Pemetrexed Continuation Maintenance in Patients with Nonsquamous Non-small Cell Lung Cancer: Review of Two East Asian Trials in Reference to PARAMOUNT.

PubMed

Yang, James Chin-Hsin; Ahn, Myung-Ju; Nakagawa, Kazuhiko; Tamura, Tomohide; Barraclough, Helen; Enatsu, Sotaro; Cheng, Rebecca; Orlando, Mauro

2015-07-01

A recent phase III study (PARAMOUNT) demonstrated that pemetrexed continuation maintenance therapy is a new treatment paradigm for advanced nonsquamous non-small cell lung cancer (NSCLC). The majority of patients enrolled in PARAMOUNT were Caucasian (94%). We reviewed efficacy and safety data from two clinical trials, which enrolled East Asian (EA) patients, to supplement data from PARAMOUNT on pemetrexed continuation maintenance therapy in patients with nonsquamous NSCLC. Study S110 was a phase II, multicenter, randomized, controlled, open-label trial in never-smoker, chemonaïve, EA patients (n=31) with locally advanced or metastatic nonsquamous NSCLC (n=27). Study JMII was a multicenter, open-label, single-arm, post-marketing, clinical trial in Japanese patients (n=109) with advanced nonsquamous NSCLC. PARAMOUNT was a multicenter, randomized, double-blind, placebo-controlled trial in patients with advanced nonsquamous NSCLC. In EA patients with nonsquamous NSCLC, the median progression-free survival (PFS) for pemetrexed continuation maintenance therapy was 4.04 months (95% confidence interval [CI], 3.22 to 5.29 months) in study S110 and 3.9 months (95% CI, 3.2 to 5.2 months) in study JMII. The median PFS for pemetrexed continuation maintenance therapy in PARAMOUNT was 4.1 months (95% CI, 3.2 to 4.6 months). Pemetrexed continuation maintenance therapy in EA patients in studies S110 and JMII did not lead to any unexpected safety events, and was consistent with PARAMOUNT's safety profile. The efficacy and safety data in the EA trials were similar to those in PARAMOUNT despite differences in patient populations and study designs. These data represent consistent evidence for pemetrexed continuation maintenance therapy in EA patients with advanced nonsquamous NSCLC.

Information on center characteristics as costs' determinants in multicenter clinical trials: is modeling center effect worth the effort?

PubMed

Petrinco, Michele; Pagano, Eva; Desideri, Alessandro; Bigi, Riccardo; Ghidina, Marco; Ferrando, Alberto; Cortigiani, Lauro; Merletti, Franco; Gregori, Dario

2009-01-01

Several methodological problems arise when health outcomes and resource utilization are collected at different sites. To avoid misleading conclusions in multi-center economic evaluations the center effect needs to be taken into adequate consideration. The aim of this article is to compare several models, which make use of a different amount of information about the enrolling center. To model the association of total medical costs with the levels of two sets of covariates, one at patient and one at center level, we considered four statistical models, based on the Gamma model in the class of the Generalized Linear Models with a log link, which use different amount of information on the enrolling centers. Models were applied to Cost of Strategies after Myocardial Infarction data, an international randomized trial on costs of uncomplicated acute myocardial infarction (AMI). The simple center effect adjustment based on a single random effect results in a more conservative estimation of the parameters as compared with approaches which make use of deeper information on the centers characteristics. This study shows, with reference to a real multicenter trial, that center information cannot be neglected and should be collected and inserted in the analysis, better in combination with one or more random effect, taking into account in this way also the heterogeneity among centers because of unobserved centers characteristics.

The effectiveness and safety of amisulpride in Chinese patients with schizophrenia: An 8‐week, prospective, open‐label, multicenter, single‐arm study

PubMed Central

Liang, Ying; Cao, Changan; Zhu, Cheng; Wang, Chuanyue; Zhang, Congpei; Dong, Fang; Yang, Fude; Deng, Hong; Yu, Jingjie; Tang, Jisheng; Su, Lei; Xin, Limin; Hong, Ling; Gao, Minglong; Tang, Muni; Xie, Shiping; Lu, Shuiping; Liu, Tiebang; Xu, Xiaojin; Wang, Xijin; Li, Xuanzi; Wang, Xueyi; Li, Yi; Zhang, Yong; Chen, Zhiyu

2016-01-01

Abstract Introduction This study evaluated the effectiveness and safety of amisulpride in Chinese schizophrenia patients. Methods A multicenter, single‐arm Phase IV study (NCT01795183). Chinese patients with schizophrenia received amisulpride for 8 weeks. The primary endpoint was ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. Results A total of 316 patients were enrolled; 295 were included in the effectiveness analysis; 66.8% (197/295) achieved ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. Nine patients discontinued treatment because of adverse events. Discussion Amisulpride had clinical effectiveness and was relatively well tolerated in Chinese patients with schizophrenia. PMID:27020720

Feasibility of Patient Reporting of Symptomatic Adverse Events via the PRO-CTCAE in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial

PubMed Central

Basch, Ethan; Pugh, Stephanie L; Dueck, Amylou C; Mitchell, Sandra A; Berk, Lawrence; Fogh, Shannon; Rogak, Lauren J; Gatewood, Marcha; Reeve, Bryce B; Mendoza, Tito R; O’Mara, Ann; Denicoff, Andrea; Minasian, Lori; Bennett, Antonia V; Setser, Ann; Schrag, Deborah; Roof, Kevin; Moore, Joan K; Gergel, Thomas; Stephans, Kevin; Rimner, Andreas; DeNittis, Albert; Bruner, Deborah Watkins

2017-01-01

Purpose To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Methods and Materials Patients enrolled in Trial XXXX (XXXX) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly x4 during treatment; 12-weeks post-treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. Results Among 226 study sites participating in Trial XXXX, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients of which 34 (43%) required tablet computers to be provided. All 152 patients in Trial XXXX agreed to self-report using the PRO-CTCAE (median age 66; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range 30–240), and median time for CRAs to teach a patient to self-report was 10 minutes (range 2–60). Compliance was high, particularly during active treatment when patients self-reported at 86% of expected time points, although compliance was lower post-treatment (72%). Common reasons for non-compliance were institutional errors such as forgetting to provide computers to participants; patients missing clinic visits; internet connectivity; and patients feeling “too sick”. Conclusions Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic adverse events at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between-visits, and by employing central compliance monitoring. These approaches are being incorporated into ongoing studies. PMID:28463161

Single-Incision Multiport/Single Port Laparoscopic Abdominal Surgery (SILAP): A Prospective Multicenter Observational Quality Study.

PubMed

Mantke, Rene; Diener, Markus; Kropf, Siegfried; Otto, Ronny; Manger, Thomas; Vestweber, Boris; Mirow, Lutz; Winde, Günther; Lippert, Hans

2016-09-07

Increasing experience with minimally invasive surgery and the development of new instruments has resulted in a tendency toward reducing the number of abdominal skin incisions. Retrospective and randomized prospective studies could show the feasibility of single-incision surgery without any increased risk to the patient. However, large prospective multicenter observational datasets do not currently exist. This prospective multicenter observational quality study will provide a relevant dataset reflecting the feasibility and safety of single-incision surgery. This study focuses on external validity, clinical relevance, and the patients' perspective. Accordingly, the single-incision multiport/single port laparoscopic abdominal surgery (SILAP) study will supplement the existing evidence, which does not currently allow evidence-based surgical decision making. The SILAP study is an international prospective multicenter observational quality study. Mortality, morbidity, complications during surgery, complications postoperatively, patient characteristics, and technical aspects will be monitored. We expect more than 100 surgical centers to participate with 5000 patients with abdominal single-incision surgery during the study period. Funding was obtained in 2012. Enrollment began on January 01, 2013, and will be completed on December 31, 2018. As of January 2016, 2119 patients have been included, 106 German centers are registered, and 27 centers are very active (>5 patients per year). This prospective multicenter observational quality study will provide a relevant dataset reflecting the feasibility and safety of single-incision surgery. An international enlargement and recruitment of centers outside of Germany is meaningful. German Clinical Trials Register: DRKS00004594; https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00004594 (Archived by WebCite at http://www.webcitation.org/6jK6ZVyUs).

Biofilm removal from implants supported restoration using different instruments: a 6-month comparative multicenter clinical study.

PubMed

Blasi, Andrea; Iorio-Siciliano, Vincenzo; Pacenza, Carina; Pomingi, Francesca; Matarasso, Sergio; Rasperini, Giulio

2016-02-01

The aim of this study was to compare the efficacy of different instruments on biofilm removal from implant supported restorations. The study was designed as comparative multicenter clinical study including patients proceeding from the Milan, Naples, and Buenos Aires, with a peri-implant mucositis. Implants enrolled for the study were allocated in 4 groups and treated with ultrasonic scalers with plastic tips, with titanium curettes, with airflow with glycine powder, and with rubber cup and polishing paste, respectively. mPI was assessed at baseline, immediately after therapy, at 1, 3, and 6 months. mBI, PD, and REC were assessed at baseline, 1, 3, and 6 months. All parameters were recorded on six sites per implant. Kruskal-Wallis and Mann-Whitney tests were used to compare groups and centers. A generalized linear model for repeated measures was chosen for inter-group comparison. An intra-group comparison was performed with repeated measure ANOVA test to assess differences between baseline and recalls. A total of 89 patients (39 males, 50 females) were enrolled in the study, and 141 implants were available for the analysis. 55 implants were enrolled in University of Buenos Aires, 32 in University of Milan, and 54 in University of Naples. There were no significant differences between the four groups in inflammatory status reduction of peri-implant mucosa. Non-surgical therapy is effective in reducing peri-implant mucositis. Sonic scaler with plastic tip and rubber cup with polishing paste showed higher efficacy when compared with titanium curettes or airflow with glycine powder. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A phase II study of apatinib in patients with recurrent epithelial ovarian cancer.

