outcome of this trial is patient ratings of general satisfaction on 100 mm visual analog scales. Assessments of the prostheses and oral health-related quality of life will also be recorded as patient-reported outcomes. The secondary outcomes are cost and time for treatment. Masticatory efficiency and cognitive capacity will also be recorded. Furthermore, qualitative research will be performed to investigate the factors associated with success of these mandibular denture types. Clinical outcomes, such as implant survival rate, marginal bone loss, and prosthodontic complications, will also be recorded. The results of this randomized crossover trial will clarify whether mandibular single implants and overdentures for edentulous individuals provide better patient general satisfaction when compared to conventional complete dentures. This clinical trial was registered at the University Hospital Medical Information Network (UMIN) Center (UMIN000017883).

Effect of eicosapentaenoic acid/docosahexaenoic acid on coronary high-intensity plaques detected with non-contrast T1-weighted imaging (the AQUAMARINE EPA/DHA study): study protocol for a randomized controlled trial.

PubMed

Nakao, Kazuhiro; Noguchi, Teruo; Asaumi, Yasuhide; Morita, Yoshiaki; Kanaya, Tomoaki; Fujino, Masashi; Hosoda, Hayato; Yoneda, Shuichi; Kawakami, Shoji; Nagai, Toshiyuki; Nishihira, Kensaku; Nakashima, Takahiro; Kumasaka, Reon; Arakawa, Tetsuo; Otsuka, Fumiyuki; Nakanishi, Michio; Kataoka, Yu; Tahara, Yoshio; Goto, Yoichi; Yamamoto, Haruko; Hamasaki, Toshimitsu; Yasuda, Satoshi

2018-01-08

Despite the success of HMG-CoA reductase inhibitor (statin) therapy in reducing atherosclerotic cardiovascular events, a residual risk for cardiovascular events in patients with coronary artery disease (CAD) remains. Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are promising anti-atherosclerosis agents that might reduce the residual CAD risk. Non-contrast T1-weighted imaging (T1WI) with cardiac magnetic resonance (CMR) less invasively identifies high-risk coronary plaques as high-intensity signals. These high-intensity plaques (HIPs) are quantitatively assessed using the plaque-to-myocardium signal intensity ratio (PMR). Our goal is to assess the effect of EPA/DHA on coronary HIPs detected with T1WI in patients with CAD on statin treatment. This prospective, controlled, randomized, open-label study examines the effect of 12 months of EPA/DHA therapy and statin treatment on PMR of HIPs detected with CMR and computed tomography angiography (CTA) in patients with CAD. The primary endpoint is the change in PMR after EPA/DHA treatment. Secondary endpoints include changes in Hounsfield units, plaque volume, vessel area, and plaque area measured using CTA. Subjects are randomly assigned to either of three groups: the 2 g/day EPA/DHA group, the 4 g/day EPA/DHA group, or the no-treatment group. This trial will help assess whether EPA/DHA has an anti-atherosclerotic effect using PMR of HIPs detected by CMR. The trial outcomes will provide novel insights into the effect of EPA/DHA on high-risk coronary plaques and may provide new strategies for lowering the residual risk in patients with CAD on statin therapy. The University Hospital Medical Information Network (UMIN) Clinical Trials Registry, ID: UMIN000015316 . Registered on 2 October 2014.

Effects of an Internet-Based Cognitive Behavioral Therapy (iCBT) Program in Manga Format on Improving Subthreshold Depressive Symptoms among Healthy Workers: A Randomized Controlled Trial

PubMed Central

Imamura, Kotaro; Kawakami, Norito; Furukawa, Toshi A.; Matsuyama, Yutaka; Shimazu, Akihito; Umanodan, Rino; Kawakami, Sonoko; Kasai, Kiyoto

2014-01-01

Objective The purpose of this study was to develop a new Internet-based computerized cognitive behavior therapy (iCBT) program in Manga format, the Japanese cartoon, for workers and to examine the effects of the iCBT program on improving subthreshold depression using a randomized controlled trial (RCT) design among workers employed in private companies in Japan. Method All workers in a company (n = 290) and all workers in three departments (n = 1,500) at the headquarters of another large company were recruited by an invitation e-mail. Participants who fulfilled the inclusion criteria were randomly allocated to intervention or control groups (N = 381 for each group). A six-week, six-lesson iCBT program using Manga (Japanese comic) story was developed. The program included several CBT skills: self-monitoring, cognitive restructuring, assertiveness, problem solving, and relaxation. The intervention group studied the iCBT program at a frequency of one lesson per week. Depression (Beck Depression Inventory II; BDI-II) was assessed as a primary outcome at baseline, and three- and six-month follow-ups for both intervention and control groups were performed. Results The iCBT program showed a significant intervention effect on BDI-II (t = −1.99, p<0.05) with small effect sizes (Cohen's d: −0.16, 95% Confidence Interval: −0.32 to 0.00, at six-month follow-up). Conclusions The present study first demonstrated that a computerized cognitive behavior therapy delivered via the Internet was effective in improving depression in the general working population. It seems critical to improve program involvement of participants in order to enhance the effect size of an iCBT program. Trial Registration UMIN Clinical Trials Registry UMIN000006210 PMID:24844530

Effect of magnesium added to local anesthetics for caudal anesthesia on postoperative pain in pediatric surgical patients: A systematic review and meta-analysis with Trial Sequential Analysis.

PubMed

Kawakami, Hiromasa; Mihara, Takahiro; Nakamura, Nobuhito; Ka, Koui; Goto, Takahisa

2018-01-01

Magnesium has been investigated as an adjuvant for neuraxial anesthesia, but the effect of caudal magnesium on postoperative pain is inconsistent. The aim of this systematic review and meta-analysis was to evaluate the analgesic effect of caudal magnesium. We searched six databases, including trial registration sites. Randomized clinical trials reporting the effect of caudal magnesium on postoperative pain after general anesthesia were eligible. The risk ratio for use of rescue analgesics after surgery was combined using a random-effects model. We also assessed adverse events. The I2 statistic was used to assess heterogeneity. We assessed risk of bias with Cochrane domains. We controlled type I and II errors due to sparse data and repetitive testing with Trial Sequential Analysis. We assessed the quality of evidence with GRADE. Four randomized controlled trials (247 patients) evaluated the need for rescue analgesics. In all four trials, 50 mg of magnesium was administered with caudal ropivacaine. The results suggested that the need for rescue analgesia was reduced significantly by caudal magnesium administration (risk ratio 0.45; 95% confidence interval 0.24-0.86). There was considerable heterogeneity as indicated by an I2 value of 62.5%. The Trial Sequential Analysis-adjusted confidence interval was 0.04-5.55, indicating that further trials are required. The quality of evidence was very low. The rate of adverse events was comparable between treatment groups. Caudal magnesium may reduce the need for rescue analgesia after surgery, but further randomized clinical trials with a low risk of bias and a low risk of random errors are necessary to assess the effect of caudal magnesium on postoperative pain and adverse events. University Hospital Medical Information Network Clinical Trials Registry UMIN000025344.

Treatment using oxaliplatin and S-1 adjuvant chemotherapy for pathological stage III gastric cancer: a multicenter phase II study (TOSA trial) protocol.

PubMed

Namikawa, Tsutomu; Maeda, Hiromichi; Kitagawa, Hiroyuki; Oba, Koji; Tsuji, Akihito; Yoshikawa, Takaki; Kobayashi, Michiya; Hanazaki, Kazuhiro

2018-02-13

Recent studies demonstrated the efficacy of S-1-based adjuvant chemotherapy administered for six months after curative surgery for stage III gastric cancer; however, it is unproven whether this type of combination chemotherapy is more effective than the standard adjuvant chemotherapy of S-1 for one year. This multicenter phase II study evaluate the efficacy and safety of adjuvant chemotherapy using S-1 plus oxaliplatin followed by S-1 for up to one year for curatively resected stage III gastric cancer in patients aged over 20 years. Treatment initially comprises oral fluoropyrimidine S-1 (80 mg/m 2 ) administered twice daily for the first 2 weeks of a 3-week cycle. On day 1 of a second 3-week cycle, patients will receive 100 mg/m 2 of intravenous oxaliplatin followed by 80 mg/m 2 of S-1 (maximum 8 cycles). Then, the patients will receive 80 mg/m 2 of S-1 daily for 4 weeks, followed by 2 weeks of no chemotherapy. This 6-week cycle will be repeated during the first year after surgery. The primary endpoint is relapse-free survival for 3 years and secondary endpoints are safety, including the incidence of adverse events, and grading of neuropathy with each treatment cycle. The planned sample size of 75 patients is appropriate for this trial. The data will be analyzed on an intention-to-treat basis, assuming a two-sided test with a 5% level of significance. In contrast to previous trials, the current study involves administration of S-1 until one year after surgery in addition to prior S-1 plus oxaliplatin, and is the first study to evaluate the safety and efficacy of S-1 plus oxaliplatin followed by S-1 for up to one year in patients with curatively resected stage III gastric cancer. This trial is registered in the University Hospital Medical Information Network's Clinical Trials Registry (UMIN-CTR) registration number, R000029656  ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000029656 ). Registered January 24, 2017.

Effectiveness and Cost-Effectiveness of Occupation-Based Occupational Therapy Using the Aid for Decision Making in Occupation Choice (ADOC) for Older Residents: Pilot Cluster Randomized Controlled Trial

PubMed Central

Nagayama, Hirofumi; Tomori, Kounosuke; Ohno, Kanta; Takahashi, Kayoko; Ogahara, Kakuya; Sawada, Tatsunori; Uezu, Sei; Nagatani, Ryutaro; Yamauchi, Keita

2016-01-01

Background Care-home residents are mostly inactive, have little interaction with staff, and are dependent on staff to engage in daily occupations. We recently developed an iPad application called the Aid for Decision-making in Occupation Choice (ADOC) to promote shared decision-making in activities and occupation-based goal setting by choosing from illustrations describing daily activities. This study aimed to evaluate if interventions based on occupation-based goal setting using the ADOC could focus on meaningful activities to improve quality of life and independent activities of daily living, with greater cost-effectiveness than an impairment-based approach as well as to evaluate the feasibility of conducting a large cluster, randomized controlled trial. Method In this single (assessor)-blind pilot cluster randomized controlled trial, the intervention group (ADOC group) received occupational therapy based on occupation-based goal setting using the ADOC, and the interventions were focused on meaningful occupations. The control group underwent an impairment-based approach focused on restoring capacities, without goal setting tools. In both groups, the 20-minute individualized intervention sessions were conducted twice a week for 4 months. Main Outcome Measures Short Form-36 (SF-36) score, SF-6D utility score, quality adjusted life years (QALY), Barthel Index, and total care cost. Results We randomized and analyzed 12 facilities (44 participants, 18.5% drop-out rate), with 6 facilities each allocated to the ADOC (n = 23) and control (n = 21) groups. After the 4-month intervention, the ADOC group had a significantly greater change in the BI score, with improved scores (P = 0.027, 95% CI 0.41 to 6.87, intracluster correlation coefficient = 0.14). No other outcome was significantly different. The incremental cost-effectiveness ratio, calculated using the change in BI score, was $63.1. Conclusion The results suggest that occupational therapy using the ADOC for older residents might be effective and cost-effective. We also found that conducting an RCT in the occupational therapy setting is feasible. Trial Registration UMIN Clinical Trials Registry UMIN000012994 PMID:26930191

Efficacy of deep rTMS for neuropathic pain in the lower limb: a randomized, double-blind crossover trial of an H-coil and figure-8 coil.

PubMed

Shimizu, Takeshi; Hosomi, Koichi; Maruo, Tomoyuki; Goto, Yuko; Yokoe, Masaru; Kageyama, Yu; Shimokawa, Toshio; Yoshimine, Toshiki; Saitoh, Youichi

2017-11-01

OBJECTIVE Electrical motor cortex stimulation can relieve neuropathic pain (NP), but its use requires patients to undergo an invasive procedure. Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) using a figure-8 coil can relieve NP noninvasively, but its ability to relieve lower limb pain is still limited. Deep rTMS using an H-coil can effectively stimulate deep brain regions and has been widely used for the treatment of various neurological diseases; however, there have been no clinical studies comparing the effectiveness of figure-8 coils and H-coils. This study assessed the clinical effectiveness of 5 once-daily stimulations with H-coils and figure-8 coils in patients with NP. METHODS This randomized, double-blind, 3-way crossover trial examined 18 patients with NP who sequentially received 3 types of stimulations in the M1 for 5 consecutive days; each 5-day stimulation period was followed by a 17-day follow-up period before crossing over to the next type of stimulation. During each rTMS session, patients received a 5-Hz rTMS to the M1 region corresponding to the painful lower limb. The visual analog scale (VAS) and the Japanese version of the short-form McGill Pain Questionnaire 2 (SF-MPQ2-J) were used to measure pain intensity. The primary outcome was VAS score reduction immediately after and 1 hour after intervention. RESULTS Both the VAS and SF-MPQ2-J showed significant pain improvement immediately after deep rTMS with an H-coil as compared with the sham group (p < 0.001 and p = 0.049, respectively). However, neither outcome measure showed significant pain improvement when using a figure-8 coil. The VAS also showed significant pain improvement 1 hour after deep rTMS with an H-coil (p = 0.004) but not 1 hour after rTMS using a figure-8 coil. None of the patients exhibited any serious adverse events. CONCLUSIONS The current findings suggest that the use of deep rTMS with an H-coil in the lower limb region of the M1 in patients with NP was tolerable and could provide significant short-term pain relief. Clinical trial registration no.: UMIN000010536 ( http://www.umin.ac.jp/ctr/ ).

Endothelial dysfunction, abnormal vascular structure and lower urinary tract symptoms in men and women.

PubMed

Matsui, Shogo; Kajikawa, Masato; Maruhashi, Tatsuya; Iwamoto, Yumiko; Oda, Nozomu; Kishimoto, Shinji; Hashimoto, Haruki; Hidaka, Takayuki; Kihara, Yasuki; Chayama, Kazuaki; Hida, Eisuke; Goto, Chikara; Aibara, Yoshiki; Nakashima, Ayumu; Yusoff, Farina Mohamad; Noma, Kensuke; Kuwahara, Yoshitaka; Matsubara, Akio; Higashi, Yukihito

2018-06-15

Lower urinary tract symptoms (LUTS) is not only common symptoms in elderly men and women but also risk of future cardiovascular events. The purpose of this study was to evaluate the relationships of vascular function and structure with LUTS in men and women. We investigated flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) as vascular function, brachial-ankle pulse wave velocity (baPWV) as vascular structure, and LUTS assessed by International Prostate Symptom Score (IPSS) in 287 men and 147 women. IPSS was significantly correlated with traditional cardiovascular risk factors, Framingham risk score, FMD, NID and baPWV. Moderate to severe LUTS was associated with the prevalence of coronary heart disease in men but not in women. In men, FMD and NID were significantly lower in the moderate to severe LUTS group than in the none to mild LUTS group (2.1 ± 2.0% vs. 4.0 ± 3.0% and 9.3 ± 6.1% vs. 12.8 ± 6.6%, P < 0.001, respectively). baPWV was significantly higher in the moderate to severe LUTS group than in the none to mild LUTS group (1722 ± 386 cm/s vs. 1509 ± 309 cm/s, P < 0.001). In multivariate analysis, FMD was independently associated with a decrease in the odds ratio of moderate to severe LUTS in men (OR: 0.83, 95% CI, 0.72-0.95; P = 0.008) but not in women. NID and baPWV were not independently associated with moderate to severe LUTS either in men or women. These findings suggest that endothelial dysfunction is associated with LUTS in men. LUTS in men may be useful for a predictor of cardiovascular events. URL for Clinical Trial: http://UMIN; Registration Number for Clinical Trial: UMIN000003409. Copyright © 2018 Elsevier B.V. All rights reserved.

Dose reduction of risperidone and olanzapine and estimated dopamine D₂ receptor occupancy in stable patients with schizophrenia: findings from an open-label, randomized, controlled study.

PubMed

Takeuchi, Hiroyoshi; Suzuki, Takefumi; Bies, Robert R; Remington, Gary; Watanabe, Koichiro; Mimura, Masaru; Uchida, Hiroyuki

2014-11-01

While acute-phase antipsychotic response has been attributed to 65%-80% dopamine D₂ receptor blockade, the degree of occupancy for relapse prevention in the maintenance treatment of schizophrenia remains unknown. In this secondary study of an open-label, 28-week, randomized, controlled trial conducted between April 2009 and August 2011, clinically stable patients with schizophrenia (DSM-IV) treated with risperidone or olanzapine were randomly assigned to the reduction group (dose reduced by 50%) or maintenance group (dose kept constant). Plasma antipsychotic concentrations at peak and trough before and after dose reduction were estimated with population pharmacokinetic techniques, using 2 collected plasma samples. Corresponding dopamine D₂ occupancy levels were then estimated using the model we developed. Relapse was defined as worsening in 4 Positive and Negative Syndrome Scale-Positive subscale items: delusion, conceptual disorganization, hallucinatory behavior, and suspiciousness. Plasma antipsychotic concentrations were available for 16 and 15 patients in the reduction and maintenance groups, respectively. Estimated dopamine D₂ occupancy (mean ± SD) decreased following dose reduction from 75.6% ± 4.9% to 66.8% ± 6.4% at peak and 72.3% ± 5.7% to 62.0% ± 6.8% at trough. In the reduction group, 10 patients (62.5%) did not demonstrate continuous D₂ receptor blockade above 65% (ie, < 65% at trough) after dose reduction; furthermore, 7 patients (43.8%) did not achieve a threshold of 65% occupancy even at peak. Nonetheless, only 1 patient met our relapse criteria after dose reduction during the 6 months of the study. The results suggest that the therapeutic threshold regarding dopamine D₂ occupancy may be lower for those who are stable in antipsychotic maintenance versus acute-phase treatment. Positron emission tomography studies are warranted to further test our preliminary findings. UMIN Clinical Trials Registry identifier: UMIN000001834. © Copyright 2014 Physicians Postgraduate Press, Inc.

Effect of Interpersonal Interaction on Festinating Gait Rehabilitation in Patients with Parkinson's Disease.

PubMed

Uchitomi, Hirotaka; Ogawa, Ken-Ichiro; Orimo, Satoshi; Wada, Yoshiaki; Miyake, Yoshihiro

2016-01-01

Although human walking gait rhythms are generated by native individual gait dynamics, these gait dynamics change during interactions between humans. A typical phenomenon is synchronization of gait rhythms during cooperative walking. Our previous research revealed that fluctuation characteristics in stride interval of subjects with Parkinson's disease changed from random to 1/f fluctuation as fractal characteristics during cooperative walking with the gait assist system Walk-Mate, which emulates a human interaction using interactive rhythmic cues. Moreover, gait dynamics were relearned through Walk-Mate gait training. However, the system's clinical efficacy was unclear because the previous studies did not focus on specific gait rhythm disorder symptoms. Therefore, this study aimed to evaluate the effect of Walk-Mate on festinating gait among subjects with Parkinson's disease. Three within-subject experimental conditions were used: (1) preinteraction condition, (2) interaction condition, and (3) postinteraction condition. The only difference between conditions was the interactive rhythmic cues generated by Walk-Mate. Because subjects with festinating gait gradually and involuntarily decreased their stride interval, the regression slope of stride interval as an index of severity of preinteraction festinating gait was elevated. The regression slope in the interaction condition was more gradual than during the preinteraction condition, indicating that the interactive rhythmic cues contributed to relieving festinating gait and stabilizing gait dynamics. Moreover, the gradual regression slope was carried over to the postinteraction condition, indicating that subjects with festinating gait have the potential to relearn stable gait dynamics. These results suggest that disordered gait dynamics are clinically restored through interactive rhythmic cues and that Walk-Mate may have the potential to assist therapists in more effective rehabilitation. UMIN Clinical Trials Registry UMIN000012591.

Study protocol for the G-SPIRIT trial: a randomised, placebo-controlled, double-blinded phase III trial of granulocyte colony-stimulating factor-mediated neuroprotection for acute spinal cord injury

PubMed Central

Koda, Masao; Hanaoka, Hideki; Sato, Takatoshi; Fujii, Yasuhisa; Hanawa, Michiko; Takahashi, Sho; Furuya, Takeo; Ijima, Yasushi; Saito, Junya; Kitamura, Mitsuhiro; Ohtori, Seiji; Matsumoto, Yukei; Abe, Tetsuya; Watanabe, Kei; Hirano, Toru; Ohashi, Masayuki; Shoji, Hirokazu; Mizouchi, Tatsuki; Takahashi, Ikuko; Kawahara, Norio; Kawaguchi, Masahito; Orita, Yugo; Sasamoto, Takeshi; Yoshioka, Masahito; Fujii, Masafumi; Yonezawa, Katsutaka; Soma, Daisuke; Taneichi, Hiroshi; Takeuchi, Daisaku; Inami, Satoshi; Moridaira, Hiroshi; Ueda, Haruki; Asano, Futoshi; Shibao, Yosuke; Aita, Ikuo; Takeuchi, Yosuke; Mimura, Masaya; Shimbo, Jun; Someya, Yukio; Ikenoue, Sumio; Sameda, Hiroaki; Takase, Kan; Ikeda, Yoshikazu; Nakajima, Fumitake; Hashimoto, Mitsuhiro; Ozawa, Tomoyuki; Hasue, Fumio; Fujiyoshi, Takayuki; Kamiya, Koshiro; Watanabe, Masahiko; Katoh, Hiroyuki; Matsuyama, Yukihiro; Yamamoto, Yu; Togawa, Daisuke; Hasegawa, Tomohiko; Kobayashi, Sho; Yoshida, Go; Oe, Shin; Banno, Tomohiro; Arima, Hideyuki; Akeda, Koji; Kawamoto, Eiji; Imai, Hiroshi; Sakakibara, Toshihiko; Sudo, Akihiro; Ito, Yasuo; Kikuchi, Tsuyoshi; Osaki, Shuhei; Tanaka, Nobuhiro; Nakanishi, Kazuyoshi; Kamei, Naosuke; Kotaka, Shinji; Baba, Hideo; Okudaira, Tsuyoshi; Konishi, Hiroaki; Yamaguchi, Takayuki; Ito, Keigo; Katayama, Yoshito; Matsumoto, Taro; Matsumoto, Tomohiro; Idota, Masaru; Kanno, Haruo; Aizawa, Toshimi; Hashimoto, Ko; Eto, Toshimitsu; Sugaya, Takehiro; Matsuda, Michiharu; Fushimi, Kazunari; Nozawa, Satoshi; Iwai, Chizuo; Taguchi, Toshihiko; Kanchiku, Tsukasa; Suzuki, Hidenori; Nishida, Norihiro; Funaba, Masahiro; Yamazaki, Masashi

2018-01-01

Introduction Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial. Methods and analysis The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m2/day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients). Ethics and dissemination The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper. Trial registration number UMIN000018752. PMID:29730616

The Beneficial Effects of Cognitive Training With Simple Calculation and Reading Aloud (SCRA) in the Elderly Postoperative Population: A Pilot Randomized Controlled Trial.

PubMed

Kulason, Kay; Nouchi, Rui; Hoshikawa, Yasushi; Noda, Masafumi; Okada, Yoshinori; Kawashima, Ryuta

2018-01-01

Background: There has been little research conducted regarding cognitive treatments for the elderly postsurgical population. Patients aged ≥60 years have an increased risk of postoperative cognitive decline, a condition in which cognitive functions are negatively affected. This cognitive decline can lead to a decline in quality of life. In order to maintain a high quality of life, the elderly postsurgical population may benefit from treatment to maintain and/or improve their cognitive functions. This pilot study investigates the effect of simple calculation and reading aloud (SCRA) cognitive training in elderly Japanese postsurgical patients. Methods: Elderly patients undergoing non-cardiovascular thoracic surgery under general anesthesia were recruited ( n = 12). Subjects were randomly divided into two groups-one that receives 12 weeks of SCRA intervention, and a waitlisted control group. Before and after the intervention, we measured cognitive function [Mini-Mental Status Exam-Japanese (MMSE-J), Frontal Assessment Battery (FAB), computerized Cogstate Brief Battery (CBB)] and emotional state [General Health Questionnaire-12 (GHQ-12), Geriatric Depression Scale (GDS), Quality of Life Scale-5 (QOL-5)]. Results: Group difference analyses using ANCOVA with permutation test showed that the intervention SCRA group had a significant improvement in FAB motor programming sub-score, GDS, and QOL-5 compared to the control group. Within-group analyses using Wilcoxon signed-rank test to compare baseline and follow-up showed that the SCRA intervention group total FAB scores, FAB motor programming sub-scores, and QOL-5 scores were significantly improved. Discussion: This pilot study showed that there are important implications for the beneficial effects of SCRA intervention on cognitive function and emotional state in the postoperative elderly population; however, further investigations are necessary to reach any conclusions. Trial registration: This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN000019832).

The Beneficial Effects of Cognitive Training With Simple Calculation and Reading Aloud (SCRA) in the Elderly Postoperative Population: A Pilot Randomized Controlled Trial

PubMed Central

Kulason, Kay; Nouchi, Rui; Hoshikawa, Yasushi; Noda, Masafumi; Okada, Yoshinori; Kawashima, Ryuta

2018-01-01

Background: There has been little research conducted regarding cognitive treatments for the elderly postsurgical population. Patients aged ≥60 years have an increased risk of postoperative cognitive decline, a condition in which cognitive functions are negatively affected. This cognitive decline can lead to a decline in quality of life. In order to maintain a high quality of life, the elderly postsurgical population may benefit from treatment to maintain and/or improve their cognitive functions. This pilot study investigates the effect of simple calculation and reading aloud (SCRA) cognitive training in elderly Japanese postsurgical patients. Methods: Elderly patients undergoing non-cardiovascular thoracic surgery under general anesthesia were recruited (n = 12). Subjects were randomly divided into two groups—one that receives 12 weeks of SCRA intervention, and a waitlisted control group. Before and after the intervention, we measured cognitive function [Mini-Mental Status Exam-Japanese (MMSE-J), Frontal Assessment Battery (FAB), computerized Cogstate Brief Battery (CBB)] and emotional state [General Health Questionnaire-12 (GHQ-12), Geriatric Depression Scale (GDS), Quality of Life Scale-5 (QOL-5)]. Results: Group difference analyses using ANCOVA with permutation test showed that the intervention SCRA group had a significant improvement in FAB motor programming sub-score, GDS, and QOL-5 compared to the control group. Within-group analyses using Wilcoxon signed-rank test to compare baseline and follow-up showed that the SCRA intervention group total FAB scores, FAB motor programming sub-scores, and QOL-5 scores were significantly improved. Discussion: This pilot study showed that there are important implications for the beneficial effects of SCRA intervention on cognitive function and emotional state in the postoperative elderly population; however, further investigations are necessary to reach any conclusions. Trial registration: This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN000019832). PMID:29643802

Lifestyle intervention using Internet of Things (IoT) for the elderly: A study protocol for a randomized control trial (the BEST-LIFE study).

PubMed

Kato, Sawako; Ando, Masahiko; Kondo, Takaaki; Yoshida, Yasuko; Honda, Hiroyuki; Maruyama, Shoichi

2018-05-01

Modification of lifestyle habits, including diet and physical activity, is essential for the prevention and control of type 2 diabetes mellitus (T2DM) in elderly patients. However, individualized treatment is more critical for the elderly than for general patients. This study aimed to determine lifestyle interventions that resulted in lowering hemoglobin A 1c (HbA 1c ) in Japanese pre- and early diabetic elderly subjects. The BEST-LIFE trial is an ongoing, open-label, 6-month, randomized (1:1) parallel group trial. Subjects with HbA 1c of ≥5.6%-randomly assigned to the intervention or control group -use wearable monitoring devices loaded with Internet of things (IoT) systems that aids them with self-management and obtaining monthly remote health guidance from a public health nurse. The primary outcome is changes in HbA 1c after a 6-month intervention relative to the baseline values. The secondary outcome is the change of behavior modification stages. The background, rationale, and study design of this trial are also presented. One hundred forty-five subjects have already been enrolled in this lifestyle intervention program, which will end in 2019. The BEST-LIFE trial will provide new evidence regarding the effectiveness and safety of our program on lowering HbA 1c in elderly subjects with T2DM. It will also investigate whether information communication technology tools and monitoring devices loaded with IoT can support health care in elderly subjects. The trial registration number is UMIN-CTR: UMIN 000023356.

Impact of patient access to Internet health records on glaucoma medication: randomized controlled trial.

PubMed

Kashiwagi, Kenji; Tsukahara, Shigeo

2014-01-15

Glaucoma is one of the leading causes of blindness. Reduction of intraocular pressure is the only proven way to prevent progression of glaucomatous optic neuropathy. The majority of glaucoma patients need to use antiglaucoma ophthalmic solutions over the course of their life. Thus, good adherence and persistency of glaucoma treatment are important factors for better glaucoma care. The purpose of this study was to investigate the impact of an Internet-based glaucoma care support system on glaucoma medication use. Patients were randomly divided into two groups. The non-Internet access (NIA) group consisted of patients who had access to the Internet-based glaucoma care support system during the 4-year period only when they were examined by ophthalmologists. The Internet access (IA) group consisted of patients who had the same Internet-based glaucoma care support system access as the NIA group for the first 2 years following enrollment but who were also given free access to the glaucoma care support system for the remaining 2 years. Changes in glaucoma medication use were investigated. In total, 81 patients in the IA group and 90 patients in the NIA group satisfied the study protocol. The number of antiglaucoma ophthalmic solutions used during the study period significantly increased in the NIA group (P<.03) but not in the IA group. The percentages of patients with unchanged, increased, and decreased antiglaucoma ophthalmic solution use during the study period were 61.1% (55/90), 17.8% (16/90), and 3.3% (3/90), respectively, in the NIA group, and 56.8% (46/81), 8.6% (7/81), and 13.6% (11/81), respectively, in the IA group (P<.001). Internet access significantly shifted from an increasing intraocular pressure trend to a decreasing trend in the IA group (P=.002) among the patients who did not have any medication changes. Allowing patients to browse their medical data may reduce the use and improve the effectiveness of glaucoma medication. UMIN-CTR Clinical Trial Number: UMIN000006982; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000008238&language=E (Archived by WebCite at http://www.webcitation.org/6MRPQeEAv).

Prevalence of gastroesophageal reflux disease symptoms and effects of esomeprazole on the quality of life related to reflux and dyspepsia in patients on maintenance hemodialysis.

PubMed

Namikoshi, Tamehachi; Harada, Kazuhiro; Hatta, Hidekazu; Tokura, Takehiko; Oshiro, Yoshiyuki; Nishizaki, Tetsuichi; Obata, Takahiro; Mori, Masahiro; Fueki, Takaaki; Fujimoto, Sohachi; Haruna, Yoshisuke; Kuwabara, Atsunori; Yorimitsu, Daisuke; Ihoriya, Chieko; Kadoya, Hiroyuki; Itano, Seiji; Fujimoto, Yasuo; Komai, Norio; Sasaki, Tamaki; Kashihara, Naoki

2016-02-01

The prevalence of gastroesophageal reflux disease (GERD) symptoms has not been investigated in patients on maintenance hemodialysis in Japan, and few studies have reported the effect of proton pump inhibitors (PPIs) in hemodialysis patients with GERD symptoms. Here, we investigated the prevalence of GERD symptoms and the effects of the PPI esomeprazole on the quality of life related to reflux and dyspepsia in patients on maintenance hemodialysis. This was a cross-sectional/cohort study of hemodialysis outpatients implemented in 10 Japanese medical facilities from October 2012 to March 2014. The trial was registered in the UMIN Clinical Trial Registry (UMIN000009124). Forty-one of 385 patients (11%) reported GERD symptoms on the Global Overall Symptom (GOS) questionnaire. Multivariate logistic regression analysis identified the independent prognostic factors for GERD symptoms as a history of gastric ulcer and use of sevelamer hydrochloride or calcium polystyrene sulfonate. Participants with GERD symptoms completed the Quality of Life in Reflux and Dyspepsia, Japanese version (QOLRAD-J) questionnaire and were assigned to receive 4-week esomeprazole treatment (20 mg/day). This PPI therapy significantly improved all QOLRAD-J domains in the full analysis set (n = 28) and improved the GERD symptoms listed in the GOS questionnaire. Significantly impaired disease-specific quality of life (QOL) in the QOLRAD-J domains was observed in 44.4-74.1% of patients who had symptoms before treatment. The mean GOS and QOLRAD-J scores correlated significantly. Therapy with 20 mg/day esomeprazole appears to be efficacious for improving disease-specific QOL and GERD symptoms in Japanese patients on maintenance hemodialysis.

Krill Oil Improves Mild Knee Joint Pain: A Randomized Control Trial.

PubMed

Suzuki, Yoshio; Fukushima, Minoru; Sakuraba, Keishoku; Sawaki, Keisuke; Sekigawa, Kazuaki

2016-01-01

Krill oil is an edible oil extracted from krill, a small red-colored crustacean found in the Antarctic Ocean. The administration of krill oil is reported to mitigate inflammation in patients with cardiac disease, rheumatoid arthritis, or osteoarthritis. However, the effect of krill oil on mild knee pain has not yet been determined. To assess the effect of krill oil on mild knee pain. A randomized, double-blind, parallel-group, placebo-controlled trial of fifty adults (38-85 years old) with mild knee pain attending the Fukushima Orthopedic Clinic (Tochigi, Japan) between September 2014 and March 2015. Participants were randomized to receive 2 g per day of either krill oil or an identical placebo for 30 days. The primary outcome was improvement in subjective symptoms of knee pain as assessed by the Japanese Knee Osteoarthritis Measure (JKOM) and Japanese Orthopaedic Association score (JOA). Secondary outcomes included blood and urine biochemical parameters. Both the placebo and krill oil groups showed significant improvements in the questions in the JKOM and JOA questionnaires after administration. After the intervention, krill oil group showed more improvements than placebo group in two questions regarding the pain and stiffness in knees in JKOM. Controlling for age, sex, weight, and smoking and drinking habits, krill oil significantly mitigated knee pain in sleeping (P < 0.001), standing (P < 0.001) and the range of motion of both right and left knees (both P = 0.011) compared to placebo. Krill oil administration raised plasma EPA (P = 0.048) and EPA/AA ratio (P = 0.003). This study indicates that krill oil administration (2 g/day, 30 days) improved the subjective symptoms of knee pain in adults with mild knee pain. UMIN-CTR; ID UMIN000014413.

Esophageal Motility and Rikkunshito Treatment for Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease: A Prospective, Uncontrolled, Open-Label Pilot Study Trial.

PubMed

Odaka, Takeo; Yamato, Shigeru; Yokosuka, Osamu

2017-01-01

Only a few reports focused on esophageal motility in patients with proton pump inhibitor (PPI)-refractory nonerosive reflux disease (NERD) and there has been no established strategy for treatment. To clarify the characteristics of esophageal motility in patients with PPI-refractory NERD, we evaluated esophageal function using combined multichannel intraluminal impedance and esophageal manometry (MII-EM). In addition, we evaluated the efficacy of rikkunshito (RKT), which is a gastrointestinal prokinetic agent. Thirty patients with NERD were enrolled and underwent MII-EM. After 8 weeks of RKT (7.5 g/d) treatment, MII-EM was repeated on patients with PPI-refractory NERD. Symptoms were assessed by the Gastrointestinal Symptom Rating Scale. In patients with PPI-refractory NERD, measures of complete bolus transit, peristaltic contractions, and residual pressure of the lower esophageal sphincter during swallowing deviated from the standard values and esophageal clearance was found to be deteriorated. RKT significantly improved the peristaltic contractions ( P < 0.05), the complete bolus transit ( P < 0.01), and the residual pressure of lower esophageal sphincter ( P < 0.05) in these patients. The overall score ( P < 0.01) and the subscale scores of acid reflux syndrome ( P < 0.05), abdominal pain ( P < 0.05), and indigestion syndrome ( P < 0.01) in the Gastrointestinal Symptom Rating Scale were significantly improved by the 8-week RKT treatment. In the pilot study, patients with PPI-refractory NERD had disorders of esophageal and lower esophageal sphincter motility that were improved by RKT. Further studies examining esophageal motor activity of RKT in PPI-refractory NERD are required. University hospital Medical Information Network (UMIN) Clinical Trial Registry identifier: UMIN000003092.

The Ratio of Eicosapentaenoic Acid (EPA) to Arachidonic Acid may be a Residual Risk Marker in Stable Coronary Artery Disease Patients Receiving Treatment with Statin Following EPA Therapy.

PubMed

Tani, Shigemasa; Nagao, Ken; Kawauchi, Kenji; Yagi, Tsukasa; Atsumi, Wataru; Matsuo, Rei; Hirayama, Atsushi

2017-10-01

We investigated the relationship between the eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio and non-high-density lipoprotein cholesterol (non-HDL-C) level, a major residual risk of coronary artery disease (CAD), in statin-treated CAD patients following EPA therapy. We conducted a 6-month, prospective, randomized clinical trial to investigate the effect of the additional administration of EPA on the EPA/AA ratio and the serum non-HDL-C level in stable CAD patients receiving statin treatment. We assigned CAD patients already receiving statin therapy to an EPA group (1800 mg/day; n = 50) or a control group (n = 50). A significant reduction in the serum non-HDL-C level was observed in the EPA group, compared with the control group (-9.7 vs. -1.2%, p = 0.01). A multiple-regression analysis with adjustments for coronary risk factors revealed that achieved EPA/AA ratio was more reliable as an independent and significant predictor of a reduction in the non-HDL-C level at a 6-month follow-up examination (β = -0.324, p = 0.033) than the absolute change in the EPA/AA ratio. Interestingly, significant negative correlations were found between the baseline levels and the absolute change values of both non-HDL-C and triglyceride-rich lipoproteins, both markers of residual risk of CAD, indicating that patients with a higher baseline residual risk achieved a greater reduction. The present results suggest that the achieved EPA/AA ratio, but not the absolute change in EPA/AA ratio, following EPA therapy might be a useful marker for the risk stratification of CAD among statin-treated patients with a high non-HDL-C level. UMIN ( http://www.umin.ac.jp/ ) Study ID: UMIN000010452.

Understanding by the general public of newspaper reports on publicly reported cancer survival in Japan: a randomized controlled trial.

PubMed

Nakamura, Fumiaki; Higashi, Takahiro; Saruki, Nobuhiro; Fukuhara, Shunichi; Sobue, Tomotaka

2014-07-01

This study was aimed to examine how well readers of newspapers understand cancer survival rate data, and the effect of this understanding on their behavioral intent. We recruited 1950 persons who were 20 years old or older registered with a market research company. Participants were randomly divided into 10 groups; 9 were assigned one of nine newspaper articles, and the remaining group was assigned the excerpt of the official Association of Clinical Cancer Centers web pages. The primary outcome was the proportion of respondents with 'sufficient understanding', who gave 70% or more correct answers on a 10-item knowledge question. The proportion of participants with sufficient understanding varied across the groups (range: 0.8-22.1%, overall, P<0.001). Only around 15% of participants answered that they would consider other hospitals in a scenario where the only hospital in the participants' area had a 5-year survival of 5% or less, and answers did not significantly vary between groups (range: 11.1-21.0%, overall P=0.77). The level of understanding of cancer survival rate varied by variation in media reporting. However, the effect of behavioral intent on hospital choice did not differ between articles. UMIN CTR UMIN000004885. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A prospective randomized comparison between pylorus- and subtotal stomach-preserving pancreatoduodenectomy on postoperative delayed gastric emptying occurrence and long-term nutritional status.

PubMed

Matsumoto, Ippei; Shinzeki, Makoto; Asari, Sadaki; Goto, Tadahiro; Shirakawa, Sachiyo; Ajiki, Tetsuo; Fukumoto, Takumi; Suzuki, Yasuyuki; Ku, Yonson

2014-06-01

Pylorus-preserving pancreatoduodenectomy (PPPD) has been associated with a high incidence of delayed gastric emptying (DGE). There are few studies comparing DGE associated with PPPD and subtotal stomach-preserving pancreatoduodenectomy (SSPPD). Moreover, differences between the procedures with respect to long-term results have not been reported. A prospective randomized study was conducted to compare perioperative complications and long-term nutritional status with PPPD and SSPPD. One hundred patients with periampullary lesions were randomized to receive either PPPD (n = 50) or SSPPD (n = 50). All patients were followed up for 3 years after surgery or to the time of recurrence to evaluate nutritional status for the study. The effects of the procedure, age, and malignancy on changes in nutritional indicators were estimated with linear mixed models. This study was registered at UMIN Clinical Trials Registry (UMIN 000012337). The incidence of DGE assessed by the International Study Group of Pancreatic Surgery was 20% with PPPD and 12% with SSPPD (P = 0.414). There were no significant differences between the two procedures on postoperative serum albumin levels, serum total cholesterol levels, and body mass index during the 3-year follow-up period. SSPPD is equally effective in DGE occurrence rate and long-term nutritional status comparing to PPPD. © 2014 Wiley Periodicals, Inc.

JCOG0911 INTEGRA study: a randomized screening phase II trial of interferonβ plus temozolomide in comparison with temozolomide alone for newly diagnosed glioblastoma.

PubMed

Wakabayashi, Toshihiko; Natsume, Atsushi; Mizusawa, Junki; Katayama, Hiroshi; Fukuda, Haruhiko; Sumi, Minako; Nishikawa, Ryo; Narita, Yoshitaka; Muragaki, Yoshihiro; Maruyama, Takashi; Ito, Tamio; Beppu, Takaaki; Nakamura, Hideo; Kayama, Takamasa; Sato, Shinya; Nagane, Motoo; Mishima, Kazuhiko; Nakasu, Yoko; Kurisu, Kaoru; Yamasaki, Fumiyuki; Sugiyama, Kazuhiko; Onishi, Takanori; Iwadate, Yasuo; Terasaki, Mizuhiko; Kobayashi, Hiroyuki; Matsumura, Akira; Ishikawa, Eiichi; Sasaki, Hikaru; Mukasa, Akitake; Matsuo, Takayuki; Hirano, Hirofumi; Kumabe, Toshihiro; Shinoura, Nobusada; Hashimoto, Naoya; Aoki, Tomokazu; Asai, Akio; Abe, Tatsuya; Yoshino, Atsuo; Arakawa, Yoshiki; Asano, Kenichiro; Yoshimoto, Koji; Shibui, Soichiro

2018-07-01

This study explored the superiority of temozolomide (TMZ) + interferonβ (IFNβ) to standard TMZ as treatment for newly diagnosed glioblastoma (GBM) via randomized phase II screening design. Eligibility criteria included histologically proven GBM, with 50% of the tumor located in supratentorial areas, without involvement of the optic, olfactory nerves, and pituitary gland and without multiple lesions and dissemination. Patients in the TMZ + radiotherapy (RT) arm received RT (2.0 Gy/fr/day, 30 fr) with TMZ (75 mg/m 2 , daily) followed by TMZ maintenance (100-200 mg/m 2 /day, days 1-5, every 4 weeks) for 2 years. Patients in the TMZ + IFNβ + RT arm intravenously received IFNβ (3 MU/body, alternative days during RT and day 1, every 4 weeks during maintenance period) and TMZ + RT. The primary endpoint was overall survival (OS). The planned sample size was 120 (one-sided alpha 0.2; power 0.8). Between Apr 2010 and Jan 2012, 122 patients were randomized. The median OS with TMZ + RT and TMZ + IFNβ + RT was 20.3 and 24.0 months (HR 1.00, 95% CI 0.65-1.55; one-sided log rank P = 0.51). The median progression-free survival times were 10.1 and 8.5 months (HR 1.25, 95% CI 0.85-1.84). The incidence of neutropenia with the TMZ + RT and the TMZ + IFNβ + RT (grade 3-4, CTCAE version 3.0) was 12.7 versus 20.7% during concomitant period and was 3.6 versus 9.3% during maintenance period. The incidence of lymphopenia was 54.0 versus 63.8% and 34.5 versus 41.9%. TMZ + IFNβ + RT is not considered as a candidate for the following phase III trial, and TMZ + RT remained to be a most promising treatment. This trial was registered with the UMIN Clinical Trials Registry: UMIN000003466.

Effectiveness and Cost-Effectiveness of Occupation-Based Occupational Therapy Using the Aid for Decision Making in Occupation Choice (ADOC) for Older Residents: Pilot Cluster Randomized Controlled Trial.

PubMed

Nagayama, Hirofumi; Tomori, Kounosuke; Ohno, Kanta; Takahashi, Kayoko; Ogahara, Kakuya; Sawada, Tatsunori; Uezu, Sei; Nagatani, Ryutaro; Yamauchi, Keita

2016-01-01

Care-home residents are mostly inactive, have little interaction with staff, and are dependent on staff to engage in daily occupations. We recently developed an iPad application called the Aid for Decision-making in Occupation Choice (ADOC) to promote shared decision-making in activities and occupation-based goal setting by choosing from illustrations describing daily activities. This study aimed to evaluate if interventions based on occupation-based goal setting using the ADOC could focus on meaningful activities to improve quality of life and independent activities of daily living, with greater cost-effectiveness than an impairment-based approach as well as to evaluate the feasibility of conducting a large cluster, randomized controlled trial. In this single (assessor)-blind pilot cluster randomized controlled trial, the intervention group (ADOC group) received occupational therapy based on occupation-based goal setting using the ADOC, and the interventions were focused on meaningful occupations. The control group underwent an impairment-based approach focused on restoring capacities, without goal setting tools. In both groups, the 20-minute individualized intervention sessions were conducted twice a week for 4 months. Short Form-36 (SF-36) score, SF-6D utility score, quality adjusted life years (QALY), Barthel Index, and total care cost. We randomized and analyzed 12 facilities (44 participants, 18.5% drop-out rate), with 6 facilities each allocated to the ADOC (n = 23) and control (n = 21) groups. After the 4-month intervention, the ADOC group had a significantly greater change in the BI score, with improved scores (P = 0.027, 95% CI 0.41 to 6.87, intracluster correlation coefficient = 0.14). No other outcome was significantly different. The incremental cost-effectiveness ratio, calculated using the change in BI score, was $63.1. The results suggest that occupational therapy using the ADOC for older residents might be effective and cost-effective. We also found that conducting an RCT in the occupational therapy setting is feasible. UMIN Clinical Trials Registry UMIN000012994.

Rationale and design of a multicenter randomized controlled study to evaluate the preventive effect of ipragliflozin on carotid atherosclerosis: the PROTECT study.

PubMed

Tanaka, Atsushi; Murohara, Toyoaki; Taguchi, Isao; Eguchi, Kazuo; Suzuki, Makoto; Kitakaze, Masafumi; Sato, Yasunori; Ishizu, Tomoko; Higashi, Yukihito; Yamada, Hirotsugu; Nanasato, Mamoru; Shimabukuro, Michio; Teragawa, Hiroki; Ueda, Shinichiro; Kodera, Satoshi; Matsuhisa, Munehide; Kadokami, Toshiaki; Kario, Kazuomi; Nishio, Yoshihiko; Inoue, Teruo; Maemura, Koji; Oyama, Jun-Ichi; Ohishi, Mitsuru; Sata, Masataka; Tomiyama, Hirofumi; Node, Koichi

2016-09-13

Type 2 diabetes mellitus is associated strongly with an increased risk of micro- and macro-vascular complications, leading to impaired quality of life and shortened life expectancy. In addition to appropriate glycemic control, multi-factorial intervention for a wide range of risk factors, such as hypertension and dyslipidemia, is crucial for management of diabetes. A recent cardiovascular outcome trial in diabetes patients with higher cardiovascular risk demonstrated that a SGLT2 inhibitor markedly reduced mortality, but not macro-vascular events. However, to date there is no clinical evidence regarding the therapeutic effects of SGLT2 inhibitors on arteriosclerosis. The ongoing PROTECT trial was designed to assess whether the SGLT2 inhibitors, ipragliflozin, prevented progression of carotid intima-media thickness in Japanese patients with type 2 diabetes mellitus. A total of 480 participants with type 2 diabetes mellitus with a HbA1c between 6 and 10 % despite receiving diet/exercise therapy and/or standard anti-diabetic agents for at least 3 months, will be randomized systematically (1:1) into either ipragliflozin or control (continuation of conventional therapy) groups. After randomization, ipragliflozin (50-100 mg once daily) will be added on to the background therapy in participants assigned to the ipragliflozin group. The primary endpoint of the study is the change in mean intima-media thickness of the common carotid artery from baseline to 24 months. Images of carotid intima-media thickness will be analyzed at a central core laboratory in a blinded manner. The key secondary endpoints include the change from baseline in other parameters of carotid intima-media thickness, various metabolic parameters, and renal function. Other cardiovascular functional tests are also planned for several sub-studies. The PROTECT study is the first to assess the preventive effect of ipragliflozin on progression of carotid atherosclerosis using carotid intima-media thickness as a surrogate marker. The study has potential to clarify the protective effects of ipragliflozin on atherosclerosis. Trial registration Unique Trial Number, JPRN/UMIN000018440 ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021348 ).

Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder.

PubMed

Saad, Khaled; Abdel-Rahman, Ahmed A; Elserogy, Yasser M; Al-Atram, Abdulrahman A; El-Houfey, Amira A; Othman, Hisham A-K; Bjørklund, Geir; Jia, Feiyong; Urbina, Mauricio A; Abo-Elela, Mohamed Gamil M; Ahmad, Faisal-Alkhateeb; Abd El-Baseer, Khaled A; Ahmed, Ahmed E; Abdel-Salam, Ahmad M

2018-01-01

Autism spectrum disorder (ASD) is a frequent developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and nonverbal communication, and stereotyped patterns of interests and activities. It has been previously reported that there is vitamin D deficiency in autistic children; however, there is a lack of randomized controlled trials of vitamin D supplementation in ASD children. This study is a double-blinded, randomized clinical trial (RCT) that was conducted on 109 children with ASD (85 boys and 24 girls; aged 3-10 years). The aim of this study was to assess the effects of vitamin D supplementation on the core symptoms of autism in children. ASD patients were randomized to receive vitamin D3 or placebo for 4 months. The serum levels of 25-hydroxycholecalciferol (25 (OH)D) were measured at the beginning and at the end of the study. The autism severity and social maturity of the children were assessed by the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and the Autism Treatment Evaluation Checklist (ATEC). UMIN-CTR Study Design: trial number: UMIN000020281. Supplementation of vitamin D was well tolerated by the ASD children. The daily doses used in the therapy group was 300 IU vitamin D3/kg/day, not to exceed 5,000 IU/day. The autism symptoms of the children improved significantly, following 4-month vitamin D3 supplementation, but not in the placebo group. This study demonstrates the efficacy and tolerability of high doses of vitamin D3 in children with ASD. This study is the first double-blinded RCT proving the efficacy of vitamin D3 in ASD patients. Depending on the parameters measured in the study, oral vitamin D supplementation may safely improve signs and symptoms of ASD and could be recommended for children with ASD. At this stage, this study is a single RCT with a small number of patients, and a great deal of additional wide-scale studies are needed to critically validate the efficacy of vitamin D in ASD. © 2016 Association for Child and Adolescent Mental Health.

Effect of magnesium added to local anesthetics for caudal anesthesia on postoperative pain in pediatric surgical patients: A systematic review and meta-analysis with Trial Sequential Analysis

PubMed Central

Mihara, Takahiro; Nakamura, Nobuhito; Ka, Koui; Goto, Takahisa

2018-01-01

Background Magnesium has been investigated as an adjuvant for neuraxial anesthesia, but the effect of caudal magnesium on postoperative pain is inconsistent. The aim of this systematic review and meta-analysis was to evaluate the analgesic effect of caudal magnesium. Methods We searched six databases, including trial registration sites. Randomized clinical trials reporting the effect of caudal magnesium on postoperative pain after general anesthesia were eligible. The risk ratio for use of rescue analgesics after surgery was combined using a random-effects model. We also assessed adverse events. The I2 statistic was used to assess heterogeneity. We assessed risk of bias with Cochrane domains. We controlled type I and II errors due to sparse data and repetitive testing with Trial Sequential Analysis. We assessed the quality of evidence with GRADE. Results Four randomized controlled trials (247 patients) evaluated the need for rescue analgesics. In all four trials, 50 mg of magnesium was administered with caudal ropivacaine. The results suggested that the need for rescue analgesia was reduced significantly by caudal magnesium administration (risk ratio 0.45; 95% confidence interval 0.24–0.86). There was considerable heterogeneity as indicated by an I2 value of 62.5%. The Trial Sequential Analysis-adjusted confidence interval was 0.04–5.55, indicating that further trials are required. The quality of evidence was very low. The rate of adverse events was comparable between treatment groups. Conclusion Caudal magnesium may reduce the need for rescue analgesia after surgery, but further randomized clinical trials with a low risk of bias and a low risk of random errors are necessary to assess the effect of caudal magnesium on postoperative pain and adverse events. Trial registration University Hospital Medical Information Network Clinical Trials Registry UMIN000025344. PMID:29293586

The Efficacy of a Web-Based Screening and Brief Intervention for Reducing Alcohol Consumption Among Japanese Problem Drinkers: Protocol for a Single-Blind Randomized Controlled Trial.

PubMed

Hamamura, Toshitaka; Suganuma, Shinichiro; Takano, Ayumi; Matsumoto, Toshihiko; Shimoyama, Haruhiko

2018-05-30

The literature shows that computer-delivered interventions with personalized normative feedback can reduce problem drinking for up to 6 months in the West. Meanwhile, no studies have been conducted to examine the effects of such interventions among Japanese problem drinkers. Possible moderators associated with effectiveness of the intervention need to be also explored. The purpose of this study is to conduct a trial and examine the efficacy of a brief intervention with personal normative feedback and psychoeducation on several measures of alcohol consumption among Japanese problem drinkers. Additionally, this study will examine whether the level of alcohol use disorder and beliefs about the physical and psychological outcomes of drinking moderate the effect of the intervention on outcome measures. This study will conduct a single-blind, 2-armed randomized controlled trial. Japanese adults with an Alcohol Use Disorder Identification Test score of 8 or higher will be enrolled in the trial. Participants allocated to the intervention group will receive the intervention immediately after the baseline measurements, and participants allocated to the waitlist group will receive the intervention at the end of the trial. Outcome measures include drinking quantity, drinking frequency, and alcohol-related consequences. Follow-up assessment will take place at 1 month, 2 months, and 6 months following the baseline measurement. The authors will not know the group allocation during trial. The authors will plan to collect a sample of 600 participants. Mixed-effect analyses of variance will be used to examine the main effects of condition, the main effects of time, and the interaction effects between condition and time on outcome variables. Enrollment for the trial began on January 6, 2018 and data are expected to be available by August 2018. This study will contribute to the literature by demonstrating the efficacy of Web-based screenings and brief interventions among Japanese problem drinkers and indicating several possible moderators between the intervention and outcomes. This type of Web-based brief intervention has the possibility of being implemented in Japanese schools and workplaces as a prevention tool. UMIN Clinical Trials Registry R000034388; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi? recptno=R000034388 (Archived by WebCite at http://www.webcitation.org/6xmOoTfTI). RR1-10.2196/10650. ©Toshitaka Hamamura, Shinichiro Suganuma, Ayumi Takano, Toshihiko Matsumoto, Haruhiko Shimoyama. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 30.05.2018.

Effectiveness of web-based self-disclosure peer-to-peer support for weight loss: randomized controlled trial.

PubMed

Imanaka, Mie; Ando, Masahiko; Kitamura, Tetsuhisa; Kawamura, Takashi

2013-07-09

Obesity is one of the most common public health problems in the industrialized world as a cause of noncommunicable diseases. Although primarily used for one-on-one communication, email is available for uninterrupted support for weight loss, but little is known about the effects of dietitian group counseling for weight control via the Internet. We developed a Web-based self-disclosure health support (WSHS) system for weight loss. This study aims to compare the effect of weight change between those using the WSHS and those using the email health support (EHS). This study was designed as an open prospective individual randomized controlled trial. Eligible participants were aged 35 to 65 years with a body mass index (BMI) of ≥25.0 in their latest health examination. Participants were randomly assigned to either the WSHS group or the EHS group. Thirteen registered dietitians under the direction of a principal dietitian each instructed 6 to 8 participants from the respective groups. All participants in the WSHS group could receive nutritional advice and calculate their nutritive intake from a photograph of a meal on their computer screen from the Internet sent to them by their dietitian, receive supervision from the registered dietitian, and view fellow participants' weight changes and lifestyle modifications. In the EHS group, a participant could receive one-on-one nutritional advice and calculate his/her nutritive intake from the photograph of a meal on computer screen sent by email from his/her dietitian, without being able to view fellow participants' status. The follow-up period was 12 weeks for both groups. The primary outcome measure was change in body weight. The secondary outcome measure included changes in BMI and waist circumference. The intergroup comparison of the changes before and after intervention was evaluated using analysis of covariance. A total of 193 participants were randomly assigned to either the WSHS group (n=97) or the EHS group (n=96). Ten from the WSHS group and 8 from the EHS group dropped out during the study period, and the remaining 87 in the WSHS group and 88 in the EHS group were followed up completely. Weight loss was significantly greater in the WSHS group than in the EHS group (-1.6 kg vs -0.7 kg; adjusted P=.04). However, there were few differences in waist circumference between the 2 groups. (-3.3 cm vs -3.0 cm; adjusted P=.71). Our newly developed WSHS system using forced self-disclosure had better short-term weight loss results. Further study in a longer-term trial is necessary to determine what effects this type of intervention might have on long-term cardiovascular disease. University Hospital Medical Information Network Clinical Trial Registration (UMIN-CTR): UMIN000009147; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000010719&language=E (Archived by WebCite at http://www.webcitation.org/6HTCkhb1p).

Effectiveness of Web-Based Self-Disclosure Peer-to-Peer Support for Weight Loss: Randomized Controlled Trial

PubMed Central

Imanaka, Mie; Kitamura, Tetsuhisa; Kawamura, Takashi

2013-01-01

Background Obesity is one of the most common public health problems in the industrialized world as a cause of noncommunicable diseases. Although primarily used for one-on-one communication, email is available for uninterrupted support for weight loss, but little is known about the effects of dietitian group counseling for weight control via the Internet. Objective We developed a Web-based self-disclosure health support (WSHS) system for weight loss. This study aims to compare the effect of weight change between those using the WSHS and those using the email health support (EHS). Methods This study was designed as an open prospective individual randomized controlled trial. Eligible participants were aged 35 to 65 years with a body mass index (BMI) of ≥25.0 in their latest health examination. Participants were randomly assigned to either the WSHS group or the EHS group. Thirteen registered dietitians under the direction of a principal dietitian each instructed 6 to 8 participants from the respective groups. All participants in the WSHS group could receive nutritional advice and calculate their nutritive intake from a photograph of a meal on their computer screen from the Internet sent to them by their dietitian, receive supervision from the registered dietitian, and view fellow participants’ weight changes and lifestyle modifications. In the EHS group, a participant could receive one-on-one nutritional advice and calculate his/her nutritive intake from the photograph of a meal on computer screen sent by email from his/her dietitian, without being able to view fellow participants’ status. The follow-up period was 12 weeks for both groups. The primary outcome measure was change in body weight. The secondary outcome measure included changes in BMI and waist circumference. The intergroup comparison of the changes before and after intervention was evaluated using analysis of covariance. Results A total of 193 participants were randomly assigned to either the WSHS group (n=97) or the EHS group (n=96). Ten from the WSHS group and 8 from the EHS group dropped out during the study period, and the remaining 87 in the WSHS group and 88 in the EHS group were followed up completely. Weight loss was significantly greater in the WSHS group than in the EHS group (–1.6 kg vs –0.7 kg; adjusted P=.04). However, there were few differences in waist circumference between the 2 groups. (–3.3 cm vs –3.0 cm; adjusted P=.71). Conclusions Our newly developed WSHS system using forced self-disclosure had better short-term weight loss results. Further study in a longer-term trial is necessary to determine what effects this type of intervention might have on long-term cardiovascular disease. Trial Registration University Hospital Medical Information Network Clinical Trial Registration (UMIN-CTR): UMIN000009147; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000010719&language=E (Archived by WebCite at http://www.webcitation.org/6HTCkhb1p). PMID:23838533

Efficacy of Mobile Serious Games in Increasing HIV Risk Perception in Swaziland: A Randomized Control Trial (SGprev Trial) Research Protocol

PubMed Central

Musumari, Patou; El-Saaidi, Christina; Techasrivichien, Teeranee; Suguimoto, S. Pilar; Ono Kihara, Masako; Kihara, Masahiro

2016-01-01

Background The human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) continue to be a major public health problem in Sub-Saharan Africa (SSA), particularly in Swaziland, which has the highest HIV prevalence in this region. A wide range of strategies and interventions have been used to promote behavior change, though almost all such interventions have involved mass media. Therefore, innovative behavior change strategies beyond mass media communication are urgently needed. Serious games have demonstrated effectiveness in advancing health in the developed world; however, no rigorous serious games interventions have been implemented in HIV prevention in SSA. Objective We plan to test whether a serious game intervention delivered on mobile phones to increase HIV risk perception, increase intention to reduce sexual partnerships, and increase intention to know own and partners HIV status will be more effective compared with current prevention efforts. Methods This is a two-arm randomized intervention trial. We will recruit 380 participants who meet the following eligibility criteria: 18-29 years of age, own a smartphone running an Android-based operating system, have the WhatsApp messaging app, live in Swaziland, and can adequately grant informed consent. Participants will be allocated into a smartphone interactive, educational story game, and a wait-list control group in a 1:1 allocation ratio. Subsequently, a self-administered Web-based questionnaire will be issued at baseline and after 4 weeks of exposure to the game. We hypothesize that the change in HIV risk perception between pre- and post-intervention assessment is greater in the intervention group compared with the change in the control group. Our primary hypothesis is based on the assumption that increased perceived risk of HIV provides cues to engage in protective behavior. Our primary outcome measure is HIV risk perceived mean change between pre- and post-intervention compared with the mean change in the wait-list control group at 4-weeks post-intervention. We will use standardized regression coefficients to calculate the effect of the intervention on our primary outcome with P values. We will conduct both intention to treat and as treated analysis. Results This study is funded by Hayao Nakayama Foundation for Science & Technology and Culture; Grant number H26-A2-41. The research and development approval has been obtained from Kyoto University Graduate School and Faculty of Medicine Ethics Committee, Japan, and Swaziland’s Ministry of Health Ethics and Scientific committee. Results are expected in February 2017. Conclusions This study will provide evidence on the efficiency of a mobile phone interactive game in increasing HIV risk perception in Swaziland. Our findings may also be generalizable to similar settings in SSA. Trial Registration University Hospital Medical Information Network Clinical Trial Registry ID number (UMIN-CTR):UMIN000021781; URL:https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000025103 (Archived by WebCite at http://www.webcitation.org/6hOphB11a). PMID:27876685

Three-Year Outcomes of Surgical Versus Endovascular Revascularization for Critical Limb Ischemia

PubMed Central

Takahara, Mitsuyoshi; Soga, Yoshimitsu; Kodama, Akio; Terashi, Hiroto; Azuma, Nobuyoshi

2017-01-01

Background— The aim of this study was to compare clinical outcomes between surgical reconstruction and endovascular therapy (EVT) for critical limb ischemia (CLI) in today’s real-world settings. Methods and Results— This multicenter, prospective, observational study registered and followed 548 Japanese CLI patients. The registration was in advance of revascularization; 197 patients were scheduled to receive surgical reconstruction, and the remaining 351 were scheduled to receive EVT. The primary end point was 3-year amputation-free survival, compared between the 2 treatments in an intention-to-treat manner, using propensity score matching. Interaction analysis was additionally performed to explore which subgroups had better outcomes with surgical reconstruction or EVT. After propensity score matching, the 3-year amputation-free survival was not significantly different between the 2 groups (52% [95% confidence interval, 43%–60%] and 52% [95% confidence interval, 44–60%]; P=0.26). Subsequent interaction analysis identified (1) Wound, Ischemia, and foot Infection (WIfI) classification W-3, (2) fI-2/3, (3) history of ipsilateral minor amputation, (4) history of revascularization after CLI onset, and (5) bilateral CLI as the factors more favorable for surgical reconstruction, whereas (1) diabetes mellitus, (2) renal failure, (3) anemia, (4) history of nonadherence to cardiovascular risk management, and (5) contralateral major amputation were as those less favorable for surgical reconstruction. Conclusions— The 3-year amputation-free survival was not different between surgical reconstruction and EVT in the overall CLI population. The subsequent interaction analysis suggested that there would be a subgroup more suited for surgical reconstruction and another benefiting more from EVT. Clinical Trial Registration— URL: http://www.umin.ac.jp/ctr/. Unique identifier: UMIN000007050. PMID:29246911

Effects of acotiamide on esophageal motor function and gastroesophageal reflux in healthy volunteers.

PubMed

Ishimura, Norihisa; Mori, Mami; Mikami, Hironobu; Shimura, Shino; Uno, Goichi; Aimi, Masahito; Oshima, Naoki; Ishihara, Shunji; Kinoshita, Yoshikazu

2015-09-11

The prevalence of gastroesophageal reflux disease (GERD) has been increasing worldwide, with proton pump inhibitor (PPI) administration the current mainstay therapy for affected individuals. However, PPI efficacy is insufficient especially for non-erosive reflux disease. Although it has been reported that prokinetic drugs improve GERD, their effects on esophageal function remain to be clearly investigated. In the present study, we evaluated the direct effects of acotiamide, a novel prokinetic agent for the treatment of functional dyspepsia, on esophageal motor function and gastroesophageal reflux. Ten adult healthy volunteers (average age 24 years, range 20-36 years; 7 males, 3 females) were enrolled. Esophageal body peristaltic contractions and lower esophageal sphincter (LES) pressure with and without acotiamide administration were recorded using high resolution manometry using a cross-over protocol. Total and acidic reflux levels for 24 h and during the postprandial period were also recorded using a multichannel intraluminal impedance and pH monitoring system. Data were analyzed blind by one observer. Acotiamide at a standard dose of 300 mg/day did not significantly stimulate esophageal motor function. Although the frequency of swallows with weak contraction tended to decrease with acotiamide administration, the difference as compared to no administration was not statistically significant. In addition, the drug neither decreased total or postprandial gastroesophageal acid/non-acid reflux events nor accelerated esophageal clearance time. Acotiamide, a novel gastrointestinal motility modulator, at a standard dose did not significantly affect esophageal motor functions or gastroesophageal reflux in healthy adults. Additional investigations with GERD patients are necessary to elucidate its clinical significance. This study was registered on 1st August 2013 with the University Hospital Medical Information Network (UMIN) clinical trials registry, as number: UMIN000011260.

A phase I/II clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer.

PubMed

Murakami, Naoya; Kato, Shingo; Nakano, Takashi; Uno, Takashi; Yamanaka, Takeharu; Sakurai, Hideyuki; Yoshimura, Ryoichi; Hiratsuka, Junichi; Kuroda, Yuki; Yoshio, Kotaro; Itami, Jun

2016-08-17

This paper describes about a study protocol of phase I/II multicenter prospective clinical trial evaluating the feasibility and efficacy of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced uterine cervical cancer patients. Patients with histologically confirmed FIGO stage IB2, IIA2, IIB, and IIIB uterine cervical carcinoma width of which is larger than 5 cm assessed by MRI will be entered to this clinical trial. Protocol therapy is 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP (40 mg/m(2)), followed by 24 Gy in 4 fractions of HBT and central shield EBRT up to 50-50.4 Gy in 25-28 fractions. Tumor width is assessed again within one week before the first HBT and if the tumor width is larger than 4 cm, patients proceed to the secondary registration. In phase I section, feasibility of this will be investigated. If less than 10 % out of 20 patients experienced greater than grade 3 acute non-hematologic adverse effects, the study proceeds to phase II part. In phase II part a total of 55 patients will be accrued and the efficacy of the HBT will be investigated comparing with historical control data. If the lower margin of 90 % confidence interval of the 2-year pelvic progression-free survival of the HBT trial is higher than 64 %, the HBT is considered to be more effective than conventional ICBT. The aim of this study is to demonstrate the feasibility and efficacy of the HBT for locally advanced cervical cancer. This trial will clarify the indication, feasibility, and efficacy of this new technique. UMIN000019081 ; Registration date: 2015/9/30.

Feasibility of a Smartphone website to support antenatal Perineal massage in pregnant women.

PubMed

Takeuchi, Shoko; Horiuchi, Shigeko

2017-10-16

In Japan, 85% of pregnant women do not practice antenatal perineal massage. Therefore, we developed a smartphone website to support the practice of antenatal perineal massage. The purpose of the present study was to evaluate the feasibility of our smartphone website. Pregnant women were recruited at five hospitals or clinics in Tokyo, Japan. Participants assigned to the smartphone website group (n = 74) were asked to register on the smartphone website. After completing registration, they could login and use all the contents of the website. After giving birth, participants completed a 5-item questionnaire evaluating the acceptability of the smartphone website. Participants assigned to the leaflet group (n = 71) received a leaflet on antenatal perineal massage and completed a similar 4-item questionnaire evaluating the leaflet. Data were collected from April 2014 to November 2014. Data analysis was performed using chi-square and t-tests to analyze responses to close-ended questions, and content analysis was conducted to analyze responses of open-ended questions. In the smartphone website group, 9 women (12.2%) did not register on the smartphone website. Approximately 80% of the women who responded indicated that the smartphone site was easy to understand and useful for practicing antenatal perineal massage. In the smartphone website group, the reply rate for reporting the frequency of massage was 43.6%. Although the ratings and frequency at which the material was accessed tended to be higher in the smartphone website group than in the leaflet group, there were no significant differences. Most pregnant women in the smartphone website group provided a favorable evaluation for the smartphone website. However, some participants had suggestions for improvement, which need to be incorporated in a revised version of the website. Therefore, the present study's results demonstrate the feasibility of a smartphone website to support the practice of antenatal perineal massage, and they may aid in the development of similar web-based educational material for pregnant women. This trial was registered with the UMIN Clinical Trials Registry ( UMIN000013979 ) on May 16, 2014.

The Tokyo Oldest Old Survey on Total Health (TOOTH): A longitudinal cohort study of multidimensional components of health and well-being

PubMed Central

2010-01-01

Background With the rapid worldwide increase in the oldest old population, considerable concern has arisen about the social and economic burden of diseases and disability in this age group. Understanding of multidimensional structure of health and its life-course trajectory is an essential prerequisite for effective health care delivery. Therefore, we organized an interdisciplinary research team consisting of geriatricians, dentists, psychologists, sociologists, and epidemiologists to conduct a longitudinal observational study. Methods/Design For the Tokyo Oldest Old Survey on Total Health (TOOTH) study, a random sample of inhabitants of the city of Tokyo, aged 85 years or older, was drawn from the basic city registry. The baseline comprehensive assessment consists of an in-home interview, a self-administered questionnaire, and a medical/dental examination. To perform a wide variety of biomedical measurements, including carotid ultrasonography and a detailed dental examination, participants were invited to our study center at Keio University Hospital. For those who were not able to visit the study center, we provided the option of a home-based examination, in which participants were simultaneously visited by a geriatrician and a dentist. Of 2875 eligible individuals, a total of 1152 people were recruited, of which 542 completed both the in-home interview and the medical/dental examination, with 442 completed the in-home interview only, and another 168 completed self or proxy-administered data collection only. Carotid ultrasonography was completed in 458 subjects, which was 99.6% of the clinic visitors (n = 460). Masticatory assessment using a colour-changeable chewing gum was completed in 421 subjects, a 91.5% of the clinic visitors. Discussion Our results demonstrated the feasibility of a new comprehensive study that incorporated non-invasive measurements of subclinical diseases and a detailed dental examination aiming at community-dwelling individuals aged 85 years or older. The bimodal recruitment strategy is critically important to capture a broad range of health profiles among the oldest old. Results form the TOOTH study will help develop new models of health promotion, which are expected to contribute to an improvement in lifelong health and well-being. Trial Registration This study has been registered in the UMIN-Clinical Trial Registry (CTR), ID: UMIN000001842. PMID:20529368

A phase I study of combination vaccine treatment of five therapeutic epitope-peptides for metastatic colorectal cancer; safety, immunological response, and clinical outcome.

PubMed

Hazama, Shoichi; Nakamura, Yusuke; Takenouchi, Hiroko; Suzuki, Nobuaki; Tsunedomi, Ryouichi; Inoue, Yuka; Tokuhisa, Yoshihiro; Iizuka, Norio; Yoshino, Shigefumi; Takeda, Kazuyoshi; Shinozaki, Hirokazu; Kamiya, Akira; Furukawa, Hiroyuki; Oka, Masaaki

2014-03-10

To evaluate the safety of combination vaccine treatment of multiple peptides, phase I clinical trial was conducted for patients with advanced colorectal cancer using five novel HLA-A*2402-restricted peptides, three peptides derived from oncoantigens, ring finger protein 43 (RNF43), 34 kDa-translocase of the outer mitochondrial membrane (TOMM34), and insulin-like growth factor-II mRNA binding protein 3 (KOC1), and the remaining two from angiogenesis factors, vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2. Eighteen HLA- A*2402-positive colorectal cancer patients who had failed to standard therapy were enrolled in this study. 0.5 mg, 1.0 mg or 3.0 mg each of the peptides was mixed with incomplete Freund's adjuvant and then subcutaneously injected at five separated sites once a week. We also examined possible effect of a single site injection of "the cocktail of 5 peptides" on the immunological responses. ELISPOT assay was performed before and after vaccinations in the schedule of every 4 weeks. The vaccine treatment using multiple peptides was well tolerated without any severe treatment-associated systemic adverse events. Dose-dependent induction of peptide-specific cytotoxic T lymphocytes was observed. The single injection of "peptides cocktail" did not diminish the immunological responses. Regarding the clinical outcome, one patient achieved complete response and 6 patients revealed stable disease for 4 to 7 months. The median overall survival time (MST) was 13.5 months. Patients, in which we detected induction of cytotoxic T lymphocytes specific to 3 or more peptides, revealed significantly better prognosis (MST; 27.8 months) than those with poorer immune responses (MST; 3.7 months) (p = 0.032). Our cancer vaccine treatment using multiple peptides is a promising approach for advanced colorectal cancer with the minimum risk of systemic adverse reactions. UMIN-CTR number UMIN000004948.

Study protocol for a randomised controlled trial of cognitive processing therapy for post-traumatic stress disorder among Japanese patients: the Safety, Power, Intimacy, Esteem, Trust (SPINET) study

PubMed Central

Ito, Masaya; Horikoshi, Masaru; Resick, Patricia A; Katayanagi, Akiko; Miyamae, Mitsuhiro; Takagishi, Yuriko; Takebayashi, Yoshitake; Kanie, Ayako; Hirabayashi, Naotsugu; Furukawa, Toshiaki A

2017-01-01

Introduction Cognitive processing therapy (CPT) is widely regarded as a safe and effective first-line treatment for individuals with post-traumatic stress disorder (PTSD); however, no comparative studies have been conducted to examine the treatment outcomes in an Asian population. The aim of the present trial is to investigate the efficacy of CPT (individual format) as a treatment for PTSD in a population of Japanese patients. Methods and analysis A 16-week, single-centre, assessor-masked, randomised, parallel-group superiority trial has been designed to compare the efficacy of CPT in conjunction with treatment as usual (mostly pharmacotherapy and clinical monitoring) versus treatment as usual alone. The Clinician-Administered PTSD Scale for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) will be our primary outcome measure of the post-traumatic stress symptoms at 17 weeks, whereas the PTSD Checklist for DSM-5 and determination of the operationally defined responder status will be used to assess the secondary outcomes. An estimated sample size of 29 participants in each group will be required to detect an expected effect size of 1.4 (95% CI 0.85 to 1.95). Ethics and dissemination The institutional review board at the National Center of Neurology and Psychiatry in Japan approved this study. The results of this clinical trial will be presented at conferences and disseminated through publication in a peer-reviewed journal. Trial registration number UMIN000021670 (registered on 1 April 2016). PMID:28667201

Study protocol for the G-SPIRIT trial: a randomised, placebo-controlled, double-blinded phase III trial of granulocyte colony-stimulating factor-mediated neuroprotection for acute spinal cord injury.

PubMed

Koda, Masao; Hanaoka, Hideki; Sato, Takatoshi; Fujii, Yasuhisa; Hanawa, Michiko; Takahashi, Sho; Furuya, Takeo; Ijima, Yasushi; Saito, Junya; Kitamura, Mitsuhiro; Ohtori, Seiji; Matsumoto, Yukei; Abe, Tetsuya; Watanabe, Kei; Hirano, Toru; Ohashi, Masayuki; Shoji, Hirokazu; Mizouchi, Tatsuki; Takahashi, Ikuko; Kawahara, Norio; Kawaguchi, Masahito; Orita, Yugo; Sasamoto, Takeshi; Yoshioka, Masahito; Fujii, Masafumi; Yonezawa, Katsutaka; Soma, Daisuke; Taneichi, Hiroshi; Takeuchi, Daisaku; Inami, Satoshi; Moridaira, Hiroshi; Ueda, Haruki; Asano, Futoshi; Shibao, Yosuke; Aita, Ikuo; Takeuchi, Yosuke; Mimura, Masaya; Shimbo, Jun; Someya, Yukio; Ikenoue, Sumio; Sameda, Hiroaki; Takase, Kan; Ikeda, Yoshikazu; Nakajima, Fumitake; Hashimoto, Mitsuhiro; Ozawa, Tomoyuki; Hasue, Fumio; Fujiyoshi, Takayuki; Kamiya, Koshiro; Watanabe, Masahiko; Katoh, Hiroyuki; Matsuyama, Yukihiro; Yamamoto, Yu; Togawa, Daisuke; Hasegawa, Tomohiko; Kobayashi, Sho; Yoshida, Go; Oe, Shin; Banno, Tomohiro; Arima, Hideyuki; Akeda, Koji; Kawamoto, Eiji; Imai, Hiroshi; Sakakibara, Toshihiko; Sudo, Akihiro; Ito, Yasuo; Kikuchi, Tsuyoshi; Osaki, Shuhei; Tanaka, Nobuhiro; Nakanishi, Kazuyoshi; Kamei, Naosuke; Kotaka, Shinji; Baba, Hideo; Okudaira, Tsuyoshi; Konishi, Hiroaki; Yamaguchi, Takayuki; Ito, Keigo; Katayama, Yoshito; Matsumoto, Taro; Matsumoto, Tomohiro; Idota, Masaru; Kanno, Haruo; Aizawa, Toshimi; Hashimoto, Ko; Eto, Toshimitsu; Sugaya, Takehiro; Matsuda, Michiharu; Fushimi, Kazunari; Nozawa, Satoshi; Iwai, Chizuo; Taguchi, Toshihiko; Kanchiku, Tsukasa; Suzuki, Hidenori; Nishida, Norihiro; Funaba, Masahiro; Yamazaki, Masashi

2018-05-05

Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial. The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m 2 /day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients). The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper. UMIN000018752. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Tailored message interventions versus typical messages for increasing participation in colorectal cancer screening among a non-adherent population: A randomized controlled trial.

PubMed

Hirai, Kei; Ishikawa, Yoshiki; Fukuyoshi, Jun; Yonekura, Akio; Harada, Kazuhiro; Shibuya, Daisuke; Yamamoto, Seiichiro; Mizota, Yuri; Hamashima, Chisato; Saito, Hiroshi

2016-05-24

The purpose of this study was to examine the effectiveness and cost-efficiency of a tailored message intervention compared with a non-tailored message intervention for increasing colorectal cancer (CRC) screening rates among a non-adherent population, in a community-based client reminder program. After a baseline survey for psychological segmentation, 2140 eligible individuals were randomly assigned either to a group with a tailored matched-message condition (N = 356), a group with a non-tailored unmatched-message condition (N = 355), or to two control groups, one using a typical message with a professional design (N = 717) and one without a professional design (N = 712). The main outcome measure was attendance rates in a community-organized CRC screening program within five months of receiving a print reminder. There was a significant difference in fecal occult blood test (FOBT) attendance rates at follow-up assessments between the tailored matched-message condition (14.0 %) and the control (9.9 %; OR = 1.48, p = 0.026), while there was no significant difference between the unmatched-message condition (11.0 %) and the control (OR = 1.12, p = 0.558), and between the matched-message condition and the unmatched-message condition (OR = 1.32, p = 0.219). The cost of a one-person increase in FOBT screening was 3,740 JPY for the tailored matched-message condition, while it was 2,747 JPY for the control. A tailored-message intervention for segmented individuals designed to increase CRC screening rates in a community-based client reminder program was significantly effective compared to a usual reminder, but not more effective than an unmatched message in a randomized controlled trial, and was not sufficiently effective to highlight its value from a cost perspective. Therefore, the tailored intervention including target segmentation needs to be improved for future implementation in a CRC screening program for a non-adherent population. UMIN Clinical Trials Registry UMIN000004384 . Date of Registration: March 2011.

Efficacy of Mobile Serious Games in Increasing HIV Risk Perception in Swaziland: A Randomized Control Trial (SGprev Trial) Research Protocol.

PubMed

Lukhele, Bhekumusa Wellington; Musumari, Patou; El-Saaidi, Christina; Techasrivichien, Teeranee; Suguimoto, S Pilar; Ono Kihara, Masako; Kihara, Masahiro

2016-11-22

The human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) continue to be a major public health problem in Sub-Saharan Africa (SSA), particularly in Swaziland, which has the highest HIV prevalence in this region. A wide range of strategies and interventions have been used to promote behavior change, though almost all such interventions have involved mass media. Therefore, innovative behavior change strategies beyond mass media communication are urgently needed. Serious games have demonstrated effectiveness in advancing health in the developed world; however, no rigorous serious games interventions have been implemented in HIV prevention in SSA. We plan to test whether a serious game intervention delivered on mobile phones to increase HIV risk perception, increase intention to reduce sexual partnerships, and increase intention to know own and partners HIV status will be more effective compared with current prevention efforts. This is a two-arm randomized intervention trial. We will recruit 380 participants who meet the following eligibility criteria: 18-29 years of age, own a smartphone running an Android-based operating system, have the WhatsApp messaging app, live in Swaziland, and can adequately grant informed consent. Participants will be allocated into a smartphone interactive, educational story game, and a wait-list control group in a 1:1 allocation ratio. Subsequently, a self-administered Web-based questionnaire will be issued at baseline and after 4 weeks of exposure to the game. We hypothesize that the change in HIV risk perception between pre- and post-intervention assessment is greater in the intervention group compared with the change in the control group. Our primary hypothesis is based on the assumption that increased perceived risk of HIV provides cues to engage in protective behavior. Our primary outcome measure is HIV risk perceived mean change between pre- and post-intervention compared with the mean change in the wait-list control group at 4-weeks post-intervention. We will use standardized regression coefficients to calculate the effect of the intervention on our primary outcome with P values. We will conduct both intention to treat and as treated analysis. This study is funded by Hayao Nakayama Foundation for Science & Technology and Culture; Grant number H26-A2-41. The research and development approval has been obtained from Kyoto University Graduate School and Faculty of Medicine Ethics Committee, Japan, and Swaziland's Ministry of Health Ethics and Scientific committee. Results are expected in February 2017. This study will provide evidence on the efficiency of a mobile phone interactive game in increasing HIV risk perception in Swaziland. Our findings may also be generalizable to similar settings in SSA. University Hospital Medical Information Network Clinical Trial Registry ID number (UMIN-CTR):UMIN000021781; URL:https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000025103 (Archived by WebCite at http://www.webcitation.org/6hOphB11a). ©Bhekumusa Wellington Lukhele, Patou Musumari, Christina El-Saaidi, Teeranee Techasrivichien, S. Pilar Suguimoto, Masako Ono Kihara, Masahiro Kihara. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 22.11.2016.

Short-term influence of cataract surgery on circadian biological rhythm and related health outcomes (CLOCK-IOL trial): study protocol for a randomized controlled trial.

PubMed

Saeki, Keigo; Obayashi, Kenji; Nishi, Tomo; Miyata, Kimie; Maruoka, Shinji; Ueda, Tetsuo; Okamoto, Masahiro; Hasegawa, Taiji; Matsuura, Toyoaki; Tone, Nobuhiro; Ogata, Nahoko; Kurumatani, Norio

2014-12-29

Light information is the most important cue of circadian rhythm which synchronizes biological rhythm with external environment. Circadian misalignment of biological rhythm and external environment is associated with increased risk of depression, insomnia, obesity, diabetes, cardiovascular disease, and cancer. Increased light transmission by cataract surgery may improve circadian misalignment and related health outcomes. Although some observational studies have shown improvement of depression and insomnia after cataract surgery, randomized controlled trials are lacking. We will conduct a parallel-group, assessor-blinded, simple randomized controlled study comparing a cataract surgery group at three months after surgery with a control group to determine whether cataract surgery improves depressive symptoms, sleep quality, body mass regulation, and glucose and lipid metabolism. We will recruit patients who are aged 60 years and over, scheduled to receive their first cataract surgery, and have grade 2 or higher nuclear opacification as defined by the lens opacities classification system III. Exclusion criteria will be patients with major depression, severe corneal opacity, severe glaucoma, vitreous haemorrhage, proliferative diabetic retinopathy, macular oedema, age-related macular degeneration, and patients needing immediate or combined cataract surgery. After baseline participants will be randomized to two groups. Outcomes will be measured at three months after surgery among the intervention group, and three months after baseline among the control group. We will assess depressive symptoms as a primary outcome, using the short version geriatric depression scale (GDS-15). Secondary outcomes will be subjective and actigraph-measured sleep quality, sleepiness, glycated haemoglobin, fasting plasma glucose and triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, body mass index, abdominal circumference, circadian rhythms of physical activity and wrist skin temperature, and urinary melatonin metabolite. Chronotype and visual function will be assessed using the 'morningness-eveningness' questionnaire, the Munich chronotype questionnaire, and the National Eye Institute Visual Function Questionnaire. Although there are potential limitations due to the difference in duration from baseline survey to outcome measurements between two groups, any seasonal effect on the outcome measurement will be balanced as a result of continuous inclusion of participants through the year, and outcomes will be adjusted for day length at outcome measurements at analysis. UMIN000014559, UMIN Clinical Trials Registry, registered on 15 July 2014.

Effects of exercise and horticultural intervention on the brain and mental health in older adults with depressive symptoms and memory problems: study protocol for a randomized controlled trial [UMIN000018547].

PubMed

Makizako, Hyuma; Tsutsumimoto, Kota; Doi, Takehiko; Hotta, Ryo; Nakakubo, Sho; Liu-Ambrose, Teresa; Shimada, Hiroyuki

2015-11-04

Depressive symptoms and memory problems are significant risk factors for dementia. Exercise can reduce depressive symptoms and improve cognitive function in older people. In addition, the benefits of horticultural activity on physical and mental well-being have been demonstrated in people with dementia. Although evidence of such non-pharmacological interventions is mounting, no studies have examined whether physical exercise and horticultural activity exert a positive impact on brain and mental health (e.g., depressive symptoms) in non-demented older adults at high risk of cognitive impairment and depression. Therefore, we propose a randomized controlled trial to assess the efficacy and efficiency of physical exercise and horticultural activity in improving brain and mental health in community-dwelling older adults with memory problems and depressive symptoms. The 20-week randomized controlled trial will include 90 community-dwelling adults aged 65 years or older with memory problems and depressive symptoms. Participants will be randomized to one of three experiments: exercise, horticultural activity, or educational control group, using a 1:1:1 allocation ratio. The combined exercise program and horticultural activity program will consist of 20 weekly 90-minute sessions. Participants in the exercise group will practice aerobic exercise, muscle strength training, postural balance retraining, and dual-task training. The horticultural activity program will include crop-related activities, such as field cultivation, growing, and harvesting. Participants in the educational control group will attend two 90-minute educational classes during the 6-month trial period. Depressive symptoms and memory performance will be measured by the Geriatric Depression Scale-15, and the Logical Memory subtests of the Wechsler Memory Scale-Revised will be used to measure depressive symptoms and memory performance as primary outcomes, at baseline (prior to randomization), immediately following intervention (6 months from baseline), and 6 months after intervention. Hippocampal volume will be measured at baseline and immediately after intervention, using magnetic resonance imaging. Secondary outcomes will comprise cognitive function, including language, attention/executive performance, and processing speed; brain-derived neurotrophic-factor serum levels; and health-related quality of life. This intervention study will determine the clinical importance and efficacy of physical exercise and horticultural activity as non-pharmacological interventions in community-dwelling older adults at high risk of poor brain and mental health. UMIN000018547 ; registered 7 August 2015.

Chronological Changes in Ropivacaine Concentration and Analgesic Effects Between Transversus Abdominis Plane Block and Rectus Sheath Block.

PubMed

Murouchi, Takeshi; Iwasaki, Soshi; Yamakage, Michiaki

2015-01-01

Transversus abdominis plane block (TAPB) and rectus sheath block (RSB) are popular methods of controlling postoperative pain. Chronological changes in blood concentrations of local anesthetics have not been described, although a large amount of local anesthetic is required to block these compartments. We postulated that blood concentrations of anesthetics would peak earlier during TAPB than RSB (primary end point). Secondary end points were elapsed time from block until first postoperative rescue analgesia and affected dermatomes. This prospective, randomized study included 22 patients scheduled for laparoscopic ovarian surgery under general anesthesia. The patients were randomized to receive either a bilateral single-shot TAPB or a bilateral RSB (15 mL of 0.5% ropivacaine per side). Arterial blood was sampled 10, 20, 30, 45, 60, 90, and 120 minutes after ropivacaine administration. This trial was registered at the UMIN-Clinical Trials Registry (UMIN000012133) before patient recruitment. Arterial ropivacaine levels after block peaked earlier in the TAPB than in RSB [Tmax: 35 (12) vs 53 (16) minutes; P = 0.02], whereas peak ropivacaine concentrations did not significantly differ between the groups [Cmax: 1.83 (0.41) vs 1.79 (0.33) μg/mL; P = 0.54]. Peak ropivacaine concentrations exceeded 2.2 μg/mL in 1 and 2 patients in the RSB and TAPB groups, respectively, although symptoms of local anesthetic systemic toxicity were not evident in any of them. The median [interquartile range] duration of analgesia was significantly longer for TAPB than RSB (421 [335-536] vs 196 [168-277] minutes; P = 0.01). Peak ropivacaine concentrations were comparable during TAPB and RSB, but peaked earlier during TAPB. Although 150 mg of ropivacaine remained effective significantly longer during TAPB than RSB during laparoscopic surgery, this dose could cause local anesthetic systemic toxicity. The analgesic effects of blocks with less ropivacaine should be assessed.

A comparative study of three conservative treatments in patients with lumbar spinal stenosis: lumbar spinal stenosis with acupuncture and physical therapy study (LAP study).

PubMed

Oka, Hiroyuki; Matsudaira, Ko; Takano, Yuichi; Kasuya, Daichi; Niiya, Masaki; Tonosu, Juichi; Fukushima, Masayoshi; Oshima, Yasushi; Fujii, Tomoko; Tanaka, Sakae; Inanami, Hirohiko

2018-01-19

Although the efficiency of conservative management for lumbar spinal stenosis (LSS) has been examined, different conservative management approaches have not been compared. We have performed the first comparative trial of three types of conservative management (medication with acetaminophen, exercise, and acupuncture) in Japanese patients with LSS. Patients with L5 root radiculopathy associated with LSS who visited our hospital for surgical treatment were enrolled between December 2011 and January 2014. In this open-label study, patients were assigned to three treatment groups (medication, exercise, acupuncture) according to the visit time. The primary outcomes were Zurich claudication questionnaire (ZCQ) scores before and after 4 weeks of treatment. Least square mean analysis was used to assess the following dependent variables in the treatment groups: changes in symptom severity and physical function scores of the ZCQ and the ZCQ score of patient's satisfaction after treatment. Thirty-eight, 40, and 41 patients were allocated to the medication, exercise, and acupuncture groups, respectively. No patient underwent surgical treatment during the study period. The symptom severity scores of the ZCQ improved significantly after treatment in the medication (p = 0.048), exercise (p = 0.003), and acupuncture (p = 0.04) groups. The physical function score improved significantly in the acupuncture group (p = 0.045) but not in the medication (p = 0.20) and exercise (p = 0.29) groups. The mean reduction in the ZCQ score for physical function was significantly greater for acupuncture than for exercise. The mean ZCQ score for treatment satisfaction was significantly greater for acupuncture than for medication. Acupuncture was significantly more effective than physical exercise according to the physical function score of the ZCQ and than medication according to the satisfaction score. The present study provides new important information that will aid decision making in LSS treatment. This study was registered with the UMIN Clinical Trials Registry ( UMIN000006957 ).

The impact of exercise and vitamin D supplementation on physical function in community-dwelling elderly individuals: A randomized trial.