PubMed

Miao, Mingming; Deng, Guanming; Luo, Sujuan; Zhou, Jiajia; Chen, Le; Yang, Jun; He, Jie; Li, Junjun; Yao, Jing; Tan, Shanmei; Tang, Jie

2018-02-01

Antiangiogenic treatments have been implicated to play a major role in epithelial ovarian cancer (EOC). Apatinib, a novel oral antiangiogenic agent targeting vascular endothelial growth factor receptor (VEGFR2), is currently being studied in different tumor types and is already used in gastric adenocarcinoma. This study was performed to assess the efficacy and safety of apatinib in patients with recurrent, pretreated EOC. Patients with recurrent, platinum-resistant, pre-treated EOC who failed available standard chemotherapy were enrolled. Apatinib was administered as 500mg daily. Primary objective is the overall response rate (ORR) according to MASS criteria. Secondary objectives are progression free survival (PFS), overall survival (OS), disease control rate (DCR), safety and tolerability. The treatment duration is until disease progression or intolerability of apatinib. 29 eligible patients were enrolled in this multicenter, open-label, single arm study and received apatinib for a median of 36.8weeks (range 13-64.8weeks). Median follow-up time was 12months. 28 patients were eligible for efficacy analysis. ORR is 41.4% (95% confidence interval (CI), 23.3%-59.4%). DCR is 68.9% (95% CI, 52.1%-85.8%). Median PFS is 5.1months (95% CI, 3.8m-6.5m). Median OS is 14.5months (95% CI, 12.4m-16.4m). The most common treatment-related adverse events (AEs) were hand-foot syndrome (51.7%), hypertension (34.6%), nausea and vomiting (31.0%). 3 patients had no significant toxicity. 9 patients experienced grade 3 treatment-related AEs. Apatinib 500mg daily p.o. is a feasible treatment in patients with recurrent, platinum-resistant, pretreated EOC. Multi-center prospective studies enrolling more patients are needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Multicenter, double-blind, parallel group study investigating the non-inferiority of efficacy and safety of a 2% miconazole nitrate shampoo in comparison with a 2% ketoconazole shampoo in the treatment of seborrhoeic dermatitis of the scalp.

PubMed

Buechner, Stanislaw A

2014-06-01

This study investigated the non-inferiority of efficacy and tolerance of 2% miconazole nitrate shampoo in comparison with 2% ketoconazole shampoo in the treatment of scalp seborrheic dermatitis. A randomized, double-blind, comparative, parallel group, multicenter study was done. A total of 274 patients (145 miconazole, 129 ketoconazole) were enrolled. Treatment was twice-weekly for 4 weeks. Safety and efficacy assessments were made at baseline and at weeks 2 and 4. Assessments included symptoms of erythema, itching, scaling ['Symptom Scale of Seborrhoeic Dermatitis' (SSSD)], disease severity and global change [Clinical Global Impressions (CGIs) and Patient Global Impressions (PGIs)]. Miconazole shampoo is at least as effective and safe as ketoconazole shampoo in treating scalp seborrheic dermatitis scalp.

The Global Enteric Multicenter Study (GEMS) of Diarrheal Disease in Infants and Young Children in Developing Countries: Epidemiologic and Clinical Methods of the Case/Control Study

PubMed Central

Kotloff, Karen L.; Blackwelder, William C.; Nasrin, Dilruba; Nataro, James P.; Farag, Tamer H.; van Eijk, Annemieke; Adegbola, Richard A.; Alonso, Pedro L.; Breiman, Robert F.; Golam Faruque, Abu Syed; Saha, Debasish; Sow, Samba O.; Sur, Dipika; Zaidi, Anita K. M.; Biswas, Kousick; Panchalingam, Sandra; Clemens, John D.; Cohen, Dani; Glass, Roger I.; Mintz, Eric D.; Sommerfelt, Halvor; Levine, Myron M.

2012-01-01

Background. Diarrhea is a leading cause of illness and death among children aged <5 years in developing countries. This paper describes the clinical and epidemiological methods used to conduct the Global Enteric Multicenter Study (GEMS), a 3-year, prospective, age-stratified, case/control study to estimate the population-based burden, microbiologic etiology, and adverse clinical consequences of acute moderate-to-severe diarrhea (MSD) among a censused population of children aged 0–59 months seeking care at health centers in sub-Saharan Africa and South Asia. Methods. GEMS was conducted at 7 field sites, each serving a population whose demography and healthcare utilization practices for childhood diarrhea were documented. We aimed to enroll 220 MSD cases per year from selected health centers serving each site in each of 3 age strata (0–11, 12–23, and 24–59 months), along with 1–3 matched community controls. Cases and controls supplied clinical, epidemiologic, and anthropometric data at enrollment and again approximately 60 days later, and provided enrollment stool specimens for identification and characterization of potential diarrheal pathogens. Verbal autopsy was performed if a child died. Analytic strategies will calculate the fraction of MSD attributable to each pathogen and the incidence, financial costs, nutritional consequences, and case fatality overall and by pathogen. Conclusions. When completed, GEMS will provide estimates of the incidence, etiology, and outcomes of MSD among infants and young children in sub-Saharan Africa and South Asia. This information can guide development and implementation of public health interventions to diminish morbidity and mortality from diarrheal diseases. PMID:23169936

Classification and possible bacterial infection in outpatients with eczema and dermatitis in China: A cross-sectional and multicenter study.

PubMed

Wang, Xin; Shi, Xiao-Dong; Li, Lin-Feng; Zhou, Ping; Shen, Yi-Wei

2017-09-01

Little is known about the classification and bacterial infection in outpatients with eczema and dermatitis in China.To investigate the prevalence of eczema and dermatitis in outpatients of dermatology clinics in China, examine classification and proportion of common types of dermatitis and the possible bacterial infection, and analyze the possible related factors.Outpatients with eczema or dermatitis from 39 tertiary hospitals of 15 provinces in mainland China from July 1 to September 30, 2014, were enrolled in this cross-sectional and multicenter study. Among 9393 enrolled outpatients, 636 patients (6.7%) were excluded because of incomplete information.The leading subtypes of dermatitis were unclassified eczema (35.5%), atopic dermatitis (13.4%), irritant dermatitis (9.2%), and widespread eczema (8.7%). Total bacterial infection rate was 52.3%, with widespread eczema, stasis dermatitis, and atopic dermatitis being the leading three (65.7%, 61.8%, and 61.4%, respectively). Clinically very likely bacterial infection has a significant positive correlation with disease duration, history of allergic disease, history of flexion dermatitis, and severe itching.Atopic dermatitis has become a common subtype of dermatitis in China. Secondary bacterial infection is common in all patients with dermatitis, and more attentions should be paid on this issue in other type of dermatitis apart from atopic dermatitis.

Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial

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

Basch, Ethan, E-mail: ebasch@med.unc.edu; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; Pugh, Stephanie L.

Purpose: To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Methods and Materials: Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visitsmore » when an expected PRO-CTCAE assessment was completed. Results: Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling “too sick.” Conclusions: Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies.« less

Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial.

PubMed

Basch, Ethan; Pugh, Stephanie L; Dueck, Amylou C; Mitchell, Sandra A; Berk, Lawrence; Fogh, Shannon; Rogak, Lauren J; Gatewood, Marcha; Reeve, Bryce B; Mendoza, Tito R; O'Mara, Ann M; Denicoff, Andrea M; Minasian, Lori M; Bennett, Antonia V; Setser, Ann; Schrag, Deborah; Roof, Kevin; Moore, Joan K; Gergel, Thomas; Stephans, Kevin; Rimner, Andreas; DeNittis, Albert; Bruner, Deborah Watkins

2017-06-01

To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling "too sick." Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Retrieval of the Leadless Cardiac Pacemaker: A Multicenter Experience.

PubMed

Reddy, Vivek Y; Miller, Marc A; Knops, Reinoud E; Neuzil, Petr; Defaye, Pascal; Jung, Werner; Doshi, Rahul; Castellani, Mark; Strickberger, Adam; Mead, R Hardwin; Doppalapudi, Harish; Lakkireddy, Dhanunjaya; Bennett, Matthew; Sperzel, Johannes

2016-12-01

Leadless cardiac pacemakers have emerged as a safe and effective alternative to conventional transvenous single-chamber ventricular pacemakers. Herein, we report a multicenter experience on the feasibility and safety of acute retrieval (<6 weeks) and chronic retrieval (>6 weeks) of the leadless cardiac pacemaker in humans. This study included patients enrolled in 3 multicenter trials, who received a leadless cardiac pacemaker implant and who subsequently underwent a device removal attempt. The overall leadless pacemaker retrieval success rate was 94%: for patients whose leadless cardiac pacemaker had been implanted for <6 weeks (acute retrieval cohort), complete retrieval was achieved in 100% (n=5/5); for those implanted for ≥ 6 weeks (chronic retrieval cohort), retrieval was achieved in 91% (n=10/11) of patients. The mean duration of time from implant to retrieval attempt was 346 days (range, 88-1188 days) in the chronic retrieval cohort, and nearly two thirds (n=7; 63%) had been implanted for >6 months before the retrieval attempt. There were no procedure-related adverse events at 30 days post retrieval procedure. This multicenter experience demonstrated the feasibility and safety of retrieving a chronically implanted single-chamber (right ventricle) active fixation leadless pacemaker. URL: https://www.clinicaltrials.gov. Unique identifiers: NCT02051972, NCT02030418, and NCT01700244. © 2016 American Heart Association, Inc.

The association between physiologic dead-space fraction and mortality in subjects with ARDS enrolled in a prospective multi-center clinical trial.

PubMed

Kallet, Richard H; Zhuo, Hanjing; Liu, Kathleen D; Calfee, Carolyn S; Matthay, Michael A

2014-11-01

We tested the association between pulmonary dead-space fraction (ratio of dead space to tidal volume [V(D)/V(T)]) and mortality in subjects with ARDS (Berlin definition, P(aO2)/F(IO2) ≤ 300 mm Hg; PEEP ≥ 5 cm H2O) enrolled into a clinical trial incorporating lung-protective ventilation. We conducted a prospective, multi-center study at medical-surgical ICUs in the United States. A total of 126 ALI subjects with acute lung injury were enrolled into a phase 3 randomized, placebo-controlled study of aerosolized albuterol. V(D)/V(T) and pulmonary mechanics were measured within 4 h of enrollment and repeated daily on study days 1 and 2 in subjects requiring arterial blood gases for clinical management. At baseline, non-survivors had a trend toward higher V(D)/V(T) compared with survivors (0.62 ± 0.11 vs 0.56 ± 0.11, respectively, P = .08). Differences in V(D)/V(T) between non-survivors and survivors became significant on study days 1 (0.64 ± 0.12 vs 0.55 ± 0.11, respectively, P = .01) and 2 (0.67 ± 0.12 vs 0.56 ± 0.11, respectively, P = .004). Likewise, the association between VD/VT and mortality was significant on study day 1 (odds ratio per 0.10 change in V(D)/V(T) [95% CI]: 6.84 [1.62-28.84] P = .01; and study day 2: 4.90 [1.28-18.73] P = .02) after adjusting for V(D)/V(T), P(aO2)/F(IO2), oxygenation index, vasopressor use, and the primary risk for ARDS. Using a Cox proportional hazard model, V(D)/V(T) was associated with a trend toward higher mortality (HR = 4.37 [CI 0.99-19.32], P = .052) that became significant when the analysis was adjusted for daily oxygenation index (HR = 1.74 [95% CI 1.12-3.35] P = .04). Markedly elevated V(D)/V(T) (≥ 0.60) in early ARDS is associated with higher mortality. Measuring V(D)/V(T) may be useful in identifying ARDS patients at increased risk of death who are enrolled into a therapeutic trial. Copyright © 2014 by Daedalus Enterprises.

Safety and efficacy of a 10% intravenous immunoglobulin preparation in patients with immune thrombocytopenic purpura: results of two international, multicenter studies.

PubMed

Kovaleva, Lidia; Apte, Shashikant; Damodar, Sharat; Ramanan, Vijay; Loriya, Svetlana; Navarro-Puerto, Jordi; Khojasteh, Ali

2016-12-01

To assess safety and efficacy of a 10% intravenous immunoglobulin in patients with primary immune thrombocytopenic purpura (ITP). ITP patients in two multicenter studies (Trials A/B) were treated with 2 g/kg Flebogamma ® 10% DIF (over 2-5 days) and were followed up to 1-3 months. 18 patients in Trial A and 58 in Trial B were enrolled (12 children in Trial B). The response rate (platelet count ≥50 × 10 9 /l) was 72.2% (Trial A) and 76.1/100% (adults/children; Trial B). Most patients improved bleedings (83.3% Trial A; 88.9% Trial B). Potential treatment-related adverse events were reported by 38.9% (Trial A) and 30.4/83.3% (adults/children; Trial B) of patients. All serious adverse events (five patients) resolved without sequelae. Flebogamma 10% DIF was effective and safe in patients with primary ITP.

Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis.

PubMed

Davis, Stephanie D; Ratjen, Felix; Brumback, Lyndia C; Johnson, Robin C; Filbrun, Amy G; Kerby, Gwendolyn S; Panitch, Howard B; Donaldson, Scott H; Rosenfeld, Margaret

2016-05-01

The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint. Secondary analysis of ISIS data was conducted in order to assess feasibility of iPFT measures and their associations with respiratory symptoms. Standard deviations were calculated to aid in power calculations for future clinical trials. Seventy-three participants enrolled, 70 returned for the final visit; 62 (89%) and 45 (64%) had acceptable paired functional residual capacity (FRC) and raised volume measurements, respectively. Mean baseline FEV0.5, FEF75 and FRC z-scores were 0.3 (SD: 1.2), -0.2 (SD: 2.0), and 1.8 (SD: 2.0). iPFTs are not appropriate primary endpoints for multicenter clinical trials due to challenges of obtaining acceptable data and near-normal average raised volume measurements. Raised volume measures have potential to serve as secondary endpoints in future clinical CF trials. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Differences in recruitment and early retention among ethnic minority participants in a large pediatric cohort: The TEDDY Study

PubMed Central

Baxter, Judith; Vehik, Kendra; Johnson, Suzanne Bennett; Lernmark, Barbro; Roth, Roswith; Simell, Tuula

2013-01-01

Objective The TEDDY Study is an international, multi-center prospective study designed to identify the environmental triggers of type 1 diabetes (T1D) in genetically at-risk children. This report investigates ethnic minority (EM) differences in patterns of enrollment and retention in the US centers. Methods As of June 2009, 267,739 newborns had been screened at birth for high risk T1D genotypes. Data collected at the time of screening, enrollment and at the baseline visit were used. Descriptive and multiple-logistic regression analyses assessed differences between EM groups regarding exclusion, enrollment and early withdrawal. Results Of the 10,975 eligible subjects, 6,912 (67%) were invited to participate. EM subjects were more likely to be excluded because of an inability to contact. Of those invited 3,265 (47%) enrolled by the age of 4.5 months. Adjusted analyses showed that except for those classified as other EM, the odds of enrolling were similar across groups. EM subjects had elevated early withdrawal rates. Adjusted models demonstrated that this was significantly more likely among Hispanic subjects. Conclusion Understanding patterns associated with EM participation in research extends our ability to make more accurate inferences and permits assessment of strategies that promote inclusion of EM to better address health disparities. PMID:22484339

Reasons for non-participation in an international multicenter trial of a new drug for tuberculosis treatment.

PubMed

Lamunu, D; Chapman, K N; Nsubuga, P; Muzanyi, G; Mulumba, Y; Mugerwa, M A; Goldberg, S; Bozeman, L; Engle, M; Saukkonen, J; Mastranunzio, S; Mayanja-Kizza, H; Johnson, J L

2012-04-01

Clinical trials can provide a high standard of patient care and contribute to scientific knowledge; however, only a fraction of the patients screened participate and receive treatment as part of a trial. To explore reasons why patients were not enrolled in an international tuberculosis (TB) treatment trial and to compare experiences among study sites. An analysis of reasons why patients were not enrolled was conducted among patients screened for a TB clinical trial at 26 sites in North and South America, Africa, and Europe. Staff at study sites screened 1119 potential candidates for the trial: 61% (n = 686) were not enrolled due to 1) failure to meet eligibility criteria (n = 405, 59%), 2) site's decision (n = 168, 24%), or 3) candidate's choice (n = 113, 16%). Study staff recorded a total of 144 reasons for why they believed patients chose not to participate, including concerns over research (28%), conflicts with work or school (21%), and lifestyle and family issues (20%). Socio-demographic and geographic factors also influenced participation. Increased evaluation of screening outcomes and of specific interventions, such as improved education and communication about trial procedures, may increase the efficiency of screening and enrollment in clinical trials.

The impact of cardiovascular disease prevalence on women's enrollment in landmark randomized cardiovascular trials: a systematic review.

PubMed

Tsang, Wendy; Alter, David A; Wijeysundera, Harindra C; Zhang, Tony; Ko, Dennis T

2012-01-01

Many studies have demonstrated that women are substantially underrepresented in cardiovascular trials, but few have considered that women develop cardiovascular disease at older ages than men. The extent to which observed gender enrollment inequalities persist after accounting for age-gender differences in disease prevalence is unknown. The purpose of the study was to compare observed rates of women participating in cardiovascular clinical trials with expected rates of female participation based on age- and gender-specific population disease prevalence. Publications between 1997 and 2009 in the three leading medical journals were included to calculate observed women's enrollment rates. Population-based data in Canada were used to determine the expected enrollment rates of women. Multicenter, randomized cardiovascular clinical trials that enrolled both men and women were analyzed. Two reviewers independently extracted data on women's enrollment and important clinical trial characteristics. The female enrollment rate was 30% in the included 325 trials, which ranged from 27% in trials of coronary artery disease, 27% in heart failure, 31% in arrhythmia, to 45% in primary prevention. Increased female enrollment correlated strongly with increasing age at recruitment in cardiovascular clinical trials (P < 0.001). After accounting for age- and gender-specific differences in disease prevalence, gaps in female enrollment were much lower than the expected enrollment rates estimated by 5% in coronary artery disease, 13% in heart failure, 9% in arrhythmia, and 3% in primary prevention. Only cardiovascular trials were evaluated in our study. Female underrepresentation in cardiovascular clinical trials is smaller than conventionally believed after accounting for age- and gender-specific population disease prevalence. Our findings suggest that greater representation of women in cardiovascular clinical trials can be achieved through the recruitment of older populations.

Estimating exposures in the asphalt industry for an international epidemiological cohort study of cancer risk.

PubMed

Burstyn, Igor; Boffetta, Paolo; Kauppinen, Timo; Heikkilä, Pirjo; Svane, Ole; Partanen, Timo; Stücker, Isabelle; Frentzel-Beyme, Rainer; Ahrens, Wolfgang; Merzenich, Hiltrud; Heederik, Dick; Hooiveld, Mariëtte; Langård, Sverre; Randem, Britt G; Järvholm, Bengt; Bergdahl, Ingvar; Shaham, Judith; Ribak, Joseph; Kromhout, Hans

2003-01-01

An exposure matrix (EM) for known and suspected carcinogens was required for a multicenter international cohort study of cancer risk and bitumen among asphalt workers. Production characteristics in companies enrolled in the study were ascertained through use of a company questionnaire (CQ). Exposures to coal tar, bitumen fume, organic vapor, polycyclic aromatic hydrocarbons, diesel fume, silica, and asbestos were assessed semi-quantitatively using information from CQs, expert judgment, and statistical models. Exposures of road paving workers to bitumen fume, organic vapor, and benzo(a)pyrene were estimated quantitatively by applying regression models, based on monitoring data, to exposure scenarios identified by the CQs. Exposures estimates were derived for 217 companies enrolled in the cohort, plus the Swedish asphalt paving industry in general. Most companies were engaged in road paving and asphalt mixing, but some also participated in general construction and roofing. Coal tar use was most common in Denmark and The Netherlands, but the practice is now obsolete. Quantitative estimates of exposure to bitumen fume, organic vapor, and benzo(a)pyrene for pavers, and semi-quantitative estimates of exposure to these agents among all subjects were strongly correlated. Semi-quantitative estimates of exposure to bitumen fume and coal tar exposures were only moderately correlated. EM assessed non-monotonic historical decrease in exposures to all agents assessed except silica and diesel exhaust. We produced a data-driven EM using methodology that can be adapted for other multicenter studies. Copyright 2003 Wiley-Liss, Inc.

Prevalence of Neuropathic Pain in Patients with Traumatic Brachial Plexus Injury: A Multicenter Prospective Hospital-Based Study.

PubMed

Ciaramitaro, Palma; Padua, Luca; Devigili, Grazia; Rota, Eugenia; Tamburin, Stefano; Eleopra, Roberto; Cruccu, Giorgio; Truini, Andrea

2017-12-01

Prevalence and clinical characteristics of neuropathic pain due to traumatic brachial plexus injury. Observational epidemiological study. Hospital-based multicenter study. One hundred seven prospectively enrolled patients with brachial plexus injury. All the patients underwent clinical examination and neurophysiological testing for a definitive diagnosis of the brachial plexus lesion. The DN4 questionnaire was used to identify neuropathic pain, and the Neuropathic Pain Symptom Inventory (NPSI) to evaluate the different symptoms of neuropathic pain. The SF36 questionnaire and the Beck Depression Inventory (BDI) were used to assess quality of life and mood disturbances in patients with neuropathic pain. Of the 107 enrolled patients, 74 had pain (69%); neuropathic pain, as assessed by means of the DN4, was identified in 60 (56%) of these patients. According to the NPSI, the most frequent and severe pain type was the spontaneous burning pain. Clinical and neurophysiological findings showed that pain is unrelated to age but is associated with the severity of peripheral nerve damage. The SF36 questionnaire and BDI showed that neuropathic pain impairs quality of life and causes depression. Our study provides information on the prevalence, characteristics, and variables associated with neuropathic pain due to traumatic brachial plexus injuries that might provide a basis for improving the clinical management of this condition. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Effect of berberine on insulin resistance in women with polycystic ovary syndrome: study protocol for a randomized multicenter controlled trial.