PubMed

Aoki, Kana; Sakuma, Mayumi; Endo, Naoto

2018-04-25

We investigated the impact of exercise and vitamin D supplementation on physical function and locomotor dysfunction in community-dwelling elderly individuals. In total, 148 community-dwelling elderly individuals (aged ≥60 years) who were not taking osteoporosis medications participated in a 24-week intervention. The participants were randomly divided into an exercise group, vitamin D group, and exercise and vitamin D group. The participants and outcome-assessing staff were not blinded to group assignment. Exercise comprised three daily sets each of single-leg standing (1 min/leg/set) and squatting (5-6 repetitions/set); vitamin D supplementation was 1000 IU/day. Participants were contacted every 2 weeks to check on their condition and encourage continued participation. The primary outcome was lower limb muscle strength and mass; secondary outcomes were several physical function measurements, serum 25-hydroxyvitamin D levels, and results of a self-assessment questionnaire completed pre- and post-intervention. We analyzed data from 45, 42, and 43 participants in the exercise, vitamin D, and exercise and vitamin D groups, respectively, who completed the intervention. Locomotive syndrome, which involves reduced mobility due to locomotive organ impairment, was diagnosed in 99 participants (76.2%). Many physical function measurements improved in all groups. Lower limb muscle mass increased significantly in all three groups, with no significant differences between the groups in the degree of change. The average serum 25-hydroxyvitamin D of all vitamin D-supplemented participants increased from 28.1 ng/ml to 47.3 ng/ml after vitamin D supplementation. Both exercise and vitamin D supplementation independently improved physical function and increased muscle mass in community-dwelling elderly individuals. Moreover, the combination of exercise and vitamin D supplementation might further enhance these positive effects. UMIN Clinical Trial, UMIN000028229. Copyright © 2018. Published by Elsevier B.V.

A randomized controlled trial of comprehensive early intervention care in patients with first-episode psychosis in Japan: 1.5-year outcomes from the J-CAP study.

PubMed

Nishida, Atsushi; Ando, Shuntaro; Yamasaki, Syudo; Koike, Shinsuke; Ichihashi, Kayo; Miyakoshi, Yuji; Maekawa, Sanae; Nakamura, Tomohisa; Natsubori, Tatsunobu; Ichikawa, Eriko; Ishigami, Hiroki; Sato, Kojiro; Matsunaga, Asami; Smith, Jo; French, Paul; Harima, Hirohiko; Kishi, Yoshiki; Fujita, Izumi; Kasai, Kiyoto; Okazaki, Yuji

2018-04-08

The first episode of psychosis represents a critical period wherein comprehensive early intervention in psychosis (EIP) may alter the course of illness. However, evidence from randomized controlled trials that have examined the impact of comprehensive EIP care on clinical and functional recovery assessed by independent blinded raters is limited. The objective of this study was to conduct a single-blinded multicenter trial comparing comprehensive EIP care and standard care in young patients with first-episode psychosis (FEP) in Japan (J-CAP Study). A total of 77 participants with FEP (aged 15-35 years) were randomized to receive standard care or specialized comprehensive EIP care and were followed up for 1.5 years (trial no.: UMIN000005092). Function (measured with the Global Assessment of Functioning) and clinical remission (defined by internationally standardized criteria proposed by the Remission in Schizophrenia Working Group) were evaluated by independent raters who were blinded to group assignment. Dropout rate and other secondary outcomes were also examined. The specialized EIP care group had a higher clinical remission rate (odds ratio, 6.3; 95% confidence interval, 1.0-37.9) and lower treatment dropout rate (odds ratio, 0.038; 95% confidence interval, 0.002-0.923) than the standard care group, even after adjusting for baseline characteristics. Functional improvement in the specialized EIP care group was slightly higher than that in the standard care group, but this difference was not statistically significant (p = 0.195). From the results, we conclude that comprehensive EIP care may provide advantages over standard care in patients with FEP. Copyright © 2018. Published by Elsevier Ltd.

Therapeutic effects of flurbiprofen axetil on mesenteric traction syndrome: randomized clinical trial.

PubMed

Takahashi, Hidemasa; Shida, Dai; Tagawa, Kyoko; Iwamoto, Ryo; Arita, Makoto; Arai, Hiroyuki; Suzuki, Takeo

2017-08-11

This study aimed to reveal the appropriate timing for the intravenous administration of flurbiprofen axetil for preventing mesenteric traction syndrome (MTS), caused by prostacyclin release. In this prospective, randomized, clinical study, forty-five patients who were undergoing elective surgery for colorectal cancer via laparotomy were enrolled. Patients were randomly divided into 3 groups: a preoperative group (n = 16) receiving flurbiprofen axetil directly before surgery; a post-MTS group (n = 14) receiving following MTS onset; and a control group (n = 15) who were not administered flurbiprofen axetil. 6-keto-PGF1α, a stable metabolite of prostacyclin, levels were measured and mean blood pressures were recorded. In the preoperative group, 6-keto-PGF1α levels did not increase, blood pressure levels did not decrease, and no facial flushing was observed. In both the post-MTS and control groups, 6-keto-PGF1α levels increased markedly after mesenteric traction and blood pressure decreased significantly. The post-MTS group exhibited a faster decreasing trend in 6-keto-PGF1α levels and quick restore of the mean blood pressure, and the use of vasopressors and phenylephrine were lower than that in the control group. Even therapeutic administration of flurbiprofen axetil after the onset of MTS has also effects on MTS by suppressing prostacyclin production. Clinical trial number: UMIN000009111 . (Registered 14 October 2012).

[Development of Peptide Vaccines for Triple-Negative Breast Cancer Treatment].

PubMed

Toh, Uhi; Saku, Shuko; Okabe, Mina; Iwakuma, Nobutaka; Kimitsuki, Yuko; Akashi, Momoko; Ogo, Etsuyo; Yamada, Akira; Shichijo, Shigeki; Itoh, Kyogo; Akagi, Yoshito

2016-10-01

Our previous phase II clinical trial showed that therapeutically selected personalized peptide vaccines(PPVs)were effective at boosting anticancer immunity; the immune response after PPV was associated with a clinical outcome as a prognostic factor for metastatic breast cancer(mBC). We conducted an early phase II study to evaluate the safety and efficacy of a new regimen using multiple peptide vaccines(KRM-19)for patients with metastatictriple -negative breast cancer. KRM-19 consisted of 19 mixed peptides chosen from the previously reported 31 PPVs according to their anti-tumor immunologiceffec ts and safety profiles for patients with mBC. All patients had histologically confirmed measurable ER-PgR-HER2- mBC and their human leukocyte antigen(HLA) / -A molecules were A2, A3, A11, A24, A26, A31, or A33. KRM-19(19mg/mL)was administrated subcutaneously every week for a total of 6 doses. Concurrent conventional chemo- and/or endocrine therapy were not permitted during treatment. This was an open-label, early phase II study. The primary endpoint was safety and anti-tumor immunologic effect, while the secondary endpoints were clinical responses and progression-free survival(PFS). The estimated enrollment was 10-15 and 8 patients were enrolled(Clinical trial registry number: UMIN000014616). Measurement of peptide-specific cytotoxic T lymphocyte and IgG responses were conducted before and after vaccination. The correlation between PFS and the increased IgG response and/or CTL levels were investigated.

The effects of daily bathing on symptoms of patients with bronchial asthma

PubMed Central

Arimoto, Yoshihito; Homma, Chie; Takeoka, Shinjiro; Fukusumi, Munehisa; Mouri, Atsuto; Hamamoto, Yoichiro

2016-01-01

Background The influence of bathing in asthma patients is not yet fully known. Objective We conducted an observational study to investigate changes in symptoms and their degree by bathing in asthmatic patients. Methods A questionnaire focusing on ever experienced bathing-induced symptom changes and their degree, as well as contributing factors, was designed and administered to asthmatic patients in the outpatient department of our institute between January 2012 and November 2013. Results Two hundred fifteen cases were recruited. In 60 cases (27.9%), asthmatic symptoms appeared, including 20 cases of chest discomfort (33.3%), 19 cases of cough (31.7%), and 21 cases of wheezing (35.0%). The triggering factors included vapor inhalation (32 cases, 53.3%), hydrostatic pressure on the thorax due to body immersion in the bathtub (26 cases, 43.3%), and sudden change of air temperature (16 cases, 26.7%). Thirty-eight cases (17.7%) experienced improvement in active asthmatic symptoms by bathing. Vapor inhalation was the most common contributing factor (34 cases, 89.5%), followed by warming of the whole body (13 cases, 34.2%). There was no relationship between asthma severity and the appearance of bathing-induced symptoms or improvement of active asthmatic symptoms by bathing. Conclusion The effects of bathing in asthmatic patients widely differed from patient to patient and their etiology includes several factors. For those who suffer from bathing-induced asthma symptoms, preventive methods, such as premedication with bronchodilators before bathing, should be established. This study is registered in the University Hospital Medical Information Network (UMIN) clinical trials registry in Japan with the registration number UMIN000015641. PMID:27141485

Randomized clinical trial of immersive virtual reality tour of the operating theatre in children before anaesthesia.

PubMed

Ryu, J-H; Park, S-J; Park, J-W; Kim, J-W; Yoo, H-J; Kim, T-W; Hong, J S; Han, S-H

2017-11-01

A virtual reality (VR) tour of the operating theatre before anaesthesia could provide a realistic experience for children. This study was designed to determine whether a preoperative VR tour could reduce preoperative anxiety in children. Children scheduled for elective surgery under general anaesthesia were randomized into a control or VR group. The control group received conventional information regarding anaesthesia and surgery. The VR group watched a 4-min video showing Pororo, the famous little penguin, visiting the operating theatre and explaining what is in it. The main outcome was preoperative anxiety, assessed using the modified Yale Preoperative Anxiety Scale (m-YPAS) before entering the operating theatre. Secondary outcomes included induction compliance checklist (ICC) and procedural behaviour rating scale (PBRS) scores during anaesthesia. A total of 69 children were included in the analysis, 35 in the control group and 34 in the VR group. Demographic data and induction time were similar in the two groups. Children in the VR group had a significantly lower m-YPAS score than those in the control group (median 31·7 (i.q.r. 23·3-37·9) and 51·7 (28·3-63·3) respectively; P < 0·001). During anaesthesia, the VR group had lower ICC and PBRS scores than the control group. This preoperative VR tour of the operating theatre was effective in alleviating preoperative anxiety and increasing compliance during induction of anaesthesia in children undergoing elective surgery. Registration number: UMIN000025232 (http://www.umin.ac.jp/ctr). © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

A community-wide campaign to promote physical activity in middle-aged and elderly people: a cluster randomized controlled trial

PubMed Central

2013-01-01

Background We aimed to evaluate the effectiveness of a community-wide campaign (CWC) for promoting physical activity in middle-aged and elderly people. Methods A cluster randomized controlled trial (RCT) with a community as the unit of randomization was performed using a population-based random-sampled evaluation by self-administered questionnaires in the city of Unnan, Shimane Prefecture, Japan. The evaluation sample included 6000 residents aged 40 to 79 years. We randomly allocated nine communities to the intervention group and three to the control group. The intervention was a CWC from 2009 to 2010 to promote physical activity, and it comprised information, education, and support delivery. The primary outcome was a change in engaging in regular aerobic, flexibility, and/or muscle-strengthening activities evaluated at the individual level. Results In total, 4414 residents aged 40–79 years responded to a self-administered questionnaire (73.6% response rate). Awareness of the CWC was 79% in the intervention group. Awareness and knowledge were significantly different between the intervention and control groups, although there were no significant differences in belief and intention. The 1-year CWC did not significantly promote the recommended level of physical activity (adjusted odds ratio: 0.97; 95% confidence interval: 0.84–1.14). Conclusions This cluster RCT showed that the CWC did not promote physical activity in 1 year. Significant differences were observed in awareness and knowledge between intervention and control groups as short-term impacts of the campaign. Trial registration UMIN-CTR UMIN000002683 PMID:23570536

Do emergency medicine journals promote trial registration and adherence to reporting guidelines? A survey of "Instructions for Authors".

PubMed

Sims, Matthew T; Henning, Nolan M; Wayant, C Cole; Vassar, Matt

2016-11-24

The aim of this study was to evaluate the current state of two publication practices, reporting guidelines requirements and clinical trial registration requirements, by analyzing the "Instructions for Authors" of emergency medicine journals. We performed a web-based data abstraction from the "Instructions for Authors" of the 27 Emergency Medicine journals catalogued in the Expanded Science Citation Index of the 2014 Journal Citation Reports and Google Scholar Metrics h5-index to identify whether each journal required, recommended, or made no mention of the following reporting guidelines: EQUATOR Network, ICMJE, ARRIVE, CARE, CONSORT, STARD, TRIPOD, CHEERS, MOOSE, STROBE, COREQ, SRQR, SQUIRE, PRISMA-P, SPIRIT, PRISMA, and QUOROM. We also extracted whether journals required or recommended trial registration. Authors were blinded to one another's ratings until completion of the data validation. Cross-tabulations and descriptive statistics were calculated using IBM SPSS 22. Of the 27 emergency medicine journals, 11 (11/27, 40.7%) did not mention a single guideline within their "Instructions for Authors," while the remaining 16 (16/27, 59.3%) mentioned one or more guidelines. The QUOROM statement and SRQR were not mentioned by any journals whereas the ICMJE guidelines (18/27, 66.7%) and CONSORT statement (15/27, 55.6%) were mentioned most often. Of the 27 emergency medicine journals, 15 (15/27, 55.6%) did not mention trial or review registration, while the remaining 12 (12/27, 44.4%) at least mentioned one of the two. Trial registration through ClinicalTrials.gov was mentioned by seven (7/27, 25.9%) journals while the WHO registry was mentioned by four (4/27, 14.8%). Twelve (12/27, 44.4%) journals mentioned trial registration through any registry platform. The aim of this study was to evaluate the current state of two publication practices, reporting guidelines requirements and clinical trial registration requirements, by analyzing the "Instructions for Authors" of emergency medicine journals. In this study, there was not a single reporting guideline mentioned in more than half of the journals. This undermines efforts of other journals to improve the completeness and transparency of research reporting. Reporting guidelines are infrequently required or recommended by emergency medicine journals. Furthermore, few require clinical trial registration. These two mechanisms may limit bias and should be considered for adoption by journal editors in emergency medicine. UMIN000022486.

Comparison of Pressure Changes by Head and Neck Position between High-Volume Low-Pressure and Taper-Shaped Cuffs: A Randomized Controlled Trial

PubMed Central

Komasawa, Nobuyasu; Mihara, Ryosuke; Imagawa, Kentaro; Hattori, Kazuo; Minami, Toshiaki

2015-01-01

The present study compared changes in cuff pressure by head and neck position between high-volume low-pressure (HVLP) and taper-shaped (taper) cuffs in a prospective randomized clinical trial. Methods. Forty patients were intubated using tracheal tubes with either HVLP (n = 20; HVLP group) or taper-shaped (n = 20; Taper group) cuffs. Initial cuff pressure was adjusted to 15, 20, or 25 cmH2O in the neutral position. Cuff pressure was evaluated after changing the head and neck positions to flexion, extension, and rotation. Results. Cuff pressure significantly increased with flexion in both HVLP and Taper groups at all initial cuff pressures. It significantly increased with extension in the HVLP group, but not in the Taper group. Cuff pressure did not significantly differ with rotation in either group and was significantly smaller in the Taper group during flexion and extension than in the HVLP group, regardless of initial cuff pressure. Conclusion. Cuff pressure changes with head and neck flexion and extension were smaller in the Taper group than in the HVLP group. Our results highlight the potential for taper cuffs to prevent excessive cuff pressure increases with positional changes in the head and neck. This trial is registered with UMIN000016119. PMID:26509152

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zenda, Sadamoto, E-mail: szenda@east.ncc.go.jp; Kojima, Takashi; Kato, Ken

Purpose: To clarify, in a multicenter, single-arm, phase 2 study (UMIN Clinical Trials Registry no. UMIN000001439), the clinical profile of chemoradiotherapy (CRT) for cervical esophageal cancer. Patients and Methods: Patients with operable cervical esophageal cancer, excluding candidates for endoscopic resection, were enrolled. Protocol treatment consisted of CRT and adjuvant chemotherapy (CT). First, patients received concurrent CRT with 5-fluorouracil (5-FU) plus cisplatin (CDDP). Chemotherapy consisted of 5-FU at 700 mg/m{sup 2} intravenous on days 1 to 4 and CDDP at 70 mg/m{sup 2} intravenous on day 1, repeated every 4 weeks for 2 cycles. Radiation therapy consisted of 60 Gy in 30 fractions. After completion ofmore » CRT, 2 additional cycles of CT with 5-FU (800 mg/m{sup 2}, days 1-5) and CDDP (80 mg/m{sup 2}, day 1) were repeated at a 4-week interval. The primary endpoint was 3-year overall survival. Results: Thirty patients were enrolled across 8 institutions in Japan, consisting of 26 men and 4 women with a median age of 64.5 years (range, 50-75 years). No grade 4 hematologic toxicity was seen in the CRT phase, and 1 grade 4 thrombocytopenia was seen in the CT phase. Grade 3 nonhematologic acute toxicities in the CRT phase were nausea (10%), mucositis (13.3%), and dysphagia (13.3%). No treatment-related death in either phase occurred. Overall complete response rate was 73%, and 3-year overall and laryngectomy-free survival were 66.5% and 52.5%, respectively. Regarding T4 disease, 3-year overall and laryngectomy-free survival were 58.3% and 38.5%, respectively. Conclusions: This study, the first prospective study for cervical esophageal cancer, showed that CRT has sufficient efficacy and safety for use as an alternative to surgery for these patients.« less

Magnetic Resonance Imaging More Accurately Classifies Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease Than Transient Elastography.

PubMed

Imajo, Kento; Kessoku, Takaomi; Honda, Yasushi; Tomeno, Wataru; Ogawa, Yuji; Mawatari, Hironori; Fujita, Koji; Yoneda, Masato; Taguri, Masataka; Hyogo, Hideyuki; Sumida, Yoshio; Ono, Masafumi; Eguchi, Yuichiro; Inoue, Tomio; Yamanaka, Takeharu; Wada, Koichiro; Saito, Satoru; Nakajima, Atsushi

2016-03-01

Noninvasive methods have been evaluated for the assessment of liver fibrosis and steatosis in patients with nonalcoholic fatty liver disease (NAFLD). We compared the ability of transient elastography (TE) with the M-probe, and magnetic resonance elastography (MRE) to assess liver fibrosis. Findings from magnetic resonance imaging (MRI)-based proton density fat fraction (PDFF) measurements were compared with those from TE-based controlled attenuation parameter (CAP) measurements to assess steatosis. We performed a cross-sectional study of 142 patients with NAFLD (identified by liver biopsy; mean body mass index, 28.1 kg/m(2)) in Japan from July 2013 through April 2015. Our study also included 10 comparable subjects without NAFLD (controls). All study subjects were evaluated by TE (including CAP measurements), MRI using the MRE and PDFF techniques. TE identified patients with fibrosis stage ≥2 with an area under the receiver operating characteristic (AUROC) curve value of 0.82 (95% confidence interval [CI]: 0.74-0.89), whereas MRE identified these patients with an AUROC curve value of 0.91 (95% CI: 0.86-0.96; P = .001). TE-based CAP measurements identified patients with hepatic steatosis grade ≥2 with an AUROC curve value of 0.73 (95% CI: 0.64-0.81) and PDFF methods identified them with an AUROC curve value of 0.90 (95% CI: 0.82-0.97; P < .001). Measurement of serum keratin 18 fragments or alanine aminotransferase did not add value to TE or MRI for identifying nonalcoholic steatohepatitis. MRE and PDFF methods have higher diagnostic performance in noninvasive detection of liver fibrosis and steatosis in patients with NAFLD than TE and CAP methods. MRI-based noninvasive assessment of liver fibrosis and steatosis is a potential alternative to liver biopsy in clinical practice. UMIN Clinical Trials Registry No. UMIN000012757. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Efficacy of polymyxin B-immobilized fiber hemoperfusion for patients with septic shock caused by Gram-negative bacillus infection.

PubMed

Saito, Nobuyuki; Sugiyama, Kazuhiro; Ohnuma, Testu; Kanemura, Takashi; Nasu, Michitaka; Yoshidomi, Yuya; Tsujimoto, Yuta; Adachi, Hiroshi; Koami, Hiroyuki; Tochiki, Aito; Hori, Kota; Wagatsuma, Yukiko; Matsumoto, Hisashi

2017-01-01

Septic shock-associated mortality in intensive care units (ICUs) remains high, with reported rates ranging 30-50%. In particular, Gram-negative bacilli (GNB), which induce significant inflammation and consequent multiple organ failure, are the etiological bacterial agent in 40% of severe sepsis cases. Hemoperfusion using polymyxin B-immobilized fiber (PMX), which adsorbs endotoxin, is expected to reduce the inflammatory sepsis cascade due to GNB. However, the clinical efficacy of this treatment has not yet been demonstrated. Here, we aimed to verify the efficacy of endotoxin adsorption therapy using PMX through a retrospective analysis of 413 patients who received broad spectrum antimicrobial treatment for GNB-related septic shock between January 2009 and December 2012 in 11 ICUs of Japanese tertiary hospitals. After aligning the patients' treatment time phases, we classified patients in two groups depending on whether PMX hemoperfusion (PMXHP) therapy was administered or not within 24 hours after ICU admission (PMXHP group: n = 134, conventional group: n = 279). The primary study endpoint was the mortality rate at 28 days after ICU admission. The mean age was 72.4 (standard deviation: 12.6) years, and the mean Sequential Organ Failure Assessment score at ICU admission was 9.9 (3.4). The infection sites included intra-abdominal (38.0%), pulmonary (18.9%), and urinary tract (32.2%), and two thirds of all patients had GNB-related bacteremia. Notably, the mortality at 28 days after ICU admission did not differ between the groups (PMXHP: 29.1% vs. conventional: 29.0%, P = 0.98), and PMXHP therapy was not found to improve this outcome in a Cox regression analysis (hazard ratio = 1.16; 95% confidence interval, 0.81-1.64, P = 0.407). We conclude that PMX-based endotoxin adsorption within 24 hours from ICU admission was not associated with mortality among patients with septic shock due to GNB. University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012748).

Reactive Oxygen Metabolites are Closely Associated With the Diagnosis and Prognosis of Coronary Artery Disease

PubMed Central

Hirata, Yoshihiro; Yamamoto, Eiichiro; Tokitsu, Takanori; Kusaka, Hiroaki; Fujisue, Koichiro; Kurokawa, Hirofumi; Sugamura, Koichi; Maeda, Hirofumi; Tsujita, Kenichi; Kaikita, Koichi; Hokimoto, Seiji; Sugiyama, Seigo; Ogawa, Hisao

2015-01-01

Background Reactive oxygen species (ROS) are associated with development of coronary artery disease (CAD). However, there's no useful biomarker of ROS in CAD. Methods and Results We recruited 395 consecutive CAD patients who were performed coronary angiography (262 male and 133 female, age 70.2±10), and we measured serum derivatives of reactive oxidative metabolites (DROM) were measured. Two hundred twenty‐seven non‐CAD patients were also enrolled. We performed follow‐up study in these 395 CAD patients and case‐control study after risk factor and 1:1 pair matching (both, n=163). As subgroup analysis, DROM were also measured at the aortic root and the coronary sinus in 59 CAD patients. DROM were significantly higher in CAD patients (n=163, median [inter‐quartile range, IQR]=338 [302 to 386]) than in risk factor‐matched non‐CAD patients (n=163, 311 [282 to 352.5], effect size=0.33, P<0.001). During a mean follow‐up period of 20 months of 395 CAD patients, 83 cardiovascular events were recorded. Kaplan‐Meier analysis showed a higher probability of cardiovascular events in the high‐DROM group (>346 U.CARR) than in the low‐DROM group (≤346 U.CARR) (P=0.001 [log‐rank test]). Multivariate Cox hazard analysis identified ln‐DROM as an independent predictor for cardiovascular events (hazard ratio: 10.8, 95% confidence interval: 2.76 to 42.4, P=0.001). The transcardiac gradient of DROM was significantly higher in CAD patients than in non‐CAD patients (−2.0 [−9.0 to 9.0] versus 8 [−8.0 to 28.3], effect size=0.21, P=0.04), indicating that DROM production in coronary circulation is associated with development of CAD. Conclusion DROM are increased in CAD patients and associated with future cardiovascular events. DROM might provide clinical benefits for risk stratification of CAD. Clinical Trial Registration URL: http://www.umin.ac.jp/ctr/. Unique identifier: UMIN000012990. PMID:25630910

Study protocol for a randomised controlled trial of cognitive processing therapy for post-traumatic stress disorder among Japanese patients: the Safety, Power, Intimacy, Esteem, Trust (SPINET) study.

PubMed

Ito, Masaya; Horikoshi, Masaru; Resick, Patricia A; Katayanagi, Akiko; Miyamae, Mitsuhiro; Takagishi, Yuriko; Takebayashi, Yoshitake; Kanie, Ayako; Hirabayashi, Naotsugu; Furukawa, Toshiaki A

2017-06-30

Cognitive processing therapy (CPT) is widely regarded as a safe and effective first-line treatment for individuals with post-traumatic stress disorder (PTSD); however, no comparative studies have been conducted to examine the treatment outcomes in an Asian population. The aim of the present trial is to investigate the efficacy of CPT (individual format) as a treatment for PTSD in a population of Japanese patients. A 16-week, single-centre, assessor-masked, randomised, parallel-group superiority trial has been designed to compare the efficacy of CPT in conjunction with treatment as usual (mostly pharmacotherapy and clinical monitoring) versus treatment as usual alone. The Clinician-Administered PTSD Scale for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) will be our primary outcome measure of the post-traumatic stress symptoms at 17 weeks, whereas the PTSD Checklist for DSM-5 and determination of the operationally defined responder status will be used to assess the secondary outcomes. An estimated sample size of 29 participants in each group will be required to detect an expected effect size of 1.4 (95% CI 0.85 to 1.95). The institutional review board at the National Center of Neurology and Psychiatry in Japan approved this study. The results of this clinical trial will be presented at conferences and disseminated through publication in a peer-reviewed journal. UMIN000021670 (registered on 1 April 2016). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Comparison of liraglutide plus basal insulin and basal-bolus insulin therapy (BBIT) for glycemic control, body weight stability, and treatment satisfaction in patients treated using BBIT for type 2 diabetes without severe insulin deficiency: A randomized prospective pilot study.

PubMed

Yamamoto, Saki; Hayashi, Toshiyuki; Ohara, Makoto; Goto, Satoshi; Sato, Jun; Nagaike, Hiroe; Fukase, Ayako; Sato, Nobuko; Hiromura, Munenori; Tomoyasu, Masako; Nakanishi, Noriko; Lee, Soushou; Osamura, Anna; Yamamoto, Takeshi; Fukui, Tomoyasu; Hirano, Tsutomu

2018-03-26

We examined whether 0.9 mg/day liraglutide plus basal insulin (Lira-basal) is superior to basal-bolus insulin therapy (BBIT) for type 2 diabetes (T2DM) without severe insulin deficiency as determined by glucagon stimulation. Fifty patients receiving BBIT were enrolled in this 24-week, prospective, randomized, open-labeled study. After excluding subjects with fasting C-peptide immunoreactivity (CPR) < 1.0 ng/mL and CPR increase < 1.0 ng/mL at 6 min post glucagon injection, 25 were randomly allocated to receive Lira-basal (n = 12) or continued BBIT (n = 13). Primary endpoint was change in HbA1c. Secondary endpoints were changes in body weight (BW), 7-point self-monitored blood glucose (SMBG), and Diabetes Treatment Satisfaction Questionnaire status (DTSQs) scores. The Lira-basal group demonstrated reduced HbA1c, whereas the BBIT group showed no change. BW was reduced in the Lira-basal group but increased in the BBIT group. The Lira-basal group also exhibited significantly reduced pre-breakfast and pre-lunch SMBG. DTSQs scores improved in the Lira-basal group but not the BBIT group. Plasma lipids, liver function, and kidney function were not significantly changed in either group. Lira-basal therapy is superior to BBIT for T2DM without severe insulin deficiency. This study was registered with UMIN Clinical Trials Registry (UMIN000028313). Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Effects of a job crafting intervention program on work engagement among Japanese employees: a pretest-posttest study.

PubMed

Sakuraya, Asuka; Shimazu, Akihito; Imamura, Kotaro; Namba, Katsuyuki; Kawakami, Norito

2016-10-24

Job crafting, an employee-initiated job design/redesign, has become important for employees' well-being such as work engagement. This study examined the effectiveness of a newly developed job crafting intervention program on work engagement (as primary outcome), as well as job crafting and psychological distress (as secondary outcomes), using a pretest-posttest study design among Japanese employees. Participants were managers of a private company and a private psychiatric hospital in Japan. The job crafting intervention program consisted of two 120-min sessions with a two-week interval between them. Outcomes were assessed at baseline (Time 1), post-intervention (Time 2), and a one-month follow-up (Time 3). The mixed growth model analyses were conducted using time (Time 1, Time 2, and Time 3) as an indicator of intervention effect. Effect sizes were calculated using Cohen's d. The program showed a significant positive effect on work engagement (t = 2.20, p = 0.03) in the mixed growth model analyses, but with only small effect sizes (Cohen's d = 0.33 at Time 2 and 0.26 at Time 3). The program also significantly improved job crafting (t = 2.36, p = 0.02: Cohen's d = 0.36 at Time 2 and 0.47 at Time 3) and reduced psychological distress (t = -2.06, p = 0.04: Cohen's d = -0.15 at Time 2 and -0.31 at Time 3). The study indicated that the newly developed job crafting intervention program was effective in increasing work engagement, as well as in improving job crafting and decreasing psychological distress, among Japanese managers. UMIN Clinical Trials Registry UMIN000024062 . Retrospectively registered 15 September 2016.

Pretreatment evaluation of fluorescence resonance energy transfer-based drug sensitivity test for patients with chronic myelogenous leukemia treated with dasatinib.

PubMed

Kondo, Takeshi; Fujioka, Mari; Tsuda, Masumi; Murai, Kazunori; Yamaguchi, Kohei; Miyagishima, Takuto; Shindo, Motohiro; Nagashima, Takahiro; Wakasa, Kentaro; Fujimoto, Nozomu; Yamamoto, Satoshi; Yonezumi, Masakatsu; Saito, Souichi; Sato, Shinji; Ogawa, Kazuei; Chou, Takaaki; Watanabe, Reiko; Kato, Yuichi; Takahashi, Shuichiro; Okano, Yoshiaki; Yamamoto, Joji; Ohta, Masatsugu; Iijima, Hiroaki; Oba, Koji; Kishino, Satoshi; Sakamoto, Junichi; Ishida, Yoji; Ohba, Yusuke; Teshima, Takanori

2018-05-02

Tyrosine kinase inhibitors (TKI) are used for primary therapy in patients with newly diagnosed CML. However, a reliable method for optimal selection of a TKI from the viewpoint of drug sensitivity of CML cells has not been established. We have developed a FRET-based drug sensitivity test in which a CrkL-derived fluorescent biosensor efficiently quantifies the kinase activity of BCR-ABL of living cells and sensitively evaluates the inhibitory activity of a TKI against BCR-ABL. Here, we validated the utility of the FRET-based drug sensitivity test carried out at diagnosis for predicting the molecular efficacy. Sixty-two patients with newly diagnosed chronic phase CML were enrolled in this study and treated with dasatinib. Bone marrow cells at diagnosis were subjected to FRET analysis. The ΔFRET value was calculated by subtraction of FRET efficiency in the presence of dasatinib from that in the absence of dasatinib. Treatment response was evaluated every 3 months by the BCR-ABL1 International Scale. Based on the ΔFRET value and molecular response, a threshold of the ΔFRET value in the top 10% of FRET efficiency was set to 0.31. Patients with ΔFRET value ≥0.31 had significantly superior molecular responses (MMR at 6 and 9 months and both MR4 and MR4.5 at 6, 9, and 12 months) compared with the responses in patients with ΔFRET value <0.31. These results suggest that the FRET-based drug sensitivity test at diagnosis can predict early and deep molecular responses. This study is registered with UMIN Clinical Trials Registry (UMIN000006358). © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine: a randomized placebo-controlled double-blind crossover study.

PubMed

Takiguchi, Kazuo; Uezato, Akihito; Itasaka, Michio; Atsuta, Hidenori; Narushima, Kenji; Yamamoto, Naoki; Kurumaji, Akeo; Tomita, Makoto; Oshima, Kazunari; Shoda, Kosaku; Tamaru, Mai; Nakataki, Masahito; Okazaki, Mitsutoshi; Ishiwata, Sayuri; Ishiwata, Yasuyoshi; Yasuhara, Masato; Arima, Kunimasa; Ohmori, Tetsuro; Nishikawa, Toru

2017-07-12

It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs. We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales. D-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower. It was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity. UMIN Clinical Trials Registry (number UMIN000000468 ). Registered 18 August 2006.

Efficacy and safety of inhaled N-acetylcysteine in idiopathic pulmonary fibrosis: A prospective, single-arm study.

PubMed

Okuda, Ryo; Matsushima, Hidekazu; Oba, Tomohiro; Kawabe, Rie; Matsubayashi, Minako; Amano, Masako; Nishizawa, Tomotaka; Honda, Koujiro

2016-05-01

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with few treatment options. The efficacy of N-acetylcysteine in patients with IPF remains controversial. The aim of this research was to investigate the efficacy of inhaled N-acetylcysteine. This study was designed as a single-center, single-arm, prospective clinical trial. Each patient who had IPF received 352.4mg of inhaled N-acetylcysteine twice daily. In total, 28 patients were enrolled. The mean values of the respiratory function parameters at the initiation of therapy were as follows: forced vital capacity (FVC), 2.27L and %FVC, 76.2%. The mean change in FVC during 26 weeks prior to the inhaled N-acetylcysteine therapy was -170mL, a significant decrease (p=0.019). The mean change in FVC during 26 weeks after the initiation of inhaled N-acetylcysteine therapy was -70mL (p=0.06). When the patients were classified into two groups according to the degree of decline in FVC (≥100mL vs. <100mL) during the 26-week period prior to the initiation of therapy, inhaled N-acetylcysteine showed a greater efficacy in attenuating FVC decline in the ≥100-mL group than in the <100-mL group. Inhaled N-acetylcysteine therapy was effective in patients with mild-to-moderate IPF and was more beneficial in patients who had greater declines in FVC before the initiation of therapy. (UMIN title: Efficacy and safety of inhaled N-acetylcysteine in idiopathic pulmonary fibrosis, UMIN000016706, 2015/03/04.). Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

School-based intervention to prevent overweight and disordered eating in secondary school Malaysian adolescents: a study protocol.

PubMed

Sharif Ishak, Sharifah Intan Zainun; Chin, Yit Siew; Mohd Taib, Mohd Nasir; Mohd Shariff, Zalilah

2016-10-20

Obesity, eating disorders and unhealthy weight-loss practices have been associated with diminished growth in adolescents worldwide. Interventions that address relevant behavioural dimensions have been lacking in Malaysia. This paper describes the protocol of an integrated health education intervention namely 'Eat Right, Be Positive About Your Body and Live Actively' (EPaL), a primary prevention which aimed to promote healthy lifestyle in preventing overweight and disordered eating among secondary school adolescents aged 13-14 years old. Following quasi-experimental design, the intervention is conducted in two secondary schools located in the district of Hulu Langat, Selangor, Malaysia. Adolescents aged 13-14 years will be included in the study. A peer-education strategy is adopted to convey knowledge and teach skills relevant to achieving a healthy lifestyle. The intervention mainly promoted: healthy eating, positive body image and active lifestyle. The following parameters will be assessed: body weight, disordered eating status, stages of change (for healthy diet, breakfast, food portion size, screen viewing and physical activity), body image, health-related quality of life, self-esteem, eating and physical activity behaviours; and knowledge, attitude and practice towards a healthy lifestyle. Assessment will be conducted at three time points: baseline, post-intervention and 3-month follow-up. It is hypothesized that EPaL intervention will contribute in preventing overweight and disordered eating by giving the positive effects on body weight status, healthy lifestyle behaviour, as well as health-related quality of life of peer educators and participants. It may serve as a model for similar future interventions designed for the Malaysian community, specifically adolescents. UMIN Clinical Trial Registration UMIN000024349 (Date of registration: 11th. October 2016, retrospectively registered).

Changes in Energy Metabolism after Continuous Positive Airway Pressure for Obstructive Sleep Apnea.

PubMed

Tachikawa, Ryo; Ikeda, Kaori; Minami, Takuma; Matsumoto, Takeshi; Hamada, Satoshi; Murase, Kimihiko; Tanizawa, Kiminobu; Inouchi, Morito; Oga, Toru; Akamizu, Takashi; Mishima, Michiaki; Chin, Kazuo

2016-09-15

Disrupted energy homeostasis in obstructive sleep apnea (OSA) may lead to weight gain. Paradoxically, treating OSA with continuous positive airway pressure (CPAP) may also promote weight gain, although the underlying mechanism remains unclear. To explore the underlying mechanism by which patients with OSA gain weight after CPAP. A comprehensive assessment of energy metabolism was performed in 63 newly diagnosed OSA study participants (51 men; 60.8 ± 10.1 yr; apnea-hypopnea index >20 h(-1)) at baseline, CPAP initiation, and at a 3-month follow-up. Measurements included polysomnography, body weight, body composition, basal metabolic rate (BMR), hormones (norepinephrine, cortisol, leptin, ghrelin, insulin-like growth factor-1), dietary intake, eating behavior, and physical activity. BMR significantly decreased after CPAP (1,584 kcal/d at baseline, 1,561 kcal/d at CPAP initiation, and 1,508 kcal/d at follow-up; P < 0.001), whereas physical activity and total caloric intake did not significantly change. In multivariate regression, baseline apnea-hypopnea index, Δurine norepinephrine, and CPAP adherence were significant predictors of ΔBMR. The weight gainers had higher leptin levels, lower ghrelin levels, and higher eating behavior scores than the non-weight gainers, indicating a positive energy balance and disordered eating behavior among the weight gainers. Among the parameters related to energy metabolism, increased caloric intake was a particularly significant predictor of weight gain. Although a reduction in BMR after CPAP predisposes to a positive energy balance, dietary intake and eating behavior had greater impacts on weight change. These findings highlight the importance of lifestyle modifications combined with CPAP. Clinical trial registered with http://www.umin.ac.jp/english/ (UMIN000012639).

Basal-Bolus Insulin Therapy with Gla-300 During Hospitalization Reduces Nocturnal Hypoglycemia in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study.

PubMed

Okajima, Fumitaka; Nakamura, Yuko; Yamaguchi, Yuji; Shuto, Yuki; Kato, Katsuhito; Sugihara, Hitoshi; Emoto, Naoya

2018-04-04

Although reduction in the incidence of nocturnal hypoglycemia, as estimated by symptom or self-monitored plasma glucose, was shown to be more pronounced with 300 units/mL insulin glargine (Gla-300) than with 100 units/mL insulin glargine (Gla-100) in type 2 diabetes patients, the exact frequency of nocturnal hypoglycemia estimated with continuous glucose monitoring (CGM) has not been reported. Forty patients with type 2 diabetes who were admitted for glycemic control with basal-bolus insulin therapy (BBT) were randomized into the Gla-100 and Gla-300 groups. Insulin doses were adjusted to maintain blood glucose levels within 100-120 mg/dL at each meal. Plasma glucose and C-peptide profiles were estimated serially after admission and before discharge. Daily CGM was also performed before discharge. In the Gla-100 and Gla-300 groups, the mean duration of hospitalization was 15 ± 2 and 15 ± 1 days, respectively, and the mean basal insulin dose before discharge was 13 ± 7 and 15 ± 10 units, respectively. The dose of meal-time insulin was not different between the two groups. Compared with the Gla-300 group, the Gla-100 group had significantly lower nocturnal profiles of plasma glucose and C-peptide, but significantly higher frequency of CGM-estimated nocturnal hypoglycemia (10.7% ± 18.4% versus 1.2% ± 3.6%, P = 0.033). In type 2 diabetic patients, reduction in the incidence of CGM-estimated nocturnal hypoglycemia by BBT under tightly controlled diet therapy was higher with Gla-300 than with Gla-100. UMIN clinical trials registry (UMIN000023360).

High-dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma.

PubMed

Akiyama, Hiroki; Takase, Hiroshi; Kubo, Fumito; Miki, Tohru; Yamamoto, Masahide; Tomita, Makoto; Mochizuki, Manabu; Miura, Osamu; Arai, Ayako

2016-10-01

In order to prevent central nervous system (CNS) involvement and improve the prognosis of primary intraocular lymphoma (PIOL), we prospectively evaluated the efficacy of combined therapy using intravitreal methotrexate (MTX) and systemic high-dose MTX on treatment-naïve PIOL. Patients with newly diagnosed PIOL whose lymphoma was limited to the eyes were enrolled. The patients were treated with weekly intravitreal MTX until the ocular lesions were resolved, followed by five cycles of systemic high-dose MTX (3.5 g/m 2 ) every other week. Ten patients were enrolled in this study and completed the treatment. All patients achieved complete response for their ocular lesions with rapid decrease of intravitreal interleukin-10 concentration. Adverse events of intravitreal and systemic high-dose MTX were mild and tolerable. With a median follow-up of 29.5 months, four patients (40%) experienced the CNS disease development and the mean CNS lymphoma-free survival (CLFS) time was 51.1 months. Two-year CLFS, which was the primary end-point of the study, was 58.3% (95% confidence interval, 23.0-82.1%). In contrast, eight patients were treated with intravitreal MTX alone in our institute, and their 2-year CLFS was 37.5% (95% confidence interval, 8.7-67.4%). In conclusion, systemic high-dose MTX following intravitreal MTX is feasible and might be effective in preventing CNS involvement of PIOL. Further arrangements are worth considering in order to improve the effects. This study was registered with UMIN Clinical Trials Registry (UMIN000003921). © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Effect of Daikenchuto (TJ-100) on gastrointestinal symptoms following laparoscopic colectomy in patients with colon cancer: study protocol for a randomized controlled trial.

PubMed

Hoshino, Nobuaki; Kawada, Kenji; Hida, Koya; Wada, Toshiaki; Takahashi, Ryo; Yoshitomi, Mami; Sakai, Yoshiharu

2017-11-21

Postoperative paralytic ileus can be a difficult complication for both surgeons and patients. Causes and treatments have been discussed for more than two centuries, but have not yet been fully resolved. Daikenchuto (TJ-100, DKT) is a traditional Japanese herbal medicine. Recently, some beneficial mechanisms of DKT to relieve paralytic ileus have been reported. DKT can suppress inflammation, increase intestinal blood flow, and accelerate bowel movements. Therefore, we have designed a randomized controlled trial to investigate the effects of DKT on postoperative gastrointestinal symptoms following laparoscopic colectomy in patients with left-sided colon cancer at a single institution. As primary endpoints, the following outcomes will be evaluated: (i) grade of abdominal pain determined using the numeric rating scale (NRS), (ii) grade of abdominal distention determined using the NRS, and (iii) quality of life determined using the Gastrointestinal Quality Life Index (GIQLI). As secondary endpoints, the following will be evaluated: (i) postoperative nutritional status (Onodera's Prognostic Nutritional Index (PNI) and the Controlling Nutritional Status score (CONUT score)), (ii) duration to initial flatus, (iii) duration to initial defecation, (iv) bowel gas volume, (v) character of stool (Bristol Stool Form Scale), (vi) defecation frequency per day, (vii) postoperative complications (Clavien-Dindo classification), (viii) length of postoperative hospital stay, and (ix) metabolites in the stool and blood. This trial is an open-label study, and needs to include 40 patients (20 patients per group) and is expected to span 2 years. To our knowledge, this is the first randomized controlled trial to investigate the effects of DKT on postoperative subjective outcomes (i.e., postoperative quality of life) following laparoscopic colectomy as primary endpoints. Exploratory metabolomics analysis of metabolites in stool and blood will be conducted in this trial, which previously has only been performed in a few human studies. The study aims to guide a future full-scale pragmatic randomized trial to assess the overall effectiveness of DKT to improve the postoperative quality of life following laparoscopic colectomy. UMIN-CTR (Japan), UMIN000023318 . Registered on 25 July 2016.

Effect of canagliflozin on left ventricular diastolic function in patients with type 2 diabetes.

PubMed

Matsutani, Daisuke; Sakamoto, Masaya; Kayama, Yosuke; Takeda, Norihiko; Horiuchi, Ryuzo; Utsunomiya, Kazunori

2018-05-22

Type 2 diabetes mellitus (T2DM) greatly increases the risks of cardiovascular disease and heart failure. In particular, left ventricular diastolic dysfunction that develops from the early stages of T2DM is an important factor in the onset and exacerbation of heart failure. The effect of sodium-glucose cotransporter 2 inhibitors on left ventricular diastolic function has not been elucidated. We have performed the first prospective study on the effects of canagliflozin on left ventricular diastolic function in T2DM. This study was performed to evaluate the effects of additional treatment with canagliflozin for 3 months on left ventricular diastolic function in patients with T2DM. A total of 38 patients with T2DM were consecutively recruited for this study. Left ventricular diastolic function was assessed by echocardiography. The primary study outcome was a change in the septal E/e' as a parameter of left ventricular diastolic function. A total of 37 patients (25 males and 12 females) were included in the analysis. Mean age of participants was 64.2 ± 8.1 years (mean ± SD), mean duration of diabetes was 13.5 ± 8.1 years, and mean HbA1c was 7.9 ± 0.7%. Of the participants, 86.5% had hypertension, 100% had dyslipidemia, and 32.4% had cardiovascular disease. Canagliflozin significantly improved left ventricular diastolic function (septal E/e' ratio 13.7 ± 3.5-12.1 ± 2.8, p = 0.001). Furthermore, among the various parameters that changed through the administration of canagliflozin, only changes in hemoglobin significantly correlated with changes in the septal E/e' ratio (p = 0.002). In multiple regression analysis, changes in hemoglobin were also revealed to be an independent predictive factor for changes in the septal E/e' ratio. This study showed for the first time that canagliflozin could improve left ventricular diastolic function within 3 months in patients with T2DM. The benefit was especially apparent in patients with substantially improved hemoglobin values. Trial registration UMIN Clinical Trials Registry UMIN000028141.

Does attending an exercise class with a spouse improve long-term exercise adherence among people aged 65 years and older: a 6-month prospective follow-up study.

PubMed

Osuka, Yosuke; Jung, Songee; Kim, Taeho; Okubo, Yoshiro; Kim, Eunbi; Tanaka, Kiyoji

2017-07-31

Family support can help older adults better adhere to exercise routine, but it remains unclear whether an exercise program targeting older married couples would have stronger effects on exercise adherence than would a program for individuals. The purpose of this study was to determine the effects of an exercise program on the exercise adherence of older married couples over a 24-week follow-up period. Thirty-four older married couples and 59 older adults participated in this study as couple and non-couple groups (CG and NCG, respectively). All participants attended an 8-week supervised program (once a week and a home-based exercise program comprising walking and strength exercises) and then participated in a follow-up measurement (24 weeks after post-intervention measurement). Exercise adherence was prospectively measured via an exercise habituation diary during the follow-up period-specifically, we asked them to record practice rates for walking (≥2 days/week) and strength exercises (≥6 items for 2 days/week). A multivariate logistic regression analysis was conducted to obtain the CG's odds ratios (ORs) and 95% confidence intervals (CIs) for adherence to walking and strength exercise adjusted for potential confounders (with NCG as the reference). Although the adherence rate of walking exercise in the CG was significantly higher than that in the NCG (29.2%; P < 0.001), there was no significant difference in the adherence rate of strength exercise between the two groups (P = 0.199). The multivariate logistic regression analysis showed that CG had significantly higher odds of adherence to walking exercise compared with the NCG (3.68 [1.57-8.60]). However, the odds of adherence to strength exercise did not significantly differ between the two groups (1.30 [0.52-3.26]). These results suggest that an exercise program targeting older married couples may be a useful strategy for maintaining walking adherence, even six months after the supervised program has ceased. A blinded randomized controlled trial will be needed to confirm this conclusion. Retrospectively registered. UMIN Clinical Trials Registry (Registered: 02/11/16) UMIN000024689 .

Randomized clinical trial of oral and intravenous versus intravenous antibiotic prophylaxis for laparoscopic colorectal resection.

PubMed

Ikeda, A; Konishi, T; Ueno, M; Fukunaga, Y; Nagayama, S; Fujimoto, Y; Akiyoshi, T; Yamaguchi, T

2016-11-01

The use of oral prophylactic antibiotics for the prevention of surgical-site infection (SSI) in patients undergoing laparoscopic surgery for colorectal cancer is controversial. The aim of this RCT was to evaluate whether intravenous perioperative antibiotics are inferior to combined preoperative oral and perioperative intravenous antibiotics in this setting. Patients undergoing elective laparoscopic colorectal resection in a single cancer centre were assigned randomly to combined preoperative oral antibiotics (metronidazole and kanamycin) and perioperative intravenous antibiotics (cefmetazole) (oral/IV group) or to perioperative intravenous antibiotics (cefmetazole) alone (IV-only group). Patients were stratified for the analyses based on type of operation (colonic surgery, anterior resection or abdominoperineal resection), preoperative use of mechanical bowel preparation, preoperative chemoradiotherapy and the presence of diabetes mellitus. The primary endpoint was the overall rate of SSI. Secondary endpoints were the rates of incisional site infection, organ/space infection, anastomotic leakage, intra-abdominal abscess, adverse events and postoperative complications. Of 540 patients offered participation in the trial in 2013-2014, 515 agreed to take part and were randomized. Some 256 patients in the IV-only group and 255 in the oral/IV group completed the treatment per protocol. The overall rate of SSI was 7·8 per cent (20 of 256) in the IV-only group and 7·8 per cent (20 of 255) in the oral/IV group, confirming that perioperative administration of intravenous antibiotics alone was not inferior to the combined regimen (P = 0·017). There were no differences in rates of incisional site infection (5·5 versus 5·9 per cent respectively), organ/space infection (2·3 versus 2·0 per cent) or other secondary endpoints between the two groups. Intravenous perioperative antimicrobial prophylaxis alone is not inferior to combined preoperative oral and intravenous perioperative prophylaxis with regard to SSI in patients with colorectal cancer undergoing elective laparoscopic resection. Registration number: UMIN000019339 ( http://www.umin.ac.jp/ctr/). © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

A phase II trial evaluating the efficacy and safety of perioperative pirfenidone for prevention of acute exacerbation of idiopathic pulmonary fibrosis in lung cancer patients undergoing pulmonary resection: West Japan Oncology Group 6711 L (PEOPLE Study).

PubMed

Iwata, Takekazu; Yoshino, Ichiro; Yoshida, Shigetoshi; Ikeda, Norihiko; Tsuboi, Masahiro; Asato, Yuji; Katakami, Nobuyuki; Sakamoto, Kazuhiro; Yamashita, Yoshinori; Okami, Jiro; Mitsudomi, Tetsuya; Yamashita, Motohiro; Yokouchi, Hiroshi; Okubo, Kenichi; Okada, Morihito; Takenoyama, Mitsuhiro; Chida, Masayuki; Tomii, Keisuke; Matsuura, Motoki; Azuma, Arata; Iwasawa, Tae; Kuwano, Kazuyoshi; Sakai, Shuji; Hiroshima, Kenzo; Fukuoka, Junya; Yoshimura, Kenichi; Tada, Hirohito; Nakagawa, Kazuhiko; Nakanishi, Yoichi

2016-07-22

Idiopathic pulmonary fibrosis (IPF) often accompanies lung cancer, and life-threatening acute exacerbation (AE) of IPF (AE-IPF) is reported to occur in 20 % of IPF patients who undergo lung cancer surgery. Pirfenidone is an anti-fibrotic agent known to reduce disease progression in IPF patients. A phase II study was conducted to evaluate whether perioperative pirfenidone treatment could reduce the incidence of postoperative AE-IPF patients with lung cancer. Pirfenidone was orally administered to IPF patients who were candidates for lung cancer surgery; pirfenidone was dosed at 600 mg/day for the first 2 weeks, followed by 1200 mg/day. Surgery was performed after at least 2 weeks of 1200-mg/day administration. The primary endpoint was non-AE-IPF rate during postoperative days 0-30, compared to the null value of 80 %, and the secondary endpoint was safety. Radiologic and pathologic diagnoses of IPF and AE-IPF were confirmed by an independent review committee. From June 2012 to January 2014, 43 cases were enrolled, and 39 were eligible (full analysis set [FAS]). Both pirfenidone treatment and surgery were performed in 36 patients (per protocol set [PPS]). AE-IPF did not occur in 37/39 patients (94.9 % [95 % confidential interval: 82.7-99.4 %, p = 0.01]) in the FAS, and in 38/39 patients (97.2 % [95 % confidential interval: 85.5-99.9 %, p = 0.004] in the PPS. A grade 5 adverse event (death) occurred in 1 patient, after AE-IPF; no other grade 3-5 adverse events were observed. Perioperative pirfenidone treatment is safe, and is promising for reducing AE-IPF after lung cancer surgery in IPF patients. This clinical trial was registered with the University Hospital Medical Information Network (UMIN) on April 16th, 2012 (REGISTRATION NUMBER: UMIN000007774 ).

Effects of home-based exercise on pre-dialysis chronic kidney disease patients: a randomized pilot and feasibility trial.

PubMed

Hiraki, Koji; Shibagaki, Yugo; Izawa, Kazuhiro P; Hotta, Chiharu; Wakamiya, Akiko; Sakurada, Tsutomu; Yasuda, Takashi; Kimura, Kenjiro

2017-06-17

Only a few research is available on the effects of home-based exercise training on pre-dialysis chronic kidney disease (CKD) patients. Therefore, we aimed to elucidate the effect of home-based exercise therapy on kidney function and arm and leg muscle strength in pre-dialysis CKD patients. Thirty-six male stage 3-4 pre-dialysis CKD patients (age, 68.7 ± 6.8 years; estimated glomerular filtration rate (eGFR), 39.0 ± 11.6 ml/min/1.73 m 2 ) who were being treated as outpatients were included. The subjects were randomly assigned to an exercise intervention group (Ex group: 18) and a control group (C group: 18). The Ex group wore accelerometer pedometers and were instructed to perform home-based aerobic and resistance exercises, such as brisk walking for 30 min per day, for 12 months. The C group subjects wore accelerometer pedometers but received no exercise therapy guidance; the number of steps covered during normal daily activities was recorded for the C group. The outcome measures were changes in kidney function and handgrip and knee extension muscle strength. Values at the baseline (T1) and 12 months later (T2) were compared. There were no significant differences in baseline characteristics between the two groups; however, the C group was more physically active than the Ex group. Eight subjects dropped out, and 28 subjects (14 in each group) were included in the final analysis. Physical activity increased significantly only in the Ex group. Grip strength (F = 7.0, p = 0.01) and knee extension muscle strength (F = 14.3, p < 0.01) were found to improve only in the Ex group. Further, the changes in eGFR were not significantly different between the two groups (F = 0.01, p = 0.93). Home-based exercise therapy for pre-dialysis CKD patients was feasible and improved arm and leg muscle strength without affecting kidney function. UMIN Clinical Trials Registry ( UMIN000005091 ). Registered 2/15/2011.

A foot-care program to facilitate self-care by the elderly: a non-randomized intervention study.

PubMed

Omote, Shizuko; Watanabe, Arisu; Hiramatsu, Tomoko; Saito, Emiko; Yokogawa, Masami; Okamoto, Rie; Sakakibara, Chiaki; Ichimori, Akie; Kyota, Kaoru; Tsukasaki, Keiko

2017-11-09

We aimed to evaluate a foot-care awareness program designed to improve foot morphology, physical functioning, and fall prevention among the community-dwelling elderly. Eleven independent community-dwelling elderly women (aged 61-83 years) were provided with foot-care advice and shown effective foot-care techniques to perform regularly for 6 months, and compared with a control group of 10 elderly women who did not receive any intervention. Measurements of foot form, functional capacity, subjective foot movement, and physical function were taken at baseline and 6-month follow-up. At follow-up, improvements were seen in the intervention group in foot morphology, subjective foot movement, foot pressure, and balance. In the intervention group, 90% of women had maintained or improved foot form and none of them had fallen during the post-intervention period, compared to the control group where 30% improved foot form (p = 0.0075) and four (40%) of them had fallen. Therefore, a foot-care program may have the potential to prevent falls and improve mobility among the elderly. Trial Registration UMIN-CTR No. UMIN000029632. Date of Registration: October 19, 2017.

Intrinsic development of choroidal and thalamic collaterals in hemorrhagic-onset moyamoya disease: case-control study of the Japan Adult Moyamoya Trial.

PubMed

Fujimura, Miki; Funaki, Takeshi; Houkin, Kiyohiro; Takahashi, Jun C; Kuroda, Satoshi; Tomata, Yasutake; Tominaga, Teiji; Miyamoto, Susumu

2018-05-04

OBJECTIVE This study was performed to identify the angiographic features of hemorrhagic-onset moyamoya disease (MMD) in comparison with those of patients with ischemic-onset MMD. METHODS This case-control study compared the data set of the Japan Adult Moyamoya (JAM) Trial with the angiographic data of adult patients with ischemic-onset MMD. The authors analyzed angiograms obtained at onset, classifying the collaterals into 3 subtypes: lenticulostriate anastomosis, thalamic anastomosis, and choroidal anastomosis. They then compared the extent of these collaterals, as indicated by the collateral development grade from 0 to 2 in each subtype, between the JAM Trial group and the ischemic-onset group. They also compared the involvement of the posterior cerebral artery (PCA) and Suzuki's angiographic staging between each group. RESULTS Among 89 ischemic-onset patients, 103 symptomatic hemispheres in 80 patients were analyzed and compared with 75 hemorrhagic hemispheres from the JAM Trial. The hemorrhagic-onset patients showed a significantly higher proportion of thalamic anastomosis (p = 0.043) and choroidal anastomosis (< 0.001), as indicated by grade 2 in each subtype, compared with ischemic-onset patients. Suzuki's angiographic staging was significantly higher in the hemorrhagic group (< 0.038). There was no difference in the extent of lenticulostriate anastomosis and PCA involvement between the groups. CONCLUSIONS In adult MMD, the characteristic pattern of the abnormal vascular networks at the base of the brain is different between each onset type. In light of the more prominent development of thalamic and choroidal anastomosis in the JAM Trial group in the present study, development of these collaterals, especially the choroidal collateral extending beyond the lateral ventricle, may play a critical role in hemorrhagic presentation in MMD. Clinical trial registration no. C000000166 ( http://www.umin.ac.jp/ctr/index.htm ).

A Clinic-based Survey of Clinical Characteristics and Practice Pattern of Dry Eye in Japan.

PubMed

Kawashima, Motoko; Yamada, Masakazu; Suwaki, Kazuhisa; Shigeyasu, Chika; Uchino, Miki; Hiratsuka, Yoshimune; Yokoi, Norihiko; Tsubota, Kazuo

2017-03-01

The aim of this study was to investigate the clinical characteristics and practice pattern of patients with dry eye disease (DED) in eye clinics across Japan. A multi-center, cross-sectional study was conducted among patients with DED who visited eye clinics in Japan. Subjective symptoms, patient's background, ocular surface features, and tear function were evaluated. Main outcome measures were tear break-up time (TBUT), Schirmer I value, kerato-conjunctival staining score, and dry eye symptom questionnaire score. Initially, 463 subjects were enrolled, and 449 cases (63 male and 386 female; mean age, 62.6 ± 15.7 years) were included in the final analysis. Overall, 94.9% of patients had a shortened TBUT (≤5 s), and 54.6% had an aqueous tear deficiency (Schirmer I value ≤5 mm). The most prevalent subtype of dry eye was aqueous-deficient dry eye, which was present in 35.0% of all patients, followed by short-BUT-type dry eye, which was seen in 26.7%. The two most common DED subtypes were aqueous-deficient and short-BUT-type dry eye. Shortened TBUT is the most common feature of dry eye, regardless of subtype. The current treatment choice mainly consisted of hyaluronic acid, two novel mucin secretagogues, diquafosol and rebamipide, and steroidal eye drops. University Hospital Medical Information Network: UMIN (registries no. UMIN 000015890). Japan Dry Eye Society, Tokyo, Japan, and Santen Pharmaceutical Co., Ltd., Osaka, Japan.

Smartphone Cognitive Behavioral Therapy as an Adjunct to Pharmacotherapy for Refractory Depression: Randomized Controlled Trial.

PubMed

Mantani, Akio; Kato, Tadashi; Furukawa, Toshi A; Horikoshi, Masaru; Imai, Hissei; Hiroe, Takahiro; Chino, Bun; Funayama, Tadashi; Yonemoto, Naohiro; Zhou, Qi; Kawanishi, Nao

2017-11-03

In the treatment of major depression, antidepressants are effective but not curative. Cognitive behavioral therapy (CBT) is also effective, alone or in combination with pharmacotherapy, but accessibility is a problem. The aim is to evaluate the effectiveness of a smartphone CBT app as adjunctive therapy among patients with antidepressant-resistant major depression. A multisite, assessor-masked, parallel-group randomized controlled trial was conducted in 20 psychiatric clinics and hospitals in Japan. Participants were eligible if they had a primary diagnosis of major depression and were antidepressant-refractory after taking one or more antidepressants at an adequate dosage for four or more weeks. After a 1-week run-in in which participants started the medication switch and had access to the welcome session of the app, patients were randomized to medication switch alone or to medication switch plus smartphone CBT app via the centralized Web system. The smartphone app, called Kokoro-app ("kokoro" means "mind" in Japanese), included sessions on self-monitoring, behavioral activation, and cognitive restructuring presented by cartoon characters. The primary outcome was depression severity as assessed by masked telephone assessors with the Patient Health Questionnaire-9 (PHQ-9) at week 9. The secondary outcomes included the Beck Depression Inventory-II (BDI-II) and Frequency, Intensity, and Burden of Side Effects Ratings (FIBSER). In the total sample (N=164), 81 participants were allocated to the smartphone CBT in addition to medication change and 83 to medication change alone. In the former group, all but one participant (80/81, 99%) completed at least half, and 71 (88%) completed at least six of eight sessions. In the intention-to-treat analysis, patients allocated the CBT app scored 2.48 points (95% CI 1.23-3.72, P<.001; standardized mean difference 0.40) lower on PHQ-9 than the control at week 9. The former group also scored 4.1 points (95% CI 1.5-6.6, P=.002) lower on BDI-II and 0.76 points (95% CI -0.05 to 1.58, P=.07) lower on FIBSER. In the per-protocol sample (comfortable with the smartphone app, still symptomatic, and adherent to medication with mild or less side effects after run-in), the intervention group (n=60) scored 1.72 points (95% CI 0.25-3.18, P=.02) lower on PHQ-9, 3.2 points (95% CI -0.01 to 6.3, P=.05) lower on BDI-II, and 0.75 points (95% CI 0.03-1.47, P=.04) lower on FIBSER than the control (n=57). The treatment benefits were maintained up to week 17. This is the first study to demonstrate the effectiveness of a smartphone CBT in the treatment of clinically diagnosed depression. Given the merits of the mobile mental health intervention, including accessibility, affordability, quality control, and effectiveness, it is clinically worthwhile to consider adjunctive use of a smartphone CBT app when treating patients with antidepressant-resistant depression. Research into its effectiveness in wider clinical contexts is warranted. Japanese Clinical Trials Registry UMIN CTR 000013693; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ ctr_view.cgi?recptno=R000015984 (Archived by WebCite at http://www.webcitation.org/6u6pxVwik). ©Akio Mantani, Tadashi Kato, Toshi A Furukawa, Masaru Horikoshi, Hissei Imai, Takahiro Hiroe, Bun Chino, Tadashi Funayama, Naohiro Yonemoto, Qi Zhou, Nao Kawanishi. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 03.11.2017.

Antimicrobial photodynamic therapy suppresses dental plaque formation in healthy adults: a randomized controlled clinical trial.

PubMed

Ichinose-Tsuno, Akiko; Aoki, Akira; Takeuchi, Yasuo; Kirikae, Teruo; Shimbo, Takuro; Lee, Masaichi-Chang-Il; Yoshino, Fumihiko; Maruoka, Yutaka; Itoh, Toshiyuki; Ishikawa, Isao; Izumi, Yuichi

2014-12-15

Oral care is important for oral and systemic health, especially for elderly institutionalized individuals and compromised patients. However, conventional mechanical plaque control is often difficult for these patients because of the pain or the risk of aspiration. Although antimicrobial photodynamic therapy (aPDT), which is considered an alternative or adjunct to mechanical approaches, has potential application as a less stressful method of daily plaque control, no clinical application of this technique has been reported. We investigated the inhibitory effect of a combination of toluidine blue O (TBO), and a red light-emitting diode (LED) on dental plaque formation in healthy volunteers. The optimal concentration of TBO was determined in preliminary in vitro experiments to evaluate the bactericidal effect of aPDT on Streptococcus oralis and to clarify its safety in fibroblast cells. To survey the mechanism of TBO-mediated aPDT, the quality and quantity of reactive oxygen species (ROS) generated during aPDT were also examined using electron spin resonance (ESR) spectroscopy. Subsequently, the inhibitory effect of aPDT on dental plaque formation was investigated in eleven subjects as a clinical pilot study. The right or left mandibular premolars were randomly assigned to the treatment (with aPDT) or control (without aPDT) groups. In total, aPDT was applied six times (twice per day) to the teeth in the test group over a period of four days. On the fourth day, the study concluded and the analyses were performed. A combination of 500 or 1000 μg/ml TBO and LED irradiation for 20 s significantly decreased the number of colony forming units of Streptococcus oralis. The cytotoxicity of aPDT was comparable to that of standard antiseptics used in the oral cavity. Hydroxyl radicals were detected by ESR analysis, but singlet oxygen was not. A randomized controlled trial demonstrated that aPDT with 1000 μg/ml TBO and red LED irradiation significantly suppressed dental plaque formation without harming teeth or the surrounding tissues. aPDT has the potential to be a promising novel technical modality for dental plaque control. This trial was registered with University Hospital Medical Information Network Clinical Trials Registry (number UMIN000012504).

Management of Intractable Nasal Hyperreactivity by Selective Resection of Posterior Nasal Nerve Branches

PubMed Central

Takahara, Daisuke; Hamamoto, Takao; Ishino, Takashi; Hirakawa, Katsuhiro

2017-01-01

The posterior nasal nerves emerge from the sphenopalatine foramen and contain sensory and autonomic nerve components. Posterior nasal neurectomy is an effective method to remove pathological neural networks surrounding the inferior turbinate that cause unregulated nasal hypersensitivity with excess secretion in patients with severe allergic rhinitis (AR). We describe the sophisticated endoscopic surgical procedure that allows feasible access to the confined area and selective resection of the nerve branches with the preservation of the sphenopalatine artery (SPA). We retrospectively analyzed the cases of 23 symptomatic severe AR patients who failed to respond to standard medical treatment and underwent surgery. There have been no major complications after surgery including nasal bleeding or transient numbness of the upper teeth. The mean total nasal symptom scores (TNSS) were decreased by 70.2% at 12 months after the procedure. Our comparison of the clinical effectiveness based on the number of severed nerve branches revealed that the improvement of the TNSS was significantly higher in patients with >2 branches. We conclude that this minimally invasive technique that preserves the SPA is clinically useful and decreases the rate of postoperative complications. This trial is registered with UMIN000029025. PMID:29379524

Management of Intractable Nasal Hyperreactivity by Selective Resection of Posterior Nasal Nerve Branches.

PubMed

Takahara, Daisuke; Takeno, Sachio; Hamamoto, Takao; Ishino, Takashi; Hirakawa, Katsuhiro

2017-01-01

The posterior nasal nerves emerge from the sphenopalatine foramen and contain sensory and autonomic nerve components. Posterior nasal neurectomy is an effective method to remove pathological neural networks surrounding the inferior turbinate that cause unregulated nasal hypersensitivity with excess secretion in patients with severe allergic rhinitis (AR). We describe the sophisticated endoscopic surgical procedure that allows feasible access to the confined area and selective resection of the nerve branches with the preservation of the sphenopalatine artery (SPA). We retrospectively analyzed the cases of 23 symptomatic severe AR patients who failed to respond to standard medical treatment and underwent surgery. There have been no major complications after surgery including nasal bleeding or transient numbness of the upper teeth. The mean total nasal symptom scores (TNSS) were decreased by 70.2% at 12 months after the procedure. Our comparison of the clinical effectiveness based on the number of severed nerve branches revealed that the improvement of the TNSS was significantly higher in patients with >2 branches. We conclude that this minimally invasive technique that preserves the SPA is clinically useful and decreases the rate of postoperative complications. This trial is registered with UMIN000029025.

Effectiveness of a psycho-oncology training program for oncology nurses: a randomized controlled trial.

PubMed

Kubota, Yosuke; Okuyama, Toru; Uchida, Megumi; Umezawa, Shino; Nakaguchi, Tomohiro; Sugano, Koji; Ito, Yoshinori; Katsuki, Fujika; Nakano, Yumi; Nishiyama, Takeshi; Katayama, Yoshiko; Akechi, Tatsuo

2016-06-01

Oncology nurses are expected to play an important role in psychosocial care for cancer patients. The aim of this study was to examine whether a novel training program aimed at enhancing oncology nurses' ability to assess and manage common psychological problems in cancer patients would improve participants' self-reported confidence, knowledge, and attitudes regarding care of patients with common psychological problems (trial register: UMIN000008559). Oncology nurses were assigned randomly to either the intervention group (N = 50) or the waiting list control group (N = 46). The intervention group received a 16-h program, the content of which focused on four psychological issues: normal reactions, clinically significant distress, suicidal thoughts, and delirium. Each session included a role-play exercise, group work, and didactic lecture regarding assessment and management of each problem. Primary outcomes were changes in self-reported confidence, knowledge, and attitudes toward the common psychological problems between pre-intervention and 3 months post-intervention. Secondary outcomes were job-related stress and burnout. Intervention acceptability to participants was also assessed. In the intervention group, confidence and knowledge but not attitudes were significantly improved relative to the control group. No significant intervention effects were found for job- related stress and burnout. A high percentage (98%) of participants considered the program useful in clinical practice. This psycho-oncology training program improved oncology nurses' confidence and knowledge regarding care for patients with psychological problems. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Effects of lifestyle education program for type 2 diabetes patients in clinics: study design of a cluster randomized trial.

PubMed

Adachi, Misa; Yamaoka, Kazue; Watanabe, Mariko; Nishikawa, Masako; Hida, Eisuke; Kobayashi, Itsuro; Tango, Toshiro

2010-11-30

The number of patients with type 2 diabetes is drastically increasing worldwide. It is a serious health problem in Japan as well. Lifestyle interventions can reduce progression from impaired glucose tolerance to type 2 diabetes, and glycemic control has been shown to improve postprandial plasma glucose levels. Moreover, several studies have suggested that continuous interventions (combined diet and exercise) can improve the plasma glucose level and reduce dosage of hypoglycemic agents.Although many interventional studies of lifestyle education for persons with diabetes in hospitals have been reported, only a few have been clinic-based studies employing an evidence-based lifestyle education program. This article describes the design of a cluster randomized controlled trial of the effectiveness of lifestyle education for patients with type 2 diabetes in clinics by registered dietitians. In Japan, general practitioners generally have their own medical clinics to provide medical care for outpatients in the community, including those with type 2 diabetes. With the collaboration of such general practitioners, the study patients were enrolled in the present study. Twenty general practitioners were randomly allocated to each provide patients for entry into either an intervention group (10) or a control group (10). In total, 200 participants will be included in the study. The intervention group will receive intensive education on lifestyle improvement related to type 2 diabetes by registered dietitians in clinics. Lifestyle education will be conducted several times during the study period. The control group will receive information on dietary intake and standard advice on glycemic control by registered dietitians. The primary endpoint is the change from the baseline value of HbA1c at 6 months. Data on health behavior and related issues will be gathered continuously over a 6-month period. This is the first study to evaluate lifestyle education in clinics by a cluster randomization trial in Japan. The proposed study will provide practical information about the usefulness of the intensive lifestyle improvement education program in primary care settings. The study was started in September 2007 and entry of subjects was completed in December 2010. Data on the effect evaluation will be available in 2011. UMIN000004049.

Effects of adaptive servo-ventilation therapy on cardiac function and remodeling in patients with chronic heart failure (SAVIOR-C): study protocol for a randomized controlled trial.

PubMed

Seino, Yoshihiko; Momomura, Shin-Ichi; Kihara, Yasuki; Adachi, Hitoshi; Yasumura, Yoshio; Yokoyama, Hiroyuki

2015-01-16

Adaptive servo-ventilation (ASV) therapy, which is a form of noninvasive positive pressure ventilation therapy and uses an innovative ventilator that has simple operability and provides good patient adherence, potentially has therapeutic benefits-suppression of the deterioration and progression of chronic heart failure (CHF) and a reduction in the number of repeated hospitalizations. Therefore, ASV therapy draws attention as a novel, noninvasive nonpharmacotherapy for patients with CHF owing to its hemodynamics-improving effect, and it is currently being accepted in real-world clinical settings in Japan. However, clinical evidence sufficient for treatment recommendation is lacking because a multicenter, randomized, controlled study of ASV therapy has never been conducted. The present study is a confirmatory, prospective, multicenter, collaborative, open-label, blinded-endpoint, parallel-group, randomized, controlled study. At 40 medical institutions in Japan, 200 Japanese outpatients with mild to severe CHF (age: ≥ 20 years; New York Heart Association classification: greater than or equal to class II) will be randomly assigned to either of the following two study groups: the ASV group, in which 100 outpatients undergo guideline-directed medical therapy and ASV therapy for 24 weeks; and the control group, in which 100 outpatients undergo only guideline-directed medical therapy for 24 weeks. The objective of the present study is to confirm whether the ASV group is superior to the control group concerning the improvement of left ventricular contractility and remodeling, both assessed by two-dimensional echocardiography. Furthermore, the present study will also secondarily examine the effects of ASV therapy on the prognosis and quality of life of patients with CHF. ASV therapy using the device has the potential to provide therapeutic benefits based on its simple operability and good patient adherence and possesses the potential to improve left ventricular contractility and remodeling. Therefore, the present study is expected to afford more solid scientific evidence regarding ASV therapy as a novel, noninvasive, nonpharmacological, in-home, long-term ventilation therapy for patients with mild to severe CHF. UMIN identifier: UMIN000006549 , registered on 17 October, 2011.

Changes in salivary oxytocin after inhalation of clary sage essential oil scent in term-pregnant women: a feasibility pilot study.

PubMed

Tadokoro, Yuriko; Horiuchi, Shigeko; Takahata, Kaori; Shuo, Takuya; Sawano, Erika; Shinohara, Kazuyuki

2017-12-08

This pilot study using a quasi-experimental design was conducted to evaluate the feasibility (i.e., limited efficacy, practicality, and acceptability) of our intervention protocol involving inhalation of the scent of clary sage essential oil by pregnant women and measurement of their preinhalation and postinhalation oxytocin levels. Participants were women of singleton pregnancies between 38 and 40 gestation weeks (N = 11). The experiment group (n = 5) inhaled the scent of clary sage essential oil diluted 50-fold with 10 mL of odorless propylene glycol for 20 min. Regarding limited efficacy, the oxytocin level 15 min postinhalation increased in 3 women and was unmeasurable in 2. The control group (n = 6) inhaled similarly without the 50-fold dilution of clary sage essential oil. Their oxytocin level increased in 2 women, decreased in 2, and was unmeasurable in 2. Uterine contraction was not observed in both groups. Regarding practicality, 3 of the 11 women could not collect sufficient saliva. The cortisol level decreased in both groups postinhalation. The protocol had no negative effects. Regarding acceptability, burden of the protocol was not observed. Trial registration The Clinical Trials Registry of University Hospital Medical Information Network in Japan-UMIN000017830. Registered:  June 8, 2015.

The effect of febuxostat to prevent a further reduction in renal function of patients with hyperuricemia who have never had gout and are complicated by chronic kidney disease stage 3: study protocol for a multicenter randomized controlled study

PubMed Central

2014-01-01

Background Hyperuricemia is a risk factor for the onset of chronic kidney disease (CKD) and is significantly associated with the progression of CKD. However, there is no sufficient evidence by interventional research supporting a cause-effect relationship. Hyperuricemic patients without gouty arthritis, whose serum urate (SUA) concentration is ≥8.0 mg/dL and who have a complication, are treated by pharmacotherapy in addition to lifestyle guidance. Nevertheless, there is no evidence that rationalizes pharmacotherapy for patients with hyperuricemia who have no complication and whose SUA concentration is below 9.0 mg/dL. Methods/Design The FEATHER (FEbuxostat versus placebo rAndomized controlled Trial regarding reduced renal function in patients with Hyperuricemia complicated by chRonic kidney disease stage 3) study is a prospective, multicenter, double-blind, randomized, placebo-controlled trial of febuxostat—a novel, nonpurine, selective, xanthine oxidase inhibitor. The present study will enroll, at 64 medical institutions in Japan, 400 Japanese patients aged 20 years or older who have hyperuricemia without gouty arthritis, who present CKD stage 3, and whose SUA concentration is 7.1-10.0 mg/dL. Patients are randomly assigned to either the febuxostat or the control group, in which febuxostat tablets and placebo are administered orally, respectively. The dosage of the study drugs should be one 10-mg tablet/day at weeks 1 to 4 after study initiation, increased to one 20-mg tablet/day at weeks 5 to 8, and elevated to one 40-mg tablet/day at week 9 and then maintained until week 108. The primary endpoint is estimated glomerular filtration rate (eGFR) slope. The secondary endpoints include the amount and percent rate of change in eGFR from baseline to week 108, the amount and percent rate of change in SUA concentration from baseline to week 108, the proportion of patients who achieved an SUA concentration ≤6.0 mg/dL, and the incidence of renal function deterioration. Discussion The present study aims to examine whether febuxostat prevents a further reduction in renal function as assessed with eGFR in subjects and will (1) provide evidence to indicate the inverse association between a reduction in SUA concentration and an improvement in renal function and (2) rationalize pharmacotherapy for subjects and clarify its clinical relevance. Trial registration UMIN Identifier: UMIN000008343 PMID:24433285

A cognitive-behavioral intervention for emotion regulation in adults with high-functioning autism spectrum disorders: study protocol for a randomized controlled trial.

PubMed

Kuroda, Miho; Kawakubo, Yuki; Kuwabara, Hitoshi; Yokoyama, Kazuhito; Kano, Yukiko; Kamio, Yoko

2013-07-23

Adults with high-functioning autism spectrum disorders (ASD) have difficulties in social communication; thus, these individuals have trouble understanding the mental states of others. Recent research also suggests that adults with ASD are unable to understand their own mental states, which could lead to difficulties in emotion-regulation. Some studies have reported the efficacy of cognitive-behavioral therapy (CBT) in improving emotion-regulation among children with ASD. The current study will investigate the efficacy of group-based CBT for adults with ASD. The study is a randomized, waitlist controlled, single-blinded trial. The participants will be 60 adults with ASD; 30 will be assigned to a CBT group and 30 to a waitlist control group. Primary outcome measures are the 20-item Toronto Alexithymia Scale, the Coping Inventory for Stressful Situations, the Motion Picture Mind-Reading task, and an ASD questionnaire. The secondary outcome measures are the Center for Epidemiological Studies Depression Scale, the World Health Organization Quality of Life Scale 26-item version, the Global Assessment of Functioning, State-trait Anxiety Inventory, Social Phobia and Anxiety Inventory, and Liebowitz Social Anxiety Scale. All will be administered during the pre- and post-intervention, and 12 week follow-up periods. The CBT group will receive group therapy over an 8 week period (one session per week) with each session lasting approximately 100 minutes. Group therapy will consist of four or five adults with ASD and two psychologists. We will be using visual materials for this program, mainly the Cognitive Affective Training kit. This trial will hopefully indicate the efficacy of group-based CBT for adults with high- functioning ASD. This trial was registered in The University Hospital Medical Information Network Clinical Trials Registry No. UMIN000006236.

Educational program for middle-level public health nurses to develop new health services regarding community health needs: protocol for a randomized controlled trial.

PubMed

Yoshioka-Maeda, Kyoko; Katayama, Takafumi; Shiomi, Misa; Hosoya, Noriko

2018-01-01

Developing health services is a key strategy for improving the community health provided by public health nurses. However, an effective educational program for improving their skills in planning such services has not been developed. To describe our program and its evaluation protocol for the education of middle-level public health nurses to improve their skills in developing new health services to fulfil community health needs in Japan. In this randomized control trial, eligible participants in Japan will be randomly allocated to an intervention group and a control wait-list group. We will provide 8 modules of web-based learning for public health nurses from July to October 2018. To ensure fairness of educational opportunity, the wait-list group will participate in the same program as the intervention group after collection of follow-up data of the intervention group. The primary outcomes will be evaluated using the scale of competency measurement of creativity for public health nurses at baseline, immediately after the intervention. Secondary outcomes will be knowledge and performance regarding program development of public health nurses. This study will enable the analysis of the effects of the educational program on public health nurses for improving their competency to develop new health services for fulfilling community health needs and enriching health care systems. We registered our study protocol to the University hospital Medical Information Network- Clinical Trials Registry approved by International Committee of Medical Journal Editors (No. UMIN000032176, April, 2018).

The first multicenter, randomized, controlled trial of home telemonitoring for Japanese patients with heart failure: home telemonitoring study for patients with heart failure (HOMES-HF).

PubMed

Kotooka, Norihiko; Kitakaze, Masafumi; Nagashima, Kengo; Asaka, Machiko; Kinugasa, Yoshiharu; Nochioka, Kotaro; Mizuno, Atsushi; Nagatomo, Daisuke; Mine, Daigo; Yamada, Yoko; Kuratomi, Akiko; Okada, Norihiro; Fujimatsu, Daisuke; Kuwahata, So; Toyoda, Shigeru; Hirotani, Shin-Ichi; Komori, Takahiro; Eguchi, Kazuo; Kario, Kazuomi; Inomata, Takayuki; Sugi, Kaoru; Yamamoto, Kazuhiro; Tsutsui, Hiroyuki; Masuyama, Tohru; Shimokawa, Hiroaki; Momomura, Shin-Ichi; Seino, Yoshihiko; Sato, Yasunori; Inoue, Teruo; Node, Koichi

2018-02-15

Home telemonitoring is becoming more important to home medical care for patients with heart failure. Since there are no data on home telemonitoring for Japanese patients with heart failure, we investigated its effect on cardiovascular outcomes. The HOMES-HF study was the first multicenter, open-label, randomized, controlled trial (RCT) to elucidate the effectiveness of home telemonitoring of physiological data, such as body weight, blood pressure, and pulse rate, for Japanese patients with heart failure (UMIN Clinical Trials Registry 000006839). The primary end-point was a composite of all-cause death or rehospitalization due to worsening heart failure. We analyzed 181 recently hospitalized patients with heart failure who were randomly assigned to a telemonitoring group (n = 90) or a usual care group (n = 91). The mean follow-up period was 15 (range 0-31) months. There was no statistically significant difference in the primary end-point between groups [hazard ratio (HR), 0.95; 95% confidence interval (CI), 0.548-1.648; p = 0.572]. Home telemonitoring for Japanese patients with heart failure was feasible; however, beneficial effects in addition to those of usual care were not demonstrated. Further investigation of more patients with severe heart failure, participation of home medical care providers, and use of a more integrated home telemonitoring system emphasizing communication as well as monitoring of symptoms and physiological data are required.

Health-related quality of life of adjuvant chemotherapy with S-1 versus gemcitabine for resected pancreatic cancer: Results from a randomised phase III trial (JASPAC 01).

PubMed

Hagiwara, Yasuhiro; Ohashi, Yasuo; Uesaka, Katsuhiko; Boku, Narikazu; Fukutomi, Akira; Okamura, Yukiyasu; Konishi, Masaru; Matsumoto, Ippei; Kaneoka, Yuji; Shimizu, Yasuhiro; Nakamori, Shoji; Sakamoto, Hirohiko; Morinaga, Soichiro; Kainuma, Osamu; Imai, Koji; Sata, Naohiro; Hishinuma, Shoichi; Ojima, Hitoshi; Yamaguchi, Ryuzo; Hirano, Satoshi; Sudo, Takeshi

2018-04-01

Adjuvant chemotherapy with S-1 for resected pancreatic cancer demonstrated survival benefits compared with gemcitabine in the JASPAC 01 trial. We investigated the effect of these agents on health-related quality of life (HRQOL) of patients in the JASPAC 01 trial. Patients with resected pancreatic cancer were randomly assigned to receive gemcitabine (1000 mg/m 2 weekly for three of four weeks for up to six cycles) or S-1 (40, 50, or 60 mg twice daily for four of six weeks for up to four cycles). HRQOL was assessed using the EuroQol-5D-3L (EQ-5D) questionnaire at baseline, months three and six, and every 6 months thereafter. HRQOL end-points included change in EQ-5D index from baseline, responses to five items in the EQ-5D, and quality-adjusted life months up to 24 months. Of randomised 385 patients, 354 patients were included in HRQOL analysis. Mean change in the EQ-5D index was similar in the S-1 and gemcitabine groups within 6 months from treatment initiation (difference, 0.024; P = 0.112), whereas corresponding mean from 12 to 24 months was better in the S-1 group than in the gemcitabine group (difference, 0.071; P < 0.001). Problems in mobility and pain/discomfort were also less frequent in the S-1 group than in the gemcitabine group in that period. Quality-adjusted life months were longer in the S-1 group than in the gemcitabine group (P < 0.001). Adjuvant chemotherapy with S-1 does not improve HRQOL within 6 months from treatment initiation but does improve HRQOL thereafter and quality-adjusted life months. UMIN000000655 at UMIN CTR. Copyright © 2018 Elsevier Ltd. All rights reserved.

Therapist Experience and Knowledge Acquisition in Internet-Delivered CBT for Social Anxiety Disorder: A Randomized Controlled Trial

PubMed Central

Andersson, Gerhard; Carlbring, Per; Furmark, Tomas

2012-01-01

Background Guided internet-delivered cognitive behavior therapy (ICBT) has been tested in several trials on social anxiety disorder (SAD) with moderate to large effects. The aims of this study were threefold. First, to compare the effects of ICBT including online discussion forum with a moderated online discussion forum only. Second, to investigate if knowledge about SAD increased following treatment and third to compare the effects of inexperienced versus experienced therapists on patient outcomes. Methods A total of 204 participants with a primary diagnosis of SAD were included and randomized to either guided ICBT or the control condition. ICBT consisted of a 9-week treatment program which was guided by either psychology students at MSc level (n = 6) or by licensed psychologists with previous experience of ICBT (n = 7). A knowledge test dealing with social anxiety was administered before and after treatment. Measures of social anxiety and secondary outcomes dealing with general anxiety, depression, and quality of life were administered before and after treatment. In addition, a 1-year follow-up was conducted on the treated individuals. Results Immediately following treatment, the ICBT group showed superior outcome on the Liebowitz Social Anxiety Scale self-report version with a between group posttreatment Hedges g effect size of g = 0.75. In addition, significant differences on all the secondary outcomes were observed. Gains were well maintained one year later. Knowledge, as assessed by the knowledge test, increased following treatment with little gain in the control group. Therapist experience did not result in different outcomes, but experienced therapists logged in less frequently compared to the inexperienced therapists, suggesting that they needed less time to support patients. Discussion We conclude that guided ICBT reduce symptoms of SAD, increase knowledge about SAD and that therapist experience does not make a difference apart from the finding that experienced therapist may require less time to guide patients. Trial Registration UMIN.ac.jp UMIN000001383 PMID:22649526

Brain Training Game Boosts Executive Functions, Working Memory and Processing Speed in the Young Adults: A Randomized Controlled Trial

PubMed Central

Nouchi, Rui; Taki, Yasuyuki; Takeuchi, Hikaru; Hashizume, Hiroshi; Nozawa, Takayuki; Kambara, Toshimune; Sekiguchi, Atsushi; Miyauchi, Carlos Makoto; Kotozaki, Yuka; Nouchi, Haruka; Kawashima, Ryuta

2013-01-01

Background Do brain training games work? The beneficial effects of brain training games are expected to transfer to other cognitive functions. Yet in all honesty, beneficial transfer effects of the commercial brain training games in young adults have little scientific basis. Here we investigated the impact of the brain training game (Brain Age) on a wide range of cognitive functions in young adults. Methods We conducted a double-blind (de facto masking) randomized controlled trial using a popular brain training game (Brain Age) and a popular puzzle game (Tetris). Thirty-two volunteers were recruited through an advertisement in the local newspaper and randomly assigned to either of two game groups (Brain Age, Tetris). Participants in both the Brain Age and the Tetris groups played their game for about 15 minutes per day, at least 5 days per week, for 4 weeks. Measures of the cognitive functions were conducted before and after training. Measures of the cognitive functions fell into eight categories (fluid intelligence, executive function, working memory, short-term memory, attention, processing speed, visual ability, and reading ability). Results and Discussion Our results showed that commercial brain training game improves executive functions, working memory, and processing speed in young adults. Moreover, the popular puzzle game can engender improvement attention and visuo-spatial ability compared to playing the brain training game. The present study showed the scientific evidence which the brain training game had the beneficial effects on cognitive functions (executive functions, working memory and processing speed) in the healthy young adults. Conclusions Our results do not indicate that everyone should play brain training games. However, the commercial brain training game might be a simple and convenient means to improve some cognitive functions. We believe that our findings are highly relevant to applications in educational and clinical fields. Trial Registration UMIN Clinical Trial Registry 000005618. PMID:23405164

Adding smartphone-based cognitive-behavior therapy to pharmacotherapy for major depression (FLATT project): study protocol for a randomized controlled trial.

PubMed

Watanabe, Norio; Horikoshi, Masaru; Yamada, Mitsuhiko; Shimodera, Shinji; Akechi, Tatsuo; Miki, Kazuhira; Inagaki, Masatoshi; Yonemoto, Naohiro; Imai, Hissei; Tajika, Aran; Ogawa, Yusuke; Takeshima, Nozomi; Hayasaka, Yu; Furukawa, Toshi A

2015-07-07

Major depression is one of the most debilitating diseases in terms of quality of life. Less than half of patients suffering from depression can achieve remission after adequate antidepressant treatment. Another promising treatment option is cognitive-behavior therapy (CBT). However, the need for experienced therapists and substantive dedicated time prevent CBT from being widely disseminated. In the present study, we aim to examine the effectiveness of switching antidepressants and starting a smartphone-based CBT program at the same time, in comparison to switching antidepressants only, among patients still suffering from depression after adequate antidepressant treatment. A multi-center randomized trial is currently being conducted since September 2014. The smartphone-based CBT program, named the "Kokoro-App," for major depression has been developed and its feasibility has been confirmed in a previous open study. The program consists of an introduction, 6 sessions and an epilogue, and is expected to be completed within 9 weeks by patients. In the present trial, 164 patients with DSM-5 major depressive disorder and still suffering from depressive symptoms after adequate antidepressant treatment for more than 4 weeks will be allocated to the Kokoro-App plus switching antidepressant group or the switching antidepressant alone group. The participants allocated to the latter group will receive full components of the Kokoro-App after 9 weeks. The primary outcome is the change in the total score on the Patient Health Questionnaire through the 9 weeks of the program, as assessed at week 0, 1, 5 and 9 via telephone by blinded raters. The secondary outcomes include the change in the total score of the Beck Depression Inventory-II, change in side effects as assessed by the Frequency, Intensity and Burden of Side Effects Rating, and treatment satisfaction. An effective and reachable intervention may not only lead to healthier mental status among depressed patients, but also to reduced social burden from this illness. This paper outlines the background and methods of a trial that evaluates the possible additive value of a smartphone-based CBT program for treatment-resistant depression. UMIN-CTR: UMIN000013693 (registered on 1 June 2014).

Phase I trial of S-1 every other day in combination with gemcitabine/cisplatin for inoperable biliary tract cancer.

PubMed

Uwagawa, Tadashi; Sakamoto, Taro; Abe, Kyohei; Okui, Norimitsu; Hata, Daigo; Shiba, Hiroaki; Futagawa, Yasuro; Aiba, Keisuke; Yanaga, Katsuhiko

2015-01-01

To date, gemcitabine-based or fluoropyrimidine-based regimens are recommended for unresectable advanced biliary tract cancer. Then, we conducted a phase I study of gemcitabine/cisplatin and S-1 that is an oral fluoropyrimidine. The aim of this study was to determine the dose-limiting toxicity (DLT), maximum-tolerated dose, and a recommended phase II dose of S-1. Response was assessed as a secondary endpoint. Patients who have been diagnosed with unresectable or postoperative recurrent biliary tract cancer received cisplatin (25 mg/m² i.v. for 120 min) followed by gemcitabine (1,000 mg/m² i.v. for 30 min) on days 1 and 8, and oral S-1 on alternate days; this regimen was repeated at 21-day intervals. A standard '3 + 3' phase I dose-escalation design was adopted. This study was registered with University hospital Medical Information Network (UMIN) Center in Japan, number UMIN000008415. Twelve patients were evaluable in this study. No patients developed DLTs. Recommended dose of S-1 was 80 (<1.25 m²), 100 (1.25 ≤ 1.5 m²), and 120 mg (1.5 m²≥) per day. One patient could achieve conversion to curative surgery. This phase I study was performed safely and demonstrated encouraging response.

Rationale and design of a multicenter randomized study for evaluating vascular function under uric acid control using the xanthine oxidase inhibitor, febuxostat: the PRIZE study.