PubMed

Li, Yan; Ma, Hongli; Zhang, Yuehui; Kuang, Hongying; Ng, Ernest Hung Yu; Hou, Lihui; Wu, Xiaoke

2013-07-18

Insulin resistance and hyperinsulinemia play a key role in the pathogenesis of polycystic ovary syndrome (PCOS), which is characterized by hyperandrogenism, ovulatory dysfunction, and presence of polycystic ovaries on pelvic scanning. Insulin resistance is significantly associated with the long-term risks of metabolic syndrome and cardiovascular disease. Berberine has effects on insulin resistance but its use in women with PCOS has not been fully investigated. In this paper, we present a research design evaluating the effects of berberine on insulin resistance in women with PCOS. This is a multicenter, randomized, placebo-controlled and double-blind trial. A total of 120 patients will be enrolled in this study and will be randomized into two groups. Berberine or placebo will be taken orally for 12 weeks. The primary outcome is the whole body insulin action assessed with the hyperinsulinemic-euglycemic clamp. We postulate that women with PCOS will have improved insulin resistance following berberine administration. This study is registered at ClinicalTrials.gov, NCT01138930.

DUrable polymer-based sTent CHallenge of Promus ElemEnt versus ReSolute integrity (DUTCH PEERS): rationale and study design of a randomized multicenter trial in a Dutch all-comers population.

PubMed

Tandjung, Kenneth; Basalus, Mounir W Z; Sen, Hanim; Jessurun, Gillian A J; Danse, Peter W; Stoel, Martin; Linssen, Gerard C M; Derks, Anita; van Loenhout, Ton T; Nienhuis, Mark B; Hautvast, Raymond W M; von Birgelen, Clemens

2012-04-01

Drug-eluting stents (DES) are increasingly used for the treatment of coronary artery disease. An optimized DES performance is desirable to successfully treat various challenging coronary lesions in a broad population of patients. In response to this demand, third-generation DES with an improved deliverability were developed. Promus Element (Boston Scientific, Natick, MA) and Resolute Integrity (Medtronic Vascular, Santa Rosa, CA) are 2 novel third-generation DES for which limited clinical data are available. Accordingly, we designed the current multicenter study to investigate in an all-comers population whether the clinical outcome is similar after stenting with Promus Element versus Resolute Integrity. DUTCH PEERS is a multicenter, prospective, single-blinded, randomized trial in a Dutch all-comers population. Patients with all clinical syndromes who require percutaneous coronary interventions with DES implantation are eligible. In these patients, the type of DES implanted will be randomized in a 1:1 ratio between Resolute Integrity versus Promus Element. The trial is powered based on a noninferiority hypothesis. For each stent arm, 894 patients will be enrolled, resulting in a total study population of 1,788 patients. The primary end point is the incidence of target vessel failure at 1-year follow-up. DUTCH PEERS is the first randomized multicenter trial with a head-to-head comparison of Promus Element and Resolute Integrity to investigate the safety and efficacy of these third-generation DES. Copyright © 2012 Mosby, Inc. All rights reserved.

Short-term results of a prospective randomized evaluator blinded multicenter study comparing TVT and TVT-Secur.

PubMed

Andrada Hamer, Maria; Larsson, Per-Göran; Teleman, Pia; Etén-Bergqvist, Christina; Persson, Jan

2011-07-01

The aim of this prospective randomized multicenter study was to compare TVT (tension-free vaginal tape) with TVT-Secur in terms of efficacy and safety. We set out to enrol 280 stress incontinent women with a half time interim analysis of short-term cure and a continuous registration of adverse events. Of 133 randomized women, 126 were operated and 123 (TVT n = 62, TVT-Secur n = 61) available for 2 months follow-up. No significant differences were found between groups regarding demographics or grade of incontinence. At 2 months follow-up, subjective cure rate following TVT-Secur was significantly lower than for TVT (72% and 92%, respectively, p = 0.01). Three major complications occurred in the TVT-Secur group: tape erosion into the urethra, a tape inadvertently placed inside the bladder, and an immediate postoperative bleeding from the corona mortis. No major complications occurred in the TVT group. No significant differences were found between groups regarding perioperative bleeding, hospital stay, urge symptoms, or postoperative urinary tract infections. Median time for surgery was 13 and 22 min for TVT-Secur and TVT, respectively (p < 0.0001). In a prospective randomized controlled study, the TVT-Secur procedure had a significantly lower subjective cure rate than the retropubic TVT procedure. Due to this, in addition to three serious complications in the TVT-Secur group, we decided to stop further enrolment after the interim analysis. We discourage from further use of the TVT-Secur.

A Prospective Multicenter Study Evaluating Secondary Adrenal Suppression After Antiemetic Dexamethasone Therapy in Cancer Patients Receiving Chemotherapy: A Korean South West Oncology Group Study.

PubMed

Han, Hye Sook; Park, Ji Chan; Park, Suk Young; Lee, Kyu Taek; Bae, Sang Byung; Kim, Han Jo; Kim, Samyoung; Yun, Hwan Jung; Bae, Woo Kyun; Shim, Hyun-Jeong; Hwang, Jun-Eul; Cho, Sang-Hee; Park, Moo-Rim; Shim, Hyeok; Kwon, Jihyun; Choi, Moon Ki; Kim, Seung Taik; Lee, Ki Hyeong

2015-12-01

In a previous pilot study, adrenal suppression was found to be common after antiemetic dexamethasone therapy in cancer patients. The objective of this large prospective multicenter study was to confirm the incidence and factors associated with secondary adrenal suppression related to antiemetic dexamethasone therapy in cancer patients receiving chemotherapy. Chemotherapy-naïve patients who were scheduled to receive at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Patients with a suppressed adrenal response before chemotherapy or those administered corticosteroids within 6 months of enrollment in the study were excluded. Between October 2010 and August 2014, 481 patients receiving chemotherapy underwent the rapid adrenocorticotropic hormone (ACTH) stimulation test to assess eligibility; 350 of these patients were included in the final analysis. Fifty-six patients (16.0%) showed a suppressed adrenal response in the rapid ACTH stimulation test at 3 or 6 months after the start of the first chemotherapy. The incidence of adrenal suppression was affected by age, performance status, stage, and use of megestrol acetate in univariate analysis. Multivariate analysis revealed that secondary adrenal suppression associated with antiemetic dexamethasone therapy was significantly associated with megestrol acetate treatment (odds ratio: 3.06; 95% confidence interval: 1.60 to 5.86; p < .001). This large prospective study indicates that approximately 15% of cancer patients receiving chemotherapy with a normal adrenal response show suppressed adrenal responses after antiemetic dexamethasone therapy. This result was particularly significant for patients cotreated with megestrol acetate. ©AlphaMed Press.

Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis.

PubMed

Papachristou, Georgios I; Machicado, Jorge D; Stevens, Tyler; Goenka, Mahesh Kumar; Ferreira, Miguel; Gutierrez, Silvia C; Singh, Vikesh K; Kamal, Ayesha; Gonzalez-Gonzalez, Jose A; Pelaez-Luna, Mario; Gulla, Aiste; Zarnescu, Narcis O; Triantafyllou, Konstantinos; Barbu, Sorin T; Easler, Jeffrey; Ocampo, Carlos; Capurso, Gabriele; Archibugi, Livia; Cote, Gregory A; Lambiase, Louis; Kochhar, Rakesh; Chua, Tiffany; Tiwari, Subhash Ch; Nawaz, Haq; Park, Walter G; de-Madaria, Enrique; Lee, Peter J; Wu, Bechien U; Greer, Phil J; Dugum, Mohannad; Koutroumpakis, Efstratios; Akshintala, Venkata; Gougol, Amir

2017-01-01

We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials.

Differences in recruitment and early retention among ethnic minority participants in a large pediatric cohort: the TEDDY Study.

PubMed

Baxter, Judith; Vehik, Kendra; Johnson, Suzanne Bennett; Lernmark, Barbro; Roth, Roswith; Simell, Tuula

2012-07-01

The TEDDY Study is an international, multi-center prospective study designed to identify the environmental triggers of type 1 diabetes (T1D) in genetically at-risk children. This report investigates ethnic minority (EM) differences in patterns of enrollment and retention in the US centers. As of June 2009, 267,739 newborns had been screened at birth for high risk T1D genotypes. Data collected at the time of screening, enrollment and at the baseline visit were used. Descriptive and multiple-logistic regression analyses assessed differences between EM groups regarding exclusion, enrollment and early withdrawal. Of the 10,975 eligible subjects, 6,912 (67%) were invited to participate. EM subjects were more likely to be excluded because of an inability to contact. Of those invited 3,265 (47%) enrolled by the age of 4.5 months. Adjusted analyses showed that except for those classified as other EM, the odds of enrolling were similar across groups. EM subjects had elevated early withdrawal rates. Adjusted models demonstrated that this was significantly more likely among Hispanic subjects. Understanding patterns associated with EM participation in research extends our ability to make more accurate inferences and permits assessment of strategies that promote inclusion of EM to better address health disparities. Copyright © 2012 Elsevier Inc. All rights reserved.

Electric charge requirements of pediatric cochlear implant recipients enrolled in the Childhood Development After Cochlear Implantation study.

PubMed

Zwolan, Teresa A; O'Sullivan, Mary Beth; Fink, Nancy E; Niparko, John K

2008-02-01

To evaluate mapping characteristics of children with cochlear implants who are enrolled in the Childhood Development After Cochlear Implantation (CDACI) multicenter study. Longitudinal evaluation during 24 months of speech processor maps of children with cochlear implants prospectively enrolled in the study. Six tertiary referral centers. One hundred eighty-eight children enrolled in the CDACI study who were 5 years old or younger at the time of enrollment. Of these children, 184 received unilateral implants, and 4 received simultaneous bilateral implants. Children attended regular mapping sessions at their implant clinic as part of the study protocol. Maps were examined for each subject at 4 different time intervals: at device activation and 6, 12, and 24 months postactivation. Mean C/M levels (in charge per phase) were compared for 4 different time intervals, for 3 different devices, for 6 different implant centers, and for children with normal and abnormal cochleae. All 3 types of implant devices demonstrate significant increases in C/M levels between device activation and the 24-month appointment. Significant differences in mean C/M levels were noted between devices. Children with cochlear anomalies demonstrate significantly greater C/M levels than children with normal cochleae. The CDACI study has enabled us to evaluate the mapping characteristics of pediatric patients who use 3 different devices and were implanted at a variety of implant centers. Analysis of such data enables us to better understand the mapping characteristics of children with cochlear implants.

Nailfold Videocapillaroscopic Features and Other Clinical Risk Factors for Digital Ulcers in Systemic Sclerosis: A Multicenter, Prospective Cohort Study.