PubMed

Oyama, Jun-Ichi; Tanaka, Atsushi; Sato, Yasunori; Tomiyama, Hirofumi; Sata, Masataka; Ishizu, Tomoko; Taguchi, Isao; Kuroyanagi, Takanori; Teragawa, Hiroki; Ishizaka, Nobukazu; Kanzaki, Yumiko; Ohishi, Mitsuru; Eguchi, Kazuo; Higashi, Yukihito; Yamada, Hirotsugu; Maemura, Koji; Ako, Junya; Bando, Yasuko K; Ueda, Shinichiro; Inoue, Teruo; Murohara, Toyoaki; Node, Koichi

2016-06-18

Xanthine oxidase inhibitors are anti-hyperuricemic drugs that decrease serum uric acid levels by inhibiting its synthesis. Xanthine oxidase is also recognized as a pivotal enzyme in the production of oxidative stress. Excess oxidative stress induces endothelial dysfunction and inflammatory reactions in vascular systems, leading to atherosclerosis. Many experimental studies have suggested that xanthine oxidase inhibitors have anti-atherosclerotic effects by decreasing in vitro and in vivo oxidative stress. However, there is only limited evidence on the clinical implications of xanthine oxidase inhibitors on atherosclerotic cardiovascular disease in patients with hyperuricemia. We designed the PRIZE study to evaluate the effects of febuxostat on a surrogate marker of cardiovascular disease risk, ultrasonography-based intima-media thickness of the carotid artery in patients with hyperuricemia. The study is a multicenter, prospective, randomized, open-label and blinded-endpoint evaluation (PROBE) design. A total of 500 patients with asymptomatic hyperuricemia (uric acid >7.0 mg/dL) and carotid intima-media thickness ≥1.1 mm will be randomized centrally to receive either febuxostat (10-60 mg/day) or non-pharmacological treatment. Randomization is carried out using the dynamic allocation method stratified according to age (<65, ≥65 year), gender, presence or absence of diabetes mellitus, serum uric acid (<8.0, ≥8.0 mg/dL), and carotid intima-media thickness (<1.3, ≥1.3 mm). In addition to administering the study drug, we will also direct lifestyle modification in all participants, including advice on control of body weight, sleep, exercise and healthy diet. Carotid intima-media thickness will be evaluated using ultrasonography performed by skilled technicians at a central laboratory. Follow-up will be continued for 24 months. The primary endpoint is percentage change in mean intima-media thickness of the common carotid artery 24 months after baseline, measured by carotid ultrasound imaging. PRIZE will be the first study to provide important data on the effects of febuxostat on atherosclerosis in patients with asymptomatic hyperuricemia. Trial Registration Unique trial Number, UMIN000012911 ( https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000015081&language=E ).

α-Glucosidase inhibitor miglitol attenuates glucose fluctuation, heart rate variability and sympathetic activity in patients with type 2 diabetes and acute coronary syndrome: a multicenter randomized controlled (MACS) study.

PubMed

Shimabukuro, Michio; Tanaka, Atsushi; Sata, Masataka; Dai, Kazuoki; Shibata, Yoshisato; Inoue, Yohei; Ikenaga, Hiroki; Kishimoto, Shinji; Ogasawara, Kozue; Takashima, Akira; Niki, Toshiyuki; Arasaki, Osamu; Oshiro, Koichi; Mori, Yutaka; Ishihara, Masaharu; Node, Koichi

2017-07-06

Little is known about clinical associations between glucose fluctuations including hypoglycemia, heart rate variability (HRV), and the activity of the sympathetic nervous system (SNS) in patients with acute phase of acute coronary syndrome (ACS). This pilot study aimed to evaluate the short-term effects of glucose fluctuations on HRV and SNS activity in type 2 diabetes mellitus (T2DM) patients with recent ACS. We also examined the effect of suppressing glucose fluctuations with miglitol on these variables. This prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group comparative study included 39 T2DM patients with recent ACS, who were randomly assigned to either a miglitol group (n = 19) or a control group (n = 20). After initial 24-h Holter electrocardiogram (ECG) (Day 1), miglitol was commenced and another 24-h Holter ECG (Day 2) was recorded. In addition, continuous glucose monitoring (CGM) was performed throughout the Holter ECG. Although frequent episodes of subclinical hypoglycemia (≤4.44 mmo/L) during CGM were observed on Day 1 in the both groups (35% of patients in the control group and 31% in the miglitol group), glucose fluctuations were decreased and the minimum glucose level was increased with substantial reduction in the episodes of subclinical hypoglycemia to 7.7% in the miglitol group on Day 2. Holter ECG showed that the mean and maximum heart rate and mean LF/HF were increased on Day 2 in the control group, and these increases were attenuated by miglitol. When divided 24-h time periods into day-time (0700-1800 h), night-time (1800-0000 h), and bed-time (0000-0700 h), we found increased SNS activity during day-time, increased maximum heart rate during night-time, and glucose fluctuations during bed-time, which were attenuated by miglitol treatment. In T2DM patients with recent ACS, glucose fluctuations with subclinical hypoglycemia were associated with alterations of HRV and SNS activity, which were mitigated by miglitol, suggesting that these pathological relationships may be a residual therapeutic target in such patients. Trial registration Unique Trial Number, UMIN000005874 ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000006929 ).

Efficacy of 10-day Sitafloxacin-Containing Third-Line Rescue Therapies for Helicobacter pylori Strains Containing the gyrA Mutation.

PubMed

Mori, Hideki; Suzuki, Hidekazu; Matsuzaki, Juntaro; Tsugawa, Hitoshi; Fukuhara, Seiichiro; Miyoshi, Sawako; Hirata, Kenro; Seino, Takashi; Matsushita, Misako; Masaoka, Tatsuhiro; Kanai, Takanori

2016-08-01

Sitafloxacin-containing Helicobacter pylori eradication therapy is a promising third-line therapeutic approach, but there is no previous studies between gyrA mutation status of H. pylori strains and the efficacy of 10-day sitafloxacin-containing regimens. Here, we assessed the efficacy of 2 different 10-day sitafloxacin-containing rescue regimens. Patients who failed first- and second-line eradication therapies were enrolled. The minimum inhibitory concentrations (MICs) of sitafloxacin, amoxicillin, and metronidazole and the gyrA mutation status of the H. pylori strains were determined before treatment. The patients were randomized to receive a 10-day triple therapy containing either esomeprazole (20 mg, b.i.d.), amoxicillin (500 mg, q.i.d.), and sitafloxacin (100 mg, b.i.d.) (EAS regimen) or esomeprazole (20 mg, b.i.d.), metronidazole (250 mg, b.i.d.), and sitafloxacin (100 mg, b.i.d.) (EMS regimen). Eradication rates were evaluated by the [13C] urea breath test or the H. pylori stool antigen test. All patients with gyrA mutation-negative strains (24 in EAS and 16 in EMS) showed successful eradication, irrespective of the regimen they received. In patients with gyrA mutation-positive strains, we found eradication rates of 70.3% (26/37) and 66.7% (26/39) in the EAS and EMS groups in per-protocol population, respectively (p = .81). According to logistic regression analyses, the MICs of sitafloxacin, which were strongly associated with gyrA mutation status, were independently associated with successful eradication in both groups. This study was registered in the UMIN Clinical Trials Registry as UMIN000006483. There is no significant difference in the eradication rates between EAS and EMS, regardless of the gyrA mutation status of the H. pylori strains. GyrA mutation status was an important factor in predicting successful eradication with sitafloxacin-containing rescue therapies. © 2015 John Wiley & Sons Ltd.

Providing Japanese health care information for international visitors: digital animation intervention.

PubMed

Nishikawa, Mariko; Yamanaka, Masaaki; Kiriya, Junko; Jimba, Masamine

2018-05-21

Over 24 million international visitors came to Japan in 2016 and the number is expected to increase. Visitors could be at a risk of illness or injury that may result in hospitalization in Japan. We assessed the effects of a four-minute digital animation titled Mari Info Japan on the level of anxiety experienced by international visitors to Japan. We conducted a non-randomized, controlled study at Narita International Airport outside Tokyo in December 2014. On the first day, we recruited international visitors for the intervention group at predetermined departure gates and, the following day, we sampled visitors for the control group at the same gates. We repeated this procedure twice over 4 days. The intervention group watched the digital animation and the control group read a standard travel guidebook in English. After receiving either intervention, they completed a questionnaire on their level of anxiety. The outcome was assessed using the Mari Meter-X, The State-Trait Anxiety Inventory Form Y (STAI-Y), and a face scale, before and immediately after the intervention. We analyzed data with Wilcoxon rank sum tests. We recruited 265 international visitors (134 in the intervention group, 131 in the control group), 241 (91%) of whom completed the questionnaire. Most of them had no previous Japanese health information before arrival in Japan. The level of anxiety about health services in Japan was significantly reduced in the intervention group (Mari Meter-X median: - 5 and 0, p < 0.001 and STAI-Y median: - 3 and 0, p < 0.001). The face scale analysis showed no significant difference. Watching a digital animation is more effective in reducing anxiety among international visitors to Japan compared with reading a standard brochure or guidebook. Such effective animations of health information should be more widely distributed to international visitors. UMIN-CTR (University Hospital Medical Information Network Center Clinical Trials Registry), UMIN000015023 , September 3, 2014.

Comparison of semi-automated center-dot and fully automated endothelial cell analyses from specular microscopy images.

PubMed

Maruoka, Sachiko; Nakakura, Shunsuke; Matsuo, Naoko; Yoshitomi, Kayo; Katakami, Chikako; Tabuchi, Hitoshi; Chikama, Taiichiro; Kiuchi, Yoshiaki

2017-10-30

To evaluate two specular microscopy analysis methods across different endothelial cell densities (ECDs). Endothelial images of one eye from each of 45 patients were taken by using three different specular microscopes (three replicates each). To determine the consistency of the center-dot method, we compared SP-6000 and SP-2000P images. CME-530 and SP-6000 images were compared to assess the consistency of the fully automated method. The SP-6000 images from the two methods were compared. Intraclass correlation coefficients (ICCs) for the three measurements were calculated, and parametric multiple comparisons tests and Bland-Altman analysis were performed. The ECD mean value was 2425 ± 883 (range 516-3707) cells/mm 2 . ICC values were > 0.9 for all three microscopes for ECD, but the coefficients of variation (CVs) were 0.3-0.6. For ECD measurements, Bland-Altman analysis revealed that the mean difference was 42 cells/mm 2 between the SP-2000P and SP-6000 for the center-dot method; 57 cells/mm 2 between the SP-6000 measurements from both methods; and -5 cells/mm 2 between the SP-6000 and CME-530 for the fully automated method (95% limits of agreement: - 201 to 284 cell/mm 2 , - 410 to 522 cells/mm 2 , and - 327 to 318 cells/mm 2 , respectively). For CV measurements, the mean differences were - 3, - 12, and 13% (95% limits of agreement - 18 to 11, - 26 to 2, and - 5 to 32%, respectively). Despite using three replicate measurements, the precision of the center-dot method with the SP-2000P and SP-6000 software was only ± 10% for ECD data and was even worse for the fully automated method. Japan Clinical Trials Register ( http://www.umin.ac.jp/ctr/index/htm9 ) number UMIN 000015236.

The proinsulin/insulin (PI/I) ratio is reduced by postprandial targeting therapy in type 2 diabetes mellitus: a small-scale clinical study

PubMed Central

2013-01-01

Background An elevated PI/I ratio is attributable to increased secretory demand on β-cells. However, the effect of postprandial targeting therapy on proinsulin level is unknown. We evaluated the metabolic effect of glinide and sulfonylurea (SU) using the meal tolerance test (MTT). Methods MTT was applied to previously untreated Type 2 Diabetes Mellitus (T2DM) subjects. Twenty-two participants were given a test meal (450 kcal). Plasma glucose and insulin were measured at 0 (fasting), 30, 60, 120, and 180 min. Serum proinsulin and C-peptide immunoreactivity (CPR) were measured at 0 and 120 min. Postprandial profile was assessed at baseline and following 3 months treatment with either mitiglinide or glimepiride. Results Plasma glucose level at 30, 60, 120, and 180 min was significantly improved by mitiglinide. Whereas, glimepiride showed a significant improve plasma glucose at 0, 180 min. Peak IRI shifted from 120 to 30 min by mitiglinide treatment. The pattern of insulin secretion was not changed by glimepiride treatment. Whereas mitiglinide did not affect the PI/I ratio, glimepiride tended to increase the PI/I ratio. Moreover, although mitiglinide did not affect PI/I ratio as a whole, marked reduction was noted in some patients treated by mitiglinide. PI/I ratio was reduced significantly in the responder group. The responder subgroup exhibited less insulin resistance and higher insulinogenic index at baseline than non-responders. Moreover, the triglyceride level of responders was significantly lower than that of non-responders. Conclusions Mitiglinide improved postprandial insulin secretion pattern and thereby suppressed postprandial glucose spike. In T2DM patients with low insulin resistance and low triglyceride, mitiglinide recovered impaired β-cell function from the viewpoint of the PI/I ratio. Trial registration UMIN-CTR: UMIN000010467 PMID:24215809

First-line eradication for Helicobacter pylori-positive gastritis by esomeprazole-based triple therapy is influenced by CYP2C19 genotype

PubMed Central

Saito, Yoshimasa; Serizawa, Hiroshi; Kato, Yukako; Nakano, Masaru; Nakamura, Masahiko; Saito, Hidetsugu; Suzuki, Hidekazu; Kanai, Takanori

2015-01-01

AIM: To evaluate the effect of first line esomeprazole (EPZ)-based triple therapy on Helicobacter pylori (H. pylori) eradication. METHODS: A total of 80 Japanese patients with gastritis who were diagnosed as positive for H. pylori infection by endoscopic biopsy-based or 13C-urea breath tests were included in this study. The average age of the patients was 57.2 years (male/female, 42/38). These patients were treated by first-line eradication therapy with EPZ 40 mg/d, amoxicillin 1500 mg/d, and clarithromycin 400 mg/d for 7 d. All drugs were given twice per day. Correlations between H. pylori eradication, CYP2C19 genotype, and serum pepsinogen (PG) level were analyzed. This study was registered with the UMIN Clinical Trials Registry (UMIN000009642). RESULTS: The H. pylori eradication rates by EPZ-based triple therapy evaluated by intention-to-treat and per protocol were 67.5% and 68.4%, respectively, which were similar to triple therapies with other first-generation proton pump inhibitors (PPIs). The eradication rates in three different CYP2C19 genotypes, described as extensive metabolizer (EM), intermediate metabolizer, and poor metabolizer, were 52.2%, 72.1%, and 84.6%, respectively. The H. pylori eradication rate was significantly lower in EM than non-EM (P < 0.05). The serum PG I level and PG I/II ratio were significantly increased after eradication of H. pylori (P < 0.01), suggesting that gastric atrophy was improved by H. pylori eradication. Thus, first-line eradication by EPZ-based triple therapy for patients with H. pylori-positive gastritis was influenced by CYP2C19 genotype, and the eradication rate was on the same level with other first-generation PPIs in the Japanese population. CONCLUSION: The results from this study suggest that there is no advantage to EPZ-based triple therapy on H. pylori eradication compared to other first-generation PPIs. PMID:26730167

Possible Increase in Serum FABP4 Level Despite Adiposity Reduction by Canagliflozin, an SGLT2 Inhibitor.

PubMed

Furuhashi, Masato; Matsumoto, Megumi; Hiramitsu, Shinya; Omori, Akina; Tanaka, Marenao; Moniwa, Norihito; Yoshida, Hideaki; Ishii, Junnichi; Miura, Tetsuji

2016-01-01

Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is secreted from adipocytes in association with catecholamine-induced lipolysis, and elevated serum FABP4 level is associated with obesity, insulin resistance and atherosclerosis. Secreted FABP4 as a novel adipokine leads to insulin resistance via increased hepatic glucose production (HGP). Sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease blood glucose level via increased urinary glucose excretion, though HGP is enhanced. Here we investigated whether canagliflozin, an SGLT2 inhibitor, modulates serum FABP4 level. Canagliflozin (100 mg/day) was administered to type 2 diabetic patients (n = 39) for 12 weeks. Serum FABP4 level was measured before and after treatment. At baseline, serum FABP4 level was correlated with adiposity, renal dysfunction and noradrenaline level. Treatment with canagliflozin significantly decreased adiposity and levels of fasting glucose and HbA1c but increased average serum FABP4 level by 10.3% (18.0 ± 1.0 vs. 19.8 ± 1.2 ng/ml, P = 0.008), though elevation of FABP4 level after treatment was observed in 26 (66.7%) out of 39 patients. Change in FABP4 level was positively correlated with change in levels of fasting glucose (r = 0.329, P = 0.044), HbA1c (r = 0.329, P = 0.044) and noradrenaline (r = 0.329, P = 0.041) but was not significantly correlated with change in adiposity or other variables. Canagliflozin paradoxically increases serum FABP4 level in some diabetic patients despite amelioration of glucose metabolism and adiposity reduction, possibly via induction of catecholamine-induced lipolysis in adipocytes. Increased FABP4 level by canagliflozin may undermine the improvement of glucose metabolism and might be a possible mechanism of increased HGP by inhibition of SGLT2. UMIN-CTR Clinical Trial UMIN000018151.

Current use of guideline-based medical therapy in elderly patients admitted with acute heart failure with reduced ejection fraction and its impact on event-free survival.

PubMed

Akita, Keitaro; Kohno, Takashi; Kohsaka, Shun; Shiraishi, Yasuyuki; Nagatomo, Yuji; Izumi, Yuki; Goda, Ayumi; Mizuno, Atsushi; Sawano, Mitsuaki; Inohara, Taku; Fukuda, Keiichi; Yoshikawa, Tsutomu

2017-05-15

Acute heart failure (HF) is a frequently encountered cardiac condition. Its prevalence increases exponentially with age. In spite of this, elderly patients are underrepresented in clinical trials and the implementation of guideline-based medical therapy (GBMT) in them is not well established. We investigated the current use of GBMT and its effects on mortality and HF rehospitalization among elderly patients with acute HF with reduced ejection fraction (HFrEF) using data obtained from a contemporary multi-center registry. We analyzed data from 1,441 consecutive acute HF patients registered in the West Tokyo Heart Failure (WET-HF) registry (mean age 73.2 ± 13.6 years). Reduced ejection fraction (<45%) was noted in 803 patients (55.7%), of which 237 were aged ≥80 years (elderly group). The prescription rate of GBMT (use of renin-angiotensin system inhibitors and β-blockers at discharge) was significantly lower in the elderly than in the younger (aged < 80 years) group (46.8% vs. 66.9%, p<0.001). Although GBMT at discharge was associated with reductions in HF readmission or the composite endpoint of cardiac death and HF readmission (HR 0.49, 95% CI 0.30-0.80; and HR 0.53, 95% CI 0.32-0.89, respectively) in the younger group, this association was not observed in the elderly group (HR 1.41, 95% CI 0.68-2.92; and HR 1.54, 95% CI 0.76-3.13, respectively) CONCLUSIONS: GBMT implementation in elderly patients with HFrEF was found to be suboptimal. However, the underuse of GBMT did not appear to be responsible for poorer outcomes in elderly HFrEF patients. Further research is required to establish an ideal therapeutic approach for this population. URL: http://www.umin.ac.jp/icdr/index-j.html. Unique identifier: UMIN000001171. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Distinct Phenotypes of Cigarette Smokers Identified by Cluster Analysis of Patients with Severe Asthma.

PubMed

Konno, Satoshi; Taniguchi, Natsuko; Makita, Hironi; Nakamaru, Yuji; Shimizu, Kaoruko; Shijubo, Noriharu; Fuke, Satoshi; Takeyabu, Kimihiro; Oguri, Mitsuru; Kimura, Hirokazu; Maeda, Yukiko; Suzuki, Masaru; Nagai, Katsura; Ito, Yoichi M; Wenzel, Sally E; Nishimura, Masaharu

2015-12-01

Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses. To explore novel severe asthma phenotypes by cluster analysis when including cigarette smokers. We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics. Twelve clinical variables obtained during a 2-day hospital stay were used for cluster analysis. After clustering using clinical variables, the sputum levels of 14 molecules were measured to biologically characterize the clinical clusters. Five clinical clusters were identified, including two characterized by high pack-year exposure to cigarette smoking and low FEV1/FVC. There were marked differences between the two clusters of cigarette smokers. One had high levels of circulating eosinophils, high IgE levels, and a high sinus disease score. The other was characterized by low levels of the same parameters. Sputum analysis revealed increased levels of IL-5 in the former cluster and increased levels of IL-6 and osteopontin in the latter. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 1 year later. This study reveals two distinct phenotypes of severe asthma in current and former cigarette smokers with potentially different biological pathways contributing to fixed airflow limitation. Clinical trial registered with www.umin.ac.jp (000003254).

The 23-valent pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis: a double-blinded, randomized, placebo-controlled trial.

PubMed

Izumi, Yasumori; Akazawa, Manabu; Akeda, Yukihiro; Tohma, Shigeto; Hirano, Fuminori; Ideguchi, Haruko; Matsumura, Ryutaro; Miyamura, Tomoya; Mori, Shunsuke; Fukui, Takahiro; Iwanaga, Nozomi; Jiuchi, Yuka; Kozuru, Hideko; Tsutani, Hiroshi; Saisyo, Kouichirou; Sugiyama, Takao; Suenaga, Yasuo; Okada, Yasumasa; Katayama, Masao; Ichikawa, Kenji; Furukawa, Hiroshi; Kawakami, Kenji; Oishi, Kazunori; Migita, Kiyoshi

2017-01-25

Pneumococcal pneumonia is the most frequent form of pneumonia. We herein assessed the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in the prevention of pneumonia overall in rheumatoid arthritis (RA) patients at risk for infections. We hypothesized that PPSV23 vaccination is superior in preventing pneumococcal pneumonia compared with placebo in RA patients. A prospective, multicenter, double-blinded, randomized, placebo-controlled (1:1) trial was conducted across departments of rheumatology in Japanese National Hospital Organization hospitals. RA patients (n = 900) who had been treated with biological or immunosuppressive agents were randomly assigned PPSV23 or placebo (sodium chloride). The primary endpoints were the incidences of all-cause pneumonia and pneumococcal pneumonia. The secondary endpoint was death from pneumococcal pneumonia, all-cause pneumonia, or other causes. Cox regression models were used to estimate the risk of pneumonia overall for the placebo group compared with the vaccine group. Seventeen (3.7%) of 464 patients in the vaccine group and 15 (3.4%) of 436 patients in the placebo group developed pneumonia. There was no difference in the rates of pneumonia between the two study groups. The overall rate of pneumonia was 21.8 per 1000 person-years for patients with RA. The presence of interstitial pneumonia (hazard ratio: 3.601, 95% confidence interval: 1.547-8.380) was associated with an increased risk of pneumonia in RA patients. PPSV23 does not prevent against pneumonia overall in RA patients at relative risk for infections. Our results also confirm that the presence of interstitial lung disease is associated with pneumonia in Japanese patients with RA. UMIN-CTR UMIN000009566 . Registered 17 December 2012.

Memantine in Japanese patients with moderate to severe Alzheimer's disease: meta-analysis of multiple-index responder analyses.

PubMed

Okuizumi, Kaoru; Kamata, Teruyoshi; Matsui, Daiju; Saito, Kengo; Matsumoto, Takuyuki; Fukuchi, Yoshikazu

2018-04-01

Responder analyses assessing clinical worsening have attempted to clarify clinically meaningful drug efficacy enhancements in patients with Alzheimer's disease (AD). This was a meta-analysis of two multicenter, randomized, double-blind, parallel-group, 24-week studies of 633 Japanese patients with moderate to severe AD receiving memantine 20 mg/day (n = 318) or placebo (n = 315). The clinical trial registration number is UMIN000026013. Overall odds ratios (OR) for a reduced likelihood of clinical worsening (memantine versus placebo) were statistically significant on the following individual and combined rating scales: Severe Impairment Battery-Japanese version (SIB-J, OR 0.52; 95% CI: 0.37, 0.73; p = 0.0001); Behavioral Pathology in AD Rating Scale (BEHAVE-AD, OR 0.53; 95% CI: 0.37, 0.75; p = 0.0003); and SIB-J + Clinician's Interview-Based Impression of Change-plus-Japanese version (SIB-J + CIBIC-plus-J; OR 0.53; 95% CI: 0.37, 0.77; p = 0.0009). A significantly reduced risk of triple worsening was evident in the memantine versus placebo group on the combined SIB-J + CIBIC-plus-J + BEHAVE-AD rating scales (OR 0.38; 95% CI: 0.22, 0.65; p = 0.0003). Memantine is a viable treatment option for patients with AD presenting not only with cognitive impairment, but also with a broader range of symptoms, including the behavioral and psychological symptoms of dementia.

Effects of Lactobacillus salivarius-containing tablets on caries risk factors: a randomized open-label clinical trial

PubMed Central

2014-01-01

Background To evaluate the effects of the lactic acid bacterium Lactobacillus salivarius on caries risk factors. Methods The study was performed in 64 healthy volunteers to evaluate the effects of L. salivarius-containing tablets on caries risk factors. The participants were divided randomly into four groups, and took tablets containing L. salivarius WB21, L. salivarius TI 2711, Ovalgen® DC (antibody against glucosyltransferase from Streptococcus mutans), or xylitol. Levels of mutans streptococci and lactobacilli, amount of salivary flow, salivary pH, and salivary buffering capacity were assessed before and after taking the tablets. Subsequently, a short-term administration trial using L. salivarius WB21-containing tablets was performed in eight healthy volunteers. The participants took L. salivarius WB21-containing tablets (2.0 × 109 colony forming units/day) for 2 weeks, and the numbers of mutans streptococci in saliva were counted. Results The levels of mutans streptococci seemed to decrease in the L. salivarius WB21, TI 2711, and Ovalgen® DC groups compared to the xylitol group, with no significant differences between the groups. Lactobacilli levels significantly increased in the L. salivarius WB21 and TI 2711 groups compared to the other groups. Concerning salivary flow and salivary pH, no significant differences were observed between the groups. The salivary buffering capacity significantly increased in the L. salivarius TI 2711 group (P = 0.003) and Ovalgen® DC group (P = 0.002) compared to the xylitol group. The short-term administration trial showed that the L. salivarius WB21-containing tablets significantly decreased the number of mutans streptococci (P = 0.039). Conclusion L. salivarius-containing tablets were suggested to increase resistance to caries risk factors. Trial registration UMIN000013160 (registration date: February 14, 2014). PMID:25178882

Symptoms after Ingestion of Pig Whipworm Trichuris suis Eggs in a Randomized Placebo-Controlled Double-Blind Clinical Trial

PubMed Central

Bager, Peter; Kapel, Christian; Roepstorff, Allan; Thamsborg, Stig; Arnved, John; Rønborg, Steen; Kristensen, Bjarne; Poulsen, Lars K.; Wohlfahrt, Jan; Melbye, Mads

2011-01-01

Symptoms after human infection with the helminth Trichuris suis have not previously been described. Exposure to helminths has been suggested as immune therapy against allergy and autoimmune diseases. We randomized adults with allergic rhinitis to ingest a dose of 2500 T. suis eggs or placebo every 21 days for 168 days (total 8 doses) in a double-blind clinical trial. In a previous publication, we reported a lack of efficacy and a high prevalence of adverse gastrointestinal reactions. The aim of the present study was to present a detailed description of the adverse event data and post-hoc analyses of gastrointestinal reactions. Adverse events and severity (mild, moderate, severe) were recorded daily by subjects, classified by organ using MedDRA 10.0, and event rates compared between subjects on T. suis treatment vs. subjects on placebo. T. suis-specific serum IgG antibodies were measured by a fluoroenzymeimmunoassay (Phadia ApS). During 163 days complete follow-up, subjects ingesting T. suis eggs (N = 49) had a three to 19-fold higher rate of events (median duration, 2 days) with gastrointestinal reactions (moderate to severe flatulence, diarrhea, and upper abdominal pain) compared with placebo subjects (N = 47). The highest incidence of affected subjects was seen from the first few days and until day 42 (3rd dose): 63% vs. 29% for placebo; day 163: 76% vs. 49% for placebo. Seroprevalences increased concurrently in the T. suis group: Day 59, 50%; day 90, 91%; day 170, 93%. The combined duration of episodes with onset before day 42 was ≤14 days in 80% of affected subjects. Age, gender, total IgE, and recent intestinal symptoms at baseline did not predict gastrointestinal side effects. In conclusion, during the first 2 months, repeated ingestions of 2500 T. suis eggs caused frequent gastrointestinal reactions lasting up to 14 days, whereas 4 months further treatment mainly provoked a subclinical stimulation. Trial registration University hospital Medical Information Network trial registry Reg. no. R000001298, Trial ID UMIN000001070. PMID:21829616

The Persistence of Silodosin Monotherapy and the Reasons for Withdrawal from Treatment of Previously Untreated Japanese Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia

PubMed Central

Tanuma, Yasushi

2017-01-01

Objectives The persistence of silodosin and the reasons for withdrawal from treatment of previously untreated Japanese patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) were evaluated in real-life clinical practice. Methods A total of 81 previously untreated Japanese patients diagnosed with LUTS/BPH were treated with silodosin monotherapy and prospectively followed for 4 years. The persistence rate was estimated using the Kaplan-Meier method. If silodosin had to be terminated or a patient did not come to the hospital, the reason was determined. Results The 6-month, 1-year, 2-year, 3-year, and 4-year persistence rates were 63.0%, 56.8%, 50.6%, 44.4%, and 35.8%, respectively. The most frequent reason (22.2%) for withdrawal was symptom resolution. After silodosin treatment, the international prostate symptom score and the quality of life index were significantly improved and maintained for 4 years. Conclusions 35.8% of previously untreated Japanese patients continued silodosin for 4 years. Many patients terminated silodosin for various reasons, the most frequent of which was symptom resolution. The effects of silodosin were maintained when the patients continued treatment. Trial Registration This study was approved by the institutional review board of Hokkaido Prefectural Esashi Hospital (number 2007-2) and was registered in a public trial registry (UMIN000026910). PMID:28694823

A prospective observational study to examine the relationship between quality of life and adverse events of first-line chemotherapy plus cetuximab in patients with KRAS wild-type unresectable metastatic colorectal cancer: QUACK Trial.

PubMed

Ooki, Akira; Ando, Masahiko; Sakamoto, Junichi; Sato, Atushi; Fujii, Hirofumi; Yamaguchi, Kensei

2014-04-01

We have planned a multicentre prospective study to examine the relative impact of the efficacy and adverse events of cetuximab plus first-line chemotherapy on the quality of life in Japanese patients with KRAS wild-type unresectable colorectal cancer. The Dermatology Life Quality Index and the European Organization for Research Treatment of Cancer Quality of Life Questionnaire Core 30 will be used to assess dermatology-specific and health-related quality of life. The severity of adverse events will be assessed by using the National Cancer Institute Common Terminology Criteria for adverse Events ver. 4.0. The endpoints will be the following associations: adverse events, including skin toxicity and quality of life; efficacy and skin toxicity; efficacy and quality of life; and skin-related quality of life and health-related quality of life. A total of 140 patients are considered to be appropriate for inclusion in this study. The results of this study will provide more information to both patients and physicians regarding the practical use of cetuximab and its impact on quality of life in patients with unresectable colorectal cancer in Japan. This study was registered at the University Hospital Medical Information Network Clinical Trial Registry as UMIN000010985.

Randomized controlled trial of perioperative antimicrobial therapy based on the results of preoperative bile cultures in patients undergoing biliary reconstruction.

PubMed

Okamura, Kunishige; Tanaka, Kimitaka; Miura, Takumi; Nakanishi, Yoshitsugu; Noji, Takehiro; Nakamura, Toru; Tsuchikawa, Takahiro; Okamura, Keisuke; Shichinohe, Toshiaki; Hirano, Satoshi

2017-07-01

The high frequency of surgical site infections (SSIs) after hepato-pancreato-biliary (HPB) surgery is a problem that needs to be addressed. This prospective, randomized, controlled study examined whether perioperative prophylactic use of antibiotics based on preoperative bile culture results in HPB surgery could decrease SSI. Participants comprised 126 patients who underwent HPB (bile duct, gallbladder, ampullary, or pancreatic) cancer surgery with biliary reconstruction at Hokkaido University Hospital between August 2008 and March 2013 (UMIN Clinical Trial Registry #00001278). Before surgery, subjects were randomly allocated to a targeted group administered antibiotics based on bile culture results or a standard group administered cefmetazole. The primary endpoint was SSI rates within 30 days after surgery. Secondary endpoint was SSI rates for each operative procedure. Of the 126 patients, 124 were randomly allocated (targeted group, n = 62; standard group, n = 62). Frequency of SSI after surgery was significantly lower in the targeted group (27 patients, 43.5%) than in the standard group (44 patients, 71.0%; P = 0.002). Among patients who underwent pancreaticoduodenectomy and hepatectomy, SSI occurred significantly less frequently in the targeted group (P = 0.001 and P = 0.025, respectively). This study demonstrated that preoperative bile culture-targeted administration of prophylactic antibiotics decreased SSIs following HBP surgery with biliary reconstruction. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Haloperidol prophylaxis for preventing aggravation of postoperative delirium in elderly patients: a randomized, open-label prospective trial.

PubMed

Fukata, Shinji; Kawabata, Yasuji; Fujishiro, Ken; Kitagawa, Yuichi; Kuroiwa, Kojiro; Akiyama, Hirotoshi; Takemura, Marie; Ando, Masahiko; Hattori, Hideyuki

2017-07-01

The aim of this study was to evaluate the safety and efficacy of the early administration haloperidol in preventing the aggravation of postoperative delirium in elderly patients. A total of 201 patients (age ≥75 years) who underwent elective surgery were enrolled. The patients were divided into two groups: the intervention group (n = 101) received prophylactic haloperidol (5 mg); the control group (n = 100) did not. Haloperidol was administered daily during postoperative days 0-5 to the patients who presented with NEECHAM scores of 20-24 when measured at 18:00. The primary endpoint was the incidence of severe postoperative delirium. The incidence of severe postoperative delirium in all patients was 25.1%. The incidence of severe postoperative delirium in the intervention group (18.2%) was significantly lower than that in the control group (32.0%) (p = 0.02). The difference between the two groups was larger when the analysis was limited to the 70 patients who had NEECHAM scores of 20-24 for at least one day during postoperative days 0-5. No adverse effects of the haloperidol were observed. The prophylactic administration of haloperidol at the early stage of delirium significantly reduced the incidence of severe postoperative delirium in elderly patients. Clinical Trial Registration UMIN000007204.

Prediction of functional profiles of gut microbiota from 16S rRNA metagenomic data provides a more robust evaluation of gut dysbiosis occurring in Japanese type 2 diabetic patients.

PubMed

Inoue, Ryo; Ohue-Kitano, Ryuji; Tsukahara, Takamitsu; Tanaka, Masashi; Masuda, Shinya; Inoue, Takayuki; Yamakage, Hajime; Kusakabe, Toru; Hasegawa, Koji; Shimatsu, Akira; Satoh-Asahara, Noriko

2017-11-01

We assessed whether gut microbial functional profiles predicted from 16S rRNA metagenomics differed in Japanese type 2 diabetic patients. A total of 22 Japanese subjects were recruited from our outpatient clinic in an observational study. Fecal samples were obtained from 12 control and 10 type 2 diabetic subjects. 16S rRNA metagenomic data were generated and functional profiles predicted using "Phylogenetic Investigation of Communities by Reconstruction of Unobserved States" software. We measured the parameters of glucose metabolism, gut bacterial taxonomy and functional profile, and examined the associations in a cross-sectional manner. Eleven of 288 "Kyoto Encyclopedia of Genes and Genomes" pathways were significantly enriched in diabetic patients compared with control subjects ( p <0.05, q<0.1). The relative abundance of almost all pathways, including the Insulin signaling pathway and Glycolysis/Gluconeogenesis , showed strong, positive correlations with hemoglobin A 1c (HbA 1c ) and fasting plasma glucose (FPG) levels. Bacterial taxonomic analysis showed that genus Blautia significantly differed between groups and had negative correlations with HbA 1c and FPG levels. Our findings suggest a novel pathophysiological relationship between gut microbial communities and diabetes, further highlighting the significance and utility of combining prediction of functional profiles with ordinal bacterial taxonomic analysis (UMIN Clinical Trails Registry number: UMIN000026592).

The clinical usefulness of extravascular lung water and pulmonary vascular permeability index to diagnose and characterize pulmonary edema: a prospective multicenter study on the quantitative differential diagnostic definition for acute lung injury/acute respiratory distress syndrome

PubMed Central

2012-01-01

Introduction Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria. Methods The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy. Results Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P < 0.01). PVPI was higher in ALI/ARDS patients than in cardiogenic edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P < 0.01). In ALI/ARDS patients, EVLWI increased with increasing pulmonary vascular permeability (r = 0.729, P < 0.01) and was weakly correlated with intrathoracic blood volume (r = 0.236, P < 0.01). EVLWI was weakly correlated with the PaO2/FiO2 ratio in the ALI/ARDS and cardiogenic edema patients. A PVPI value of 2.6 to 2.85 provided a definitive diagnosis of ALI/ARDS (specificity, 0.90 to 0.95), and a value < 1.7 ruled out an ALI/ARDS diagnosis (specificity, 0.95). Conclusion PVPI may be a useful quantitative diagnostic tool for ARDS in patients with hypoxemic respiratory failure and radiographic infiltrates. Trial registration UMIN-CTR ID UMIN000003627 PMID:23232188

A randomized, double-blind, crossover, placebo-controlled clinical trial to assess effects of the single ingestion of a tablet containing lactoferrin, lactoperoxidase, and glucose oxidase on oral malodor.

PubMed

Nakano, Manabu; Shimizu, Eiju; Wakabayashi, Hiroyuki; Yamauchi, Koji; Abe, Fumiaki

2016-03-22

The main components of oral malodor have been identified as volatile sulfur compounds (VSCs) including hydrogen sulfide (H2S) and methyl mercaptan (CH3SH). VSCs also play an important role in the progression of periodontal disease. The aim of the present study was to assess the effects of the single ingestion of a tablet containing 20 mg of lactoferrin, 2.6 mg of lactoperoxidase, and 2.6 mg of glucose oxidase on VSCs in the mouth. Subjects with VSCs greater than the olfactory threshold in their mouth air ingested a test or placebo tablet in two crossover phases. The concentrations of VSCs were monitored at baseline and 10 and 30 min after ingestion of the tablets using portable gas chromatography. Thirty-nine subjects were included in the efficacy analysis based on a full analysis set (FAS). The concentrations of total VSCs and H2S at 10 min were significantly lower in the test group than in the placebo group (-0.246 log ng/10 ml [95 % CI -0.395 to -0.098], P = 0.002; -0.349 log ng/10 ml; 95 % CI -0.506 to -0.192; P < 0.001, respectively). In the subgroup analysis, a significant difference in the concentration of total VSCs between the groups was also observed when subjects were fractionated by sex (male or female) and age (20-55 or 56-65 years). The reducing effect on total VSCs positively correlated with the probing pocket depth (P = 0.035). These results suggest that the ingestion of a tablet containing lactoferrin, lactoperoxidase, and glucose oxidase has suppressive effects on oral malodor. This trial was registered with the University Hospital Medical Information Network Clinical Trial Registry (number: UMIN000015140 , date of registration: 16/09/2014).

Brain training game boosts executive functions, working memory and processing speed in the young adults: a randomized controlled trial.

PubMed

Nouchi, Rui; Taki, Yasuyuki; Takeuchi, Hikaru; Hashizume, Hiroshi; Nozawa, Takayuki; Kambara, Toshimune; Sekiguchi, Atsushi; Miyauchi, Carlos Makoto; Kotozaki, Yuka; Nouchi, Haruka; Kawashima, Ryuta

2013-01-01

Do brain training games work? The beneficial effects of brain training games are expected to transfer to other cognitive functions. Yet in all honesty, beneficial transfer effects of the commercial brain training games in young adults have little scientific basis. Here we investigated the impact of the brain training game (Brain Age) on a wide range of cognitive functions in young adults. We conducted a double-blind (de facto masking) randomized controlled trial using a popular brain training game (Brain Age) and a popular puzzle game (Tetris). Thirty-two volunteers were recruited through an advertisement in the local newspaper and randomly assigned to either of two game groups (Brain Age, Tetris). Participants in both the Brain Age and the Tetris groups played their game for about 15 minutes per day, at least 5 days per week, for 4 weeks. Measures of the cognitive functions were conducted before and after training. Measures of the cognitive functions fell into eight categories (fluid intelligence, executive function, working memory, short-term memory, attention, processing speed, visual ability, and reading ability). Our results showed that commercial brain training game improves executive functions, working memory, and processing speed in young adults. Moreover, the popular puzzle game can engender improvement attention and visuo-spatial ability compared to playing the brain training game. The present study showed the scientific evidence which the brain training game had the beneficial effects on cognitive functions (executive functions, working memory and processing speed) in the healthy young adults. Our results do not indicate that everyone should play brain training games. However, the commercial brain training game might be a simple and convenient means to improve some cognitive functions. We believe that our findings are highly relevant to applications in educational and clinical fields. UMIN Clinical Trial Registry 000005618.

Rationale, Design, and Baseline Characteristics of the Utopia Trial for Preventing Diabetic Atherosclerosis Using an SGLT2 Inhibitor: A Prospective, Randomized, Open-Label, Parallel-Group Comparative Study.

PubMed

Katakami, Naoto; Mita, Tomoya; Yoshii, Hidenori; Shiraiwa, Toshihiko; Yasuda, Tetsuyuki; Okada, Yosuke; Umayahara, Yutaka; Kaneto, Hideaki; Osonoi, Takeshi; Yamamoto, Tsunehiko; Kuribayashi, Nobuichi; Maeda, Kazuhisa; Yokoyama, Hiroki; Kosugi, Keisuke; Ohtoshi, Kentaro; Hayashi, Isao; Sumitani, Satoru; Tsugawa, Mamiko; Ohashi, Makoto; Taki, Hideki; Nakamura, Tadashi; Kawashima, Satoshi; Sato, Yasunori; Watada, Hirotaka; Shimomura, Iichiro

2017-10-01

Sodium-glucose co-transporter-2 (SGLT2) inhibitors are anti-diabetic agents that improve glycemic control with a low risk of hypoglycemia and ameliorate a variety of cardiovascular risk factors. The aim of the ongoing study described herein is to investigate the preventive effects of tofogliflozin, a potent and selective SGLT2 inhibitor, on the progression of atherosclerosis in subjects with type 2 diabetes (T2DM) using carotid intima-media thickness (IMT), an established marker of cardiovascular disease (CVD), as a marker. The Study of Using Tofogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA) trial is a prospective, randomized, open-label, blinded-endpoint, multicenter, and parallel-group comparative study. The aim was to recruit a total of 340 subjects with T2DM but no history of apparent CVD at 24 clinical sites and randomly allocate these to a tofogliflozin treatment group or a conventional treatment group using drugs other than SGLT2 inhibitors. As primary outcomes, changes in mean and maximum IMT of the common carotid artery during a 104-week treatment period will be measured by carotid echography. Secondary outcomes include changes in glycemic control, parameters related to β-cell function and diabetic nephropathy, the occurrence of CVD and adverse events, and biochemical measurements reflecting vascular function. This is the first study to address the effects of SGLT2 inhibitors on the progression of carotid IMT in subjects with T2DM without a history of CVD. The results will be available in the very near future, and these findings are expected to provide clinical data that will be helpful in the prevention of diabetic atherosclerosis and subsequent CVD. Kowa Co., Ltd. UMIN000017607.

Anti-albuminuric effects of spironolactone in patients with type 2 diabetic nephropathy: a multicenter, randomized clinical trial.

PubMed

Kato, Sawako; Maruyama, Shoichi; Makino, Hirofumi; Wada, Jun; Ogawa, Daisuke; Uzu, Takashi; Araki, Hisazumi; Koya, Daisuke; Kanasaki, Keizo; Oiso, Yutaka; Goto, Motomitsu; Nishiyama, Akira; Kobori, Hiroyuki; Imai, Enyu; Ando, Masahiko; Matsuo, Seiichi

2015-12-01

Several studies have demonstrated that spironolactone has an anti-albuminuric property in diabetic nephropathy. As an adverse event, spironolactone often induces the elevation of creatinine levels with hypotension and hyperkalemia. Therefore, we aimed to evaluate the efficacy and safety of spironolactone in Japanese patients with type 2 diabetes treated with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Fifty-two Japanese patients with diabetic nephropathy and albuminuria (100 mg/gCr-2000 mg/gCr) treated with renin-angiotensin system (RAS) blockade were enrolled in a prospective, randomized, open-label study. The patients were subjected to add-on treatment with spironolactone 25 mg once daily and compared with matched controls for 8 weeks. The primary outcome was a reduction in the rate of albuminuria at 8 weeks compared with the baseline value. This study was registered with UMIN Clinical Trials Registry (000008016). Albuminuria was reduced by 33 % (95 % confidence interval: 22-54; P = 0.0002) at 8 weeks with spironolactone. In the spironolactone group, blood pressure tended to lower and the estimated glomerular filtration rate (eGFR) was significantly decreased compared to those in the control group. When adjusted by systolic blood pressure and eGFR, spironolactone treatment still showed a significant effect on albuminuria reduction in a linear mixed model (coefficient ± standard error; 514.4 ± 137.6 mg/gCr, P < 0.0005). No patient was excluded from the study because of hyperkalemia. Spironolactone reduced albuminuria along with conventional RAS inhibitors in patients with diabetic nephropathy. Our study suggests that spironolactone exerts anti-albuminuric effects independent of systemic hemodynamic alterations.

Small Acute Benefits of 4 Weeks Processing Speed Training Games on Processing Speed and Inhibition Performance and Depressive Mood in the Healthy Elderly People: Evidence from a Randomized Control Trial

PubMed Central

Nouchi, Rui; Saito, Toshiki; Nouchi, Haruka; Kawashima, Ryuta

2016-01-01

Background: Processing speed training using a 1-year intervention period improves cognitive functions and emotional states of elderly people. Nevertheless, it remains unclear whether short-term processing speed training such as 4 weeks can benefit elderly people. This study was designed to investigate effects of 4 weeks of processing speed training on cognitive functions and emotional states of elderly people. Methods: We used a single-blinded randomized control trial (RCT). Seventy-two older adults were assigned randomly to two groups: a processing speed training game (PSTG) group and knowledge quiz training game (KQTG) group, an active control group. In PSTG, participants were asked to play PSTG (12 processing speed games) for 15 min, during five sessions per week, for 4 weeks. In the KQTG group, participants were asked to play KQTG (four knowledge quizzes) for 15 min, during five sessions per week, for 4 weeks. We measured several cognitive functions and emotional states before and after the 4 week intervention period. Results: Our results revealed that PSTG improved performances in processing speed and inhibition compared to KQTG, but did not improve performance in reasoning, shifting, short term/working memory, and episodic memory. Moreover, PSTG reduced the depressive mood score as measured by the Profile of Mood State compared to KQTG during the 4 week intervention period, but did not change other emotional measures. Discussion: This RCT first provided scientific evidence related to small acute benefits of 4 week PSTG on processing speed, inhibition, and depressive mood in healthy elderly people. We discuss possible mechanisms for improvements in processing speed and inhibition and reduction of the depressive mood. Trial registration: This trial was registered in The University Hospital Medical Information Network Clinical Trials Registry (UMIN000022250). PMID:28066229

Small Acute Benefits of 4 Weeks Processing Speed Training Games on Processing Speed and Inhibition Performance and Depressive Mood in the Healthy Elderly People: Evidence from a Randomized Control Trial.

PubMed

Nouchi, Rui; Saito, Toshiki; Nouchi, Haruka; Kawashima, Ryuta

2016-01-01

Background: Processing speed training using a 1-year intervention period improves cognitive functions and emotional states of elderly people. Nevertheless, it remains unclear whether short-term processing speed training such as 4 weeks can benefit elderly people. This study was designed to investigate effects of 4 weeks of processing speed training on cognitive functions and emotional states of elderly people. Methods: We used a single-blinded randomized control trial (RCT). Seventy-two older adults were assigned randomly to two groups: a processing speed training game (PSTG) group and knowledge quiz training game (KQTG) group, an active control group. In PSTG, participants were asked to play PSTG (12 processing speed games) for 15 min, during five sessions per week, for 4 weeks. In the KQTG group, participants were asked to play KQTG (four knowledge quizzes) for 15 min, during five sessions per week, for 4 weeks. We measured several cognitive functions and emotional states before and after the 4 week intervention period. Results: Our results revealed that PSTG improved performances in processing speed and inhibition compared to KQTG, but did not improve performance in reasoning, shifting, short term/working memory, and episodic memory. Moreover, PSTG reduced the depressive mood score as measured by the Profile of Mood State compared to KQTG during the 4 week intervention period, but did not change other emotional measures. Discussion: This RCT first provided scientific evidence related to small acute benefits of 4 week PSTG on processing speed, inhibition, and depressive mood in healthy elderly people. We discuss possible mechanisms for improvements in processing speed and inhibition and reduction of the depressive mood. Trial registration: This trial was registered in The University Hospital Medical Information Network Clinical Trials Registry (UMIN000022250).

Effects of milk product intake on thigh muscle strength and NFKB gene methylation during home-based interval walking training in older women: A randomized, controlled pilot study

PubMed Central

Masuki, Shizue; Nishida, Kensei; Hashimoto, Shigenari; Morikawa, Mayuko; Takasugi, Satoshi; Nagata, Masashi; Taniguchi, Shun'ichiro; Rokutan, Kazuhito

2017-01-01

Background Muscle atrophy with aging is closely associated with chronic systemic inflammation and lifestyle-related diseases. In the present study, we assessed whether post-exercise milk product intake during 5-month interval walking training (IWT) enhanced the increase in thigh muscle strength and ameliorated susceptibility to inflammation in older women. Methods Subjects [n = 37, 66±5 (standard deviation) yrs] who had been performing IWT for >6 months participated in this study. They were randomly divided into the following 3 groups: IWT alone (CNT, n = 12), IWT + low-dose post-exercise milk product intake (LD, n = 12; 4 g protein and 3 g carbohydrate) or IWT + a 3-times higher dose of milk product intake than the LD group (HD, n = 13). They were instructed to repeat ≥5 sets of fast and slow walking for 3 min each at ≥70% and 40% peak aerobic capacity for walking, respectively, per day for ≥4 days/week. Results After IWT, thigh muscle strength increased in the HD group (8±2%) more than in the CNT group (-2±3%, P = 0.022), despite similar IWT achievements between the groups (P>0.15). Pyrosequencing analysis using whole blood showed that methylation of NFKB1 and NFKB2, master genes of inflammation, was enhanced in the HD group (29±7% and 44±11%, respectively) more than in the CNT group (-20±6% and -10±6%, respectively; P<0.001). Moreover, the genome-wide DNA methylation analysis showed that several inflammation-related genes were hyper-methylated in the HD group compared with that in the CNT group, suggesting greater pro-inflammatory cytokine gene suppression in the HD group. Conclusion HD milk product intake after exercise produced a greater percent increase in thigh muscle strength and NFKB1 and NFKB2 gene methylation during IWT in physically active older women. Trial registration UMIN-CTR No. UMIN000024544 and No. UMIN000024912 PMID:28520754

Effects of a programme of interventions on regional comprehensive palliative care for patients with cancer: a mixed-methods study.

PubMed

Morita, Tatsuya; Miyashita, Mitsunori; Yamagishi, Akemi; Akiyama, Miki; Akizuki, Nobuya; Hirai, Kei; Imura, Chizuru; Kato, Masashi; Kizawa, Yoshiyuki; Shirahige, Yutaka; Yamaguchi, Takuhiro; Eguchi, Kenji

2013-06-01

Improvement of palliative care is an important public health issue, but knowledge about how to deliver palliative care throughout a region remains inadequate. We used surveys and in-depth interviews to assess changes in the quality of palliative care after regional interventions and to gain insights for improvement of palliative care at a regional level. In this mixed-methods study, a comprehensive programme of interventions for regional palliative care for patients with cancer was implemented from April 1, 2008, to March 31, 2011 in Tsuruoka, Kashiwa, Hamamatsu, and Nagasaki in Japan. Interventions included education, specialist support, and networking. We surveyed patients, bereaved family members, physicians, and nurses before and after the interventions were introduced. We also did qualitative interviews with health-care professionals after the interventions were introduced. Primary endpoints were numbers of home deaths, coverage of specialist services, and patient-reported and family-reported qualities of care. This trial is registered with UMIN Clinical Trial Registry, Japan (UMIN000001274). 859 patients, 1110 bereaved family members, 911 physicians, and 2378 nurses provided analysable preintervention surveys; 857 patients, 1137 bereaved family members, 706 physicians, and 2236 nurses provided analysable postintervention surveys. Proportions of home deaths increased significantly, from 348 of 5147 (6.76%) before the intervention programme to 581 of 5546 (10.48%) after the intervention programme (p<0.0001). Furthermore, 194 of 221 (87.78%) family members of patients who died at home answered that these patients had wanted to die at home. The ratio of patients who received palliative care services to all patients who died of cancer increased significantly (from 0.31 to 0.50; p<0.0001). The patient-reported (effect size 0.14; adjusted p=0.0027) and family-reported (0.23; p<0.0001) qualities of care were significantly better after interventions than before interventions. Physician-reported and nurse-reported difficulties decreased significantly after the introduction of the interventions. Qualitative interviews showed improved communication and cooperation between health-care professionals because of greater opportunities for interactions at various levels. A regional programme of interventions could improve the quality of palliative care. Improvement of communication between health-care professionals is key to improvement of services. Third Term Comprehensive Control Research for Cancer Health and Labor Sciences Research Grants of the Ministry of Health, Labour and Welfare of Japan. Copyright © 2013 Elsevier Ltd. All rights reserved.

Symptoms after ingestion of pig whipworm Trichuris suis eggs in a randomized placebo-controlled double-blind clinical trial.

PubMed

Bager, Peter; Kapel, Christian; Roepstorff, Allan; Thamsborg, Stig; Arnved, John; Rønborg, Steen; Kristensen, Bjarne; Poulsen, Lars K; Wohlfahrt, Jan; Melbye, Mads

2011-01-01

Symptoms after human infection with the helminth Trichuris suis have not previously been described. Exposure to helminths has been suggested as immune therapy against allergy and autoimmune diseases. We randomized adults with allergic rhinitis to ingest a dose of 2500 T. suis eggs or placebo every 21 days for 168 days (total 8 doses) in a double-blind clinical trial. In a previous publication, we reported a lack of efficacy and a high prevalence of adverse gastrointestinal reactions. The aim of the present study was to present a detailed description of the adverse event data and post-hoc analyses of gastrointestinal reactions. Adverse events and severity (mild, moderate, severe) were recorded daily by subjects, classified by organ using MedDRA 10.0, and event rates compared between subjects on T. suis treatment vs. subjects on placebo. T. suis-specific serum IgG antibodies were measured by a fluoroenzymeimmunoassay (Phadia ApS). During 163 days complete follow-up, subjects ingesting T. suis eggs (N = 49) had a three to 19-fold higher rate of events (median duration, 2 days) with gastrointestinal reactions (moderate to severe flatulence, diarrhea, and upper abdominal pain) compared with placebo subjects (N = 47). The highest incidence of affected subjects was seen from the first few days and until day 42 (3(rd) dose): 63% vs. 29% for placebo; day 163: 76% vs. 49% for placebo. Seroprevalences increased concurrently in the T. suis group: Day 59, 50%; day 90, 91%; day 170, 93%. The combined duration of episodes with onset before day 42 was ≤ 14 days in 80% of affected subjects. Age, gender, total IgE, and recent intestinal symptoms at baseline did not predict gastrointestinal side effects. In conclusion, during the first 2 months, repeated ingestions of 2500 T. suis eggs caused frequent gastrointestinal reactions lasting up to 14 days, whereas 4 months further treatment mainly provoked a subclinical stimulation. University hospital Medical Information Network trial registry Reg. no. R000001298, Trial ID UMIN000001070.

Subset Analysis of a Multicenter, Randomized Controlled Trial to Compare Magnifying Chromoendoscopy with Endoscopic Ultrasonography for Stage Diagnosis of Early Stage Colorectal Cancer.

PubMed

Yamada, Tomonori; Shimura, Takaya; Ebi, Masahide; Hirata, Yoshikazu; Nishiwaki, Hirotaka; Mizushima, Takashi; Asukai, Koki; Togawa, Shozo; Takahashi, Satoru; Joh, Takashi

2015-01-01

Our recent prospective study found equivalent accuracy of magnifying chromoendoscopy (MC) and endoscopic ultrasonography (EUS) for diagnosing the invasion depth of colorectal cancer (CRC); however, whether these tools show diagnostic differences in categories such as tumor size and morphology remains unclear. Hence, we conducted detailed subset analysis of the prospective data. In this multicenter, prospective, comparative trial, a total of 70 patients with early, flat CRC were enrolled from February 2011 to December 2012, and the results of 66 lesions were finally analyzed. Patients were randomly allocated to primary MC followed by EUS or to primary EUS followed by MC. Diagnoses of invasion depth by each tool were divided into intramucosal to slight submucosal invasion (invasion depth <1000 μm) and deep submucosal invasion (invasion depth ≥1000 μm), and then compared with the final pathological diagnosis by an independent pathologist blinded to clinical data. To standardize diagnoses among examiners, this trial was started after achievement of a mean κ value of ≥0.6 which was calculated from the average of κ values between each pair of participating endoscopists. Both MC and EUS showed similar diagnostic outcomes, with no significant differences in prediction of invasion depth in subset analyses according to tumor size, location, and morphology. Lesions that were consistently diagnosed as Tis/T1-SMS or ≥T1-SMD with both tools revealed accuracy of 76-78%. Accuracy was low in borderline lesions with irregular pit pattern in MC and distorted findings of the third layer in EUS (MC, 58.5%; EUS, 50.0%). MC and EUS showed the same limited accuracy for predicting invasion depth in all categories of early CRC. Since the irregular pit pattern in MC, distorted findings to the third layer in EUS and inconsistent diagnosis between both tools were associated with low accuracy, further refinements or even novel methods are still needed for such lesions. University hospital Medical Information Network Clinical Trials Registry UMIN 000005085.

Treatment Rationale and Design for J-SONIC: A Randomized Study of Carboplatin Plus Nab-paclitaxel With or Without Nintedanib for Advanced Non-Small-cell Lung Cancer With Idiopathic Pulmonary Fibrosis.

PubMed

Otsubo, Kohei; Kishimoto, Junji; Kenmotsu, Hirotsugu; Minegishi, Yuji; Ichihara, Eiki; Shiraki, Akira; Kato, Terufumi; Atagi, Shinji; Horinouchi, Hidehito; Ando, Masahiko; Kondoh, Yasuhiro; Kusumoto, Masahiko; Ichikado, Kazuya; Yamamoto, Nobuyuki; Nakanishi, Yoichi; Okamoto, Isamu

2018-01-01

We describe the treatment rationale and procedure for a randomized study (J-SONIC; University Hospital Medical Information Network Clinical Trials Registry identification no., UMIN000026799) of carboplatin plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) with or without nintedanib for patients with advanced non-small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF). The study was designed to examine the efficacy and safety of nintedanib administered with carboplatin plus nab-paclitaxel versus carboplatin plus nab-paclitaxel alone in chemotherapy-naive patients with advanced NSCLC associated with IPF. Eligible patients (enrollment target, n = 170) will be randomized at a 1:1 ratio to receive 4 cycles of carboplatin (area under the curve, 6 on day 1) plus nab-paclitaxel (100 mg/m 2 on days 1, 8, and 15) administered every 3 weeks either without (arm A) or with (arm B) nintedanib (150 mg twice daily), to be followed in arm B by single-agent administration of nintedanib (150 mg twice daily). The present trial is the first randomized controlled study for the treatment of NSCLC associated with IPF. The goal of the study is to demonstrate that nintedanib combined with carboplatin plus nab-paclitaxel prolongs the interval to acute exacerbation of IPF compared with carboplatin plus nab-paclitaxel alone. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of trelagliptin on vascular endothelial functions and serum adiponectin level in patients with type 2 diabetes: a preliminary single-arm prospective pilot study.

PubMed

Ida, Satoshi; Murata, Kazuya; Betou, Katunori; Kobayashi, Chiaki; Ishihara, Yuki; Imataka, Kanako; Uchida, Akihiro; Monguchi, Kou; Kaneko, Ryutaro; Fujiwara, Ryoko; Takahashi, Hiroka

2016-11-04

Trelagliptin, an oral DPP-4 inhibitor, which is administered once per week and characterized by a long half-life in blood. The effects of trelagliptin on vascular endothelial functions have not been clarified to date. The objective of the present study was to examine the effects of trelagliptin on vascular endothelial functions in patients with type 2 diabetes mellitus (DM) using flow-mediated dilatation (FMD), adiponectin, and asymmetric dimethylarginine (ADMA) as evaluation indicators. This study was a preliminary single-arm prospective pilot study. The subjects of this study were type 2 DM patients aged 20-74 years, who visited our outpatient department. The patients were treated with trelagliptin, and their FMD, adiponectin, and ADMA levels were measured at baseline and at 12 weeks after initial treatment to determine the changes during the study period. A total of 27 patients, excluding three dropouts, were included in the population for analysis. Trelagliptin treatment showed no significant changes in FMD (2.42 ± 2.7% at baseline vs. 2.66 ± 3.8% post-treatment, P = 0.785) and ADMA (0.41 ± 0.0 µg/mL at baseline vs. 0.40 ± 0.0 µg/mL post-treatment, P = 0.402). Trelagliptin treatment resulted in a significant increase of serum adiponectin level (7.72 ± 6.9 µg/mL at baseline vs. 8.82 ± 8.3 µg/mL post-treatment, P < 0.002). In this pilot study, trelagliptin treatment showed no significant changes in FMD. On the other hand, it was believed that trelagliptin treatment may increase serum adiponectin level. Trial Registration http://www.umin.ac.jp (Trial ID UMIN000018311).

Response to rocuronium and its determinants in patients with myasthenia gravis: A case-control study.

PubMed

Fujimoto, Masafumi; Terasaki, Shuhei; Nishi, Masaaki; Yamamoto, Tatsuo

2015-10-01

Several previous studies using univariate analysis have suggested that the pre-anaesthetic train-of-four (TOF) ratio, concentration of anti-acetylcholine receptor (AChR) antibodies and the presence of preoperative generalised muscular involvement are determinants of an increased response to neuromuscular blocking agents (NMBAs) in patients with myasthenia gravis. However, the determinants of the response of patients with myasthenia gravis to rocuronium, which is expected to be used more frequently since the advent of sugammadex, have not been studied. To clarify whether previously suggested determinants of the response to other intermediate-acting NMBAs would also affect the response to rocuronium and to reveal the determinants of the increased response to rocuronium in individual patients with myasthenia gravis using multivariate analysis. Case control study. Kumamoto University Hospital, November 2010 to September 2013. Thirty-eight patients with myasthenia gravis having surgery using a total intravenous anaesthetic technique were investigated. After induction of general anaesthesia, the 95% effective dose (ED95) of rocuronium was calculated using cumulative dose-finding methods. Neuromuscular function was monitored by acceleromyographic assessment of TOF responses of the adductor pollicis muscle to ulnar nerve stimulation. Patients were then divided into the increased response (ED95 <0.15 mg kg, n = 13) and non-increased response groups (ED95 ≥0.15 mg kg, n = 25). Demographic data, TOF ratio before rocuronium injection (baseline TOF ratio), concentration of anti-AChR antibodies, Osserman classification and treatment for myasthenia gravis in the two groups were compared. Stepwise logistic regression identified baseline TOF ratio and age of onset of myasthenia gravis as determinants of the increased response to rocuronium in patients with myasthenia gravis [odds ratios (95% confidence interval) of 0.87 (0.77 to 0.98; P = 0.02) and 0.92 (0.86 to 0.99; P = 0.03), respectively]. Multivariate analysis identified baseline TOF ratio and age of disease onset as determinants of the increased response to rocuronium in patients with myasthenia gravis. Registered with UMIN Clinical Trials Registry, identifier: UMIN000006766.

Randomized Controlled Study to Investigate the Effect of Topical Diquafosol Tetrasodium on Corneal Sensitivity in Short Tear Break-Up Time Dry Eye.

PubMed

Kaido, Minako; Kawashima, Motoko; Shigeno, Yuta; Yamada, Yoshiaki; Tsubota, Kazuo

2018-05-01

Complex mechanisms underlie dry eye (DE) symptom provocation. In particular, corneal hypersensitivity may provoke symptoms in short tear break-up time (BUT) DE characterized by tear film instability. We hypothesized that improved tear film stability may alleviate corneal sensitivity in patients with short tear BUT DE. Therefore, we investigated the effect of topical diquafosol tetrasodium (DQS) on corneal sensitivity in unstable tear film DE. This prospective, randomized study included 27 subjects (age: 39.1 ± 8.4 years; range: 25-59 years) with short tear BUT DE, defined based on the presence of DE symptoms and tear film instability. Subjects were randomly divided into DQS (3% DQS, 12 subjects) and artificial tear (AT; preservative-free AT, 15 subjects) groups. Subjects applied the medication 6 times a day for 5 weeks. The perception of touch (S-touch) and pain (S-pain) sensitivity was measured using a Cochet-Bonnet esthesiometer. Tear evaluation, corneal sensitivity, and DE symptoms were compared before and after DQS or AT administration. The correlation between the improvement degrees of corneal sensitivity and DE symptoms following medication was analyzed. DQS significantly improved tear BUT and tear meniscus height (TMH) scores (p < 0.05), while AT significantly improved tear BUT (p < 0.05) but not TMH score. Mean S-pain and DE symptom scores were lower after medication use in the DQS (S-pain and DE symptoms: p  < 0.05) and AT groups (S-pain: p  = 0.05; DE symptoms: p  < 0.05). However, S-touch did not change significantly in either group. A positive correlation was observed between the improvement degrees of S-pain and DE symptoms in the overall subjects studied. Both DQS and AT alleviate corneal hypersensitivity and DE symptoms in eyes with short tear BUT DE. However, DQS seems to be more effective to adjust tear environment, leading to the normalization of corneal sensitivity and DE symptoms. UMIN Clinical Trials Registry Identifier, UMIN000014536.

Multicenter, Randomized, Controlled Study Comparing Tafluprost/Timolol Fixed Combination with Latanoprost/Timolol Fixed Combination in Primary Open-Angle Glaucoma and Ocular Hypertension.

PubMed

Suzuki, Katsuyoshi; Otsuka, Naomi; Hizaki, Hiroko; Hashimoto, Masayo; Kuwayama, Yasuaki

2018-06-05

This was the first exploratory randomized controlled study to compare the efficacy and safety of a preserved tafluprost/timolol fixed combination (TAF/TIM) with a preserved latanoprost/timolol fixed combination (LAT/TIM). This prospective, randomized, open-label study was conducted in Japanese patients with primary open-angle glaucoma, including normal-tension glaucoma or ocular hypertension. Following a 4-week LAT/TIM run-in period, eligible patients entered a 12-week treatment period, during which they received either LAT/TIM or TAF/TIM. The efficacy endpoint was the change in intraocular pressure (IOP) from baseline to week 12 and the safety endpoints included the changes from baseline to week 12 in superficial punctate keratopathy (SPK) score, tear breakup time (TBUT), and hyperemia score, as well as adverse events (AEs). At week 6, ocular symptoms were evaluated using a questionnaire. In total, 131 patients provided informed consent. Of these, 115 completed the run-in period and were assigned to receive TAF/TIM (n = 60) or LAT/TIM (n = 55). At week 12, there were no significant differences between the TAF/TIM and LAT/TIM groups in the change from baseline in trough IOP and IOP at 4-6 h after instillation. There were no significant differences between the two groups in the change from baseline to week 12 in SPK score, TBUT, and hyperemia score. However, only in the TAF/TIM group, the total SPK score and the inferior cornea SPK score were significantly lower at week 12 compared with baseline. Eye irritation and eye pain were significantly decreased in the TAF/TIM group compared with the LAT/TIM group. Two treatment-related AEs were reported in the TAF/TIM group (3.3%) and none in the LAT/TIM group, while no serious AEs were reported in either group. TAF/TIM is as effective as LAT/TIM in terms of IOP-reducing effect, with fewer ocular symptoms. TAF/TIM was associated with a significant improvement in SPK scores. UMIN Clinical Trials Registry Identifier, UMIN000023862. Santen Pharmaceutical Co., Ltd., Osaka, Japan.

Early control treatment with montelukast in preschool children with asthma: A randomized controlled trial.

PubMed

Nagao, Mizuho; Ikeda, Masanori; Fukuda, Norimasa; Habukawa, Chizu; Kitamura, Tetsuro; Katsunuma, Toshio; Fujisawa, Takao

2018-01-01

While Japanese guideline recommends initial control treatment for preschool children with asthma symptoms more than once a month, Western guidelines do not. To determine whether control treatment with montelukast was more effective than as-needed β 2 -agonists in this population, we conducted a randomized controlled trial. Eligible patients were children aged 1-5 years who had asthma symptoms more than once a month but less than once a week. Patients were randomly assigned in a 1:1 ratio to receive montelukast 4 mg daily for 48 weeks or as-needed β 2 -agonists. The primary endpoint was the number of acute asthma exacerbations before starting step-up treatment with inhaled corticosteroids. This study is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000002219. From September 2009 to November 2012, 93 patients (47 in the montelukast group and 46 in the no-controller group) were enrolled into the study. All patients were included in the analysis. During the study, 13 patients (28%) in the montelukast group and 23 patients (50%) in the no-controller group had acute exacerbations with the mean numbers of 0.9 and 1.9/year, respectively (P = 0.027). In addition, 10 (21%) and 19 (41%) patients received step-up treatment, respectively. Cumulative incidence of step-up treatment was significantly lower in the montelukast group (hazard ratio 0.45, 95% confidence interval 0.21 to 0.92; P = 0.033). Montelukast is an effective control treatment for preschool children who had asthma symptoms more than once a month but less than once a week. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

A Smartphone Application to Reduce the Time to Automated External Defibrillator Delivery After a Witnessed Out-of-Hospital Cardiac Arrest: A Randomized Simulation-Based Study.

PubMed

Hatakeyama, Toshihiro; Nishiyama, Chika; Shimamoto, Tomonari; Kiyohara, Kosuke; Kiguchi, Takeyuki; Chida, Izumi; Izawa, Junichi; Matsuyama, Tasuku; Kitamura, Tetsuhisa; Kawamura, Takashi; Iwami, Taku

2018-04-13

We developed a new smartphone application to deliver an automated external defibrillator (AED) to out-of-hospital cardiac arrest scene. The aim of this study was to evaluate whether an AED could be delivered earlier with or without an application in a simulated randomized controlled trial. Participants, who were asked to work as bystanders, were randomly assigned to either an application group or control group and were asked to bring an AED in both groups. The bystanders in the application group sent a signal notification using the application to two responders, who were stationed within 200 meters of the arrest scene, to carry an AED. The primary outcome was the AED delivery time by either the bystander or his/her responder. In total, 61 bystanders were eligible and randomized to either the application group (32) or the control group (29). The 52 with time data were available and analyzed. The AED delivery time by either the bystander or his/her responder was significantly shorter in the application group than in the control group [133.6 (44.4) seconds vs. 202.2 (122.2) seconds, P = 0.01]. In this simulation-based trial, AED delivery time was shortened by our newly developed smartphone application for the bystander to ask nearby responders to find and bring an AED to the cardiac arrest scene (UMIN-Clinical Trials Registry 000016506).This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Effects of Lactobacillus salivarius-containing tablets on caries risk factors: a randomized open-label clinical trial.

PubMed

Nishihara, Tetsuyo; Suzuki, Nao; Yoneda, Masahiro; Hirofuji, Takao

2014-09-02

To evaluate the effects of the lactic acid bacterium Lactobacillus salivarius on caries risk factors. The study was performed in 64 healthy volunteers to evaluate the effects of L. salivarius-containing tablets on caries risk factors. The participants were divided randomly into four groups, and took tablets containing L. salivarius WB21, L. salivarius TI 2711, Ovalgen® DC (antibody against glucosyltransferase from Streptococcus mutans), or xylitol. Levels of mutans streptococci and lactobacilli, amount of salivary flow, salivary pH, and salivary buffering capacity were assessed before and after taking the tablets. Subsequently, a short-term administration trial using L. salivarius WB21-containing tablets was performed in eight healthy volunteers. The participants took L. salivarius WB21-containing tablets (2.0 × 10(9) colony forming units/day) for 2 weeks, and the numbers of mutans streptococci in saliva were counted. The levels of mutans streptococci seemed to decrease in the L. salivarius WB21, TI 2711, and Ovalgen® DC groups compared to the xylitol group, with no significant differences between the groups. Lactobacilli levels significantly increased in the L. salivarius WB21 and TI 2711 groups compared to the other groups. Concerning salivary flow and salivary pH, no significant differences were observed between the groups. The salivary buffering capacity significantly increased in the L. salivarius TI 2711 group (P = 0.003) and Ovalgen® DC group (P = 0.002) compared to the xylitol group. The short-term administration trial showed that the L. salivarius WB21-containing tablets significantly decreased the number of mutans streptococci (P = 0.039). L. salivarius-containing tablets were suggested to increase resistance to caries risk factors. UMIN000013160 (registration date: February 14, 2014).

Carperitide and atrial fibrillation after coronary bypass grafting: the Nihon University working group study of low-dose HANP infusion therapy during cardiac surgery trial for postoperative atrial fibrillation.

PubMed

Sezai, Akira; Iida, Mitsuru; Yoshitake, Isamu; Wakui, Shinji; Osaka, Shunji; Kimura, Haruka; Yaoita, Hiroko; Hata, Hiroaki; Shiono, Motomi; Nakai, Toshiko; Takayama, Tadateru; Kunimoto, Satoshi; Kasamaki, Yuji; Hirayama, Atsushi

2015-06-01

Occurrence of atrial fibrillation after cardiac surgery is associated with long-term mortality. We investigated whether infusion of human atrial natriuretic peptide (carperitide) could prevent postoperative atrial fibrillation. A total of 668 patients who underwent isolated coronary artery bypass grafting were randomized to receive infusion of carperitide or physiological saline from the initiation of cardiopulmonary bypass. Patients were monitored continuously for 1 week after surgery to detect atrial fibrillation. The risk factors were investigated by Cox proportional hazard model. Postoperative atrial fibrillation occurred in 41 of 335 patients (12.2%) from the carperitide group versus 110 of 333 patients (32.7%) from the placebo group (P<0.0001). Postoperative levels of angiotensin-II, aldosterone, creatine kinase MB isoenzyme, human heart fatty acid-binding protein, and brain natriuretic peptide were all significantly lower in the carperitide group. The risk factors for postoperative atrial fibrillation by the Cox proportional hazard model were an age ≥70 years, emergency surgery, preoperative aldosterone level >150 ng/mL, preoperative nonuse of angiotensin receptor antagonists, preoperative use of calcium antagonists, postoperative nonuse of β-blockers, postoperative nonuse of aldosterone blockers, and nonuse of carperitide. -Perioperative carperitide infusion reduced the occurrence of postoperative atrial fibrillation. Accordingly, carperitide could be a useful option for preventing postoperative atrial fibrillation. -URL: http://www.umin.ac.jp. Unique Identifier: UMIN000003958. © 2015 American Heart Association, Inc.

Cognitive and Behavioral Skills Exercises Completed by Patients with Major Depression During Smartphone Cognitive Behavioral Therapy: Secondary Analysis of a Randomized Controlled Trial

PubMed Central

Horikoshi, Masaru; Fujita, Hirokazu; Tsujino, Naohisa; Jinnin, Ran; Kako, Yuki; Ogawa, Sei; Sato, Hirotoshi; Kitagawa, Nobuki; Shinagawa, Yoshihiro; Ikeda, Yoshio; Imai, Hissei; Tajika, Aran; Ogawa, Yusuke; Akechi, Tatsuo; Yamada, Mitsuhiko; Shimodera, Shinji; Watanabe, Norio; Inagaki, Masatoshi; Hasegawa, Akio

2018-01-01

Background A strong and growing body of evidence has demonstrated the effectiveness of cognitive behavioral therapy (CBT), either face-to-face, in person, or as self-help via the Internet, for depression. However, CBT is a complex intervention consisting of several putatively effective components, and how each component may or may not contribute to the overall effectiveness of CBT is poorly understood. Objective The aim of this study was to investigate how the users of smartphone CBT use and benefit from various components of the program. Methods This is a secondary analysis from a 9-week, single-blind, randomized controlled trial that has demonstrated the effectiveness of adjunctive use of smartphone CBT (Kokoro-App) over antidepressant pharmacotherapy alone among patients with drug-resistant major depressive disorder (total n=164, standardized mean difference in depression severity at week 9=0.40, J Med Internet Res). Kokoro-App consists of three cognitive behavioral skills of self-monitoring, behavioral activation, and cognitive restructuring, with corresponding worksheets to fill in. All activities of the participants learning each session of the program and completing each worksheet were uploaded onto Kokoro-Web, which each patient could use for self-check. We examined what use characteristics differentiated the more successful users of the CBT app from the less successful ones, split at the median of change in depression severity. Results A total of 81 patients with major depression were allocated to the smartphone CBT. On average, they completed 7.0 (standard deviation [SD] 1.4) out of 8 sessions of the program; it took them 10.8 (SD 4.2) days to complete one session, during which they spent 62 min (SD 96) on the app. There were no statistically significant differences in the number of sessions completed, time spent for the program, or the number of completed self-monitoring worksheets between the beneficiaries and the nonbeneficiaries. However, the former completed more behavioral activation tasks, engaged in different types of activities, and also filled in more cognitive restructuring worksheets than the latter. Activities such as “test-drive a new car,” “go to a coffee shop after lunch,” or “call up an old friend” were found to be particularly rewarding. All cognitive restructuring strategies were found to significantly decrease the distress level, with “What would be your advice to a friend who has a similar problem?” found more helpful than some other strategies. Conclusions The CBT program offered via smartphone and connected to the remote server is not only effective in alleviating depression but also opens a new avenue in gathering information of what and how each participant may utilize the program. The activities and strategies found useful in this analysis will provide valuable information in brush-ups of the program itself and of mobile health (mHealth) in general. Trial Registration Japanese Clinical Trials Registry UMIN CTR 000013693; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ ctr_view.cgi?recptno=R000015984 (Archived by WebCite at http://www.webcitation.org/6u6pxVwik) PMID:29326098

A randomized-controlled trial focusing on socio-economic status for promoting vegetable intake among adults using a web-based nutrition intervention programme: study protocol.

PubMed

Nakamura, Saki; Inayama, Takayo; Arao, Takashi

2017-01-13

Web-based nutritional education programmes appear to be comparable to those delivered face-to-face. However, no existing web-based nutrition education or similar programme has yet been evaluated with consideration of socio-economic status. The objective of a nutritional education programme of promoting vegetable intake designed a randomized controlled trial (RCT) is to evaluate the results of intervention and to determine how socio-economic status influences the programme effects. Participants will be randomly sampled individuals (aged 30-59) stratified according national population statistics for sex, age, and household income. Participants were consented to survey participation (n = 1500), and will be randomly divided into intervention and control groups. The intervention period is 5 weeks with one step of diet-related education per week. The main outcome of the programme is dietary behaviour as eating vegetable (350 g per day, five small bowl). To encourage behavioural changes, the programme contents are prepared using behavioural theories and techniques tailored to the assumed group stages of behavioural change. In the first step, we employ the health belief model to encourage a shift from the pre-contemplative to the contemplative phase; in the second and third steps, social cognitive theory is used to encourage transition to the preparatory phase; in the fourth step, social cognitive theory and strengthening social support are used to promote progression to the execution phase; finally, in the fifth step, strengthening social capital and social support are used to promote the shift to the maintenance phase. The baseline, post intervention and follow-up survey was assessed using a self-administered questionnaire. For process evaluation, we use five items relating to programme participation and satisfaction. A follow-up survey of participants will be carried out 3 months after intervention completion. The fact that this study is an RCT with an established control group is a strong advantage. Information and communications technology is not limited by time or place. If we could show this web-based nutrition education programmes has a positive effect, it may be an appropriate tool for reaching individuals in lower socio-economic state. Current Controlled Trials UMIN-ICDR UMIN 000019376 (Registered October 16, 2015).

A randomised controlled trial of repeated filmed social contact on reducing mental illness-related stigma in young adults.

PubMed

Koike, S; Yamaguchi, S; Ojio, Y; Ohta, K; Shimada, T; Watanabe, K; Thornicroft, G; Ando, S

2018-04-01

Public stigma alters attitudes towards people with mental illness, and is a particular concern for young people since most mental health problems occur in adolescence and young adulthood. However, little is known about the long-term effects of repeated filmed social contact (FSC) on reducing mental health-related stigma among young adults in the general population, compared with self-instructional Internet search (INS) and control interventions. This study is a parallel-group randomised controlled trial over 12 months conducted in Tokyo, Japan. A total of 259 university students (male n = 150, mean age = 20.0 years, s.d. = 1.2) were recruited from 20 colleges and universities between November 2013 and July 2014, without being provided information about the mental health-related survey or trial. Participants were assigned to one of three groups before completion of the baseline survey (FSC/INS/control = 89/83/87). The FSC group received a computer-based 30-min social contact film with general mental health education and five follow-up web-based FSCs at 2-month intervals. The INS group undertook a 30-min search for mental health-related information with five follow-up web-based reminders for self-instructional searches at 2-month intervals. The control group played PC games and had no follow-up intervention. The main outcome measures were the future (intended behaviour) domain of the Reported and Intended Behaviour Scale at 12 months after the intervention. Analysis was conducted in September 2015. At the 12-month follow-up, 218 participants completed the survey (84.1%, 75:70:73). The FSC group showed the greatest change at the 12-month follow-up (FSC: mean change 2.11 [95% CI 1.49, 2.73], INS: 1.04 [0.29, 1.80], control: 0.71 [0.09, 1.33]; FSC v. INS p = 0.037, FSC v. controls p = 0.004). No adverse events were reported during the follow-up period. FSC was more successful in reducing stigma at 12 months after intervention than INS or control interventions. FSC could be used to reduce stigma in educational lectures and anti-stigma campaigns targeted at young people. This study is registered at UMIN-CTR (No. UMIN000012239).

Virtual bronchoscopic navigation without X-ray fluoroscopy to diagnose peripheral pulmonary lesions: a randomized trial.

PubMed

Asano, Fumihiro; Ishida, Takashi; Shinagawa, Naofumi; Sukoh, Noriaki; Anzai, Masaki; Kanazawa, Kenya; Tsuzuku, Akifumi; Morita, Satoshi

2017-12-11

Transbronchial biopsy for peripheral pulmonary lesions is generally performed under X-ray fluoroscopy. Virtual bronchoscopic navigation (VBN) is a method in which virtual images of the bronchial route to the lesion are produced based on CT images obtained before VBN, and the bronchoscope is guided using these virtual images, improving the diagnostic yield of peripheral pulmonary lesions. VBN has the possibility of eliminating the need for X-ray fluoroscopy in the bronchoscopic diagnosis of peripheral lesions. To determine whether VBN can be a substitute for X-ray fluoroscopy, a randomized multicenter trial (non-inferiority trial) was performed in VBN and X-ray fluoroscopy (XRF) -assisted groups. The non-inferiority margin in the VBN-assisted group compared with the XRF-assisted group was set at 15%. The subjects consisted of 140 patients with peripheral pulmonary lesions with a mean diameter > 3 cm. In the VBN-assisted group, the bronchoscope was guided to the lesion using a VBN system without X-ray fluoroscopy. In the XRF-assisted group, the same bronchoscope was guided to the lesion under X-ray fluoroscopy. Subsequently, in both groups, the lesion was visualized using endobronchial ultrasonography with a guide sheath (EBUS/GS), and biopsy was performed. In this serial procedure, X-ray fluoroscopy was not used in the VBNA group. The subjects of analysis consisted of 129 patients. The diagnostic yield was 76.9% (50/65) in the VBN-assisted group and 85.9% (55/64) in the XRF-assisted group. The difference in the diagnostic yield between the two groups was -9.0% (95% confidence interval: -22.3% ~ 4.3%). The non-inferiority of the VBN-assisted group could not be confirmed. The rate of visualizing lesions by EBUS was 95.4% (62/65) in the VBN-assisted group and 96.9% (62/64) in the XRF-assisted group, being high in both groups. On EBUS/GS, a bronchoscope and biopsy instruments may be guided to the lesions using VBN without X-ray fluoroscopy, but X-ray fluoroscopy is necessary to improve the accuracy of sample collection from lesions. During transbronchial biopsy for peripheral pulmonary lesions, VBN cannot be a substitute for X-ray fluoroscopy. UMIN-CTR (UMIN000001710); registered 16 February 2009.

Possible clinical effects of molecular hydrogen (H2) delivery during hemodialysis in chronic dialysis patients: Interim analysis in a 12 month observation

PubMed Central

Nakayama, Masaaki; Itami, Noritomo; Suzuki, Hodaka; Hamada, Hiromi; Osaka, Naoyuki; Yamamoto, Ryo; Tsunoda, Kazumasa; Nakano, Hirofumi; Watanabe, Kimio; Zhu, Wan-Jun; Maruyama, Yukio; Terawaki, Hiroyuki; Kabayama, Shigeru; Nakazawa, Ryoichi; Miyazaki, Mariko; Ito, Sadayoshi

2017-01-01

Background and aim It is supposed that enhanced oxidative stress and inflammation are involved with the poor clinical outcomes in patients on chronic dialysis treatment. Recent studies have shown that molecular hydrogen (H2) is biologically active as an anti-inflammatory agent. Thus, we developed a novel hemodialysis (E-HD) system which delivers H2 (30 to 80 ppb)-enriched dialysis solution, to conduct a prospective observational study (UMIN000004857) in order to compare the long-term outcomes between E-HD and conventional-HD (C-HD) in Japan. The present interim analysis aimed to look at potential clinical effects of E-HD during the first 12 months observation. Subjects and method 262 patients (140, E-HD; 122, C-HD) were subjected for analysis for comprehensive clinical profiles. They were all participating in the above mentioned study, and they had been under the respective HD treatment for 12 consecutive months without hospitalization. Collected data, such as, physical and laboratory examinations, medications, and self-assessment questionnaires on subjective symptoms (i.e., fatigue and pruritus) were compared between the two groups. Results In a 12-month period, no clinical relevant differences were found in dialysis-related parameters between the two groups. However, there were differences in the defined daily dose of anti-hypertensive agents, and subjective symptoms, such as severe fatigue, and pruritus, which were all less in the E-HD group. Multivariate analysis revealed E-HD was an independent significant factor for the reduced use of anti-hypertensive agents as well as the absence of severe fatigue and pruritus at 12 months after adjusting for confounding factors. Conclusion The data indicates E-HD could have substantial clinical benefits beyond conventional HD therapy, and support the rationale to conduct clinical trials of H2 application to HD treatment. PMID:28902900

Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial.

PubMed

van de Velde, Cornelis J H; Rea, Daniel; Seynaeve, Caroline; Putter, Hein; Hasenburg, Annette; Vannetzel, Jean-Michel; Paridaens, Robert; Markopoulos, Christos; Hozumi, Yasuo; Hille, Elysee T M; Kieback, Dirk G; Asmar, Lina; Smeets, Jan; Nortier, Johan W R; Hadji, Peyman; Bartlett, John M S; Jones, Stephen E

2011-01-22

Aromatase inhibitors improved disease-free survival compared with tamoxifen when given as an initial adjuvant treatment or after 2-3 years of tamoxifen to postmenopausal women with hormone-receptor-positive breast cancer. We therefore compared the long-term effects of exemestane monotherapy with sequential treatment (tamoxifen followed by exemestane). The Tamoxifen Exemestane Adjuvant Multinational (TEAM) phase 3 trial was conducted in hospitals in nine countries. Postmenopausal women (median age 64 years, range 35-96) with hormone-receptor-positive breast cancer were randomly assigned in a 1:1 ratio to open-label exemestane (25 mg once a day, orally) alone or following tamoxifen (20 mg once a day, orally) for 5 years. Randomisation was by use of a computer-generated random permuted block method. The primary endpoint was disease-free survival (DFS) at 5 years. Main analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, NCT00279448, NCT00032136, and NCT00036270; NTR 267; Ethics Commission Trial27/2001; and UMIN, C000000057. 9779 patients were assigned to sequential treatment (n=4875) or exemestane alone (n=4904), and 4868 and 4898 were analysed by intention to treat, respectively. 4154 (85%) patients in the sequential group and 4186 (86%) in the exemestane alone group were disease free at 5 years (hazard ratio 0·97, 95% CI 0·88-1·08; p=0·60). In the safety analysis, sequential treatment was associated with a higher incidence of gynaecological symptoms (942 [20%] of 4814 vs 523 [11%] of 4852), venous thrombosis (99 [2%] vs 47 [1%]), and endometrial abnormalities (191 [4%] vs 19 [<1%]) than was exemestane alone. Musculoskeletal adverse events (2448 [50%] vs 2133 [44%]), hypertension (303 [6%] vs 219 [5%]), and hyperlipidaemia (230 [5%] vs 136 [3%]) were reported more frequently with exemestane alone. Treatment regimens of exemestane alone or after tamoxifen might be judged to be appropriate options for postmenopausal women with hormone-receptor-positive early breast cancer. Pfizer. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cefozopran, meropenem, or imipenem-cilastatin compared with cefepime as empirical therapy in febrile neutropenic adult patients: A multicenter prospective randomized trial.

PubMed

Nakane, Takahiko; Tamura, Kazuo; Hino, Masayuki; Tamaki, Toshiharu; Yoshida, Isao; Fukushima, Toshihiro; Tatsumi, Youichi; Nakagawa, Yasuaki; Hatanaka, Kazuo; Takahashi, Tsutomu; Akiyama, Nobu; Tanimoto, Mitsune; Ohyashiki, Kazuma; Urabe, Akio; Masaoka, Toru; Kanamaru, Akihisa

2015-01-01

We conducted an open-label, randomized study to evaluate the clinical efficacy of cefozopran, meropenem or imipenem-cilastatin using cefepime as a control in febrile neutropenia (FN) patients. Three hundred and seventy-six patients received cefepime, cefozopran, meropenem or imipenem-cilastatinas initial therapy for FN. The primary endpoint was the non-inferiority of response rates including modification at day 7 in cefozopran, meropenem or imipenem-cilastatin patients compared with cefepime in the per-protocol population (delta = 10%). The response rates for cefozopran, meropenem and imipenem-cilastatin were not significantly different compared with cefepime (cefozopran: 54/90 (60%), meropenem: 60/92 (65%), and IPM/CS: 63/88 (72%) versus cefepime: 56/85 (66%) (p = 0.44, 1.0 and 0.51, respectively)), and the differences in treatment success for cefozopran, meropenem and imipenem-cilastatin compared with cefepime were -5.9% (95% confidence interval (CI): -20.1-8.4), -0.7% (95% CI: -14.6-13.3), and 5.7% (95% CI: -8.1-19.4), respectively. The same tendency was seen in the modified intention-to-treat population. Based on the evaluation of initial drug efficacy performed on days 3-5, there was no significant difference between the four drugs. In the subgroup with an absolute neutrophil count ≤ 100 × 10(6)/L for longer than seven days, there was significantly better efficacy in the carbapenem arm compared to 4th generation beta-lactams (52% versus 27% at days 3-5, p = 0.006, and 76% versus 48% at day 7, p = 0.002). Our results suggest that the effects of these four drugs as empiric therapy were virtually the same for adult FN patients, although non-inferiority was shown only in imipenem-cilastatin compared with cefepime (clinical trial number: UMIN000000462). Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

To treat or not to treat: On what should surgical therapy be based?

PubMed

Jones, James W; McCullough, Laurence B

2015-12-01

Dr C. Autious has just returned from the most prestigious vascular surgery meeting in America. At the meeting, one of the most prominent complex aneurysm surgeons arose to discuss a paper concerning a procedure he had developed and popularized over the last decade. Dr L. Uminous stunned the audience with his declaration that he no longer recommends that his namesake procedure be performed. Instead, he proclaimed that a new, radically different procedure be adopted immediately. He showed slides detailing the novel proposal but did not give data concerning results obtained. The recommended procedure is technically possible but seems to require a different skill set. Dr Autious has a patient scheduled for elective surgery that he had planned to use the Uminous procedure to treat. What should he do? A. Do the recommended procedure as best you can. B. Refer the patient to Dr Uminous. C. Offer the recommended procedure with full disclosure. D. Give full disclosure and let the patient decide which procedure to use. E. Put the procedure on hold until more information becomes available. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Predictors of stent dysfunction after self-expandable metal stent placement for malignant gastric outlet obstruction: tumor ingrowth in uncovered stents and migration of covered stents.

PubMed

Hori, Yasuki; Naitoh, Itaru; Hayashi, Kazuki; Ban, Tesshin; Natsume, Makoto; Okumura, Fumihiro; Nakazawa, Takahiro; Takada, Hiroki; Hirano, Atsuyuki; Jinno, Naruomi; Togawa, Shozo; Ando, Tomoaki; Kataoka, Hiromi; Joh, Takashi

2017-10-01

Endoscopic metallic stenting is widely accepted as a palliation therapy for malignant gastric outlet obstruction (GOO). However, the predictors of stent dysfunction have not been clarified. We aimed to evaluate the predictors, especially tumor ingrowth in uncovered self-expandable metallic stents (U-SEMS) and migration of covered self-expandable metallic stents (C-SEMS), which are the main causes related to the stent characteristics. In this multicenter retrospective study, we compared patients with U-SEMS and C-SEMS in terms of clinical outcomes, and predictors of stent dysfunction. In total, 252 patients (126 with U-SEMS and 126 with C-SEMS) were enrolled. There were no significant differences in technical success, clinical success, GOO score, or time to stent dysfunction. Tumor ingrowth was significantly more frequent in U-SEMS (U-SEMS, 11.90% vs. C-SEMS, 0.79%; p = 0.002), and stent migration was significantly more frequent for C-SEMS (C-SEMS, 8.73% vs. U-SEMS, 0.79%; p = 0.005). Karnofsky performance status (p = 0.04), no presence of ascites (p = 0.02), and insufficient (<30%) stent expansion (p = 0.003) were significantly associated with tumor ingrowth in U-SEMS. Meanwhile, a shorter stent length (p = 0.05) and chemotherapy (p = 0.03) were predictors of C-SEMS migration. Both U-SEMS and C-SEMS are effective with comparable patencies. Tumor ingrowth and stent migration are the main causes of stent dysfunction for U-SEMS and C-SEMS, respectively. With regard to stent dysfunction, U-SEMS might be a good option for patients receiving chemotherapy, while C-SEMS with longer stents for patients in good condition. (Clinical trial registration number: UMIN000024059).

Brain Training Game Improves Executive Functions and Processing Speed in the Elderly: A Randomized Controlled Trial

PubMed Central

Nouchi, Rui; Taki, Yasuyuki; Takeuchi, Hikaru; Hashizume, Hiroshi; Akitsuki, Yuko; Shigemune, Yayoi; Sekiguchi, Atsushi; Kotozaki, Yuka; Tsukiura, Takashi; Yomogida, Yukihito; Kawashima, Ryuta

2012-01-01

Background The beneficial effects of brain training games are expected to transfer to other cognitive functions, but these beneficial effects are poorly understood. Here we investigate the impact of the brain training game (Brain Age) on cognitive functions in the elderly. Methods and Results Thirty-two elderly volunteers were recruited through an advertisement in the local newspaper and randomly assigned to either of two game groups (Brain Age, Tetris). This study was completed by 14 of the 16 members in the Brain Age group and 14 of the 16 members in the Tetris group. To maximize the benefit of the interventions, all participants were non-gamers who reported playing less than one hour of video games per week over the past 2 years. Participants in both the Brain Age and the Tetris groups played their game for about 15 minutes per day, at least 5 days per week, for 4 weeks. Each group played for a total of about 20 days. Measures of the cognitive functions were conducted before and after training. Measures of the cognitive functions fell into four categories (global cognitive status, executive functions, attention, and processing speed). Results showed that the effects of the brain training game were transferred to executive functions and to processing speed. However, the brain training game showed no transfer effect on any global cognitive status nor attention. Conclusions Our results showed that playing Brain Age for 4 weeks could lead to improve cognitive functions (executive functions and processing speed) in the elderly. This result indicated that there is a possibility which the elderly could improve executive functions and processing speed in short term training. The results need replication in large samples. Long-term effects and relevance for every-day functioning remain uncertain as yet. Trial Registration UMIN Clinical Trial Registry 000002825 PMID:22253758

High and low negative pressure suction techniques in EUS-guided fine-needle tissue acquisition by using 25-gauge needles: a multicenter, prospective, randomized, controlled trial.

PubMed

Kudo, Taiki; Kawakami, Hiroshi; Hayashi, Tsuyoshi; Yasuda, Ichiro; Mukai, Tsuyoshi; Inoue, Hiroyuki; Katanuma, Akio; Kawakubo, Kazumichi; Ishiwatari, Hirotoshi; Doi, Shinpei; Yamada, Reiko; Maguchi, Hiroyuki; Isayama, Hiroyuki; Mitsuhashi, Tomoko; Sakamoto, Naoya

2014-12-01

EUS-guided FNA (EUS-FNA) has a high diagnostic accuracy for pancreatic diseases. However, although most reports have typically focused on cytology, histological tissue quality has rarely been investigated. The effectiveness of EUS-FNA combined with high negative pressure (HNP) suction was recently indicated for tissue acquisition, but has not thus far been tested in a prospective, randomized clinical trial. To evaluate the adequacy of EUS-FNA with HNP for the histological diagnosis of pancreatic lesions by using 25-gauge needles. Prospective, single-blind, randomized, controlled crossover trial. Seven tertiary referral centers. Patients referred for EUS-FNA of pancreatic solid lesions. From July 2011 to April 2012, 90 patients underwent EUS-FNA of pancreatic solid masses by using normal negative pressure (NNP) and HNP with 2 respective passes. The order of the passes was randomized, and the sample adequacy, quality, and histology were evaluated by a single expert pathologist. EUS-FNA by using NNP and HNP. The adequacy of tissue acquisition and the accuracy of histological diagnoses made by using the EUS-FNA technique with HNP. We found that 72.2% (65/90) and 90% (81/90) of the specimens obtained using NNP and HNP, respectively, were adequate for histological diagnosis (P = .0003, McNemar test). For 73.3% (66/90) and 82.2% (74/90) of the specimens obtained by using NNP and HNP, respectively, an accurate diagnosis was achieved (P = .06, McNemar test). Pancreatitis developed in 1 patient after this procedure, which subsided with conservative therapy. This was a single-blinded, crossover study. Biopsy procedures that combine the EUS-FNA with HNP techniques are superior to EUS-FNA with NNP procedures for tissue acquisition. ( UMIN000005939.). Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Immunogenicity and safety after booster vaccination of diphtheria, tetanus, and acellular pertussis in young adults: an open randomized controlled trial in Japan.

PubMed

Hara, Megumi; Okada, Kenji; Yamaguchi, Yuko; Uno, Shingo; Otsuka, Yasuko; Shimanoe, Chisato; Nanri, Hinako; Horita, Mikako; Ozaki, Iwata; Nishida, Yuichiro; Tanaka, Keitaro

2013-12-01

The recent increase of pertussis in young adults in Japan is hypothesized to be due in part to waning protection from the acellular pertussis vaccine. While a booster immunization may prevent an epidemic of pertussis among these young adults, little is known about the safety and immunogenicity of such a booster with the diphtheria, tetanus, and acellular pertussis vaccine (DTaP), which is currently available in Japan. One hundred and eleven medical students with a mean age of 19.4 years were randomly divided into 2 groups of 55 and 56 subjects and received, respectively, 0.2 or 0.5 ml of DTaP. Immunogenicity was assessed by performing the immunoassay using serum, and the geometric mean concentration (GMC), GMC ratio (GMCR), seropositive rate, and booster response rate were calculated. Adverse reactions and adverse events were monitored for 7 days after vaccination. After booster vaccination in the two groups, significant increases were found in the antibodies against pertussis toxin, filamentous hemagglutinin, diphtheria toxoid, and tetanus toxoid, and the booster response rates for all subjects reached 100%. The GMCs and GMCRs against all antigens were significantly higher in the 0.5-ml group than in the 0.2-ml group. No serious adverse events were observed. Frequencies of local reactions were similar in the 2 groups, although the frequency of severe local swelling was significantly higher in the 0.5-ml group. These data support the acceptability of booster immunization using both 0.2 and 0.5 ml of DTaP for young adults for controlling pertussis. (This study was registered at UMIN-CTR under registration number UMIN000010672.).

Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia

PubMed Central

Narita, Atsushi; Muramatsu, Hideki; Sekiya, Yuko; Okuno, Yusuke; Sakaguchi, Hirotoshi; Nishio, Nobuhiro; Yoshida, Nao; Wang, Xinan; Xu, Yinyan; Kawashima, Nozomu; Doisaki, Sayoko; Hama, Asahito; Takahashi, Yoshiyuki; Kudo, Kazuko; Moritake, Hiroshi; Kobayashi, Masao; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

2015-01-01

Acquired aplastic anemia is an immune-mediated disease characterized by severe defects in stem cell number resulting in hypocellular marrow and peripheral blood cytopenias. Minor paroxysmal nocturnal hemoglobinuria populations and a short telomere length were identified as predictive biomarkers of immunosuppressive therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia patients (63 boys and 50 girls) in this study to evaluate their response to immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations and telomere length were detected by flow cytometry. Forty-seven patients (42%) carried a minor paroxysmal nocturnal hemoglobinuria population. The median telomere length of aplastic anemia patients was −0.99 standard deviation (SD) (range −4.01–+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive therapy after six months. Multivariate logistic regression analysis identified the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter telomere length as independent unfavorable predictors of immunosuppressive therapy response at six months. The cohort was stratified into a group of poor prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria positive and/or longer telomere length; 76 patients), respectively. The response rates of the poor prognosis and good prognosis groups at six months were 19% and 70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal hemoglobinuria population and a short telomere length is an efficient predictor of poor immunosuppressive therapy response, which should be considered while deciding treatment options: immunosuppressive therapy or first-line hematopoietic stem cell transplantation. The trial was registered in www.umin.ac.jp with number UMIN000017972. PMID:26315930

An alternative option for "resect and discard" strategy, using magnifying narrow-band imaging: a prospective "proof-of-principle" study.

PubMed

Takeuchi, Yoji; Hanafusa, Masao; Kanzaki, Hiromitsu; Ohta, Takashi; Hanaoka, Noboru; Yamamoto, Sachiko; Higashino, Koji; Tomita, Yasuhiko; Uedo, Noriya; Ishihara, Ryu; Iishi, Hiroyasu

2015-10-01

The "resect and discard" strategy is beneficial for cost savings on screening and surveillance colonoscopy, but it has the risk to discard lesions with advanced histology or small invasive cancer (small advanced lesion; SALs). The aim of this study was to prove the principle of new "resect and discard" strategy with consideration for SALs using magnifying narrow-band imaging (M-NBI). Patients undergoing colonoscopy at a tertiary center were involved in this prospective trial. For each detected polyp <10 mm, optical diagnosis (OD) and virtual management ("leave in situ", "discard" or "send for pathology") were independently made using non-magnifying NBI (N-NBI) and M-NBI, and next surveillance interval were predicted. Histological and optical diagnosis results of all polyps were compared. While the management could be decided in 82% of polyps smaller than 10 mm, 24/31 (77%) SALs including two small invasive cancers were not discarded based on OD using M-NBI. The sensitivity [90% confidence interval (CI)] of M-NBI for SALs was 0.77 (0.61-0.89). The risk for discarding SALs using N-NBI was significantly higher than that using M-NBI (53 vs. 23%, p = 0.02). The diagnostic accuracy (95% CI) of M-NBI in distinguishing neoplastic from non-neoplastic lesions [0.88 (0.86-0.90)] was significantly better than that of N-NBI [0.84 (0.82-0.87)] (p = 0.005). The results of our study indicated that our "resect and discard" strategy using M-NBI could work to reduce the risk for discarding SALs including small invasive cancer (UMIN-CTR, UMIN000003740).

Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia.

PubMed

Narita, Atsushi; Muramatsu, Hideki; Sekiya, Yuko; Okuno, Yusuke; Sakaguchi, Hirotoshi; Nishio, Nobuhiro; Yoshida, Nao; Wang, Xinan; Xu, Yinyan; Kawashima, Nozomu; Doisaki, Sayoko; Hama, Asahito; Takahashi, Yoshiyuki; Kudo, Kazuko; Moritake, Hiroshi; Kobayashi, Masao; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

2015-12-01

Acquired aplastic anemia is an immune-mediated disease characterized by severe defects in stem cell number resulting in hypocellular marrow and peripheral blood cytopenias. Minor paroxysmal nocturnal hemoglobinuria populations and a short telomere length were identified as predictive biomarkers of immunosuppressive therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia patients (63 boys and 50 girls) in this study to evaluate their response to immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations and telomere length were detected by flow cytometry. Forty-seven patients (42%) carried a minor paroxysmal nocturnal hemoglobinuria population. The median telomere length of aplastic anemia patients was -0.99 standard deviation (SD) (range -4.01-+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive therapy after six months. Multivariate logistic regression analysis identified the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter telomere length as independent unfavorable predictors of immunosuppressive therapy response at six months. The cohort was stratified into a group of poor prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria positive and/or longer telomere length; 76 patients), respectively. The response rates of the poor prognosis and good prognosis groups at six months were 19% and 70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal hemoglobinuria population and a short telomere length is an efficient predictor of poor immunosuppressive therapy response, which should be considered while deciding treatment options: immunosuppressive therapy or first-line hematopoietic stem cell transplantation. The trial was registered in www.umin.ac.jp with number UMIN000017972. Copyright© Ferrata Storti Foundation.

Prospective trial of biodegradable stents for refractory benign esophageal strictures after curative treatment of esophageal cancer.

PubMed

Yano, Tomonori; Yoda, Yusuke; Nomura, Shogo; Toyosaki, Kayo; Hasegawa, Hiromi; Ono, Hiroyuki; Tanaka, Masaki; Morimoto, Hiroyuki; Horimatsu, Takahiro; Nonaka, Satoru; Kaneko, Kazuhiro; Sato, Akihiro

2017-09-01

Biodegradable stents are reportedly effective for refractory benign esophageal strictures; however, little is known about their use in patients with refractory stricture after endoscopic submucosal dissection (ESD) or chemoradiotherapy (CRT) for esophageal cancer. This study aimed to evaluate the effectiveness of biodegradable stents for these patients. Patients with refractory benign esophageal stricture with a dysphagia score (DS) of 2 or worse and for whom the passage of a standard size endoscope was not possible were eligible. The primary endpoint was the proportion of those who improved their DSs (% DS improved) at 12 weeks after stent placement, and the secondary endpoints were the proportion of those who improved their DSs at 24 weeks, dysphagia-free survival (DFS), and adverse events. Eighteen patients (men:women, 15:3; median age, 72 years; range, 53-80) were enrolled. Twelve patients improved their DS at 12 weeks (% DS improved, 66.7%; 90% CI, 44.6%-84.4%). Also, 8 of 11 patients (72.7%) after esophagectomy, 4 of 6 patients (66.7%) after ESD, and 3 of 4 patients (75%) after CRT improved at 12 weeks. Three patients who were treated with esophagectomy maintained their DS improvement at 24 weeks (% DS improved, 16.7%; 95% CI, 3.6%-41.4%). The median DFS was 14.1 weeks (95% CI, 13.0-19.0). One patient who had ESD and CRT developed an esophagobronchial fistula 3 months after stent placement. Biodegradable stents are effective and tolerable for refractory benign esophageal strictures after treatment for esophageal cancer; however, long-term efficacy was limited, especially after ESD or CRT. (Clinical trial registration number: UMIN000008054.). Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Japan useful medication program for schizophrenia (JUMPs)-long-term study on discontinuation rate, resolution and remission, and improvement in social functioning rate associated with atypical antipsychotic medications in patients with schizophrenia

PubMed Central

2013-01-01

Background It is desirable to establish evidence for the selection of antipsychotics from the viewpoint of recovery of social activity in individual patient with schizophrenia receiving medication. From this perspective, awareness of the importance of studies about drug effectiveness on treatment discontinuation rate, remission rate, and improvement in QOL has grown recently. In Western countries, numerous reports are available in effectiveness studies, which are related to olanzapine and risperidone primarily, whereas evidence for other second-generation antipsychotics (SGAs) is poor. In Japan, no effectiveness study has been reported: thus, it is desirable to collect data that will serve as evidence for selection of the 3 SGAs approved after olanzapine. Methods The present study was a long-term effectiveness study under healthcare setting in Japan. It was designed as an open-label, multicenter, randomized, comparative study involving 104-week oral treatment with 1 of the 3 drugs (aripiprazole, blonanserin, and paliperidone) in patients with schizophrenia aged 20 years or over who required antipsychotic medication or switching of the current medication to others for reasons such as lack of efficacy and intolerability. The primary endpoint is treatment discontinuation rate for any causes. The secondary endpoints include remission rate, improvement of social activity, alleviation, aggravation or recurrence of psychiatric symptoms, and safety. The target number of subjects was set at 300. Discussion Because this study is expected to yield evidence regarding the selection of antipsychotics for facilitating the recovery of social activity in patients with schizophrenia, it is considered highly valuable to perform this effectiveness study under ordinary healthcare setting in Japan. Trial registration UMIN Clinical Trials Registry 000007942 PMID:24090047

The Effect of Sitagliptin on the Regression of Carotid Intima-Media Thickening in Patients with Type 2 Diabetes Mellitus: A Post Hoc Analysis of the Sitagliptin Preventive Study of Intima-Media Thickness Evaluation.

PubMed

Mita, Tomoya; Katakami, Naoto; Shiraiwa, Toshihiko; Yoshii, Hidenori; Gosho, Masahiko; Shimomura, Iichiro; Watada, Hirotaka

2017-01-01

Background. The effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on the regression of carotid IMT remains largely unknown. The present study aimed to clarify whether sitagliptin, DPP-4 inhibitor, could regress carotid intima-media thickness (IMT) in insulin-treated patients with type 2 diabetes mellitus (T2DM). Methods . This is an exploratory analysis of a randomized trial in which we investigated the effect of sitagliptin on the progression of carotid IMT in insulin-treated patients with T2DM. Here, we compared the efficacy of sitagliptin treatment on the number of patients who showed regression of carotid IMT of ≥0.10 mm in a post hoc analysis. Results . The percentages of the number of the patients who showed regression of mean-IMT-CCA (28.9% in the sitagliptin group versus 16.4% in the conventional group, P  = 0.022) and left max-IMT-CCA (43.0% in the sitagliptin group versus 26.2% in the conventional group, P  = 0.007), but not right max-IMT-CCA, were higher in the sitagliptin treatment group compared with those in the non-DPP-4 inhibitor treatment group. In multiple logistic regression analysis, sitagliptin treatment significantly achieved higher target attainment of mean-IMT-CCA ≥0.10 mm and right and left max-IMT-CCA ≥0.10 mm compared to conventional treatment. Conclusions . Our data suggested that DPP-4 inhibitors were associated with the regression of carotid atherosclerosis in insulin-treated T2DM patients. This study has been registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000007396).

Multicenter, randomized, open-label Phase II study comparing S-1 alternate-day oral therapy with the standard daily regimen as a first-line treatment in patients with unresectable advanced pancreatic cancer.

PubMed

Yamaue, Hiroki; Shimizu, Atsushi; Hagiwara, Yasuhiro; Sho, Masayuki; Yanagimoto, Hiroaki; Nakamori, Shoji; Ueno, Hideki; Ishii, Hiroshi; Kitano, Masayuki; Sugimori, Kazuya; Maguchi, Hiroyuki; Ohkawa, Shinichi; Imaoka, Hiroshi; Hashimoto, Daisuke; Ueda, Kazuki; Nebiki, Hiroko; Nagakawa, Tatsuya; Isayama, Hiroyuki; Yokota, Isao; Ohashi, Yasuo; Shirasaka, Tetsuhiko

2017-04-01

Non-inferiority for overall survival (OS) following alternate-day treatment with the oral anticancer drug S-1 compared with standard daily treatment was assessed in Japanese patients with unresectable advanced pancreatic cancer in a multicenter, randomized, phase II study. This trial was registered at the UMIN Clinical Trials Registry (no. 000008604). Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned 2:1 to treatment with alternate-day (twice daily on alternate days from days 1 through 42 of a 42-day cycle) or daily (twice daily on days 1 through 28 of a 42-day cycle) treatment with S-1. The primary endpoint was OS. Secondary endpoints were progression-free survival (PFS), time to treatment failure, response rate, quality of life assessments, and safety. A total of 190 patients were enrolled, of which 185 were included in the final analysis (alternate-day: 121; daily: 64). Median OS was 9.4 for the alternate-day group and 10.4 months for the daily group [hazard ratio (HR), 1.19; 95% credible interval, 0.86 to 1.64], indicating that non-inferiority of alternate-day treatment to daily treatment was not demonstrated. Median PFS was 3.0 for the alternate-day group and 4.2 months for the daily group (HR, 1.65; 95% credible interval, 1.20-2.29). The incidence of anorexia, fatigue, neutrophils, pigmentation, and pneumonitis was lower in alternate-day treatment compared with daily treatment. S-1 for advanced pancreatic cancer should be taken daily as recommended, based on the decreased OS and PFS and marginal improvement in safety observed in the alternate-day group.

Study for every other day administration of vonoprazan in maintenance treatment of erosive GERD: study protocol for a multicentre randomised cross-over study

PubMed Central

Kato, Mototsugu; Ito, Noriko; Demura, Mamiko; Kubo, Kimitoshi; Mabe, Katsuhiro; Harada, Naohiko

2018-01-01

Introduction The first drug selected for treatment of gastro-oesophageal reflux disease (GERD) and prevention of the recurrence is a proton pump inhibitor (PPI), but recently, a potassium-competitive acid blocker (P-CAB) was put on the market in Japan. Its onset of effect is faster than PPI, and it takes more than 2 days to recover acid secretion after the withdrawal period. Therefore, unlike PPI, the usefulness of every other day administration or discontinuous administration is expected. Methods and analysis This study is a prospective, multicentre, open-label, two-period randomised cross-over study to compare the efficacy and safety of PPI every other day administration and P-CAB every other day administration in 120 patients who receive erosive GERD maintenance therapy with PPI. Patients will be randomly allocated to receive 4 weeks P-CAB or PPI followed by 4 weeks cross over, where those on P-CAB will receive PPI and vice versa. The primary endpoint is proportion of asymptomatic patients. Secondary endpoints are suppressive effect of GERD symptoms, proportion of asymptomatic patients at each time point, safety and cost-saving effect of P-CAB every other day administration, compliance with every other day administration, and proportion of asymptomatic patients at the first month of study drug administration. Ethics and dissemination This study was approved by the National Hospital Organization Central Review Board for Clinical Trials (5 December 2017). Discussion If P-CAB every other day administration is established as one of GERD maintenance therapies, there is merit in both medical cost reduction and the safety to alleviate elevation in serum gastrin. Trial registration number UMIN000034701. PMID:29527318

Brain training game improves executive functions and processing speed in the elderly: a randomized controlled trial.

PubMed

Nouchi, Rui; Taki, Yasuyuki; Takeuchi, Hikaru; Hashizume, Hiroshi; Akitsuki, Yuko; Shigemune, Yayoi; Sekiguchi, Atsushi; Kotozaki, Yuka; Tsukiura, Takashi; Yomogida, Yukihito; Kawashima, Ryuta

2012-01-01

The beneficial effects of brain training games are expected to transfer to other cognitive functions, but these beneficial effects are poorly understood. Here we investigate the impact of the brain training game (Brain Age) on cognitive functions in the elderly. Thirty-two elderly volunteers were recruited through an advertisement in the local newspaper and randomly assigned to either of two game groups (Brain Age, Tetris). This study was completed by 14 of the 16 members in the Brain Age group and 14 of the 16 members in the Tetris group. To maximize the benefit of the interventions, all participants were non-gamers who reported playing less than one hour of video games per week over the past 2 years. Participants in both the Brain Age and the Tetris groups played their game for about 15 minutes per day, at least 5 days per week, for 4 weeks. Each group played for a total of about 20 days. Measures of the cognitive functions were conducted before and after training. Measures of the cognitive functions fell into four categories (global cognitive status, executive functions, attention, and processing speed). Results showed that the effects of the brain training game were transferred to executive functions and to processing speed. However, the brain training game showed no transfer effect on any global cognitive status nor attention. Our results showed that playing Brain Age for 4 weeks could lead to improve cognitive functions (executive functions and processing speed) in the elderly. This result indicated that there is a possibility which the elderly could improve executive functions and processing speed in short term training. The results need replication in large samples. Long-term effects and relevance for every-day functioning remain uncertain as yet. UMIN Clinical Trial Registry 000002825.

Spread of Quadratus Lumborum Block to the Paravertebral Space Via Intramuscular Injection: A Volunteer Study.

PubMed

Tamura, Takahiro; Kitamura, Kana; Yokota, Shuichi; Ito, Shigeki; Shibata, Yasuyuki; Nishiwaki, Kimitoshi

2018-05-01

Several types of quadratus lumborum block (QLB) are used for postoperative analgesia and are believed to be effective against both somatic and visceral pain via a local anesthetic (LA) effect in the paravertebral space (PVS). However, it remains unclear whether all QLB techniques result in LA spread into the PVS. We hypothesized that LA administered via intramuscular QLB would spread into the paravertebral space and investigated the spread and sensory block area of LA in intramuscular QLB. This volunteer study included 5 healthy men and 1 woman, with no previous medical history. Intramuscular QLB and lateral transversus abdominis plane block were performed under real-time ultrasound guidance for comparison of sensory deprivation range. Two days later, the same procedure was performed on the contralateral side of the body. The spread of LA via intramuscular QLB spread to the PVS was assessed 1 hour after the first injections using magnetic resonance imaging. Sensory perception was also evaluated by the pinprick test at 90 minutes after injection. In total, we performed 11 intramuscular QLBs and 11 lateral transversus abdominis plane blocks. Magnetic resonance imaging showed that LA did not spread into the PVS after ultrasound-guided intramuscular QLB. The analgesic area corresponded to the side of the body that was ipsilateral to the block. Ultrasound-guided intramuscular QLBs are not clinically useful for procedures requiring LA spread into the PVS but do result in an ipsilateral analgesic effect in healthy volunteers. This study was registered at University Hospital Medical Information Network Clinical Trials Registry, UMIN 000019149.

Effect of mirtazapine versus selective serotonin reuptake inhibitors on benzodiazepine use in patients with major depressive disorder: a pragmatic, multicenter, open-label, randomized, active-controlled, 24-week trial.

PubMed

Hashimoto, Tasuku; Shiina, Akihiro; Hasegawa, Tadashi; Kimura, Hiroshi; Oda, Yasunori; Niitsu, Tomihisa; Ishikawa, Masatomo; Tachibana, Masumi; Muneoka, Katsumasa; Matsuki, Satoshi; Nakazato, Michiko; Iyo, Masaomi

2016-01-01

This study aimed to evaluate whether selecting mirtazapine as the first choice for current depressive episode instead of selective serotonin reuptake inhibitors (SSRIs) reduces benzodiazepine use in patients with major depressive disorder (MDD). We concurrently examined the relationship between clinical responses and serum mature brain-derived neurotrophic factor (BDNF) and its precursor, proBDNF. We conducted an open-label randomized trial in routine psychiatric practice settings. Seventy-seven MDD outpatients were randomly assigned to the mirtazapine or predetermined SSRIs groups, and investigators arbitrarily selected sertraline or paroxetine. The primary outcome was the proportion of benzodiazepine users at weeks 6, 12, and 24 between the groups. We defined patients showing a ≥50 % reduction in Hamilton depression rating scale (HDRS) scores from baseline as responders. Blood samples were collected at baseline, weeks 6, 12, and 24. Sixty-five patients prescribed benzodiazepines from prescription day 1 were analyzed for the primary outcome. The percentage of benzodiazepine users was significantly lower in the mirtazapine than in the SSRIs group at weeks 6, 12, and 24 (21.4 vs. 81.8 %; 11.1 vs. 85.7 %, both P  < 0.001; and 12.5 vs. 81.8 %, P  = 0.0011, respectively). No between-group difference was observed in HDRS score changes. Serum proBDNF levels were significantly decreased ( χ 2  = 8.5, df  = 3, P  = 0.036) and serum mature BDNF levels were temporarily significantly decreased ( F  = 3.5, df  = 2.4, P  = 0.027) in the responders of both groups at week 24. This study demonstrated mirtazapine as the first-choice antidepressant for current depressive episodes may reduce benzodiazepine use in patients with MDD. Trial registration UMIN000004144. Registered 2nd September 2010. The date of enrolment of the first participant to the trial was 24th August 2010. This study was retrospectively registered 9 days after the first participant was enrolled.

Medium-Chain Triglycerides in Combination with Leucine and Vitamin D Increase Muscle Strength and Function in Frail Elderly Adults in a Randomized Controlled Trial.

PubMed

Abe, Sakiko; Ezaki, Osamu; Suzuki, Motohisa

2016-05-01

Sarcopenia, the loss of skeletal muscle mass, strength, and function, is common in elderly individuals but difficult to treat. A combination of nutrients was investigated to treat sarcopenia in very frail elderly adults. We enrolled 38 elderly nursing home residents (11 men and 27 women with a mean ± SD age of 86.6 ± 4.8 y) in a 3-mo randomized, controlled, single-blind, parallel group trial. The participants were randomly allocated to 3 groups. The first group received a daily l-leucine (1.2 g) and cholecalciferol (20 μg)-enriched supplement with 6 g medium-chain triglycerides (TGs) (MCTs) (LD + MCT); the second group received the same leucine and cholecalciferol-enriched supplement with 6 g long-chain TGs (LD + LCT); and the third group did not receive any supplements (control). The supplement and oils were taken at dinner, and changes in muscle mass, strength, and function were monitored. The increase in body weight in the LD + MCT (1.1 ± 1.0 kg) and LD + LCT (0.8 ± 1.1 kg) groups was greater than that in the control group (-0.5 ± 0.9 kg) (P < 0.05). After 3 mo, participants in the LD + MCT group had a 13.1% increase in right-hand grip strength (1.2 ± 1.0 kg, P < 0.01), a 12.5% increase in walking speed (0.078 ± 0.080 m/s, P < 0.05), a 68.2% increase in a 10-s leg open-and-close test performance (2.31 ± 1.68 n/10 s, P < 0.001), and a 28.2% increase in peak expiratory flow (53 ± 59 L/min, P < 0.01). No significant improvements in muscle mass, strength, or function were observed in the LD + LCT or control groups. The combined supplementation of MCTs (6 g), leucine-rich amino acids, and cholecalciferol at dinner may improve muscle strength and function in frail elderly individuals. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry as UMIN000017567. © 2016 American Society for Nutrition.

A phase ΙI study of five peptides combination with oxaliplatin-based chemotherapy as a first-line therapy for advanced colorectal cancer (FXV study)

PubMed Central

2014-01-01

Background We previously conducted a phase I trial for advanced colorectal cancer (CRC) using five HLA-A*2402-restricted peptides, three derived from oncoantigens and two from vascular endothelial growth factor (VEGF) receptors, and confirmed safety and immunological responses. To evaluate clinical benefits of cancer vaccination treatment, we conducted a phase II trial using the same peptides in combination with oxaliplatin-based chemotherapy as a first-line therapy. Methods The primary objective of the study was the response rates (RR). Progression free survival (PFS), overall survival (OS), and immunological parameters were evaluated as secondary objective. The planned sample size was more than 40 patients for both HLA2402-matched and -unmatched groups. All patients received a cocktail of five peptides (3 mg each) mixed with 1.5 ml of IFA which was subcutaneously administered weekly for the first 12 weeks followed by biweekly administration. Presence or absence of the HLA-A*2402 genotype were used for classification of patients into two groups. Results Between February 2009 and November 2012, ninety-six chemotherapy naïve CRC patients were enrolled under the masking of their HLA-A status. Ninety-three patients received mFOLFOX6 and three received XELOX. Bevacizumab was added in five patients. RR was 62.0% and 60.9% in the HLA-A*2402-matched and -unmatched groups, respectively (p = 0.910). The median OS was 20.7 months in the HLA-A*2402-matched group and 24.0 months in the unmatched group (log-rank, p = 0.489). In subgroup with a neutrophil/lymphocyte ratio (NLR) of < 3.0, patients in the HLA-matched group did not survive significantly longer than those in the unmatched group (log-rank, p = 0.289) but showed a delayed response. Conclusions Although no significance was observed for planned statistical efficacy endpoints, a delayed response was observed in subgroup with a NLR of < 3.0. Biomarkers such as NLR might be useful for selecting patients with a better treatment outcome by the vaccination. Trial registration Trial registration: UMIN000001791. PMID:24884643

Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial.

PubMed

Iijima, Kazumoto; Sako, Mayumi; Nozu, Kandai; Mori, Rintaro; Tuchida, Nao; Kamei, Koichi; Miura, Kenichiro; Aya, Kunihiko; Nakanishi, Koichi; Ohtomo, Yoshiyuki; Takahashi, Shori; Tanaka, Ryojiro; Kaito, Hiroshi; Nakamura, Hidefumi; Ishikura, Kenji; Ito, Shuichi; Ohashi, Yasuo

2014-10-04

Rituximab could be an effective treatment for childhood-onset, complicated, frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS). We investigated the efficacy and safety of rituximab in patients with high disease activity. We did a multicentre, double-blind, randomised, placebo-controlled trial at nine centres in Japan. We screened patients aged 2 years or older experiencing a relapse of FRNS or SDNS, which had originally been diagnosed as nephrotic syndrome when aged 1-18 years. Patients with complicated FRNS or SDNS who met all other criteria were eligible for inclusion after remission of the relapse at screening. We used a computer-generated sequence to randomly assign patients (1:1) to receive rituximab (375 mg/m(2)) or placebo once weekly for 4 weeks, with age, institution, treatment history, and the intervals between the previous three relapses as adjustment factors. Patients, guardians, caregivers, physicians, and individuals assessing outcomes were masked to assignments. All patients received standard steroid treatment for the relapse at screening and stopped taking immunosuppressive agents by 169 days after randomisation. Patients were followed up for 1 year. The primary endpoint was the relapse-free period. Safety endpoints were frequency and severity of adverse events. Patients who received their assigned intervention were included in analyses. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000001405. Patients were centrally registered between Nov 13, 2008, and May 19, 2010. Of 52 patients who underwent randomisation, 48 received the assigned intervention (24 were given rituximab and 24 placebo). The median relapse-free period was significantly longer in the rituximab group (267 days, 95% CI 223-374) than in the placebo group (101 days, 70-155; hazard ratio: 0·27, 0·14-0·53; p<0·0001). Ten patients (42%) in the rituximab group and six (25%) in the placebo group had at least one serious adverse event (p=0·36). Rituximab is an effective and safe treatment for childhood-onset, complicated FRNS and SDNS. Japanese Ministry of Health, Labour and Welfare. Copyright © 2014 Elsevier Ltd. All rights reserved.

Randomized controlled trial of toremifene 120 mg compared with exemestane 25 mg after prior treatment with a non-steroidal aromatase inhibitor in postmenopausal women with hormone receptor-positive metastatic breast cancer

PubMed Central

2013-01-01

Background After the failure of a non-steroidal aromatase inhibitor (nsAI) for postmenopausal patients with metastatic breast cancer (mBC), it is unclear which of various kinds of endocrine therapy is the most appropriate. A randomized controlled trial was performed to compare the efficacy and safety of daily toremifene 120 mg (TOR120), a selective estrogen receptor modulator, and exemestane 25 mg (EXE), a steroidal aromatase inhibitor. The primary end point was the clinical benefit rate (CBR). The secondary end points were objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicity. Methods Initially, a total of 91 women was registered in the study and randomly assigned to either TOR120 (n = 46) or EXE (n = 45) from October 2008 to November 2011. Three of the 46 patients in the TOR120 arm were not received treatment, 2 patients having withdrawn from the trial by their preference and one having been dropped due to administration of another SERM. Results When analyzed after a median observation period of 16.9 months, the intention-to-treat analysis showed that there were no statistical difference between TOR120 (N = 46) and EXE (n = 45) in terms of CBR (41.3% vs. 26.7%; P = 0.14), ORR (10.8% vs. 2.2%; P = 0.083), and OS (Hazard ratio, 0.60; P = 0.22). The PFS of TOR120 was longer than that of EXE, the difference being statistically significant (Hazard ratio, 0.61, P = 0.045). The results in treatment-received cohort (N = 88) were similar to those in ITT cohort. Both treatments were well-tolerated with no severe adverse events, although the treatment of 3 of 43 women administered TOR120 was stopped after a few days because of nausea, general fatigue, hot flush and night sweating. Conclusions TOR120, as a subsequent endocrine therapy for mBC patients who failed non-steroidal AI treatment, could potentially be more beneficial than EXE. Trial registration number UMIN000001841 PMID:23679192

One year follow-up after a randomized controlled trial of a 130 g/day low-carbohydrate diet in patients with type 2 diabetes mellitus and poor glycemic control

PubMed Central

Kanazawa, Akio; Hatae, Chie; Makita, Sumiko; Komiya, Koji; Shimizu, Tomoaki; Ikeda, Fuki; Tamura, Yoshifumi; Ogihara, Takeshi; Mita, Tomoya; Goto, Hiromasa; Uchida, Toyoyoshi; Miyatsuka, Takeshi; Ohmura, Chie; Watanabe, Takehito; Kobayashi, Kiyoe; Miura, Yoshiko; Iwaoka, Manami; Hirashima, Nao; Watada, Hirotaka

2017-01-01

Background & aims Recently, we conducted a prospective randomized controlled trial (RCT) showing that a 6-month 130g/day low-carbohydrate diet (LCD) reduced HbA1c and BMI more than a calorie restricted diet (CRD). [1] To assess whether the benefits of the LCD persisted after the intensive intervention, we compared HbA1c and BMI between the LCD and CRD groups at 1 year after the end of the 6-month RCT. Methods Following the end of the 6-month RCT, patients were allowed to manage their own diets with periodic outpatient visits. One year later, we analyzed clinical and nutrition data. Results Of the 66 participants in the original study, 27 in the CRD group and 22 in the LCD group completed this trial. One year after the end of the original RCT, the carbohydrate intake was comparable between the groups (215 [189–243]/day in the CRD group and 214 (176–262) g/day in the LCD group). Compared with the baseline data, HbA1c and BMI were decreased in both groups (CRD: HbA1c -0.4 [-0.9 to 0.3] % and BMI -0.63 [-1.20 to 0.18] kg/m2; LCD: HbA1c -0.35 [-1.0 to 0.35] % and BMI -0.77 [-1.15 to -0.12] kg/m2). There were no significant differences in HbA1c and BMI between the groups. Conclusions One year after the diet therapy intervention, the beneficial effect of the LCD on reduction of HbA1c and BMI did not persist in comparison with CRD. However, combining the data of both groups, significant improvements in HbA1c and BMI from baseline were observed. Although the superiority of the LCD disappeared 1 year after the intensive intervention, these data suggest that well-constructed nutrition therapy programs, both CRD and LCD, were equally effective in improving HbA1c for at least 1 year. Trial registration University Hospital Medical Information Network (UMIN) ID000010663 PMID:29206237

Beneficial effects of reading aloud and solving simple arithmetic calculations (learning therapy) on a wide range of cognitive functions in the healthy elderly: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Almost all cognitive functions decline with age. Results of previous studies have shown that cognitive training related to everyday life (reading aloud and solving simple arithmetic calculations), namely learning therapy, can improve two cognitive function (executive functions and processing speed) in elderly people. However, it remains unclear whether learning therapy engenders improvement of various cognitive functions or not. We investigate the impact of learning therapy on various cognitive functions (executive functions, episodic memory, short-term memory, working memory, attention, reading ability, and processing speed) in healthy older adults. Methods We use a single-blinded intervention with two parallel groups (a learning therapy group and a waiting list control group). Testers are blind to the study hypothesis and the group membership of participants. Through an advertisement in local newspaper, 64 healthy older adults are recruited. They will be assigned randomly to a learning therapy group or a waiting list control group. In the learning therapy group, participants are required to perform two cognitive tasks for 6 months: reading Japanese aloud and solving simple calculations. The waiting list group does not participate in the intervention. The primary outcome measure is the Stroop test score: a measure of executive function. Secondary outcome measures are assessments including the following: verbal fluency task, logical memory, first and second names, digit span forward, digit span backward, Japanese reading test, digit cancellation task, digit symbol coding, and symbol search. We assess these outcome measures before and after the intervention. Discussion This report is the first study which investigates the beneficial effects of learning therapy on a wide range of cognitive functions of elderly people. Our study provides sufficient evidence of learning therapy effectiveness. Most cognitive functions, which are correlated strongly with daily life activities, decrease with age. These study results can elucidate effects of cognitive training on elderly people. Trial registration This trial was registered in The University Hospital Medical Information Network Clinical Trials Registry (No. UMIN000006998). PMID:22483196

Endogenous flow-induced superoxide stimulates Na/H exchange activity via PKC in thick ascending limbs

PubMed Central

Garvin, Jeffrey L.

2014-01-01

Luminal flow stimulates Na reabsorption along the nephron and activates protein kinase C (PKC) which enhances endogenous superoxide (O2−) production by thick ascending limbs (TALs). Exogenously-added O2− augments TAL Na reabsorption, a process also dependent on PKC. Luminal Na/H exchange (NHE) mediates NaHCO3 reabsorption. However, whether flow-stimulated, endogenously-produced O2− enhances luminal NHE activity and the signaling pathway involved are unclear. We hypothesized that flow-induced production of endogenous O2− stimulates luminal NHE activity via PKC in TALs. Intracellular pH recovery was measured as an indicator of NHE activity in isolated, perfused rat TALs. Increasing luminal flow from 5 to 20 nl/min enhanced total NHE activity from 0.104 ± 0.031 to 0.167 ± 0.036 pH U/min, 81%. The O2− scavenger tempol decreased total NHE activity by 0.066 ± 0.011 pH U/min at 20 nl/min but had no significant effect at 5 nl/min. With the NHE inhibitor EIPA in the bath to block basolateral NHE, tempol reduced flow-enhanced luminal NHE activity by 0.029 ± 0.010 pH U/min, 30%. When experiments were repeated with staurosporine, a nonselective PKC inhibitor, tempol had no effect. Because PKC could mediate both induction of O2− by flow and the effect of O2− on luminal NHE activity, we used hypoxanthine/xanthine oxidase to elevate O2−. Hypoxanthine/xanthine oxidase increased luminal NHE activity by 0.099 ± 0.020 pH U/min, 137%. Staurosporine and the PKCα/β1-specific inhibitor Gö6976 blunted this effect. We conclude that flow-induced O2− stimulates luminal NHE activity in TALs via PKCα/β1. This accounts for part of flow-stimulated bicarbonate reabsorption by TALs. PMID:25080525

Characterization of circulating CD4+ CD8+ double positive and CD4- CD8- double negative T-lymphocyte in children with β-thalassemia major.

PubMed

Zahran, Asmaa M; Saad, Khaled; Elsayh, Khalid I; Alblihed, Mohamd A

2017-03-01

Infectious complications represent the second most common cause of mortality and a major cause of morbidity in β-thalassemia major (BTM), with a prevalence of 12-13%. The data on unconventional T-lymphocyte subsets in BTM children are limited. The aim of the present study was to investigate and evaluate phenotypic alterations in CD4 + CD8 + double positive (DP), CD4 - CD8 - double negative (DN), and natural killer T-lymphocytes (NKT) in BTM children in comparison to healthy controls. Our case control study included 80 children with BTM and 40 healthy children as controls. Assessment of unconventional T-lymphocyte populations was done using sensitive four-color flow cytometry (FACSCalibur). Our analysis of the data showed a significantly higher frequency CD4 + CD8 + (double-positive) T cells, CD4 - CD8 - (double negative) T cells, and natural killer T cells in the peripheral blood of both BTM groups (splenectomized and non-splenectomized) as compared to healthy controls, suggesting that these cells may play a role in the clinical course of BTM. The relationship of the unconventional T-lymphocytes to immune disorders in BTM children remains to be determined. Further longitudinal study with a larger sample size is warranted to elucidate the role these cells in BTM. TRIAL NUMBER: UMIN000018950.

Treatment rationale and design of the RAMNITA study: A phase II study of the efficacy of docetaxel + ramucirumab for non-small cell lung cancer with brain metastasis.

PubMed

Tanimura, Keiko; Uchino, Junji; Tamiya, Nobuyo; Kaneko, Yoshiko; Yamada, Tadaaki; Yoshimura, Kenichi; Takayama, Koichi

2018-06-01

We described the treatment rationale and procedure for a phase II study of docetaxel plus ramucirumab for non-small cell lung cancer (NSCLC) patients with brain metastasis (RAMNITA study: University Information Network Clinical Trials Registry identification no. [UMIN]: 000024551). Combination therapy of angiogenetic inhibitor with chemotherapy improved the outcome of patients with brain metastasis in previous reports; however, the efficacy of ramucirumab, a vascular endothelial growth factor receptor-2 monoclonal antibody, for brain metastasis has not been shown. This RAMNITA study is a prospective, multicenter, open-label, single-arm phase II study designed to evaluate efficacy and safety of docetaxel and ramucirumab for advanced NSCLC patients with brain metastasis. Eligible patients will receive docetaxel (60 mg/m) and ramucirumab (10 mg/kg) every 21 days until disease progression. The primary endpoint is progression-free survival (PFS), and secondary endpoints are overall survival, intracranial PFS, response rate, and safety. Sixty-five participants will be recruited from September 2017 to December 2019 and followed up for 1 year after final registration. The results from this study may suggest a treatment option for brain metastasis in NSCLC. The protocol was approved by the institutional review board of each study center. Written informed consent will be obtained from all patients before registration, in accordance with the Declaration of Helsinki.

Effect of Behavior Modification on Outcome in Early- to Moderate-Stage Chronic Kidney Disease: A Cluster-Randomized Trial

PubMed Central

Yamagata, Kunihiro; Makino, Hirofumi; Iseki, Kunitoshi; Ito, Sadayoshi; Kimura, Kenjiro; Kusano, Eiji; Shibata, Takanori; Tomita, Kimio; Narita, Ichiei; Nishino, Tomoya; Fujigaki, Yoshihide; Mitarai, Tetsuya; Watanabe, Tsuyoshi; Wada, Takashi; Nakamura, Teiji; Matsuo, Seiichi

2016-01-01

Objectives Owing to recent changes in our understanding of the underlying cause of chronic kidney disease (CKD), the importance of lifestyle modification for preventing the progression of kidney dysfunction and complications has become obvious. In addition, effective cooperation between general physicians (GPs) and nephrologists is essential to ensure a better care system for CKD treatment. In this cluster-randomized study, we studied the effect of behavior modification on the outcome of early- to moderate-stage CKD. Design Stratified open cluster-randomized trial. Setting A total of 489 GPs belonging to 49 local medical associations (clusters) in Japan. Participants A total of 2,379 patients (1,195 in group A (standard intervention) and 1,184 in group B (advanced intervention)) aged between 40 and 74 years, who had CKD and were under consultation with GPs. Intervention All patients were managed in accordance with the current CKD guidelines. The group B clusters received three additional interventions: patients received both educational intervention for lifestyle modification and a CKD status letter, attempting to prevent their withdrawal from treatment, and the group B GPs received data sheets to facilitate reducing the gap between target and practice. Main outcome measure The primary outcome measures were 1) the non-adherence rate of accepting continuous medical follow-up of the patients, 2) the collaboration rate between GPs and nephrologists, and 3) the progression of CKD. Results The rate of discontinuous clinical visits was significantly lower in group B (16.2% in group A vs. 11.5% in group B, p = 0.01). Significantly higher referral and co-treatment rates were observed in group B (p<0.01). The average eGFR deterioration rate tended to be lower in group B (group A: 2.6±5.8 ml/min/1.73 m2/year, group B: 2.4±5.1 ml/min/1.73 m2/year, p = 0.07). A significant difference in eGFR deterioration rate was observed in subjects with Stage 3 CKD (group A: 2.4±5.9 ml/min/1.73 m2/year, group B: 1.9±4.4 ml/min/1.73 m2/year, p = 0.03). Conclusion Our care system achieved behavior modification of CKD patients, namely, significantly lower discontinuous clinical visits, and behavior modification of both GPs and nephrologists, namely significantly higher referral and co-treatment rates, resulting in the retardation of CKD progression, especially in patients with proteinuric Stage 3 CKD. Trial registration The University Hospital Medical Information Network clinical trials registry UMIN000001159 PMID:26999730

A phase II study of HMB/Arg/Gln against oral mucositis induced by chemoradiotherapy for patients with head and neck cancer.

PubMed

Yokota, Tomoya; Hamauchi, Satoshi; Yoshida, Yukio; Yurikusa, Takashi; Suzuki, Miho; Yamashita, Aiko; Ogawa, Hirofumi; Onoe, Tsuyoshi; Mori, Keita; Onitsuka, Tetsuro

2018-04-07

This phase II trial assessed the clinical benefit of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine (HMB/Arg/Gln) for preventing chemoradiotherapy (CRT)-induced oral mucositis (OM) in patients with head and neck cancer (HNC). Patients with HNC receiving definitive or postoperative cisplatin-based CRT were enrolled. HMB/Arg/Gln was administered orally or per percutaneous endoscopic gastrostomy from the first day of CRT up to its completion. All patients received opioid-based pain control and oral care programs that we previously reported. The primary endpoint was the incidence of grade ≥ 3 OM (functional/symptomatic) according to the Common Terminology Criteria of Adverse Events version 3.0. Quality of life (EORTC QLQ-C30/PROMS) at baseline and upon radiotherapy at a dosage of 50 Gy were assessed. Thirty-five patients with HNC were enrolled. Sixteen of them (45.7%) developed grade ≥ 3 OM (i.e., functional/symptomatic). The incidence of grade ≤ 1 OM (functional/symptomatic) was 51.5% at 2 weeks and 82.9% at 4 weeks after radiotherapy completion. Clinical examination revealed that 10 patients (28.6%) developed grade ≥ 3 OM. The incidence of grade ≤ 1 OM (clinical exam) was 80.0% at 2 weeks and 100% at 4 weeks after radiotherapy completion. Adverse events related to HMB/Arg/Gln were an increase in blood urea nitrogen and diarrhea, but were easily managed. The addition of HMB/Arg/Gln to opioid-based pain control and oral care programs was feasible but still insufficient at reducing the incidence of CRT-induced severe OM. However, the benefit of HMB/Arg/Gln should not be neglected given the findings of clinical examinations and the rapid recovery from severe OM. UMIN000016453.

Effect of Behavior Modification on Outcome in Early- to Moderate-Stage Chronic Kidney Disease: A Cluster-Randomized Trial.

PubMed

Yamagata, Kunihiro; Makino, Hirofumi; Iseki, Kunitoshi; Ito, Sadayoshi; Kimura, Kenjiro; Kusano, Eiji; Shibata, Takanori; Tomita, Kimio; Narita, Ichiei; Nishino, Tomoya; Fujigaki, Yoshihide; Mitarai, Tetsuya; Watanabe, Tsuyoshi; Wada, Takashi; Nakamura, Teiji; Matsuo, Seiichi

2016-01-01

Owing to recent changes in our understanding of the underlying cause of chronic kidney disease (CKD), the importance of lifestyle modification for preventing the progression of kidney dysfunction and complications has become obvious. In addition, effective cooperation between general physicians (GPs) and nephrologists is essential to ensure a better care system for CKD treatment. In this cluster-randomized study, we studied the effect of behavior modification on the outcome of early- to moderate-stage CKD. Stratified open cluster-randomized trial. A total of 489 GPs belonging to 49 local medical associations (clusters) in Japan. A total of 2,379 patients (1,195 in group A (standard intervention) and 1,184 in group B (advanced intervention)) aged between 40 and 74 years, who had CKD and were under consultation with GPs. All patients were managed in accordance with the current CKD guidelines. The group B clusters received three additional interventions: patients received both educational intervention for lifestyle modification and a CKD status letter, attempting to prevent their withdrawal from treatment, and the group B GPs received data sheets to facilitate reducing the gap between target and practice. The primary outcome measures were 1) the non-adherence rate of accepting continuous medical follow-up of the patients, 2) the collaboration rate between GPs and nephrologists, and 3) the progression of CKD. The rate of discontinuous clinical visits was significantly lower in group B (16.2% in group A vs. 11.5% in group B, p = 0.01). Significantly higher referral and co-treatment rates were observed in group B (p<0.01). The average eGFR deterioration rate tended to be lower in group B (group A: 2.6±5.8 ml/min/1.73 m2/year, group B: 2.4±5.1 ml/min/1.73 m2/year, p = 0.07). A significant difference in eGFR deterioration rate was observed in subjects with Stage 3 CKD (group A: 2.4±5.9 ml/min/1.73 m2/year, group B: 1.9±4.4 ml/min/1.73 m2/year, p = 0.03). Our care system achieved behavior modification of CKD patients, namely, significantly lower discontinuous clinical visits, and behavior modification of both GPs and nephrologists, namely significantly higher referral and co-treatment rates, resulting in the retardation of CKD progression, especially in patients with proteinuric Stage 3 CKD. The University Hospital Medical Information Network clinical trials registry UMIN000001159.

Cognitive and Behavioral Skills Exercises Completed by Patients with Major Depression During Smartphone Cognitive Behavioral Therapy: Secondary Analysis of a Randomized Controlled Trial.

PubMed

Furukawa, Toshi A; Horikoshi, Masaru; Fujita, Hirokazu; Tsujino, Naohisa; Jinnin, Ran; Kako, Yuki; Ogawa, Sei; Sato, Hirotoshi; Kitagawa, Nobuki; Shinagawa, Yoshihiro; Ikeda, Yoshio; Imai, Hissei; Tajika, Aran; Ogawa, Yusuke; Akechi, Tatsuo; Yamada, Mitsuhiko; Shimodera, Shinji; Watanabe, Norio; Inagaki, Masatoshi; Hasegawa, Akio

2018-01-11

A strong and growing body of evidence has demonstrated the effectiveness of cognitive behavioral therapy (CBT), either face-to-face, in person, or as self-help via the Internet, for depression. However, CBT is a complex intervention consisting of several putatively effective components, and how each component may or may not contribute to the overall effectiveness of CBT is poorly understood. The aim of this study was to investigate how the users of smartphone CBT use and benefit from various components of the program. This is a secondary analysis from a 9-week, single-blind, randomized controlled trial that has demonstrated the effectiveness of adjunctive use of smartphone CBT (Kokoro-App) over antidepressant pharmacotherapy alone among patients with drug-resistant major depressive disorder (total n=164, standardized mean difference in depression severity at week 9=0.40, J Med Internet Res). Kokoro-App consists of three cognitive behavioral skills of self-monitoring, behavioral activation, and cognitive restructuring, with corresponding worksheets to fill in. All activities of the participants learning each session of the program and completing each worksheet were uploaded onto Kokoro-Web, which each patient could use for self-check. We examined what use characteristics differentiated the more successful users of the CBT app from the less successful ones, split at the median of change in depression severity. A total of 81 patients with major depression were allocated to the smartphone CBT. On average, they completed 7.0 (standard deviation [SD] 1.4) out of 8 sessions of the program; it took them 10.8 (SD 4.2) days to complete one session, during which they spent 62 min (SD 96) on the app. There were no statistically significant differences in the number of sessions completed, time spent for the program, or the number of completed self-monitoring worksheets between the beneficiaries and the nonbeneficiaries. However, the former completed more behavioral activation tasks, engaged in different types of activities, and also filled in more cognitive restructuring worksheets than the latter. Activities such as "test-drive a new car," "go to a coffee shop after lunch," or "call up an old friend" were found to be particularly rewarding. All cognitive restructuring strategies were found to significantly decrease the distress level, with "What would be your advice to a friend who has a similar problem?" found more helpful than some other strategies. The CBT program offered via smartphone and connected to the remote server is not only effective in alleviating depression but also opens a new avenue in gathering information of what and how each participant may utilize the program. The activities and strategies found useful in this analysis will provide valuable information in brush-ups of the program itself and of mobile health (mHealth) in general. Japanese Clinical Trials Registry UMIN CTR 000013693; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ ctr_view.cgi?recptno=R000015984 (Archived by WebCite at http://www.webcitation.org/6u6pxVwik). ©Toshi A Furukawa, Masaru Horikoshi, Hirokazu Fujita, Naohisa Tsujino, Ran Jinnin, Yuki Kako, Sei Ogawa, Hirotoshi Sato, Nobuki Kitagawa, Yoshihiro Shinagawa, Yoshio Ikeda, Hissei Imai, Aran Tajika, Yusuke Ogawa, Tatsuo Akechi, Mitsuhiko Yamada, Shinji Shimodera, Norio Watanabe, Masatoshi Inagaki, Akio Hasegawa. Originally published in JMIR Mental Health (http://mental.jmir.org), 11.01.2018.

Community-wide promotion of physical activity in middle-aged and older Japanese: a 3-year evaluation of a cluster randomized trial.

PubMed

Kamada, Masamitsu; Kitayuguchi, Jun; Abe, Takafumi; Taguri, Masataka; Inoue, Shigeru; Ishikawa, Yoshiki; Harada, Kazuhiro; Lee, I-Min; Bauman, Adrian; Miyachi, Motohiko

2015-06-23

Promotion of physical activity (PA) is a key strategy to prevent non-communicable diseases. However, evidence on the effectiveness of community-wide interventions (CWIs) for promoting PA is limited. To evaluate the effectiveness of a 3-year CWI for promoting PA in middle-aged and older adults compared with usual public health services. This study is an extension to an original 1-year investigation study. Cluster randomized controlled trial with community as unit of randomization and individual as unit of analysis. 12 communities in Unnan, Japan were randomly allocated to the intervention (9) or the control (3). Additionally intervention communities were randomly allocated to aerobic activity promotion (Group A), flexibility and muscle-strengthening activities promotion (Group FM), or aerobic, flexibility, and muscle-strengthening activities promotion (Group AFM), each consisting of three communities. Randomly-sampled 4414 residents aged 40 to 79 years responded to the baseline survey (74%), and were analyzed in 2013-2014. A 3-year CWI based on social marketing, to promote PA from 2009 to 2012. The primary outcome was a change in regular aerobic, flexibility, and/or muscle-strengthening activities, defined by (1) engaging in 150 mins/week or more of walking, (2) engaging in daily flexibility activity, or (3) engaging 2 or more days/week in muscle-strengthening activities, evaluated at the individual level. Secondary outcomes were changes in specific types of PA and musculoskeletal pain. Outcomes were measured at baseline and at 1 and 3 years (2009, 2010, and 2012). The CWI did not significantly increase the proportion of adults who reached recommended levels of aerobic, flexibility, and/or muscle-strengthening activities (adjusted change difference = 1.6% [95% CI: -3.5, 6.6]). In the subgroup analysis, compared to the controls, adults doing flexibility activity daily significantly increased in Group FM (6.3% [95% CI: 1.9, 10.7]). In Group A and AFM for PA outcomes and in all groups for pain outcomes, there was no significant change compared to controls. The CWI did not achieve significant increase in the proportion of adults who reached recommended PA levels. However, it might be effective in promoting flexibility activity in middle-aged and older Japanese. UMIN-CTR UMIN000002683 .

Dose escalation study of proton beam therapy with concurrent chemotherapy for stage III non-small cell lung cancer.

PubMed

Harada, Hideyuki; Fuji, Hiroshi; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Yamashita, Haruo; Asakura, Hirofumi; Nishimura, Tetsuo; Takahashi, Toshiaki; Murayama, Shigeyuki

2016-07-01

The purpose of this study is to determine the recommended dose (RD) of proton beam therapy (PBT) for inoperable stage III non-small cell lung cancer (NSCLC). We tested two prescribed doses of PBT: 66 Gy (relative biological effectiveness [RBE]) in 33 fractions and 74 Gy (RBE) in 37 fractions in arms 1 and 2, respectively. The planning target volume (PTV) included the primary tumor and metastatic lymph nodes with adequate margins. Concurrent chemotherapy included intravenous cisplatin (60 mg/m(2) , day 1) and oral S-1 (80, 100 or 120 mg based on body surface area, days 1-14), repeated as four cycles every 4 weeks. Dose-limiting toxicity (DLT) was defined as grade 3 or severe toxicities related to PBT during days 1-90. Each dose level was performed in three patients, and then escalated to the next level if no DLT occurred. When one patient developed a DLT, three additional patients were enrolled. Overall, nine patients (five men, four women; median age, 72 years) were enrolled, including six in arm 1 and three in arm 2. The median follow-up time was 43 months, and the median progression-free survival was 15 months. In arm 1, grade 3 infection occurred in one of six patients, but no other DLT was reported. Similarly, no DLT occurred in arm 2. However, one patient in arm 2 developed grade 3 esophageal fistula at 9 months after the initiation of PBT. Therefore, we determined that 66 Gy (RBE) is the RD from a clinical viewpoints. (Clinical trial registration no. UMIN000005585). © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Covered duodenal self-expandable metal stents prolong biliary stent patency in double stenting: The largest series of bilioduodenal obstruction.

PubMed

Hori, Yasuki; Naitoh, Itaru; Hayashi, Kazuki; Kondo, Hiromu; Yoshida, Michihiro; Shimizu, Shuya; Hirano, Atsuyuki; Okumura, Fumihiro; Ando, Tomoaki; Jinno, Naruomi; Takada, Hiroki; Togawa, Shozo; Joh, Takashi

2018-03-01

Endoscopic biliary and duodenal stenting (DS; double stenting) is widely accepted as a palliation therapy for malignant bilioduodenal obstruction. The aim of the current study was to investigate the patency and adverse events of duodenal and biliary stents in patients with DS. Patients who underwent DS from April 2004 to March 2017 were analyzed retrospectively with regard to clinical outcomes and predictive factors of recurrent biliary and duodenal obstruction (recurrent biliary obstruction [RBO] and recurrent duodenal obstruction [RDO]). A total of 109 consecutive patients was enrolled. Technical success of DS was achieved in 108 patients (99.1%). Symptoms due to biliary and duodenal obstruction were improved in 89 patients (81.7%). RBO occurred in 25 patients (22.9%) and RDO in 13 (11.9%). The median times to RBO and RDO from DS were 87 and 76 days, respectively. Placement of a duodenal uncovered self-expandable metal stent (U-SEMS) was significantly associated with RBO in the multivariable analysis (P = 0.007). Time to RBO was significantly longer in the duodenal covered self-expandable metal stent group than in the U-SEMS group (P = 0.003). No predictive factors of RDO were detected, and duodenal stent type was not associated with the time to RDO (P = 0.724). Double stenting was safe and effective for malignant bilioduodenal obstruction. Duodenal U-SEMS is a risk factor for RBO. The covered self-expandable metal stent is the preferred type of duodenal SEMS in patients with DS (Clinical trial registration number: UMIN000027606). © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Preventive effect of irsogladine or omeprazole on non-steroidal anti-inflammatory drug-induced esophagitis, peptic ulcers, and small intestinal lesions in humans, a prospective randomized controlled study.

PubMed

Kuramoto, Takanori; Umegaki, Eiji; Nouda, Sadaharu; Narabayashi, Ken; Kojima, Yuichi; Yoda, Yukiko; Ishida, Kumi; Kawakami, Ken; Abe, Yosuke; Takeuchi, Toshihisa; Inoue, Takuya; Murano, Mitsuyuki; Tokioka, Satoshi; Higuchi, Kazuhide

2013-05-14

Proton-pump inhibitors such as omeprazole are a standard treatment to prevent non-steroidal anti-inflammatory drug-induced upper gastrointestinal mucosal injuries. However, it is unclear which drugs may protect against all NSAID-induced digestive-tract injuries. Here, we compare the efficacy of the gastromucoprotective drug irsogladine with omeprazole in preventing NSAID-induced esophagitis, peptic ulcers, and small-intestinal mucosal injury in healthy subjects. Thirty-two healthy volunteers were assigned to an irsogladine group (Group I; n = 16) receiving diclofenac sodium 75 mg and irsogladine 4 mg daily for 14 days, or an omeprazole group (Group O; n = 16) receiving diclofenac sodium 75 mg and omeprazole 10 mg daily for 14 days. Esophagitis and peptic ulcers were evaluated by esophagogastroduodenoscopy and small-intestinal injuries by capsule endoscopy, fecal calprotectin, and fecal occult blood before and after treatment. There was no significant difference between Group I and Group O with respect to the change in lesion score in the esophagus, stomach, and duodenum before and after treatment.NSAID treatment significantly increased the number of small intestinal mucosal breaks per subject by capsule endoscopic evaluation, from a basal level of 0.1 ± 0.3 up to 1.9 ± 2.0 lesions in Group O (p = 0.0002). In contrast, there were no significant changes in the mean number of mucosal breaks before and after co-treatment in Group I (0.3 ± 0.8 to 0.5 ± 0.7, p = 0.62), and the between-group difference was significant (p = 0.0040). Fecal calprotectin concentration, when the concentration before treatment was defined as 1, was significantly increased both in Group O (from 1.0 ± 0.0 to 18.1 ± 37.1, p = 0.0002) and Group I (from 1.0 ± 0.0 to 6.0 ± 11.1, p = 0.0280); the degree of increase in Group O was significantly higher compared with that in Group I (p<0.05). In addition, fecal occult blood levels increased significantly in Group O (p = 0.0018), but there was no change in Group I (p = 1.0), and the between-group difference was significant (p = 0.0031). Irsogladine protected against NSAID-induced mucosal injuries throughout the gastrointestinal tract, from esophagus to small intestine, significantly better than omeprazole. This study was registered in the UMIN Clinical Trials Registry (Registry ID number; UMIN000008114).

The effect of tolvaptan on renal excretion of electrolytes and urea nitrogen in patients undergoing coronary artery bypass surgery.

PubMed

Kato, Tomoko S; Nakamura, Hiroshi; Murata, Mai; Kuroda, Kishio; Suzuki, Hitoshi; Yokoyama, Yasutaka; Shimada, Akie; Matsushita, Satoshi; Yamamoto, Taira; Amano, Atsushi

2016-09-13

Adequate fluid management is an important component of patient care following cardiac surgery. Our aim in this study was to determine the benefits of tolvaptan, an oral selective vasopressin-2 receptor antagonist that causes electrolyte-free water diuresis, in postoperative fluid management. We prospectively examined the effect of tolvaptan on renal excretion of electrolytes and urea nitrogen in cardiac surgery patients. Patients undergoing coronary artery bypass surgery were randomized to receive conventional loop diuretics (Group C, n = 30) or conventional loop diuretic therapy plus tolvaptan (Group T, n = 27). Fractional excretions of sodium (FENA), potassium (FEK) and urea nitrogen (FEUN) were measured in both groups during post-surgical hospitalization. Urine output was greater with tolvaptan (Group T) than without it (Group C), and some patients in Group C required intravenous as well as oral loop diuretics. Serum sodium concentrations decreased after surgery in Group C, but were unchanged in Group T (postoperative day [POD] 3, 139.8 ± 3.5 vs. 142.3 ± 2.6 mEq/L, p = 0.006). However, postoperative FENA values in Group C did not decrease, and the values were similar in both groups. Serum potassium levels remained lower and FEK values remained higher than the preoperative values, but only in Group C (all p < 0.05). BUN increased postoperatively in both groups, but it remained higher than its preoperative value only in Group C (all p < 0.01). Group T showed an initial increase in BUN, which peaked and then returned to its preoperative value within a week. The FEUN increased postoperatively in both groups, but the change was more pronounced in Group T (POD7, 52.7 ± 9.3 vs. 58.2 ± 6.5 %, p = 0.025). Renal excretion of sodium and potassium reflects the changes in serum concentration in patients treated with tolvaptan. Patients treated only with loop diuretics showed a continuous excretion of sodium and potassium that led to electrolyte imbalance, whereas the combination of loop diuretics and tolvaptan increased renal urea nitrogen elimination. Tolvaptan therefore appears to be an effective diuretic that minimally affects serum electrolytes while adequately promoting the elimination of urea nitrogen from the kidneys in patients undergoing coronary artery bypass surgery. The present study is registered with the UMIN Clinical Trials Registry (ID: UMIN000011039 ).

Independent exercise for glottal incompetence to improve vocal problems and prevent aspiration pneumonia in the elderly: a randomized controlled trial.

PubMed

Fujimaki, Yoko; Tsunoda, Koichi; Kobayashi, Rika; Tonghyo, Chong; Tanaka, Fujinobu; Kuroda, Hiroyuki; Numata, Tsutomu; Ishii, Toyota; Kuroda, Reiko; Masuda, Sawako; Hashimoto, Sho; Misawa, Hayato; Shindo, Naoko; Mori, Takahiro; Mori, Hiroko; Uchiyama, Naoki; Kamei, Yuichirou; Tanaka, Masashi; Hamaya, Hironobu; Funatsuki, Shingo; Usui, Satoko; Ito, Ikuno; Hamada, Kohei; Shindo, Akihito; Tokumaru, Yutaka; Morita, Yoko; Ueha, Rumi; Nito, Takaharu; Kikuta, Shu; Sekimoto, Sotaro; Kondo, Kenji; Sakamoto, Takashi; Itoh, Kenji; Yamasoba, Tatsuya; Matsumoto, Sumio

2017-08-01

To evaluate the effect of a self-controlled vocal exercise in elderly people with glottal closure insufficiency. Parallel-arm, individual randomized controlled trial. Patients who visited one of 10 medical centers under the National Hospital Organization group in Japan for the first time, aged 60 years or older, complaining of aspiration or hoarseness, and endoscopically confirmed to have glottal closure insufficiency owing to vocal cord atrophy, were enrolled in this study. They were randomly assigned to an intervention or a control group. The patients of the intervention group were given guidance and a DVD about a self-controlled vocal exercise. The maximum phonation time which is a measure of glottal closure was evaluated, and the number of patients who developed pneumonia during the six months was compared between the two groups. Of the 543 patients enrolled in this trial, 259 were allocated into the intervention group and 284 into the control; 60 of the intervention group and 75 of the control were not able to continue the trial. A total of 199 patients (age 73.9 ±7.25 years) in the intervention group and 209 (73.3 ±6.68 years) in the control completed the six-month trial. Intervention of the self-controlled vocal exercise extended the maximum phonation time significantly ( p < 0.001). There were two hospitalizations for pneumonia in the intervention group and 18 in the control group, representing a significant difference ( p < 0.001). The self-controlled vocal exercise allowed patients to achieve vocal cord adduction and improve glottal closure insufficiency, which reduced the rate of hospitalization for pneumonia significantly. gov Identifier-UMIN000015567.

High plasma levels of soluble programmed cell death ligand 1 are prognostic for reduced survival in advanced lung cancer.

PubMed

Okuma, Yusuke; Hosomi, Yukio; Nakahara, Yoshiro; Watanabe, Kageaki; Sagawa, Yukiko; Homma, Sadamu

2017-02-01

Programmed cell death-ligand 1 (PD-L1) expressed in tumor tissues is a key molecule for immune suppression, given its role in immune checkpoints. The significance and implication of soluble PD-L1 (sPD-L1) in the blood of lung cancer patients remain unknown. Blood samples were prospectively collected from patients with advanced lung cancer, and the plasma sPD-L1 concentrations were measured by enzyme-linked immunosorbent assay. The correlations of the plasma sPD-L1 levels with clinico-pathological status, laboratory data, and survival of the patients were analyzed. Ninety-six patients with advanced lung cancer were analyzed, including 73 with adenocarcinoma, 12 with squamous cell carcinoma, and seven with small-cell lung cancer. Sixty-five were naïve to chemotherapy, and 20 had received two or more lines of chemotherapy. The mean plasma sPD-L1 concentration of all the patients was 6.95±2.90ng/ml (range 2.30-20.0ng/ml), and this value is significantly increased compared with that previously reported for normal subjects. No correlation of the plasma sPD-L1 level with histological subtypes, adenocarcinoma genetic status, smoking history, clinical stage or laboratory data was found. However, overall survival was significantly reduced in patients with high (≥7.32ng/ml) compared with low (<7.32ng/ml) plasma sPD-L1 levels (13.0 vs. 20.4 months, p=0.037). Multivariate analysis revealed that high sPD-L1 levels were significantly related to poor prognosis (hazard ratio 1.99, p=0.041). High plasma sPD-L1 levels were associated with poor prognosis in patients with advanced lung cancer, possibly associated with suppression of anti-tumor immunity. Clinical trial register and their clinical registration number: UMIN%000014760. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Influence of preoperative oral rehydration on arterial plasma rocuronium concentrations and neuromuscular blocking effects: A randomised controlled trial.

PubMed

Ishigaki, Sayaka; Ogura, Takahiro; Kanaya, Ayana; Miyake, Yu; Masui, Kenichi; Kazama, Tomiei

2017-01-01

The influence of preoperative rehydration on the action of rocuronium has not yet been investigated. The objective is to evaluate the hypothesis that preoperative rehydration lowers arterial rocuronium plasma concentrations and changes its associated neuromuscular blocking effects during induction of anaesthesia. Randomised, single-blinded study. A secondary hospital from October 2013 to July 2014. In total, 46 men undergoing elective surgery were eligible to participate and were randomly allocated into two groups. Exclusion criteria were severe hepatic, renal or cardiovascular disorder; neuromuscular disease; history of allergy to rocuronium; BMI more than 30 kg m; receiving medication known to influence neuromuscular function. Participants received 1500 ml of oral rehydration solution (rehydration group) or none (control group) until 2 hours before anaesthesia. Arterial blood samples were obtained 60, 90 and 120 s and 30 min after rocuronium (0.6 mg kg) administration during total intravenous anaesthesia. Responses to 0.1-Hz twitch stimuli were measured at the adductor pollicis muscle using acceleromyography. Arterial plasma rocuronium concentrations. Arterial plasma rocuronium concentrations at 60, 90 and 120 s in the rehydration and control groups were 9.9 and 13.7, 6.8 and 9.5 and 6.2 and 8.1 μg ml, respectively (P = 0.02, 0.003 and 0.02, respectively); the onset times in the rehydration and control groups were 92.0 and 69.5 s (P = 0.01), and the times to twitch re-appearance were 25.3 and 30.4 min (P = 0.004), respectively. Preoperative rehydration significantly reduces arterial plasma rocuronium concentrations in the first 2 minutes after administration, prolonging the onset time and shortening the duration of effect. A higher dose or earlier administration should be considered for patients who receive preoperative rehydration. Umin identifier: UMIN000011981.

Resistance Training Augments Cerebral Blood Flow Pulsatility: Cross-Sectional Study.

PubMed

Nakamura, Nobuhiro; Muraoka, Isao

2018-06-11

Increased central arterial stiffness and/or decreased compliance reduces buffer function and increases cerebral blood flow (CBF) pulsatility, which leads to increased cerebral microvascular damage, resulting in the augmentation of the risk of cerebrovascular diseases. Resistance-trained men showed higher central arterial stiffness and lower arterial compliance than age-matched, sedentary men. This study examined the effect of increased central arterial stiffness and/or decreased arterial compliance on CBF pulsatility. The study participants included 31 young healthy men (15 resistance-trained men, aged 21 ± 1 years; and 16 controls, aged 23 ± 1 years). β-Stiffness index and arterial compliance were measured in the right carotid artery as index of central arterial stiffness and compliance, respectively. The pulsatility index (PI) was measured in the middle cerebral artery as index of CBF pulsatility. β-Stiffness index and PI were significantly higher in the resistance-trained group than in the control group (β-stiffness index: 5.3 ± 0.3 vs. 3.5 ± 0.3 a.u., P < 0.05, PI: 0.80 ± 0.02 vs. 0.70 ± 0.02, P < 0.05). The resistance-trained group showed significantly lower arterial compliance than the control group (0.16 ± 0.01 vs. 0.23 ± 0.01 mm2/mm Hg, P < 0.05). Positive and negative correlations were observed between β-stiffness index and PI (r = 0.39, P < 0.05), and between arterial compliance and PI (r = -0.59, P < 0.05), respectively. The resistance-trained group showed higher central arterial stiffness and PI and lower arterial compliance. Central arterial stiffness and arterial compliance were associated with PI. Increased arterial stiffness and decreased arterial compliance with resistance training impair buffer function, resulting in increased CBF pulsatility. Trial Number UMIN000023816 URL: http://www.umin.ac.jp/icdr/index.html Official scientific title of the study: effect of increase arterial stiffness by resistance training on cerebral hemodynamic.

Long-term retention of cardiopulmonary resuscitation skills after shortened chest compression-only training and conventional training: a randomized controlled trial.

PubMed

Nishiyama, Chika; Iwami, Taku; Kitamura, Tetsuhisa; Ando, Masahiko; Sakamoto, Tetsuya; Marukawa, Seishiro; Kawamura, Takashi

2014-01-01

It is unclear how much the length of a cardiopulmonary resuscitation (CPR) training program can be reduced without ruining its effectiveness. The authors aimed to compare CPR skills 6 months and 1 year after training between shortened chest compression-only CPR training and conventional CPR training. Participants were randomly assigned to either the compression-only CPR group, which underwent a 45-minute training program consisting of chest compressions and automated external defibrillator (AED) use with personal training manikins, or the conventional CPR group, which underwent a 180-minute training program with chest compressions, rescue breathing, and AED use. Participants' resuscitation skills were evaluated 6 months and 1 year after the training. The primary outcome measure was the proportion of appropriate chest compressions 1 year after the training. A total of 146 persons were enrolled, and 63 (87.5%) in the compression-only CPR group and 56 (75.7%) in the conventional CPR group completed the 1-year evaluation. The compression-only CPR group was superior to the conventional CPR group regarding the proportion of appropriate chest compression (mean ± SD = 59.8% ± 40.0% vs. 46.3% ± 28.6%; p = 0.036) and the number of appropriate chest compressions (mean ± SD = 119.5 ± 80.0 vs. 77.2 ± 47.8; p = 0.001). Time without chest compression in the compression-only CPR group was significantly shorter than that in the conventional CPR group (mean ± SD = 11.8 ± 21.1 seconds vs. 52.9 ± 14.9 seconds; p < 0.001). The shortened compression-only CPR training program appears to help the general public retain CPR skills better than the conventional CPR training program. UMIN-CTR UMIN000001675. © 2013 by the Society for Academic Emergency Medicine.

Effects of exercise on brain activity during walking in older adults: a randomized controlled trial.

PubMed

Shimada, Hiroyuki; Ishii, Kenji; Makizako, Hyuma; Ishiwata, Kiichi; Oda, Keiichi; Suzukawa, Megumi

2017-05-30

Physical activity may preserve neuronal plasticity, increase synapse formation, and cause the release of hormonal factors that promote neurogenesis and neuronal function. Previous studies have reported enhanced neurocognitive function following exercise training. However, the specific cortical regions activated during exercise training remain largely undefined. In this study, we quantitatively and objectively evaluated the effects of exercise on brain activity during walking in healthy older adults. A total of 24 elderly women (75-83 years old) were randomly allocated to either an intervention group or a control group. Those in the intervention group attended 3 months of biweekly 90-min sessions focused on aerobic exercise, strength training, and physical therapy. We monitored changes in regional cerebral glucose metabolism during walking in both groups using positron emission tomography (PET) and [ 18 F]fluorodeoxyglucose (FDG). All subjects completed the 3-month experiment and the adherence to the exercise program was 100%. Compared with the control group, the intervention group showed a significantly greater step length in the right foot after 3 months of physical activity. The FDG-PET assessment revealed a significant post-intervention increase in regional glucose metabolism in the left posterior entorhinal cortex, left superior temporal gyrus, and right superior temporopolar area in the intervention group. Interestingly, the control group showed a relative increase in regional glucose metabolism in the left premotor and supplemental motor areas, left and right somatosensory association cortex, and right primary visual cortex after the 3-month period. We found no significant differences in FDG uptake between the intervention and control groups before vs. after the intervention. Exercise training increased activity in specific brain regions, such as the precuneus and entorhinal cortices, which play an important role in episodic and spatial memory. Further investigation is required to confirm whether alterations in glucose metabolism within these regions during walking directly promote physical and cognitive performance. UMIN-CTR ( UMIN000021829 ). Retrospectively registered 10 April 2016.

Phase II study of tailored S-1 monotherapy with a 1-week interval after a 2-week dosing period in elderly patients with advanced non-small cell lung cancer.

PubMed

Goto, Hisatsugu; Okano, Yoshio; Machida, Hisanori; Hatakeyama, Nobuo; Ogushi, Fumitaka; Haku, Takashi; Kanematsu, Takanori; Urata, Tomoyuki; Kakiuchi, Soji; Hanibuchi, Masaki; Sone, Saburo; Nishioka, Yasuhiko

2018-01-01

S-1 is an oral fluoropyrimidine that is active in the treatment of non-small cell lung cancer (NSCLC); however, an optimal treatment schedule and appropriate dose adjustments of S-1 in elderly patients have not yet been established. We conducted a phase II trial to evaluate the efficacy and safety of a 2-week S-1 monotherapy treatment followed by a 1-week interval as a first-line treatment of elderly NSCLC patients, by adjusting the dose based on the individual creatinine clearance (Ccr) and body surface area (BSA). The primary endpoint was the disease control rate. Forty patients were enrolled. The disease control and response rates were 89.5% (95% confidence interval [CI] = 79.8-99.2) and 7.9% (95% CI = 0.0-16.4), respectively. The median progression-free survival and overall survival times were 4.4 months (95% CI = 4.2-8.5) and 17.0 months (95% CI = 11.2-18.7), respectively. Neutropenia, anorexia, hyponatremia, hypokalemia, and pneumonia of grade ≥ 3 occurred in 5.0%, 7.5%, 5.0%, 2.5%, and 2.5% of patients, respectively. Among the patient-reported outcomes, most of the individual factors in the patients' quality of life, including upper intestine-related symptoms improved with the treatment, except for dyspnea, which slightly albeit continuously worsened throughout the study. In elderly patients with previously untreated advanced NSCLC, a 2-week S-1 monotherapy treatment, tailored to both the Ccr and BSA, with a 1-week interval was well tolerated and demonstrated promising efficacy. This study was registered at the University Hospital Medical Information Network (UMIN) Center (ID: UMIN000002035), Japan. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Efficacy of Statin Therapy in Inducing Coronary Plaque Regression in Patients with Low Baseline Cholesterol Levels

PubMed Central

Nozue, Tsuyoshi; Yamamoto, Shingo; Tohyama, Shinichi; Fukui, Kazuki; Umezawa, Shigeo; Onishi, Yuko; Kunishima, Tomoyuki; Sato, Akira; Miyake, Shogo; Morino, Yoshihiro; Yamauchi, Takao; Muramatsu, Toshiya; Hibi, Kiyoshi; Terashima, Mitsuyasu; Suzuki, Hiroshi; Michishita, Ichiro

2016-01-01

Aim: The efficacy of statin therapy in inducing coronary plaque regression may depend on baseline cholesterol levels. We aimed to determine the efficacy of statin therapy in inducing coronary plaque regression in statin-naïve patients with low cholesterol levels using serial intravascular ultrasound (IVUS) data from the treatment with statin on atheroma regression evaluated by virtual histology IVUS (TRUTH) study. Methods: The TRUTH study is a prospective, multicenter trial, comparing the efficacies of pitavastatin and pravastatin in coronary plaque regression in 164 patients. All patients were statin-naïve and received statin therapy only after study enrollment. The primary endpoint was the observation of coronary plaque progression, despite statin therapy. Results: Serial IVUS data, at baseline and after an 8-month follow-up, were available for 119 patients. The patients were divided into three groups based on non-high-density lipoprotein cholesterol (HDL-C) levels—low: ≤ 140 mg/dl, n = 38; moderate: 141–169 mg/dl, n = 42; and high: ≥ 170 mg/dl, n = 39. Coronary plaque progression was noted in the low cholesterol group, whereas plaque regression was noted in the moderate and high cholesterol groups [%Δplaque volume: 2.3 ± 7.4 vs. − 2.7 ± 10.7 vs. − 3.2 ± 7.5, p = 0.004 (analysis of variance)]. After adjusting for all variables, a low non-HDLC level (≤ 140 mg/dl) was identified as an independent predictor of coronary plaque progression [odds ratio, 3.7; 95% confidence interval, 1.5–9.1, p = 0.004]. Conclusion: Serial IVUS data analysis indicated that statin therapy was less effective in inducing coronary plaque regression in patients with low cholesterol levels but more effective in those with high cholesterol levels at baseline. University Hospital Medical Information Network (UMIN) (UMIN ID: C000000311). PMID:27040362

Evaluation of an e-learning system for diagnosis of gastric lesions using magnifying narrow-band imaging: a multicenter randomized controlled study.

PubMed

Nakanishi, Hiroyoshi; Doyama, Hisashi; Ishikawa, Hideki; Uedo, Noriya; Gotoda, Takuji; Kato, Mototsugu; Nagao, Shigeaki; Nagami, Yasuaki; Aoyagi, Hiroyuki; Imagawa, Atsushi; Kodaira, Junichi; Mitsui, Shinya; Kobayashi, Nozomu; Muto, Manabu; Takatori, Hajime; Abe, Takashi; Tsujii, Masahiko; Watari, Jiro; Ishiyama, Shuhei; Oda, Ichiro; Ono, Hiroyuki; Kaneko, Kazuhiro; Yokoi, Chizu; Ueo, Tetsuya; Uchita, Kunihisa; Matsumoto, Kenshi; Kanesaka, Takashi; Morita, Yoshinori; Katsuki, Shinichi; Nishikawa, Jun; Inamura, Katsuhisa; Kinjo, Tetsu; Yamamoto, Katsumi; Yoshimura, Daisuke; Araki, Hiroshi; Kashida, Hiroshi; Hosokawa, Ayumu; Mori, Hirohito; Yamashita, Haruhiro; Motohashi, Osamu; Kobayashi, Kazuhiko; Hirayama, Michiaki; Kobayashi, Hiroyuki; Endo, Masaki; Yamano, Hiroo; Murakami, Kazunari; Koike, Tomoyuki; Hirasawa, Kingo; Miyaoka, Youichi; Hamamoto, Hidetaka; Hikichi, Takuto; Hanabata, Norihiro; Shimoda, Ryo; Hori, Shinichiro; Sato, Tadashi; Kodashima, Shinya; Okada, Hiroyuki; Mannami, Tomohiko; Yamamoto, Shojiro; Niwa, Yasumasa; Yashima, Kazuo; Tanabe, Satoshi; Satoh, Hiro; Sasaki, Fumisato; Yamazato, Tetsuro; Ikeda, Yoshiou; Nishisaki, Hogara; Nakagawa, Masahiro; Matsuda, Akio; Tamura, Fumio; Nishiyama, Hitoshi; Arita, Keiko; Kawasaki, Keisuke; Hoppo, Kazushige; Oka, Masashi; Ishihara, Shinichi; Mukasa, Michita; Minamino, Hiroaki; Yao, Kenshi

2017-10-01

Background and study aim  Magnifying narrow-band imaging (M-NBI) is useful for the accurate diagnosis of early gastric cancer (EGC). However, acquiring skill at M-NBI diagnosis takes substantial effort. An Internet-based e-learning system to teach endoscopic diagnosis of EGC using M-NBI has been developed. This study evaluated its effectiveness. Participants and methods  This study was designed as a multicenter randomized controlled trial. We recruited endoscopists as participants from all over Japan. After completing Test 1, which consisted of M-NBI images of 40 gastric lesions, participants were randomly assigned to the e-learning or non-e-learning groups. Only the e-learning group was allowed to access the e-learning system. After the e-learning period, both groups received Test 2. The analysis set was participants who scored < 80 % accuracy on Test 1. The primary end point was the difference in accuracy between Test 1 and Test 2 for the two groups. Results  A total of 395 participants from 77 institutions completed Test 1 (198 in the e-learning group and 197 in the non-e-learning group). After the e-learning period, all 395 completed Test 2. The analysis sets were e-learning group: n = 184; and non-e-learning group: n = 184. The mean Test 1 score was 59.9 % for the e-learning group and 61.7 % for the non-e-learning group. The change in accuracy in Test 2 was significantly higher in the e-learning group than in the non-e-learning group (7.4 points vs. 0.14 points, respectively; P  < 0.001). Conclusion This study clearly demonstrated the efficacy of the e-learning system in improving practitioners' capabilities to diagnose EGC using M-NBI.Trial registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN000008569). © Georg Thieme Verlag KG Stuttgart · New York.

Randomized controlled trial of toremifene 120 mg compared with exemestane 25 mg after prior treatment with a non-steroidal aromatase inhibitor in postmenopausal women with hormone receptor-positive metastatic breast cancer.

PubMed

Yamamoto, Yutaka; Ishikawa, Takashi; Hozumi, Yasuo; Ikeda, Masahiko; Iwata, Hiroji; Yamashita, Hiroko; Toyama, Tatsuya; Chishima, Takashi; Saji, Shigehira; Yamamoto-Ibusuki, Mutsuko; Iwase, Hirotaka

2013-05-16

After the failure of a non-steroidal aromatase inhibitor (nsAI) for postmenopausal patients with metastatic breast cancer (mBC), it is unclear which of various kinds of endocrine therapy is the most appropriate. A randomized controlled trial was performed to compare the efficacy and safety of daily toremifene 120 mg (TOR120), a selective estrogen receptor modulator, and exemestane 25 mg (EXE), a steroidal aromatase inhibitor. The primary end point was the clinical benefit rate (CBR). The secondary end points were objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicity. Initially, a total of 91 women was registered in the study and randomly assigned to either TOR120 (n = 46) or EXE (n = 45) from October 2008 to November 2011. Three of the 46 patients in the TOR120 arm were not received treatment, 2 patients having withdrawn from the trial by their preference and one having been dropped due to administration of another SERM. When analyzed after a median observation period of 16.9 months, the intention-to-treat analysis showed that there were no statistical difference between TOR120 (N = 46) and EXE (n = 45) in terms of CBR (41.3% vs. 26.7%; P = 0.14), ORR (10.8% vs. 2.2%; P = 0.083), and OS (Hazard ratio, 0.60; P = 0.22). The PFS of TOR120 was longer than that of EXE, the difference being statistically significant (Hazard ratio, 0.61, P = 0.045). The results in treatment-received cohort (N = 88) were similar to those in ITT cohort. Both treatments were well-tolerated with no severe adverse events, although the treatment of 3 of 43 women administered TOR120 was stopped after a few days because of nausea, general fatigue, hot flush and night sweating. TOR120, as a subsequent endocrine therapy for mBC patients who failed non-steroidal AI treatment, could potentially be more beneficial than EXE. UMIN000001841.

Sensitivity and specificity of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anti-cancer Randomized Trial (J-START): a randomised controlled trial.

PubMed

Ohuchi, Noriaki; Suzuki, Akihiko; Sobue, Tomotaka; Kawai, Masaaki; Yamamoto, Seiichiro; Zheng, Ying-Fang; Shiono, Yoko Narikawa; Saito, Hiroshi; Kuriyama, Shinichi; Tohno, Eriko; Endo, Tokiko; Fukao, Akira; Tsuji, Ichiro; Yamaguchi, Takuhiro; Ohashi, Yasuo; Fukuda, Mamoru; Ishida, Takanori

2016-01-23

Mammography is the only proven method for breast cancer screening that reduces mortality, although it is inaccurate in young women or women with dense breasts. We investigated the efficacy of adjunctive ultrasonography. Between July, 2007, and March, 2011, we enrolled asymptomatic women aged 40-49 years at 42 study sites in 23 prefectures into the Japan Strategic Anti-cancer Randomized Trial (J-START). Eligible women had no history of any cancer in the previous 5 years and were expected to live for more than 5 years. Randomisation was done centrally by the Japan Clinical Research Support Unit. Participants were randomly assigned in 1:1 ratio to undergo mammography and ultrasonography (intervention group) or mammography alone (control group) twice in 2 years. The primary outcome was sensitivity, specificity, cancer detection rate, and stage distribution at the first round of screening. Analysis was by intention to treat. This study is registered, number UMIN000000757. Of 72,998 women enrolled, 36,859 were assigned to the intervention group and 36,139 to the control group. Sensitivity was significantly higher in the intervention group than in the control group (91·1%, 95% CI 87·2-95·0 vs 77·0%, 70·3-83·7; p=0·0004), whereas specificity was significantly lower (87·7%, 87·3-88·0 vs 91·4%, 91·1-91·7; p<0·0001). More cancers were detected in the intervention group than in the control group (184 [0·50%] vs 117 [0·32%], p=0·0003) and were more frequently stage 0 and I (144 [71·3%] vs 79 [52·0%], p=0·0194). 18 (0·05%) interval cancers were detected in the intervention group compared with 35 (0·10%) in the control group (p=0·034). Adjunctive ultrasonography increases sensitivity and detection rate of early cancers. Ministry of Health, Labour and Welfare of Japan. Copyright © 2016 Elsevier Ltd. All rights reserved.

Study protocol for a multi-institutional, randomised, double-blinded, placebo-controlled phase III trial investigating additive efficacy of duloxetine for neuropathic cancer pain refractory to opioids and gabapentinoids: the DIRECT study.