PubMed

Cutolo, Maurizio; Herrick, Ariane L; Distler, Oliver; Becker, Mike O; Beltran, Emma; Carpentier, Patrick; Ferri, Clodoveo; Inanç, Murat; Vlachoyiannopoulos, Panayiotis; Chadha-Boreham, Harbajan; Cottreel, Emmanuelle; Pfister, Thomas; Rosenberg, Daniel; Torres, Juan V; Smith, Vanessa

2016-10-01

To identify nailfold videocapillaroscopic features and other clinical risk factors for new digital ulcers (DUs) during a 6-month period in patients with systemic sclerosis (SSc). In this multicenter, prospective, observational cohort study, the videoCAPillaroscopy (CAP) study, we evaluated 623 patients with SSc from 59 centers (14 countries). Patients were stratified into 2 groups: a DU history group and a no DU history group. At enrollment, patients underwent detailed nailfold videocapillaroscopic evaluation and assessment of demographic characteristics, DU status, and clinical and SSc characteristics. Risk factors for developing new DUs were assessed using univariable and multivariable logistic regression (MLR) analyses. Of the 468 patients in the DU history group (mean ± SD age 54.0 ± 13.7 years), 79.5% were female, 59.8% had limited cutaneous SSc, and 22% developed a new DU during follow-up. The strongest risk factors for new DUs identified by MLR in the DU history group included the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs (categorized as 0, 1, 2, or ≥3), and the presence of critical digital ischemia. The receiver operating characteristic (ROC) of the area under the curve (AUC) of the final MLR model was 0.738 (95% confidence interval [95% CI] 0.681-0.795). Internal validation through bootstrap generated a ROC AUC of 0.633 (95% CI 0.510-0.756). This international prospective study, which included detailed nailfold videocapillaroscopic evaluation and extensive clinical characterization of patients with SSc, identified the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs at enrollment, and the presence of critical digital ischemia at enrollment as risk factors for the development of new DUs. © 2016, American College of Rheumatology.

Nailfold Videocapillaroscopic Features and Other Clinical Risk Factors for Digital Ulcers in Systemic Sclerosis: A Multicenter, Prospective Cohort Study

PubMed Central

Herrick, Ariane L.; Distler, Oliver; Becker, Mike O.; Beltran, Emma; Carpentier, Patrick; Ferri, Clodoveo; Inanç, Murat; Vlachoyiannopoulos, Panayiotis; Chadha‐Boreham, Harbajan; Cottreel, Emmanuelle; Pfister, Thomas; Rosenberg, Daniel; Torres, Juan V.; Cutolo, Maurizio; Herrick, Ariane L.; Distler, Oliver; Becker, Mike; Beltran, Emma; Carpentier, Patrick; Ferri, Clodoveo; Inanç, Murat; Vlachoyiannopoulos, Panayiotis; Smith, Vanessa; Erlacher, L; Hirschl, M; Kiener, HP; Pilger, E; Smith, V; Blockmans, D; Wautrecht, J‐C; Becvár, R; Carpentier, P; Frances, C; Lok, C; Sparsa, A; Hachulla, E; Quere, I; Allanore, Y; Agard, C; Riemekasten, G; Hunzelmann, N; Stücker, M; Ahmadi‐Simab, K; Sunderkötter, C; Wohlrab, J; Müller‐Ladner, U; Schneider, M; Vlachoyianopoulos, P; Vassilopoulos, D; Drosos, A; Antonopoulos, A; Balbir‐Gurman, A; Langevitz, P; Rosner, I; Levy, Y; Cutolo, M; Bombardieri, S; Ferraccioli, G; Mazzuca, S; Grassi, W; Lunardi, C; Airó, P; Riccieri, V; Voskuyl, AE; Schuerwegh, A; Santos, L; Rodrigues, AC; Grilo, A; Amaral, MC; Román Ivorra, JA; Castellvi, I; Distler, O; Spertini, F; Müller, R; Inanç, M; Oksel, F; Turkcapar, N; Herrick, A; Denton, C; McHugh, N; Chattopadhyay, C; Hall, F; Buch, M

2016-01-01

Objective To identify nailfold videocapillaroscopic features and other clinical risk factors for new digital ulcers (DUs) during a 6‐month period in patients with systemic sclerosis (SSc). Methods In this multicenter, prospective, observational cohort study, the videoCAPillaroscopy (CAP) study, we evaluated 623 patients with SSc from 59 centers (14 countries). Patients were stratified into 2 groups: a DU history group and a no DU history group. At enrollment, patients underwent detailed nailfold videocapillaroscopic evaluation and assessment of demographic characteristics, DU status, and clinical and SSc characteristics. Risk factors for developing new DUs were assessed using univariable and multivariable logistic regression (MLR) analyses. Results Of the 468 patients in the DU history group (mean ± SD age 54.0 ± 13.7 years), 79.5% were female, 59.8% had limited cutaneous SSc, and 22% developed a new DU during follow‐up. The strongest risk factors for new DUs identified by MLR in the DU history group included the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs (categorized as 0, 1, 2, or ≥3), and the presence of critical digital ischemia. The receiver operating characteristic (ROC) of the area under the curve (AUC) of the final MLR model was 0.738 (95% confidence interval [95% CI] 0.681–0.795). Internal validation through bootstrap generated a ROC AUC of 0.633 (95% CI 0.510–0.756). Conclusion This international prospective study, which included detailed nailfold videocapillaroscopic evaluation and extensive clinical characterization of patients with SSc, identified the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs at enrollment, and the presence of critical digital ischemia at enrollment as risk factors for the development of new DUs. PMID:27111549

Development and Feasibility Testing of a Critical Care EEG Monitoring Database for Standardized Clinical Reporting and Multicenter Collaborative Research.

PubMed

Lee, Jong Woo; LaRoche, Suzette; Choi, Hyunmi; Rodriguez Ruiz, Andres A; Fertig, Evan; Politsky, Jeffrey M; Herman, Susan T; Loddenkemper, Tobias; Sansevere, Arnold J; Korb, Pearce J; Abend, Nicholas S; Goldstein, Joshua L; Sinha, Saurabh R; Dombrowski, Keith E; Ritzl, Eva K; Westover, Michael B; Gavvala, Jay R; Gerard, Elizabeth E; Schmitt, Sarah E; Szaflarski, Jerzy P; Ding, Kan; Haas, Kevin F; Buchsbaum, Richard; Hirsch, Lawrence J; Wusthoff, Courtney J; Hopp, Jennifer L; Hahn, Cecil D

2016-04-01

The rapid expansion of the use of continuous critical care electroencephalogram (cEEG) monitoring and resulting multicenter research studies through the Critical Care EEG Monitoring Research Consortium has created the need for a collaborative data sharing mechanism and repository. The authors describe the development of a research database incorporating the American Clinical Neurophysiology Society standardized terminology for critical care EEG monitoring. The database includes flexible report generation tools that allow for daily clinical use. Key clinical and research variables were incorporated into a Microsoft Access database. To assess its utility for multicenter research data collection, the authors performed a 21-center feasibility study in which each center entered data from 12 consecutive intensive care unit monitoring patients. To assess its utility as a clinical report generating tool, three large volume centers used it to generate daily clinical critical care EEG reports. A total of 280 subjects were enrolled in the multicenter feasibility study. The duration of recording (median, 25.5 hours) varied significantly between the centers. The incidence of seizure (17.6%), periodic/rhythmic discharges (35.7%), and interictal epileptiform discharges (11.8%) was similar to previous studies. The database was used as a clinical reporting tool by 3 centers that entered a total of 3,144 unique patients covering 6,665 recording days. The Critical Care EEG Monitoring Research Consortium database has been successfully developed and implemented with a dual role as a collaborative research platform and a clinical reporting tool. It is now available for public download to be used as a clinical data repository and report generating tool.

Extracorporeal shockwave myocardial therapy is efficacious in improving symptoms in patients with refractory angina pectoris--a multicenter study.

PubMed

Prasad, Megha; Wan Ahmad, Wan Azman; Sukmawan, Renan; Magsombol, Edward-Bengie L; Cassar, Andrew; Vinshtok, Yuri; Ismail, Muhammad Dzafir; Mahmood Zuhdi, Ahmad Syadi; Locnen, Sue Ann; Jimenez, Rodney; Callleja, Homobono; Lerman, Amir

2015-05-01

Medically refractory angina remains a significant health concern despite major advances in revascularization techniques and emerging medical therapies. We aimed to determine the safety and efficacy of extracorporeal shockwave myocardial therapy (ESMT) in managing angina pectoris. A single-arm multicenter prospective study was designed aiming to determine the safety and efficacy of ESMT. Patients of functional Canadian Cardiovascular Society class II-IV, despite stable and optimal medical management, with documented myocardial segments with reversible ischemia and/or hibernation on the basis of echocardiography/single-photon emission computerized tomography (SPECT) were enrolled from 2010 to 2012. A total of 111 patients were enrolled, 33 from Indonesia, 21 from Malaysia, and 57 from Philippines. Patients underwent nine cycles of ESMT over 9 weeks. Patients were followed up for 3-6 months after ESMT treatment. During follow-up, patients were subjected to clinical evaluation, the Seattle Angina Questionnaire, assessment of nitrate intake, the 6-min walk test, echocardiography, and SPECT. The mean age of the population was 62.9±10.9 years. The summed difference score on pharmacologically induced stress SPECT improved from 9.53±17.87 at baseline to 7.77±11.83 at follow-up (P=0.0086). Improvement in the total Seattle Angina Questionnaire score was seen in 83% of patients (P<0.0001). Sublingual nitroglycerin use significantly decreased (1.14±1.01 tablets per week at baseline to 0.52±0.68 tablets per week at follow-up; P=0.0215). There were no changes in left ventricular function on echocardiography (0.33±9.97, P=0.93). The Canadian Cardiovascular Society score improved in 74.1% of patients. This multicenter prospective trial demonstrated that ESMT is both a safe and an efficacious means of managing medically refractory angina.

Chymodiactin in patients with herniated lumbar intervertebral disc(s). An open-label, multicenter study.

PubMed

McDermott, D J; Agre, K; Brim, M; Demma, F J; Nelson, J; Wilson, R R; Thisted, R A

1985-04-01

To extent the safety information for Chymodiactin (chymopapain for injection), 37 neurologic and orthopedic surgeons conducted an open-label, multicenter, phase 3 clinical study. A total of 1,498 patients with one or two herniated lumbar intervertebral discs were enrolled. Therapeutic results were generally favorable, with the percentages of patients achieving either excellent or good (or successful) results ranging from 79.6% to 88.9%, depending on criteria employed in the tabulation. There were 13 cases of anaphylaxis, and 2 of these patients died of complications of anaphylaxis. Two additional patients experienced serious neurologic problems. The first of these two patients developed transverse myelitis and paraplegia approximately 3 weeks following chemonucleolysis. Transdural discograms at three levels had been done approximately 2 days prior to chemonucleolysis, in violation of the protocol. The second patient developed acute cauda equina syndrome, and, despite emergency laminectomy, had permanent neurologic sequelae. Back spasm and stiffness/soreness were the most frequently encountered adverse experiences.

Prediction of accrual closure date in multi-center clinical trials with discrete-time Poisson process models.

PubMed

Tang, Gong; Kong, Yuan; Chang, Chung-Chou Ho; Kong, Lan; Costantino, Joseph P

2012-01-01

In a phase III multi-center cancer clinical trial or a large public health study, sample size is predetermined to achieve desired power, and study participants are enrolled from tens or hundreds of participating institutions. As the accrual is closing to the target size, the coordinating data center needs to project the accrual closure date on the basis of the observed accrual pattern and notify the participating sites several weeks in advance. In the past, projections were simply based on some crude assessment, and conservative measures were incorporated in order to achieve the target accrual size. This approach often resulted in excessive accrual size and subsequently unnecessary financial burden on the study sponsors. Here we proposed a discrete-time Poisson process-based method to estimate the accrual rate at time of projection and subsequently the trial closure date. To ensure that target size would be reached with high confidence, we also proposed a conservative method for the closure date projection. The proposed method was illustrated through the analysis of the accrual data of the National Surgical Adjuvant Breast and Bowel Project trial B-38. The results showed that application of the proposed method could help to save considerable amount of expenditure in patient management without compromising the accrual goal in multi-center clinical trials. Copyright © 2012 John Wiley & Sons, Ltd.

Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Demographic and Clinical Characteristics

ERIC Educational Resources Information Center

Frazier, Jean A.; McClellan, Jon; Findling, Robert L.; Vitiello, Benedetto; Anderson, Robert; Zablotsky, Benjamin; Williams, Emily; McNamara, Nora K.; Jackson, Joseph A.; Ritz, Louise; Hlastala, Stefanie A.; Pierson, Leslie; Varley, Jennifer A.; Puglia, Madeline; Maloney, Ann E.; Ambler, Denisse; Hunt-Harrison, Tyehimba; Hamer, Robert M.; Noyes, Nancy; Lieberman, Jeffrey A.; Sikich, Linmarie

2007-01-01

Objective: We examined baseline demographic and clinical profiles of youths enrolled from 2001 to 2006 in the publicly funded multicenter, randomized controlled trial Treatment of Early-Onset Schizophrenia Spectrum Disorders. Method: Youths (8-19 years) with schizophrenia (SZ) and schizoaffective disorder were recruited at four academic sites.…

A multicenter observational study of US adults with acute asthma: who are the frequent users of the emergency department?

PubMed

Hasegawa, Kohei; Sullivan, Ashley F; Tovar Hirashima, Eva; Gaeta, Theodore J; Fee, Christopher; Turner, Stuart J; Massaro, Susan; Camargo, Carlos A

2014-01-01

Despite the substantial burden of asthma-related emergency department (ED) visits, there have been no recent multicenter efforts to characterize this high-risk population. We aimed to characterize patients with asthma according to their frequency of ED visits and to identify factors associated with frequent ED visits. A multicenter chart review study of 48 EDs across 23 US states. We identified ED patients ages 18 to 54 years with acute asthma during 2011 and 2012. Primary outcome was frequency of ED visits for acute asthma in the past year, excluding the index ED visit. Of the 1890 enrolled patients, 863 patients (46%) had 1 or more (frequent) ED visits in the past year. Specifically, 28% had 1 to 2 visits, 11% had 3 to 5 visits, and 7% had 6 or more visits. Among frequent ED users, guideline-recommended management was suboptimal. For example, of patients with 6 or more ED visits, 85% lacked evidence of prior evaluation by an asthma specialist, and 43% were not treated with inhaled corticosteroids. In a multivariable model, significant predictors of frequent ED visits were public insurance, no insurance, and markers for chronic asthma severity (all P < .05). Stronger associations were found among those with a higher frequency of asthma-related ED visits (eg, 6 or more ED visits). This multicenter study of US adults with acute asthma demonstrated many frequent ED users and suboptimal preventive management in this high-risk population. Future reductions in asthma morbidity and associated health care utilization will require continued efforts to bridge these major gaps in asthma care. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study Protocol

PubMed Central

Woo, Daniel; Rosand, Jonathan; Kidwell, Chelsea; McCauley, Jacob L.; Osborne, Jennifer; Brown, Mark W.; West, Sandra E.; Rademacher, Eric W.; Waddy, Salina; Roberts, Jamie N.; Koch, Sebastian; Gonzales, Nicole R.; Sung, Gene; Kittner, Steven J.; Birnbaum, Lee; Frankel, Michael; Daniel Testai, Fernando; Hall, Christiana E.; Elkind, Mitchell S. V.; Flaherty, Matthew; Coull, Bruce; Chong, Ji Y.; Warwick, Tanya; Malkoff, Marc; James, Michael L.; Ali, Latisha K.; Worrall, Bradford B.; Jones, Floyd; Watson, Tiffany; Leonard, Anne; Martinez, Rebecca; Sacco, Ralph I; Langefeld, Carl D.

2013-01-01

Background and Purpose Epidemiologic studies of intracerebral hemorrhage (ICH) have consistently demonstrated variation in incidence, location, age at presentation, and outcomes among non-Hispanic white, black, and Hispanic populations. We report here the design and methods for this large, prospective, multi-center case-control study of ICH. Methods The ERICH study is a multi-center, prospective case-control study of ICH. Cases are identified by hot-pursuit and enrolled using standard phenotype and risk factor information and include neuroimaging and blood sample collection. Controls are centrally identified by random digit dialing to match cases by age (+/−5 years), race, ethnicity, gender and metropolitan region. Results As of March 22, 2013, 1,655 cases of ICH had been recruited into the study which is 101.5% of the target for that date and 851 controls had been recruited which is 67.2% of the target for that date (1,267 controls) for a total of 2,506 subjects which is 86.5% of the target for that date (2,897 subjects). Of the 1,655 cases enrolled, 1,640 cases had the case interview entered into the database of which 628 (38%) were non-Hispanic black, 458 (28%) were non-Hispanic white and 554 (34%) were Hispanic. Of the 1,197 cases with imaging submitted, 876 (73.2%) had a 24 hour follow-up CT available In addition to CT imaging, 607 cases have had MRI evaluation. Conclusion The ERICH study is a large, case-control study of ICH with particular emphasis on recruitment of minority populations for the identification of genetic and epidemiologic risk factors for ICH and outcomes after ICH. PMID:24021679

Electromagnetic navigation bronchoscopy to access lung lesions in 1,000 subjects: first results of the prospective, multicenter NAVIGATE study.

PubMed

Khandhar, Sandeep J; Bowling, Mark R; Flandes, Javier; Gildea, Thomas R; Hood, Kristin L; Krimsky, William S; Minnich, Douglas J; Murgu, Septimiu D; Pritchett, Michael; Toloza, Eric M; Wahidi, Momen M; Wolvers, Jennifer J; Folch, Erik E

2017-04-11

Electromagnetic navigation bronchoscopy (ENB) is an image-guided, minimally invasive approach that uses a flexible catheter to access pulmonary lesions. NAVIGATE is a prospective, multicenter study of the superDimension™ navigation system. A prespecified 1-month interim analysis of the first 1,000 primary cohort subjects enrolled at 29 sites in the United States and Europe is described. Enrollment and 24-month follow-up are ongoing. ENB index procedures were conducted for lung lesion biopsy (n = 964), fiducial marker placement (n = 210), pleural dye marking (n = 17), and/or lymph node biopsy (n = 334; primarily endobronchial ultrasound-guided). Lesions were in the peripheral/middle lung thirds in 92.7%, 49.7% were <20 mm, and 48.4% had a bronchus sign. Radial EBUS was used in 54.3% (543/1,000 subjects) and general anesthesia in 79.7% (797/1,000). Among the 964 subjects (1,129 lesions) undergoing lung lesion biopsy, navigation was completed and tissue was obtained in 94.4% (910/964). Based on final pathology results, ENB-aided samples were read as malignant in 417/910 (45.8%) subjects and non-malignant in 372/910 (40.9%) subjects. An additional 121/910 (13.3%) were read as inconclusive. One-month follow-up in this interim analysis is not sufficient to calculate the true negative rate or diagnostic yield. Tissue adequacy for genetic testing was 80.0% (56 of 70 lesions sent for testing). The ENB-related pneumothorax rate was 4.9% (49/1,000) overall and 3.2% (32/1,000) CTCAE Grade ≥2 (primary endpoint). The ENB-related Grade ≥2 bronchopulmonary hemorrhage and Grade ≥4 respiratory failure rates were 1.0 and 0.6%, respectively. One-month results of the first 1,000 subjects enrolled demonstrate low adverse event rates in a generalizable population across diverse practice settings. Continued enrollment and follow-up are required to calculate the true negative rate and delineate the patient, lesion, and procedural factors contributing to diagnostic yield. ClinicalTrials.gov NCT02410837 . Registered 31 March 2015.

Vestibular migraine in multicenter neurology clinics according to the appendix criteria in the third beta edition of the International Classification of Headache Disorders.

PubMed

Cho, Soo-Jin; Kim, Byung-Kun; Kim, Byung-Su; Kim, Jae-Moon; Kim, Soo-Kyoung; Moon, Heui-Soo; Song, Tae-Jin; Cha, Myoung-Jin; Park, Kwang-Yeol; Sohn, Jong-Hee

2016-04-01

Vestibular migraine (VM), the common term for recurrent vestibular symptoms with migraine features, has been recognized in the appendix criteria of the third beta edition of the International Classification of Headache Disorders (ICHD-3β). We applied the criteria for VM in a prospective, multicenter headache registry study. Nine neurologists enrolled consecutive patients visiting outpatient clinics for headache. The presenting headache disorder and additional VM diagnoses were classified according to the ICHD-3β. The rates of patients diagnosed with VM and probable VM using consensus criteria were assessed. A total of 1414 patients were enrolled. Of 631 migraineurs, 65 were classified with VM (10.3%) and 16 with probable VM (2.5%). Accompanying migraine subtypes in VM were migraine without aura (66.2%), chronic migraine (29.2%), and migraine with aura (4.6%). Probable migraine (75%) was common in those with probable VM. The most common vestibular symptom was head motion-induced dizziness with nausea in VM and spontaneous vertigo in probable VM. The clinical characteristics of VM did not differ from those of migraine without VM. We diagnosed VM in 10.3% of first-visit migraineurs in neurology clinics using the ICHD-3β. Applying the diagnosis of probable VM can increase the identification of VM. © International Headache Society 2015.