PubMed

Matsuoka, Hiromichi; Ishiki, Hiroto; Iwase, Satoru; Koyama, Atsuko; Kawaguchi, Takashi; Kizawa, Yoshiyuki; Morita, Tatsuya; Matsuda, Yoshinobu; Miyaji, Tempei; Ariyoshi, Keisuke; Yamaguchi, Takuhiro

2017-08-28

Management of patients with cancer suffering from neuropathic pain refractory to opioids and gabapentinoids remains an important challenge. Duloxetine is one of the choices after first-line treatment fails. The efficacy of duloxetine has been reported in patients with non-cancer disease and in chemotherapy-induced peripheral neuropathy, but no randomised clinical trials have examined its effects on neuropathic cancer pain refractory to first-line treatment. The objective of this study is to assess the analgesic efficacy of duloxetine in patients suffering from neuropathic cancer pain refractory to opioids and gabapentinoids. A multi-institutional, prospective, randomised, double-blind, placebo-controlled, two-parallel trial is planned. The inclusion criteria are adult patients with cancer suffering from neuropathic cancer pain refractory to opioids and gabapentinoids, patients with a Numerical Rating Scale (NRS) pain score of 4 or higher and patients with a total Hospital Anxiety and Depression Scale score of less than 20. Patients with chemotherapy-induced peripheral neuropathy are excluded. The study will take place at 14 sites across Japan. Participants will be randomised (1:1 allocation ratio) to a duloxetine intervention group or a placebo control group. Evaluations will be made at baseline (T0 randomisation), day 0 (T1), day 3 (T2) and day 10 (T3). The primary endpoint is defined as the difference in NRS score for pain intensity (average over the previous 24 hours) at T3 between the duloxetine and placebo groups. A sample size of 70 patients will be examined between July 2015 and March 2018. Ethics approval was obtained at all participating sites.The results of this study will be submitted for publication in international peer-reviewed journals and the key findings presented at international scientific conferences. UMIN000017647; Pre-results. 2.2, 26 April 2017. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Beneficial effects of reading aloud and solving simple arithmetic calculations (learning therapy) on a wide range of cognitive functions in the healthy elderly: study protocol for a randomized controlled trial.

PubMed

Nouchi, Rui; Taki, Yasuyuki; Takeuchi, Hikaru; Hashizume, Hiroshi; Nozawa, Takayuki; Sekiguchi, Atsushi; Nouchi, Haruka; Kawashima, Ryuta

2012-04-06

Almost all cognitive functions decline with age. Results of previous studies have shown that cognitive training related to everyday life (reading aloud and solving simple arithmetic calculations), namely learning therapy, can improve two cognitive function (executive functions and processing speed) in elderly people. However, it remains unclear whether learning therapy engenders improvement of various cognitive functions or not. We investigate the impact of learning therapy on various cognitive functions (executive functions, episodic memory, short-term memory, working memory, attention, reading ability, and processing speed) in healthy older adults. We use a single-blinded intervention with two parallel groups (a learning therapy group and a waiting list control group). Testers are blind to the study hypothesis and the group membership of participants. Through an advertisement in local newspaper, 64 healthy older adults are recruited. They will be assigned randomly to a learning therapy group or a waiting list control group. In the learning therapy group, participants are required to perform two cognitive tasks for 6 months: reading Japanese aloud and solving simple calculations. The waiting list group does not participate in the intervention. The primary outcome measure is the Stroop test score: a measure of executive function. Secondary outcome measures are assessments including the following: verbal fluency task, logical memory, first and second names, digit span forward, digit span backward, Japanese reading test, digit cancellation task, digit symbol coding, and symbol search. We assess these outcome measures before and after the intervention. This report is the first study which investigates the beneficial effects of learning therapy on a wide range of cognitive functions of elderly people. Our study provides sufficient evidence of learning therapy effectiveness. Most cognitive functions, which are correlated strongly with daily life activities, decrease with age. These study results can elucidate effects of cognitive training on elderly people. This trial was registered in The University Hospital Medical Information Network Clinical Trials Registry (No. UMIN000006998).

Bursectomy versus omentectomy alone for resectable gastric cancer (JCOG1001): a phase 3, open-label, randomised controlled trial.

PubMed

Kurokawa, Yukinori; Doki, Yuichiro; Mizusawa, Junki; Terashima, Masanori; Katai, Hitoshi; Yoshikawa, Takaki; Kimura, Yutaka; Takiguchi, Shuji; Nishida, Yasunori; Fukushima, Norimasa; Iwasaki, Yoshiaki; Kaji, Masahide; Hirao, Motohiro; Katayama, Hiroshi; Sasako, Mitsuru

2018-04-27

The role of bursectomy, in which the peritoneal lining covering the pancreas and the anterior plane of the transverse mesocolon are dissected, has long been controversial for preventing peritoneal metastasis. We investigated the survival benefit of bursectomy in patients with resectable gastric cancer. This phase 3, open-label, randomised controlled trial was done at 57 hospitals in Japan. Patients aged 20-80 years who had cT3(SS)-cT4a(SE) histologically proven gastric adenocarcinoma with an Eastern Cooperative Oncology Group performance status of 0 or 1 and body-mass index less than 30 kg/m 2 and who did not have distant metastasis or bulky lymph nodes were randomly assigned (1:1) during surgery to receive omentectomy alone (non-bursectomy) or bursectomy. Randomisation was done by telephone or website to the Japan Clinical Oncology Group Data Center and used a minimisation method with a random component to adjust for institution, cT status (T3 vs T4a), and type of gastrectomy (distal vs total). Both groups had total or distal gastrectomy with D2 lymphadenectomy. The primary endpoint was overall survival, analysed in the intention-to-treat population. The study is registered with UMIN-CTR, number UMIN000003688. Between June 1, 2010, and March 30, 2015, 1503 patients were enrolled based on preoperative inclusion and exclusion criteria. Intraoperative inclusion and exclusion criteria were met in 1204 patients, of which 602 were allocated to the non-bursectomy group and 602 were allocated to the bursectomy group. At the planned second interim analysis on Sept 17, 2016, the JCOG Data and Safety Monitoring Committee independently reviewed the results and recommended their early publication on the basis of futility because overall survival was lower in the bursectomy group than the non-bursectomy group, and because the predictive probability of overall survival being significantly higher in bursectomy than non-bursectomy patients at the final analysis was only 12·7%. 5-year overall survival was 76·7% (95% CI 72·0-80·6) in the non-bursectomy group and 76·9% (72·6-80·7) in the bursectomy group (hazard ratio 1·05, 95% CI 0·81-1·37, one-sided p=0·65). 64 (11%) of 601 in the non-bursectomy group and 77 (13%) of 600 patients in the bursectomy group had grade 3-4 operative morbidity. Pancreatic fistula was significantly more common in the bursectomy group than in the non-bursectomy group (29 [5%] vs 15 [2%]; p=0·032). Six deaths occurred either in hospital or within 1 month of surgery: five in the non-bursectomy group and one in the bursectomy group. Bursectomy did not provide a survival advantage over non-bursectomy. D2 dissection with omentectomy alone should be done as a standard surgery for resectable cT3-T4a gastric cancer. Japan Agency for Medical Research and Development, the Ministry of Health, Labour and Welfare of Japan, and the National Cancer Centre Research and Development Fund. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of endoscopic transpapillary biliary drainage with/without endoscopic sphincterotomy on post-endoscopic retrograde cholangiopancreatography pancreatitis in patients with biliary stricture (E-BEST): a protocol for a multicentre randomised controlled trial

PubMed Central

Kato, Shin; Kuwatani, Masaki; Sugiura, Ryo; Sano, Itsuki; Kawakubo, Kazumichi; Ono, Kota; Sakamoto, Naoya

2017-01-01

Introduction The effect of endoscopic sphincterotomy prior to endoscopic biliary stenting to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis remains to be fully elucidated. The aim of this study is to prospectively evaluate the non-inferiority of non-endoscopic sphincterotomy prior to stenting for naïve major duodenal papilla compared with endoscopic sphincterotomy prior to stenting in patients with biliary stricture. Methods and analysis We designed a multicentre randomised controlled trial, for which we will recruit 370 patients with biliary stricture requiring endoscopic biliary stenting from 26 high-volume institutions in Japan. Patients will be randomly allocated to the endoscopic sphincterotomy group or the non-endoscopic sphincterotomy group. The main outcome measure is the incidence of pancreatitis within 2 days of initial transpapillary biliary drainage. Data will be analysed on completion of the study. We will calculate the 95% confidence intervals (CIs) of the incidence of pancreatitis in each group and analyse weather the difference in both groups with 95% CIs is within the non-inferiority margin (6%) using the Wald method. Ethics and dissemination This study has been approved by the institutional review board of Hokkaido University Hospital (IRB: 016–0181). Results will be submitted for presentation at an international medical conference and published in a peer-reviewed journal. Trial registration number The University Hospital Medical Information Network ID: UMIN000025727 Pre-results. PMID:28801436

Effect of low-dose calcium supplements on bone loss in perimenopausal and postmenopausal Asian women: a randomized controlled trial.

PubMed

Nakamura, Kazutoshi; Saito, Toshiko; Kobayashi, Ryosaku; Oshiki, Rieko; Kitamura, Kaori; Oyama, Mari; Narisawa, Sachiko; Nashimoto, Mitsue; Takahashi, Shunsuke; Takachi, Ribeka

2012-11-01

Current standard-dose calcium supplements (eg, 1000 mg/d) may increase the risk for cardiovascular events. Effectiveness of lower-dose supplements in preventing bone loss should thus be considered. This study aimed to assess whether calcium supplements of 500 or 250 mg/d effectively prevent bone loss in perimenopausal and postmenopausal Japanese women. We recruited 450 Japanese women between 50 and 75 years of age. They were randomly assigned to receive 500 mg of calcium (as calcium carbonate), 250 mg of calcium, or placebo daily. Medical examinations conducted three times over a 2-year follow-up period assessed bone mineral density (BMD) of the lumbar spine and femoral neck. One-factor repeated measures ANOVA was used for statistical tests. Subgroup analyses were also conducted. Average total daily calcium intake at baseline for the 418 subjects who underwent follow-up examinations was 493 mg/d. Intention-to-treat analysis showed less dramatic decreases in spinal BMD for the 500-mg/d calcium supplement group compared to the placebo group (1.2% difference over 2 years, p = 0.027). Per-protocol analysis (≥80% compliance) revealed that spinal BMD for the 500-mg/d and 250-mg/d calcium supplement groups decreased less than the placebo group (1.6%, p = 0.010 and 1.0%, p = 0.078, respectively), and that femoral neck BMD for the 500-mg/d calcium supplement group decreased less relative to the placebo group (1.0%, p = 0.077). A low-dose calcium supplement of 500 mg/d can effectively slow lumbar spine bone loss in perimenopausal and postmenopausal women with habitually low calcium intake, but its effect on the femoral neck is less certain. Calcium supplementation dosage should thus be reassessed. (Clinical Trials Registry number: UMIN000001176). Copyright © 2012 American Society for Bone and Mineral Research.

Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial.

PubMed

Aoki, Y; Watanabe, T; Abe, O; Kuwabara, H; Yahata, N; Takano, Y; Iwashiro, N; Natsubori, T; Takao, H; Kawakubo, Y; Kasai, K; Yamasue, H

2015-04-01

The neuropeptide oxytocin may be an effective therapeutic strategy for the currently untreatable social and communication deficits associated with autism. Our recent paper reported that oxytocin mitigated autistic behavioral deficits through the restoration of activity in the ventromedial prefrontal cortex (vmPFC), as demonstrated with functional magnetic resonance imaging (fMRI) during a socio-communication task. However, it is unknown whether oxytocin exhibited effects at the neuronal level, which was outside of the specific task examined. In the same randomized, double-blind, placebo-controlled, within-subject cross-over clinical trial in which a single dose of intranasal oxytocin (24 IU) was administered to 40 men with high-functioning autism spectrum disorder (UMIN000002241/000004393), we measured N-acetylaspartate (NAA) levels, a marker for neuronal energy demand, in the vmPFC using (1)H-magnetic resonance spectroscopy ((1)H-MRS). The differences in the NAA levels between the oxytocin and placebo sessions were associated with oxytocin-induced fMRI signal changes in the vmPFC. The oxytocin-induced increases in the fMRI signal could be predicted by the NAA differences between the oxytocin and placebo sessions (P=0.002), an effect that remained after controlling for variability in the time between the fMRI and (1)H-MRS scans (P=0.006) and the order of administration of oxytocin and placebo (P=0.001). Furthermore, path analysis showed that the NAA differences in the vmPFC triggered increases in the task-dependent fMRI signals in the vmPFC, which consequently led to improvements in the socio-communication difficulties associated with autism. The present study suggests that the beneficial effects of oxytocin are not limited to the autistic behavior elicited by our psychological task, but may generalize to other autistic behavioral problems associated with the vmPFC.

Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial

PubMed Central

Aoki, Y; Watanabe, T; Abe, O; Kuwabara, H; Yahata, N; Takano, Y; Iwashiro, N; Natsubori, T; Takao, H; Kawakubo, Y; Kasai, K; Yamasue, H

2015-01-01

The neuropeptide oxytocin may be an effective therapeutic strategy for the currently untreatable social and communication deficits associated with autism. Our recent paper reported that oxytocin mitigated autistic behavioral deficits through the restoration of activity in the ventromedial prefrontal cortex (vmPFC), as demonstrated with functional magnetic resonance imaging (fMRI) during a socio-communication task. However, it is unknown whether oxytocin exhibited effects at the neuronal level, which was outside of the specific task examined. In the same randomized, double-blind, placebo-controlled, within-subject cross-over clinical trial in which a single dose of intranasal oxytocin (24 IU) was administered to 40 men with high-functioning autism spectrum disorder (UMIN000002241/000004393), we measured N-acetylaspartate (NAA) levels, a marker for neuronal energy demand, in the vmPFC using 1H-magnetic resonance spectroscopy (1H-MRS). The differences in the NAA levels between the oxytocin and placebo sessions were associated with oxytocin-induced fMRI signal changes in the vmPFC. The oxytocin-induced increases in the fMRI signal could be predicted by the NAA differences between the oxytocin and placebo sessions (P=0.002), an effect that remained after controlling for variability in the time between the fMRI and 1H-MRS scans (P=0.006) and the order of administration of oxytocin and placebo (P=0.001). Furthermore, path analysis showed that the NAA differences in the vmPFC triggered increases in the task-dependent fMRI signals in the vmPFC, which consequently led to improvements in the socio-communication difficulties associated with autism. The present study suggests that the beneficial effects of oxytocin are not limited to the autistic behavior elicited by our psychological task, but may generalize to other autistic behavioral problems associated with the vmPFC. PMID:25070538

Multicenter retrospective analysis of systemic chemotherapy for advanced neuroendocrine carcinoma of the digestive system.

PubMed

Yamaguchi, Tomohiro; Machida, Nozomu; Morizane, Chigusa; Kasuga, Akiyoshi; Takahashi, Hideaki; Sudo, Kentaro; Nishina, Tomohiro; Tobimatsu, Kazutoshi; Ishido, Kenji; Furuse, Junji; Boku, Narikazu; Okusaka, Takuji

2014-09-01

This study analyzed outcomes of systemic chemotherapy for advanced neuroendocrine carcinoma (NEC) of the digestive system. Clinical data from 258 patients with unresectable or recurrent NEC of the gastrointestinal tract (GI) or hepato-biliary-pancreatic system (HBP), who received chemotherapy, were collected from 23 Japanese institutions and analyzed retrospectively. Patients had primary sites in the esophagus (n = 85), stomach (n = 70), small bowel (n = 6), colorectum (n = 31), hepato-biliary system (n = 31) and pancreas (n = 31). Median overall survival (OS) was 13.4 months the esophagus, 13.3 months for the stomach, 29.7 months for the small bowel, 7.6 months for the colorectum, 7.9 months for the hepato-biliary system and 8.5 months for the pancreas. Irinotecan plus cisplatin (IP) and etoposide plus cisplatin (EP) were most commonly selected for GI-NEC and HBP-NEC. For patients treated with IP/EP (n = 160/46), the response rate was 50/28% and median OS was 13.0/7.3 months. Multivariate analysis among patients treated with IP or EP showed that the primary site (GI vs HBP; hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.35-0.97) and baseline serum lactate dehydrogenase levels (not elevated vs elevated; HR 0.65, 95% CI 0.46-0.94) were independent prognostic factors for OS, while the efficacy of IP was slightly better than for EP (HR 0.80, 95% CI 0.48-1.33; P = 0.389). IP and EP are the most common treatment regimens for NEC of the digestive system. HBP primary sites and elevated lactate dehydrogenase levels are unfavorable prognostic factors for survival. A randomized controlled trial is required to establish the appropriate chemotherapy regimen for advanced NEC of the digestive system. This study was registered at UMIN as trial number 000005176. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Exploratory clinical trial of combination wound therapy with a gelatin sheet and platelet-rich plasma in patients with chronic skin ulcers: study protocol.

PubMed

Morimoto, Naoki; Kakudo, Natsuko; Matsui, Makoto; Ogura, Tsunetaka; Hara, Tomoya; Suzuki, Kenji; Yamamoto, Masaya; Tabata, Yasuhiko; Kusumoto, Kenji

2015-05-11

Chronic skin ulcers, such as diabetic ulcers, venous leg ulcers and pressure ulcers, are intractable and increasing in prevalence, representing a costly problem in healthcare. We developed a combination therapy with a gelatin sheet, capable of providing sustained release of platelet-rich plasma (PRP). The objective of this study is to investigate the safety and efficacy of autologous PRP covered with a hydrocolloid dressing and PRP covered with a gelatin sheet in the treatment of chronic skin ulcers. Thirty patients with chronic skin ulcers who have not healed with conventional therapy for at least 1 month are being recruited. The patients will receive PRP after debridement, and the wounds will be covered with a hydrocolloid dressing or gelatin sheet. The efficacy will be evaluated according to the time from the beginning of PRP application to secondary healing or the day on which wound closure is achieved with a relatively simple surgical procedure, such as skin grafting or suturing. All patients will be followed up until 6 weeks after application to observe adverse events related to the application of PRP and the dressings. This study was designed to address and compare the safety and efficacy of PRP covered with a hydrocolloid dressing versus a gelatin sheet. If successful, this combination therapy may be an alternative to bioengineered skin substitutes containing living cells and lead to substantial progress in the management of chronic skin ulcers. The study protocol was approved by the Institutional Review Board of Kansai Medical University (KMU Number 0649-1, 4 August 2014: V.1.0). The findings of this trial will be disseminated through peer-reviewed journals, and national and international scientific meetings as well as to the patients. UMIN000015689. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The Septic Shock 3.0 Definition and Trials: A Vasopressin and Septic Shock Trial Experience.

PubMed

Russell, James A; Lee, Terry; Singer, Joel; Boyd, John H; Walley, Keith R

2017-06-01

The Septic Shock 3.0 definition could alter treatment comparisons in randomized controlled trials in septic shock. Our first hypothesis was that the vasopressin versus norepinephrine comparison and 28-day mortality of patients with Septic Shock 3.0 definition (lactate > 2 mmol/L) differ from vasopressin versus norepinephrine and mortality in Vasopressin and Septic Shock Trial. Our second hypothesis was that there are differences in plasma cytokine levels in Vasopressin and Septic Shock Trial for lactate less than or equal to 2 versus greater than 2 mmol/L. Retrospective analysis of randomized controlled trial. Multicenter ICUs. We compared vasopressin-to-norepinephrine group 28- and 90-day mortality in Vasopressin and Septic Shock Trial in lactate subgroups. We measured 39 cytokines to compare patients with lactate less than or equal to 2 versus greater than 2 mmol/L. Patients with septic shock with lactate greater than 2 mmol/L or less than or equal to 2 mmol/L, randomized to vasopressin or norepinephrine. Concealed vasopressin (0.03 U/min.) or norepinephrine infusions. The Septic Shock 3.0 definition would have decreased sample size by about half. The 28- and 90-day mortality rates were 10-12 % higher than the original Vasopressin and Septic Shock Trial mortality. There was a significantly (p = 0.028) lower mortality with vasopressin versus norepinephrine in lactate less than or equal to 2 mmol/L but no difference between treatment groups in lactate greater than 2 mmol/L. Nearly all cytokine levels were significantly higher in patients with lactate greater than 2 versus less than or equal to 2 mmol/L. The Septic Shock 3.0 definition decreased sample size by half and increased 28-day mortality rates by about 10%. Vasopressin lowered mortality versus norepinephrine if lactate was less than or equal to 2 mmol/L. Patients had higher plasma cytokines in lactate greater than 2 versus less than or equal to 2 mmol/L, a brisker cytokine response to infection. The Septic Shock 3.0 definition and our findings have important implications for trial design in septic shock.

Comparison of effects of sitagliptin and voglibose on left ventricular diastolic dysfunction in patients with type 2 diabetes: results of the 3D trial.

PubMed

Oe, Hiroki; Nakamura, Kazufumi; Kihara, Hajime; Shimada, Kenei; Fukuda, Shota; Takagi, Tsutomu; Miyoshi, Toru; Hirata, Kumiko; Yoshikawa, Junichi; Ito, Hiroshi

2015-06-19

Left ventricular (LV) diastolic dysfunction is frequently observed in patients with type 2 diabetes. Dipeptidyl peptidase-4 inhibitor (DPP-4i) attenuates postprandial hyperglycemia (PPH) and may have cardio-protective effects. It remains unclear whether DPP-4i improves LV diastolic function in patients with type 2 diabetes, and, if so, it is attributable to the attenuation of PPH or to a direct cardiac effect of DPP-4i. We compared the effects of the DPP-4i, sitagliptin, and the alpha-glucosidase inhibitor, voglibose, on LV diastolic function in patients with type 2 diabetes. We conducted a prospective, randomized, open-label, multicenter study of 100 diabetic patients with LV diastolic dysfunction. Patients received sitagliptin (50 mg/day) or voglibose (0.6 mg/day). The primary endpoints were changes in the e' velocity and E/e' ratio from baseline to 24 weeks later. The secondary efficacy measures included HbA1c, GLP-1, lipid profiles, oxidative stress markers and inflammatory markers. The study was completed with 40 patients in the sitagliptin group and 40 patients in the voglibose group. There were no significant changes in the e' velocity and E/e' ratio from baseline to 24 weeks later in both groups. However, analysis of covariance demonstrated that pioglitazone use is an independent factor associated with changes in the e' and E/e' ratio. Among patients not using pioglitazone, e' increased and the E/e' ratio decreased in both the sitagliptin and voglibose groups. GLP-1 level increased from baseline to 24 weeks later only in the sitagliptin group (4.8 ± 4.7 vs. 7.3 ± 5.5 pmol/L, p < 0.05). The reductions in HbA1c and body weight were significantly greater in the sitagliptin group than in the voglibose group (-0.7 ± 0.6 % vs. -0.3 ± 0.4, p < 0.005; -1.3 ± 3.2 kg vs. 0.4 ± 2.8 kg, p < 0.05, respectively). There were no changes in lipid profiles and inflammatory markers in both groups. Our trial showed that sitagliptin reduces HbA1c levels more greatly than voglibose does, but that neither was associated with improvement in the echocardiographic parameters of LV diastolic function in patients with diabetes. Registered at http://www.umin.ac.jp under UMIN000003784.

Effectiveness of the new 'Mobile AED Map' to find and retrieve an AED: A randomised controlled trial.

PubMed

Sakai, Tomohiko; Iwami, Taku; Kitamura, Tetsuhisa; Nishiyama, Chika; Kawamura, Takashi; Kajino, Kentaro; Tanaka, Hiroshi; Marukawa, Seishiro; Tasaki, Osamu; Shiozaki, Tadahiko; Ogura, Hiroshi; Kuwagata, Yasuyuki; Shimazu, Takeshi

2011-01-01

Although early shock with an automated external defibrillator (AED) is one of the several key elements to save out-of-hospital cardiac arrest (OHCA) victims, it is not always easy to find and retrieve a nearby AED in emergency settings. We developed a cell phone web system, the Mobile AED Map, displaying nearby AEDs located anywhere. The simulation trial in the present study aims to compare the time and travel distance required to access an AED and retrieve it with and without the Mobile AED Map. Randomised controlled trial. Two fields where it was estimated to take 2min (120-170m) to access the nearest AED. Participants were randomly assigned to either the Mobile AED Map group or the control group. We provided each participant in both groups with an OHCA scenario, and measured the time and travel distance to find and retrieve a nearby AED. Forty-three volunteers were enrolled and completed the protocol. The time to access and retrieve an AED was not significantly different between the Mobile AED Map group (400±238s) and the control group (407±256s, p=0.92). The travel distance was significantly shorter in the Mobile AED Map group (606m vs. 891m, p=0.019). Trial field conditions affected the results differently. Although the new Mobile AED Map reduced the travel distance to access and retrieve the AED, it failed to shorten the time. Further technological improvements of the system are needed to increase its usefulness in emergency settings (UMIN000002043). Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Effect of Aggressive lipid-lowering treatment with Rosuvastatin on vascular endoTHelium function: evaluation of vascular endothelium function (EARTH study).

PubMed

Takayama, Tadateru; Hiro, Takafumi; Yoda, Shunichi; Fukamachi, Daisuke; Haruta, Hironori; Kogo, Takaaki; Mineki, Takashi; Murata, Hironobu; Oshima, Toru; Hirayama, Atsushi

2018-06-01

Vascular endothelial dysfunction plays an important role in the process of atherosclerosis up to the final stage of plaque rupture. Vascular endothelial dysfunction is reversible, and can be recovered by medications and life-style changes. Improvement in endothelial function may reduce cardiovascular events and improve long-term prognosis. A total of 50 patients with stable angina and dyslipidemia were enrolled, including patients who had not received prior treatment with statins and had serum LDL-C levels ≥ 100 mg/dL, and patients who had previously received statin treatment. All agreed to register regardless of their LDL-C level. Rosuvastatin was initially administered at a dose of 2.5 mg and appropriately titrated up to the maximum dose of 20 mg or until LDL-C levels lower than 80 mg/dL were achieved, for 24 weeks. Endothelial function was assessed by the reactive hyperemia peripheral arterial tonometry (RH-PAT) index in the radial artery by Endo-PAT ® 2000 (Endo-PAT ® 2000, software version 3.0.4, Itamar Medical Ltd., Caesarea, Israel). RH-PAT data were digitally analyzed online by Endo-PAT ® 2000 at baseline and at 24 weeks. LDL-C and MDA-LDL-C decreased from 112.6 ± 23.3 to 85.5 ± 20.2 mg/dL and from 135.1 ± 36.4 to 113.9 ± 23.5 mg/dL respectively (p < 0.0001). However, HDL-C, hs-CRP and TG did not change significantly after treatment. RH-PAT index levels significantly improved, from 1.60 ± 0.31 to 1.77 ± 0.57 (p = 0.04) after treatment, and the percent change of the RH-PAT index was 12.8 ± 36.9%. Results of multivariate analysis show that serum LDL-C levels over 24 weeks did not act as a predictor of improvement of the RH-PAT index. However, HbA1c at baseline was an independent predictor which influenced the 24-week RH-PAT index level. The RH-PAT index of patients with high HbA1c at baseline did not improve after administration of rosuvastatin but it did improve in patients with low HbA1c at baseline. Aggressive lowering of LDL-C with rosuvastatin significantly improved the RH-PAT index, suggesting that it may improve endothelial function in patients with coronary artery disease.Clinical Trial Registration No: UMIN-CTR, UMIN000010040.

Alcohol Consumption and Multiple Dysplastic Lesions Increase Risk of Squamous Cell Carcinoma in the Esophagus, Head, and Neck.

PubMed

Katada, Chikatoshi; Yokoyama, Tetsuji; Yano, Tomonori; Kaneko, Kazuhiro; Oda, Ichiro; Shimizu, Yuichi; Doyama, Hisashi; Koike, Tomoyuki; Takizawa, Kohei; Hirao, Motohiro; Okada, Hiroyuki; Yoshii, Takako; Konishi, Kazuo; Yamanouchi, Takenori; Tsuda, Takashi; Omori, Tai; Kobayashi, Nozomu; Shimoda, Tadakazu; Ochiai, Atsushi; Amanuma, Yusuke; Ohashi, Shinya; Matsuda, Tomonari; Ishikawa, Hideki; Yokoyama, Akira; Muto, Manabu

2016-11-01

Some patients develop multiple squamous cell carcinomas (SCCs) in the upper aerodigestive tract, attributed to field cancerization; alcohol consumption has been associated with this process. We examined the association between multiple areas of dysplastic squamous epithelium with the development of SCC of the esophagus or head and neck cancer, as well as alcohol consumption and smoking. We examined 331 patients with early stage esophageal SCC using Lugol chromoendoscopy to evaluate the dysplastic squamous epithelium in the esophagus. Patients then were assigned to 3 groups, based on the number of Lugol-voiding lesions: A, no lesion; B, 1-9 lesions; or C, 10 or more lesions. Participants completed lifestyle surveys on their history of drinking, smoking, and diet. All participants were evaluated by laryngopharyngoscopy before registration; only those without head and neck cancer were included, except for patients with superficial SCC limited to the subepithelial layer. Lesions detected in the esophagus and head and neck by surveillance were considered to be metachronous. The study end point was the cumulative incidence of metachronous SCCs in the esophagus and head and neck after endoscopic resection of esophageal SCC, according to the grade of Lugol-voiding lesions. At study entry, all patients were instructed to abstain from alcohol and smoking. Over the 2-year study period, metachronous SCCs of the esophagus were detected in 4% of patients in group A, in 9.4% of patients in group B, and in 24.7% of patients in group C (P < .0001 for patients in group A vs B or B vs C). Head and neck SCCs were detected in none of the patients in group A, in 1.7% of the patients in group B, and in 8.6% of the patients in group C (P = .016 for patients in group A vs C and P = .008 for patients in group B vs C). SCC of the esophagus or head and neck developed in 4.0% of patients in group A, in 10.0% of patients in group B, and in 31.4% of patients in group C (P < .0001 for group A vs B or A vs C). Alcohol abstinence decreased the risk of multiple SCCs of the esophagus (adjusted hazard ratio, 0.47, 95% confidence interval, 0.25-0.91; P = .025), whereas smoking abstinence did not. Multiple dysplastic lesions in the esophagus increase the risk of multiple SCCs. Alcohol abstinence reduces the risk of metachronous SCCs. Clinical Trials registry: UMIN000001676 and UMIN000005466. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Effects of a Japan Diet Intake Program on Metabolic Parameters in Middle-Aged Men.

PubMed

Maruyama, Chizuko; Nakano, Rena; Shima, Mitsuha; Mae, Asumi; Shijo, Yuri; Nakamura, Eri; Okabe, Yuuna; Park, Sunmi; Kameyama, Noriko; Hirai, Satomi; Nakanishi, Mamoru; Uchida, Kagehiro; Nishiyama, Hiroshi

2017-04-03

We conducted a pilot study to clarify the effects of the Japan Diet nutritional education program on metabolic risk factors for atherosclerotic cardiovascular disease in middle-aged men who were brought up in the westernized dietary environment of modern Japan. Thirty-three men, 30-49 years of age, attended a nutrition education class to learn food items and recommended volumes comprising the Japan Diet (more fish, soybeans and soy products, vegetables, seaweed, mushrooms and unrefined cereals, and less animal fat, meat and poultry with fat, sweets, desserts and snacks, and alcoholic drinks), and were encouraged to consume the Japan Diet for 6 weeks. Anthropometric and biochemical parameters were measured and 3-day weighted dietary records were kept before and at completion of the intervention. Ninety-one percent of participants showed improvements in more than one cardiovascular risk factor after 6 weeks. Body weight, serum low density lipoprotein (LDL) cholesterol, malondialdehyde modified (MDA)-LDL and triglyceride concentrations decreased significantly, while high density lipoprotein cholesterol was unchanged. Fish, soy, and sum of seaweed, mushrooms and konjak intakes doubled, and green and yellow vegetable intakes also increased as compared to baseline. Meanwhile, intakes of refined cereals, meat and poultry, sweets, desserts and snacks, and margarine and shortening decreased. Total energy, lipid, and saturated and monounsaturated fatty acid intakes decreased, while n-3 polyunsaturated fatty acid, dietary fiber, beta-carotene, vitamins D and K, potassium, and magnesium increased, with no change in sodium intake. The Japan Diet is suggested to improve atherosclerotic cardiovascular disease risk factors in middle-aged Japanese men.The clinical trial registration number: UMIN000020639.

A Randomized Clinical Trial of Preoperative Administration of Branched-Chain Amino Acids to Prevent Postoperative Ascites in Patients with Liver Resection for Hepatocellular Carcinoma.

PubMed

Kikuchi, Yutaro; Hiroshima, Yukihiko; Matsuo, Kenichi; Kawaguchi, Daisuke; Murakami, Takashi; Yabushita, Yasuhiro; Endo, Itaru; Taguri, Masataka; Koda, Keiji; Tanaka, Kuniya

2016-10-01

Massive postoperative ascites remains a major threat that can lead to liver failure and other fatal complications, especially in patients with poor liver function. Branched-chain amino acid (BCAA) administration increases biosynthesis and secretion of albumin by hepatocytes and increases oncotic pressure by elevating blood albumin concentration, thereby decreasing peripheral edema, ascites, and pleural effusion. We randomly allocated consecutive patients undergoing major liver resection for hepatocellular carcinoma to either a group where oral BCAA administration was initiated 3 weeks before liver resection, or a non-BCAA group. The primary study endpoint was development of postoperative ascites. Overall, 39 patients were allocated to the BCAA group, while 38 were assigned to the non-BCAA group. No significant difference in the rate of refractory ascites, considered alone, was evident between the BCAA (5.1 %) and non-BCAA groups (13.2 %; p = 0.263). However, the occurrence of refractory ascites and/or pleural effusion was significantly less frequent in the BCAA group (5.1 %) than in the non-BCAA group (21.1 %; p = 0.047). Furthermore, the postoperative serum concentration of reduced-state albumin was greater immediately after liver resection in the BCAA group than in the non-BCAA group. Preoperative administration of BCAA did not significantly improve prevention of refractory ascites, but significant effectiveness in preventing ascites, pleural effusion, or both, as well as improving metabolism of albumin, was demonstrated [University Hospital Medical Information Network (UMIN) reference number 000004244].

A randomized controlled trial of the different impression methods for the complete denture fabrication: Patient reported outcomes.

PubMed

Jo, Ayami; Kanazawa, Manabu; Sato, Yusuke; Iwaki, Maiko; Akiba, Norihisa; Minakuchi, Shunsuke

2015-08-01

To compare the effect of conventional complete dentures (CD) fabricated using two different impression methods on patient-reported outcomes in a randomized controlled trial (RCT). A cross-over RCT was performed with edentulous patients, required maxillomandibular CDs. Mandibular CDs were fabricated using two different methods. The conventional method used a custom tray border moulded with impression compound and a silicone. The simplified used a stock tray and an alginate. Participants were randomly divided into two groups. The C-S group had the conventional method used first, followed by the simplified. The S-C group was in the reverse order. Adjustment was performed four times. A wash out period was set for 1 month. The primary outcome was general patient satisfaction, measured using visual analogue scales, and the secondary outcome was oral health-related quality of life, measured using the Japanese version of the Oral Health Impact Profile for edentulous (OHIP-EDENT-J) questionnaire scores. Twenty-four participants completed the trial. With regard to general patient satisfaction, the conventional method was significantly more acceptable than the simplified. No significant differences were observed between the two methods in the OHIP-EDENT-J scores. This study showed CDs fabricated with a conventional method were significantly more highly rated for general patient satisfaction than a simplified. CDs, fabricated with the conventional method that included a preliminary impression made using alginate in a stock tray and subsequently a final impression made using silicone in a border moulded custom tray resulted in higher general patient satisfaction. UMIN000009875. Copyright © 2015 Elsevier Ltd. All rights reserved.

Efficacy of inhaled HYdrogen on neurological outcome following BRain Ischemia During post-cardiac arrest care (HYBRID II trial): study protocol for a randomized controlled trial.

PubMed

Tamura, Tomoyoshi; Hayashida, Kei; Sano, Motoaki; Onuki, Shuko; Suzuki, Masaru

2017-10-23

Hydrogen gas inhalation (HI) improved survival and neurological outcomes in an animal model of post-cardiac arrest syndrome (PCAS). The feasibility and safety of HI for patients with PCAS was confirmed in a pilot study. The objective of this study is to evaluate the efficacy of HI for patients with PCAS. The efficacy of inhaled HYdrogen on neurological outcome following BRain Ischemia During post-cardiac arrest care (HYBRID II) trial is an investigator-initiated, randomized, double-blind, placebo-controlled trial designed to enroll 360 adult comatose (Glasgow Coma Scale score < 8) patients who will be resuscitated following an out-of-hospital cardiac arrest of a presumed cardiac cause. The patients will be randomized (1:1) to either the HI or control group. Patients in the HI group will inhale 2% hydrogen with 24% to 50% oxygen, and those in the control group will inhale 24% to 50% oxygen for 18 h after admission via mechanical ventilation. Multidisciplinary post-arrest care, including targeted temperature management (TTM) between 33 °C and 36 °C, will be provided in accordance with the latest guidelines. The primary outcome of interest is the 90-day neurological outcome, as evaluated using the Cerebral Performance Categories scale (CPC). The secondary outcomes of interest are the 90-day survival rate and other neurological outcomes. This study will provide 80% power to detect a 15% change in the proportion of patients with good neurological outcomes (CPCs of 1 and 2), from 50% to 65%, with an overall significance level of 0.05. The first multicenter randomized trial is underway to confirm the efficacy of HI on neurological outcomes in comatose out-of-hospital cardiac arrest survivors. Our study has the potential to address HI as an appealing and innovative therapeutic strategy for PCAS in combination with TTM. University Hospital Medical Information Network (UMIN), 000019820 . Registered on 17 November 2015.

A randomized trial of aripiprazole vs blonanserin for the treatment of acute schizophrenia and related disorders.

PubMed

Kishi, Taro; Matsuda, Yuki; Matsunaga, Shinji; Mukai, Tomohiko; Moriwaki, Masatsugu; Tabuse, Hideaki; Fujita, Kiyoshi; Iwata, Nakao

2016-01-01

There has been no direct comparison of aripiprazole and blonanserin for schizophrenia treatment. We conducted a 24-week, rater-masked, randomized trial of aripiprazole (6-30 mg/d) vs blonanserin (4-24 mg/d) in schizophrenia patients who were not taking any antipsychotic medication for more than 2 weeks before enrollment (UMIN000011194). The primary outcome measure for efficacy was improvement of Positive and Negative Syndrome Scale (PANSS) total score at week 24. Secondary outcomes were PANSS subscale scores, 21-item Hamilton Rating Scale for Depression (HAMD-21) score, response rate, discontinuation rate, and individual adverse events. Forty-four patients were recruited. The discontinuation rate was 86.4% in the aripiprazole group and 68.2% in the blonanserin treatment group. There was no significant difference in mean time to discontinuation between the groups. Although both treatment groups showed significant reductions in the PANSS total score, PANSS subscale scores, and HAMD-21 scores at week 24, the magnitudes of the changes did not differ between the groups. There were no significant differences in the incidences of adverse events including somnolence, extrapyramidal symptoms, prolactin-related adverse events, and weight change between the groups. Our results suggest similar efficacy and safety profiles of aripiprazole and blonanserin in the patients with schizophrenia. Double-blind controlled studies are needed to further explore the efficacy and safety of aripiprazole and blonanserin in schizophrenia.

Effects of long-term self-massage at the musculotendinous junction on hamstring extensibility, stiffness, stretch tolerance, and structural indices: A randomized controlled trial.

PubMed

Akazawa, Naoki; Okawa, Naomi; Kishi, Masaki; Nakatani, Kiyoshi; Nishikawa, Katsuya; Tokumura, Daichi; Matsui, Yuji; Moriyama, Hideki

2016-09-01

The purpose of this study was to examine the effect of long-term self-massage at the musculotendinous junction on hamstring extensibility, stiffness, stretch tolerance, and structural indices. Single-blind, randomized, controlled trial. Laboratory. Thirty-seven healthy men. The right or left leg of each participant was randomly assigned to the massage group, and the other leg was assigned to the control group. The participants conducted self-massage at the musculotendinous junction for 3 min daily, five times per week, for 12 weeks. Hamstring extensibility, stiffness, stretch tolerance, and structural indices were measured by a blinded examiner prior to the massage intervention and after 6 and 12 weeks of intervention. The maximum hip flexion angle (HFA) and the maximum passive pressure after 6 and 12 weeks of intervention in the massage group were significantly higher than prior to intervention. The visual analog scale (for pain perception) at maximum HFA, the stiffness of the hamstring, and the structural indices did not differ in either group over the 12 week period. Our results suggest that long-term self-massage at the musculotendinous junction increases hamstring extensibility by improving stretch tolerance. However, this intervention does not change hamstring stiffness. University Hospital Medical Information Network registration number UMIN000011233. Copyright © 2016 Elsevier Ltd. All rights reserved.

Different responses to treatment across classified diseases and severities in Japanese patients with microscopic polyangiitis and granulomatosis with polyangiitis: a nationwide prospective inception cohort study.

PubMed

Sada, Ken-ei; Yamamura, Masahiro; Harigai, Masayoshi; Fujii, Takao; Takasaki, Yoshinari; Amano, Koichi; Fujimoto, Shouichi; Muso, Eri; Murakawa, Yohko; Arimura, Yoshihiro; Makino, Hirofumi

2015-11-02

This study aims to elucidate the prognosis and the effectiveness of current treatments for Japanese patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Patients with newly diagnosed MPA and GPA were enrolled in a nationwide, prospective, inception cohort study from 22 tertiary Japanese institutions, and treatment patterns and responses were evaluated for 24 months. Primary outcome measures were rates of remission (Birmingham Vasculitis Activity Score, 0) and remission with low-dose glucocorticoids (GC) (prednisolone ≤ 10 mg) (GC remission). Of 156 enrolled patients, 78 MPA patients and 33 GPA patients were included. Concomitant cyclophosphamide (CY) was used in 24 MPA (31 %) and 20 GPA (60 %) patients during the initial 3 weeks of treatment. After 6 months, remission was achieved in 66 MPA (85 %) and 29 GPA (87 %) patients, while GC remission was obtained in only 31 MPA (40 %) and 13 GPA (39 %) patients. During the 24-month period, 14 MPA patients and 2 GPA patients died; end stage renal disease (ESRD) was noted in 13 MPA patients but no GPA patients. Patients with severe disease, according to the European Vasculitis Study Group (EUVAS) classification, showed poorer ESRD-free and overall survival rates than those with generalized disease (p < 0.0001). There were no differences in relapse-free survival rates between GPA and MPA, among EUVAS-defined disease severity categories, and between anti-neutrophil cytoplasmic antibody subspecialties. The majority of Japanese patients with MPA and GPA received treatment with high-dose GC and limited CY use, and showed high remission and relapse-free survival rates but low GC remission rates in clinical practice. University Hospital Medical Information Network Clinical Trials Registry UMIN000001648 . Registered 28 February 2009.

A randomized controlled trial of multicomponent exercise in older adults with mild cognitive impairment.

PubMed

Suzuki, Takao; Shimada, Hiroyuki; Makizako, Hyuma; Doi, Takehiko; Yoshida, Daisuke; Ito, Kengo; Shimokata, Hiroshi; Washimi, Yukihiko; Endo, Hidetoshi; Kato, Takashi

2013-01-01

To examine the effect of multicomponent exercise program on memory function in older adults with mild cognitive impairment (MCI), and identify biomarkers associated with improvement of cognitive functions. Subjects were 100 older adults (mean age, 75 years) with MCI. The subjects were classified to an amnestic MCI group (n = 50) with neuroimaging measures, and other MCI group (n = 50) before the randomization. Subjects in each group were randomized to either a multicomponent exercise or an education control group using a ratio of 1∶1. The exercise group exercised for 90 min/d, 2 d/wk, 40 times for 6 months. The exercise program was conducted under multitask conditions to stimulate attention and memory. The control group attended two education classes. A repeated-measures ANOVA revealed that no group × time interactions on the cognitive tests and brain atrophy in MCI patients. A sub-analysis of amnestic MCI patients for group × time interactions revealed that the exercise group exhibited significantly better Mini-Mental State Examination (p = .04) and logical memory scores (p = .04), and reducing whole brain cortical atrophy (p<.05) compared to the control group. Low total cholesterol levels before the intervention were associated with an improvement of logical memory scores (p<.05), and a higher level of brain-derived neurotrophic factor was significantly related to improved ADAS-cog scores (p<.05). The results suggested that an exercise intervention is beneficial for improving logical memory and maintaining general cognitive function and reducing whole brain cortical atrophy in older adults with amnestic MCI. Low total cholesterol and higher brain-derived neurotrophic factor may predict improvement of cognitive functions in older adults with MCI. Further studies are required to determine the positive effects of exercise on cognitive function in older adults with MCI. UMIN-CTR UMIN000003662 ctr.cgi?function = brows&action = brows&type = summary&recptno = R000004436&language = J.

Pace-capture-guided ablation after contact-force-guided pulmonary vein isolation: results of the randomized controlled DRAGON trial.

PubMed

Masuda, Masaharu; Fujita, Masashi; Iida, Osamu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Kanda, Takashi; Sunaga, Akihiro; Tsujimura, Takuya; Matsuda, Yasuhiro; Ohashi, Takuya; Uematsu, Masaaki

2017-11-17

Before the discovery of contact-force guidance, eliminating pacing capture along the pulmonary vein (PV) isolation line had been reported to improve PV isolation durability and rhythm outcomes. DRAGON (UMIN-CTR, UMIN000015332) aimed to elucidate the efficacy of pace-capture-guided ablation following contact-force-guided PV isolation ablation in paroxysmal atrial fibrillation (AF) patients. A total of 156 paroxysmal AF patients with AF-trigger ectopies from any of the four PVs induced by isoproterenol were randomly assigned to undergo pace-capture-guided ablation along a contact-force-guided isolation line around AF-trigger PVs (PC group, n = 76) or contact-force-guided PV isolation ablation alone (control group, n = 80). Follow-up of at least 1 year commenced with serial 24 h Holter and symptom-triggered ambulatory monitoring. There was no significant difference in acute PV reconnection rates during a 20 min waiting period after the last ablation or adenosine infusion testing between the PC and the control groups (per patient, 21% vs. 27%, P = 0.27; per AF-trigger PV, 5.9% vs. 7.3%, P = 0.70; and per non-AF-trigger PV, 7.1% vs. 7.4%, P = 0.92). Atrial tachyarrhythmia-free survival rates off antiarrhythmic drugs after the initial session were comparable at 19.3 ± 6.2 months between the two groups (82% vs. 80%, P = 0.80). Among 22 patients who required a second ablation procedure, there was no difference between the PC and the control groups in the PV reconnection rates at both previously AF-trigger (29% vs. 43%, P = 0.70) and non-AF-trigger PVs (18% vs. 19%, P = 0.88). Pace-capture-guided ablation performed after contact-force-guided PV isolation demonstrated no improvement in PV isolation durability or rhythm outcome. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Combined effect of new complete dentures and simple dietary advice on nutritional status in edentulous patients: study protocol for a randomized controlled trial.

PubMed

Komagamine, Yuriko; Kanazawa, Manabu; Iwaki, Maiko; Jo, Ayami; Suzuki, Hiroyuki; Amagai, Noriko; Minakuchi, Shunsuke

2016-11-09

Individuals who are edentulous have a lower intake of fruit, vegetables, fiber, and protein compared with their dentate counterparts because tooth loss is accompanied by a decrease in ability to chew. Whether or not a combination of prosthetic rehabilitation and simple dietary advice produces improvement in dietary intake among edentulous persons is unclear. We aim to investigate the effect of a simultaneous combination of simple dietary advice delivered by dentists and provision of new complete dentures on dietary intake in edentulous individuals who request new dentures. Through a double-blinded, parallel, randomized controlled trial in which 70 edentate persons who request new complete dentures will be enrolled, eligible study participants will be randomly allocated to either a dietary intervention group receiving dietary advice or to a control group receiving only advice on the care and maintenance of dentures. Outcome measures include daily intake of nutrients and food items, assessed using a brief self-administered diet history questionnaire; antioxidant capacity, determined using blood and urine samples; nutritional status, assessed with the Mini-Nutritional Assessment-Short Form; oral health-related quality of life, assessed with the Japanese version of the Oral Health Impact Profile-EDENT and the Geriatric Oral Health Assessment Index; subjective chewing ability; masticatory performance, assessed using a color-changeable chewing gum and a gummy jelly; patient self-assessment of dentures; mild cognitive impairment, assessed with the Japanese version of the Montreal Cognitive Assessment; and functional capacity, assessed with the Japan Science and Technology Agency Index of Competence. Outcome measures, except for antioxidant capacity, are to be implemented at three time points: at baseline and at 3 and 6 months following intervention. Antioxidant capacity data are to be collected twice: at baseline and at 3 months following intervention. Differences between the groups at 3 and 6 months and within-group changes are to be compared using the paired t test. Simple dietary advice that can be implemented by a dentist would be more practical in clinical practice than tailored dietary counseling. The results of this study will provide beneficial information on dietary intake changes for both edentulous individuals requesting new complete dentures and dentists. University Hospital Medical Information Network Center Unique Trial Number: UMIN000017879 . Registered on 12 June 2015.

Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial.

PubMed

Gordon, Anthony C; Mason, Alexina J; Thirunavukkarasu, Neeraja; Perkins, Gavin D; Cecconi, Maurizio; Cepkova, Magda; Pogson, David G; Aya, Hollmann D; Anjum, Aisha; Frazier, Gregory J; Santhakumaran, Shalini; Ashby, Deborah; Brett, Stephen J

2016-08-02

Norepinephrine is currently recommended as the first-line vasopressor in septic shock; however, early vasopressin use has been proposed as an alternative. To compare the effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. A factorial (2×2), double-blind, randomized clinical trial conducted in 18 general adult intensive care units in the United Kingdom between February 2013 and May 2015, enrolling adult patients who had septic shock requiring vasopressors despite fluid resuscitation within a maximum of 6 hours after the onset of shock. Patients were randomly allocated to vasopressin (titrated up to 0.06 U/min) and hydrocortisone (n = 101), vasopressin and placebo (n = 104), norepinephrine and hydrocortisone (n = 101), or norepinephrine and placebo (n = 103). The primary outcome was kidney failure-free days during the 28-day period after randomization, measured as (1) the proportion of patients who never developed kidney failure and (2) median number of days alive and free of kidney failure for patients who did not survive, who experienced kidney failure, or both. Rates of renal replacement therapy, mortality, and serious adverse events were secondary outcomes. A total of 409 patients (median age, 66 years; men, 58.2%) were included in the study, with a median time to study drug administration of 3.5 hours after diagnosis of shock. The number of survivors who never developed kidney failure was 94 of 165 patients (57.0%) in the vasopressin group and 93 of 157 patients (59.2%) in the norepinephrine group (difference, -2.3% [95% CI, -13.0% to 8.5%]). The median number of kidney failure-free days for patients who did not survive, who experienced kidney failure, or both was 9 days (interquartile range [IQR], 1 to -24) in the vasopressin group and 13 days (IQR, 1 to -25) in the norepinephrine group (difference, -4 days [95% CI, -11 to 5]). There was less use of renal replacement therapy in the vasopressin group than in the norepinephrine group (25.4% for vasopressin vs 35.3% for norepinephrine; difference, -9.9% [95% CI, -19.3% to -0.6%]). There was no significant difference in mortality rates between groups. In total, 22 of 205 patients (10.7%) had a serious adverse event in the vasopressin group vs 17 of 204 patients (8.3%) in the norepinephrine group (difference, 2.5% [95% CI, -3.3% to 8.2%]). Among adults with septic shock, the early use of vasopressin compared with norepinephrine did not improve the number of kidney failure-free days. Although these findings do not support the use of vasopressin to replace norepinephrine as initial treatment in this situation, the confidence interval included a potential clinically important benefit for vasopressin, and larger trials may be warranted to assess this further. clinicaltrials.gov Identifier: ISRCTN 20769191.

Clinical Evaluation of a Royal Jelly Supplementation for the Restoration of Dry Eye: A Prospective Randomized Double Blind Placebo Controlled Study and an Experimental Mouse Model

PubMed Central

Inoue, Sachiko; Kawashima, Motoko; Hisamura, Ryuji; Imada, Toshihiro; Izuta, Yusuke; Nakamura, Shigeru; Ito, Masataka; Tsubota, Kazuo

2017-01-01

Background Dry eye is a multifactorial disease characterized by ocular discomfort and visual impairment. Lacrimal gland function has been shown to decrease with aging, a known potent risk factor for dry eye. We have previously found that orally administrated royal jelly (RJ) restored tear secretion in a rat model of dry eye. Methods and Findings We examined the effects of RJ oral administration on dry eye in this prospective, randomized, double-blind, placebo-controlled study. Forty-three Japanese patients aged 20–60 years with subjective dry eye symptoms were randomized to an RJ group (1200 mg/tablet, six tablets daily) or a placebo group for 8 weeks. Keratoconjunctival epithelial damage, tear film break-up time, tear secretion volume, meibum grade, biochemical data, and subjective dry eye symptoms based on a questionnaire were investigated at baseline, and at 4 and 8 weeks after intervention. Adverse events were reported via medical interviews. In the RJ group, tear volume significantly increased after intervention (p = 0.0009). In particular, patients with a baseline Schirmer value of ≤10 mm showed a significant increase compared with baseline volume (p = 0.0005) and volume in the placebo group (p = 0.0051). No adverse events were reported. We also investigated the effect of RJ (300 mg/kg per day) administration using a mouse model of dry eye. Orally repeated administration of RJ preserved tear secretion, potentially through direct activation of the secretory function of the lacrimal glands. Conclusion Our results suggest that RJ improves tear volume in patients with dry eye. Trial Registration Registered NO. the University Hospital Medical Information Network in Japan (UMIN000014446) PMID:28060936

Study for every other day administration of vonoprazan in maintenance treatment of erosive GERD: study protocol for a multicentre randomised cross-over study.

PubMed

Kato, Mototsugu; Ito, Noriko; Demura, Mamiko; Kubo, Kimitoshi; Mabe, Katsuhiro; Harada, Naohiko

2018-01-01

The first drug selected for treatment of gastro-oesophageal reflux disease (GERD) and prevention of the recurrence is a proton pump inhibitor (PPI), but recently, a potassium-competitive acid blocker (P-CAB) was put on the market in Japan. Its onset of effect is faster than PPI, and it takes more than 2 days to recover acid secretion after the withdrawal period. Therefore, unlike PPI, the usefulness of every other day administration or discontinuous administration is expected. This study is a prospective, multicentre, open-label, two-period randomised cross-over study to compare the efficacy and safety of PPI every other day administration and P-CAB every other day administration in 120 patients who receive erosive GERD maintenance therapy with PPI. Patients will be randomly allocated to receive 4 weeks P-CAB or PPI followed by 4 weeks cross over, where those on P-CAB will receive PPI and vice versa. The primary endpoint is proportion of asymptomatic patients. Secondary endpoints are suppressive effect of GERD symptoms, proportion of asymptomatic patients at each time point, safety and cost-saving effect of P-CAB every other day administration, compliance with every other day administration, and proportion of asymptomatic patients at the first month of study drug administration. This study was approved by the National Hospital Organization Central Review Board for Clinical Trials (5 December 2017). If P-CAB every other day administration is established as one of GERD maintenance therapies, there is merit in both medical cost reduction and the safety to alleviate elevation in serum gastrin. UMIN000034701.

Clinical Implication of Plasma Hydrogen Sulfide Levels in Japanese Patients with Type 2 Diabetes.

PubMed

Suzuki, Kunihiro; Sagara, Masaaki; Aoki, Chie; Tanaka, Seiichi; Aso, Yoshimasa

Objective The goal of the present study was to investigate the plasma hydrogen sulfide (H 2 S) levels in patients with type 2 diabetes, as the plasma H 2 S levels in Japanese patients with type 2 diabetes remain unclear. Methods The plasma H 2 S levels were measured in 154 outpatients with type 2 diabetes and 66 outpatients without diabetes. All blood samples were collected in the outpatient department from 09:00 to 10:00. The patients had fasted from 21:00 the previous evening and had not consumed alcohol or caffeine or smoked until sample collection. The plasma H 2 S levels were measured using the methylene blue assay. The plasma H 2 S levels were determined in triplicate, and the average concentrations were calculated against a calibration curve of sodium sulfide. Results The patients with type 2 diabetes showed a progressive reduction in the plasma H 2 S levels (45.115.5 M versus 54.026.4 M, p<0.05), which paralleled poor glycemic control. There was a significant correlation between a reduction in the plasma H 2 S levels and the HbA1c levels (=-0.505, p<0.01), Furthermore, a reduction in the plasma H 2 S levels was found to be related to a history of cardiovascular diseases in patients with type 2 diabetes (39.913.8 M versus 47.515.9 M, p<0.01). Conclusion Collectively, the plasma H 2 S levels were reduced in patients with type 2 diabetes, which may have implications in the pathophysiology of cardiovascular disease in diabetic patients. The trial was registered with the University Hospital Medical Information Network (UMIN no. #000020549).

Direct comparison of two different mesalamine formulations for the maintenance of remission in patients with ulcerative colitis: a double-blind, randomized study.

PubMed

Ito, Hiroaki; Iida, Mitsuo; Matsumoto, Takayuki; Suzuki, Yasuo; Aida, Yoshiyuki; Yoshida, Toyomitsu; Takano, Yuichi; Hibi, Toshifumi

2010-09-01

Mesalamine has been used as the first-line medication for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two different mesalamine formulations in the maintenance of remission in patients with UC. In a multicenter, double-blind, randomized study, 131 patients with quiescent UC were assigned to two groups: 65 to receive a pH-dependent release formulation of mesalamine at 2.4 g/day (pH-2.4 g) and 66 to receive a time-dependent release formulation of mesalamine at 2.25 g/day (Time-2.25 g). Both formulations were administered three times daily for 48 weeks. The primary endpoint was the proportion of patients without bloody stools. In the full analysis set (n = 130), the proportion of patients without bloody stools was 76.9% in the pH-2.4 g and 69.2% in the Time-2.25 g, demonstrating the noninferiority of pH-2.4 g to Time-2.25 g. No statistically significant difference in time to bloody stools was found between the two formulations (P = 0.27, log-rank test), but the time to bloody stools tended to be longer in pH-2.4 g compared to Time-2.25 g, and a similar trend was observed with regard to the time to relapse. No differences were observed between the safety profiles of the two formulations. The pH- and time-dependent release of mesalamine formulations were similarly safe and effective. Interestingly, the remission phase tended to be longer in the group that received the pH-dependent formulation compared to the group that received the time-dependent formulation (UMIN Clinical Trials Registry, no. C000000289).

Effects of a Japan Diet Intake Program on Metabolic Parameters in Middle-Aged Men: A Pilot Study

PubMed Central

Nakano, Rena; Shima, Mitsuha; Mae, Asumi; Shijo, Yuri; Nakamura, Eri; Okabe, Yuuna; Park, Sunmi; Kameyama, Noriko; Hirai, Satomi; Nakanishi, Mamoru; Uchida, Kagehiro; Nishiyama, Hiroshi

2017-01-01

Aim: We conducted a pilot study to clarify the effects of the Japan Diet nutritional education program on metabolic risk factors for atherosclerotic cardiovascular disease in middle-aged men who were brought up in the westernized dietary environment of modern Japan. Methods: Thirty-three men, 30–49 years of age, attended a nutrition education class to learn food items and recommended volumes comprising the Japan Diet (more fish, soybeans and soy products, vegetables, seaweed, mushrooms and unrefined cereals, and less animal fat, meat and poultry with fat, sweets, desserts and snacks, and alcoholic drinks), and were encouraged to consume the Japan Diet for 6 weeks. Anthropometric and biochemical parameters were measured and 3-day weighted dietary records were kept before and at completion of the intervention. Results: Ninety-one percent of participants showed improvements in more than one cardiovascular risk factor after 6 weeks. Body weight, serum low density lipoprotein (LDL) cholesterol, malondialdehyde modified (MDA)-LDL and triglyceride concentrations decreased significantly, while high density lipoprotein cholesterol was unchanged. Fish, soy, and sum of seaweed, mushrooms and konjak intakes doubled, and green and yellow vegetable intakes also increased as compared to baseline. Meanwhile, intakes of refined cereals, meat and poultry, sweets, desserts and snacks, and margarine and shortening decreased. Total energy, lipid, and saturated and monounsaturated fatty acid intakes decreased, while n-3 polyunsaturated fatty acid, dietary fiber, beta-carotene, vitamins D and K, potassium, and magnesium increased, with no change in sodium intake. Conclusions: The Japan Diet is suggested to improve atherosclerotic cardiovascular disease risk factors in middle-aged Japanese men. The clinical trial registration number: UMIN000020639. PMID:27667329

The Nonsteroidal Anti-inflammatory Drug Diclofenac Reduces Acid-Induced Heartburn Symptoms in Healthy Volunteers.

PubMed

Kondo, Takashi; Oshima, Tadayuki; Tomita, Toshihiko; Fukui, Hirokazu; Okada, Hiroki; Watari, Jiro; Miwa, Hiroto

2015-07-01

We investigated the effects of diclofenac, a nonsteroidal anti-inflammatory drug that inhibits prostaglandin production, on induction of esophageal sensation by acid perfusion in healthy men. We performed a prospective, double-blind, placebo-controlled, 2-period, cross-over study over 3 visits in 12 healthy men. Diclofenac was given 6 hours and 2 hours before an acid perfusion test. During the test, hydrochloric acid (0.15 mol/L) was perfused into the lower esophagus for 30 minutes; we evaluated upper gastrointestinal symptoms using a validated categoric rating scale. Then, we calculated and assessed the acid perfusion sensitivity score (APSS). Biopsy specimens were collected by endoscopy of the distal esophagus before and after acid perfusion; levels of prostaglandin E2 (PGE2) (pg/mg) were measured in the samples using an enzyme-linked immunosorbent assay. Compared with placebo, diclofenac significantly reduced the APSS for heartburn (82.2 ± 12.2 for placebo and 47.5 ± 8.9 for diclofenac; P < .01). Of the upper gastrointestinal symptoms, only the APSS for heartburn was reduced significantly by diclofenac. Compared with placebo, diclofenac reduced the overproduction of PGE2 by esophageal tissues after acid perfusion (23.3 ± 5.2 for placebo and 11.4 ± 3.5 for diclofenac; P < .05). APSS correlated with the development of heartburn and esophageal levels of PGE2 (r = 0.53; P < .05 for heartburn vs PGE2). Diclofenac attenuated acid-induced heartburn by inhibiting PGE2 overproduction in the esophagus. Esophageal PGE2 might be involved in producing heartburn symptoms. Clinical Trials Registry no: UMIN000014595. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children.

PubMed

Saad, Khaled; Abdel-Rahman, Ahmed A; Elserogy, Yasser M; Al-Atram, Abdulrahman A; Cannell, John J; Bjørklund, Geir; Abdel-Reheim, Mohamed K; Othman, Hisham A K; El-Houfey, Amira A; Abd El-Aziz, Nafisa H R; Abd El-Baseer, Khaled A; Ahmed, Ahmed E; Ali, Ahmed M

2016-10-01

Autism spectrum disorder (ASD) is a developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and non-verbal communication, and stereotyped patterns of interests and activities. Vitamin-D deficiency was previously reported in autistic children. However, the data on the relationship between vitamin D deficiency and the severity of autism are limited. We performed a case-controlled cross-sectional analysis conducted on 122 ASD children, to assess their vitamin D status compared to controls and the relationship between vitamin D deficiency and the severity of autism. We also conducted an open trial of vitamin D supplementation in ASD children. Fifty-seven percent of the patients in the present study had vitamin D deficiency, and 30% had vitamin D insufficiency. The mean 25-OHD levels in patients with severe autism were significantly lower than those in patients with mild/moderate autism. Serum 25-OHD levels had significant negative correlations with Childhood Autism Rating Scale (CARS) scores. Of the ASD group, 106 patients with low-serum 25-OHD levels (<30 ng/ml) participated in the open label trial. They received vitamin D3 (300 IU/kg/day not to exceed 5000 IU/day) for 3 months. Eighty-three subjects completed 3 months of daily vitamin D treatment. Collectively, 80.72% (67/83) of subjects who received vitamin D3 treatment had significantly improved outcome, which was mainly in the sections of the CARS and aberrant behavior checklist subscales that measure behavior, stereotypy, eye contact, and attention span. Vitamin D is inexpensive, readily available and safe. It may have beneficial effects in ASD subjects, especially when the final serum level is more than 40 ng/ml. UMIN-CTR Study Design: trial Number: R000016846.

Effect of cooking classes for housewives on salt reduction in family members: a cluster randomized controlled trial.

PubMed

Takada, T; Imamoto, M; Fukuma, S; Yamamoto, Y; Sasaki, S; Uchida, M; Miura, Y; Shimizu, S; Nihata, K; Fukuhara, S

2016-11-01

Sodium reduction is very important in preventing cardiovascular diseases, especially in regions with high salt intake such as Japan. One strategy for salt reduction is to raise consumer awareness of the need to reduce daily salt intake. We investigated whether cooking classes given to housewives focussing on salt reduction would influence not only their own consumption behaviour but also that of their family members. Single-blinded, cluster randomized trial. We randomly assigned housewives to participate in cooking classes focussing on salt reduction (intervention group) or lectures about a healthy lifestyle (control group). The main outcome measure was the difference in estimated daily salt intake by spot urine sampling of housewives and their family members 2 months after intervention between the groups. A total of 35 housewives and 33 family members were randomized. The mean daily salt intake was 10.00 (standard deviation [SD] 1.75) g/day in the control group (17 housewives and 15 family members) and 9.57 (SD 2.45) g/day in the intervention group (18 housewives and 18 family members) at baseline. Two months after the intervention, the mean salt intake was 10.30 (SD 1.78) g/day in the control group and 8.95 (SD 2.45) g/day in the intervention group. The mean difference was -1.19 g/day (95% confidence interval -2.29, -0.09; P = 0.034). A similar tendency was observed in the subgroups of housewives and family members. Our trial suggested that the effects of cooking classes focussing on salt reduction for housewives could be transferred to family members (UMIN-CTR: 000018870). Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Cardiac ischemia in patients with septic shock randomized to vasopressin or norepinephrine

PubMed Central

2013-01-01

Introduction Cardiac troponins are sensitive and specific biomarkers of myocardial necrosis. We evaluated troponin, CK, and ECG abnormalities in patients with septic shock and compared the effect of vasopressin (VP) versus norepinephrine (NE) on troponin, CK, and ECGs. Methods This was a prospective substudy of a randomized trial. Adults with septic shock randomly received, blinded, a low-dose infusion of VP (0.01 to 0.03 U/min) or NE (5 to 15 μg/min) in addition to open-label vasopressors, titrated to maintain a mean blood pressure of 65 to 75 mm Hg. Troponin I/T, CK, and CK-MB were measured, and 12-lead ECGs were recorded before study drug, and 6 hours, 2 days, and 4 days after study-drug initiation. Two physician readers, blinded to patient data and drug, independently interpreted ECGs. Results We enrolled 121 patients (median age, 63.9 years (interquartile range (IQR), 51.1 to 75.3), mean APACHE II 28.6 (SD 7.7)): 65 in the VP group and 56 in the NE group. At the four time points, 26%, 36%, 32%, and 21% of patients had troponin elevations, respectively. Baseline characteristics and outcomes were similar between patients with positive versus negative troponin levels. Troponin and CK levels and rates of ischemic ECG changes were similar in the VP and the NE groups. In multivariable analysis, only APACHE II was associated with 28-day mortality (OR, 1.07; 95% CI, 1.01 to 1.14; P = 0.033). Conclusions Troponin elevation is common in adults with septic shock. We observed no significant differences in troponin, CK, and ECGs in patients treated with vasopressin and norepinephrine. Troponin elevation was not an independent predictor of mortality. Trial registration Controlled-trials.com ISRCTN94845869 PMID:23786655

CITRUS, cervical cancer screening trial by randomization of HPV testing intervention for upcoming screening: Design, methods and baseline data of 18,471 women.

PubMed

Morisada, Tohru; Teramoto, Katsuhiro; Takano, Hirokuni; Sakamoto, Ikuko; Nishio, Hiroshi; Iwata, Takashi; Hashi, Akihiko; Katoh, Ryohei; Okamoto, Aikou; Sasaki, Hiroshi; Nakatani, Eiji; Teramukai, Satoshi; Aoki, Daisuke

2017-10-01

To assess the efficacy of screening with concurrent liquid-based cytology and human papillomavirus (HPV) testing for primary cervical cancer screening, we initiated a randomized trial entitled CervIcal cancer screening Trial by Randomization of HPV testing intervention for Upcoming Screening (CITRUS). Between June 2013 and March 2015, women aged 30-64 years of age who participated in a regular cervical cancer screening program (every 2 years) were invited to enrollment of our study. After giving their informed consent, 18,402 women were randomly assigned to liquid-based cytology as the control group (n=9145) or to HPV DNA testing with liquid-based cytology as the intervention group (n=9257). We subsequently compared the incidence rate of cervical intraepithelial neoplasia (CIN), the rate of false positive tests and the rate of overdiagnosis, as well as assessing the risks and benefits of receiving screening for women in both groups. The primary outcome of our study was the incidence of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) during the study period of around 6 years. In the control group, 97.9% of women were NILM, and 2.06% ASC-US or worse (ASC-US+). In the intervention group, 87.13% of women were NILM/HPV negative, 0.72% ASC-US/HPV negative, 10.34% NILM/HPV positive, 0.69% ASC-US/HPV positive, 0.90% worse than ASC-US/either HPV. Positive HPV testing was not linearly related to age in our study. Insights from CITRUS will provide future prospects for cervical cancer screening focused on the use of HPV testing in Japan. NCT01895517, UMIN000010843, TRIUC1312. Copyright © 2017 Elsevier Ltd. All rights reserved.

The beneficial effects of cognitive training with simple calculation and reading aloud in an elderly postsurgical population: study protocol for a randomized controlled trial.

PubMed

Kulason, Kay; Nouchi, Rui; Hoshikawa, Yasushi; Noda, Masafumi; Okada, Yoshinori; Kawashima, Ryuta

2016-07-22

This project proposes a pilot study to investigate the positive healing effects of cognitive training with simple arithmetic and reading aloud on elderly postsurgical patients. Elderly patients undergoing surgery have an increased risk of Postoperative Cognitive Decline (POCD), a condition in which learning, memory, and processing speed is greatly reduced after surgery. Since elderly patients are more likely to exhibit symptoms of POCD, the incidence is increasing as the population receiving surgery has aged. Little effort has been expended, however, to find treatments for POCD. Learning therapy, which consists of a combination of reading aloud and solving simple arithmetic problems, was developed in Japan as a treatment for Alzheimer's Disease to improve cognitive functions. Because patients with Alzheimer's Disease experience similar issues as those with POCD in learning, memory, and processing speed, a cognitive intervention based on the learning-therapy treatments used for Alzheimer's Disease could show advantageous outcomes for those at risk of POCD. Cognitive function will be measured before and after surgery using three different tests (Mini-Mental Status Exam, Frontal Assessment Battery, and Cogstate computerized tests). Subjects will be randomly divided into two groups-one that receives a Simple Calculation and Reading Aloud intervention (SCRA) and a waitlisted control group that does not receive SCRA. To measure cognition before and after the intervention, the previously mentioned three tests will be used. The obtained data will be analyzed using statistical tests such as ANCOVA to indicate whether the cognitive intervention group has made improvements in their cognitive functions. In addition, questionnaires will also be administered to collect data on mental and emotional statuses. This report will be the first pilot study to investigate the beneficial effects of SCRA on elderly surgical patients. Previous studies have shown sufficient evidence on the effectiveness of learning therapy in healthy elderly people and in those with Dementia. Therefore, this study will clarify whether SCRA can improve cognitive function in the more specialized group of elderly surgical patients. University Hospital Medical Information Network Clinical Trial Registry, UMIN000019832 . Registered on 18 November 2015.

Duration of the action of rocuronium in patients with BMI of less than 25: An observational study.

PubMed

Takahata, Osamu; Takahoko, Ken-Ichi; Sasakawa, Tomoki; Inagaki, Yasuyoshi; Takahoko, Hiroyuki; Kunisawa, Takayuki

2018-05-02

The duration of rocuronium in patients with BMI more than 30 kg m is prolonged. Whether the reverse is true when BMI is less than 18.5 kg m is unclear. The objective of this study was to investigate whether a BMI less than 25 kg m affects the duration of rocuronium in doses adjusted for actual body weight. A prospective, observational, single-centre study. The operating room of a teaching hospital from 1 June 2008 to 30 June 2015. Thirty patients with American Society of Anesthesiologists physical status I or II who were scheduled to undergo elective surgery (BMI < 25 kg m, aged 23 to 74 years) maintained by 0.7 minimum alveolar concentration sevoflurane and remifentanil. Repetitive train-of-four stimulation was applied and contractions of the adductor pollicis muscle were recorded. Duration of the initial dose of rocuronium (D1) was defined as the time from injection of rocuronium 0.6 mg kg to return of first twitch height to 25% of the control. Duration of additional doses (D2) was the time from a supplement of 0.15 mg kg rocuronium to return of first twitch height to 25% of the control. The relationship between D1 or D2 and BMI was examined using linear regression analysis. Linear regression analysis revealed a significant correlation between duration of initial dose and BMI (R = 0.246; P = 0.00531). A significant correlation between the duration of the additional dose and BMI was also found (R = 0.316; P = 0.00122). The lower the BMI, the shorter the duration of rocuronium at initial and additional doses determined by the actual body weight in adult patients with a BMI less than 25 kg m. www.umin.ac.jp/ctr/index/htm with registry number UMIN 00009337 and UMIN 000015407.

Overall safety profile and effectiveness of tramadol hydrochloride/acetaminophen in patients with chronic noncancer pain in Japanese real-world practice.

PubMed

Yoshizawa, K; Kawai, K; Fujie, M; Suzuki, J; Ogawa, Y; Yajima, T; Yokomori, J

2015-11-01

To evaluate the overall safety profile and clinical effectiveness of tramadol hydrochloride/acetaminophen (TA) combination tablets in Japanese patients with chronic noncancer pain unrelieved by non-opioid drugs for up to 12 weeks in real-world practice. This survey was a multicenter, prospective, longitudinal registry on the use of TA as a newly initiated pain treatment for chronic noncancer pain incurable by non-opioid analgesics that was conducted under the Good Post Marketing Study Practice regulation controlled by the Japan Ministry of Health, Labor and Welfare. Collected data included socio-demographics, treatment information, incidence of adverse drug reactions (ADRs), numerical rating scale for intensity of pain, EuroQol-5D (EQ-5D) scale, and physician's global impression (PGI) during the 12 week observation period. A total of 1316 patients were registered. ADRs were reported in 259 patients (20.5%); most events were nonserious (99.4%), including nausea (n = 87 [6.9%]), constipation (n = 63 [5.0%]), dizziness and somnolence (n = 29 [2.3%] each), and vomiting (n = 21 [1.7%]). No event related to drug dependence or respiratory depression was reported. In addition, 82.8% of patients showed acceptable effectiveness based on PGI at Week 4. Numerical rating scale for intensity of pain and EQ-5D utility scores were improved by -2.7 (SD 2.3) and 0.16 (SD 0.20) at Week 4, respectively, and the improvement was maintained until Week 12. This is a first report to evaluate the risk-benefit profile of TA in Japanese real-world practice using large size registry data. It is suggested that the favorable risk-benefit balance of TA was confirmed for patients with chronic noncancer pain unrelieved by non-opioid drugs in real-world practice. Limitations of this study were those inherent to open-label and non-interventional study designs. This registry survey is registered at umin.ac.jp (identifier: UMIN000015901).

Morning and Evening Home Blood Pressure and Risks of Incident Stroke and Coronary Artery Disease in the Japanese General Practice Population: The Japan Morning Surge-Home Blood Pressure Study.

PubMed

Hoshide, Satoshi; Yano, Yuichiro; Haimoto, Hajime; Yamagiwa, Kayo; Uchiba, Kiyoshi; Nagasaka, Shoichiro; Matsui, Yoshio; Nakamura, Akira; Fukutomi, Motoki; Eguchi, Kazuo; Ishikawa, Joji; Kario, Kazuomi

2016-07-01

Our aim is to determine the optimal time schedule for home blood pressure (BP) monitoring that best predicts stroke and coronary artery disease in general practice. The Japan Morning Surge-Home Blood Pressure (J-HOP) study is a nationwide practice-based study that included 4310 Japanese with a history of or risk factors for cardiovascular disease, or both (mean age, 65 years; 79% used antihypertensive medication). Home BP measures were taken twice daily (morning and evening) over 14 days at baseline. During a mean follow-up of 4 years (16 929 person-years), 74 stroke and 77 coronary artery disease events occurred. Morning systolic BP (SBP) improved the discrimination of incident stroke (C statistics, 0.802; 95% confidence interval, 0.692-0.911) beyond traditional risk factors including office SBP (0.756; 0.646-0.866), whereas the changes were smaller with evening SBP (0.764; 0.653-0.874). The addition of evening SBP to the model (including traditional risk factors plus morning SBP) significantly reduced the discrimination of incident stroke (C statistics difference, -0.008; 95% confidence interval: -0.015 to -0.008; P=0.03). The category-free net reclassification improvement (0.3606; 95% confidence interval, 0.1317-0.5896), absolute integrated discrimination improvement (0.015; SE, 0.005), and relative integrated discrimination improvement (58.3%; all P<0.01) with the addition of morning SBP to the model (including traditional risk factors) were greater than those with evening SBP and with combined morning and evening SBP. Neither morning nor evening SBP improved coronary artery disease risk prediction. Morning home SBP itself should be evaluated to ensure best stroke prediction in clinical practice, at least in Japan. This should be confirmed in the different ethnic groups. URL: http://www.umin.ac.jp/ctr/. Unique identifier: UMIN000000894. © 2016 American Heart Association, Inc.

Safety data from the phase III Japanese ACHIEVE trial: part of an international, prospective, planned pooled analysis of six phase III trials comparing 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer

PubMed Central

Kotaka, Masahito; Yamanaka, Takeharu; Yoshino, Takayuki; Manaka, Dai; Eto, Tetsuya; Hasegawa, Junichi; Takagane, Akinori; Nakamura, Masato; Kato, Takeshi; Munemoto, Yoshinori; Nakamura, Fumitaka; Bando, Hiroyuki; Taniguchi, Hiroki; Gamoh, Makio; Shiozawa, Manabu; Saji, Shigetoyo; Maehara, Yoshihiko; Mizushima, Tsunekazu; Ohtsu, Atsushi; Mori, Masaki

2018-01-01

Background The International Duration Evaluation of Adjuvant chemotherapy project investigated whether a shorter duration of oxaliplatin-based adjuvant chemotherapy was as effective as 6 months of identical chemotherapy for resected stage III colon cancer. As part of this project, we report safety data from the Japanese ACHIEVE study (JFMC47-1202-C3). Patients and methods ACHIEVE was an open-label, multicentre trial randomising patients with stage III colon cancer to receive 3 m or 6 m of mFOLFOX6/CAPOX after surgery. Choice of regimen was declared before randomisation by a site investigator. Results Between August 2012 and June 2014, 1313 patients were enrolled and, of those, 1277 were analysed for the safety analysis, with 635 in arm 6 (mFOLFOX6, n=158; CAPOX, n=477) and 642 in arm 3 (mFOLFOX6, n=161; CAPOX, n=481). Grade 3 or worse peripheral sensory neuropathy (PSN) developed in 5%/0.6% of patients receiving mFOLFOX6 in arm 6/3 (p=0.019) and 6%/1% of those receiving CAPOX in arm 6/3 (p<0.001). Similarly, grade 2 or worse PSN developed in 36%/11% of patients receiving mFOLFOX6 in arm 6/3 (p<0.001) and 37%/14% of those receiving CAPOX in arm 6/3 (p<0.001). An association between baseline creatinine clearance (CCr) and adverse events (AEs) was found that patients with CAPOX were significantly more likely to develop AEs ≥grade 3 when they had a CCr ≤50 (OR 1.67; p=0.048). Conclusions We confirmed in the Japanese population that the shorter duration of adjuvant chemotherapy resulted in a significant reduction of PSN. In patients with CAPOX, renal function was significantly related to severe AEs. Trial registration number UMIN000008543, Results. PMID:29713499

A randomized trial of aripiprazole vs blonanserin for the treatment of acute schizophrenia and related disorders

PubMed Central

Kishi, Taro; Matsuda, Yuki; Matsunaga, Shinji; Mukai, Tomohiko; Moriwaki, Masatsugu; Tabuse, Hideaki; Fujita, Kiyoshi; Iwata, Nakao

2016-01-01

Objective There has been no direct comparison of aripiprazole and blonanserin for schizophrenia treatment. We conducted a 24-week, rater-masked, randomized trial of aripiprazole (6−30 mg/d) vs blonanserin (4−24 mg/d) in schizophrenia patients who were not taking any antipsychotic medication for more than 2 weeks before enrollment (UMIN000011194). Methods The primary outcome measure for efficacy was improvement of Positive and Negative Syndrome Scale (PANSS) total score at week 24. Secondary outcomes were PANSS subscale scores, 21-item Hamilton Rating Scale for Depression (HAMD-21) score, response rate, discontinuation rate, and individual adverse events. Results Forty-four patients were recruited. The discontinuation rate was 86.4% in the aripiprazole group and 68.2% in the blonanserin treatment group. There was no significant difference in mean time to discontinuation between the groups. Although both treatment groups showed significant reductions in the PANSS total score, PANSS subscale scores, and HAMD-21 scores at week 24, the magnitudes of the changes did not differ between the groups. There were no significant differences in the incidences of adverse events including somnolence, extrapyramidal symptoms, prolactin-related adverse events, and weight change between the groups. Conclusion Our results suggest similar efficacy and safety profiles of aripiprazole and blonanserin in the patients with schizophrenia. Double-blind controlled studies are needed to further explore the efficacy and safety of aripiprazole and blonanserin in schizophrenia. PMID:27932884

Differences in Predictive Factors for Sustained Clinical Remission with Abatacept Between Younger and Elderly Patients with Biologic-naive Rheumatoid Arthritis: Results from the ABROAD Study.

PubMed

Sekiguchi, Masahiro; Fujii, Takao; Matsui, Kiyoshi; Murakami, Kosaku; Morita, Satoshi; Ohmura, Koichiro; Kawahito, Yutaka; Nishimoto, Norihiro; Mimori, Tsuneyo; Sano, Hajime

2016-11-01

To differentiate predictive factors for sustained clinical remission between elderly and younger patients with rheumatoid arthritis (RA) receiving abatacept (ABA) as an initial biological disease-modifying antirheumatic drug. The study involved 277 biologic-naive patients with RA with high or moderate disease activity, who were treated with intravenous ABA and evaluated for 48 weeks in 43 Japanese hospitals and rheumatology clinics (the ABatacept Research Outcomes as a First-line Biological Agent in the Real WorlD study: UMIN000004651). Predictive factors associated with sustained clinical remission defined by the 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) during the 24-48-week or 36-48-week periods were determined in elderly (≥ 65 yrs, n = 148) and younger patient groups (< 65 yrs, n = 129) using logistic regression analysis. Clinical remission was achieved at 24 and 48 weeks in 35.1% and 36.5% of patients in the elderly group and 34.9% and 43.4% in the younger group, respectively. In elderly patients, anticitrullinated protein antibody (ACPA) positivity and a lower DAS28-CRP score were significantly associated with sustained clinical remission; however, a lower Health Assessment Questionnaire-Disability Index (HAQ-DI) score was not related to sustained clinical remission. In younger patients, lower DAS28-CRP and HAQ-DI scores were predictive factors for sustained clinical remission, whereas ACPA positivity was not a useful predictive factor for sustained clinical remission. Although the effectiveness of ABA in biologic-naive patients with RA was equally recognized in elderly and younger patients, the baseline clinical characteristics associated with sustained clinical remission were substantially different.

Optimal regimens of sulfamethoxazole-trimethoprim for chemoprophylaxis of Pneumocystis pneumonia in patients with systemic rheumatic diseases: results from a non-blinded, randomized controlled trial.

PubMed

Utsunomiya, Masako; Dobashi, Hiroaki; Odani, Toshio; Saito, Kazuyoshi; Yokogawa, Naoto; Nagasaka, Kenji; Takenaka, Kenchi; Soejima, Makoto; Sugihara, Takahiko; Hagiyama, Hiroyuki; Hirata, Shinya; Matsui, Kazuo; Nonomura, Yoshinori; Kondo, Masahiro; Suzuki, Fumihito; Tomita, Makoto; Kihara, Mari; Yokoyama, Waka; Hirano, Fumio; Yamazaki, Hayato; Sakai, Ryoko; Nanki, Toshihiro; Koike, Ryuji; Kohsaka, Hitoshi; Miyasaka, Nobuyuki; Harigai, Masayoshi

2017-01-18

Sulfamethoxazole-trimethoprim (SMX/TMP) is a standard drug for the prophylaxis of Pneumocystis pneumonia (PJP) in immunosuppressed patients with systemic rheumatic diseases, but is sometimes discontinued due to adverse events (AEs). The objective of this non-blinded, randomized, 52-week non-inferiority trial was to quest an effective chemoprophylaxis regimen for PJP with a low drug discontinuation rate. Results at week 24 were reported. Adult patients with systemic rheumatic diseases who started prednisolone ≥0.6 mg/kg/day were randomized into three dosage groups: a single-strength group (SS, SMX/TMP of 400/80 mg daily), half-strength group (HS, 200/40 mg daily), and escalation group (ES, started with 40/8 mg daily, increasing incrementally to 200/40 mg daily). The primary endpoint was non-incidence rates (non-IR) of PJP at week 24. Of 183 patients randomly allocated at a 1:1:1 ratio into the three groups, 58 patients in SS, 59 in HS, and 55 in ES started SMX/TMP. A total of 172 patients were included in the analysis. No cases of PJP were reported up to week 24. Estimated non-IR of PJP in patients who received daily SMX/TMP of 200/40 mg, either starting at this dose or increasing incrementally, was 96.8-100% using the exact confidence interval as a post-hoc analysis. The overall discontinuation rate was significantly lower with HS compared to SS (p = 0.007). The discontinuation rates due to AEs were significantly lower with HS (p = 0.006) and ES (p = 0.004) compared to SS. The IR of AEs requiring reduction in the dose of SMX/TMP (p = 0.009) and AEs of special interest (p = 0.003) were different among the three groups with significantly higher IR in SS compared to HS and ES. Although there were no PJP cases, the combined group of HS and ES had an excellent estimated non-IR of PJP and both were superior in safety to SS. From the perspective of feasibility and drug discontinuation rates, the daily half-strength regimen was suggested to be optimal for prophylaxis of PJP in patients with systemic rheumatic diseases. The University Hospital Medical Information Network Clinical Trials Registry number is UMIN000007727 , registered 10 April 2012.

Impact of pectoral nerve block on postoperative pain and quality of recovery in patients undergoing breast cancer surgery: A randomised controlled trial.

PubMed

Kamiya, Yoshinori; Hasegawa, Miki; Yoshida, Takayuki; Takamatsu, Misako; Koyama, Yu

2018-03-01

In recent years, thoracic wall nerve blocks, such as the pectoral nerve (PECS) block and the serratus plane block have become popular for peri-operative pain control in patients undergoing breast cancer surgery. The effect of PECS block on quality of recovery (QoR) after breast cancer surgery has not been evaluated. To evaluate the ability of PECS block to decrease postoperative pain and anaesthesia and analgesia requirements and to improve postoperative QoR in patients undergoing breast cancer surgery. Randomised controlled study. A tertiary hospital. Sixty women undergoing breast cancer surgery between April 2014 and February 2015. The patients were randomised to receive a PECS block consisting of 30 ml of levobupivacaine 0.25% after induction of anaesthesia (PECS group) or a saline mock block (control group). The patients answered a 40-item QoR questionnaire (QoR-40) before and 1 day after breast cancer surgery. Numeric Rating Scale score for postoperative pain, requirement for intra-operative propofol and remifentanil, and QoR-40 score on postoperative day 1. PECS block combined with propofol-remifentanil anaesthesia significantly improved the median [interquartile range] pain score at 6 h postoperatively (PECS group 1 [0 to 2] vs. Control group 1 [0.25 to 2.75]; P = 0.018]. PECS block also reduced propofol mean (± SD) estimated target blood concentration to maintain bispectral index (BIS) between 40 and 50 (PECS group 2.65 (± 0.52) vs. Control group 3.08 (± 0.41) μg ml; P < 0.001) but not remifentanil consumption (PECS group 10.5 (± 4.28) vs. Control group 10.4 (± 4.68) μg kg h; P = 0.95). PECS block did not improve the QoR-40 score on postoperative day 1 (PECS group 182 [176 to 189] vs. Control group 174.5 [157.75 to 175]). In patients undergoing breast cancer surgery, PECS block combined with general anaesthesia reduced the requirement for propofol but not that for remifentanil, due to the inability of the PECS block to reach the internal mammary area. Further, PECS block improved postoperative pain but not the postoperative QoR-40 score due to the factors that cannot be measured by analgesia immediately after surgery, such as rebound pain. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000013435).

Production of Polyclonal Antibodies in Rabbits

DTIC Science & Technology

1995-10-01

injections of bovine fetal serum acetylcholinesterase and horse serum butyrylcholinesterase in rabbits. Concentrations of these enzymes became...13 2. Horse Serum Butyrylcholinesterase (E-BChE) 14 3. Bovine Serum Albumin (BSA) and Rabbit Serum Al4umin (RSA) 14 4. Suppocire-D 14 5. Triglyceride...Extraction from Calcium Sulfate Microspheres 16 c. Removal of Sealant and Polymer Overcoat from Calcium 17 Sulfate Microspheres 5. Size Distribution 17 6. In

Effect of endoscopic transpapillary biliary drainage with/without endoscopic sphincterotomy on post-endoscopic retrograde cholangiopancreatography pancreatitis in patients with biliary stricture (E-BEST): a protocol for a multicentre randomised controlled trial.

PubMed

Kato, Shin; Kuwatani, Masaki; Sugiura, Ryo; Sano, Itsuki; Kawakubo, Kazumichi; Ono, Kota; Sakamoto, Naoya

2017-08-11

The effect of endoscopic sphincterotomy prior to endoscopic biliary stenting to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis remains to be fully elucidated. The aim of this study is to prospectively evaluate the non-inferiority of non-endoscopic sphincterotomy prior to stenting for naïve major duodenal papilla compared with endoscopic sphincterotomy prior to stenting in patients with biliary stricture. We designed a multicentre randomised controlled trial, for which we will recruit 370 patients with biliary stricture requiring endoscopic biliary stenting from 26 high-volume institutions in Japan. Patients will be randomly allocated to the endoscopic sphincterotomy group or the non-endoscopic sphincterotomy group. The main outcome measure is the incidence of pancreatitis within 2 days of initial transpapillary biliary drainage. Data will be analysed on completion of the study. We will calculate the 95% confidence intervals (CIs) of the incidence of pancreatitis in each group and analyse weather the difference in both groups with 95% CIs is within the non-inferiority margin (6%) using the Wald method. This study has been approved by the institutional review board of Hokkaido University Hospital (IRB: 016-0181). Results will be submitted for presentation at an international medical conference and published in a peer-reviewed journal. The University Hospital Medical Information Network ID: UMIN000025727 Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Features of Clinical Register of Chinese Medicine and Pharmacy Based on ClinicalTrials.gov. (USA)].

PubMed

Lu, Peng-fei; Liao, Xing; Xie, Yan-ming; Wang, Zhi-guo

2015-11-01

In recent 10 years, clinical trials of Chinese medicine and pharmacy (cMP) at clinicalTrials.gov.(USA) are gradually increasing. In order to analyze features of CMP clinical register, ClinicalTrials.gov register database were comprehensively retrieved in this study. Included clinical trials were input one item after another using EXCEL. A final of 348 CMP clinical trials were included. Results showed that China occupied the first place in CMP clinical register, followed by USA. CMP clinical trials, sponsored mainly by colleges/universities and hospitals, mostly covered interventional studies on evaluating safety/effectiveness of CMP. The proportions of studies, sponsored by mainland China and companies, recruitment trials and multi-center clinical trials in interventional trials were increasing. The proportions of studies sponsored by Hong Kong and Taiwan, research completed trials, unclear research status, phase III clinical trials, and published research trials in interventional trials were decreasing. Published ratios of CMP clinical trials were quite low. There were more missing types and higher proportions in trial register information.

The Health Initiative Program for Kids (HIP Kids): effects of a 1-year multidisciplinary lifestyle intervention on adiposity and quality of life in obese children and adolescents--a longitudinal pilot intervention study.