Opportunistic diseases among HIV-infected patients: a multicenter-nationwide Korean HIV/AIDS cohort study, 2006 to 2013

PubMed Central

Kim, Youn Jeong; Woo, Jun Hee; Kim, Min Ja; Park, Dae Won; Song, Joon-Young; Kim, Shin Woo; Choi, Jun Yong; Kim, June Myung; Han, Sang Hoon; Lee, Jin-Soo; Choi, Bo Youl; Lee, Joo Shil; Kim, Sung-Soon; Kee, Mee-Kyung; Kang, Moon Won; Kim, Sang Il

2016-01-01

Background/Aims: The frequencies of opportunistic diseases (ODs) vary across countries based on genetic, environmental, and social differences. The Korean HIV/AIDS cohort study was initiated in 2006 to promote research on human immunodeficiency virus (HIV) infection in Korea, and to provide a logistical network to support multicenter projects on epidemiological, clinical, and laboratory aspects of HIV infection. This study evaluated the prevalence of ODs among HIV-infected patients in the era of highly active antiretroviral therapy, and the risk factors associated with ODs. Methods: The study enrolled 1,086 HIV-infected patients from 19 hospitals. This study examined the baseline data of the HIV/AIDS Korean cohort study at the time of enrollment from December 2006 to July 2013. Results: Candidiasis was the most prevalent opportunistic infection (n = 176, 16.2%), followed by Mycobacterium tuberculosis infection (n = 120, 10.9%), Pneumocystis jirovecii pneumonia (n = 121, 11.0%), cytomegalovirus infection (n = 52, 4.7%), and herpes zoster (n = 44, 4.0%). The prevalence rates of Kaposi’s sarcoma (n = 8, 0.7%) and toxoplasmosis (n = 4, 0.4%) were very low compared with other countries. The risk factors for ODs were a low CD4 T cell count at the time of HIV diagnosis (odds ratio [OR], 1.01; p < 0.01), current smoking (OR, 2.27; p = 0.01), current alcohol use (OR, 2.57; p = 0.04), and a history of tuberculosis (OR, 5.23; p < 0.01). Conclusions: Using recent Korean nationwide data, this study demonstrated that an important predictor of ODs was a low CD4 T cell count at the time of HIV diagnosis. Tuberculosis remains one of the most important ODs in HIV-infected patients in Korea. PMID:27117317

Recruitment methods in a clinical trial of provoked vulvodynia: Predictors of enrollment.

PubMed

Bachour, Candi C; Bachmann, Gloria A; Foster, David C; Wan, Jim Y; Rawlinson, Leslie A; Brown, Candace S

2017-02-01

Successful recruitment in clinical trials for chronic pain conditions is challenging, especially in women with provoked vulvodynia due to reluctance in discussing pain associated with sexual intercourse. The most successful recruitment methods and the characteristics of women reached with these methods are unknown. To compare the effectiveness and efficiency of four recruitment methods and to determine socioeconomic predictors for successful enrollment in a National Institutes of Health-sponsored multicenter clinical trial evaluating a gabapentin intervention in women with provoked vulvodynia. Recruitment methods utilized mass mailing, media, clinician referrals and community outreach. Effectiveness (number of participants enrolled) and efficiency (proportion screened who enrolled) were determined. Socioeconomic variables including race, educational level, annual household income, relationship status, age, menopausal status and employment status were also evaluated regarding which recruitment strategies were best at targeting specific cohorts. Of 868 potential study participants, 219 were enrolled. The most effective recruitment method in enrolling participants was mass mailing ( p < 0.001). There were no statistically significant differences in efficiency between recruitment methods ( p = 0.11). Relative to clinician referral, black women were 13 times as likely to be enrolled through mass mailing (adjusted odds ratio 12.5, 95% confidence interval, 3.6-43.1) as white women. There were no differences in enrollment according to educational level, annual income, relationship status, age, menopausal status, or employment status and recruitment method. In this clinical trial, mass mailing was the most effective recruitment method. Race of participants enrolled in a provoked vulvodynia trial was related to the recruitment method.

Hemorrhoids and matrix metalloproteinases: A multicenter study on the predictive role of biomarkers.

PubMed

Serra, Raffaele; Gallelli, Luca; Grande, Raffaele; Amato, Bruno; De Caridi, Giovanni; Sammarco, Giuseppe; Ferrari, Francesco; Butrico, Lucia; Gallo, Gaetano; Rizzuto, Antonia; de Franciscis, Stefano; Sacco, Rosario

2016-02-01

An association between hemorrhoidal disease and matrix metalloproteinases (MMPs) has been described previously. MMPs regulate extracellular structural proteins and tissue remodeling. Neutrophil gelatinase-associated lipocalin (NGAL) is involved in the regulation of MMP activity. The aim of this work was to study the relationship between tissue immunoreactive levels of MMPs and NGAL and different stages of hemorrhoids. In a multicenter, open-label, prospective study, the population under investigation consisted of 2 groups: group I (with symptomatic hemorrhoids; Goligher grade I-IV) and group II (healthy volunteers). We enrolled 97 patients with hemorrhoids: 21 with grade I hemorrhoids, 37 with grade II, 14 with grade III, and 25 with grade IV. Finally, 90 healthy volunteers (53 males and 37 females; age range, 19-70 years; median, 56) were enrolled in group II. Enzyme-linked immunosorbent assay and Western blot analysis revealed greater levels of immunoreactive MMPs and NGAL in all patients with hemorrhoids. We recorded significantly greater levels of MMP-1 and MMP-3 in grade I and II patients compared with control, and greater levels of MMP-3, MMP-7, MMP-8, and MMP-9 in grade III compared with grade II. MMP-9 and NGAL were particularly increased in patients with grade IV especially in case of thrombosed hemorrhoids. These results provide potentially important insights into the understanding of the natural history of hemorrhoids. MMPs and NGAL play a role in development of disease and may represent molecular markers for the complications such as hemorrhoidal thrombosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Longitudinal Changes of Fixation Location and Stability within 12 Months in Stargardt Disease: ProgStar Report No. 12.

PubMed

Schönbach, Etienne M; Strauss, Rupert W; Kong, Xiangrong; Muñoz, Beatriz; Ibrahim, Mohamed A; Sunness, Janet S; Birch, David G; Hahn, Gesa-Astrid; Nasser, Fadi; Zrenner, Eberhart; Sadda, SriniVas R; West, Sheila K; Scholl, Hendrik P N

2018-06-08

To investigate the natural history of Stargardt disease (STGD1) using fixation location and fixation stability. Multicenter, international, prospective cohort study. Fixation testing was performed using the Nidek MP-1 microperimeter as part of the prospective, multicenter, natural history study on the Progression of Stargardt disease (ProgStar). A total of 238 patients with ABCA4-related STGD1 were enrolled at baseline (bilateral enrollment in 86.6 %) and underwent repeat testing at month 6 and 12. Outcome measures included the distance of the preferred retinal locus from the fovea (PRL) and the bivariate contour ellipse area (BCEA). After 12 months of follow-up, the change in the eccentricity of the PRL from the anatomical fovea was -0.0014 deg (95 % CI, - 0.27deg - 0.27 deg; p = 0.99). The deterioration in the stability of fixation as expressed by a larger BCEA encompassing 1 SD of all fixation points was 1.21 deg 2 (95 % CI, -1.23 deg 2 , 3.65 deg 2 ; p = 0.33). Eyes with increases and decreases in PRL eccentricity and/or BCEA values were observed. Our observations point to the complexity of fixation parameters. The association of increasingly eccentric and unstable fixation with longer disease duration that is typically found in cross-sectional studies may be countered within individual patients by poorly understood processes like neuronal adaptation. Nevertheless, fixation parameters may serve as useful secondary outcome parameters in selected cases and for counseling patients to explain changes to their visual functionality. Copyright © 2018 Elsevier Inc. All rights reserved.

Coordination and management of multicenter clinical studies in trauma: Experience from the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study.

PubMed

Rahbar, Mohammad H; Fox, Erin E; del Junco, Deborah J; Cotton, Bryan A; Podbielski, Jeanette M; Matijevic, Nena; Cohen, Mitchell J; Schreiber, Martin A; Zhang, Jiajie; Mirhaji, Parsa; Duran, Sarah J; Reynolds, Robert J; Benjamin-Garner, Ruby; Holcomb, John B

2012-04-01

Early death due to hemorrhage is a major consequence of traumatic injury. Transfusion practices differ among hospitals and it is unknown which transfusion practices improve survival. This report describes the experience of the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study Data Coordination Center in designing and coordinating a study to examine transfusion practices at ten Level 1 trauma centers in the US. PROMMTT was a multisite prospective observational study of severely injured transfused trauma patients. The clinical sites collected real-time information on the timing and amounts of blood product infusions as well as colloids and crystalloids, vital signs, initial diagnostic and clinical laboratory tests, life saving interventions and other clinical care data. Between July 2009 and October 2010, PROMMTT screened 12,561 trauma admissions and enrolled 1245 patients who received one or more blood transfusions within 6h of Emergency Department (ED) admission. A total of 297 massive transfusions were observed over the course of the study at a combined rate of 5.0 massive transfusion patients/week. PROMMTT is the first multisite study to collect real-time prospective data on trauma patients requiring transfusion. Support from the Department of Defense and collaborative expertise from the ten participating centers helped to demonstrate the feasibility of prospective trauma transfusion studies. The observational data collected from this study will be an invaluable resource for research in trauma surgery and it will guide the design and conduct of future randomized trials. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Coordination and management of multicenter clinical studies in trauma: Experience from the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study

PubMed Central

Rahbar, Mohammad H.; Fox, Erin E.; del Junco, Deborah J.; Cotton, Bryan A.; Podbielski, Jeanette M.; Matijevic, Nena; Cohen, Mitchell J.; Schreiber, Martin A.; Zhang, Jiajie; Mirhaji, Parsa; Duran, Sarah; Reynolds, Robert J.; Benjamin-Garner, Ruby; Holcomb, John B.

2011-01-01

Aim Early death due to hemorrhage is a major consequence of traumatic injury. Transfusion practices differ among hospitals and it is unknown which transfusion practices improve survival. This report describes the experience of the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study Data Coordination Center in designing and coordinating a study to examine transfusion practices at ten Level 1 trauma centers in the U.S. Methods PROMMTT was a multisite prospective observational study of severely injured transfused trauma patients. The clinical sites collected real-time information on the timing and amounts of blood product infusions as well as colloids and crystalloids, vital signs, initial diagnostic and clinical laboratory tests, life saving interventions and other clinical care data. Results Between July 2009 and October 2010, PROMMTT screened 12,561 trauma admissions and enrolled 1,245 patients who received one or more blood transfusions within 6 hours of ED admission. A total of 297 massive transfusions were observed over the course of the study at a combined rate of 5.0 massive transfusion patients/week. Conclusion PROMMTT is the first multisite study to collect real-time prospective data on trauma patients requiring transfusion. Support from the Department of Defense and collaborative expertise from the ten participating centers helped to demonstrate the feasibility of prospective trauma transfusion studies. The observational data collected from this study will be an invaluable resource for research in trauma surgery and it will guide the design and conduct of future randomized trials. PMID:22001613

Filgrastim mobilization and collection of allogeneic blood progenitor cells from adult family donors: first interim report of a prospective German multicenter study.