PubMed

Bock, Dirk E; Robinson, Tracy; Seabrook, Jamie A; Rombeek, Meghan; Norozi, Kambiz; Filler, Guido; Rauch, Ralf; Clarson, Cheril L

2014-12-05

Though recent data suggest that multidisciplinary outpatient interventions can have a positive effect on childhood obesity, it is still unclear which program components are most beneficial and how they affect quality of life (QoL). The aim of this study was to determine if a 1-year multidisciplinary, family-centered outpatient intervention based on social cognitive theory would be effective in (i) preventing further increases in BMI and BMI z-score, and (ii) improving QoL in obese children and adolescents. Obese children and adolescents 8-17 years of age and their families participated in this 1-year longitudinal pilot intervention study. The intervention consisted of fifteen 90-minute educational sessions led by a dietitian, exercise specialist, and social worker. Anthropometric measures, body composition, and QoL (Pediatric Quality of Life Inventory 4.0), were assessed at baseline, 3 months, and 12 months. Laboratory values were measured at baseline and 12 months. The primary outcome measures were change in BMI and BMI z-score, secondary outcome measures included change in QoL and body composition. A paired sample t-test was used to assess within-group differences and 95% confidence intervals were reported for the mean differences. 42 obese children and adolescents (21 girls) completed the 1-year intervention (mean age 12.8 ± 3.14 years). Mean baseline BMI was 31.96 ± 5.94 kg/m(2) and BMI z-score was +2.19 ± 0.34. Baseline QoL (self-assessments and parental assessments) was impaired: mean baseline scores were 74.5 ± 16.5 and 63.7 ± 19.4 for physical functioning and 69.0 ± 14.9 and 64.0 ± 18.3 for emotional functioning, respectively. At 12 months, BMI z-score had decreased (-0.07 ± 0.11, 95% CI: -0.11 to -0.04). BMI (0.80 ± 1.57 kg/m(2), 95% CI 0.31 to 1.29) and fat-free mass (4.02 ± 6.27 kg, 95% CI 1.90 to 6.14) increased, but % body fat and waist circumference did not. Both the parent-reported physical (11.3 ± 19.2, 95% CI 4.7 to 17.9) and emotional (7.7 ± 15.7, 95% CI 2.3 to 13.0) functioning QoL scores and the children's self-reported physical (5.3 ± 17.1, 95% CI 0.5 to 11.1) and emotional (7.9 ± 14.3, 95% CI 3.2 to 12.7) functioning scores significantly improved. Following a 1-year intervention, the participants' BMI z-scores and QoL improved, while other adiposity-related measures of body composition remained unchanged. UMIN Clinical Trials Registry UMIN000015622 .

Current status of registry of vaccine clinical trials conducted by Korean investigators in ClinicalTrials.gov, database of US National Institutes of Health.

PubMed

Cho, Jahyang; Kim, Bo Bae; Bae, Chong-Woo; Cha, Sung-Ho

2013-01-01

PubMed is not only includes international medical journals but also has a registration site for the ongoing clinical trials, such as ClinicalTrials.gov, under the supervision of US National Institutes of Health. We analyzed current status of vaccine clinical trials conducted by Korean investigators in database of ClinicalTrial.gov. As of October 2012, there are total of 72 trials found on registry of vaccine clinical trials conducted by Korean investigators in database of ClinicalTrial.gov. These trials were analyzed and classified by conditions of vaccine clinical trials, biologicals or drugs used in vaccine clinical trials, status of proceeding research, and list of sponsor and collaborators. Total 72 trials of vaccine clinical trials conducted by Korean investigators are classified by groups of infection (64 trials), cancer (4 trials), and others (4 trials). Infections group shown are as follows: poliomyelitis, pertussis, diphtheria, tetanus, and Haemophilus influenzae type b (10), influenza (9), human papillomavirus infection (8), pneumococcal vaccine (6), herpes zoster (4), smallpox (4), hepatitis B (4), etc. One trial of each in lung cancer, breast cancer, prostate cancer, and colorectal cancer are shown in cancer group. One trial of each in Crohn's disease, ulcerative colitis, renal failure, and rheumatoid arthritis are shown in other group. Vaccine clinical trials conducted by Korean investigators in ClinicalTrial.gov reflects the current status of Korean research on vaccine clinical trials at the international level and can indicate research progress. It is hoped that this aids the development of future vaccine clinical trials in Korea.

Classification and characteristics of Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study.

PubMed

Sada, Ken-ei; Yamamura, Masahiro; Harigai, Masayoshi; Fujii, Takao; Dobashi, Hiroaki; Takasaki, Yoshinari; Ito, Satoshi; Yamada, Hidehiro; Wada, Takashi; Hirahashi, Junichi; Arimura, Yoshihiro; Makino, Hirofumi

2014-04-23

We investigated the clinical and serological features of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan using data from a nationwide, prospective, inception cohort study. In total, 156 Japanese patients with newly diagnosed AAV were classified according to the European Medicines Agency (EMEA) algorithm with exploratory surrogate markers for AAV-related non-granulomatous pulmonary lesions, predefined as alveolar haemorrhage and interstitial lung disease (ILD), and their clinical and serological features were evaluated. Using the EMEA algorithm, we identified 14 patients (9.0%) with eosinophilic granulomatosis with polyangiitis (EGPA), 33 (21.2%) with granulomatosis with polyangiitis (GPA), 78 (50.0%) with microscopic polyangiitis and renal-limited vasculitis (MPA/RLV), and 31 (19.9%) with unclassifiable vasculitis. The average ages of patients with EGPA (male/female, 5/9), GPA (12/21), and MPA/RLV (35/43) and unclassifiable (9/22) were 58.0, 63.6, 71.1, and 70.6 years, respectively. Myeloperoxidase (MPO)-ANCA and proteinase-3 ANCA positivity was 50.0% and 0% for EGPA, 54.6% and 45.5% for GPA, 97.4% and 2.6% for MPA/RLV, and 93.5% and 3.2% for unclassifiable, respectively. According to the Birmingham Vasculitis Activity Score (BVAS), cutaneous (71.4%) and nervous system (92.9%) manifestations were prominent in EGPA and ear, nose, and throat manifestations (84.9%) and chest manifestations (66.7%) in GPA. Renal manifestations developed frequently in MPA/RLV (91.0%) and GPA (63.6%). The average serum creatinine levels were 0.71 mg/dL for EGPA, 1.51 mg/dL for GPA, 2.46 mg/dL for MPA/RLV, and 0.69 mg/dL for unclassifiable. The percentages of patients with ILD were 14.3% for EGPA, 9.0% for GPA, 47.4% for MPA/RLV, and 61.3% for unclassifiable. Patients with ILD (n = 61) had significantly lower BVAS (P = 0.019) with fewer ear, nose, and throat and cardiovascular manifestations than patients without ILD (n = 95). MPO-ANCA-positive MPA/RLV is the most common form of AAV in Japanese patients, and one-half of patients with GPA were positive for MPO-ANCA. ILD is an important clinical manifestation in Japanese patients with AAV. Unclassifiable vasculitis with MPO-ANCA positivity and ILD may represent a novel variant of MPA. The University Hospital Medical Information Network Clinical Trials Registry: UMIN000001648. Registered 28 February 2009.

U. S. Naval Forces, Vietnam Monthly Historical Summary for November 1968

DTIC Science & Technology

1968-11-01

8217~ -..-. .,-.. 4* November 1968 Coastal activit7 cont.Uriedd to drop of f due to sea and surf cona-mdtona along4 the 3=th China Sea. 4umin; thds...uncov*ored Ur-)wru -wit ±h ;;n exacasve * sj~aant of medicina in theifr posesossiotu Th4 wCmeO o1L4moAi t~hey wre taking t~be medicine t~o their

Biobleaching of industrial important dyes with peroxidase partially purified from garlic.

PubMed

Osuji, Akudo Chigozirim; Eze, Sabinus Oscar O; Osayi, Emmanuel Emeka; Chilaka, Ferdinand Chiemeka

2014-01-01

An acidic peroxidase was extracted from garlic (Allium sativum) and was partially purified threefold by ammonium sulphate precipitation, dialysis, and gel filtration chromatography using sephadex G-200. The specific activity of the enzyme increased from 4.89 U/mg after ammonium sulphate precipitation to 25.26 U/mg after gel filtration chromatography. The optimum temperature and pH of the enzyme were 50°C and 5.0, respectively. The Km and V max for H2O2 and o-dianisidine were 0.026 mM and 0.8 U/min, and 25 mM and 0.75 U/min, respectively. Peroxidase from garlic was effective in decolourizing Vat Yellow 2, Vat Orange 11, and Vat Black 27 better than Vat Green 9 dye. For all the parameters monitored, the decolourization was more effective at a pH range, temperature, H2O2 concentration, and enzyme concentration of 4.5-5.0, 50°C, 0.6 mM, and 0.20 U/mL, respectively. The observed properties of the enzyme together with its low cost of extraction (from local sources) show the potential of this enzyme for practical application in industrial wastewater treatment especially with hydrogen peroxide. These Vat dyes also exhibited potentials of acting as peroxidase inhibitors at alkaline pH range.

High- Versus Low-Gradient Severe Aortic Stenosis: Demographics, Clinical Outcomes, and Effects of the Initial Aortic Valve Replacement Strategy on Long-Term Prognosis.

PubMed

Taniguchi, Tomohiko; Morimoto, Takeshi; Shiomi, Hiroki; Ando, Kenji; Kanamori, Norio; Murata, Koichiro; Kitai, Takeshi; Kawase, Yuichi; Izumi, Chisato; Miyake, Makoto; Mitsuoka, Hirokazu; Kato, Masashi; Hirano, Yutaka; Matsuda, Shintaro; Inada, Tsukasa; Nagao, Kazuya; Murakami, Tomoyuki; Takeuchi, Yasuyo; Yamane, Keiichiro; Toyofuku, Mamoru; Ishii, Mitsuru; Minamino-Muta, Eri; Kato, Takao; Inoko, Moriaki; Ikeda, Tomoyuki; Komasa, Akihiro; Ishii, Katsuhisa; Hotta, Kozo; Higashitani, Nobuya; Kato, Yoshihiro; Inuzuka, Yasutaka; Maeda, Chiyo; Jinnai, Toshikazu; Morikami, Yuko; Saito, Naritatsu; Minatoya, Kenji; Kimura, Takeshi

2017-05-01

There is considerable debate on the management of patients with low-gradient severe aortic stenosis (LG-AS), defined as aortic valve area <1 cm 2 with peak aortic jet velocity ≤4.0 m/s, and mean aortic pressure gradient ≤40 mm Hg. In the CURRENT AS registry (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis), there were 2097 patients (initial aortic valve replacement [AVR] strategy: n=977, and conservative strategy: n=1120) with high-gradient severe aortic stenosis (HG-AS) and 1712 patients (initial AVR strategy: n=219, and conservative strategy: n=1493) with LG-AS. AVR was more frequently performed in HG-AS patients than in LG-AS patients (60% versus 28%) during the entire follow-up. In the comparison between the initial AVR and conservative groups, the propensity score-matched cohorts were developed in both HG-AS (n=887 for each group) and LG-AS (n=218 for each group) strata. The initial AVR strategy when compared with the conservative strategy was associated with markedly lower risk for a composite of aortic valve-related death or heart failure hospitalization in both HG-AS and LG-AS strata (hazard ratio, 0.30; 95% confidence interval, 0.25-0.37; P <0.001 and hazard ratio, 0.46; 95% confidence interval, 0.32-0.67; P <0.001, respectively). Among 1358 patients with LG-AS with preserved left ventricular ejection fraction, the initial AVR strategy was associated with a better outcome than the conservative strategy (adjusted hazard ratio, 0.37; 95% confidence interval, 0.23-0.59; P <0.001). The initial AVR strategy was associated with better outcomes than the conservative strategy in both HG-AS and LG-AS patients, although AVR was less frequently performed in LG-AS patients than in HG-AS patients. The favorable effect of initial AVR strategy was also seen in patients with LG-AS with preserved left ventricular ejection fraction. URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000012140. © 2017 American Heart Association, Inc.

Balloon catheter versus basket catheter for endoscopic bile duct stone extraction: a multicenter randomized trial.

PubMed

Ishiwatari, Hirotoshi; Kawakami, Hiroshi; Hisai, Hiroyuki; Yane, Kei; Onodera, Manabu; Eto, Kazunori; Haba, Shin; Okuda, Toshinori; Ihara, Hideyuki; Kukitsu, Takehiro; Matsumoto, Ryusuke; Kitaoka, Keisuke; Sonoda, Tomoko; Hayashi, Tsuyoshi

2016-04-01

Endoscopic bile duct stone (BDS) removal is a well-established treatment; however, the preference for basket or balloon catheters for extraction is operator-dependent. We therefore conducted a multicenter prospective randomized trial to compare catheter performance. We enrolled patients with a BDS diameter ≤ 10 mm and common bile duct diameter ≤ 15 mm. Participants were randomly assigned to groups that were treated with basket or balloon catheters between October 2013 and September 2014. The primary endpoint was the rate of complete clearance of the duct; the secondary endpoints were the rate and time to complete clearance in one endoscopic session. We initially enrolled 172 consecutive patients; 14 were excluded after randomization. The complete clearance rates were 92.3 % (72/78) in the balloon group and 80.0 % (64 /80) in the basket group. The difference in the rates between the two groups was 12.3 percentage points, indicating non-inferiority of the balloon method (non-inferiority limit -10 %; P < 0.001 for non-inferiority). Moreover, the balloon was superior to the basket (P = 0.037). The rate of complete clearance in one endoscopic session was 97.4 % using the balloon and 97.5 % using the basket (P = 1.00). The median times to complete clearance in one endoscopic session were 6.0 minutes (1 - 30) and 7.8 minutes (1 - 37) in the balloon and basket groups, respectively (P = 0.15). For extraction of BDSs ≤ 10 mm, complete endoscopic treatment with a single catheter is more likely when choosing a balloon catheter over a basket catheter.University Hospital Medical Information Network Trials Registry: UMIN000011887. © Georg Thieme Verlag KG Stuttgart · New York.

Oxytocin for Male Subjects with Autism Spectrum Disorder and Comorbid Intellectual Disabilities: A Randomized Pilot Study

PubMed Central

Munesue, Toshio; Nakamura, Hiroyuki; Kikuchi, Mitsuru; Miura, Yui; Takeuchi, Noriyuki; Anme, Tokie; Nanba, Eiji; Adachi, Kaori; Tsubouchi, Kiyotaka; Sai, Yoshimichi; Miyamoto, Ken-ichi; Horike, Shin-ichi; Yokoyama, Shigeru; Nakatani, Hideo; Niida, Yo; Kosaka, Hirotaka; Minabe, Yoshio; Higashida, Haruhiro

2016-01-01

Approximately half of autism spectrum disorder (ASD) individuals suffer from comorbid intellectual disabilities (IDs). Oxytocin (OXT) receptors are highly expressed in temporal lobe structures and are likely to play a modulatory role in excitatory/inhibitory balance, at least based on animal model findings. Thus, it is feasible that in the highly representative group of Kanner-type ASD subjects, OXT could have a beneficial effect on social communication and social interaction. The aim of this pilot study is to investigate the feasibility and adverse events, such as epilepsy, of the long-term administration of intranasal OXT for adolescent and adult ASD subjects with ID because such patients frequently have seizures. We also addressed the question on how to scale the OXT effects to the core symptoms of social deficits because of the relative difficulty in obtaining objective measurements. Twenty-nine males (aged 15–40 years old) participated in a randomized, double-blind, and placebo-controlled crossover study (each for 8 weeks) with OXT (16 IU/day). Except for seizures experienced by one participant, other serious adverse events did not occur. The primary and secondary outcomes measured using the Childhood Autism Rating Scale and several standard scales, respectively, revealed no difference between the OXT and placebo groups. Instead, in an exploratory analysis, the social interactions observed in the play sessions or in daily life were significantly more frequent in the initial half period in the OXT-first arm of the crossover trial. There were also significant correlations between the plasma OXT concentration and subscale scores for irritability on the Aberrant Behavior Checklist. In conclusion, this pilot study demonstrates that long-term administration of intranasal OXT is tolerable in a representative cohort of ASD individuals with ID and suggests that future multicenter trials of OXT are warranted and should include measurements of reciprocal social interactions based on daily life under closer surveillance for epilepsy. Trial registration: UMIN000007250. PMID:26834651

Safety data from the phase III Japanese ACHIEVE trial: part of an international, prospective, planned pooled analysis of six phase III trials comparing 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer.

PubMed

Kotaka, Masahito; Yamanaka, Takeharu; Yoshino, Takayuki; Manaka, Dai; Eto, Tetsuya; Hasegawa, Junichi; Takagane, Akinori; Nakamura, Masato; Kato, Takeshi; Munemoto, Yoshinori; Nakamura, Fumitaka; Bando, Hiroyuki; Taniguchi, Hiroki; Gamoh, Makio; Shiozawa, Manabu; Saji, Shigetoyo; Maehara, Yoshihiko; Mizushima, Tsunekazu; Ohtsu, Atsushi; Mori, Masaki

2018-01-01

The International Duration Evaluation of Adjuvant chemotherapy project investigated whether a shorter duration of oxaliplatin-based adjuvant chemotherapy was as effective as 6 months of identical chemotherapy for resected stage III colon cancer. As part of this project, we report safety data from the Japanese ACHIEVE study (JFMC47-1202-C3). ACHIEVE was an open-label, multicentre trial randomising patients with stage III colon cancer to receive 3 m or 6 m of mFOLFOX6/CAPOX after surgery. Choice of regimen was declared before randomisation by a site investigator. Between August 2012 and June 2014, 1313 patients were enrolled and, of those, 1277 were analysed for the safety analysis, with 635 in arm 6 (mFOLFOX6, n=158; CAPOX, n=477) and 642 in arm 3 (mFOLFOX6, n=161; CAPOX, n=481). Grade 3 or worse peripheral sensory neuropathy (PSN) developed in 5%/0.6% of patients receiving mFOLFOX6 in arm 6/3 (p=0.019) and 6%/1% of those receiving CAPOX in arm 6/3 (p<0.001). Similarly, grade 2 or worse PSN developed in 36%/11% of patients receiving mFOLFOX6 in arm 6/3 (p<0.001) and 37%/14% of those receiving CAPOX in arm 6/3 (p<0.001). An association between baseline creatinine clearance (CCr) and adverse events (AEs) was found that patients with CAPOX were significantly more likely to develop AEs ≥grade 3 when they had a CCr ≤50 (OR 1.67; p=0.048). We confirmed in the Japanese population that the shorter duration of adjuvant chemotherapy resulted in a significant reduction of PSN. In patients with CAPOX, renal function was significantly related to severe AEs. UMIN000008543, Results.

Taurine supplementation for prevention of stroke-like episodes in MELAS: a multicentre, open-label, 52-week phase III trial.

PubMed

Ohsawa, Yutaka; Hagiwara, Hiroki; Nishimatsu, Shin-Ichiro; Hirakawa, Akihiro; Kamimura, Naomi; Ohtsubo, Hideaki; Fukai, Yuta; Murakami, Tatsufumi; Koga, Yasutoshi; Goto, Yu-Ichi; Ohta, Shigeo; Sunada, Yoshihide

2018-04-17

The aim of this study was to evaluate the efficacy and safety of high-dose taurine supplementation for prevention of stroke-like episodes of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), a rare genetic disorder caused by point mutations in the mitochondrial DNA that lead to a taurine modification defect at the first anticodon nucleotide of mitochondrial tRNA Leu(UUR) , resulting in failure to decode codons accurately. After the nationwide survey of MELAS, we conducted a multicentre, open-label, phase III trial in which 10 patients with recurrent stroke-like episodes received high-dose taurine (9 g or 12 g per day) for 52 weeks. The primary endpoint was the complete prevention of stroke-like episodes during the evaluation period. The taurine modification rate of mitochondrial tRNA Leu(UUR) was measured before and after the trial. The proportion of patients who reached the primary endpoint (100% responder rate) was 60% (95% CI 26.2% to 87.8%). The 50% responder rate, that is, the number of patients achieving a 50% or greater reduction in frequency of stroke-like episodes, was 80% (95% CI 44.4% to 97.5%). Taurine reduced the annual relapse rate of stroke-like episodes from 2.22 to 0.72 (P=0.001). Five patients showed a significant increase in the taurine modification of mitochondrial tRNA Leu(UUR) from peripheral blood leukocytes (P<0.05). No severe adverse events were associated with taurine. The current study demonstrates that oral taurine supplementation can effectively reduce the recurrence of stroke-like episodes and increase taurine modification in mitochondrial tRNA Leu(UUR) in MELAS. UMIN000011908. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Efficacy of advice from healthcare professionals to pregnant women on avoiding constrictive clothing around the trunk: a study protocol for a randomised controlled trial

PubMed Central

Takehara, Kenji; Kato, Sachiko; Sasaki, Aiko; Jwa, Seung Chik; Kakee, Naoko; Sago, Haruhiko; Noguchi, Yuko; Aoki, Tomoko; Inoue, Eisuke; Nitta, Chieko; Ishii, Yumiko

2015-01-01

Introduction As a component of midwife care, eliminating clothing that constricts the trunk has been shown to markedly elevate the uterine fundus, soften the uterus and abdomen, and reduce the abdominal wall tension in women admitted to hospital due to the risk of miscarriage or premature delivery. However, no prospective study has conclusively verified the efficacy of avoiding constrictive clothes around the trunk in pregnant women. We aim to verify the efficacy of instructing pregnant women to wear loose clothing that does not constrict the trunk to reduce the risk of premature birth and improve quality of life (QoL) during pregnancy. Methods and analysis We will conduct a randomised controlled trial of pregnant women scheduled to deliver at the National Center for Child Health and Development in Tokyo, Japan. A total of 616 pregnant women, from whom written informed consent will be obtained, will be allocated randomly to an intervention group or a control group. Women in the control group will be provided with anaemia prevention leaflets at 20 weeks’ gestation and skin-care leaflets at 30 weeks’ gestation. Women in the intervention group will be provided with the same leaflets and will also receive health advice from health professionals to avoid constrictive clothing around the trunk. The primary outcome will be a difference between these groups in the frequency of any one of the following category variables: (1) cervical length <30 mm up to 28 weeks’ gestation, (2) hospital admission for threatened premature delivery, or (3) premature delivery. Secondary outcomes will include QoL during pregnancy, maternal state of health, and status of fetal development. Ethics and dissemination The Institutional Review Board and Ethics Committee at the National Center for Child Health and Development, Japan, has approved this study. Our findings will be widely disseminated through conference presentations and peer-reviewed publications. Trial registration number UMIN000016853. PMID:26423851

Study protocol for a randomised controlled trial to test the effectiveness of providing information on childbirth and postnatal period to partners of pregnant women

PubMed Central

Takehara, Kenji; Okamura, Makoto; Sugiura, Naomi; Suto, Maiko; Sasaki, Hatoko; Mori, Rintaro

2016-01-01

Introduction The objective of this study is to investigate the effect of the distribution of a booklet providing information to fathers during their partners' pregnancies on fathers' and mothers' postpartum mental health and quality of life (QOL), as well as on fathers' childcare participation and living situations. Methods and analysis This randomised controlled trial will comprise 554 couples consisting of pregnant women due to give birth at an obstetric institution in Aichi Prefecture, Japan and their partners. Participants will be recruited during prenatal check-ups in the third trimester, and those who provide written consent will be allocated randomly to an intervention and a control group. The pregnant women's partners allocated to the intervention group will be given a booklet written for men containing information on childbirth and postnatal period. Its content will include matters such as what preparations the partner should make before birth and tips for housework and childcare as well as how to prevent unintentional injury to the baby. The control group will not receive any intervention. A baseline survey in the third trimester and follow-up surveys at 1 and 3 months post partum will be carried out using self-administered questionnaires. The primary outcome is the proportion of new mothers' partners at risk for paternal depression (Edinburgh Postnatal Depression Scale score ≥8). Secondary outcomes include the risk of postnatal depression in new mothers, QOL of new mothers and their partners, partners' knowledge of and engagement in housework and childcare, marital relations and parenting stress on the part of new mothers. Ethics and dissemination This study has been approved by the Ethical Committee at the National Center for Child Health and Development, Tokyo, Japan. The results of the study will be widely disseminated as peer-reviewed papers and at international conferences, with the aim of improving public health services in Japan. Trial registration number UMIN000021475; Pre-results. PMID:27466241

A randomized controlled trial of 130 g/day low-carbohydrate diet in type 2 diabetes with poor glycemic control.

PubMed

Sato, Junko; Kanazawa, Akio; Makita, Sumiko; Hatae, Chie; Komiya, Koji; Shimizu, Tomoaki; Ikeda, Fuki; Tamura, Yoshifumi; Ogihara, Takeshi; Mita, Tomoya; Goto, Hiromasa; Uchida, Toyoyoshi; Miyatsuka, Takeshi; Takeno, Kageumi; Shimada, Satoshi; Ohmura, Chie; Watanabe, Takehito; Kobayashi, Kiyoe; Miura, Yoshiko; Iwaoka, Manami; Hirashima, Nao; Fujitani, Yoshio; Watada, Hirotaka

2017-08-01

The usefulness of low-carbohydrate diet (LCD) for Japanese patients with type 2 diabetes mellitus (T2DM) has not been fully investigated. Therefore, we compared the effectiveness and safety of LCD with calorie restricted diet (CRD). This prospective, randomized, open-label, comparative study included 66 T2DM patients with HbA1c >7.5% even after receiving repeated education programs on CRD. They were randomly allocated to either the 130g/day LCD group (n = 33) or CRD group (n = 33). Patients received personal nutrition education of CRD or LCD for 30 min at baseline, 1, 2, 4, and 6 months. Patients of the CRD group were advised to maintain the intake of calories and balance of macronutrients (28× ideal body weight calories per day). Patients of the LCD group were advised to maintain the intake of 130 g/day carbohydrate without other specific restrictions. Several parameters were assessed at baseline and 6 months after each intervention. The primary endpoint was a change in HbA1c level from baseline to the end of the study. At baseline, BMI and HbA1c were 26.5 (24.6-30.1) and 8.3 (8.0-9.3), and 26.7 (25.0-30.0) kg/m 2 and 8.0 (7.6-8.9) %, in the CRD and LCD, respectively. At the end of the study, HbA1c decreased by -0.65 (-1.53 to -0.10) % in the LCD group, compared with 0.00 (-0.68 to 0.40) % in the CRD group (p < 0.01). Also, the decrease in BMI in the LCD group [-0.58 (-1.51 to -0.16) kg/m 2 ] exceeded that observed in the CRD group (p = 0.03). Our study demonstrated that 6-month 130 g/day LCD reduced HbA1c and BMI in poorly controlled Japanese patients with T2DM. LCD is a potentially useful nutrition therapy for Japanese patients who cannot adhere to CRD. This trial was registered at http://www.umin.ac.jp/english/ (University Hospital Medical Information Network: study ID number 000010663). Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The postcard intervention against depression among community-dwelling older adults: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Depression in older adults deteriorates quality of life and increases morbidity, mortality, and medical expenses. Medicine and social policy should work together to decrease this burden. Existing prevention studies are often based on time-consuming psychotherapies, which therefore are not feasible for a wide application at the community level. Postcard interventions have been shown to be effective for patients after hospitalization for major depression, drug overdose, or self-harm. This paper describes the protocol of a pragmatic, randomized controlled trial designed to examine the efficacy of a postcard intervention for depression among community-dwelling individuals aged 65 years or older. Methods/Design This is a pragmatic, non-blinded, parallel comparison, randomized controlled trial using Zelen’s design in a community setting. Participants will include community-dwelling older adults (aged 65 years or older) with limited social support (indicated by eating meals alone) and with symptoms of depression (scoring 4 or higher on the 15-item Geriatric Depression Scale (GDS)). The intervention will consist of sending postcards with handwritten messages and seasonal reports from a historical city to participants once a month for eight consecutive months. Self-addressed, stamped envelopes will be enclosed to facilitate non-obligatory replies. Primary outcomes will be changes in the GDS scores that are administered to all elderly inhabitants of the community every year as part of annual health checks. Secondary outcomes include quality of life as measured by a visual analogue scale, and self-rated basic and advanced activities of daily living. We will also examine the subjective sense of effectiveness of the intervention, recollection of the number of intervention mailings received, and the number of mailed replies as the index of the acceptability of the postcard intervention. The time × group interaction for two consecutive years will be analyzed using a generalized linear mixed model. To detect an effect size of 0.5 at alpha error of 0.05 and statistical power of 0.80, 63 participants per group are required. Based on an estimated consent and dropout rate of 70%, a total of 180 subjects will be recruited. Trial registration UMIN000010529 PMID:23837527

Pediatric Clinical Trials Conducted in South Korea from 2006 to 2015: An Analysis of the South Korean Clinical Research Information Service, US ClinicalTrials.gov and European Clinical Trials Registries.

PubMed

Choi, Sheung-Nyoung; Lee, Ji-Hyun; Song, In-Kyung; Kim, Eun-Hee; Kim, Jin-Tae; Kim, Hee-Soo

2017-12-01

The status of pediatric clinical trials performed in South Korea in the last decade, including clinical trials of drugs with unapproved indications for children, has not been previously examined. The aim was to provide information regarding the current state of pediatric clinical trials and create a basis for future trials performed in South Korea by reviewing three databases of clinical trials registrations. We searched for pediatric clinical studies (participants <18 years old) conducted in South Korea between 2006 and 2015 registered on the Clinical Research Information Service (CRIS), ClinicalTrials.gov, and the European Clinical Trials Registry (EuCTR). Additionally, we reviewed whether unapproved indications were involved in each trial by comparing the trials with a list of authorized trials provided by the Ministry of Food and Drug Safety (MFDS). The primary and secondary outcomes were to determine the change in number of pediatric clinical trials with unapproved indications over time and to assess the status of unauthorized pediatric clinical trials from the MFDS and the publication of articles after these clinical trials, respectively. We identified 342 clinical studies registered in the CRIS (n = 81), ClinicalTrials.gov (n = 225), and EuCTR (n = 36), of which 306 were reviewed after excluding duplicate registrations. Among them, 181 studies were interventional trials dealing with drugs and biological agents, of which 129 (71.3%) involved unapproved drugs. Of these 129 trials, 107 (82.9%) were authorized by the MFDS. Pediatric clinical trials in South Korea aiming to establish the safety and efficacy of drugs in children are increasing; however, non-MFDS-authorized studies remain an issue.

Conducting clinical trials in Singapore.

PubMed

Woo, K T

1999-04-01

All clinical trials in Singapore will now have to conform to the Medicines (Clinical Trials) Amended Regulations 1998 and the Singapore Good Clinical Practice (GCP) Guidelines 1998. The Medical Clinical Research Committee (MCRC) has been established to oversee the conduct of clinical drug trials in Singapore and together with the legislations in place, these will ensure that clinical trials conducted in Singapore are properly controlled and the well-being of trial subjects are safe guarded. All clinical drug trials require a Clinical Trial Certificate from the MCRC before the trial can proceed. The hospital ethics committee (EC) vets the application for a trial certificate before it is sent to MCRC. The drug company sponsoring the trial has to indemnify the trial investigators and the hospital for negligence arising from the trial. The MCRC, apart from ensuring the safety of trial subjects, has to provide continuing review of the clinical trial and monitors adverse events in the course of the trial. The EC will conduct continuing review of clinical trials. When a non-drug clinical trial is carried out, the EC will ensure that the proposed protocol addresses ethical concerns and meets regulatory requirements for such trials. There is great potential for pharmaceutical Research & Development (R&D) in Singapore. We must develop our skills and infrastructure in clinical trials to enable Singapore to be a regional hub for R&D of drugs in Asia.

Searching for cures: Inner-city and rural patients' awareness and perceptions of cancer clinical trials.

PubMed

Geana, Mugur; Erba, Joseph; Krebill, Hope; Doolittle, Gary; Madhusudhana, Sheshadri; Qasem, Abdulraheem; Malomo, Nikki; Sharp, Denise

2017-03-01

Fewer than 5% of cancer patients participate in clinical trials, making it challenging to test new therapies or interventions for cancer. Even within that small number, patients living in inner-city and rural areas are underrepresented in clinical trials. This study explores cancer patients' awareness and perceptions of cancer clinical trials, as well as their perceptions of patient-provider interactions related to discussing cancer clinical trials in order to improve accrual in cancer clinical trials. Interviews with 66 former and current in inner-city and rural cancer patients revealed a lack of awareness and understanding about clinical trials, as well as misconceptions about what clinical trials entail. Findings also revealed that commercials and television shows play a prominent role in forming inner-city and rural patients' attitudes and/or misconceptions about clinical trials. However, rural patients were more likely to hold unfavorable views about clinical trials than inner-city patients. Patient-provider discussions emerged as being crucial for increasing awareness of clinical trials among patients and recruiting them to trials. Findings from this study will inform communication strategies to enhance recruitment to cancer clinical trials by increasing awareness and countering misconceptions about clinical trials.

FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: the randomized phase III EAGLE study†

PubMed Central

Iwamoto, S.; Takahashi, T.; Tamagawa, H.; Nakamura, M.; Munemoto, Y.; Kato, T.; Hata, T.; Denda, T.; Morita, Y.; Inukai, M.; Kunieda, K.; Nagata, N.; Kurachi, K.; Ina, K.; Ooshiro, M.; Shimoyama, T.; Baba, H.; Oba, K.; Sakamoto, J.; Mishima, H.

2015-01-01

Background A targeted agent combined with chemotherapy is the standard treatment in patients with metastatic colorectal cancer (mCRC). The present phase III study was conducted to compare two doses of bevacizumab combined with irinotecan, 5-fluorouracil/leucovorin (FOLFIRI) in the second-line setting after first-line therapy with bevacizumab plus oxaliplatin-based therapy. Patients and methods Patients were randomly assigned to receive FOLFIRI plus bevacizumab 5 or 10 mg/kg in 2-week cycles until disease progression. The primary end point was progression-free survival (PFS), and secondary end points included overall survival (OS), time to treatment failure (TTF), and safety. Results Three hundred and eighty-seven patients were randomized between September 2009 and January 2012 from 100 institutions in Japan. Baseline patient characteristics were well balanced between the two groups. Efficacy was evaluated in 369 patients (5 mg/kg, n = 181 and 10 mg/kg, n = 188). Safety was evaluated in 365 patients (5 mg/kg, n = 180 and 10 mg/kg, n = 185). The median PFS was 6.1 versus 6.4 months (hazard ratio, 0.95; 95% confidence interval [CI] 0.75–1.21; P = 0.676), and median TTF was 5.2 versus 5.2 months (hazard ratio, 1.01; 95% CI 0.81–1.25; P = 0.967), respectively, for the bevacizumab 5 and 10 mg/kg groups. Follow-up of OS is currently ongoing. Adverse events, including hypertension and hemorrhage, occurred at similar rates in both groups. Conclusion Bevacizumab 10 mg/kg plus FOLFIRI as the second-line treatment did not prolong PFS compared with bevacizumab 5 mg/kg plus FOLFIRI in patients with mCRC. If bevacizumab is continued after first-line therapy in mCRC, a dose of 5 mg/kg is appropriate for use as second-line treatment. Clinical trial identifier UMIN000002557. PMID:25908603

Risk factors for post-colorectal endoscopic submucosal dissection (ESD) coagulation syndrome: a multicenter, prospective, observational study

PubMed Central

Arimoto, Jun; Higurashi, Takuma; Kato, Shingo; Fuyuki, Akiko; Ohkubo, Hidenori; Nonaka, Takashi; Yamaguchi, Yoshikazu; Ashikari, Keiichi; Chiba, Hideyuki; Goto, Shungo; Taguri, Masataka; Sakaguchi, Takashi; Atsukawa, Kazuhiro; Nakajima, Atsushi

2018-01-01

Background and study aims  Colorectal cancer (CRC) is one of the most common neoplasms and endoscopic submucosal dissection (ESD) is an effective treatment for early-stage CRC. However, it has been observed that patients undergoing ESD often complain of pain, even if ESD has been successfully performed. Risk factors for such pain still remain unknown. The aim of this study was to explore the risk factors for post-colorectal ESD coagulation syndrome (PECS). Patients and methods  This was a prospective multicenter observational trial (UMIN000016781) conducted in 106 of 223 patients who underwent ESD between March 2015 and April 2016. We investigated age, sex, tumor location, ESD operation time, lesion size, duration of hospitalization, and frequency of PECS. We defined PECS as local abdominal pain (evaluated on a visual analogue scale) in the region corresponding to the site of the ESD that occurred within 4 days of the procedure. Results  PECS occurred in 15/106 (14.2 %), and 10 were women ( P  = 0.01, OR: 7.74 [1.6 – 36.4]), 7 had lesions in the cecum ( P  < 0.001, OR: 20.6 [3.7 – 115.2]), and 9 in whom ESD operation time was > 90 min ( P  = 0.002, OR: 10.3 [2.4 – 44.6]). Frequency of deviation from the prescribed clinical path was significantly higher (47 % [7/15] vs. 2 % [2/91], P  < 0.001, OR: 38.9 [6.9 – 219.6]), and hospital stay was significantly longer in the PECS group.  Conclusions  Female gender, location of lesion in the cecum, and ESD operation time > 90 minutes were significant risk factors independent of PECS. These findings are important to management of PECS.  PMID:29527556

Agreement among Goldmann applanation tonometer, iCare, and Icare PRO rebound tonometers; non-contact tonometer; and Tonopen XL in healthy elderly subjects.

PubMed

Kato, Yoshitake; Nakakura, Shunsuke; Matsuo, Naoko; Yoshitomi, Kayo; Handa, Marina; Tabuchi, Hitoshi; Kiuchi, Yoshiaki

2018-04-01

To evaluate the inter-device agreement among the Goldmann applanation tonometer (GAT), iCare and Icare PRO rebound tonometers, non-contact tonometer (NCT), and Tonopen XL tonometer. Sixty healthy elderly subjects were enrolled. The intraocular pressure (IOP) in each subject's right eye was measured thrice using each of the five tonometers. Intra-device agreement was evaluated by calculating intraclass correlation coefficients (ICCs). Inter-device agreement was evaluated by ICC and Bland-Altman analyses. ICCs for intra-device agreement for each tonometer were >0.8. IOP as measured by iCare (mean ± SD, 11.6 ± 2.5 mmHg) was significantly lower (p < 0.05) than that measured by GAT (14.0 ± 2.8 mmHg), NCT (13.6 ± 2.5 mmHg), Tonopen XL (13.7 ± 4.1 mmHg), and Icare PRO (12.6 ± 2.2 mmHg; Bonferroni test). There was no significant difference in mean IOP among GAT, NCT, and Tonopen XL. Regarding inter-device agreement, ICC was lower between Tonopen XL and other tonometers (all ICCs < 0.4). However, ICCs of GAT, iCare, Icare PRO, and NCT showed good agreement (0.576-0.700). The Bland-Altman analysis revealed that the width of the 95% limits of agreement was larger between the Tonopen XL and the other tonometers ranged from 14.94 to 16.47 mmHg. Among the other tonometers, however, the widths of 95% limits of agreement ranged from 7.91 to 9.24 mmHg. There was good inter-device agreement among GAT, rebound tonometers, and NCT. Tonopen XL shows the worst agreement with the other tonometers; therefore, we should pay attention to its' respective IOP. Japan Clinical Trials Register; number: UMIN000011544.

Esophageal stenosis and the Glasgow Prognostic Score as independent factors of poor prognosis for patients with locally advanced unresectable esophageal cancer treated with chemoradiotherapy (exploratory analysis of JCOG0303).

PubMed

Okuno, Tatsuya; Wakabayashi, Masashi; Kato, Ken; Shinoda, Masayuki; Katayama, Hiroshi; Igaki, Hiroyasu; Tsubosa, Yasuhiro; Kojima, Takashi; Okabe, Hiroshi; Kimura, Yusuke; Kawano, Tatsuyuki; Kosugi, Shinichi; Toh, Yasushi; Kato, Hoichi; Nakamura, Kenichi; Fukuda, Haruhiko; Ishikura, Satoshi; Ando, Nobutoshi; Kitagawa, Yuko

2017-12-01

The aim of this study was to investigate the possible prognostic factors and predictive accuracy of the Glasgow Prognostic Score (GPS) for patients with unresectable locally advanced esophageal squamous cell carcinoma (LAESCC) treated with chemoradiotherapy. One hundred forty-two patients were enrolled in JCOG0303 and assigned to the standard cisplatin and 5-fluorouracil (PF)-radiotherapy (RT) group or the low-dose PF-RT group. One hundred thirty-one patients with sufficient data were included in this analysis. A Cox regression model was used to analyze the prognostic factors of patients with unresectable LAESCC treated with PF-RT. The GPS was classified based on the baseline C-reactive protein (CRP) and serum albumin levels. Patients with CRP ≤1.0 mg/dL and albumin ≥3.5 g/dL were classified as GPS0. If only CRP was increased or only albumin was decreased, the patients were classified as GPS1, and the patients with CRP >1.0 mg/dL and albumin <3.5 g/dL were classified as GPS2. The patients' backgrounds were as follows: median age (range), 62 (37-75); male/female, 119/12; ECOG PS 0/1/2, 64/65/2; and clinical stage (UICC 5th) IIB/III/IVA/IVB, 3/75/22/31. Multivariable analyses indicated only esophageal stenosis as a common factor for poor prognosis. In addition, overall survival tended to decrease according to the GPS subgroups (median survival time (months): GPS0/GPS1/GPS2 16.1/14.9/8.7). Esophageal stenosis was identified as a candidate stratification factor for randomized trials of unresectable LAESCC patients. Furthermore, GPS represents a prognostic factor for LAESCC patients treated with chemoradiotherapy. UMIN000000861.

Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: A double-blind, randomized study

PubMed Central

Ito, Hiroaki; Iida, Mitsuo; Matsumoto, Takayuki; Suzuki, Yasuo; Sasaki, Hidetaka; Yoshida, Toyomitsu; Takano, Yuichi; Hibi, Toshifumi

2010-01-01

Background: Mesalamine is the first-line drug for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two mesalamine formulations for the induction of remission in patients with UC. Methods: In a multicenter, double-blind, randomized study, 229 patients with mild-to-moderate active UC were assigned to 4 groups: 66 and 65 received a pH-dependent release formulation of 2.4 g/day (pH-2.4 g) or 3.6 g/day (pH-3.6 g), respectively; 65 received a time-dependent release formulation of 2.25 g/day (Time-2.25 g), and 33 received placebo (Placebo). The drugs were administered three times daily for eight weeks. The primary endpoint was a decrease in the UC disease activity index (UC-DAI). Results: In the full analysis set (n = 225) the decrease in UC-DAI in each group was 1.5 in pH-2.4 g, 2.9 in pH-3.6 g, 1.3 in Time-2.25 g and 0.3 in Placebo, respectively. These results demonstrate the superiority of pH-3.6 g over Time-2.25 g (P = 0.003) and the noninferiority of pH-2.4 g to Time-2.25 g. Among the patients with proctitis-type UC, a significant decrease in UC-DAI was observed in pH-2.4 g and pH-3.6 g as compared to Placebo, but not in Time-2.25 g. No differences were observed in the safety profiles. Conclusions: Higher dose of the pH-dependent release formulation was more effective for induction of remission in patients with mild-to-moderate active UC. Additionally, the pH-dependent release formulation was preferable to the time-dependent release formulation for patients with proctitis-type UC (UMIN Clinical Trials Registry, no. C000000288). (Inflamm Bowel Dis 2010) PMID:20049950

Direct comparison of two different mesalamine formulations for the maintenance of remission in patients with ulcerative colitis: A double-blind, randomized study

PubMed Central

Ito, Hiroaki; Iida, Mitsuo; Matsumoto, Takayuki; Suzuki, Yasuo; Aida, Yoshiyuki; Yoshida, Toyomitsu; Takano, Yuichi; Hibi, Toshifumi

2010-01-01

Background: Mesalamine has been used as the first-line medication for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two different mesalamine formulations in the maintenance of remission in patients with UC. Methods: In a multicenter, double-blind, randomized study, 131 patients with quiescent UC were assigned to two groups: 65 to receive a pH-dependent release formulation of mesalamine at 2.4 g/day (pH-2.4 g) and 66 to receive a time-dependent release formulation of mesalamine at 2.25 g/day (Time-2.25 g). Both formulations were administered three times daily for 48 weeks. The primary endpoint was the proportion of patients without bloody stools. Results: In the full analysis set (n = 130), the proportion of patients without bloody stools was 76.9% in the pH-2.4 g and 69.2% in the Time-2.25 g, demonstrating the noninferiority of pH-2.4 g to Time-2.25 g. No statistically significant difference in time to bloody stools was found between the two formulations (P = 0.27, log-rank test), but the time to bloody stools tended to be longer in pH-2.4 g compared to Time-2.25 g, and a similar trend was observed with regard to the time to relapse. No differences were observed between the safety profiles of the two formulations. Conclusions: The pH- and time-dependent release of mesalamine formulations were similarly safe and effective. Interestingly, the remission phase tended to be longer in the group that received the pH-dependent formulation compared to the group that received the time-dependent formulation (UMIN Clinical Trials Registry, no. C000000289). (Inflamm Bowel Dis 2010) PMID:20049949

Rebamipide improves chronic inflammation in the lesser curvature of the corpus after Helicobacter pylori eradication: a multicenter study.

PubMed

Kamada, Tomoari; Sato, Motonori; Tokutomi, Tadashi; Watanabe, Tetsuo; Murao, Takahisa; Matsumoto, Hiroshi; Manabe, Noriaki; Ito, Masanori; Tanaka, Shinji; Inoue, Kazuhiko; Shiotani, Akiko; Akiyama, Takashi; Hata, Jiro; Haruma, Ken

2015-01-01

Background and Aim. Although many epidemiologic studies have shown that Helicobacter pylori eradication has prophylactic effects on gastric cancer, it does not completely eliminate the risk of gastric cancer. We aimed to investigate the changes in histological gastritis in patients receiving rebamipide treatment after H. pylori eradication. Methods. 206 patients who had undergone H. pylori eradication were evaluated. Of these, 169 patients who achieved successful eradication were randomly allocated to 2 groups: the rebamipide group (n = 82) and the untreated group (n = 87). The primary endpoints were histopathological findings according to the updated Sydney system at the start of the study and after 1 year. Results. Final assessment for histological gastritis was possible in 50 cases from the rebamipide group and 53 cases from the untreated group. The activity and atrophy improved in both the rebamipide and untreated groups, and no significant intergroup differences were observed. Chronic inflammation affecting the lesser curvature of the corpus was significantly improved in the rebamipide group compared to in the untreated group (1.12 ± 0.08 versus 1.35 ± 0.08; P = 0.043). Conclusions. Rebamipide treatment after H. pylori eradication alleviated chronic inflammation in the lesser curvature of the corpus compared to that in the untreated group. This trial is registered with UMIN000002369.

A Prospective Randomized Controlled Trial of AJG522 versus Standard PEG + E as Bowel Preparation for Colonoscopy

PubMed Central

Sagawa, Toshihiko; Tomizawa, Taku; Mizuide, Masafumi; Yasuoka, Hidetoshi; Shimoyama, Yasuyuki; Kakizaki, Satoru; Kawamura, Osamu; Kusano, Motoyasu; Yamada, Masanobu

2015-01-01

Polyethylene glycol- (PEG-) based bowel preparations for colonoscopies are often poorly tolerated due to the large volumes of fluid intake required. We compared low-volume “modified” PEG + ascorbic acid (AJG522) with standard PEG with electrolytes (PEG + E) in addition to a stimulant laxative and an agent to improve bowel function for the bowel cleansing before colonoscopy to evaluate its efficacy, safety, and acceptability. Outpatients scheduled to undergo colonoscopy were randomized to receive either AJG522 or PEG + E. Bowel cleansing conditions were assessed via macroscopic fecal findings by blinded and independent investigators. A survey of the patients' feedback regarding the preparation was conducted by questionnaire. Successful cleansing was achieved in all cases, except for 4 cases in the PEG + E group, at 3 hours after taking the preparation. The fecal properties were significantly clearer in the AJG522 group than in the PEG + E group at 2 hours after taking each preparation (P = 0.013). Although the total liquid volume of the bowel preparation was not reduced, the AJG522 preparation could significantly reduce the required volume of the preparation (P < 0.0001). Moreover, the patients in the AJG522 group had better acceptability (P = 0.010). There were no significant differences in the safety profiles between groups (UMIN000013892). PMID:25688357

Impact of a clinical trial initiative on clinical trial enrollment in a multidisciplinary prostate cancer clinic.

PubMed

Madsen, Lydia T; Kuban, Deborah A; Choi, Seungtaek; Davis, John W; Kim, Jeri; Lee, Andrew K; Domain, Delora; Levy, Larry; Pisters, Louis L; Pettaway, Curtis A; Ward, John F; Logothetis, Christopher; Hoffman, Karen E

2014-07-01

Clinical oncology trials are hampered by low accrual rates, with fewer than 5% of adult patients with cancer treated on study. Clinical trial enrollment was evaluated at The University of Texas MD Anderson Cancer Center's Multidisciplinary Prostate Cancer Clinic (MPCC) to assess whether a clinical trial initiative, introduced in 2006, impacted enrollment. The trial initiative included posting trial-specific information in clinic, educating patients about appropriate clinical trial options during the treatment recommendation discussion, and providing patients with trial-specific educational information. The investigators evaluated the frequency of clinical trial enrollment for men with newly diagnosed prostate cancer seen in the MPCC from 2004 to 2008. Logistic regression evaluated the impact of patient characteristics and the clinical trial initiative on trial enrollment. The median age of the 1370 men was 64 years; 32% had low-risk, 49% had intermediate-risk, and 19% had high-risk disease. Overall, 74% enrolled in at least one trial and 29% enrolled in more than one trial. Trial enrollment increased from 39% before the initiative (127/326) to 84% (880/1044) after the trial initiative. Patient enrollment increased in laboratory studies (from 25% to 80%), quality-of-life studies (from 10% to 26%), and studies evaluating investigational treatments and systemic agents (from 6% to 15%) after the trial initiative. In multivariate analysis, younger men (P<.001) and men seen after implementation of the clinical trial initiative (P<.001) were more likely to enroll in trials. Clinical trial enrollment in the MPCC was substantially higher than that seen nationally in adult patients with cancer, and enrollment rates increased after the introduction of a clinical trial initiative. Copyright © 2014 by the National Comprehensive Cancer Network.

Does the behavioural type-specific approach for type 2 diabetes promote changes in lifestyle? Protocol of a cluster randomised trial in Japan

PubMed Central

Adachi, Misa; Yamaoka, Kazue; Watanabe, Mariko; Nemoto, Asuka; Tango, Toshiro

2017-01-01

Introduction Type 2 diabetes (T2D) is a significant problem, and lifestyle modifications including self-management are important. We have developed a structured individual-based lifestyle education (SILE) programme for T2D. With attention now being paid to techniques to change behaviour, we recently developed a behavioural type-specific SILE (BETSILE) programme. We aimed to evaluate the effectiveness of the BETSILE programme compared with the SILE programme for reducing glycated haemoglobin (HbA1c) in patients with T2D and special behavioural types by a cluster randomised controlled trial. Methods and analysis This is a 6-month cluster randomised controlled trial with two intervention arms (BETSILE vs SILE) provided in a medical care setting by randomising registered dietitians for patients with T2D aged 20–79 years. Patients’ behavioural types were classified into four types (BT1 to BT4) using an assessment sheet. We will perform independent trials for BT1 and BT2. The primary endpoint is a change from the baseline HbA1c value at 6 months. Differences between the SILE and BETSILE groups will be primarily analysed following the intention-to-treat principle. Crude and multivariate adjusted effects will be examined after adjusting for covariates, using a general linear mixed-effects model for continuous variables and a logistic regression mixed-effects model for dichotomous variables. Sample sizes needed were calculated assuming effect sizes of 0.42 and 0.33 for BT1 and BT2, respectively, an intraclass correlation of 0.02, a significance level of 5% (two-sided), a power of 80%, and equal allocation of clusters to the two arms, with each cluster having three BT1 patients for the SILE and BETSILE arms and six BT2 patients for the SILE and BETSILE arms. We will need 16 dietitians for each arm, and a total 288 patients will be required. Ethics and dissemination This study has been approved by the Medical Ethical Committee of Teikyo University (No.15–222). Findings will be disseminated widely through peer-reviewed publications, etc. Trial registration number UMIN 000023087; Pre-results. PMID:29070640

Patient Navigation As a Model to Increase Participation of African Americans in Cancer Clinical Trials.

PubMed

Fouad, Mona N; Acemgil, Aras; Bae, Sejong; Forero, Andres; Lisovicz, Nedra; Martin, Michelle Y; Oates, Gabriela R; Partridge, Edward E; Vickers, Selwyn M

2016-06-01

Less than 10% of patients enrolled in clinical trials are minorities. The patient navigation model has been used to improve access to medical care but has not been evaluated as a tool to increase the participation of minorities in clinical trials. The Increasing Minority Participation in Clinical Trials project used patient navigators (PNs) to enhance the recruitment of African Americans for and their retention in therapeutic cancer clinical trials in a National Cancer Institute-designated comprehensive cancer center. Lay individuals were hired and trained to serve as PNs for clinical trials. African American patients potentially eligible for clinical trials were identified through chart review or referrals by clinic nurses, physicians, and social workers. PNs provided two levels of services: education about clinical trials and tailored support for patients who enrolled in clinical trials. Between 2007 and 2014, 424 African American patients with cancer were referred to the Increasing Minority Participation in Clinical Trials project. Of those eligible for a clinical trial (N = 378), 304 (80.4%) enrolled in a trial and 272 (72%) consented to receive patient navigation support. Of those receiving patient navigation support, 74.5% completed the trial, compared with 37.5% of those not receiving patient navigation support. The difference in retention rates between the two groups was statistically significant (P < .001). Participation of African Americans in therapeutic cancer clinical trials increased from 9% to 16%. Patient navigation for clinical trials successfully retained African Americans in therapeutic trials compared with non-patient navigation trial participation. The model holds promise as a strategy to reduce disparities in cancer clinical trial participation. Future studies should evaluate it with racial/ethnic minorities across cancer centers. Copyright © 2016 by American Society of Clinical Oncology.

Clinical Trials in Dentistry: A Cross-sectional Analysis of World Health Organization-International Clinical Trial Registry Platform.

PubMed

Sivaramakrishnan, Gowri; Sridharan, Kannan

2016-06-01

Clinical trials are the back bone for evidence-based practice (EBP) and recently EBP has been considered the best source of treatment strategies available. Clinical trial registries serve as databases of clinical trials. As regards to dentistry in specific data on the number of clinical trials and their quality is lacking. Hence, the present study was envisaged. Clinical trials registered in WHO-ICTRP (http://apps.who.int/trialsearch/AdvSearch.aspx) in dental specialties were considered. The details assessed from the collected trials include: Type of sponsors; Health condition; Recruitment status; Study design; randomization, method of randomization and allocation concealment; Single or multi-centric; Retrospective or prospective registration; and Publication status in case of completed studies. A total of 197 trials were identified. Maximum trials were from United States (n = 30) and United Kingdom (n = 38). Seventy six trials were registered in Clinical Trials.gov, 54 from International Standards of Reporting Clinical Trials, 13 each from Australia and New Zealand Trial Register and Iranian Registry of Clinical Trials, 10 from German Clinical Trial Registry, eight each from Brazilian Clinical Trial Registry and Nederland's Trial Register, seven from Japan Clinical Trial Registry, six from Clinical Trial Registry of India and two from Hong Kong Clinical Trial Registry. A total of 78.7% studies were investigator-initiated and 64% were completed while 3% were terminated. Nearly four-fifths of the registered trials (81.7%) were interventional studies of which randomized were the large majority (94.4%) with 63.2% being open label, 20.4% using single blinding technique and 16.4% were doubled blinded. The number, methodology and the characteristics of clinical trials in dentistry have been noted to be poor especially in terms of being conducted multi-centrically, employing blinding and the method for randomization and allocation concealment. More emphasis has to be laid down on the quality of trials being conducted in order to provide justice in the name of EBP. Copyright © 2016 Elsevier Inc. All rights reserved.

Feasibility of Extracting Key Elements from ClinicalTrials.gov to Support Clinicians' Patient Care Decisions.

PubMed

Kim, Heejun; Bian, Jiantao; Mostafa, Javed; Jonnalagadda, Siddhartha; Del Fiol, Guilherme

2016-01-01

Motivation: Clinicians need up-to-date evidence from high quality clinical trials to support clinical decisions. However, applying evidence from the primary literature requires significant effort. Objective: To examine the feasibility of automatically extracting key clinical trial information from ClinicalTrials.gov. Methods: We assessed the coverage of ClinicalTrials.gov for high quality clinical studies that are indexed in PubMed. Using 140 random ClinicalTrials.gov records, we developed and tested rules for the automatic extraction of key information. Results: The rate of high quality clinical trial registration in ClinicalTrials.gov increased from 0.2% in 2005 to 17% in 2015. Trials reporting results increased from 3% in 2005 to 19% in 2015. The accuracy of the automatic extraction algorithm for 10 trial attributes was 90% on average. Future research is needed to improve the algorithm accuracy and to design information displays to optimally present trial information to clinicians.

Survival results of a randomised two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of S-1 plus cisplatin (SC) and paclitaxel plus cisplatin (PC) followed by D2 gastrectomy for resectable advanced gastric cancer.

PubMed

Yoshikawa, Takaki; Morita, Satoshi; Tanabe, Kazuaki; Nishikawa, Kazuhiro; Ito, Yuichi; Matsui, Takanori; Fujitani, Kazumasa; Kimura, Yutaka; Fujita, Junya; Aoyama, Toru; Hayashi, Tsutomu; Cho, Haruhiko; Tsuburaya, Akira; Miyashita, Yumi; Sakamoto, Junichi

2016-07-01

The prognosis for stage III gastric cancer is unsatisfactory by D2 gastrectomy and S-1 adjuvant chemotherapy. Both S-1 plus cisplatin (SC) and paclitaxel plus cisplatin (PC) are promising regimens as neoadjuvant chemotherapy; however, the optimal duration remains unclear. In this 2×2 randomised phase II trial, stage III gastric cancer patients, those with a prognosis corresponding to stage III, and macroscopically resectable stage IV cases were randomised to two or four courses of S-1 (80 mg/m(2) for 21 d with 1 week rest)/cisplatin (60 mg/m(2) at day 8) or PC (80 and 25 mg/m(2), respectively, on days 1, 8, and 15 with 1 week rest) as neoadjuvant chemotherapy. The primary end-point was the 3-year overall survival (OS). Between October 2009 and July 2011, 83 patients received 2 courses of SC (n=21), 4 courses of SC (n=20), 2 courses of PC (n=21) and 4 courses of PC (n=21). The 3-year OS was 60.9% for SC and 64.3% for PC and 64.3% for the two courses and 61.0% for the four courses. Subset analyses demonstrated no subgroup which showed any potential survival benefit by PC in comparison to SC or by four courses as in comparison to two courses. Two courses of SC as neoadjuvant chemotherapy are recommended as a test arm of a future phase III study for patients with locally advanced gastric cancer. UMIN-000002595. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial.

PubMed

Natsume, Osamu; Kabashima, Shigenori; Nakazato, Junko; Yamamoto-Hanada, Kiwako; Narita, Masami; Kondo, Mai; Saito, Mayako; Kishino, Ai; Takimoto, Tetsuya; Inoue, Eisuke; Tang, Julian; Kido, Hiroshi; Wong, Gary W K; Matsumoto, Kenji; Saito, Hirohisa; Ohya, Yukihiro

2017-01-21

Evidence is accumulating that early consumption is more beneficial than is delayed introduction as a strategy for primary prevention of food allergy. However, allergic reactions caused by early introduction of such solid foods have been a problematic issue. We investigated whether or not early stepwise introduction of eggs to infants with eczema combined with optimal eczema treatment would prevent egg allergy at 1 year of age. In this randomised, double-blind, placebo-controlled trial, we enrolled infants 4-5 months of age with eczema from two centres in Japan. Exclusion criteria were being born before 37 weeks of gestational age, experience of ingestion of hen's eggs or egg products, history of immediate allergic reaction to hen's eggs, history of non-immediate allergic reaction to a particular type of food, and complications of any severe disease. Infants were randomly assigned (block size of four; stratified by institution and sex) to early introduction of egg or placebo (1:1). Participants in the egg group consumed orally 50 mg of heated egg powder per day from 6 months to 9 months of age and 250 mg per day thereafter until 12 months of age. We aggressively treated participants' eczema at entry and maintained control without exacerbations throughout the intervention period. Participants and physicians were masked to assignment, and allocation was concealed. The primary outcome was the proportion of participants with hen's egg allergy confirmed by open oral food challenges at 12 months of age, assessed blindly by standardised methods, in all randomly allocated participants who received the intervention. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000008673. Between Sept 18, 2012, and Feb 13, 2015, we randomly allocated 147 participants (73 [50%] to the egg group and 74 [50%] to the placebo group). This trial was terminated on the basis of the results of the scheduled interim analysis of 100 participants, which showed a significant difference between the two groups (four [9%] of 47 participants had an egg allergy in the egg group vs 18 [38%] of 47 in the placebo group; risk ratio 0·222 [95% CI 0·081-0·607]; p=0·0012). In the primary analysis population, five (8%) of 60 participants had an egg allergy in the egg group compared with 23 (38%) of 61 in the placebo group (risk ratio 0·221 [0·090-0·543]; p=0·0001). The only difference in adverse events between groups was admissions to hospital (six [10%] of 60 in the egg group vs none in the placebo group; p=0·022). 19 acute events occurred in nine (15%) participants in the egg group versus 14 events in 11 (18%) participants in the placebo group after intake of the trial powder. Introduction of heated egg in a stepwise manner along with aggressive eczema treatment is a safe and efficacious way to prevent hen's egg allergy in high-risk infants. In this study, we developed a practical approach to overcome the second wave of the allergic epidemic caused by food allergy. Ministry of Health, Labour and Welfare, and National Centre for Child Health and Development, Japan. Copyright © 2017 Elsevier Ltd. All rights reserved.

An Ontology-based Architecture for Integration of Clinical Trials Management Applications

PubMed Central

Shankar, Ravi D.; Martins, Susana B.; O’Connor, Martin; Parrish, David B.; Das, Amar K.

2007-01-01

Management of complex clinical trials involves coordinated-use of a myriad of software applications by trial personnel. The applications typically use distinct knowledge representations and generate enormous amount of information during the course of a trial. It becomes vital that the applications exchange trial semantics in order for efficient management of the trials and subsequent analysis of clinical trial data. Existing model-based frameworks do not address the requirements of semantic integration of heterogeneous applications. We have built an ontology-based architecture to support interoperation of clinical trial software applications. Central to our approach is a suite of clinical trial ontologies, which we call Epoch, that define the vocabulary and semantics necessary to represent information on clinical trials. We are continuing to demonstrate and validate our approach with different clinical trials management applications and with growing number of clinical trials. PMID:18693919

The Characteristics of TCM Clinical Trials: A Systematic Review of ClinicalTrials.gov.

PubMed

Chen, Junchao; Huang, Jihan; Li, Jordan V; Lv, Yinghua; He, Yingchun; Zheng, Qingshan

2017-01-01

The aim of this review is to characterize current status of global TCM clinical trials registered in ClinicalTrials.gov. We examined all the trials registered within ClinicalTrials.gov up to 25 September 2015, focusing on study interventions to identify TCM-related trials, and extracted 1,270 TCM trials from the data set. Overall, 691 (54.4%) trials were acupuncture, and 454 (35.8%) trials were herbal medicines. Differences in TCM trial intervention types were also evident among the specific therapeutic areas. Among all trials, 55.7% that were small studies enrolled <100 subjects, and only 8.7% of completed studies had reported results of trials. As for the location, the United States was second to China in conducting the most TCM trials. This review is the first snapshot of the landscape of TCM clinical trials registered in ClinicalTrials.gov, providing the basis for treatment and prevention of diseases within TCM and offering useful information that will guide future research on TCM.

The Characteristics of TCM Clinical Trials: A Systematic Review of ClinicalTrials.gov

PubMed Central

Huang, Jihan; Li, Jordan V.; Lv, Yinghua; He, Yingchun

2017-01-01

Objective The aim of this review is to characterize current status of global TCM clinical trials registered in ClinicalTrials.gov. Methods We examined all the trials registered within ClinicalTrials.gov up to 25 September 2015, focusing on study interventions to identify TCM-related trials, and extracted 1,270 TCM trials from the data set. Results Overall, 691 (54.4%) trials were acupuncture, and 454 (35.8%) trials were herbal medicines. Differences in TCM trial intervention types were also evident among the specific therapeutic areas. Among all trials, 55.7% that were small studies enrolled <100 subjects, and only 8.7% of completed studies had reported results of trials. As for the location, the United States was second to China in conducting the most TCM trials. Conclusion This review is the first snapshot of the landscape of TCM clinical trials registered in ClinicalTrials.gov, providing the basis for treatment and prevention of diseases within TCM and offering useful information that will guide future research on TCM. PMID:29138646

Factors associated with reporting results for pulmonary clinical trials in ClinicalTrials.gov.

PubMed

Riley, Isaretta L; Boulware, L Ebony; Sun, Jie-Lena; Chiswell, Karen; Que, Loretta G; Kraft, Monica; Todd, Jamie L; Palmer, Scott M; Anderson, Monique L

2018-02-01

Background/aims The Food and Drug Administration Amendments Act mandates that applicable clinical trials report basic summary results to the ClinicalTrials.gov database within 1 year of trial completion or termination. We aimed to determine the proportion of pulmonary trials reporting basic summary results to ClinicalTrials.gov and assess factors associated with reporting. Methods We identified pulmonary clinical trials subject to the Food and Drug Administration Amendments Act (called highly likely applicable clinical trials) that were completed or terminated between 2008 and 2012 and reported results by September 2013. We estimated the cumulative percentage of applicable clinical trials reporting results by pulmonary disease category. Multivariable Cox regression modeling identified characteristics independently associated with results reporting. Results Of 1450 pulmonary highly likely applicable clinical trials, 380 (26%) examined respiratory neoplasms, 238 (16%) asthma, 175 (12%) chronic obstructive pulmonary disease, and 657 (45%) other respiratory diseases. Most (75%) were pharmaceutical highly likely applicable clinical trials and 71% were industry-funded. Approximately 15% of highly likely applicable clinical trials reported results within 1 year of trial completion, while 55% reported results over the 5-year study period. Earlier phase highly likely applicable clinical trials were less likely to report results compared to phase 4 highly likely applicable clinical trials (phases 1/2 and 2 (adjusted hazard ratio 0.41 (95% confidence interval: 0.31-0.54)), phases 2/3 and 3 (adjusted hazard ratio 0.55 (95% confidence interval: 0.42-0.72)) and phase not applicable (adjusted hazard ratio 0.43 (95% confidence interval: 0.29-0.63)). Pulmonary highly likely applicable clinical trials without Food and Drug Administration oversight were less likely to report results compared with those with oversight (adjusted hazard ratio 0.65 (95% confidence interval: 0.51-0.83)). Conclusion A total of 15% of pulmonary clinical highly likely applicable clinical trials report basic summary results to ClinicalTrials.gov within 1 year of trial completion. Strategies to improve reporting are needed within the pulmonary community.

Characteristics of clinical trials registered in ClinicalTrials.gov, 2007-2010.

PubMed

Califf, Robert M; Zarin, Deborah A; Kramer, Judith M; Sherman, Rachel E; Aberle, Laura H; Tasneem, Asba

2012-05-02

Recent reports highlight gaps between guidelines-based treatment recommendations and evidence from clinical trials that supports those recommendations. Strengthened reporting requirements for studies registered with ClinicalTrials.gov enable a comprehensive evaluation of the national trials portfolio. To examine fundamental characteristics of interventional clinical trials registered in the ClinicalTrials.gov database. A data set comprising 96,346 clinical studies from ClinicalTrials.gov was downloaded on September 27, 2010, and entered into a relational database to analyze aggregate data. Interventional trials were identified and analyses were focused on 3 clinical specialties-cardiovascular, mental health, and oncology-that together encompass the largest number of disability-adjusted life-years lost in the United States. Characteristics of registered clinical trials as reported data elements in the trial registry; how those characteristics have changed over time; differences in characteristics as a function of clinical specialty; and factors associated with use of randomization, blinding, and data monitoring committees (DMCs). The number of registered interventional clinical trials increased from 28,881 (October 2004-September 2007) to 40,970 (October 2007-September 2010), and the number of missing data elements has generally declined. Most interventional trials registered between 2007 and 2010 were small, with 62% enrolling 100 or fewer participants. Many clinical trials were single-center (66%; 24,788/37,520) and funded by organizations other than industry or the National Institutes of Health (NIH) (47%; 17,592/37,520). Heterogeneity in the reported methods by clinical specialty; sponsor type; and the reported use of DMCs, randomization, and blinding was evident. For example, reported use of DMCs was less common in industry-sponsored vs NIH-sponsored trials (adjusted odds ratio [OR], 0.11; 95% CI, 0.09-0.14), earlier-phase vs phase 3 trials (adjusted OR, 0.83; 95% CI, 0.76-0.91), and mental health trials vs those in the other 2 specialties. In similar comparisons, randomization and blinding were less frequently reported in earlier-phase, oncology, and device trials. Clinical trials registered in ClinicalTrials.gov are dominated by small trials and contain significant heterogeneity in methodological approaches, including reported use of randomization, blinding, and DMCs.

Feasibility of Extracting Key Elements from ClinicalTrials.gov to Support Clinicians’ Patient Care Decisions

PubMed Central

Kim, Heejun; Bian, Jiantao; Mostafa, Javed; Jonnalagadda, Siddhartha; Del Fiol, Guilherme

2016-01-01

Motivation: Clinicians need up-to-date evidence from high quality clinical trials to support clinical decisions. However, applying evidence from the primary literature requires significant effort. Objective: To examine the feasibility of automatically extracting key clinical trial information from ClinicalTrials.gov. Methods: We assessed the coverage of ClinicalTrials.gov for high quality clinical studies that are indexed in PubMed. Using 140 random ClinicalTrials.gov records, we developed and tested rules for the automatic extraction of key information. Results: The rate of high quality clinical trial registration in ClinicalTrials.gov increased from 0.2% in 2005 to 17% in 2015. Trials reporting results increased from 3% in 2005 to 19% in 2015. The accuracy of the automatic extraction algorithm for 10 trial attributes was 90% on average. Future research is needed to improve the algorithm accuracy and to design information displays to optimally present trial information to clinicians. PMID:28269867

What Are Clinical Trials? | NIH MedlinePlus the Magazine

MedlinePlus

... of this page please turn Javascript on. Feature: Clinical Trials What Are Clinical Trials? Past Issues / Fall 2010 Table of Contents ... conducted all the time. The Different Phases of Clinical Trials Clinical trials related to drugs are classified ...

ClinicalTrials.gov Turns 10! | NIH MedlinePlus the Magazine

MedlinePlus

... please turn Javascript on. Feature: Clinical Trials ClinicalTrials.gov Turns 10! Past Issues / Fall 2010 Table of ... and whom to contact for more information. ClinicalTrials.gov's Helpful Features ClinicalTrials.gov has many helpful consumer ...

Transparency and public accessibility of clinical trial information in Croatia: how it affects patient participation in clinical trials.

PubMed

Šolić, Ivana; Stipčić, Ana; Pavličević, Ivančica; Marušić, Ana

2017-06-15

Despite increased visibility of clinical trials through international trial registries, patients often remain uninformed of their existence, especially if they do not have access to adequate information about clinical research, including the language of the information. The aim of this study was to describe the context for transparency of clinical trials in Croatia in relation to countries in Central and Eastern Europe, and to assess how informed Croatian patients are about clinical trials and their accessibility. We assessed the transparency of clinical trials from the data available in the public domain. We also conducted an anonymous survey on a convenience sample of 257 patients visiting two family medicine offices or an oncology department in south Croatia, and members of national patients' associations. Despite legal provisions for transparency of clinical trials in Croatia, they are still not sufficiently visible in the public domain. Among countries from Central and Eastern Europe, Croatia has the fewest number of registered trials in the EU Clinical Trials Registry. 66% of the patients in the survey were aware of the existence of clinical trials but only 15% were informed about possibilities of participating in a trial. Although 58% of the respondents were willing to try new treatments, only 6% actually participated in a clinical trial. Only 2% of the respondents were aware of publicly available trial registries. Our study demonstrates that there is low transparency of clinical trials in Croatia, and that Croatian patients are not fully aware of clinical trials and the possibilities of participating in them, despite reported availability of Internet resources and good communication with their physicians. There is a need for active policy measures to increase the awareness of and access to clinical trials to patients in Croatia, particularly in their own language.

Adding value to clinical trial registries: insights from Australian Cancer Trials Online, a website for consumers.

PubMed

Dear, Rachel; Barratt, Alexandra; Askie, Lisa; McGeechan, Kevin; Arora, Sheena; Crossing, Sally; Currow, David; Tattersall, Martin

2011-02-01

Clinical trials registries are now operating in the USA, Europe, Australia, China, and India and more are planned. Trial registries could be an excellent source of information about clinical trials for patients and others affected by cancer as well as health care professionals, but may be difficult for patients to navigate and use. An opportunity arose in Australia to develop a consumer friendly cancer clinical trials website (Australian Cancer Trials Online (ACTO), www.australiancancertrials.gov.au) using an automated data feed from two large clinical trial registries. In this article, we describe aspects of this new website, and explore ways in which such a website may add value to clinical trial data which are already collected and held by trial registries. The development of ACTO was completed by a Web company working in close association with staff at the Australian New Zealand Clinical Trials Registry (ANZCTR), and with consumer representatives. Data for the website were sourced directly and only from clinical trial registries, thus avoiding the creation of an additional trials database. It receives an automated, daily data feed of newly registered cancer clinical trials from both the ANZCTR and Clinical Trials.gov. The development of ACTO exemplifies the advantage of a local clinical trial registry working with consumers to provide accessible information about cancer clinical trials to meet consumers' information needs. We found that the inclusion of a lay summary added substantial value for consumers, and recommend that consideration be given to adding a lay summary to the mandatory data items collected by all trial registries. Furthermore, improved navigation, decision support tools, and consistency in data collection between clinical trial registries will also enable consumer websites to provide additional value for users. Clinical trial registration is not compulsory in Australia. If the additional cancer items (including a lay summary) are not provided by registrants of cancer trials on ANZCTR, this can compromise the quality and usefulness of the data for the end-user, in this case consumers, as they may encounter gaps in the data. Expanding the World Health Organization Trial Registration Data Set to include this additional information, particularly the lay summary, would be valuable. A well-coordinated system of clinical trial registration is critical to the success of efforts to provide better access for all to inform about clinical trials.

What's in a title? An assessment of whether randomized controlled trial in a title means that it is one.

PubMed

Koletsi, Despina; Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

2012-06-01

In this study, we aimed to investigate whether studies published in orthodontic journals and titled as randomized clinical trials are truly randomized clinical trials. A second objective was to explore the association of journal type and other publication characteristics on correct classification. American Journal of Orthodontics and Dentofacial Orthopedics, European Journal of Orthodontics, Angle Orthodontist, Journal of Orthodontics, Orthodontics and Craniofacial Research, World Journal of Orthodontics, Australian Orthodontic Journal, and Journal of Orofacial Orthopedics were hand searched for clinical trials labeled in the title as randomized from 1979 to July 2011. The data were analyzed by using descriptive statistics, and univariable and multivariable examinations of statistical associations via ordinal logistic regression modeling (proportional odds model). One hundred twelve trials were identified. Of the included trials, 33 (29.5%) were randomized clinical trials, 52 (46.4%) had an unclear status, and 27 (24.1%) were not randomized clinical trials. In the multivariable analysis among the included journal types, year of publication, number of authors, multicenter trial, and involvement of statistician were significant predictors of correctly classifying a study as a randomized clinical trial vs unclear and not a randomized clinical trial. From 112 clinical trials in the orthodontic literature labeled as randomized clinical trials, only 29.5% were identified as randomized clinical trials based on clear descriptions of appropriate random number generation and allocation concealment. The type of journal, involvement of a statistician, multicenter trials, greater numbers of authors, and publication year were associated with correct clinical trial classification. This study indicates the need of clear and accurate reporting of clinical trials and the need for educating investigators on randomized clinical trial methodology. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Etoposide and cisplatin versus irinotecan and cisplatin in patients with limited-stage small-cell lung cancer treated with etoposide and cisplatin plus concurrent accelerated hyperfractionated thoracic radiotherapy (JCOG0202): a randomised phase 3 study.

PubMed

Kubota, Kaoru; Hida, Toyoaki; Ishikura, Satoshi; Mizusawa, Junki; Nishio, Makoto; Kawahara, Masaaki; Yokoyama, Akira; Imamura, Fumio; Takeda, Koji; Negoro, Shunichi; Harada, Masao; Okamoto, Hiroaki; Yamamoto, Nobuyuki; Shinkai, Tetsu; Sakai, Hiroshi; Matsui, Kaoru; Nakagawa, Kazuhiko; Shibata, Taro; Saijo, Nagahiro; Tamura, Tomohide

2014-01-01

Four cycles of etoposide plus cisplatin and accelerated hyperfractionated thoracic radiotherapy (AHTRT) is the standard of care for limited-stage small-cell lung cancer (SCLC). Irinotecan plus cisplatin significantly improved overall survival compared with etoposide plus cisplatin for extensive-stage SCLC. We compared these regimens for overall survival of patients with limited-stage SCLC. We did this phase 3 study in 36 institutions in Japan. Eligibility criteria included age 20-70 years, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and adequate organ functions. Eligible patients with previously untreated limited-stage SCLC received one cycle of etoposide plus cisplatin (intravenous etoposide 100 mg/m(2) on days 1-3; intravenous cisplatin 80 mg/m(2) on day 1) plus AHTRT (1.5 Gy twice daily, 5 days a week, total 45 Gy over 3 weeks). Patients without progressive disease following induction therapy were randomised (1:1 ratio, using a minimisation method with biased-coin assignment balancing on ECOG performance status [0 vs 1], response to induction chemoradiotherapy [complete response plus near complete response vs partial response and stable disease], and institution) to receive either three further cycles of consolidation etoposide plus cisplatin or irinotecan plus cisplatin (intravenous irinotecan 60 mg/m(2) on days 1, 8, 15; intravenous cisplatin 60 mg/m(2) on day 1). Patients, physicians, and investigators were aware of allocation. The primary endpoint was overall survival after randomisation; primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00144989, and the UMIN Clinical Trials Registry, number C000000095. 281 patients were enrolled between Sept 1, 2002, and Oct 2, 2006. After induction etoposide plus cisplatin and AHTRT, 258 patients were randomised to consolidation etoposide plus cisplatin (n=129) or irinotecan plus cisplatin (n=129). In the etoposide plus cisplatin group, median overall survival was 3.2 years (95% CI 2.4-4.1). In the irinotecan and cisplatin group, median overall survival was 2.8 years (95% CI 2.4-3.6); overall survival did not differ between the two groups (hazard ratio 1.09 [95% CI 0.80-1.46], one-sided stratified log-rank p=0.70). The most common adverse events of grade 3 or 4 were neutropenia (120 [95%] in the etoposide plus cisplatin group vs 101 [78%] in the irinotecan plus cisplatin group), anaemia (44 [35%] vs 50 [39%]), thrombocytopenia (26 [21%] vs six [5%]), febrile neutropenia (21 [17%] vs 18 [14%]), and diarrhoea (two [2%] vs 13 [10%]). There was one treatment-related adverse event leading to death in each group (radiation pneumonitis in the etoposide plus cisplatin group; brain infarction in the irinotecan plus cisplatin group). Four cycles of etoposide plus cisplatin and AHTRT should continue to be the standard of care for limited-stage SCLC. National Cancer Center and the Ministry of Health, Labour, and Welfare of Japan. Copyright © 2014 Elsevier Ltd. All rights reserved.

Poor reporting of scientific leadership information in clinical trial registers.

PubMed

Sekeres, Melanie; Gold, Jennifer L; Chan, An-Wen; Lexchin, Joel; Moher, David; Van Laethem, Marleen L P; Maskalyk, James; Ferris, Lorraine; Taback, Nathan; Rochon, Paula A

2008-02-20

In September 2004, the International Committee of Medical Journal Editors (ICMJE) issued a Statement requiring that all clinical trials be registered at inception in a public register in order to be considered for publication. The World Health Organization (WHO) and ICMJE have identified 20 items that should be provided before a trial is considered registered, including contact information. Identifying those scientifically responsible for trial conduct increases accountability. The objective is to examine the proportion of registered clinical trials providing valid scientific leadership information. We reviewed clinical trial entries listing Canadian investigators in the two largest international and public trial registers, the International Standard Randomized Controlled Trial Number (ISRCTN) register, and ClinicalTrials.gov. The main outcome measures were the proportion of clinical trials reporting valid contact information for the trials' Principal Investigator (PI)/Co-ordinating Investigator/Study Chair/Site PI, and trial e-mail contact address, stratified by funding source, recruiting status, and register. A total of 1388 entries (142 from ISRCTN and 1246 from ClinicalTrials.gov) comprised our sample. We found non-compliance with mandatory registration requirements regarding scientific leadership and trial contact information. Non-industry and partial industry funded trials were significantly more likely to identify the individual responsible for scientific leadership (OR = 259, 95% CI: 95-701) and to provide a contact e-mail address (OR = 9.6, 95% CI: 6.6-14) than were solely industry funded trials. Despite the requirements set by WHO and ICMJE, data on scientific leadership and contact e-mail addresses are frequently omitted from clinical trials registered in the two leading public clinical trial registers. To promote accountability and transparency in clinical trials research, public clinical trials registers should ensure adequate monitoring of trial registration to ensure completion of mandatory contact information fields identifying scientific leadership.

The state of infectious diseases clinical trials: a systematic review of ClinicalTrials.gov.

PubMed

Goswami, Neela D; Pfeiffer, Christopher D; Horton, John R; Chiswell, Karen; Tasneem, Asba; Tsalik, Ephraim L

2013-01-01

There is a paucity of clinical trials informing specific questions faced by infectious diseases (ID) specialists. The ClinicalTrials.gov registry offers an opportunity to evaluate the ID clinical trials portfolio. We examined 40,970 interventional trials registered with ClinicalTrials.gov from 2007-2010, focusing on study conditions and interventions to identify ID-related trials. Relevance to ID was manually confirmed for each programmatically identified trial, yielding 3570 ID trials and 37,400 non-ID trials for analysis. The number of ID trials was similar to the number of trials identified as belonging to cardiovascular medicine (n = 3437) or mental health (n = 3695) specialties. Slightly over half of ID trials were treatment-oriented trials (53%, vs. 77% for non-ID trials) followed by prevention (38%, vs. 8% in non-ID trials). ID trials tended to be larger than those of other specialties, with a median enrollment of 125 subjects (interquartile range [IQR], 45-400) vs. 60 (IQR, 30-160) for non-ID trials. Most ID studies are randomized (73%) but nonblinded (56%). Industry was the funding source in 51% of ID trials vs. 10% that were primarily NIH-funded. HIV-AIDS trials constitute the largest subset of ID trials (n = 815 [23%]), followed by influenza vaccine (n = 375 [11%]), and hepatitis C (n = 339 [9%]) trials. Relative to U.S. and global mortality rates, HIV-AIDS and hepatitis C virus trials are over-represented, whereas lower respiratory tract infection trials are under-represented in this large sample of ID clinical trials. This work is the first to characterize ID clinical trials registered in ClinicalTrials.gov, providing a framework to discuss prioritization, methodology, and policy.

The web of clinical trial registration obligations: have foreign clinical trials been caught?

PubMed

Hathaway, Carolyne R; Manthei, John R; Haas, J Ben; Meltzer, Elizabeth D

2009-01-01

The web of overlapping requirements, standards, recommendations and policies governing the conduct of clinical trials highlights the intense scrutiny of the ethical, data quality and public access issues raised by human trials that are conducted to demonstrate the safety and efficacy of medical products marketed in the United States. One relatively recent development is the requirement that sponsors register and make public information about their clinical trials and clinical trial results. These clinical trial registration requirements illustrate the interests of patients, providers and researchers in increased visibility, transparency and accessibility of clinical trials and the data they generate. These requirements, however, pose regulatory, logistical and practical hurdles for companies sponsoring clinical trials of drugs and medical devices.

Reporting discrepancies between the ClinicalTrials.gov results database and peer-reviewed publications.

PubMed

Hartung, Daniel M; Zarin, Deborah A; Guise, Jeanne-Marie; McDonagh, Marian; Paynter, Robin; Helfand, Mark

2014-04-01

ClinicalTrials.gov requires reporting of result summaries for many drug and device trials. To evaluate the consistency of reporting of trials that are registered in the ClinicalTrials.gov results database and published in the literature. ClinicalTrials.gov results database and matched publications identified through ClinicalTrials.gov and a manual search of 2 electronic databases. 10% random sample of phase 3 or 4 trials with results in the ClinicalTrials.gov results database, completed before 1 January 2009, with 2 or more groups. One reviewer extracted data about trial design and results from the results database and matching publications. A subsample was independently verified. Of 110 trials with results, most were industry-sponsored, parallel-design drug studies. The most common inconsistency was the number of secondary outcome measures reported (80%). Sixteen trials (15%) reported the primary outcome description inconsistently, and 22 (20%) reported the primary outcome value inconsistently. Thirty-eight trials inconsistently reported the number of individuals with a serious adverse event (SAE); of these, 33 (87%) reported more SAEs in ClinicalTrials.gov. Among the 84 trials that reported SAEs in ClinicalTrials.gov, 11 publications did not mention SAEs, 5 reported them as zero or not occurring, and 21 reported a different number of SAEs. Among 29 trials that reported deaths in ClinicalTrials.gov, 28% differed from the matched publication. Small sample that included earliest results posted to the database. Reporting discrepancies between the ClinicalTrials.gov results database and matching publications are common. Which source contains the more accurate account of results is unclear, although ClinicalTrials.gov may provide a more comprehensive description of adverse events than the publication. Agency for Healthcare Research and Quality.

Patient Engagement in Neurological Clinical Trials Design: A Conference Summary.

PubMed

Cobb, Enesha M; Meurer, William; Harney, Deneil; Silbergleit, Robert; Lake, Bray Patrick; Clark, Christina; Gipson, Debbie; Barsan, William

2015-12-01

The conference objectives included educating patients and advocates about clinical trials, educating the clinical research community about patient perspectives on participating in clinical trial design, and identifying strategies to increase participation in clinical trial design for neurological disorders. Observations were noted during a 1-day conference attended by patients, patient advocates, clinical trial staff, and investigators. The conference offered didactic sessions, small, and large group discussions. Conference participants were patients, patient advocates, clinical trial staff, students, and investigators interested in engaging patients in clinical trial design for neurological disorders. Conference participants were asked to consider lessons learned that could increase patient engagement in clinical trial design. We found that there is growing interest in including patients in the design of clinical trials for neurological disorders. Several themes emerged on how to move forward: networking; the multifaceted roles of advocates in research; training and education; creating patient-researcher partnerships; and clinical trials regulation issues. The conference provided a forum for dialogue regarding stakeholder engagement in the design of clinical trials for neurological disorders. This experience provides a template for replication and dissemination of this conference and informs next steps to accelerate the pathway from dialogue to action. © 2015 Wiley Periodicals, Inc.

Systematic review of interventional sickle cell trials registered in ClinicalTrials.gov.

PubMed

Lebensburger, Jeffrey D; Hilliard, Lee M; Pair, Lauren E; Oster, Robert; Howard, Thomas H; Cutter, Gary R

2015-12-01

The registry ClinicalTrials.gov was created to provide investigators and patients an accessible database of relevant clinical trials. To understand the state of sickle cell disease clinical trials, a comprehensive review of all 174 "closed," "interventional" sickle cell trials registered at ClinicalTrials.gov was completed in January 2015. The majority of registered sickle cell disease clinical trials listed an academic center as the primary sponsor and were an early phase trial. The primary outcome for sickle cell disease trials focused on pain (23%), bone marrow transplant (BMT) (13%), hydroxyurea (8%), iron overload (8%), and pulmonary hypertension (8%). A total of 52 trials were listed as terminated or withdrawn, including 25 (14% of all trials) terminated for failure to enroll participants. At the time of this review, only 19 trials uploaded results and 29 trials uploaded a manuscript in the ClinicalTrials.gov database. A systematic review of pubmed.gov revealed that only 35% of sickle cell studies completed prior to 2014 resulted in an identified manuscript. In comparison, of 80 thalassemia trials registered in ClinicalTrials.gov, four acknowledged failure to enroll participants as a reason for trial termination or withdrawal, and 48 trials (60%) completed prior to 2014 resulted in a currently identified manuscript. ClinicalTrials.gov can be an important database for investigators and patients with sickle cell disease to understand the current available research trials. To enhance the validity of the website, investigators must update their trial results and upload trial manuscripts into the database. This study, for the first time, quantifies outcomes of sickle cell disease trials and provides support to the belief that barriers exist to successful completion, publication, and dissemination of sickle cell trial results. © The Author(s) 2015.

Comparison of serious adverse events posted at ClinicalTrials.gov and published in corresponding journal articles.

PubMed

Tang, Eve; Ravaud, Philippe; Riveros, Carolina; Perrodeau, Elodie; Dechartres, Agnes

2015-08-14

The reporting of serious adverse events (SAEs) in clinical trials is crucial to assess the balance between benefits and risks. For trials with serious adverse events posted at ClinicalTrials.gov, we assessed the consistency between SAEs posted at ClinicalTrials.gov and those published in corresponding journal articles. All records from ClinicalTrials.gov up to February 2014 were automatically exported in XML format. Among these, we identified all phase III or IV randomized controlled trials with at least one SAE posted. For a random sample of 300 of these trials, we searched for corresponding publications using MEDLINE via PubMed and extracted safety results from the articles. Among the sample of 300 trials with SAEs posted at ClinicalTrials.gov, 78 (26%) did not have a corresponding publication, and 20 (7%) had a publication that did not match the ClinicalTrials.gov record. For the 202 remaining trials, 26 published articles (13%) did not mention SAEs, 4 (2%) reported no SAEs, and 33 (16%) did not report the total number of SAEs per treatment group. Among the remaining 139 trials, for 44 (32%), the number of SAEs per group published did not match those posted at ClinicalTrials.gov. For 31 trials, the number of SAEs was greater at ClinicalTrials.gov than in the published article, with a difference ≥30 % for at least one group for 21. Only 33 trials (11%) had a publication reporting matching numbers of SAE and describing the type of SAE. Many trials with SAEs posted at ClinicalTrials.gov are not yet published, omit the reporting of these SAEs in corresponding publications, or report a discrepant number of SAEs as compared with ClinicalTrials.gov. These results underline the need to consult ClinicalTrials.gov for more information on serious harms.

Are You "Tilting at Windmills" or Undertaking a Valid Clinical Trial?

PubMed Central

Zariffa, Jose; Kramer, John L.K.

2011-01-01

In this review, several aspects surrounding the choice of a therapeutic intervention and the conduct of clinical trials are discussed. Some of the background for why human studies have evolved to their current state is also included. Specifically, the following questions have been addressed: 1) What criteria should be used to determine whether a scientific discovery or invention is worthy of translation to human application? 2) What recent scientific advance warrants a deeper understanding of clinical trials by everyone? 3) What are the different types and phases of a clinical trial? 4) What characteristics of a human disorder should be noted, tracked, or stratified for a clinical trial and what inclusion /exclusion criteria are important to enrolling appropriate trial subjects? 5) What are the different study designs that can be used in a clinical trial program? 6) What confounding factors can alter the accurate interpretation of clinical trial outcomes? 7) What are the success rates of clinical trials and what can we learn from previous clinical trials? 8) What are the essential principles for the conduct of valid clinical trials? PMID:21786433

National Heart, Lung, and Blood Institute

MedlinePlus

... of Intramural Research Research Resources Research Meeting Summaries Technology Transfer Clinical Trials What Are Clinical Trials? Children & Clinical Studies NHLBI Trials Clinical Trial Websites News & ...

[Establishing the acupuncture-moxibustion clinical trial registry and improving the transparence of clinical trials of acupuncture and moxibustion].

PubMed

Liu, Yali; He, Liyun; Liu, Jia; Yang, Xingyue; Yan, Dongning; Wang, Xin; Luo, Lin; Li, Hongjiao; Yan, Shiyan; Wen, Tiancai; Bai, Wenjing; Wu, Taixiang; Liu, Baoyan

2017-07-12

As a kind of intervention measures of traditional Chinese medicine, acupuncture-moxibustion is highly adopted on global clinical practice. Even though the global clinical trial registration system was established more than 10 years ago, the proportion of acupuncture-moxibustion clinical trial registration is still very low; and it is very problematic on the methodological quality and report quality in the published acupuncture-moxibustion clinical trials. In order to manage particularly the acupuncture-moxibustion clinical trials, China Academy of Chinese Medical Sciences, collaborated with China Association of Acupuncture and Moxibustion and World Federation of Acupuncture Societies, established the Acupuncture-Moxibustion Clinical Trail Registry (AMCTR). AMCTR is a secondary registry platform affiliated to the Chinese Clinical Trial Registry (ChiCTR) and WHO International Clinical Trials Registry Platform (ICTRP), specifically for the acceptance and management of clinical trials in the field of acupuncture and moxibustion. It is a nonprofit academic organization, located in China Academy of Chinese Medical Sciences.

Results of a multicenter prospective clinical study in Japan for evaluating efficacy and safety of desensitization protocol based on rituximab in ABO-incompatible kidney transplantation.

PubMed

Takahashi, Kota; Saito, Kazuhide; Takahara, Shiro; Fuchinoue, Shohei; Yagisawa, Takashi; Aikawa, Atsushi; Watarai, Yoshihiko; Yoshimura, Norio; Tanabe, Kazunari; Morozumi, Kunio; Shimazu, Motohide

2017-08-01

Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy. Mycophenolate mofetil and low dose steroid were started 28 days pretransplant, followed by two doses of rituximab 375 mg/m 2 at day -14 and day -1, and postoperative immunosuppression with tacrolimus or ciclosporin and basiliximab. The primary endpoint was the non-occurrence rate of acute antibody-mediated rejection. Patient survival and graft survival were monitored for 1 year posttransplant. Eighteen patients received rituximab and underwent ABO-incompatible kidney transplantation. CD19-positive peripheral B cell count decreased rapidly after the first rituximab infusion and recovered gradually after week 36. The desensitization protocol was tolerable, and most rituximab-related infusion reactions were mild. No anti-A/B antibody-mediated rejection occurred with this series. One patient developed anti-HLA antibody-mediated rejection (Banff 07 type II) on day 2, which was successfully managed. Patient and graft survival were both 100 % after 1 year. Our desensitization protocol was confirmed to be clinically effective and with acceptable toxicities for ABO-I-KTx (University Hospital Medical Information Network Registration Number: UMIN000006635).

Clinical Trials - Multiple Languages

MedlinePlus

... new window. Arabic (العربية) Expand Section Clinical Trials - English PDF Clinical Trials - العربية (Arabic) PDF American Cancer ... Traditional (Cantonese dialect) (繁體中文) Expand Section Clinical Trials - English PDF Clinical Trials - 繁體中文 (Chinese, Traditional (Cantonese dialect)) ...

Characteristics of NIH- and industry-sponsored head and neck cancer clinical trials.

PubMed

Devaiah, Anand; Murchison, Charles

2016-09-01

Compare U.S. clinical trials sponsored by the National Institutes of Health (NIH) and industry, especially with regard to trial design, interventions studied, and results reporting rates. U.S. head and neck cancer clinical trials. We used information from ClinicalTrials.gov to compare NIH- and industry-sponsored head and neck cancer clinical trials, specifically analyzing differences in trial design and interventions studied. We examined publication rates and positive results rates using PubMed.gov. About 50% of NIH- and industry-sponsored clinical trials have their results reported in peer-reviewed literature. Industry-sponsored trials had higher rates of positive results than NIH-sponsored trials. NIH- and industry-sponsored clinical trials had similar trial designs, although industry-sponsored trials had significantly lower rates of randomization. Industry trials utilized radiation in 19% of trials and surgery in 2% of trials. NIH trials also had low utilization of both radiation and surgery (27% and 12% of trials, respectively). NIH- and industry-sponsored trials published their results in journals with comparable impact factors. There is significant underreporting of results in U.S. head and neck cancer clinical trials, whether sponsored by NIH or industry. Industry trials have significantly higher rates of positive results, although it is unclear what contributes to this. Both NIH- and industry-sponsored trials underutilize surgery and radiation as treatment modalities, despite the fact that these are standard-of-care therapies for head and neck cancer. We recommend that the NIH and industry report all results from clinical trials and use surgery and radiation as treatment arms in order to arrive at more balanced therapeutic recommendations. N/A. Laryngoscope, 126:E300-E303, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Building trust and diversity in patient-centered oncology clinical trials: An integrated model.

PubMed

Hurd, Thelma C; Kaplan, Charles D; Cook, Elise D; Chilton, Janice A; Lytton, Jay S; Hawk, Ernest T; Jones, Lovell A

2017-04-01

Trust is the cornerstone of clinical trial recruitment and retention. Efforts to decrease barriers and increase clinical trial participation among diverse populations have yielded modest results. There is an urgent need to better understand the complex interactions between trust and clinical trial participation. The process of trust-building has been a focus of intense research in the business community. Yet, little has been published about trust in oncology clinical trials or the process of building trust in clinical trials. Both clinical trials and business share common dimensions. Business strategies for building trust may be transferable to the clinical trial setting. This study was conducted to understand and utilize contemporary thinking about building trust to develop an Integrated Model of Trust that incorporates both clinical and business perspectives. A key word-directed literature search of the PubMed, Medline, Cochrane, and Google Search databases for entries dated between 1 January 1985 and 1 September 2015 was conducted to obtain information from which to develop an Integrated Model of Trust. Successful trial participation requires both participants and clinical trial team members to build distinctly different types of interpersonal trust to effect recruitment and retention. They are built under conditions of significant emotional stress and time constraints among people who do not know each other and have never worked together before. Swift Trust and Traditional Trust are sequentially built during the clinical trial process. Swift trust operates during the recruitment and very early active treatment phases of the clinical trial process. Traditional trust is built over time and operates during the active treatment and surveillance stages of clinical trials. The Psychological Contract frames the participants' and clinical trial team members' interpersonal trust relationship. The "terms" of interpersonal trust are negotiated through the psychological contract. Contract renegotiation occurs in response to cyclical changes within the trust relationship throughout trial participation. The Integrated Model of Trust offers a novel framework to interrogate the process by which diverse populations and clinical trial teams build trust. To our knowledge, this is the first model of trust-building in clinical trials that frames trust development through integrated clinical and business perspectives. By focusing on the process, rather than outcomes of trust-building diverse trial participants, clinical trials teams, participants, and cancer centers may be able to better understand, measure, and manage their trust relationships in real time. Ultimately, this may foster increased recruitment and retention of diverse populations to clinical trials.

An international survey of physicians regarding clinical trials: a comparison between Kyoto University Hospital and Seoul National University Hospital

PubMed Central

2013-01-01

Background International clinical trials are now rapidly expanding into Asia. However, the proportion of global trials is higher in South Korea compared to Japan despite implementation of similar governmental support in both countries. The difference in clinical trial environment might influence the respective physicians’ attitudes and experience towards clinical trials. Therefore, we designed a questionnaire to explore how physicians conceive the issues surrounding clinical trials in both countries. Methods A questionnaire survey was conducted at Kyoto University Hospital (KUHP) and Seoul National University Hospital (SNUH) in 2008. The questionnaire consisted of 15 questions and 2 open-ended questions on broad key issues relating to clinical trials. Results The number of responders was 301 at KUHP and 398 at SNUH. Doctors with trial experience were 196 at KUHP and 150 at SNUH. Among them, 12% (24/196) at KUHP and 41% (61/150) at SUNH had global trial experience. Most respondents at both institutions viewed clinical trials favorably and thought that conducting clinical trials contributed to medical advances, which would ultimately lead to new and better treatments. The main reason raised as a hindrance to conducting clinical trials was the lack of personnel support and time. Doctors at both university hospitals thought that more clinical research coordinators were required to conduct clinical trials more efficiently. KUHP doctors were driven mainly by pure academic interest or for their desire to find new treatments, while obtaining credits for board certification and co-authorship on manuscripts also served as motivation factors for doctors at SNUH. Conclusions Our results revealed that there might be two different approaches to increase clinical trial activity. One is a social level approach to establish clinical trial infrastructure providing sufficient clinical research professionals. The other is an individual level approach that would provide incentives to encourage doctors to participate in and conduct clinical trials. PMID:24156760

Tools in a clinical information system supporting clinical trials at a Swiss University Hospital.

PubMed

Weisskopf, Michael; Bucklar, Guido; Blaser, Jürg

2014-12-01

Issues concerning inadequate source data of clinical trials rank second in the most common findings by regulatory authorities. The increasing use of electronic clinical information systems by healthcare providers offers an opportunity to facilitate and improve the conduct of clinical trials and the source documentation. We report on a number of tools implemented into the clinical information system of a university hospital to support clinical research. In 2011/2012, a set of tools was developed in the clinical information system of the University Hospital Zurich to support clinical research, including (1) a trial registry for documenting metadata on the clinical trials conducted at the hospital, (2) a patient-trial-assignment-tool to tag patients in the electronic medical charts as participants of specific trials, (3) medical record templates for the documentation of study visits and trial-related procedures, (4) online queries on trials and trial participants, (5) access to the electronic medical records for clinical monitors, (6) an alerting tool to notify of hospital admissions of trial participants, (7) queries to identify potentially eligible patients in the planning phase as trial feasibility checks and during the trial as recruitment support, and (8) order sets to facilitate the complete and accurate performance of study visit procedures. The number of approximately 100 new registrations per year in the voluntary trial registry in the clinical information system now matches the numbers of the existing mandatory trial registry of the hospital. Likewise, the yearly numbers of patients tagged as trial participants as well as the use of the standardized trial record templates increased to 2408 documented trial enrolments and 190 reports generated/month in the year 2013. Accounts for 32 clinical monitors have been established in the first 2 years monitoring a total of 49 trials in 16 clinical departments. A total of 15 months after adding the optional feature of hospital admission alerts of trial participants, 107 running trials have activated this option, including 48 out of 97 studies (49.5%) registered in the year 2013, generating approximately 85 alerts per month. The popularity of the presented tools in the clinical information system illustrates their potential to facilitate the conduct of clinical trials. The tools also allow for enhanced transparency on trials conducted at the hospital. Future studies on monitoring and inspection findings will have to evaluate their impact on quality and safety. © The Author(s) 2014.

Integration of technology-based outcome measures in clinical trials of Parkinson and other neurodegenerative diseases.

PubMed

Artusi, Carlo Alberto; Mishra, Murli; Latimer, Patricia; Vizcarra, Joaquin A; Lopiano, Leonardo; Maetzler, Walter; Merola, Aristide; Espay, Alberto J

2018-01-01

We sought to review the landscape of past, present, and future use of technology-based outcome measures (TOMs) in clinical trials of neurodegenerative disorders. We systematically reviewed PubMed and ClinicalTrials.gov for published and ongoing clinical trials in neurodegenerative disorders employing TOMs. In addition, medical directors of selected pharmaceutical companies were surveyed on their companies' ongoing efforts and future plans to integrate TOMs in clinical trials as primary, secondary, or exploratory endpoints. We identified 164 published clinical trials indexed in PubMed that used TOMs as outcome measures in Parkinson disease (n = 132) or other neurodegenerative disorders (n = 32). The ClinicalTrials.gov search yielded 42 clinical trials using TOMs, representing 2.7% of ongoing trials. Sensor-based technology accounted for over 75% of TOMs applied. Gait and physical activity were the most common targeted domains. Within the next 5 years, 83% of surveyed pharmaceutical companies engaged in neurodegenerative disorders plan to deploy TOMs in clinical trials. Although promising, TOMs are underutilized in clinical trials of neurodegenerative disorders. Validating relevant endpoints, standardizing measures and procedures, establishing a single platform for integration of data and algorithms from different devices, and facilitating regulatory approvals should advance TOMs integration into clinical trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of a user customizable imaging informatics-based intelligent workflow engine system to enhance rehabilitation clinical trials

NASA Astrophysics Data System (ADS)

Wang, Ximing; Martinez, Clarisa; Wang, Jing; Liu, Ye; Liu, Brent

2014-03-01

Clinical trials usually have a demand to collect, track and analyze multimedia data according to the workflow. Currently, the clinical trial data management requirements are normally addressed with custom-built systems. Challenges occur in the workflow design within different trials. The traditional pre-defined custom-built system is usually limited to a specific clinical trial and normally requires time-consuming and resource-intensive software development. To provide a solution, we present a user customizable imaging informatics-based intelligent workflow engine system for managing stroke rehabilitation clinical trials with intelligent workflow. The intelligent workflow engine provides flexibility in building and tailoring the workflow in various stages of clinical trials. By providing a solution to tailor and automate the workflow, the system will save time and reduce errors for clinical trials. Although our system is designed for clinical trials for rehabilitation, it may be extended to other imaging based clinical trials as well.

Multi-level assessment protocol (MAP) for adoption in multi-site clinical trials

PubMed Central

Guydish, J.; Manser, S.T.; Jessup, M.; Tajima, B.; Sears, C.; Montini, T.

2010-01-01

The National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) is intended to test promising drug abuse treatment models in multi-site clinical trials, and to support adoption of new interventions into clinical practice. Using qualitative research methods we asked: How might the technology of multi-site clinical trials be modified to better support adoption of tested interventions? A total of 42 participants, representing 8 organizational levels ranging from clinic staff to clinical trial leaders, were interviewed about their role in the clinical trial, its interactions with clinics, and intervention adoption. Among eight clinics participating in the clinical trial, we found adoption of the tested intervention in one clinic only. In analysis of interview data we identified four conceptual themes which are likely to affect adoption and may be informative in future multi-site clinical trials. We offer the conclusion that planning for adoption in the early stages of protocol development will better serve the aim of integrating new interventions into practice. PMID:20890376

Trials, tricks and transparency: how disclosure rules affect clinical knowledge.

PubMed

Dahm, Matthias; González, Paula; Porteiro, Nicolás

2009-12-01

Scandals of selective reporting of clinical trial results by pharmaceutical firms have underlined the need for more transparency in clinical trials. We provide a theoretical framework which reproduces incentives for selective reporting and yields three key implications concerning regulation. First, a compulsory clinical trial registry complemented through a voluntary clinical trial results database can implement full transparency (the existence of all trials as well as their results is known). Second, full transparency comes at a price. It has a deterrence effect on the incentives to conduct clinical trials, as it reduces the firms' gains from trials. Third, in principle, a voluntary clinical trial results database without a compulsory registry is a superior regulatory tool; but we provide some qualified support for additional compulsory registries when medical decision-makers cannot anticipate correctly the drug companies' decisions whether to conduct trials.

Clinical trials in dentistry in India: Analysis from trial registry.

PubMed

Gowri, S; Kannan, Sridharan

2017-01-01

Evidence-based practice requires clinical trials to be performed. In India, if any clinical trial has to be performed, it has to be registered with clinical trial registry of India. Studies have shown that the report of clinical trials is poor in dentistry. Hence, the present study has been conducted to assess the type and trends of clinical trials being undertaken in dentistry in India over a span of 6 years. All the clinical trials which were registered with the Central Trial Registry of India (CTRI) (www.ctri.nic.in) from January 1, 2007 to March 3, 2014 were evaluated using the keyword "dental." Following information were collected for each of the clinical trials obtained from the search; number of centres (single center/multicentric), type of the institution undertaking the research (government/private/combined), study (observational/interventional), study design (randomized/single blinded/double-blinded), type of health condition, type of participants (healthy/patients), sponsors (academia/commercial), phase of clinical trial (Phase 1/2/3/4), publication details (published/not published), whether it was a postgraduate thesis or not and prospective or retrospective registration of clinical trials, methodological quality (method of randomization, allocation concealment). Descriptive statistics was used for analysis of various categories. Trend analysis was done to assess the changes over a period of time. The search yielded a total of 84 trials of which majority of them were single centered. Considering the study design more than half of the registered clinical trials were double-blinded (47/84 [56%]). With regard to the place of conducting a trial, most of the trials were planned to be performed in private hospitals (56/84 [66.7%]). Most (79/84, 94.1%) of the clinical trials were interventional while only 5/84 (5.9%) were observational. Majority (65/84, 77.4%) of the registered clinical trials were recruiting patients while the rest were being done in healthy participants. From 2011, some of the postgraduate thesis trials had also been registered (2011-8; 2012-8; 2013-13; 2014-6). Inadequacy in reporting the method of randomization and allocation concealment was observed in 37/67 (55.2%) and 31/67 (46.2%) clinical trials respectively. A considerable number of postgraduate theses was also registered with CTRI in dentistry and majority of the clinical trials despite being completed are not yet published. The number of clinical trials in dentistry are low in India, and more focus should be placed by dental investigators regarding the reporting standards. Furthermore, researchers and trial sponsors should aim at publication of the research findings so that it is made publically available for use. A clear-cut need exists for an increase in both the quantity and quality of clinical trials in dentistry.

Prevalence of clinical trial status discrepancies: A cross-sectional study of 10,492 trials registered on both ClinicalTrials.gov and the European Union Clinical Trials Register.

PubMed

Fleminger, Jessica; Goldacre, Ben

2018-01-01

Trial registries are a key source of information for clinicians and researchers. While building OpenTrials, an open database of public trial information, we identified errors and omissions in registries, including discrepancies between descriptions of the same trial in different registries. We set out to ascertain the prevalence of discrepancies in trial completion status using a cohort of trials registered on both the European Union Clinical Trials Register (EUCTR) and ClinicalTrials.gov. We used matching titles and registry IDs provided by both registries to build a cohort of dual-registered trials. Completion statuses were compared; we calculated descriptive statistics on the prevalence of discrepancies. 11,988 dual-registered trials were identified. 1,496 did not provide a comparable completion status, leaving 10,492 trials. 16.2% were discrepant on completion status. The majority of discrepancies (90.5%) were a 'completed' trial on ClinicalTrials.gov inaccurately marked as 'ongoing' on EUCTR. Overall, 33.9% of dual-registered trials described as 'ongoing' on EUCTR were listed as 'completed' on ClinicalTrials.gov. Completion status on registries is commonly inaccurate. Previous work on publication bias may underestimate non-reporting. We describe simple steps registry owners and trialists could take to improve accuracy.

Statistical controversies in clinical research: comparison of primary outcomes in protocols, public clinical-trial registries and publications: the example of oncology trials.

PubMed

Perlmutter, A S; Tran, V-T; Dechartres, A; Ravaud, P

2017-04-01

Protocols are often unavailable to peer-reviewers and readers. To detect outcome reporting bias (ORB), readers usually have to resort to publicly available descriptions of study design such as public clinical trial registries. We compared primary outcomes in protocols, ClinicalTrials.gov and publications of oncology trials and evaluated the use of ClinicalTrials.gov as compared with protocols in detecting discrepancies between planned and published outcomes. We searched for phase III oncology trials registered in ClinicalTrials.gov and published in the Journal of Clinical Oncology and New England Journal of Medicine between January 2014 and June 2015. We extracted primary outcomes reported in the protocol, ClinicalTrials.gov and the publication. First, we assessed the quality of primary outcome descriptions by using a published framework. Second, we evaluated modifications of primary outcomes between each source. Finally, we evaluated the agreement, specificity and sensitivity of detecting modifications between planned and published outcomes by using protocols or ClinicalTrials.gov. We included 65 trials, with 81 primary outcomes common among the 3 sources. The proportion of primary outcomes reporting all items from the framework was 73%, 22%, and 75% for protocols, ClinicalTrials.gov and publications, respectively. Eight (12%) trials presented a discrepancy between primary outcomes reported in the protocol and in the publication. Twelve (18.5%) trials presented a discrepancy between primary outcomes registered at ClinicalTrials.gov and in publications. We found a moderate agreement in detecting discrepant reporting of outcomes by using protocols or ClinicalTrials.gov [κ = 0.53, 95% confidence interval (0.25-0.81)]. Using ClinicalTrials.gov to detect discrepant reporting of outcomes showed high specificity (89.5%) but lacked sensitivity (75%) as compared with use of protocols. In oncology trials, primary outcome descriptions in ClinicalTrials.gov are often of low quality and may not reflect what is in the protocol, thus limiting the detection of modifications between planned and published outcomes. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Enhancing clinical evidence by proactively building quality into clinical trials.

PubMed

Meeker-O'Connell, Ann; Glessner, Coleen; Behm, Mark; Mulinde, Jean; Roach, Nancy; Sweeney, Fergus; Tenaerts, Pamela; Landray, Martin J

2016-08-01

Stakeholders across the clinical trial enterprise have expressed concern that the current clinical trial enterprise is unsustainable. The cost and complexity of trials have continued to increase, threatening our ability to generate reliable evidence essential for making appropriate decisions concerning the benefits and harms associated with clinical interventions. Overcoming this inefficiency rests on improving protocol design, trial planning, and quality oversight. The Clinical Trials Transformation Initiative convened a project to evaluate methods to prospectively build quality into the scientific and operational design of clinical trials ("quality-by-design"), such that trials are feasible to conduct and important errors are prevented rather than remediated. A working group evaluated aspects of trial design and oversight and developed the Clinical Trials Transformation Initiative quality-by-design principles document, outlining a series of factors generally relevant to the reliability of trial conclusions and to patient safety. These principles were then applied and further refined during a series of hands-on workshops to evaluate their utility in facilitating proactive, cross-functional dialogue, and decision-making about trial design and planning. Following these workshops, independent qualitative interviews were conducted with 19 workshop attendees to explore the potential challenges for implementing a quality-by-design approach to clinical trials. The Clinical Trials Transformation Initiative project team subsequently developed recommendations and an online resource guide to support implementation of this approach. The Clinical Trials Transformation Initiative quality-by-design principles provide a framework for assuring that clinical trials adequately safeguard participants and provide reliable information on which to make decisions on the effects of treatments. The quality-by-design workshops highlighted the value of active discussions incorporating the different perspectives within and external to an organization (e.g. clinical investigators, research site staff, and trial participants) in improving trial design. Workshop participants also recognized the value of focusing oversight on those aspects of the trial where errors would have a major impact on participant safety and reliability of results. Applying the Clinical Trials Transformation Initiative quality-by-design recommendations and principles should enable organizations to prioritize the most critical determinants of a trial's quality, identify non-essential activities that can be eliminated to streamline trial conduct and oversight, and formulate appropriate plans to define, avoid, mitigate, monitor, and address important errors. © The Author(s) 2016.

A decade of the Clinical Trials Transformation Initiative: What have we accomplished? What have we learned?

PubMed

Tenaerts, P; Madre, L; Landray, M

2018-02-01

The Clinical Trials Transformation Initiative reflects on 10 years of working to improve the quality and efficiency of clinical trials. This article highlights many of the Clinical Trials Transformation Initiative's accomplishments and offers examples of the impact that the Clinical Trials Transformation Initiative has had on the clinical trials enterprise. After conducting more than 25 projects and issuing recommendations for specific strategies to improve the design and execution of clinical trials, some common themes and lessons learned have emerged. Lessons include the importance of engaging many stakeholders, advanced planning to address critical issues, discontinuation of non-value added practices, and new opportunities presented by technology. Through its work, the Clinical Trials Transformation Initiative has also derived some operational best practices for conducting collaborative, multi-stakeholder projects covering project selection, project team dynamics and execution, and multi-stakeholder meetings and team discussions. Through these initiatives, the Clinical Trials Transformation Initiative has helped move the needle toward needed change in the clinical trials enterprise that has directly impacted stakeholders and patients alike.

Haphazard reporting of deaths in clinical trials: a review of cases of ClinicalTrials.gov records and matched publications-a cross-sectional study.

PubMed

Earley, Amy; Lau, Joseph; Uhlig, Katrin

2013-01-18

A participant death is a serious event in a clinical trial and needs to be unambiguously and publicly reported. To examine (1) how often and how numbers of deaths are reported in ClinicalTrials.gov records; (2) how often total deaths can be determined per arm within a ClinicalTrials.gov results record and its corresponding publication and (3) whether counts may be discordant. Registry-based study of clinical trial results reporting. ClinicalTrials.gov results database searched in July 2011 and matched PubMed publications. A random sample of ClinicalTrials.gov results records. Detailed review of records with a single corresponding publication. ClinicalTrials.gov records reporting number of deaths under participant flow, primary or secondary outcome or serious adverse events. Consistency in reporting of number of deaths between ClinicalTrials.gov records and corresponding publications. In 500 randomly selected ClinicalTrials.gov records, only 123 records (25%) reported a number for deaths. Reporting of deaths across data modules for participant flow, primary or secondary outcomes and serious adverse events was variable. In a sample of 27 pairs of ClinicalTrials.gov records with number of deaths and corresponding publications, total deaths per arm could only be determined in 56% (15/27 pairs) but were discordant in 19% (5/27). In 27 pairs of ClinicalTrials.gov records without any information on number of deaths, 48% (13/27) were discordant since the publications reported absence of deaths in 33% (9/27) and positive death numbers in 15% (4/27). Deaths are variably reported in ClinicalTrials.gov records. A reliable total number of deaths per arm cannot always be determined with certainty or can be discordant with number reported in corresponding trial publications. This highlights a need for unambiguous and complete reporting of the number of deaths in trial registries and publications.

Haphazard reporting of deaths in clinical trials: a review of cases of ClinicalTrials.gov records and matched publications–a cross-sectional study

PubMed Central

Earley, Amy; Lau, Joseph; Uhlig,, Katrin

2013-01-01

Context A participant death is a serious event in a clinical trial and needs to be unambiguously and publicly reported. Objective To examine (1) how often and how numbers of deaths are reported in ClinicalTrials.gov records; (2) how often total deaths can be determined per arm within a ClinicalTrials.gov results record and its corresponding publication and (3) whether counts may be discordant. Design Registry-based study of clinical trial results reporting. Setting ClinicalTrials.gov results database searched in July 2011 and matched PubMed publications. Selection criteria A random sample of ClinicalTrials.gov results records. Detailed review of records with a single corresponding publication. Main outcome measure ClinicalTrials.gov records reporting number of deaths under participant flow, primary or secondary outcome or serious adverse events. Consistency in reporting of number of deaths between ClinicalTrials.gov records and corresponding publications. Results In 500 randomly selected ClinicalTrials.gov records, only 123 records (25%) reported a number for deaths. Reporting of deaths across data modules for participant flow, primary or secondary outcomes and serious adverse events was variable. In a sample of 27 pairs of ClinicalTrials.gov records with number of deaths and corresponding publications, total deaths per arm could only be determined in 56% (15/27 pairs) but were discordant in 19% (5/27). In 27 pairs of ClinicalTrials.gov records without any information on number of deaths, 48% (13/27) were discordant since the publications reported absence of deaths in 33% (9/27) and positive death numbers in 15% (4/27). Conclusions Deaths are variably reported in ClinicalTrials.gov records. A reliable total number of deaths per arm cannot always be determined with certainty or can be discordant with number reported in corresponding trial publications. This highlights a need for unambiguous and complete reporting of the number of deaths in trial registries and publications. PMID:23335556

Publication and reporting of clinical trial results: cross sectional analysis across academic medical centers.

PubMed

Chen, Ruijun; Desai, Nihar R; Ross, Joseph S; Zhang, Weiwei; Chau, Katherine H; Wayda, Brian; Murugiah, Karthik; Lu, Daniel Y; Mittal, Amit; Krumholz, Harlan M

2016-02-17

To determine rates of publication and reporting of results within two years for all completed clinical trials registered in ClinicalTrials.gov across leading academic medical centers in the United States. Cross sectional analysis. Academic medical centers in the United States. Academic medical centers with 40 or more completed interventional trials registered on ClinicalTrials.gov. Using the Aggregate Analysis of ClinicalTrials.gov database and manual review, we identified all interventional clinical trials registered on ClinicalTrials.gov with a primary completion date between October 2007 and September 2010 and with a lead investigator affiliated with an academic medical center. The proportion of trials that disseminated results, defined as publication or reporting of results on ClinicalTrials.gov, overall and within 24 months of study completion. We identified 4347 interventional clinical trials across 51 academic medical centers. Among the trials, 1005 (23%) enrolled more than 100 patients, 1216 (28%) were double blind, and 2169 (50%) were phase II through IV. Overall, academic medical centers disseminated results for 2892 (66%) trials, with 1560 (35.9%) achieving this within 24 months of study completion. The proportion of clinical trials with results disseminated within 24 months of study completion ranged from 16.2% (6/37) to 55.3% (57/103) across academic medical centers. The proportion of clinical trials published within 24 months of study completion ranged from 10.8% (4/37) to 40.3% (31/77) across academic medical centers, whereas results reporting on ClinicalTrials.gov ranged from 1.6% (2/122) to 40.7% (72/177). Despite the ethical mandate and expressed values and mission of academic institutions, there is poor performance and noticeable variation in the dissemination of clinical trial results across leading academic medical centers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Managing multicentre clinical trials with open source.

PubMed

Raptis, Dimitri Aristotle; Mettler, Tobias; Fischer, Michael Alexander; Patak, Michael; Lesurtel, Mickael; Eshmuminov, Dilmurodjon; de Rougemont, Olivier; Graf, Rolf; Clavien, Pierre-Alain; Breitenstein, Stefan

2014-03-01

Multicentre clinical trials are challenged by high administrative burden, data management pitfalls and costs. This leads to a reduced enthusiasm and commitment of the physicians involved and thus to a reluctance in conducting multicentre clinical trials. The purpose of this study was to develop a web-based open source platform to support a multi-centre clinical trial. We developed on Drupal, an open source software distributed under the terms of the General Public License, a web-based, multi-centre clinical trial management system with the design science research approach. This system was evaluated by user-testing and well supported several completed and on-going clinical trials and is available for free download. Open source clinical trial management systems are capable in supporting multi-centre clinical trials by enhancing efficiency, quality of data management and collaboration.

[Standard Cancer Therapy Are Established by the Investigator-Initiated Post-Marketing Clinical Trials, Not by the Indication-Directed Clinical Trials].

PubMed

Shimada, Yasuhiro

2016-04-01

The financial supports for investigator-initiated post-marketing clinical trial in clinical oncology are reduced after scandals related to the other fields of clinical trials in Japan. These clinical trials are the essential final steps of clinical development in newer cancer therapy, which should be conducted in the investigator-initiated clinical trial groups with well-organized infrastructure and continuous financial supports. The present problems are discussed and summarized. Future perspectives with the national viewpoints needed to be included the idea of "health technology assessment".

Long-Term Comparison of Posterior Chamber Phakic Intraocular Lens With and Without a Central Hole (Hole ICL and Conventional ICL) Implantation for Moderate to High Myopia and Myopic Astigmatism: Consort-Compliant Article.

PubMed

Shimizu, Kimiya; Kamiya, Kazutaka; Igarashi, Akihito; Kobashi, Hidenaga

2016-04-01

The study shows a promising next-generation surgical option for the correction of moderate to high ametropia. Hole implantable collamer lens (ICL), STAAR Surgical, is a posterior chamber phakic intraocular lens with a central artificial hole. As yet, however, no long-term comparison of the clinical results of the implantation of ICLs with and without such a hole has hitherto been conducted. A prospective, randomized, controlled trial was carried out in order to compare the long-term clinical outcomes of the implantation, in such eyes, of ICLs with and without a central artificial hole.Examinations were conducted of the 64 eyes of 32 consecutive patients with spherical equivalents of -7.53 ± 2.39 diopters (D) (mean ± standard deviation) in whom implantation of a Hole ICL was performed in 1 eye, and that of a conventional ICL was carried out in the other, by randomized assignment. Before 1, 3, and 6 months, and 1, 3, and 5 years after surgery, the safety, efficacy, predictability, stability, intraocular pressure, endothelial cell density, and adverse events of the 2 surgical techniques were assessed and compared over time.The measurements of LogMAR uncorrected and corrected distance visual acuity 5 years postoperatively were -0.17 ± 0.14 and -0.24 ± 0.08 in the Hole ICL group, and -0.16 ± 0.10 and -0.25 ± 0.08 in the conventional ICL group. In these 2 groups, 96% and 100% of eyes, respectively, were within 1.0 D of the targeted correction 5 years postoperatively. Manifest refraction changed by -0.17 ± 0.41 D and -0.10 ± 0.26 D occurred in from 1 month to 5 years in the Hole and conventional ICL groups, respectively. Only 1 eye (3.1%), which was in the conventional ICL group, developed an asymptomatic anterior subcapsular cataract.Both Hole and conventional ICLs corrected of ametropia successfully throughout the 5-year observation period. It appears likely that the presence of the central hole does not significantly affect these visual and refractive outcomes. UMIN000018771.

Phase II trial of combination treatment with paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CSPOR-HN02).

PubMed

Tahara, M; Kiyota, N; Yokota, T; Hasegawa, Y; Muro, K; Takahashi, S; Onoe, T; Homma, A; Taguchi, J; Suzuki, M; Minato, K; Yane, K; Ueda, S; Hara, H; Saijo, K; Yamanaka, T

2018-04-01

The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) is combination treatment with platinum, 5-FU and cetuximab (PFE). However, this regimen requires hospitalization to ensure proper hydration and continuous infusion of 5-FU, and causes severe nausea and anorexia. We evaluated the efficacy and safety of paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with R/M SCCHN. Eligibility criteria included recurrent and/or metastatic, histologically proven SCC of the oropharynx, oral cavity, hypopharynx or larynx; PS 0-1; adequate organ function; no suitable local therapy for R/M SCCHN; and no prior systemic chemotherapy for R/M SCCHN. Chemotherapy consisted of paclitaxel 100 mg/m2 on days 1, 8; carboplatin area under the blood concentration-time curve 2.5 on days 1, 8, repeated every 3 weeks for up to 6 cycles; and cetuximab at an initial dose of 400 mg/m2, followed by 250 mg/m2 weekly until disease progression or unacceptable toxicities. Primary end point was overall response rate. Secondary end points were safety, treatment completion rate, progression-free survival, overall survival, and clinical benefit rate. Planned sample size was 45 patients. Forty-seven subjects were accrued from July 2013 to October 2014. Of 45 evaluable, 40 were male; median age was 63 years; Eastern Cooperative Oncology Group Performance Status was 0/1 in 23/22 cases; site was the hypopharynx/oropharynx/oral cavity/larynx in 17/11/10/7 cases; and 36/9 cases were smokers/nonsmokers, respectively. Overall response rate, the primary end point, was 40%. Median overall survival was 14.7 months and progression-free survival was 5.2 months. Grade 3/4 adverse events included neutropenia (68%), skin reaction (15%), fatigue (9%) and febrile neutropenia (9%). A potentially treatment-related death occurred in one patient with intestinal pneumonia. The PCE regimen shows promising activity with acceptable toxicity in the outpatient clinic. Further studies are needed to compare PCE with PFE in this population. UMIN000010507.

Effect of European Clinical Trials Directive on academic drug trials in Denmark: retrospective study of applications to the Danish Medicines Agency 1993-2006.

PubMed

Berendt, Louise; Håkansson, Cecilia; Bach, Karin Friis; Dalhoff, Kim; Andreasen, Per Buch; Petersen, Lene Grejs; Andersen, Elin; Poulsen, Henrik Enghusen

2008-01-05

To determine the impact of the European Union's Clinical Trials Directive on the number of academic drug trials carried out in Denmark. Retrospective review of applications for drug trials to the Danish Medicines Agency, 1993-2006. Applications for drug trials for alternate years were classified as academic or commercial trials. A random subset of academic trials was reviewed for number of participants in and intended monitoring of the trials. Academic and commercial drug trials showed an identical steady decline from 1993 to 2006 and no noticeable change after 2004 when good clinical practice became mandatory for academic trials. The Clinical Trials Directive introduced in May 2004 to ensure good clinical practice for academic drug trials was not associated with a decline in research activity in Denmark; presumably because good clinical practice units had already been in place in Danish universities since 1999. With such an infrastructure academic researchers can do drug trials under the same regulations as drug companies.

[Basic principles, planning and implementation of non-commercial clinical trials].

PubMed

Finger, R P; Coch, C; Coenen, M; Mengel, M; Hartmann, G; Holz, F G

2011-01-01

The proof of a drug's efficacy in randomized controlled trials is fundamental to therapeutic concepts determined by evidence-based medicine. Clinical trials according to the German Medicinal Products Act are performed by the pharmaceutical industry as company-sponsored trials (CST) driven by commercial interests or by non-commercial facilities as investigator-initiated trials (IIT), typically implemented by University Hospitals. In areas with no commercial interest, IITs are the driving force that generate scientific progress leading to treatment optimization. Therefore, non-commercial or investigator-initiated clinical trials are indispensable for improving medical care. To ensure the safety of trial participants and the quality of the data obtained, clinical trials are controlled by many legal regulations and internationally accepted quality standards. Therefore implementation of a clinical trial requires profound knowledge, qualified personnel, appropriate infrastructure, and substantial financial resources. In IITs unlike CSTs this has to be accomplished by the University without the assistance of the pharmaceutical industry. Since teaching of skills needed to perform clinical trials is still largely neglected in medical school and during residency this review addresses the (in clinical trials) inexperienced physician and outlines the characterization of a clinical trial, the range and division of responsibilities and the performance of clinical trials according to the German Medicinal Products Act.

Comparison of reporting phase I trial results in ClinicalTrials.gov and matched publications.

PubMed

Shepshelovich, D; Goldvaser, H; Wang, L; Abdul Razak, A R; Bedard, P L

2017-12-01

Background Data on completeness of reporting of phase I cancer clinical trials in publications are lacking. Methods The ClinicalTrials.gov database was searched for completed adult phase I cancer trials with reported results. PubMed was searched for matching primary publications published prior to November 1, 2016. Reporting in primary publications was compared with the ClinicalTrials.gov database using a 28-point score (2=complete; 1=partial; 0=no reporting) for 14 items related to study design, outcome measures and safety profile. Inconsistencies between primary publications and ClinicalTrials.gov were recorded. Linear regression was used to identify factors associated with incomplete reporting. Results After a review of 583 trials in ClinicalTrials.gov , 163 matching primary publications were identified. Publications reported outcomes that did not appear in ClinicalTrials.gov in 25% of trials. Outcomes were upgraded, downgraded or omitted in publications in 47% of trials. The overall median reporting score was 23/28 (interquartile range 21-25). Incompletely reported items in >25% publications were: inclusion criteria (29%), primary outcome definition (26%), secondary outcome definitions (53%), adverse events (71%), serious adverse events (80%) and dates of study start and database lock (91%). Higher reporting scores were associated with phase I (vs phase I/II) trials (p<0.001), multicenter trials (p<0.001) and publication in journals with lower impact factor (p=0.004). Conclusions Reported results in primary publications for early phase cancer trials are frequently inconsistent or incomplete compared with ClinicalTrials.gov entries. ClinicalTrials.gov may provide more comprehensive data from new cancer drug trials.

Awareness and attitudes towards clinical trials among Polish oncological patients who had never participated in a clinical trial.

PubMed

Staniszewska, Anna; Lubiejewska, Adriana; Czerw, Aleksandra; Dąbrowska-Bender, Marta; Duda-Zalewska, Aneta; Olejniczak, Dominik; Juszczyk, Grzegorz; Bujalska-Zadrożny, Magdalena

2018-03-21

Participation in a clinical trial significantly shortens waiting time associated with receiving specialist care. Furthermore, it may be the case that, through clinical trials, subjects can access medicines that are not typically available in Poland. The aim of this study was to determine the opinions of oncological patients about clinical trials. The research has been carried out during the years 2014-2016. A proprietary questionnaire consisting of 10 closed, single and multiple choice questions about awareness and perceptions of clinical trials, and 5 questions concerning demographic information was used. A group of 256 patients with cancer (54% women, 46% men), aged 21-77 years, was surveyed. Respondents were statistically more likely to decide to participate in a clinical trial as oncological patients than the healthy volunteers (Pearson's χ2 test p = 0.00006). The desire to qualify for clinical trials in no way depends on the knowledge of side effects (Pearson's χ2 test p = 0.16796). Our study found that the patients' awareness about clinical trials varied. However, a positive attitude towards research was visible. The main identified barriers to clinical trial participation were fear of possible side effects. Most patients regarded clinical trials as useful, and considered that they are conducted to introduce new treatment/new drug.

Redesigning Radiotherapy Quality Assurance: Opportunities to Develop an Efficient, Evidence-Based System to Support Clinical Trials

PubMed Central

Bekelman, Justin E.; Deye, James A.; Vikram, Bhadrasain; Bentzen, Soren M.; Bruner, Deborah; Curran, Walter J.; Dignam, James; Efstathiou, Jason A.; FitzGerald, T. J.; Hurkmans, Coen; Ibbott, Geoffrey S.; Lee, J. Jack; Merchant, Timothy E.; Michalski, Jeff; Palta, Jatinder R.; Simon, Richard; Ten Haken, Randal K.; Timmerman, Robert; Tunis, Sean; Coleman, C. Norman; Purdy, James

2012-01-01

Background In the context of national calls for reorganizing cancer clinical trials, the National Cancer Institute (NCI) sponsored a two day workshop to examine the challenges and opportunities for optimizing radiotherapy quality assurance (QA) in clinical trial design. Methods Participants reviewed the current processes of clinical trial QA and noted the QA challenges presented by advanced technologies. Lessons learned from the radiotherapy QA programs of recent trials were discussed in detail. Four potential opportunities for optimizing radiotherapy QA were explored, including the use of normal tissue toxicity and tumor control metrics, biomarkers of radiation toxicity, new radiotherapy modalities like proton beam therapy, and the international harmonization of clinical trial QA. Results Four recommendations were made: 1) Develop a tiered (and more efficient) system for radiotherapy QA and tailor intensity of QA to clinical trial objectives. Tiers include (i) general credentialing, (ii) trial specific credentialing, and (iii) individual case review; 2) Establish a case QA repository; 3) Develop an evidence base for clinical trial QA and introduce innovative prospective trial designs to evaluate radiotherapy QA in clinical trials; and 4) Explore the feasibility of consolidating clinical trial QA in the United States. Conclusion Radiotherapy QA may impact clinical trial accrual, cost, outcomes and generalizability. To achieve maximum benefit, QA programs must become more efficient and evidence-based. PMID:22425219

Searching ClinicalTrials.gov did not change the conclusions of a systematic review.

PubMed

Wilson, Lisa M; Sharma, Ritu; Dy, Sydney M; Waldfogel, Julie M; Robinson, Karen A

2017-10-01

We assessed the effect of searching ClinicalTrials.gov on the conclusions of a systematic review. We conducted this case study concurrently with a systematic review. We searched ClinicalTrials.gov on March 9, 2016, to identify trial records eligible for inclusion in the review. Two independent reviewers screened ClinicalTrials.gov records. We compared conclusions and strength of evidence grade with and without ClinicalTrials.gov records for 31 comparisons and 2 outcomes. We identified 106 trials (53 in the peer-reviewed literature only, 23 in ClinicalTrials.gov only, and 30 in both sources). For one comparison, the addition of results identified through ClinicalTrials.gov reduced the pooled effect size. We found evidence of selective outcome reporting for two comparisons and suspected publication bias for another two comparisons. For all other comparisons, searching ClinicalTrials.gov did not change conclusions or the strength of evidence grading for the two outcomes. Our search of ClinicalTrials.gov bolstered suspicions of reporting biases but did not change either the conclusions or the strength of evidence grading. Further research is needed to determine the effect of searching ClinicalTrials.gov on the conclusions of systematic reviews in different topic areas and as the new rules for registration of trial results take effect. Copyright © 2017 Elsevier Inc. All rights reserved.

An analysis of registered clinical trials in otolaryngology from 2007 to 2010: ClinicalTrials.gov.

PubMed

Witsell, David L; Schulz, Kristine A; Lee, Walter T; Chiswell, Karen

2013-11-01

To describe the conditions studied, interventions used, study characteristics, and funding sources of otolaryngology clinical trials from the ClinicalTrials.gov database; compare this otolaryngology cohort of interventional studies to clinical visits in a health care system; and assess agreement between clinical trials and clinical activity. Database analysis. Trial registration data downloaded from ClinicalTrials.gov and administrative data from the Duke University Medical Center from October 1, 2007 to September 27, 2010. Data extraction from ClinicalTrials.gov was done using MeSH and non-MeSH disease condition terms. Studies were subcategorized to create the following groupings for descriptive analysis: ear, nose, allergy, voice, sleep, head and neck cancer, thyroid, and throat. Duke Health System visits were queried by using selected ICD-9 codes for otolaryngology and non-otolaryngology providers. Visits were grouped similarly to ClinicalTrials.gov for further analysis. Chi-square tests were used to explore differences between groups. A total of 1115 of 40,970 registered interventional trials were assigned to otolaryngology. Head and neck cancer trials predominated. Study models most frequently incorporated parallel design (54.6%), 2 study groups (46.6%), and randomization (69.1%). Phase 2 or 3 studies constituted 46.4% of the cohort. Comparison of the ClinicalTrials.gov database with administrative health system visit data by disease condition showed discordance between national research activity and clinical visit volume for patients with otolaryngology complaints. Analysis of otolaryngology-related clinical research as listed in ClinicalTrials.gov can inform patients, physicians, and policy makers about research focus areas. The relative burden of otolaryngology-associated conditions in our tertiary health system exceeds research activity within the field.

Understanding Clinical Trials

Cancer.gov

Watch these videos to learn about some basic aspects of cancer clinical trials such as the different phases of clinical trials, methods used to protect patient safety, and how the costs of clinical trials are covered.

Linking ClinicalTrials.gov and PubMed to Track Results of Interventional Human Clinical Trials

PubMed Central

Huser, Vojtech; Cimino, James J.

2013-01-01

Objective In an effort to understand how results of human clinical trials are made public, we analyze a large set of clinical trials registered at ClinicalTrials.gov, the world’s largest clinical trial registry. Materials and Methods We considered two trial result artifacts: (1) existence of a trial result journal article that is formally linked to a registered trial or (2) the deposition of a trial’s basic summary results within the registry. Results The study sample consisted of 8907 completed, interventional, phase 2-or-higher clinical trials that were completed in 2006-2009. The majority of trials (72.2%) had no structured trial-article link present. A total of 2367 trials (26.6%) deposited basic summary results within the registry. Of those , 969 trials (10.9%) were classified as trials with extended results and 1398 trials (15.7%) were classified as trials with only required basic results. The majority of the trials (54.8%) had no evidence of results, based on either linked result articles or basic summary results (silent trials), while a minimal number (9.2%) report results through both registry deposition and publication. Discussion Our study analyzes the body of linked knowledge around clinical trials (which we refer to as the “trialome”). Our results show that most trials do not report results and, for those that do, there is minimal overlap in the types of reporting. We identify several mechanisms by which the linkages between trials and their published results can be increased. Conclusion Our study shows that even when combining publications and registry results, and despite availability of several information channels, trial sponsors do not sufficiently meet the mandate to inform the public either via a linked result publication or basic results submission. PMID:23874614

Efficient design of clinical trials and epidemiological research: is it possible?

PubMed

Lauer, Michael S; Gordon, David; Wei, Gina; Pearson, Gail

2017-08-01

Randomized clinical trials and large-scale, cohort studies continue to have a critical role in generating evidence in cardiovascular medicine; however, the increasing concern is that ballooning costs threaten the clinical trial enterprise. In this Perspectives article, we discuss the changing landscape of clinical research, and clinical trials in particular, focusing on reasons for the increasing costs and inefficiencies. These reasons include excessively complex design, overly restrictive inclusion and exclusion criteria, burdensome regulations, excessive source-data verification, and concerns about the effect of clinical research conduct on workflow. Thought leaders have called on the clinical research community to consider alternative, transformative business models, including those models that focus on simplicity and leveraging of digital resources. We present some examples of innovative approaches by which some investigators have successfully conducted large-scale, clinical trials at relatively low cost. These examples include randomized registry trials, cluster-randomized trials, adaptive trials, and trials that are fully embedded within digital clinical care or administrative platforms.

Trial publication after registration in ClinicalTrials.Gov: a cross-sectional analysis.

PubMed

Ross, Joseph S; Mulvey, Gregory K; Hines, Elizabeth M; Nissen, Steven E; Krumholz, Harlan M

2009-09-01

ClinicalTrials.gov is a publicly accessible, Internet-based registry of clinical trials managed by the US National Library of Medicine that has the potential to address selective trial publication. Our objectives were to examine completeness of registration within ClinicalTrials.gov and to determine the extent and correlates of selective publication. We examined reporting of registration information among a cross-section of trials that had been registered at ClinicalTrials.gov after December 31, 1999 and updated as having been completed by June 8, 2007, excluding phase I trials. We then determined publication status among a random 10% subsample by searching MEDLINE using a systematic protocol, after excluding trials completed after December 31, 2005 to allow at least 2 y for publication following completion. Among the full sample of completed trials (n = 7,515), nearly 100% reported all data elements mandated by ClinicalTrials.gov, such as intervention and sponsorship. Optional data element reporting varied, with 53% reporting trial end date, 66% reporting primary outcome, and 87% reporting trial start date. Among the 10% subsample, less than half (311 of 677, 46%) of trials were published, among which 96 (31%) provided a citation within ClinicalTrials.gov of a publication describing trial results. Trials primarily sponsored by industry (40%, 144 of 357) were less likely to be published when compared with nonindustry/nongovernment sponsored trials (56%, 110 of 198; p<0.001), but there was no significant difference when compared with government sponsored trials (47%, 57 of 122; p = 0.22). Among trials that reported an end date, 75 of 123 (61%) completed prior to 2004, 50 of 96 (52%) completed during 2004, and 62 of 149 (42%) completed during 2005 were published (p = 0.006). Reporting of optional data elements varied and publication rates among completed trials registered within ClinicalTrials.gov were low. Without greater attention to reporting of all data elements, the potential for ClinicalTrials.gov to address selective publication of clinical trials will be limited. Please see later in the article for the Editors' Summary.

Inclusion of Minority Patients in Breast Cancer Clinical Trials: The Role of the Clinical Trial Environment

DTIC Science & Technology

2007-05-01

competence of clinical trial staff, and outreach efforts. We have started to geographic, social and physical attributes of the communities surrounding the...aimed at clinical trial sites and that address specific barriers associated with the social or physical environment. 15. SUBJECT TERMS Clinical trials...and availability of trials, patient burden and benefit, site cultural competence, and outreach efforts. We will also examine the social and

Clinical Trials - Information for Participants

MedlinePlus

... Study Near You Learn More Share Clinical Trials – Information for Participants Overview Clinical research trials are at ... improved health in the future. Learn More Contact Information For more information about clinical trials conducted at ...

A data grid for imaging-based clinical trials

NASA Astrophysics Data System (ADS)

Zhou, Zheng; Chao, Sander S.; Lee, Jasper; Liu, Brent; Documet, Jorge; Huang, H. K.

2007-03-01

Clinical trials play a crucial role in testing new drugs or devices in modern medicine. Medical imaging has also become an important tool in clinical trials because images provide a unique and fast diagnosis with visual observation and quantitative assessment. A typical imaging-based clinical trial consists of: 1) A well-defined rigorous clinical trial protocol, 2) a radiology core that has a quality control mechanism, a biostatistics component, and a server for storing and distributing data and analysis results; and 3) many field sites that generate and send image studies to the radiology core. As the number of clinical trials increases, it becomes a challenge for a radiology core servicing multiple trials to have a server robust enough to administrate and quickly distribute information to participating radiologists/clinicians worldwide. The Data Grid can satisfy the aforementioned requirements of imaging based clinical trials. In this paper, we present a Data Grid architecture for imaging-based clinical trials. A Data Grid prototype has been implemented in the Image Processing and Informatics (IPI) Laboratory at the University of Southern California to test and evaluate performance in storing trial images and analysis results for a clinical trial. The implementation methodology and evaluation protocol of the Data Grid are presented.

Understanding clinical development of chimeric antigen receptor T cell therapies.

PubMed

de Wilde, Sofieke; Guchelaar, Henk-Jan; Zandvliet, Maarten Laurens; Meij, Pauline

2017-06-01

In the past decade, many clinical trials with gene- and cell-based therapies (GCTs) have been performed. Increased interest in the development of these drug products by various stakeholders has become apparent. Despite this growth in clinical studies, the number of therapies receiving marketing authorization approval (MAA) is lagging behind. To enhance the success rate of GCT development, it is essential to better understand the clinical development of these products. Chimeric antigen receptor (CAR) T cells are a GCT product subtype with promising efficacy in cancer treatment which are tested in many clinical trials, but have not yet received MAA. We generated an overview of the characteristics of CAR T-cell clinical development in the United States, Canada and Europe. Subsequently, the characteristics of clinical trials with CAR T-cell products that proceeded to a subsequent clinical trial, used as a proxy for success, were compared with those that did not proceed. From the U.S. and European Union clinical trial databases, 106 CAR T-cell trials were selected, from which 49 were linked to a subsequent trial and 57 were not. The majority of the trials had an academic sponsor from which most did not proceed, whereas most commercially sponsored trials were followed by another clinical trial. Furthermore, trials with a subsequent trial more frequently recruited large patient cohorts and were more often multicenter compared with trials that were not followed up. These characteristics can be used by investigators to better design clinical trials with CAR T cells. We encourage sponsors to plan clinical development ahead for a higher efficiency of product development and thereby achieving a higher success rate of development towards MAA. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Qualitative analysis of clinical research coordinators' role in phase I cancer clinical trials.

PubMed

Fujiwara, Noriko; Ochiai, Ryota; Shirai, Yuki; Saito, Yuko; Nagamura, Fumitaka; Iwase, Satoru; Kazuma, Keiko

2017-12-01

Clinical research coordinators play a pivotal role in phase I cancer clinical trials. We clarified the care coordination and practice for patients provided by clinical research coordinators in phase I cancer clinical trials in Japan and elucidated clinical research coordinators' perspective on patients' expectations and understanding of these trials. Fifteen clinical research coordinators participated in semi-structured interviews regarding clinical practices; perceptions of patients' expectations; and the challenges that occur before, during, and after phase I cancer clinical trials. Qualitative content analysis showed that most clinical research coordinators observed that patients have high expectations from the trials. Most listened to patients to confirm patients' understanding and reflected on responses to maintain hope, but to avoid excessive expectations; clinical research coordinators considered avoiding unplanned endings; and they aimed to establish good relationships between patients, medical staff, and among the professional team. Clinical research coordinators were insightful about the needs of patients and took a meticulous approach to the phase I cancer clinical trial process, allowing time to connect with patients and to coordinate the inter-professional research team. Additionally, education in advanced oncology care was valuable for comforting participants in cancer clinical trials.

Contribution of clinical trials to gross domestic product in Hungary

PubMed Central

Kaló, Zoltán; Antal, János; Pénzes, Miklós; Pozsgay, Csilla; Szepezdi, Zsuzsanna; Nagyjánosi, László

2014-01-01

Aim To determine the contribution of clinical trials to the gross domestic product (GDP) in Hungary. Methods An anonymous survey of pharmaceutical companies and clinical research organizations (CROs) was conducted to estimate their clinical trial-related employment and revenues. Clinical trial documents at the National Institute of Pharmacy (NIP) were analyzed to estimate trial-related revenues at health care institutions and the value of investigational medical products (IMPs) based on avoided drug costs. Financial benefits were calculated as 2010 US $ purchasing power parity (PPP) values. Results Clinical trials increased the revenue of Hungarian health care providers by US $165.6 million. The value of IMPs was US $67.0 million. Clinical trial operation and management activities generated 900 jobs and US $166.9 million in revenue among CROs and pharmaceutical companies. Conclusions The contribution of clinical trials to the Hungarian GDP in 2010 amounted to 0.2%. Participation in international clinical trials may result in health, financial, and intangible benefits that contribute to the sustainability of health care systems, especially in countries with severe resource constraints. Although a conservative approach was employed to estimate the economic benefits of clinical trials, further research is necessary to improve the generalizability of our findings. PMID:25358877

[Evidence-based quality assessment of 10-year orthodontic clinical trials in 4 major dental journals].

PubMed

Sun, Yan-nan; Lei, Fei-fei; Cao, Yan-li; Fu, Min-kui

2010-02-01

To assess the quality of orthodontic clinical trials published in 4 major dental journals in the past 10 years and establish the reference standard for orthodontic clinical trials and quality control of dental journals. All the clinical trials published in Chinese Journal of Stomatology, West China Journal of Stomatology, Journal of Practice Stomatology and Chinese Journal of Orthodontics from 1999 to 2008 were searched. The demographic information of the papers was extracted and the quality of the clinical trials according to the consolidated standards of reporting trials (CONSORT) was assessed. Four hundred and ninety-four clinical trials were retrieved, and 21.3% (105/494) of them were supported by grants. For the study design, only 26.1% (129/494) were prospective studies, and 3.8% (19/494) were randomized clinical trials. It was hard to evaluate precisely due to the lack of information about the details of the study designs. For the randomized clinical trials, the lack of details for randomization, allocation concealment, blinding and intention to treat compromised the quality. The general quality of clinical trials in orthodontics is poor. It needs to be improved both in the clinical study design and the paper writing.

78 FR 58318 - Clinical Trial Design for Intravenous Fat Emulsion Products; Public Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-23

...] Clinical Trial Design for Intravenous Fat Emulsion Products; Public Workshop AGENCY: Food and Drug... announcing a 1-day public workshop entitled ``Clinical Trial Design for Intravenous Fat Emulsion Products.'' This workshop will provide a forum to discuss trial design of clinical trials intended to support...

Patient engagement in clinical trials: The Clinical Trials Transformation Initiative's leadership from theory to practical implementation.

PubMed

Patrick-Lake, Bray

2018-02-01

Patient engagement is an increasingly important aspect of successful clinical trials. Over the past decade, as patient group involvement in clinical trials has continued to increase and diversify, the Clinical Trials Transformation Initiative has not only recognized the crucial role patients play in improving the clinical trial enterprise but also made a deep commitment to help grow and shape the emerging field of patient engagement. This article describes the evolution of patient engagement including the origins of the patient engagement movement; barriers to successful engagement and remaining challenges to full and valuable collaboration between patient groups and trial sponsors; and Clinical Trials Transformation Initiative's role in influencing the field through organizational practices, formal project work and resulting recommendations, and external advocacy efforts.

Challenges and opportunities in SLE clinical trials.

PubMed

van Vollenhoven, Ronald F

2013-09-01

To provide an update on the field of clinical trials in systemic lupus erythematosus (SLE). This review will examine failed and successful clinical trials in SLE in order to draw lessons and determine the optimal ways forward. Over the past decade, many clinical trials in SLE met with limited success, but in the past 2 years several SLE clinical trials have been successful. The two large phase III randomized controlled trials (RCTs) of belimumab achieved their primary endpoints and resulted in food and drug administration and European medicines agency approval of the drug. Characteristics of these trials were, among other things, a very large number of patients (>800 each), compound clinical endpoints, and a flexible design with regards to concomitant medication use. Likewise, large randomized controlled trials with mycophenolate mofetil, although nominally unsuccessful, clearly demonstrated the clinical benefit of this drug in lupus nephritis. Posthoc analyses of several failed trials involving abatacept and rituximab revealed design elements and/or outcomes that might have changed the outcomes of these studies. Many smaller trials have also been reported, in some instances with surprisingly positive results. An improved understanding of specific design features in SLE clinical trials combined with robust outcomes will make it possible more effectively to design and conduct clinical trials in SLE.

Review of ongoing clinical trials in non-small cell lung cancer: a status report for 2009 from the ClinicalTrials.gov website.

PubMed

Subramanian, Janakiraman; Madadi, Anusha R; Dandona, Monica; Williams, Kristina; Morgensztern, Daniel; Govindan, Ramaswamy

2010-08-01

Several new agents are being tested in clinical trials for patients with non-small cell lung cancer (NSCLC). A survey of ongoing clinical trials in NSCLC in the ClinicalTrials.gov website would help identify areas that require further attention in the future. We conducted a survey of ongoing clinical trials on NSCLC registered in the ClinicalTrials.gov website. The advanced search option was applied using the terms "non small cell lung cancer," "open studies," "interventional," and "adults 18 years or older." Of the 493 eligible trials, 77 (15.6%) were phase III, 92 (18.7%) were phase I, and 240 (48.7%) were phase II trials. Universities were listed as the primary sponsor for 224 (45.4%) trials and pharmaceutical industry for 166 (33.7%) trials. Majority of the trials were multicenter studies (56.8%) and were being conducted exclusively within the United States (51.3%). A large proportion of phase II and III clinical trials (77.2%) were focused on patients with advanced-stage disease. The most frequently used end points were progression-free survival (27.1%) followed by tumor response rate (22.9%) and overall survival (16.6%). Although biomarker analysis was included in 185 (37.5%) trials, only 39 (7.9%) trials used biomarkers for patient selection. Progression-free survival is the end point most commonly used to assess the effectiveness of experimental regimens, and biomarker-based patient selection is rarely used in ongoing clinical trials for NSCLC.

Clinical Trials in Benign Prostatic Hyperplasia: A Moving Target of Success.

PubMed

Thomas, Dominique; Chung, Caroline; Zhang, Yiye; Te, Alexis; Gratzke, Christian; Woo, Henry; Chughtai, Bilal

2018-05-24

Benign prostatic hyperplasia (BPH) affects over 50% of men above the age of 50 yr. With half of these men having bothersome lower urinary tract symptoms, this area represents a hot bed of novel treatments. Many BPH therapies have favorable short-term outcomes but lack durability or well-defined adverse events (AEs). Clinical trials are a gold standard for comparing treatments. We characterized all BPH clinical trials registered worldwide from inception to 2017. A total of 251 clinical trials were included. Of the studies, 30.1% used patient-reported outcomes such as the American Urological Association Symptom Score. Approximately 70% of clinical trials studied medical interventions, while the remaining trials investigated surgical approaches. Seventy-nine percent of trials were industry sponsored, while a minority were funded without commercial interest. Only 42% of trials had 12-mo follow-up, with the majority with <3 mo of follow-up. No trials evaluated prevention, diet, behavior, or alternative methods Overall, only 23% of trials reported results. Management options for BPH need unified benchmarks of success, AEs, durability, and standard reporting for all clinical trials, regardless of outcomes. We found that the majority of clinical trials were medical intervention, with very few trials evaluating prevention, diet, behavior, or alternative methods Furthermore, a few trials reported results in peer-reviewed journals. All clinical trials need to report results regardless of outcome, and in conclusion, standardized methods are needed in order to document the successes, adverse events, and durability for all clinical trials. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

How many research nurses for how many clinical trials in an oncology setting? Definition of the Nursing Time Required by Clinical Trial-Assessment Tool (NTRCT-AT).

PubMed

Milani, Alessandra; Mazzocco, Ketti; Stucchi, Sara; Magon, Giorgio; Pravettoni, Gabriella; Passoni, Claudia; Ciccarelli, Chiara; Tonali, Alessandra; Profeta, Teresa; Saiani, Luisa

2017-02-01

Few resources are available to quantify clinical trial-associated workload, needed to guide staffing and budgetary planning. The aim of the study is to describe a tool to measure clinical trials nurses' workload expressed in time spent to complete core activities. Clinical trials nurses drew up a list of nursing core activities, integrating results from literature searches with personal experience. The final 30 core activities were timed for each research nurse by an outside observer during daily practice in May and June 2014. Average times spent by nurses for each activity were calculated. The "Nursing Time Required by Clinical Trial-Assessment Tool" was created as an electronic sheet that combines the average times per specified activities and mathematic functions to return the total estimated time required by a research nurse for each specific trial. The tool was tested retrospectively on 141 clinical trials. The increasing complexity of clinical research requires structured approaches to determine workforce requirements. This study provides a tool to describe the activities of a clinical trials nurse and to estimate the associated time required to deliver individual trials. The application of the proposed tool in clinical research practice could provide a consistent structure for clinical trials nursing workload estimation internationally. © 2016 John Wiley & Sons Australia, Ltd.

Responsible Translation of Stem Cell Research: An Assessment of Clinical Trial Registration and Publications.

PubMed

Fung, Moses; Yuan, Yan; Atkins, Harold; Shi, Qian; Bubela, Tania

2017-05-09

We assessed the extent to which the publication of clinical trial results of innovative cell-based interventions reflects International Society for Stem Cell Research best practice guidelines. We assessed: (1) characteristics and time to publication of completed trials; (2) quality of reported trials; and (3) results of published trials. We identified and analyzed publications from 1,052 novel stem cell clinical trials: 179 (45.4%) of 393 completed trials had published results; 48 trials were registered by known stem cell tourism clinics, none of which reported results. Completed non-industry-sponsored trials initially published more rapidly, but differences with industry-sponsored trials decreased over time. Most publications reported safety, and 67.3% (mainly early-stage trials) reported positive outcomes. A higher proportion of industry trials reported positive efficacy. Heightened patient expectations for stem cell therapies give rise to ethical obligations for the transparent conduct of clinical trials. Reporting guidelines need to be developed that are specific to early-phase clinical trials. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

The Internet and Clinical Trials: Background, Online Resources, Examples and Issues

PubMed Central

Seib, Rachael; Prescott, Todd

2005-01-01

Both the Internet and clinical trials were significant developments in the latter half of the twentieth century: the Internet revolutionized global communications and the randomized controlled trial provided a means to conduct an unbiased comparison of two or more treatments. Large multicenter trials are often burdened with an extensive development time and considerable expense, as well as significant challenges in obtaining, backing up and analyzing large amounts of data. Alongside the increasing complexities of the modern clinical trial has grown the power of the Internet to improve communications, centralize and secure data as well as to distribute information. As more and more clinical trials are required to coordinate multiple trial processes in real time, centers are turning to the Internet for the tools to manage the components of a clinical trial, either in whole or in part, to produce lower costs and faster results. This paper reviews the historical development of the Internet and the randomized controlled trial, describes the Internet resources available that can be used in a clinical trial, reviews some examples of online trials and describes the advantages and disadvantages of using the Internet to conduct a clinical trial. We also extract the characteristics of the 5 largest clinical trials conducted using the Internet to date, which together enrolled over 26000 patients. PMID:15829477

Redesigning Radiotherapy Quality Assurance: Opportunities to Develop an Efficient, Evidence-Based System to Support Clinical Trials-Report of the National Cancer Institute Work Group on Radiotherapy Quality Assurance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bekelman, Justin E., E-mail: bekelman@uphs.upenn.edu; Deye, James A.; Vikram, Bhadrasain

2012-07-01

Purpose: In the context of national calls for reorganizing cancer clinical trials, the National Cancer Institute sponsored a 2-day workshop to examine challenges and opportunities for optimizing radiotherapy quality assurance (QA) in clinical trial design. Methods and Materials: Participants reviewed the current processes of clinical trial QA and noted the QA challenges presented by advanced technologies. The lessons learned from the radiotherapy QA programs of recent trials were discussed in detail. Four potential opportunities for optimizing radiotherapy QA were explored, including the use of normal tissue toxicity and tumor control metrics, biomarkers of radiation toxicity, new radiotherapy modalities such asmore » proton beam therapy, and the international harmonization of clinical trial QA. Results: Four recommendations were made: (1) to develop a tiered (and more efficient) system for radiotherapy QA and tailor the intensity of QA to the clinical trial objectives (tiers include general credentialing, trial-specific credentialing, and individual case review); (2) to establish a case QA repository; (3) to develop an evidence base for clinical trial QA and introduce innovative prospective trial designs to evaluate radiotherapy QA in clinical trials; and (4) to explore the feasibility of consolidating clinical trial QA in the United States. Conclusion: Radiotherapy QA can affect clinical trial accrual, cost, outcomes, and generalizability. To achieve maximum benefit, QA programs must become more efficient and evidence-based.« less

Redesigning radiotherapy quality assurance: opportunities to develop an efficient, evidence-based system to support clinical trials--report of the National Cancer Institute Work Group on Radiotherapy Quality Assurance.

PubMed

Bekelman, Justin E; Deye, James A; Vikram, Bhadrasain; Bentzen, Soren M; Bruner, Deborah; Curran, Walter J; Dignam, James; Efstathiou, Jason A; FitzGerald, T J; Hurkmans, Coen; Ibbott, Geoffrey S; Lee, J Jack; Merchant, Thomas E; Michalski, Jeff; Palta, Jatinder R; Simon, Richard; Ten Haken, Randal K; Timmerman, Robert; Tunis, Sean; Coleman, C Norman; Purdy, James

2012-07-01

In the context of national calls for reorganizing cancer clinical trials, the National Cancer Institute sponsored a 2-day workshop to examine challenges and opportunities for optimizing radiotherapy quality assurance (QA) in clinical trial design. Participants reviewed the current processes of clinical trial QA and noted the QA challenges presented by advanced technologies. The lessons learned from the radiotherapy QA programs of recent trials were discussed in detail. Four potential opportunities for optimizing radiotherapy QA were explored, including the use of normal tissue toxicity and tumor control metrics, biomarkers of radiation toxicity, new radiotherapy modalities such as proton beam therapy, and the international harmonization of clinical trial QA. Four recommendations were made: (1) to develop a tiered (and more efficient) system for radiotherapy QA and tailor the intensity of QA to the clinical trial objectives (tiers include general credentialing, trial-specific credentialing, and individual case review); (2) to establish a case QA repository; (3) to develop an evidence base for clinical trial QA and introduce innovative prospective trial designs to evaluate radiotherapy QA in clinical trials; and (4) to explore the feasibility of consolidating clinical trial QA in the United States. Radiotherapy QA can affect clinical trial accrual, cost, outcomes, and generalizability. To achieve maximum benefit, QA programs must become more efficient and evidence-based. Copyright © 2012 Elsevier Inc. All rights reserved.

Improving clinical trials in the critically ill.

PubMed

Angus, Derek C; Mira, Jean-Paul; Vincent, Jean-Louis

2010-02-01

To propose ways in which clinical trials in intensive care can be improved. An international roundtable conference was convened focused on improvement in three broad areas: translation of new knowledge from bench to bedside; design and conduct of clinical trials; and clinical trial infrastructure and environment. The roundtable recommendations were: improvement in clinical trials is a multistep process from better preclinical studies to better clinical trial methodology; new technologies should be used to improve models of critical illness; diseasomes and theragnostics will aid inpatient population selection and more appropriate targeting of interventions; broader study end points should include morbidity as well as mortality; more multicenter studies should be conducted by national and international networks or clinical trials groups; and better collaboration is needed with the industry. There was broad agreement among the roundtable participants regarding a number of explicit opportunities for the improvement of clinical trials in critical care.

Clinical trials attitudes and practices of Latino physicians.

PubMed

Ramirez, Amelie G; Wildes, Kimberly; Talavera, Greg; Nápoles-Springer, Anna; Gallion, Kipling; Pérez-Stable, Eliseo J

2008-07-01

Ethnic differences in physicians' attitudes and behaviors related to clinical trials might partially account for disparities in clinical trial participation among Latino patients. Literature regarding Latino physicians' clinical trials attitudes and practices, in comparison to White physicians, was lacking. Cross-sectional data from randomly selected physicians (N=695), stratified by ethnicity, were analyzed to test associations of ethnicity with physicians' participation in and attitudes toward referral of patients to clinical trials. Chi-square analyses showed significant (p<0.05) associations of physician race/ethnicity and clinical trials involvement, type of trial for which the physician is likely to recommend a patient, belief in scientific value, and factors that would influence recommendation for a patient to participate. Multivariate analyses resulted in several significant (p<0.05) predictors of clinical trials outcomes, including physician race/ethnicity. Latino physicians were significantly less involved in clinical trials than White physicians and found less scientific value in them, highlighting areas for future education and intervention.

77 FR 13513 - Modernizing the Regulation of Clinical Trials and Approaches to Good Clinical Practice; Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-07

...The Food and Drug Administration (FDA) is announcing a 2-day public hearing to obtain input from interested persons on FDA's scope and direction in modernizing the regulations, policies, and practices that apply to the conduct of clinical trials of FDA-regulated products. Clinical trials are a critical source of evidence to inform medical policy and practice, and effective regulatory oversight is needed to ensure that human subjects are protected and resulting clinical trial data are credible and accurate. FDA is aware of concerns within the clinical trial community that certain regulations and policies applicable to the conduct of clinical trials may result in inefficiencies or increased cost and may not facilitate the use of innovative methods and technological advances to improve clinical trial quality. The Agency is involved in an effort to modernize the regulatory framework that governs clinical trials and approaches to good clinical practice (GCP). The purpose of this hearing is to solicit public input from a broad group of stakeholders on the scope and direction of this effort, including encouraging the use of innovative models that may enhance the effectiveness and efficiency of the clinical trial enterprise.

[Priorities of clinical drug trials in Brazil and neglected diseases of poverty].

PubMed

Santana, Rafael Santos; Leite, Silvana Nair

2016-11-01

To identify clinical drug trials performed in Brazil between 2012 and 2015, with emphasis on those focusing on neglected diseases of poverty. Two clinical trial registries, ReBEC (Brazilian registry) and ClinicalTrials.gov were surveyed. The following aspects were investigated: distribution of clinical trials in relation to the burden of disease in Brazil, distribution of trials regarding their focus on diseases of poverty vs. diseases not linked to poverty, phase of trials, performing institution, and type of funding (private, public, or mixed). The search revealed 866 eligible trials, 88 registered in ReBEC and 778 in ClinicalTrials.gov. Of these, 73 (8.5%) were phase I trials, 610 (70.5%) were phase II and III trials, and 183 (21%) were phase IV trials. There were 38 trials (4%) focusing on neglected diseases of poverty. Regarding the burden of disease, 734 (84.8%) trials focused on noncommunicable diseases, which in fact represent the largest burden of disease in Brazil. Most trials were carried out by pharmaceutical companies (55.3%), with predominance of private funding (57.1%); however, if only the diseases of poverty are considered, 63.1% were financed by public resources. The clinical drug trials carried out in Brazil in the study period are in agreement with the proportional burden of disease for the country. However, the neglected diseases of poverty were not prioritized. More effective action is necessary to redirect clinical research on drug development to meet national needs.

The current status of clinical trials focusing on nasopharyngeal carcinoma: A comprehensive analysis of ClinicalTrials.gov database.

PubMed

Peng, Hao; Chen, Lei; Chen, Yu-Pei; Li, Wen-Fei; Tang, Ling-Long; Lin, Ai-Hua; Sun, Ying; Ma, Jun

2018-01-01

Clinical Trials have emerged as the main force in driving the development of medicine. However, little is known about the current status of clinical trials regarding nasopharyngeal carcinoma (NPC). This study aimed at providing a comprehensive landscape of NPC-related trials on the basis of ClinicalTrials.gov database. We used the keyword "nasopharyngeal carcinoma" to search the ClinicalTrials.gov database and assessed the characteristics of these trials. Up to December 30, 2016, 462 eligible trials in total were identified, of which 222 (48.0%) recruited only NPC (NPC trials) and the other 240 (52.0%) recruited both NPC and other cancers (multiple cancer trials). Moreover, 47 (10.2%) were Epstein-Barr virus (EBV)-related trials and 267 (57.8%) focused on metastatic/recurrent disease. Compared with NPC trials, the multiple cancer trials had a higher percentage of phase 1 (26.7% vs. 6.7%, P < 0.001) studies and more patients with metastatic/recurrent disease (72.5% vs. 41.9%, P < 0.001). Notably, non-EBV trials had more phase 2 or 3 (78.4% vs. 48.8%, P < 0.001) and interventional studies (89.5% vs. 70.7%, P = 0.002) than EBV trials. Obviously, more phase 2/3 or 3 trials were conducted in patients with non-metastatic/recurrent disease (29.4% vs. 4.9%, P < 0.001); however, metastatic/recurrent trials were more likely to be anticancer (94.6% vs. 63.6%, P < 0.001). The role of plasma EBV DNA in clinical trials is underestimated, and high-level randomized clinical trials should be performed for patients with metastatic/recurrent disease.

Rebamipide Improves Chronic Inflammation in the Lesser Curvature of the Corpus after Helicobacter pylori Eradication: A Multicenter Study

PubMed Central

Kamada, Tomoari; Sato, Motonori; Tokutomi, Tadashi; Watanabe, Tetsuo; Murao, Takahisa; Matsumoto, Hiroshi; Manabe, Noriaki; Ito, Masanori; Tanaka, Shinji; Inoue, Kazuhiko; Shiotani, Akiko; Akiyama, Takashi; Hata, Jiro; Haruma, Ken

2015-01-01

Background and Aim. Although many epidemiologic studies have shown that Helicobacter pylori eradication has prophylactic effects on gastric cancer, it does not completely eliminate the risk of gastric cancer. We aimed to investigate the changes in histological gastritis in patients receiving rebamipide treatment after H. pylori eradication. Methods. 206 patients who had undergone H. pylori eradication were evaluated. Of these, 169 patients who achieved successful eradication were randomly allocated to 2 groups: the rebamipide group (n = 82) and the untreated group (n = 87). The primary endpoints were histopathological findings according to the updated Sydney system at the start of the study and after 1 year. Results. Final assessment for histological gastritis was possible in 50 cases from the rebamipide group and 53 cases from the untreated group. The activity and atrophy improved in both the rebamipide and untreated groups, and no significant intergroup differences were observed. Chronic inflammation affecting the lesser curvature of the corpus was significantly improved in the rebamipide group compared to in the untreated group (1.12 ± 0.08 versus 1.35 ± 0.08; P = 0.043). Conclusions. Rebamipide treatment after H. pylori eradication alleviated chronic inflammation in the lesser curvature of the corpus compared to that in the untreated group. This trial is registered with UMIN000002369. PMID:26060821

Daily Physical Activity Assessed by a Triaxial Accelerometer Is Beneficially Associated with Waist Circumference, Serum Triglycerides, and Insulin Resistance in Japanese Patients with Prediabetes or Untreated Early Type 2 Diabetes.

PubMed

Hamasaki, Hidetaka; Noda, Mitsuhiko; Moriyama, Sumie; Yoshikawa, Reo; Katsuyama, Hisayuki; Sako, Akahito; Mishima, Shuichi; Kakei, Masafumi; Ezaki, Osamu; Yanai, Hidekatsu

2015-01-01

To investigate the association between daily physical activity and metabolic risk factors in Japanese adults with prediabetes or untreated early type 2 diabetes (T2D). Daily physical activity level was measured using a triaxial accelerometer. We assessed correlations between physical activity level and waist circumference, blood pressure, fasting levels of plasma glucose, serum triglycerides, and insulin and homeostasis model assessment-insulin resistance (HOMA-IR). A total of 80 patients were studied. After adjustment for age and body mass index, in all subjects, physical activity level was negatively associated with waist circumference (β = -0.124, P = 0.018) and fasting serum triglycerides (β = -0.239, P = 0.035), insulin (β = -0.224, P = 0.022). In men, physical activity level was negatively associated with systolic blood pressure (β = -0.351, P = 0.044), fasting plasma glucose (β = -0.369, P = 0.025) and insulin (β = -0.362, P = 0.012), and HOMA-IR (β = -0.371, P = 0.011). No significant associations were found between physical activity level and metabolic risk factors in women. Objectively measured daily physical activity is beneficially associated with waist circumference, serum triglycerides, and insulin resistance in individuals with prediabetes or untreated early T2D. (This trial is registered with UMIN000015774.).

Ethics in clinical drug trial research in private practice.

PubMed

Beran, R G; Beran, M E

2006-09-01

Private clinics and clinicians have been involved in clinical drug trials for approximately two decades. This paper reviews the ethical consideration inherent in this process. Involvement of a single community based, private, Australian neurological clinic in the conduct of trials was audited. Changes in ethical considerations were analysed. The clinic previously audited its clinical trial involvement, starting with pharmaceutical company orchestrated trials. These were vetted by hospital based ethics committees (ECs) which then refused to review private research. A private EC accommodating NH & MRC standards was formed to assess private research. Indemnity concerns forced return to institutional ECs with government guaranteed indemnification. Trials evolved to investigator initiated, company sponsored studies thence a company asking the clinic to devise, sponsor and manage a trial. The latter relegated trial co-ordination to the clinic which would control publication thereby creating new ethical standards. Private practice trial involvement evolved from reluctant inclusion to a pivotal role in privately sponsored studies. Access to ECs is government endorsed and publication is independent for investigator-sponsored trials. There has been modification of standard operating procedures and enhanced ethical standards.

The challenge of comorbidity in clinical trials for multiple sclerosis.

PubMed

Marrie, Ruth Ann; Miller, Aaron; Sormani, Maria Pia; Thompson, Alan; Waubant, Emmanuelle; Trojano, Maria; O'Connor, Paul; Reingold, Stephen; Cohen, Jeffrey A

2016-04-12

We aimed to provide recommendations for addressing comorbidity in clinical trial design and conduct in multiple sclerosis (MS). We held an international workshop, informed by a systematic review of the incidence and prevalence of comorbidity in MS and an international survey about research priorities for studying comorbidity including their relation to clinical trials in MS. We recommend establishing age- and sex-specific incidence estimates for comorbidities in the MS population, including those that commonly raise concern in clinical trials of immunomodulatory agents; shifting phase III clinical trials of new therapies from explanatory to more pragmatic trials; describing comorbidity status of the enrolled population in publications reporting clinical trials; evaluating treatment response, tolerability, and safety in clinical trials according to comorbidity status; and considering comorbidity status in the design of pharmacovigilance strategies. Our recommendations will help address knowledge gaps regarding comorbidity that interfere with the ability to interpret safety in monitored trials and will enhance the generalizability of findings from clinical trials to "real world" settings where the MS population commonly has comorbid conditions. © 2016 American Academy of Neurology.

The challenge of comorbidity in clinical trials for multiple sclerosis

PubMed Central

Miller, Aaron; Sormani, Maria Pia; Thompson, Alan; Waubant, Emmanuelle; Trojano, Maria; O'Connor, Paul; Reingold, Stephen; Cohen, Jeffrey A.

2016-01-01

Objective: We aimed to provide recommendations for addressing comorbidity in clinical trial design and conduct in multiple sclerosis (MS). Methods: We held an international workshop, informed by a systematic review of the incidence and prevalence of comorbidity in MS and an international survey about research priorities for studying comorbidity including their relation to clinical trials in MS. Results: We recommend establishing age- and sex-specific incidence estimates for comorbidities in the MS population, including those that commonly raise concern in clinical trials of immunomodulatory agents; shifting phase III clinical trials of new therapies from explanatory to more pragmatic trials; describing comorbidity status of the enrolled population in publications reporting clinical trials; evaluating treatment response, tolerability, and safety in clinical trials according to comorbidity status; and considering comorbidity status in the design of pharmacovigilance strategies. Conclusion: Our recommendations will help address knowledge gaps regarding comorbidity that interfere with the ability to interpret safety in monitored trials and will enhance the generalizability of findings from clinical trials to “real world” settings where the MS population commonly has comorbid conditions. PMID:26888986

Clinical trials finance and operations.

PubMed

O'Brien, Jennifer A

2007-01-01

The National Coverage Decision of 2000 was designed to enhance the participation in clinical trials for both patients and physicians by mandating the governmental coverage for services in a clinical trial that are considered "routine" regardless of the trial. Participation in clinical trials can be a practice builder as well as a contribution to the betterment of medical science. Without proper coverage analysis, study budgeting, accurate time estimates, and effective negotiation prior to signing the contract, participation in clinical trials can cost a practice rather than benefit it.

Clinical trial quality: From supervision to collaboration and beyond.

PubMed

Meeker-O'Connell, Ann; Glessner, Coleen

2018-02-01

Over the past decade, clinical trial quality has evolved from an after-the-fact, reactive activity to one focused on the important work of evidence generation from well-designed trials. This article explores the role the Clinical Trials Transformation Initiative has played in advancing quality as a core element of clinical trial design, through project work that initially focused on monitoring but evolved into a holistic, prospective, and comprehensive quality by design approach to clinical trial design and conduct.

Characteristics and trends of clinical trials funded by the National Institutes of Health between 2005 and 2015.

PubMed

Gresham, Gillian K; Ehrhardt, Stephan; Meinert, Jill L; Appel, Lawrence J; Meinert, Curtis L

2018-02-01

Background The National Institutes of Health is one of the largest biomedical research agencies in the world. Clinical trials are an important component of National Institutes of Health research efforts. Given the recent updates in National Institutes of Health trial reporting requirements, more information regarding the current state of National Institutes of Health-funded clinical trials is warranted. The objective of this analysis was to describe characteristics and trends of clinical trials funded by the National Institutes of Health over time and by Institutes and Centers of the National Institutes of Health. Methods Interventional studies funded by the National Institutes of Health and registered in ClinicalTrials.gov between 2005 and 2015 were included in the analysis. Trials were identified from the 27 March 2016 Clinical Trials Transformation Initiative Aggregate Analysis of ClinicalTrials.gov database. A descriptive analysis of trials by year and National Institutes of Health Institute/Center was performed. Results There were 12,987 National Institutes of Health-funded clinical trials registered between 2005 and 2015. There were 1,580, 1,116, and 930 trials registered in 2005, 2010, and 2015, respectively. The majority were early-development trials (phases 0, 1, or 2; 53%), randomized (61%), and single-center (63%). Trial demographics have remained unchanged over time. Median trial sample size was 64 (interquartile range 29-192) with 10% of trials enrolling ≥500 participants. Most trials were completed within 5 years of enrollment start (69%). Trial characteristics varied considerably across National Institutes of Health Institutes and Centers. Results were reported under the assumptions that most National Institutes of Health-funded trials are registered in ClinicalTrials.gov and that trials are being registered completely and accurately. Conclusion In conclusion, there has been a decline in the number of trials being funded over time, explained in part by a relatively constant budget, increases in trial costs, or other factors that cannot be quantified. National Institutes of Health-funded trials are relatively small and tend to be single-centered. There are substantial differences in the number and types of trials done by Institutes and Centers within the National Institutes of Health.

[How to prevent hazards and to reduce risk in clinical trials?].

PubMed

Czarkowski, Marek

2008-12-01

Different stakeholders involved in clinical trials are exposed to hazards related with this biomedical research. Beside clinical trials participants other important stakeholders are: investigators, sponsors, centers and clinical research organizations. Hazard prevention needs effective methods of hazard disclosure and analysis. A reduction of risks related with clinical trials is possible due to education, training, inspections, research discipline and penalties. Effective ways of hazard elimination or hazard reduction should be developed as well. Education and training should be offered to all stakeholders but their forms and contents should be adapted to different types of stakeholders. Direct control of the clinical trials should be held by stakeholders conducting clinical trials and outside inspections should be done by other institutions like clinical research organizations, research ethics committees and The Office for Registration of Medicinal Products, Medical Devices and Biocidal Products. Serious oversight is an absence of any independent inspection during a phase of publication of clinical trial results. We should not accept any exception from the golden rule that results of all clinical trials must be published. Indemnity for damages is a popular way of compensation for clinical trials participants. Investigators, sponsors and centers should have valid liability insurance. Drastic measures for reduction of risks in clinical trials are different kinds of penalties. They should prevent participation of unreliable stakeholders and promote those who respect regulations and high ethical standards.

[Basic considerations during outsourcing of clinical data management services].

PubMed

Shen, Tong; Liu, Yan

2015-11-01

With worldwide improvements in the regulations of international and domestic clinical trial conductions, the quality of clinical trials and trial data management are receiving a great deal of attention. To ensure the quality of clinical trials, maintain business flexibilities and effectively utilize internal and external resources, the outsourcing model is used in the management of clinical data in operation of pharmaceutical companies. The essential criteria of a successful outsourcing mode in clinical trial are selection of qualified contract research organizations (CRO); establishment of appropriate outsourcing model, and generation of effective quality control systems to ensure the authenticity, integrity and accuracy of the clinical trial data.

ClinicalTrials.gov and Drugs@FDA: A comparison of results reporting for new drug approval trials

PubMed Central

Schwartz, Lisa M.; Woloshin, Steven; Zheng, Eugene; Tse, Tony; Zarin, Deborah A.

2016-01-01

Background Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. Purpose To validate results posted on ClinicalTrials.gov against publicly-available FDA reviews on Drugs@FDA. Data sources ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical/statistical reviews). Study selection 100 parallel-group, randomized trials for new drug approvals (1/2013 – 7/2014) with results posted on ClinicalTrials.gov (3/15/2015). Data extraction Two assessors systematically extracted, and another verified, trial design, primary/secondary outcomes, adverse events, and deaths. Results The 100 trials were mostly phase 3 (90%) double-blind (92%), placebo-controlled (73%), representing 32 drugs from 24 companies. Of 137 primary outcomes from ClinicalTrials.gov, 134 (98%) had corresponding data in Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results; most differences were nominal (i.e. relative difference < 10%). Of 100 trials, primary outcome results in 14 could not be validated . Of 1,927 secondary outcomes from ClinicalTrials.gov, 1,061 (55%) definitions could be validated and 367 (19%) had results. Of 96 trials with ≥ 1 serious adverse event in either source, 14 could be compared and 7 were discordant. Of 62 trials with ≥ 1 death in either source, 25 could be compared and 17 were discordant. Limitations Unknown generalizability to uncontrolled or crossover trial results. Conclusion Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half of secondary outcomes could not be validated because Drugs@FDA only includes “key outcomes” for regulatory decision-making; nor could serious adverse events and deaths because Drugs@FDA frequently only includes results aggregated across multiple trials. PMID:27294570

Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: cross sectional study.

PubMed

Prayle, Andrew P; Hurley, Matthew N; Smyth, Alan R

2012-01-03

To examine compliance with mandatory reporting of summary clinical trial results (within one year of completion of trial) on ClinicalTrials.gov for studies that fall under the recent Food and Drug Administration Amendments Act (FDAAA) legislation. Registry based study of clinical trial summaries. ClinicalTrials.gov, searched on 19 January 2011, with cross referencing with Drugs@FDA to determine for which trials mandatory reporting was required within one year. Selection criteria Studies registered on ClinicalTrials.gov with US sites which completed between 1 January and 31 December 2009. Proportion of trials for which results had been reported. The ClinicalTrials.gov registry contained 83,579 entries for interventional trials, of which 5642 were completed within the timescale of interest. We identified trials as falling within the mandatory reporting rules if they were covered by the FDAAA (trials of a drug, device, or biological agent, which have at least one US site, and are of phase II or later) and if they investigated a drug that already had approval from the Food and Drug Administration. Of these, 163/738 (22%) had reported results within one year of completion of the trial compared with 76/727 (10%) trials that were not subject to mandatory reporting (95% confidence interval for the difference in proportions 7.8% to 15.5%; χ(2) test, P = 2.6 × 10(-9)). Later phase trials were more likely to report results (P = 4.4 × 10(-11)), as were industry funded trials (P = 2.2 × 10(-16)). Most trials subject to mandatory reporting did not report results within a year of completion.

Current globalization of drug interventional clinical trials: characteristics and associated factors, 2011-2013.

PubMed

Jeong, Sohyun; Sohn, Minji; Kim, Jae Hyun; Ko, Minoh; Seo, Hee-Won; Song, Yun-Kyoung; Choi, Boyoon; Han, Nayoung; Na, Han-Sung; Lee, Jong Gu; Kim, In-Wha; Oh, Jung Mi; Lee, Euni

2017-06-21

Clinical trial globalization is a major trend for industry-sponsored clinical trials. There has been a shift in clinical trial sites towards emerging regions of Eastern Europe, Latin America, Asia, the Middle East, and Africa. Our study objectives were to evaluate the current characteristics of clinical trials and to find out the associated multiple factors which could explain clinical trial globalization and its implications for clinical trial globalization in 2011-2013. The data elements of "phase," "recruitment status," "type of sponsor," "age groups," and "design of trial" from 30 countries were extracted from the ClinicalTrials.gov website. Ten continental representative countries including the USA were selected and the design elements were compared to those of the USA. Factors associated with trial site distribution were chosen for a multilinear regression analysis. The USA, Germany, France, Canada, and United Kingdom were the "top five" countries which frequently held clinical trials. The design elements from nine continental representative countries were quite different from those of the USA; phase 1 trials were more prevalent in India (OR 1.517, p < 0.001) while phase 3 trials were much more prevalent in all nine representative countries than in the USA. A larger number of "child" age group trials was performed in Poland (OR 1.852, p < 0.001), Israel (OR 1.546, p = 0.005), and South Africa (OR 1.963, p < 0.001) than in the USA. Multivariate analysis showed that health care expenditure per capita, Economic Freedom Index, Human Capital Index, and Intellectual Property Rights Index could explain the variance of regional distribution of clinical trials by 63.6%. The globalization of clinical trials in the emerging regions of Asia, South Africa, and Eastern Europe developed in parallel with the factors of economic drive, population for recruitment, and regulatory constraints.

Factors influencing clinical trial site selection in Europe: the Survey of Attitudes towards Trial sites in Europe (the SAT-EU Study).

PubMed

Gehring, Marta; Taylor, Rod S; Mellody, Marie; Casteels, Brigitte; Piazzi, Angela; Gensini, Gianfranco; Ambrosio, Giuseppe

2013-11-15

Applications to run clinical trials in Europe fell 25% between 2007 and 2011. Costs, speed of approvals and shortcomings of European Clinical Trial Directive are commonly invoked to explain this unsatisfactory performance. However, no hard evidence is available on the actual weight of these factors or has it been previously investigated whether other criteria may also impact clinical trial site selection. The Survey of Attitudes towards Trial sites in Europe (SAT-EU Study) was an anonymous, cross-sectional web-based survey that systematically assessed factors impacting European clinical trial site selection. It explored 19 factors across investigator-driven, hospital-driven and environment-driven criteria, and costs. It also surveyed perceptions of the European trial environment. Clinical research organisations (CROs), academic clinical trial units (CTUs) and industry invited to respond. weight assigned to each factor hypothesised to impact trial site selection and trial incidence. Secondary outcome: desirability of European countries to run clinical trials. Responses were obtained from 485 professionals in 34 countries: 49% from BioPharma, 40% from CTUs or CROs. Investigator-dependent, environment-dependent and hospital-dependent factors were rated highly important, costs being less important (p<0.0001). Within environment-driven criteria, pool of eligible patients, speed of approvals and presence of disease-management networks were significantly more important than costs or government financial incentives (p<0.0001). The pattern of response was consistent across respondent groupings (CTU vs CRO vs industry). Considerable variability was demonstrated in the perceived receptivity of countries to undertake clinical trials, with Germany, the UK and the Netherlands rated the best trial markets (p<0.0001). Investigator-dependent factors and ease of approval dominate trial site selection, while costs appear less important. Fostering competitiveness of European clinical research may not require additional government spending/incentives. Rather, harmonisation of approval processes, greater visibility of centres of excellence and reduction of 'hidden' indirect costs, may bring significantly more clinical trials to Europe.

Characteristics of randomised trials on diseases in the digestive system registered in ClinicalTrials.gov: a retrospective analysis.

PubMed

Wildt, Signe; Krag, Aleksander; Gluud, Liselotte

2011-01-01

Objectives To evaluate the adequacy of reporting of protocols for randomised trials on diseases of the digestive system registered in http://ClinicalTrials.gov and the consistency between primary outcomes, secondary outcomes and sample size specified in http://ClinicalTrials.gov and published trials. Methods Randomised phase III trials on adult patients with gastrointestinal diseases registered before January 2009 in http://ClinicalTrials.gov were eligible for inclusion. From http://ClinicalTrials.gov all data elements in the database required by the International Committee of Medical Journal Editors (ICMJE) member journals were extracted. The subsequent publications for registered trials were identified. For published trials, data concerning publication date, primary and secondary endpoint, sample size, and whether the journal adhered to ICMJE principles were extracted. Differences between primary and secondary outcomes, sample size and sample size calculations data in http://ClinicalTrials.gov and in the published paper were registered. Results 105 trials were evaluated. 66 trials (63%) were published. 30% of trials were registered incorrectly after their completion date. Several data elements of the required ICMJE data list were not filled in, with missing data in 22% and 11%, respectively, of cases concerning the primary outcome measure and sample size. In 26% of the published papers, data on sample size calculations were missing and discrepancies between sample size reporting in http://ClinicalTrials.gov and published trials existed. Conclusion The quality of registration of randomised controlled trials still needs improvement.

Timing and completeness of trial results posted at ClinicalTrials.gov and published in journals.

PubMed

Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe

2013-12-01

The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration-approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45%, p<0.001), and serious adverse events (99% versus 63%, p<0.001). The main study limitation was that we considered only the publication describing the results for the primary outcomes. Our results highlight the need to search ClinicalTrials.gov for both unpublished and published trials. Trial results, especially serious adverse events, are more completely reported at ClinicalTrials.gov than in the published article.

Chronic heart failure does not attenuate the total activity of sympathetic outflow to skin during whole-body heating.

PubMed

Cui, Jian; Boehmer, John P; Blaha, Cheryl; Lucking, Robert; Kunselman, Allen R; Sinoway, Lawrence I

2013-03-01

Previous studies show that the rise in skin blood flow and cutaneous vascular conductance during heat stress is substantially attenuated in chronic heart failure (CHF) patients. The mechanisms responsible for this finding are not clear. In particular, little is known regarding the responses of skin sympathetic nerve activity (SSNA) that control the skin blood flow during heat stress in CHF patients. We examined the effects of a modest heat stress to test the hypothesis that SSNA responses could be attenuated in CHF. We assessed SSNA (microneurography) from the peroneal nerve and skin blood flow (forearm laser Doppler) in 9 patients with stable class II-III CHF and in matched healthy subjects during passive whole-body heating with a water-perfused suit. Whole-body heating induced similar increases in internal temperature (≈0.6 °C) in both groups. Whole-body heat stress evoked similar SSNA activation in CHF patients (Δ891±110 U/min) and the control subjects (Δ787±84 U/min; P=0.66), whereas the elevation in forearm cutaneous vascular conductance in patients with CHF was significantly lower than that in healthy control subjects (Δ131±29% vs. Δ623±131%; P=0.001). The present data show that SSNA activation during a modest whole-body heat stress is not attenuated in CHF. Thus, the attenuated skin vasodilator response in CHF patients is not attributable to a reduction in total activity of sympathetic outflow to skin.

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of rehabilitation interventions for osteoarthritis.

PubMed

Fitzgerald, G K; Hinman, R S; Zeni, J; Risberg, M A; Snyder-Mackler, L; Bennell, K L

2015-05-01

A Task Force of the Osteoarthritis Research Society International (OARSI) has previously published a set of guidelines for the conduct of clinical trials in osteoarthritis (OA) of the hip and knee. Limited material available on clinical trials of rehabilitation in people with OA has prompted OARSI to establish a separate Task Force to elaborate guidelines encompassing special issues relating to rehabilitation of OA. The Task Force identified three main categories of rehabilitation clinical trials. The categories included non-operative rehabilitation trials, post-operative rehabilitation trials, and trials examining the effectiveness of devices (e.g., assistive devices, bracing, physical agents, electrical stimulation, etc.) that are used in rehabilitation of people with OA. In addition, the Task Force identified two main categories of outcomes in rehabilitation clinical trials, which include outcomes related to symptoms and function, and outcomes related to disease modification. The guidelines for rehabilitation clinical trials provided in this report encompass these main categories. The report provides guidelines for conducting and reporting on randomized clinical trials. The topics include considerations for entering patients into trials, issues related to conducting trials, considerations for selecting outcome measures, and recommendations for statistical analyses and reporting of results. The focus of the report is on rehabilitation trials for hip, knee and hand OA, however, we believe the content is broad enough that it could be applied to rehabilitation trials for other regions as well. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Phase 3 Oncology Clinical Trials in South Africa: Experimentation or Therapeutic Misconception?

PubMed

Malan, Tina; Moodley, Keymanthri

2016-02-01

Although clinical research in oncology is vital to improve current understanding of cancer and to validate new treatment options, voluntary informed consent is a critical component. Oncology research participants are a particularly vulnerable population; hence, therapeutic misconception often leads to ethical and legal challenges. We conducted a qualitative study administering semi-structured questionnaires on 29 adult, Phase 3, oncology clinical trial participants at three different private oncology clinical trial sites in South Africa. A descriptive content analysis was performed to identify perceptions of these participants regarding Phase 3 clinical trials. We found that most participants provided consent to be included in the trial for self-benefit. More than half of the participants had a poor understanding of Phase 3 clinical trials, and almost half the participants believed the clinical trial did not pose any significant risk to them. The word "hope" was used frequently by participants, displaying clear optimism with regard to the clinical trial and its outcome. This indicated that therapeutic misconception does occur in the South African oncology research setting and has the potential to lead to underestimation of the risks of a Phase 3 clinical trial. Emphasizing the experimental nature of a clinical trial during the consent process is critical to address therapeutic misconception in oncology research. © The Author(s) 2016.

Types of Cancer Clinical Trials

Cancer.gov

Information about the several types of cancer clinical trials, including treatment trials, prevention trials, screening trials, supportive and palliative care trials. Each type of trial is designed to answer different research questions.

Non-commercial vs. commercial clinical trials: a retrospective study of the applications submitted to a research ethics committee.

PubMed

Fuentes Camps, Inmaculada; Rodríguez, Alexis; Agustí, Antonia

2018-06-01

There are many difficulties in undertaking independent clinical research without support from the pharmaceutical industry. In this retrospective observational study, some design characteristics, the clinical trial public register and the publication rate of noncommercial clinical trials were compared to those of commercial clinical trials. A total of 809 applications of drug-evaluation clinical trials were submitted from May 2004 to May 2009 to the research ethics committee of a tertiary hospital, and 16.3% of trials were noncommercial. They were mainly phase IV, multicentre national, and unmasked controlled trials, compared to the commercial trials that were mainly phase II or III, multicentre international, and double-blind masked trials. The commercial trials were registered and published more often than noncommercial trials. More funding for noncommercial research is still needed. The results of the research, commercial or noncommercial, should be disseminated in order not to compromise either its scientific or its social value. © 2018 The British Pharmacological Society.

Terminated Trials in the ClinicalTrials.gov Results Database: Evaluation of Availability of Primary Outcome Data and Reasons for Termination

PubMed Central

Williams, Rebecca J.; Tse, Tony; DiPiazza, Katelyn; Zarin, Deborah A.

2015-01-01

Background Clinical trials that end prematurely (or “terminate”) raise financial, ethical, and scientific concerns. The extent to which the results of such trials are disseminated and the reasons for termination have not been well characterized. Methods and Findings A cross-sectional, descriptive study of terminated clinical trials posted on the ClinicalTrials.gov results database as of February 2013 was conducted. The main outcomes were to characterize the availability of primary outcome data on ClinicalTrials.gov and in the published literature and to identify the reasons for trial termination. Approximately 12% of trials with results posted on the ClinicalTrials.gov results database (905/7,646) were terminated. Most trials were terminated for reasons other than accumulated data from the trial (68%; 619/905), with an insufficient rate of accrual being the lead reason for termination among these trials (57%; 350/619). Of the remaining trials, 21% (193/905) were terminated based on data from the trial (findings of efficacy or toxicity) and 10% (93/905) did not specify a reason. Overall, data for a primary outcome measure were available on ClinicalTrials.gov and in the published literature for 72% (648/905) and 22% (198/905) of trials, respectively. Primary outcome data were reported on the ClinicalTrials.gov results database and in the published literature more frequently (91% and 46%, respectively) when the decision to terminate was based on data from the trial. Conclusions Trials terminate for a variety of reasons, not all of which reflect failures in the process or an inability to achieve the intended goals. Primary outcome data were reported most often when termination was based on data from the trial. Further research is needed to identify best practices for disseminating the experience and data resulting from terminated trials in order to help ensure maximal societal benefit from the investments of trial participants and others involved with the study. PMID:26011295

Terminated Trials in the ClinicalTrials.gov Results Database: Evaluation of Availability of Primary Outcome Data and Reasons for Termination.

PubMed

Williams, Rebecca J; Tse, Tony; DiPiazza, Katelyn; Zarin, Deborah A

2015-01-01

Clinical trials that end prematurely (or "terminate") raise financial, ethical, and scientific concerns. The extent to which the results of such trials are disseminated and the reasons for termination have not been well characterized. A cross-sectional, descriptive study of terminated clinical trials posted on the ClinicalTrials.gov results database as of February 2013 was conducted. The main outcomes were to characterize the availability of primary outcome data on ClinicalTrials.gov and in the published literature and to identify the reasons for trial termination. Approximately 12% of trials with results posted on the ClinicalTrials.gov results database (905/7,646) were terminated. Most trials were terminated for reasons other than accumulated data from the trial (68%; 619/905), with an insufficient rate of accrual being the lead reason for termination among these trials (57%; 350/619). Of the remaining trials, 21% (193/905) were terminated based on data from the trial (findings of efficacy or toxicity) and 10% (93/905) did not specify a reason. Overall, data for a primary outcome measure were available on ClinicalTrials.gov and in the published literature for 72% (648/905) and 22% (198/905) of trials, respectively. Primary outcome data were reported on the ClinicalTrials.gov results database and in the published literature more frequently (91% and 46%, respectively) when the decision to terminate was based on data from the trial. Trials terminate for a variety of reasons, not all of which reflect failures in the process or an inability to achieve the intended goals. Primary outcome data were reported most often when termination was based on data from the trial. Further research is needed to identify best practices for disseminating the experience and data resulting from terminated trials in order to help ensure maximal societal benefit from the investments of trial participants and others involved with the study.

Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry.

PubMed

Zhang, Xinji; Zhang, Yuan; Ye, Xiaofei; Guo, Xiaojing; Zhang, Tianyi; He, Jia

2016-11-23

Phase IV trials are often used to investigate drug safety after approval. However, little is known about the characteristics of contemporary phase IV clinical trials and whether these studies are of sufficient quality to advance medical knowledge in pharmacovigilance. We aimed to determine the fundamental characteristics of phase IV clinical trials that evaluated drug safety using the ClinicalTrials.gov registry data. A data set of 19 359 phase IV clinical studies registered in ClinicalTrials.gov was downloaded. The characteristics of the phase IV trials focusing on safety only were compared with those evaluating both safety and efficacy. We also compared the characteristics of the phase IV trials in three major therapeutic areas (cardiovascular diseases, mental health and oncology). Multivariable logistic regression was used to evaluate factors associated with the use of blinding and randomisation. A total of 4772 phase IV trials were identified, including 330 focusing on drug safety alone and 4392 evaluating both safety and efficacy. Most of the phase IV trials evaluating drug safety (75.9%) had enrolment <300 with 96.5% <3000. Among these trials, 8.2% were terminated or withdrawn. Factors associated with the use of blinding and randomisation included the intervention model, clinical specialty and lead sponsor. Phase IV trials evaluating drug safety in the ClinicalTrials.gov registry were dominated by small trials that might not have sufficient power to detect less common adverse events. An adequate sample size should be emphasised for phase IV trials with safety surveillance as main task. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Funding source and primary outcome changes in clinical trials registered on ClinicalTrials.gov are associated with the reporting of a statistically significant primary outcome: a cross-sectional study.

PubMed

Ramagopalan, Sreeram V; Skingsley, Andrew P; Handunnetthi, Lahiru; Magnus, Daniel; Klingel, Michelle; Pakpoor, Julia; Goldacre, Ben

2015-01-01

We and others have shown a significant proportion of interventional trials registered on ClinicalTrials.gov have their primary outcomes altered after the listed study start and completion dates. The objectives of this study were to investigate whether changes made to primary outcomes are associated with the likelihood of reporting a statistically significant primary outcome on ClinicalTrials.gov. A cross-sectional analysis of all interventional clinical trials registered on ClinicalTrials.gov as of 20 November 2014 was performed. The main outcome was any change made to the initially listed primary outcome and the time of the change in relation to the trial start and end date. 13,238 completed interventional trials were registered with ClinicalTrials.gov that also had study results posted on the website. 2555 (19.3%) had one or more statistically significant primary outcomes. Statistical analysis showed that registration year, funding source and primary outcome change after trial completion were associated with reporting a statistically significant primary outcome .  Funding source and primary outcome change after trial completion are associated with a statistically significant primary outcome report on clinicaltrials.gov.

Generalizability of Clinical Trial Results for Adolescent Major Depressive Disorder.

PubMed

Blanco, Carlos; Hoertel, Nicolas; Franco, Silvia; Olfson, Mark; He, Jian-Ping; López, Saioa; González-Pinto, Ana; Limosin, Frédéric; Merikangas, Kathleen R

2017-12-01

Although there have been a number of clinical trials evaluating treatments for adolescents with major depressive disorder (MDD), the generalizability of those trials to samples of depressed adolescents who present for routine clinical care is unknown. Examining the generalizability of clinical trials of pharmacological and psychotherapy interventions for adolescent depression can help administrators and frontline practitioners determine the relevance of these studies for their patients and may also guide eligibility criteria for future clinical trials in this clinical population. Data on nationally representative adolescents were derived from the National Comorbidity Survey: Adolescent Supplement. To assess the generalizability of adolescent clinical trials for MDD, we applied a standard set of eligibility criteria representative of clinical trials to all adolescents in the National Comorbidity Survey: Adolescent Supplement with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of MDD ( N = 592). From the overall MDD sample, 61.9% would have been excluded from a typical pharmacological trial, whereas 42.2% would have been excluded from a psychotherapy trial. Among those who sought treatment ( n = 412), the corresponding exclusion rates were 72.7% for a pharmacological trial and 52.2% for a psychotherapy trial. The criterion leading to the largest number of exclusions was "significant risk of suicide" in both pharmacological and psychotherapy trials. Pharmacological and, to a lesser extent, psychotherapy clinical trials likely exclude most adolescents with MDD. Careful consideration should be given to balancing eligibility criteria and internal validity with applicability in routine clinical care while ensuring patient safety. Copyright © 2017 by the American Academy of Pediatrics.

Feasibility of feature-based indexing, clustering, and search of clinical trials: A case study of breast cancer trials from ClinicalTrials.gov

PubMed Central

Boland, Mary Regina; Miotto, Riccardo; Gao, Junfeng; Weng, Chunhua

2013-01-01

Summary Background When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. Objectives This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. Methods We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. Results We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. Conclusions It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency. PMID:23666475

Feasibility of feature-based indexing, clustering, and search of clinical trials. A case study of breast cancer trials from ClinicalTrials.gov.

PubMed

Boland, M R; Miotto, R; Gao, J; Weng, C

2013-01-01

When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency.

ClinicalTrials.gov

MedlinePlus

... Terms and Conditions Disclaimer ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted ... world. ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of ...

Volunteering for Clinical Trials Can Help Improve Health Care for Everyone | NIH MedlinePlus the Magazine

MedlinePlus

... page please turn Javascript on. Feature: Clinical Trials Volunteering for Clinical Trials Can Help Improve Health Care ... save lives." Photo: Fran Sandridge For Melanie Modlin, volunteering to take part in a clinical trial was ...

77 FR 9947 - Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-21

...] Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry, Manufacturing... ``Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry, Manufacturing... for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry, Manufacturing, and...

Minorities and Clinical Trials: Patients, Physicians, Clinical Trial Characteristics, and Their Environment

DTIC Science & Technology

2011-07-01

cancer clinical trials, attitudes and knowledge about such trials, and barriers to and facilitators of participation, b) Conduct a self-administered...facilitate or hinder participation in prostate cancer trials by examining patients’ attitudes , physicians’ perceived barriers, characteristics of...cancer trials by examining patients’ attitudes , physicians’ perceived barriers, characteristics of prostate trials and sites, and broader community

Clinical Trials | Division of Cancer Prevention

Cancer.gov

Information about actively enrolling, ongoing, and completed clinical trials of cancer prevention, early detection, and supportive care, including phase I, II, and III agent and action trials and clinical trials management. |

NRG Oncology medical physicists' manpower survey quantifying support demands for multi-institutional clinical trials.

PubMed

Monroe, James I; Boparai, Karan; Xiao, Ying; Followill, David; Galvin, James M; Klein, Eric E; Low, Daniel A; Moran, Jean M; Zhong, Haoyu; Sohn, Jason W

2018-02-04

A survey was created by NRG to assess a medical physicists' percent full time equivalent (FTE) contribution to multi-institutional clinical trials. A 2012 American Society for Radiation Oncology report, "Safety Is No Accident," quantified medical physics staffing contributions in FTE factors for clinical departments. No quantification of FTE effort associated with clinical trials was included. To address this lack of information, the NRG Medical Physics Subcommittee decided to obtain manpower data from the medical physics community to quantify the amount of time medical physicists spent supporting clinical trials. A survey, consisting of 16 questions, was designed to obtain information regarding physicists' time spent supporting clinical trials. The survey was distributed to medical physicists at 1996 radiation therapy institutions included on the membership rosters of the 5 National Clinical Trials Network clinical trial groups. Of the 451 institutions who responded, 50% (226) reported currently participating in radiation therapy trials. On average, the designated physicist at each institution spent 2.4 hours (standard deviation [SD], 5.5) per week supervising or interacting with clinical trial staff. On average, 1.2 hours (SD, 3.1), 1.8 hours (SD, 3.9), and 0.6 hours (SD, 1.1) per week were spent on trial patient simulations, treatment plan reviews, and maintaining a Digital Imaging and Communications in Medicine server, respectively. For all trial credentialing activities, physicists spent an average of 32 hours (SD, 57.2) yearly. Reading protocols and supporting dosimetrists, clinicians, and therapists took an average of 2.1 hours (SD, 3.4) per week. Physicists also attended clinical trial meetings, on average, 1.2 hours (SD, 1.9) per month. On average, physicist spent a nontrivial total of 9 hours per week (0.21 FTE) supporting an average of 10 active clinical trials. This time commitment indicates the complexity of radiation therapy clinical trials and should be taken into account when staffing radiation therapy institutions. Copyright © 2018 Elsevier Inc. All rights reserved.

Clinical trial spots for cancer patients by tumor type: The cancer trials portfolio at clinicaltrials.gov

PubMed Central

Prasad, Vinay; Goldstein, Jeffery A.

2015-01-01

Background Although participation in cancer clinical trials is low, little is known about the number of available clinical trials, and open spots for patients. Moreover, it is unclear what the relationship is between clinical trial openings and the incidence and mortality of cancer subtypes. Methodology We identified the number of phase I, phase II, and phase III registered at clinicaltrials.gov by cancer (tumor) type. All counts were over the preceding 5 years (2008 to 2013). We compared these counts against the incidence and prevalence of disease reported by Surveillance, Epidemiology, and End Results (SEER) database for 32 common cancers Results From 2008 to 2013, 3879 phase I trials, 4982 phase II trials and 1379 phase III trials concerning a cancer subtype were registered in clinicaltrials.gov. These trials had a cumulative proposed recruitment of 203396, 421502, and 697787 patients, respectively. Trial enrollment varied by tumor type, with both over and under-representation occurring. Conclusion Opportunities to enroll in clinical trials vary by phase and tumor type. Oncologists must remain committed to clinical trials. PMID:26321010

Clinical trial spots for cancer patients by tumour type: The cancer trials portfolio at clinicaltrials.gov.

PubMed

Prasad, Vinay; Goldstein, Jeffery A

2015-11-01

Although participation in cancer clinical trials is low, little is known about the number of available clinical trials, and open spots for patients. Moreover, it is unclear what the relationship is between clinical trial openings and the incidence and mortality of cancer subtypes. We identified the number of phase I, phase II and phase III registered at clinicaltrials.gov by cancer (tumour) type. All counts were over the preceding 5 years (2008-2013). We compared these counts against the incidence and prevalence of disease reported by Surveillance, Epidemiology and End Results (SEER) database for 32 common cancers. From 2008 to 2013, 3879 phase I trials, 4982 phase II trials and 1379 phase III trials concerning a cancer subtype were registered in clinicaltrials.gov. These trials had a cumulative proposed recruitment of 203,396, 421,502 and 697,787 patients, respectively. Trial enrollment varied by tumour type, with both over and under-representation occurring. Opportunities to enroll in clinical trials vary by phase and tumour type. Oncologists must remain committed to clinical trials. Published by Elsevier Ltd.

Feasibility trial of a Spanish-language multimedia educational intervention.

PubMed

Wells, Kristen J; McIntyre, Jessica; Gonzalez, Luis E; Lee, Ji-Hyun; Fisher, Kate J; Jacobsen, Paul B; Meade, Cathy; Muñoz-Antonia, Teresita; Quinn, Gwendolyn P

2013-10-01

Hispanic cancer patients are underrepresented in clinical trials; research suggests lack of knowledge and language barriers contribute to low accrual. Multimedia materials offer advantages to Hispanic populations because they have high acceptability, are easy to disseminate, and can be viewed with family. Hispanic cancer patients and caregivers participated in focus groups to aid in developing a Spanish-language multimedia intervention to educate Hispanic cancer patients about clinical trials. We explored the feasibility of delivering the intervention in medical oncology clinics. A total of 35 patients were randomized to either the multimedia intervention group (n = 18) or a control group (n = 17) who were asked to read the National Cancer Institute's Spanish-language clinical trials brochure. Self-reported data on knowledge about and attitudes toward clinical trials, self-efficacy for participating in a clinical trial, intention to participate in a clinical trial if asked, and receptivity to information about a clinical trial were collected at baseline and 10 days later. Delivery of the multimedia presentation in oncology clinics was feasible. The intervention group had more knowledge about clinical trials at follow-up than the control group; scores for intention to participate in a clinical trial by participants in the intervention group increased from 3.8 to 4.0 of a possible 5, but declined in the control group from 4.5 to 4.1. No statistically significant difference was detected between groups in scores for attitudes or self-efficacy for making a decision to participate in a clinical trial. Our sample size was inadequate to identify differences between the informational methods. Although all patients were asked about their willingness to participate in a clinical trial, this decision was hypothetical. In addition, the study was conducted with a sample of Spanish-speaking Hispanic cancer patients at a comprehensive cancer center in Florida. Thus, the results may not generalize to other Hispanic populations. In the pilot project, we demonstrated the feasibility of delivering multimedia information to patients in medical oncology clinics. Because delivery in a clinical setting was found to be feasible, a larger study should be conducted to evaluate the efficacy of the multimedia intervention with respect to promoting accrual of Hispanic patients to clinical trials.

Standards for Clinical Trials in Male and Female Sexual Dysfunction: I. Phase I to Phase IV Clinical Trial Design.

PubMed

Fisher, William A; Gruenwald, Ilan; Jannini, Emmanuele A; Lev-Sagie, Ahinoam; Lowenstein, Lior; Pyke, Robert E; Reisman, Yakov; Revicki, Dennis A; Rubio-Aurioles, Eusebio

2016-12-01

This series of articles outlines standards for clinical trials of treatments for male and female sexual dysfunctions, with a focus on research design and patient-reported outcome assessment. These articles consist of revision, updating, and integration of articles on standards for clinical trials in male and female sexual dysfunction from the 2010 International Consultation on Sexual Medicine developed by the authors as part of the 2015 International Consultation on Sexual Medicine. We are guided in this effort by several principles. In contrast to previous versions of these guidelines, we merge discussion of standards for clinical trials in male and female sexual dysfunction in an integrated approach that emphasizes the common foundational practices that underlie clinical trials in the two settings. We present a common expected standard for clinical trial design in male and female sexual dysfunction, a common rationale for the design of phase I to IV clinical trials, and common considerations for selection of study population and study duration in male and female sexual dysfunction. We present a focused discussion of fundamental principles in patient- (and partner-) reported outcome assessment and complete this series of articles with specific discussions of selected aspects of clinical trials that are unique to male and to female sexual dysfunction. Our consideration of standards for clinical trials in male and female sexual dysfunction attempts to embody sensitivity to existing and new regulatory guidance and to address implications of the evolution of the diagnosis of sexual dysfunction that have been brought forward in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. The first article in this series focuses on phase I to phase IV clinical trial design considerations. Subsequent articles in this series focus on the measurement of patient-reported outcomes, unique aspects of clinical trial design for men, and unique aspects of clinical trial design for women. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Is Religiosity Related to Attitudes Towards Clinical Trials Participation?

PubMed Central

Daverio-Zanetti, Svetlana; Schultz, Kathryn; del Campo, Miguel A. Martin; Malcarne, Vanessa; Riley, Natasha; Sadler, Georgia Robins

2014-01-01

Research indicates that a low percentage of cancer patients enroll in cancer clinical trials. This is especially true among minority groups such as Hispanic Americans. Considering the importance of religion in the Hispanic American community, it is important to understand its relationship to perceptions of clinical trials. Five hundred and three Latina women completed the Barriers to Clinical Trials Participation Scale and the Duke University Religion Index. For the total sample, higher organizational and intrinsic religiosity were significantly associated with perceived lack of community support for clinical trials participation. In subgroup analysis, the relationship between organizational religiosity and lack of support was stronger among Latinas who were Spanish language-preference, and Latinas who were Catholic. Intrinsic religiosity was associated with mistrust among Spanish language-preference Latinas, and both organizational and intrinsic religiosity were associated with lack of familiarity with clinical trials among Christian (non-Catholic) Latinas. These results indicate religious institutions that serve Latinas may be an effective venue for disseminating clinical trial education programs to improve attitudes toward clinical trials participation. PMID:24953236

Social media in clinical trials.

PubMed

Thompson, Michael A

2014-01-01

Social media has potential in clinical trials for pointing out trial issues, addressing barriers, educating, and engaging multiple groups involved in cancer clinical research. Social media is being used in clinical trials to highlight issues such as poor accrual and barriers; educate potential participants and physicians about clinical trial options; and is a potential indirect or direct method to improve accrual. We are moving from a passive "push" of information to patients to a "pull" of patients requesting information. Patients and advocates are often driving an otherwise reluctant health care system into communication. Online patient communities are creating new information repositories. Potential clinical trial participants are using the Twittersphere and other sources to learn about potential clinical trial options. We are seeing more organized patient-centric and patient-engaged forums with the potential to crowd source to improve clinical trial accrual and design. This is an evolving process that will meet many individual, institutional, and regulatory obstacles as we move forward in a changed research landscape.

Can the FDA improve oversight of foreign clinical trials?: Closing the information gap and moving towards a globalized regulatory scheme.

PubMed

Ourso, André

2012-01-01

Currently, pharmaceutical companies' utilization of foreign clinical trial data is a ubiquitous and indispensable aspect of gaining approval to market drugs in the United States. Cost benefits, a larger pool of ready volunteer subjects, and greater efficiency in clinical testing are some of the reasons for conducting clinical trials overseas. Despite these advantages, lack of proper oversight may have serious public health implications regarding the integrity of clinical research, ethical treatment of human subjects, and drug safety. Due to the expansive global nature of foreign clinical trials, there are concerns with the FDA's ability to monitor and regulate these trials. This article examines the FDA's oversight of foreign clinical trials and the agency's limitations regulating these trials. In addition to looking at steps the FDA is taking to address these limitations, the article examines other potential regulatory and cooperative actions that can be taken to effectively monitor foreign clinical trials and to ensure data integrity and patient safety.

Compliance with results reporting at ClinicalTrials.gov.

PubMed

Anderson, Monique L; Chiswell, Karen; Peterson, Eric D; Tasneem, Asba; Topping, James; Califf, Robert M

2015-03-12

The Food and Drug Administration Amendments Act (FDAAA) mandates timely reporting of results of applicable clinical trials to ClinicalTrials.gov. We characterized the proportion of applicable clinical trials with publicly available results and determined independent factors associated with the reporting of results. Using an algorithm based on input from the National Library of Medicine, we identified trials that were likely to be subject to FDAAA provisions (highly likely applicable clinical trials, or HLACTs) from 2008 through 2013. We determined the proportion of HLACTs that reported results within the 12-month interval mandated by the FDAAA or at any time during the 5-year study period. We used regression models to examine characteristics associated with reporting at 12 months and throughout the 5-year study period. From all the trials at ClinicalTrials.gov, we identified 13,327 HLACTs that were terminated or completed from January 1, 2008, through August 31, 2012. Of these trials, 77.4% were classified as drug trials. A total of 36.9% of the trials were phase 2 studies, and 23.4% were phase 3 studies; 65.6% were funded by industry. Only 13.4% of trials reported summary results within 12 months after trial completion, whereas 38.3% reported results at any time up to September 27, 2013. Timely reporting was independently associated with factors such as FDA oversight, a later trial phase, and industry funding. A sample review suggested that 45% of industry-funded trials were not required to report results, as compared with 6% of trials funded by the National Institutes of Health (NIH) and 9% of trials that were funded by other government or academic institutions. Despite ethical and legal obligations to disclose findings promptly, most HLACTs did not report results to ClinicalTrials.gov in a timely fashion during the study period. Industry-funded trials adhered to legal obligations more often than did trials funded by the NIH or other government or academic institutions. (Funded by the Clinical Trials Transformation Initiative and the NIH.).

The Landscape of Clinical Trials Evaluating the Theranostic Role of PET Imaging in Oncology: Insights from an Analysis of ClinicalTrials.gov Database.

PubMed

Chen, Yu-Pei; Lv, Jia-Wei; Liu, Xu; Zhang, Yuan; Guo, Ying; Lin, Ai-Hua; Sun, Ying; Mao, Yan-Ping; Ma, Jun

2017-01-01

In the war on cancer marked by personalized medicine, positron emission tomography (PET)-based theranostic strategy is playing an increasingly important role. Well-designed clinical trials are of great significance for validating the PET applications and ensuring evidence-based cancer care. This study aimed to provide a comprehensive landscape of the characteristics of PET clinical trials using the substantial resource of ClinicalTrials.gov database. We identified 25,599 oncology trials registered with ClinicalTrials.gov in the last ten-year period (October 2005-September 2015). They were systematically reviewed to validate classification into 519 PET trials and 25,080 other oncology trials used for comparison. We found that PET trials were predominantly phase 1-2 studies (86.2%) and were more likely to be single-arm (78.9% vs. 57.9%, P <0.001) using non-randomized assignment (90.1% vs. 66.7%, P <0.001) than other oncology trials. Furthermore, PET trials were small in scale, generally enrolling fewer than 100 participants (20.3% vs. 25.7% for other oncology trials, P = 0.014), which might be too small to detect a significant theranostic effect. The funding support from industry or National Institutes of Health shrunk over time (both decreased by about 5%), and PET trials were more likely to be conducted in only one region lacking international collaboration (97.0% vs. 89.3% for other oncology trials, P <0.001). These findings raise concerns that clinical trials evaluating PET imaging in oncology are not receiving the attention or efforts necessary to generate high-quality evidence. Advancing the clinical application of PET imaging will require a concerted effort to improve the quality of trials.

The Landscape of Clinical Trials Evaluating the Theranostic Role of PET Imaging in Oncology: Insights from an Analysis of ClinicalTrials.gov Database

PubMed Central

Chen, Yu-Pei; Lv, Jia-Wei; Liu, Xu; Zhang, Yuan; Guo, Ying; Lin, Ai-Hua; Sun, Ying; Mao, Yan-Ping; Ma, Jun

2017-01-01

In the war on cancer marked by personalized medicine, positron emission tomography (PET)-based theranostic strategy is playing an increasingly important role. Well-designed clinical trials are of great significance for validating the PET applications and ensuring evidence-based cancer care. This study aimed to provide a comprehensive landscape of the characteristics of PET clinical trials using the substantial resource of ClinicalTrials.gov database. We identified 25,599 oncology trials registered with ClinicalTrials.gov in the last ten-year period (October 2005-September 2015). They were systematically reviewed to validate classification into 519 PET trials and 25,080 other oncology trials used for comparison. We found that PET trials were predominantly phase 1-2 studies (86.2%) and were more likely to be single-arm (78.9% vs. 57.9%, P <0.001) using non-randomized assignment (90.1% vs. 66.7%, P <0.001) than other oncology trials. Furthermore, PET trials were small in scale, generally enrolling fewer than 100 participants (20.3% vs. 25.7% for other oncology trials, P = 0.014), which might be too small to detect a significant theranostic effect. The funding support from industry or National Institutes of Health shrunk over time (both decreased by about 5%), and PET trials were more likely to be conducted in only one region lacking international collaboration (97.0% vs. 89.3% for other oncology trials, P <0.001). These findings raise concerns that clinical trials evaluating PET imaging in oncology are not receiving the attention or efforts necessary to generate high-quality evidence. Advancing the clinical application of PET imaging will require a concerted effort to improve the quality of trials. PMID:28042342

What we have learned: the impact of quality from a clinical trials perspective

PubMed Central

FitzGerald, T. J.

2011-01-01

In this review article we address the radiation oncology process improvements in clinical trials and review how these changes improve the quality for the next generation of trials. In recent years we have progressed from a time of limited data acquisition to the present in which we have real time influence of clinical trials quality. This enables immediate availability of the important elements including staging, eligibility, response and outcome for all trial investigators. Modern informatics platforms are well designed for future adaptive clinical trials. We review what will be needed in the informatics architecture of current and future clinical trials. PMID:22177875

Role of Clinical Trial Participation in Cancer Research: Barriers, Evidence, and Strategies

PubMed Central

Unger, Joseph M.; Cook, Elise; Tai, Eric; Bleyer, Archie

2017-01-01

OVERVIEW Fewer than 1 in 20 adult cancer patients enroll in cancer clinical trials. But although barriers to trial participation have been the subject of frequent study, the rate of trial participation has not changed substantially over time. Barriers to trial participation are structural, clinical, and attitudinal, and differ according to demographic and socioeconomic factors. In this paper, we characterize the nature of cancer clinical trial barriers, and we consider global and local strategies for reducing barriers. We also consider the specific case of adolescents with cancer, and show that the low rate of trial enrollment in this age group strongly correlates with limited improvements in cancer population outcomes compared to other age groups. Our analysis suggests that a clinical trial system that enrolls patients at higher rates produces treatment advances at a faster rate and corresponding improvements in cancer population outcomes. Viewed in this light, the issue of clinical trial enrollment is foundational, lying at the heart of the cancer clinical trial endeavor. Fewer barriers to trial participation would allow trials to be completed more quickly and would improve the generalizability of trial results. Moreover, increased accrual to trials is important to patients, since trials provide patients the opportunity to receive the newest treatments. In an era of increasing emphasis on a treatment decision-making process that incorporates the patient perspective, the opportunity for patients to choose trial participation for their care is vital. PMID:27249699

Temporal Trends and Predictors for Cancer Clinical Trial Availability for Medically Underserved Populations

PubMed Central

Lakoduk, Ashley M.; Priddy, Laurin L.; Yan, Jingsheng; Xie, Xian-Jin

2015-01-01

Background. Lack of access to available cancer clinical trials has been cited as a key factor limiting trial accrual, particularly among medically underserved populations. We examined the trends and factors in clinical trial availability within a major U.S. safety-net hospital system. Materials and Methods. We identified cancer clinical trials activated at the Harold C. Simmons Cancer from 1991 to 2014 and recorded the characteristics of the trials that were and were not activated at the Parkland Health and Hospital System satellite site. We used univariate and multivariate logistic regression to determine the association between trial characteristics and nonactivation status, and chi-square analysis to determine the association between the trial characteristics and the reasons for nonactivation. Results. A total of 773 trials were identified, of which 152 (20%) were not activated at Parkland. In multivariable analysis, nonactivation at Parkland was associated with trial year, sponsor, and phase. Compared with the 1991–2006 period, clinical trials in the 2007–2014 period were almost eightfold more likely not to be activated at Parkland. The most common reasons for nonactivation at Parkland were an inability to perform the study procedures (27%) and the startup costs (15%). Conclusion. Over time, in this single-center setting, a decreasing proportion of cancer clinical trials were available to underserved populations. Trial complexity and costs appeared to account for much of this trend. Efforts to overcome these barriers will be key to equitable access to clinical trials, efficient accrual, and the generalizability of the results. Implications for Practice: Despite numerous calls to increase and diversify cancer clinical trial accrual, the present study found that cancer clinical trial activation rates in a safety-net setting for medically underserved populations have decreased substantially in recent years. The principal reasons for study nonactivation were expenses and an inability to perform the study-related procedures, reflecting the increasing costs and complexity of cancer clinical trials. Future efforts need to focus on strategies to mitigate the increasing disparity in access to clinical research and cutting-edge therapies, which also threatens to hinder study accrual, completion rates, and generalizability. PMID:26018661

Compensation of research-related injuries in the European Union.

PubMed

Avilds, Miguelangel Ramiro

2014-12-01

The planned reform of the Clinical Trials Directive has re-opened the debate over how to implement and interpret research-related injuries regulation. In the European Union (EU), clinical trials are currently regulated by Directive 2001/20/EC, which establishes the provision of mandatory insurance before clinical trials commence but is silent on the system of liability. The proposed new Regulation will impact biomedical research assurance in all EU Member States because it points to insurance costs as being one of the causes of the fall in the number of clinical trials carried out in the EU. Despite the adoption of a risk-balance approach, the proposed new Regulation does not include a no-fault compensation system to protect subjects participating in clinical trials. An adequate protection of the rights and wellbeing of trial subjects would require not only mandatory insurance for clinical trials but also a no-fault compensation system. The new regulation should include a general clause requiring mandatory insurance and establishing liability insurance based on no-fault compensation; an exception clause, enabling the performance of clinical trials without insurance in the case of low-risk interventions or non-commercial clinical trials; and an exclusion clause, excluding compensation when there is no causal connection between injuries and clinical trial.

Physician compensation for industry-sponsored clinical trials in multiple sclerosis influences patient trust.

PubMed

Klein, E; Solomon, A J; Corboy, J; Bernat, J

2016-07-01

Perceived physician financial conflicts of interest of can affect patient trust. Payment to physicians for industry sponsored clinical trials in multiple sclerosis is a relatively new potential source of physician conflict of interest. There is limited available data on how physician payment for trial involvement in multiple sclerosis clinical trials may influence patient trust. To understand how patient trust is influenced by information about physician payment for multiple sclerosis clinical trials. An anonymous online instrument was developed. 597 people with multiple sclerosis participated in the study. The study found that 61% of patients who had not previously participated in a clinical trial estimated that they would have lower levels of trust in their physician if the physician was paid for involvement in their clinical trial. Among former clinical trial participants, 38% self-reported a lower level of trust. Other potential physician-industry relationships, such as industry consulting or giving industry-sponsored talks, also adversely affected trust, though to a lesser extent than physician payment for subject participation in clinical trials. Results of this study demonstrate that physician payment for study participation in multiple sclerosis clinical trials is a potential conflict that can adversely affect patient trust. Copyright © 2016 Elsevier B.V. All rights reserved.

A comparison of interventional clinical trials in rare versus non-rare diseases: an analysis of ClinicalTrials.gov.

PubMed

Bell, Stuart A; Tudur Smith, Catrin

2014-11-26

To provide a comprehensive characterisation of rare disease clinical trials registered in ClinicalTrials.gov, and compare against characteristics of trials in non-rare diseases. Registry based study of ClinicalTrials.gov registration entries. The ClinicalTrials.gov registry comprised 133,128 studies registered to September 27, 2012. By annotating medical subject heading descriptors to condition terms we could identify rare and non-rare disease trials. A total of 24,088 Interventional trials registered after January 1, 2006, conducted in the United States, Canada and/or the European Union were categorised as rare or non-rare. Characteristics of the respective trials were extracted and summarised with comparative statistics calculated where appropriate. Characteristics of interventional trials reported in the database categorised by rare and non-rare conditions to allow comparison. Of the 24,088 trials categorised 2,759 (11.5%) were classified as rare disease trials and 21,329 (88.5%) related to non-rare conditions. Despite the limitations of the database we found that rare disease trials differed to non-rare disease trials across all characteristics that we examined. Rare disease trials enrolled fewer participants (median 29 vs. 62), were more likely to be single arm (63.0% vs. 29.6%), non-randomised (64.5% vs. 36.1%) and open label (78.7% vs. 52.2%). A higher proportion of rare disease trials were terminated early (13.7% vs. 6.3%) and proportionally fewer rare disease studies were actively pursuing, or waiting to commence, enrolment (15.9% vs. 38.5%). Rare disease interventional trials differ from those in non-rare conditions with notable differences in enrolment, design, blinding and randomisation. However, clinical trials should aim to implement the highest trial design standards possible, regardless of whether diseases are rare or not.

The ethics and regulatory landscape of including vulnerable populations in pragmatic clinical trials.

PubMed

Welch, Mary Jane; Lally, Rachel; Miller, Jennifer E; Pittman, Stephanie; Brodsky, Lynda; Caplan, Arthur L; Uhlenbrauck, Gina; Louzao, Darcy M; Fischer, James H; Wilfond, Benjamin

2015-10-01

Policies have been developed to protect vulnerable populations in clinical research, including the US federal research regulations (45 Code of Federal Regulations 46 Subparts B, C, and D). These policies generally recognize vulnerable populations to include pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons. The aim has been to protect these populations from harm, often by creating regulatory and ethical checks that may limit their participation in many clinical trials. The recent increase in pragmatic clinical trials raises at least two questions about this approach. First, is exclusion itself a harm to vulnerable populations, as these groups may be denied access to understanding how health interventions work for them in clinical settings? Second, are groups considered vulnerable in traditional clinical trials also vulnerable in pragmatic clinical trials? We argue first that excluding vulnerable subjects from participation in pragmatic clinical trials can be harmful by preventing acquisition of data to meaningfully inform clinical decision-making in the future. Second, we argue that protections for vulnerable subjects in traditional clinical trial settings may not be translatable, feasible, or even ethical to apply in pragmatic clinical trials. We conclude by offering specific recommendations for appropriately protecting vulnerable research subjects in pragmatic clinical trials, focusing on pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons. © The Author(s) 2015.

Epidemiology of clinical trials of medicines in respiratory diseases in Europe and Italy.

PubMed

Bodini, Roberta; Santus, Pierachille; Di Marco, Fabiano; Aliberti, Stefano; Centanni, Stefano; Blasi, Francesco; Rizzi, Andrea; Recchia, Giuseppe

2017-04-01

Clinical trials play a key role in advancing medical knowledge, improving patient care and promoting economic growth in Europe. We have assessed the clinical trial activity in any respiratory diseases in Europe, with a specific focus on Italy. Information from public sources (EFPIA, clinicaltrials.gov, clinicaltrialsregister. eu, AIFA) was used to describe clinical trial activity of in respiratory diseases in Europe and by country. In 2015, 3908 clinical trials were reported in Europe, 386 in respiratory diseases (9.9%). Germany was the first country both as absolute number (76 trials) and as percentage within country trials (14%), followed by Poland. Spain, Italy and France were the countries with the lowest number and percentage of trials in respiratory diseases. In 2013, the Italian Drug Agency reported 9 trials with respiratory compounds in Italy (2.1% of overall trials, 12ˆ position in the therapeutic area rank), 33% in phase 2 and 66% in phase 3. No phase 1 or phase 4 trials were reported for respiratory trials. Prevalence of respiratory trials by non-profit sponsors (28.3%) was below the average for the country (38.3%). Europe has a greater potential for clinical research on drugs for respiratory diseases, particularly in countries with less activity, such as Spain, France and Italy, that should identify and implement actions to increase attractiveness for clinical trials of drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical trials for stem cell transplantation: when are they needed?

PubMed

Van Pham, Phuc

2016-04-27

In recent years, both stem cell research and the clinical application of these promising cells have increased rapidly. About 1000 clinical trials using stem cells have to date been performed globally. More importantly, more than 10 stem cell-based products have been approved in some countries. With the rapid growth of stem cell applications, some countries have used clinical trials as a tool to diminish the rate of clinical stem cell applications. However, the point at which stem cell clinical trials are essential remains unclear. This commentary discusses when stem cell clinical trials are essential for stem cell transplantation therapies.

Attitudes of small animal practitioners toward participation in veterinary clinical trials

PubMed Central

Gruen, Margaret E.; Griffith, Emily H.; Caney, Sarah M. A.; Rishniw, Mark; Lascelles, B. Duncan X.

2017-01-01

OBJECTIVE To determine attitudes of small animal practitioners toward veterinary clinical trials and variables influencing their likelihood of participating in such trials. DESIGN Cross-sectional survey. SAMPLE Small animal practitioners with membership in 1 of 2 online veterinary communities (n = 163 and 652). PROCEDURES An online survey was developed for each of 2 veterinary communities, and invitations to participate were sent via email. Each survey included questions designed to collect information on the respondents’ willingness to enroll their patients in clinical trials and to recommend participation to clients for their pets. RESULTS More than 80% of respondents to each survey indicated that they spend no time in clinical research. A high proportion of respondents were likely or extremely likely to recommend clinical trial participation to clients for their pets when those trials involved treatments licensed in other countries, novel treatments, respected investigators, or sponsoring by academic institutions, among other reasons. Reasons for not recommending participation included distance, time restrictions, and lack of awareness of ongoing clinical trials; 28% of respondents indicated that they did not usually learn about such clinical trials. Most respondents (79% to 92%) rated their recommendation of a trial as important to their client’s willingness to participate. CONCLUSIONS AND CLINICAL RELEVANCE Participation in veterinary clinical trials by small animal practitioners and their clients and patients appeared low. Efforts should be increased to raise practitioner awareness of clinical trials for which patients might qualify. Specific elements of trial design were identified that could be modified to increase participation. PMID:28001115

A framework for analysis of research risks and benefits to participants in standard of care pragmatic clinical trials.

PubMed

Chen, Stephanie C; Kim, Scott Yh

2016-12-01

Standard of care pragmatic clinical trials that compare treatments already in use could improve care and reduce costs, but there is considerable debate about the research risks of standard of care pragmatic clinical trials and how to apply informed consent regulations to such trials. We sought to develop a framework integrating the insights from opposing sides of the debate. We developed a formal risk-benefit analysis framework for standard of care pragmatic clinical trials and then applied it to key provisions of the US federal regulations. Our formal framework for standard of care pragmatic clinical trial risk-benefit analysis takes into account three key considerations: the ex ante estimates of risks and benefits of the treatments to be compared in a standard of care pragmatic clinical trial, the allocation ratios of treatments inside and outside such a trial, and the significance of some participants receiving a different treatment inside a trial than outside the trial. The framework provides practical guidance on how the research ethics regulations on informed consent should be applied to standard of care pragmatic clinical trials. Our proposed formal model makes explicit the relationship between the concepts used by opposing sides of the debate about the research risks of standard of care pragmatic clinical trials and can be used to clarify the implications for informed consent. © The Author(s) 2016.

Enrolling Minority and Underserved Populations in Cancer Clinical Research.

PubMed

Wallington, Sherrie F; Dash, Chiranjeev; Sheppard, Vanessa B; Goode, Tawara D; Oppong, Bridget A; Dodson, Everett E; Hamilton, Rhonda N; Adams-Campbell, Lucile L

2016-01-01

Research suggests that community involvement is integral to solving public health problems, including involvement in clinical trials-a gold standard. Significant racial/ethnic disparities exist in the accrual of participants for clinical trials. Location and cultural aspects of clinical trials influence recruitment and accrual to clinical trials. It is increasingly necessary to be aware of defining characteristics, such as location and culture of the populations from which research participants are enrolled. Little research has examined the effect of location and cultural competency in adapting clinical trial research for minority and underserved communities on accrual for clinical trials. Utilizing embedded community academic sites, the authors applied cultural competency frameworks to adapt clinical trial research in order to increase minority participation in nontherapeutic cancer clinical trials. This strategy resulted in successful accrual of participants to new clinical research trials, specifically targeting participation from minority and underserved communities in metropolitan Washington, DC. From 2012 to 2014, a total of 559 participants enrolled across six nontherapeutic clinical trials, representing a 62% increase in the enrollment of blacks in clinical research. Embedding cancer prevention programs and research in the community was shown to be yet another important strategy in the arsenal of approaches that can potentially enhance clinical research enrollment and capacity. The analyses showed that the capacity to acquire cultural knowledge about patients-their physical locales, cultural values, and environments in which they live-is essential to recruiting culturally and ethnically diverse population samples. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

"You can save time if…"-A qualitative study on internal factors slowing down clinical trials in Sub-Saharan Africa.

PubMed

Vischer, Nerina; Pfeiffer, Constanze; Limacher, Manuela; Burri, Christian

2017-01-01

The costs, complexity, legal requirements and number of amendments associated with clinical trials are rising constantly, which negatively affects the efficient conduct of trials. In Sub-Saharan Africa, this situation is exacerbated by capacity and funding limitations, which further increase the workload of clinical trialists. At the same time, trials are critically important for improving public health in these settings. The aim of this study was to identify the internal factors that slow down clinical trials in Sub-Saharan Africa. Here, factors are limited to those that exclusively relate to clinical trial teams and sponsors. These factors may be influenced independently of external conditions and may significantly increase trial efficiency if addressed by the respective teams. We conducted sixty key informant interviews with clinical trial staff working in different positions in two clinical research centres in Kenya, Ghana, Burkina Faso and Senegal. The study covered English- and French-speaking, and Eastern and Western parts of Sub-Saharan Africa. We performed thematic analysis of the interview transcripts. We found various internal factors associated with slowing down clinical trials; these were summarised into two broad themes, "planning" and "site organisation". These themes were consistently mentioned across positions and countries. "Planning" factors related to budget feasibility, clear project ideas, realistic deadlines, understanding of trial processes, adaptation to the local context and involvement of site staff in planning. "Site organisation" factors covered staff turnover, employment conditions, career paths, workload, delegation and management. We found that internal factors slowing down clinical trials are of high importance to trial staff. Our data suggest that adequate and coherent planning, careful assessment of the setting, clear task allocation and management capacity strengthening may help to overcome the identified internal factors and allow clinical trials to proceed more efficiently.

Interpreting clinical trial results by deductive reasoning: In search of improved trial design.

PubMed

Kurbel, Sven; Mihaljević, Slobodan

2017-10-01

Clinical trial results are often interpreted by inductive reasoning, in a trial design-limited manner, directed toward modifications of the current clinical practice. Deductive reasoning is an alternative in which results of relevant trials are combined in indisputable premises that lead to a conclusion easily testable in future trials. © 2017 WILEY Periodicals, Inc.

Clinical trials and the new good clinical practice guideline in Japan. An economic perspective.

PubMed

Ono, S; Kodama, Y

2000-08-01

Japanese clinical trials have been drastically changing in response to the implementation of the International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) guideline in 1997. The most important aim of the new guideline is to standardise the quality of clinical trials in the US, European Union and Japan, but it inevitably imposes substantial costs on investigators, sponsors and even patients in Japan. The study environment in Japan differs from that in the US in several ways: (i) historical lack of a formal requirement for informed consent; (ii) patients' attitudes to clinical trials in terms of expectation of positive outcomes; (iii) the implications of universal health insurance for trial participation; (iv) the historical absence of on-site monitoring by the sponsor, with the attendant effects on study quality; and (v) the lack of adequate financial and personnel support for the conduct of trials. Implementation of the new GCP guideline will improve the ethical and scientific quality of trials conducted in Japan. It may also lead to an improved relationship between medical professionals and patients if the requirement for explicit informed consent in clinical trials leads to the provision of a similar level of patient information in routine care and changes the traditional paternalistic attitude of physicians to patients. The initial response of the Japanese 'market' for clinical trials to the implementation of the ICH-GCP guideline has been clinical trial price increases and a decrease in the number of study contracts. These changes can be explained by applying a simple demand-supply scheme. Whether clinical trials undertaken in Japan become more or less attractive to the industry in the long term will depend on other factors such as international regulations on the acceptability of foreign clinical trials and the reform of domestic healthcare policies.

Effects of a Brief Multimedia Psychoeducational Intervention on the Attitudes and Interest of Patients With Cancer Regarding Clinical Trial Participation: A Multicenter Randomized Controlled Trial

PubMed Central

Jacobsen, Paul B.; Wells, Kristen J.; Meade, Cathy D.; Quinn, Gwendolyn P.; Lee, Ji-Hyun; Fulp, William J.; Gray, Jhanelle E.; Baz, Rachid C.; Springett, Gregory M.; Levine, Richard M.; Markham, Merry-Jennifer; Schreiber, Fred J.; Cartwright, Thomas H.; Burke, James M.; Siegel, Robert D.; Malafa, Mokenge P.; Sullivan, Daniel

2012-01-01

Purpose The negative attitudes of patients with cancer regarding clinical trials are an important contributor to low participation rates. This study evaluated whether a brief psychoeducational intervention was effective in improving patients' attitudes as well as their knowledge, self-efficacy for decision making, receptivity to receiving more information, and general willingness to participate in clinical trials. Patients and Methods A total of 472 adults with cancer who had not been asked previously to participate in a clinical trial were randomly assigned to receive printed educational information about clinical trials or a psychoeducational intervention that provided similar information and also addressed misperceptions and concerns about clinical trials. The primary (attitudes) and secondary outcomes (knowledge, self-efficacy, receptivity, and willingness) were assessed via patient self-report before random assignment and 7 to 28 days later. Results Patients who received the psychoeducational intervention showed more positive attitudes toward clinical trials (P = .016) and greater willingness to participate (P = .011) at follow-up than patients who received printed educational information. Evidence of an indirect effect of intervention assignment on willingness to participate (estimated at 0.168; 95% CI, 0.088 to 0.248) suggested that the benefits of psychoeducation on willingness to participate were explained by the positive impact of psychoeducation on attitudes toward clinical trials. Conclusion A brief psychoeducational intervention can improve the attitudes of patients with cancer toward clinical trials and thereby increase their willingness to participate in clinical trials. Findings support conducting additional research to evaluate effects of this intervention on quality of decision making and rates of participation among patients asked to enroll onto therapeutic clinical trials. PMID:22614993

Does information from ClinicalTrials.gov increase transparency and reduce bias? Results from a five-report case series.

PubMed

Adam, Gaelen P; Springs, Stacey; Trikalinos, Thomas; Williams, John W; Eaton, Jennifer L; Von Isenburg, Megan; Gierisch, Jennifer M; Wilson, Lisa M; Robinson, Karen A; Viswanathan, Meera; Middleton, Jennifer Cook; Forman-Hoffman, Valerie L; Berliner, Elise; Kaplan, Robert M

2018-04-16

We investigated whether information in ClinicalTrials.gov would impact the conclusions of five ongoing systematic reviews. We considered five reviews that included 495 studies total. Each review team conducted a search of ClinicalTrials.gov up to the date of the review's last literature search, screened the records using the review's eligibility criteria, extracted information, and assessed risk of bias and applicability. Each team then evaluated the impact of the evidence found in ClinicalTrials.gov on the conclusions in the review. Across the five reviews, the number of studies that had both a registry record and a publication varied widely, from none in one review to 43% of all studies identified in another. Among the studies with both a record and publication, there was also wide variability in the match between published outcomes and those listed in ClinicalTrials.gov. Of the 173 total ClinicalTrials.gov records identified across the five projects, between 11 and 43% did not have an associated publication. In the 14% of records that contained results, the new data provided in the ClinicalTrials.gov records did not change the results or conclusions of the reviews. Finally, a large number of published studies were not registered in ClinicalTrials.gov, but many of these were published before ClinicalTrials.gov's inception date of 2000. Improved prospective registration of trials and consistent reporting of results in ClinicalTrials.gov would help make ClinicalTrials.gov records more useful in finding unpublished information and identifying potential biases. In addition, consistent indexing in databases, such as MEDLINE, would allow for better matching of records and publications, leading to increased utility of these searches for systematic review projects.

Evaluation of eligibility and recruitment in breast cancer clinical trials.

PubMed

Lemieux, Julie; Forget, Geneviève; Brochu, Olyvia; Provencher, Louise; Cantin, Guy; Desbiens, Christine; Doyle, Catherine; Poirier, Brigitte; Camden, Stéphanie; Durocher, Martin

2014-08-01

Objectives of the study were to measure recruitment rates in clinical trials and to identify patients, physicians or trials characteristics associated with higher recruitment rates. Among patients who had a clinical trial available for their cancer, 83.5% (345/413) met the eligibility criteria to at least one clinical trial. At least one trial was proposed to 33.1% (113/341) of the eligible patients and 19.7% (68/345) were recruited. Overall recruitment was 16.5% (68/413). In multivariate analyses, trial proposal and enrollment were lower for elderly patients and higher in high cancer stages. Trials from pharmaceutical industry had higher recruitment rates and trials testing hormonal therapy enrolled more patients. Breast cancer patients' accrual to a clinical trial could be improved by trying to systematically identify all eligible patients and propose a trial to those eligible and to whom the treatment is planned to be equivalent to the standard arm of the trial. Copyright © 2014 Elsevier Ltd. All rights reserved.

Resource implications of preparing individual participant data from a clinical trial to share with external researchers.

PubMed

Tudur Smith, Catrin; Nevitt, Sarah; Appelbe, Duncan; Appleton, Richard; Dixon, Pete; Harrison, Janet; Marson, Anthony; Williamson, Paula; Tremain, Elizabeth

2017-07-17

Demands are increasingly being made for clinical trialists to actively share individual participant data (IPD) collected from clinical trials using responsible methods that protect the confidentiality and privacy of clinical trial participants. Clinical trialists, particularly those receiving public funding, are often concerned about the additional time and money that data-sharing activities will require, but few published empirical data are available to help inform these decisions. We sought to evaluate the activity and resources required to prepare anonymised IPD from a clinical trial in anticipation of a future data-sharing request. Data from two UK publicly funded clinical trials were used for this exercise: 2437 participants with epilepsy recruited from 90 hospital outpatient clinics in the SANAD trial and 146 children with neuro-developmental problems recruited from 18 hospitals in the MENDS trial. We calculated the time and resources required to prepare each anonymised dataset and assemble a data pack ready for sharing. The older SANAD trial (published 2007) required 50 hours of staff time with a total estimated associated cost of £3185 whilst the more recently completed MENDS trial (published 2012) required 39.5 hours of staff time with total estimated associated cost of £2540. Clinical trial researchers, funders and sponsors should consider appropriate resourcing and allow reasonable time for preparing IPD ready for subsequent sharing. This process would be most efficient if prospectively built into the standard operational design and conduct of a clinical trial. Further empirical examples exploring the resource requirements in other settings is recommended. SANAD: International Standard Randomised Controlled Trials Registry: ISRCTN38354748 . Registered on 25 April 2003. EU Clinical Trials Register Eudract 2006-004025-28 . Registered on 16 May 2007. International Standard Randomised Controlled Trials Registry: ISRCTN05534585 /MREC 07/MRE08/43. Registered on 26 January 2007.

Prospective registration of clinical trials in India: strategies, achievements & challenges.

PubMed

Tharyan, Prathap

2009-02-01

This paper traces the development of the Clinical Trial Registry-India (CTRI) against the backdrop of the inequities in healthcare and the limitations in the design, conduct, regulation, oversight and reporting of clinical trials in India. It describes the scope and goals of the CTRI, the data elements it seeks and the process of registering clinical trials. It reports progress in trial registration in India and discusses the challenges in ensuring that healthcare decisions are informed by all the evidence. A descriptive survey of developments in clinical trial registration in India from publications in the Indian medical literature supplemented by first hand knowledge of these developments and an evaluation of how well clinical trials registered in the CTRI up to 10 January, 2009 comply with the requirements of the CTRI and the World Health Organization's International Clinical Trial Registry (WHO ICTRP). Considerable inequities exist within the Indian health system. Deficiencies in healthcare provision and uneven regulation of, and access to, affordable healthcare co-exists with a large private health system of uneven quality. India is now a preferred destination for outsourced clinical trials but is plagued by poor ethical oversight of the many trial sites and scant information of their existence. The CTRI's vision of conforming to international requirements for transparency and accountability but also using trial registration as a means of improving trial design, conduct and reporting led to the selection of registry-specific dataset items in addition to those endorsed by the WHO ICTRP. Compliance with these requirements is good for the trials currently registered but these trials represent only a fraction of the trials in progress in India. Prospective trial registration is a reality in India. The challenges facing the CTRI include better engagement with key stakeholders to ensure increased prospective registration of clinical trials and utilization of existing legislative opportunities to complement these efforts. © 2009 Blackwell Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

Timing and Completeness of Trial Results Posted at ClinicalTrials.gov and Published in Journals

PubMed Central

Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe

2013-01-01

Background The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration–approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. Methods and Findings We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45%, p<0.001), and serious adverse events (99% versus 63%, p<0.001). The main study limitation was that we considered only the publication describing the results for the primary outcomes. Conclusions Our results highlight the need to search ClinicalTrials.gov for both unpublished and published trials. Trial results, especially serious adverse events, are more completely reported at ClinicalTrials.gov than in the published article. Please see later in the article for the Editors' Summary PMID:24311990

An educational video to increase clinical trials enrollment among breast cancer patients.

PubMed

Du, Wei; Mood, Darlene; Gadgeel, Shirish; Simon, Michael S

2009-09-01

Only 3% of women with breast cancer participate in cancer clinical trials nationwide. The lack of awareness about clinical trials is a significant barrier towards clinical trials participation. A study was conducted at a large urban Comprehensive Cancer Center to test (1) the effectiveness of an 18-min educational video on improving attitudes toward clinical trials and trials enrollment among new breast cancer patients seen at the Karmanos Cancer Institute, and (2) to assess racial differences in attitudes regarding clinical trials. Participants were randomized to either the educational intervention prior to their first oncology clinic appointment or to standard care. A baseline and 2-week post-intervention survey to assess attitudes toward clinical trials participation was completed by participants. Of 218 subjects recruited, 196 (55% white vs. 45% African American (AA)) eligible patients were included in the analysis. A small increase in therapeutic clinical trial enrollment was observed in the intervention arm but was not statistically significant (10.4% vs. 6.1%; P = 0.277). The intervention also did not result in a clear improvement in patients' attitudes toward clinical trials at posttest. However, a lower enrollment rate for the AA women was noted after adjusting for stage (OR = 0.282, P = 0.049). Significantly more negative scores were noted in 3 out of the 5 baseline attitudinal scales for AA women. The educational video did not significantly increase enrollment in breast cancer clinical trials. The findings that AA women had significantly more negative attitudes toward clinical trials than white women may partially explain the racial disparity in enrollment. An educational video remains a simple and cost-effective way to educate patients. Future studies should focus on designing a new educational video to specifically target cultural and attitudinal barriers in the AA population to more effectively change attitudes and increase trial enrollment.

An educational video to increase clinical trials enrollment among breast cancer patients

PubMed Central

Du, Wei; Mood, Darlene; Gadgeel, Shirish; Simon, Michael S.

2013-01-01

Only 3% of women with breast cancer participate in cancer clinical trials nationwide. The lack of awareness about clinical trials is a significant barrier towards clinical trials participation. A study was conducted at a large urban Comprehensive Cancer Center to test (1) the effectiveness of an 18-min educational video on improving attitudes toward clinical trials and trials enrollment among new breast cancer patients seen at the Karmanos Cancer Institute, and (2) to assess racial differences in attitudes regarding clinical trials. Participants were randomized to either the educational intervention prior to their first oncology clinic appointment or to standard care. A baseline and 2-week post-intervention survey to assess attitudes toward clinical trials participation was completed by participants. Of 218 subjects recruited, 196 (55% white vs. 45% African American (AA)) eligible patients were included in the analysis. A small increase in therapeutic clinical trial enrollment was observed in the intervention arm but was not statistically significant (10.4% vs. 6.1%; P = 0.277). The intervention also did not result in a clear improvement in patients’ attitudes toward clinical trials at posttest. However, a lower enrollment rate for the AA women was noted after adjusting for stage (OR = 0.282, P = 0.049). Significantly more negative scores were noted in 3 out of the 5 baseline attitudinal scales for AA women. The educational video did not significantly increase enrollment in breast cancer clinical trials. The findings that AA women had significantly more negative attitudes toward clinical trials than white women may partially explain the racial disparity in enrollment. An educational video remains a simple and cost-effective way to educate patients. Future studies should focus on designing a new educational video to specifically target cultural and attitudinal barriers in the AA population to more effectively change attitudes and increase trial enrollment. PMID:19152024

Extracting genetic alteration information for personalized cancer therapy from ClinicalTrials.gov

PubMed Central

Xu, Jun; Lee, Hee-Jin; Zeng, Jia; Wu, Yonghui; Zhang, Yaoyun; Huang, Liang-Chin; Johnson, Amber; Holla, Vijaykumar; Bailey, Ann M; Cohen, Trevor; Meric-Bernstam, Funda; Bernstam, Elmer V

2016-01-01

Objective: Clinical trials investigating drugs that target specific genetic alterations in tumors are important for promoting personalized cancer therapy. The goal of this project is to create a knowledge base of cancer treatment trials with annotations about genetic alterations from ClinicalTrials.gov. Methods: We developed a semi-automatic framework that combines advanced text-processing techniques with manual review to curate genetic alteration information in cancer trials. The framework consists of a document classification system to identify cancer treatment trials from ClinicalTrials.gov and an information extraction system to extract gene and alteration pairs from the Title and Eligibility Criteria sections of clinical trials. By applying the framework to trials at ClinicalTrials.gov, we created a knowledge base of cancer treatment trials with genetic alteration annotations. We then evaluated each component of the framework against manually reviewed sets of clinical trials and generated descriptive statistics of the knowledge base. Results and Discussion: The automated cancer treatment trial identification system achieved a high precision of 0.9944. Together with the manual review process, it identified 20 193 cancer treatment trials from ClinicalTrials.gov. The automated gene-alteration extraction system achieved a precision of 0.8300 and a recall of 0.6803. After validation by manual review, we generated a knowledge base of 2024 cancer trials that are labeled with specific genetic alteration information. Analysis of the knowledge base revealed the trend of increased use of targeted therapy for cancer, as well as top frequent gene-alteration pairs of interest. We expect this knowledge base to be a valuable resource for physicians and patients who are seeking information about personalized cancer therapy. PMID:27013523

ClinicalTrials.gov as a data source for semi-automated point-of-care trial eligibility screening.

PubMed

Pfiffner, Pascal B; Oh, JiWon; Miller, Timothy A; Mandl, Kenneth D

2014-01-01

Implementing semi-automated processes to efficiently match patients to clinical trials at the point of care requires both detailed patient data and authoritative information about open studies. To evaluate the utility of the ClinicalTrials.gov registry as a data source for semi-automated trial eligibility screening. Eligibility criteria and metadata for 437 trials open for recruitment in four different clinical domains were identified in ClinicalTrials.gov. Trials were evaluated for up to date recruitment status and eligibility criteria were evaluated for obstacles to automated interpretation. Finally, phone or email outreach to coordinators at a subset of the trials was made to assess the accuracy of contact details and recruitment status. 24% (104 of 437) of trials declaring on open recruitment status list a study completion date in the past, indicating out of date records. Substantial barriers to automated eligibility interpretation in free form text are present in 81% to up to 94% of all trials. We were unable to contact coordinators at 31% (45 of 146) of the trials in the subset, either by phone or by email. Only 53% (74 of 146) would confirm that they were still recruiting patients. Because ClinicalTrials.gov has entries on most US and many international trials, the registry could be repurposed as a comprehensive trial matching data source. Semi-automated point of care recruitment would be facilitated by matching the registry's eligibility criteria against clinical data from electronic health records. But the current entries fall short. Ultimately, improved techniques in natural language processing will facilitate semi-automated complex matching. As immediate next steps, we recommend augmenting ClinicalTrials.gov data entry forms to capture key eligibility criteria in a simple, structured format.

Extracting genetic alteration information for personalized cancer therapy from ClinicalTrials.gov.

PubMed

Xu, Jun; Lee, Hee-Jin; Zeng, Jia; Wu, Yonghui; Zhang, Yaoyun; Huang, Liang-Chin; Johnson, Amber; Holla, Vijaykumar; Bailey, Ann M; Cohen, Trevor; Meric-Bernstam, Funda; Bernstam, Elmer V; Xu, Hua

2016-07-01

Clinical trials investigating drugs that target specific genetic alterations in tumors are important for promoting personalized cancer therapy. The goal of this project is to create a knowledge base of cancer treatment trials with annotations about genetic alterations from ClinicalTrials.gov. We developed a semi-automatic framework that combines advanced text-processing techniques with manual review to curate genetic alteration information in cancer trials. The framework consists of a document classification system to identify cancer treatment trials from ClinicalTrials.gov and an information extraction system to extract gene and alteration pairs from the Title and Eligibility Criteria sections of clinical trials. By applying the framework to trials at ClinicalTrials.gov, we created a knowledge base of cancer treatment trials with genetic alteration annotations. We then evaluated each component of the framework against manually reviewed sets of clinical trials and generated descriptive statistics of the knowledge base. The automated cancer treatment trial identification system achieved a high precision of 0.9944. Together with the manual review process, it identified 20 193 cancer treatment trials from ClinicalTrials.gov. The automated gene-alteration extraction system achieved a precision of 0.8300 and a recall of 0.6803. After validation by manual review, we generated a knowledge base of 2024 cancer trials that are labeled with specific genetic alteration information. Analysis of the knowledge base revealed the trend of increased use of targeted therapy for cancer, as well as top frequent gene-alteration pairs of interest. We expect this knowledge base to be a valuable resource for physicians and patients who are seeking information about personalized cancer therapy. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Clinical trials in rheumatoid arthritis: a status report from the ClinicalTrials.gov website.

PubMed

Paul, Jisna R; Ranganathan, Prabha

2012-06-01

The aims of this study are to describe the characteristics of clinical trials in rheumatoid arthritis (RA) listed in ClinicalTrials.gov and examine existing trends in study design, funding sources, outcomes, and drugs under investigation. We conducted a survey of ongoing clinical trials in RA registered in the ClinicalTrials.gov website. We used the advanced search option and applied the following inclusion criteria, "rheumatoid arthritis", "open studies", "interventional", and "adults 18 years or older". Of 127 eligible trials, 53.5% of the studies were either phase 3 or 4, and 40.2% were phase 1, 2, and 2/3. Two-thirds of the trials were randomized (70.9%), and over half were, in addition, double-blinded (53.5%) and placebo-controlled (53.5%). Universities were listed as the primary sponsor for 18.9% of the trials and pharmaceutical industry for 73.2%. Majority of the trials were multi-center studies (93%) conducted outside the United States (54.3%). The most frequently used endpoint was drug efficacy (54.3%) followed by drug safety (25.2%). Most industry-funded trials were open for less than 12 months, whereas most university-funded trials were open for more than 24 months (58% each). Biologic therapies were the focus of most trials in the registry (78.5%). Randomized, double-blinded, placebo-controlled, phase 3 and 4 trials form the majority of ongoing clinical trials in RA. The preponderance of industry funding of RA trials and the short duration of such trials are troubling trends which need to be addressed.

Minorities and Clinical Trials: Patients, Physicians, Clinical Trial Characteristics and their Environment

DTIC Science & Technology

2012-07-01

sites to assess their discussions with physicians, intentions and actual participation in prostate cancer clinical trials, attitudes and knowledge about...with physicians, intentions and actual participation in prostate cancer clinical trials, attitudes and knowledge about such trials, and barriers to and...calculated and compared across race/ethnicity. Examination of major outcomes included willingness to participate in, knowledge of, and attitudes towards

78 FR 56904 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-16

... Infectious Diseases Special Emphasis Panel; NIAID Clinical Trial Planning Grant (R34) and Clinical Trial... Committee: National Institute of Allergy and Infectious Diseases Special Emphasis Panel; NIAID Clinical Trial Planning Grant (R34) and Clinical Trial Implementation Cooperative Agreement (U01). Date: October...

77 FR 35407 - Proposed Collection; Comment Request: Clinical Mythteries: A Video Game About Clinical Trials

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-13

... Request: Clinical Mythteries: A Video Game About Clinical Trials SUMMARY: In compliance with the... review and approval. Proposed Collection: Title: Clinical Mythteries: A Video Game About Clinical Trials... an engaging, informational ``serious video game'' for adolescents about clinical studies which: (1...

The quality of registration of clinical trials.

PubMed

Viergever, Roderik F; Ghersi, Davina

2011-02-24

Lack of transparency in clinical trial conduct, publication bias and selective reporting bias are still important problems in medical research. Through clinical trials registration, it should be possible to take steps towards resolving some of these problems. However, previous evaluations of registered records of clinical trials have shown that registered information is often incomplete and non-meaningful. If these studies are accurate, this negates the possible benefits of registration of clinical trials. A 5% sample of records of clinical trials that were registered between 17 June 2008 and 17 June 2009 was taken from the International Clinical Trials Registry Platform (ICTRP) database and assessed for the presence of contact information, the presence of intervention specifics in drug trials and the quality of primary and secondary outcome reporting. 731 records were included. More than half of the records were registered after recruitment of the first participant. The name of a contact person was available in 94.4% of records from non-industry funded trials and 53.7% of records from industry funded trials. Either an email address or a phone number was present in 76.5% of non-industry funded trial records and in 56.5% of industry funded trial records. Although a drug name or company serial number was almost always provided, other drug intervention specifics were often omitted from registration. Of 3643 reported outcomes, 34.9% were specific measures with a meaningful time frame. Clinical trials registration has the potential to contribute substantially to improving clinical trial transparency and reducing publication bias and selective reporting. These potential benefits are currently undermined by deficiencies in the provision of information in key areas of registered records.

The Quality of Registration of Clinical Trials

PubMed Central

Viergever, Roderik F.; Ghersi, Davina

2011-01-01

Background Lack of transparency in clinical trial conduct, publication bias and selective reporting bias are still important problems in medical research. Through clinical trials registration, it should be possible to take steps towards resolving some of these problems. However, previous evaluations of registered records of clinical trials have shown that registered information is often incomplete and non-meaningful. If these studies are accurate, this negates the possible benefits of registration of clinical trials. Methods and Findings A 5% sample of records of clinical trials that were registered between 17 June 2008 and 17 June 2009 was taken from the International Clinical Trials Registry Platform (ICTRP) database and assessed for the presence of contact information, the presence of intervention specifics in drug trials and the quality of primary and secondary outcome reporting. 731 records were included. More than half of the records were registered after recruitment of the first participant. The name of a contact person was available in 94.4% of records from non-industry funded trials and 53.7% of records from industry funded trials. Either an email address or a phone number was present in 76.5% of non-industry funded trial records and in 56.5% of industry funded trial records. Although a drug name or company serial number was almost always provided, other drug intervention specifics were often omitted from registration. Of 3643 reported outcomes, 34.9% were specific measures with a meaningful time frame. Conclusions Clinical trials registration has the potential to contribute substantially to improving clinical trial transparency and reducing publication bias and selective reporting. These potential benefits are currently undermined by deficiencies in the provision of information in key areas of registered records. PMID:21383991

The patient's safety and access to experimental drugs after the termination of clinical trials: regulations and trends.

PubMed

da Silva, Ricardo Eccard; Amato, Angélica Amorim; Sousa, Thiago do Rego; de Carvalho, Marta Rodrigues; Novaes, Maria Rita Carvalho Garbi

2018-05-12

Participants' rights and safety must be guaranteed not only while a clinical trial is being conducted but also when a clinical trial finishes. The criteria for post-trial access to experimental drugs, however, are unclear in various countries. The objectives of this study were (i) to ascertain if there were regulations or guidelines related to patients' access to drugs after the end of clinical trials in the countries selected in the study and (ii) to analyze trends in post-trial access in countries classified by their level of economic development. This study is a retrospective review. The data are from the records of clinical trials from 2014 registered in the World Health Organization's International Clinical Trials Registry Platform (ICTRP) database. Among the countries selected, provision of drugs post-trial is mandatory only in Argentina, Brazil, Chile, Finland, and Peru. The plans for post-trial access tend to be more present in low- and middle-income and upper middle-income countries, in comparison with high-income countries. Studies involving vulnerable populations are 2.53 times more likely to have plans for post-trial access than studies which do not. The guaranteeing of post-trial access remains mandatory in few countries. Considering that individuals seen as vulnerable have been included in clinical trials without plans for post-trial access, stakeholders must discuss the need to develop regulations mandating the guaranteeing of post-trial access in specified situations.

Pancreatic cancer clinical trials and accrual in the United States.

PubMed

Hoos, William A; James, Porsha M; Rahib, Lola; Talley, Anitra W; Fleshman, Julie M; Matrisian, Lynn M

2013-09-20

Pancreatic cancer clinical trials open in the United States and their accrual were examined to identify opportunities to accelerate progress in the treatment of pancreatic cancer. Pancreatic cancer-specific clinical trials open in the United States in the years 2011 and 2012 were obtained from the Pancreatic Cancer Action Network database. Accrual information was obtained from trial sponsors. The portfolio of pancreatic cancer clinical trials identified by type (adenocarcinoma or neuroendocrine), phase, disease stage, and treatment approach is reported. More than half of trials for patients with pancreatic ductal adenocarcinoma applied biologic insights to new therapeutic approaches, and 38% focused on optimization of radiation or chemotherapy delivery or regimens. In 2011, pancreatic cancer trials required total enrollment of 11,786 patients. Actual accrual to 93.2% of trials was 1,804 patients, an estimated 4.57% of the patients with pancreatic cancer alive in that year. The greatest need was for patients with resectable cancer. Trials open in 2011 enrolled an average of 15% of their total target accrual. Physician recommendations greatly influenced patients' decision to enroll or not enroll onto a clinical trial. Matching to a clinical trial within a 50-mile radius and identifying trials for recurrent/refractory disease were documented as challenges for patient accrual. Overall trial enrollment indicates that pancreatic cancer trials open in 2011 would require 6.7 years on average to complete accrual. These results suggest that harmonizing patient supply and demand for clinical trials is required to accelerate progress toward improving survival in pancreatic cancer.

Differences in Investigator-Initiated Trials between Japan and Other Countries: Analyses of Clinical Trials Sponsored by Academia and Government in the ClinicalTrials.gov Registry and in the Three Japanese Registries.

PubMed

Ito, Tatsuya

2016-01-01

Following the amendment of the Pharmaceutical Affairs Law in Japan in 2003 researchers were permitted to begin investigator-initiated trials (IITs). In subsequent years, however, the number of IITs remained low. In other countries in Asia as well as in Europe, North America, and South Africa, the number of IITs has increased over the past decade. The differences in the characteristics of IITs between Japan and other countries are unknown. Some studies have analyzed the characteristics of all clinical trials according to registry databases, but there has been less research focusing on IITs. The purpose of this study is to analyze the characteristics of IITs in the ClinicalTrials.gov registry and in the three Japanese registries, to identify differences in IITs between Japan and other countries. Using Thomson Reuters Pharma™, trials sponsored by academia and government as IITs in 2010 and registered in ClinicalTrials.gov were identified. IITs from 2004 to 2012 in Japan were identified in the three Japanese registries: the University Hospital Medical Information Network Clinical Trials Registry, the Japan Pharmaceutical Information Center Clinical Trials Information, and the Japan Medical Association Center for Clinical Trials, Clinical Trials Registry. Characterization was made of the trial purposes, phases, participants, masking, arms, design, controls, and other data. New and revised IITs registered in ClinicalTrials.gov during 2010 averaged about 40% of all sponsor-identified trials. IITs were nearly all early-phase studies with small numbers of participants. A total of 56 Japanese IITs were found over a period of 8 years, and these were also almost nearly all early-phase studies with small numbers of participants. There appear to be no great differences between Japan and other countries in terms of characteristics of IITs. These results should prompt a new review of the IIT environment in Japan.

Clinical differences between men and women undergoing surgery for acute Type A aortic dissection.

PubMed

Suzuki, Tomoaki; Asai, Tohru; Kinoshita, Takeshi

2018-06-01

The differences in clinical features, surgical outcome and long-term prognosis between men and women who undergo surgery for Type A aortic dissection are not well known. From January 2004 to December 2016, 303 patients, consisting of 147 women and 156 men, underwent surgery for acute Type A aortic dissection at our institution. We compared clinical outcomes between the 2 cohorts. Women were older than men (72.6 vs 63.0; P < 0.001). Operative mortality was similar between the groups (8.2% vs 8.9%; P = 0.80). The duration of intensive care unit stay (54 vs 64 h median; P = 0.03) and mechanical ventilator support (34 vs 43 h; P = 0.02) was significantly shorter in women. Multivariate logistic regression analysis revealed that preoperative cardiopulmonary resuscitation, cardiac tamponade, chronic obstructive pulmonary disease, haemodialysis and longer cardiopulmonary bypass time were independent risk factors for early death. Among the hospital survivors, the actuarial survival rate was 59.0% in women and 65.7% in men at 10 years (P = 0.81). During the follow-up period, there were 9 female and 27 male patients who underwent reoperation related to the aortic dissection. The rate of 10-year actuarial freedom from reoperation was 80.7% in women and 53.1% in men (log-rank P = 0.018). No differences were observed in both early and long-term mortality between women and men. Male patients had a significantly higher rate of reoperation. UMIN000029179.

Enrolling Minority and Underserved Populations in Cancer Clinical Research

PubMed Central

Wallington, Sherrie Flynt; Dash, Chiranjeev; Sheppard, Vanessa B.; Goode, Tawara D.; Oppong, Bridget A.; Dodson, Everett E.; Hamilton, Rhonda N.; Adams-Campbell, Lucile L.

2015-01-01

Research suggests that community involvement is integral to solving public health problems, including involvement in clinical trials—a “gold standard.” Significant racial/ethnic disparities exist in the accrual of participants for clinical trials. Location and cultural aspects of clinical trials influence recruitment and accrual to clinical trials. It is increasingly necessary to be aware of defining characteristics such as location and culture of the populations from which research participants are enrolled. Little research has examined the effect of location and cultural competency in adapting clinical trial research for minority and underserved communities on accrual for clinical trials. Utilizing embedded community academic sites, the authors applied cultural competency frameworks to adapt clinical trial research in order to increase minority participation in nontherapeutic cancer clinical trials. This strategy resulted in successful accrual of participants to new clinical research trials, specifically targeting participation from minority and underserved communities in metropolitan Washington, DC. From 2012 to 2014, a total of 559 participants enrolled across six non-therapeutic clinical trials, representing a 62% increase in the enrollment of blacks in clinical research. Embedding cancer prevention programs and research in the community was shown to be yet another important strategy in the arsenal of approaches that can potentially enhance clinical research enrollment and capacity. The analyses showed that the capacity to acquire cultural knowledge about patients—their physical locales, cultural values, and environments in which they live—is essential to recruiting culturally and ethnically diverse population samples. PMID:26470805

First-in-human Phase 1 CRISPR Gene Editing Cancer Trials: Are We Ready?

PubMed

Baylis, Francoise; McLeod, Marcus

2017-01-01

A prospective first-in-human Phase 1 CRISPR gene editing trial in the United States for patients with melanoma, synovial sarcoma, and multiple myeloma offers hope that gene editing tools may usefully treat human disease. An overarching ethical challenge with first-in-human Phase 1 clinical trials, however, is knowing when it is ethically acceptable to initiate such trials on the basis of safety and efficacy data obtained from pre-clinical studies. If the pre-clinical studies that inform trial design are themselves poorly designed - as a result of which the quality of pre-clinical evidence is deficient - then the ethical requirement of scientific validity for clinical research may not be satisfied. In turn, this could mean that the Phase 1 clinical trial will be unsafe and that trial participants will be exposed to risk for no potential benefit. To assist sponsors, researchers, clinical investigators and reviewers in deciding when it is ethically acceptable to initiate first-in-human Phase 1 CRISPR gene editing clinical trials, structured processes have been developed to assess and minimize translational distance between pre-clinical and clinical research. These processes draw attention to various features of internal validity, construct validity, and external validity. As well, the credibility of supporting evidence is to be critically assessed with particular attention to optimism bias, financial conflicts of interest and publication bias. We critically examine the pre-clinical evidence used to justify the first-inhuman Phase 1 CRISPR gene editing cancer trial in the United States using these tools. We conclude that the proposed trial cannot satisfy the ethical requirement of scientific validity because the supporting pre-clinical evidence used to inform trial design is deficient. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Knowledge and skills of cancer clinical trials nurses in Australia.

PubMed

Scott, Kathleen; White, Kate; Johnson, Catherine; Roydhouse, Jessica K

2012-05-01

  This paper is a report of the development and testing of a questionnaire measuring knowledge and skills of cancer clinical trials nurse in Australia.   The role of cancer clinical trials nurse, widely acknowledged as an integral member of the clinical research team, has evolved in recent years. Elements of the clinical trials nurse role in cancer have previously been described. To evaluate specific cancer clinical trials nurse educational and training needs, the development of a valid and reliable tool is required.   In 2009, a study was conducted in three stages. Stage I: questionnaire development and pilot testing; stage II: focus group; stage III: national survey. Internal consistency reliability testing and multi-trait analysis of item convergent/divergent validity were employed. Regression analysis was used to identify predictors of clinical trials nurse knowledge and skills.   The national survey was a 48-item questionnaire, measuring six clinical trial knowledge and seven skills sub-scales. Of 61 respondents, 90% were women, with mean age 43 years, 19 years as a Registered Nurse and 5 years as a cancer clinical trials nurse. Self-reported knowledge and skills were satisfactory to good. Internal consistency reliability was high (Cronbach's alpha: knowledge = 0·98; skills = 0·90). Criteria for item convergent/divergent validity were met. Number of years as cancer clinical trials nurse was positively related to self-reported knowledge and skills.   Preliminary data suggest that the national survey is reliable and valid. Data have contributed to better understanding the knowledge and skills of cancer clinical trials nurse in Australia and development of a postgraduate course in clinical trials. © 2011 Blackwell Publishing Ltd.

The Cooperative Landscape of Multinational Clinical Trials

PubMed Central

Hsiehchen, David; Espinoza, Magdalena; Hsieh, Antony

2015-01-01

The scale and nature of cooperative efforts spanning geopolitical borders in clinical research have not been elucidated to date. In a cross-sectional study of 110,428 interventional trials registered in Clinicaltrials.gov, we characterized the evolution, trial demographics, and network properties of multinational clinical research. We reveal that the relative growth of international collaboratives has remained stagnant in the last two decades, although clinical trials have evolved to become much larger in scale. Multinational clinical trials are also characterized by higher patient enrollments, industry funding, and specific clinical disciplines including oncology and infectious disease. Network analyses demonstrate temporal shifts in collaboration patterns between countries and world regions, with developing nations now collaborating more within themselves, although Europe remains the dominant contributor to multinational clinical trials worldwide. Performances in network centrality measures also highlight the differential contribution of nations in the global research network. A city-level clinical trial network analysis further demonstrates how collaborative ties decline with physical distance. This study clarifies evolving themes and highlights potential growth mechanisms and barriers in multinational clinical trials, which may be useful in evaluating the role of national and local policies in organizing transborder efforts in clinical endeavors. PMID:26103155

ClinicalTrials.gov and Drugs@FDA: A Comparison of Results Reporting for New Drug Approval Trials.

PubMed

Schwartz, Lisa M; Woloshin, Steven; Zheng, Eugene; Tse, Tony; Zarin, Deborah A

2016-09-20

Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. To validate results posted on ClinicalTrials.gov against publicly available U.S. Food and Drug Administration (FDA) reviews on Drugs@FDA. ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical and statistical reviews). 100 parallel-group, randomized trials for new drug approvals (January 2013 to July 2014) with results posted on ClinicalTrials.gov (15 March 2015). 2 assessors extracted, and another verified, the trial design, primary and secondary outcomes, adverse events, and deaths. Most trials were phase 3 (90%), double-blind (92%), and placebo-controlled (73%) and involved 32 drugs from 24 companies. Of 137 primary outcomes identified from ClinicalTrials.gov, 134 (98%) had corresponding data at Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results. Most differences were nominal (that is, relative difference <10%). Primary outcome results in 14 trials could not be validated. Of 1927 secondary outcomes from ClinicalTrials.gov, Drugs@FDA mentioned 1061 (55%) and included results data for 367 (19%). Of 96 trials with 1 or more serious adverse events in either source, 14 could be compared and 7 had discordant numbers of persons experiencing the adverse events. Of 62 trials with 1 or more deaths in either source, 25 could be compared and 17 were discordant. Unknown generalizability to uncontrolled or crossover trial results. Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half the secondary outcomes, as well as serious events and deaths, could not be validated because Drugs@FDA includes only "key outcomes" for regulatory decision making and frequently includes only adverse event results aggregated across multiple trials. National Library of Medicine.

[Clinical trials in nursing journals].

PubMed

Di Giulio, Paola; Campagna, Sara; Dimonte, Valerio

2014-01-01

Clinical trials are pivotal for the development of nursing knowledge. To describe the clinical trials published in nursing journals in the last two years and propose some general reflections on nursing research. A search with the key-word trial was done on PubMed (2009-2013) on Cancer Nursing, European Journal of Oncology Nursing, International Journal of Nursing Studies, Journal of Advanced Nursing, Journal of Clinical Nursing and Nursing Research. Of 228 trials identified, 104 (45.8%) were published in the last 2 years. Nurses from Asian countries published the larger number of trials. Educational and supportive interventions were the most studied (61/104 trials), followed by clinical interventions (33/104). Samples were limited and most trials are monocentric. A growing number of trials is published, on issues relevant for the nursing profession, however larger samples and multicentric studies would be necessary.

Design of a cluster-randomized minority recruitment trial: RECRUIT.

PubMed

Tilley, Barbara C; Mainous, Arch G; Smith, Daniel W; McKee, M Diane; Amorrortu, Rossybelle P; Alvidrez, Jennifer; Diaz, Vanessa; Ford, Marvella E; Fernandez, Maria E; Hauser, Robert A; Singer, Carlos; Landa, Veronica; Trevino, Aron; DeSantis, Stacia M; Zhang, Yefei; Daniels, Elvan; Tabor, Derrick; Vernon, Sally W

2017-06-01

Racial/ethnic minority groups remain underrepresented in clinical trials. Many strategies to increase minority recruitment focus on minority communities and emphasize common diseases such as hypertension. Scant literature focuses on minority recruitment to trials of less common conditions, often conducted in specialty clinics and dependent on physician referrals. We identified trust/mistrust of specialist physician investigators and institutions conducting medical research and consequent participant reluctance to participate in clinical trials as key-shared barriers across racial/ethnic groups. We developed a trust-based continuous quality improvement intervention to build trust between specialist physician investigators and community minority-serving physicians and ultimately potential trial participants. To avoid the inherent biases of non-randomized studies, we evaluated the intervention in the national Randomized Recruitment Intervention Trial (RECRUIT). This report presents the design of RECRUIT. Specialty clinic follow-up continues through April 2017. We hypothesized that specialist physician investigators and coordinators trained in the trust-based continuous quality improvement intervention would enroll a greater proportion of minority participants in their specialty clinics than specialist physician investigators in control specialty clinics. Specialty clinic was the unit of randomization. Using continuous quality improvement, the specialist physician investigators and coordinators tailored recruitment approaches to their specialty clinic characteristics and populations. Primary analyses were adjusted for clustering by specialty clinic within parent trial and matching covariates. RECRUIT was implemented in four multi-site clinical trials (parent trials) supported by three National Institutes of Health institutes and included 50 associated specialty clinics from these parent trials. Using current data, we have 88% power or greater to detect a 0.15 or greater difference from the currently observed control proportion adjusting for clustering. We detected no differences in baseline matching criteria between intervention and control specialty clinics (all p values > 0.17). RECRUIT was the first multi-site randomized control trial to examine the effectiveness of a trust-based continuous quality improvement intervention to increase minority recruitment into clinical trials. RECRUIT's innovations included its focus on building trust between specialist investigators and minority-serving physicians, the use of continuous quality improvement to tailor the intervention to each specialty clinic's specific racial/ethnic populations and barriers to minority recruitment, and the use of specialty clinics from more than one parent multi-site trial to increase generalizability. The effectiveness of the RECRUIT intervention will be determined after the completion of trial data collection and planned analyses.

Management of data from clinical trials using the ArchiMed system.

PubMed

Duftschmid, Georg; Gall, Walter; Eigenbauer, Ernst; Dorda, Wolfgang

2002-06-01

Clinical trials constitute a key source of medical research and are therefore conducted on a regular basis at university hospitals. The professional execution of trials requires, among other things, a repertoire of tools that support efficient data management. Tasks that are essential for efficient data management in clinical trials include the following: the design of the trial database, the design of electronic case report forms, recruiting patients, collection of data, and statistical analysis. The present article reports the manner in which these tasks are supported by the ArchiMed system at the University of Vienna and Graz Medical Schools. ArchiMed is customized for clinical end users, allowing them to autonomously manage their clinical trials without having to consult computer experts. An evaluation of the ArchiMed system in 12 trials recently conducted at the University of Vienna Medical School shows that the individual system functions can be usefully applied for data management in clinical trials.