PubMed

Beelen, D W; Ottinger, H; Kolbe, K; Pönisch, W; Sayer, H G; Knauf, W; Stockschläder, M; Scheid, C; Schaefer, U W

2002-12-01

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) mobilized peripheral blood progenitor cells (PBPCs) from healthy individuals are a rapidly emerging alternative source to bone marrow for allogeneic transplantation. Although widely applied in the meantime, only limited information on feasibility and safety of mobilization and collection of PBPCs is currently available from prospective multicenter studies specifically designed to investigate this donation modality. This ongoing multicenter study on the performance as well as the short- and long-term safety profile of rhG-CSF-induced mobilization and collection of PBPCs was initiated in October 1999. The study is designed to recruit a total of 300 healthy family donors who will be followed regularly for a period of 5 years after donation. The first interim report presented here summarizes results obtained after enrollment of 150 donors from nine German institutions. The study protocol allowed the individual choice between two dose regimens of rh-CSF (10 micro g/kg per day vs 2x8 micro g/kg per day of donor body weight). The primary endpoint was defined as a yield of > or =5x10(6) CD34(+) cells/kg of recipient body weight in a single leukapheresis product. This endpoint was attained by 50% of donors receiving the lower rhG-CSF dose regimen and by 75% of donors with the higher dose regimen ( p<0.0009). A total of 478 acute adverse events attributable to the mobilization procedure were recorded and manifested predominantly as transient bone pain and headaches (80%). No persistent hematologic or nonhematologic adverse events have occurred in this study so far. Thus, the current experience in a prospective multicenter study supports previous single-center and retrospective registry reports in that the collection of PBPCs after rhG-CSF mobilization is feasible and associated with frequent, but generally mild and acceptable side effects.

Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis

PubMed Central

Papachristou, Georgios I.; Machicado, Jorge D.; Stevens, Tyler; Goenka, Mahesh Kumar; Ferreira, Miguel; Gutierrez, Silvia C.; Singh, Vikesh K.; Kamal, Ayesha; Gonzalez-Gonzalez, Jose A.; Pelaez-Luna, Mario; Gulla, Aiste; Zarnescu, Narcis O.; Triantafyllou, Konstantinos; Barbu, Sorin T.; Easler, Jeffrey; Ocampo, Carlos; Capurso, Gabriele; Archibugi, Livia; Cote, Gregory A.; Lambiase, Louis; Kochhar, Rakesh; Chua, Tiffany; Tiwari, Subhash Ch.; Nawaz, Haq; Park, Walter G.; de-Madaria, Enrique; Lee, Peter J.; Wu, Bechien U.; Greer, Phil J.; Dugum, Mohannad; Koutroumpakis, Efstratios; Akshintala, Venkata; Gougol, Amir

2017-01-01

Background We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. Methods The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. Results Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. Conclusion APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials. PMID:28042246

Recruitment and retention of participants for an international type 1 diabetes prevention trial: a coordinators' perspective.

PubMed

Franciscus, Margaret; Nucci, Anita; Bradley, Brenda; Suomalainen, Heli; Greenberg, Ellen; Laforte, Diane; Kleemola, Paivi; Hyytinen, Mila; Salonen, Marja; Martin, Mary Jean; Catte, Daniel; Catteau, Jacki

2014-04-01

The Trial to Reduce Insulin Dependent Diabetes Mellitus in the Genetically at Risk (TRIGR) is the first multicenter international type 1 diabetes (T1D) prevention trial to be undertaken. A unique feature of TRIGR has been recruitment of eligible pregnant women and enrollment of newborns for long-term follow-up assessments. Our purpose is to summarize the recruitment and retention strategies used to conduct TRIGR from the perspective of the study coordinators. TRIGR was designed to test whether weaning to formula containing hydrolyzed versus intact cow's milk protein would be efficacious in decreasing risk for development of T1D-associated autoantibodies and T1D among infants identified to be at increased risk for T1D based on their human leukocyte antigen (HLA) profile and family history. Multiple strategies tailored to local issues were required to enroll and follow the target number of infants. This study was conducted in the United States, Canada, Australia, and 12 countries in Europe. Of the 5606 mothers registered worldwide, 5000 of their infants were randomized. Of these, 2159 were HLA eligible and enrolled in the 8-month intervention and 10-year follow-up phases of this study. The TRIGR study met the accrual goal after 4.7 years of recruitment, 2.7 years longer than projected initially. Challenges included difficulty in finding fathers with T1D, a higher than expected rate of premature delivery among T1D mothers, and implementation of new privacy regulations mid-trial. The majority of participants were recruited from primary care antenatal clinics located near the study centers and from a general hospital or pediatric center that was affiliated with a TRIGR Study center. Internet and magazine advertisements were found to be useful for recruitment of families. Alternative follow-up strategies are offered to families who wish to reduce or discontinue participation. Our experience is limited to a single international multicenter trial. TRIGR coordinators played key roles in the recruitment and intervention periods and continue to be instrumental in retaining families and children during the 10-year follow-up period for each child.

The Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Studies: Design and Baseline Characteristics: ProgStar Report No. 1.

PubMed

Strauss, Rupert W; Ho, Alex; Muñoz, Beatriz; Cideciyan, Artur V; Sahel, José-Alain; Sunness, Janet S; Birch, David G; Bernstein, Paul S; Michaelides, Michel; Traboulsi, Elias I; Zrenner, Eberhart; Sadda, SriniVas; Ervin, Ann-Margret; West, Sheila; Scholl, Hendrik P N

2016-04-01

To describe the design and baseline characteristics of patients enrolled into 2 natural history studies of Stargardt disease (STGD1). Multicenter retrospective and prospective cohort studies. Three hundred sixty-five unique patients aged 6 years and older at baseline harboring disease-causing variants in the ABCA4 gene and with specified ocular lesions were enrolled from 9 centers in the United States and Europe. In the retrospective study, patients contributed medical record data from at least 2 and up to 4 visits for at least 1 examination modality: fundus autofluorescence (FAF), spectral-domain (SD) optical coherence tomography (SD OCT), and/or microperimetry (MP). The total observational period was at least 2 years and up to 5 years between single visits. Demographic and visual acuity (VA) data also were obtained. In the prospective study, eligible patients were examined at baseline using a standard protocol, with 6-month follow-up visits planned for a 2-year period for serial Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected VA, SD OCT, FAF, and MP. Design and rationale of a multicenter study to determine the progression of STGD1 in 2 large retrospective and prospective international cohorts. Detailed baseline characteristics of both cohorts are presented, including demographics, and structural and functional retinal metrics. Into the retrospective study, 251 patients (458 eyes) were enrolled; mean follow-up ± standard deviation was 3.9±1.6 years. At baseline, 36% had no or mild VA loss, and 47% of the study eyes had areas of definitely decreased autofluorescence (DDAF) with an average lesion area of 2.5±2.9 mm(2) (range, 0.02-16.03 mm(2)). Two hundred fifty-nine patients (489 eyes) were enrolled in the prospective study. At baseline, 20% had no or mild VA loss, and 64% had areas of DDAF with an average lesion area of 4.0±4.4 mm(2) (range, 0.03-24.24 mm(2)). The mean retinal sensitivity with MP was 10.8±5.0 dB. The ProgStar cohorts have baseline characteristics that encompass a wide range of disease severity and are expected to provide valuable data on progression based on serial quantitative measurements derived from multiple methods, which will be critical to the design of planned clinical trials. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

The sirolimus-eluting Cypher Select coronary stent for the treatment of bare-metal and drug-eluting stent restenosis: insights from the e-SELECT (Multicenter Post-Market Surveillance) registry.

PubMed

Abizaid, Alexandre; Costa, J Ribamar; Banning, Adrian; Bartorelli, Antonio L; Dzavik, Vladimir; Ellis, Stephen; Gao, Runlin; Holmes, David R; Jeong, Muyng Ho; Legrand, Victor; Neumann, Franz-Josef; Nyakern, Maria; Orlick, Amy; Spaulding, Christian; Worthley, Stephen; Urban, Philip M

2012-01-01

This study sought to compare the 1-year safety and efficacy of Cypher Select or Cypher Select Plus (Cordis Corporation, Bridgewater, New Jersey) sirolimus-eluting stents (SES) with the treatment of bare-metal stents (BMS) and drug-eluting stent (DES) in-stent restenosis (ISR) in nonselected, real-world patients. There is paucity of consistent data on DES for the treatment of ISR, especially, DES ISR. The e-SELECT (Multicenter Post-Market Surveillance) registry is a Web-based, multicenter and international registry encompassing virtually all subsets of patients and lesions treated with at least 1 SES during the period from 2006 to 2008. We enrolled in this pre-specified subanalysis all patients with at least 1 clinically relevant BMS or DES ISR treated with SES. Primary endpoint was major adverse cardiac events and stent thrombosis rate at 1 year. Of 15,147 patients enrolled, 1,590 (10.5%) presented at least 1 ISR (BMS group, n = 1,235, DES group, n = 355). Patients with DES ISR had higher incidence of diabetes (39.4% vs. 26.9%, p < 0.001), renal insufficiency (5.8% vs. 2.3%, p = 0.003), and prior coronary artery bypass graft (20.5% vs. 11.8%, p < 0.001). At 1 year, death (1.4% for BMS vs. 2.1% for DES, p = 0.3) and myocardial infarction (2.4% for BMS and 3.3% for DES, p = 0.3) rates were similar, whereas ischemia-driven target lesion revascularization and definite/probable late stent thrombosis were higher in patients with DES ISR (6.9% vs. 3.1%, p = 0.003, and 1.8% vs. 0.5%, p = 0.04, respectively). Use of SES for either BMS or DES ISR treatment is safe and associated with low target lesion revascularization recurrence and no apparent safety concern. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Design of the multicenter standardized supervised exercise training intervention for the claudication: exercise vs endoluminal revascularization (CLEVER) study.

PubMed

Bronas, Ulf G; Hirsch, Alan T; Murphy, Timothy; Badenhop, Dalynn; Collins, Tracie C; Ehrman, Jonathan K; Ershow, Abby G; Lewis, Beth; Treat-Jacobson, Diane J; Walsh, M Eileen; Oldenburg, Niki; Regensteiner, Judith G

2009-11-01

The CLaudication: Exercise Vs Endoluminal Revascularization (CLEVER) study is the first randomized, controlled, clinical, multicenter trial that is evaluating a supervised exercise program compared with revascularization procedures to treat claudication. In this report, the methods and dissemination techniques of the supervised exercise training intervention are described. A total of 217 participants are being recruited and randomized to one of three arms: (1) optimal medical care; (2) aortoiliac revascularization with stent; or (3) supervised exercise training. Of the enrolled patients, 84 will receive supervised exercise therapy. Supervised exercise will be administered according to a protocol designed by a central CLEVER exercise training committee based on validated methods previously used in single center randomized control trials. The protocol will be implemented at each site by an exercise committee member using training methods developed and standardized by the exercise training committee. The exercise training committee reviews progress and compliance with the protocol of each participant weekly. In conclusion, a multicenter approach to disseminate the supervised exercise training technique and to evaluate its efficacy, safety and cost-effectiveness for patients with claudication due to peripheral arterial disease (PAD) is being evaluated for the first time in CLEVER. The CLEVER study will further establish the role of supervised exercise training in the treatment of claudication resulting from PAD and provide standardized methods for use of supervised exercise training in future PAD clinical trials as well as in clinical practice.

Challenges in the design and implementation of the Multicenter Uveitis Steroid Treatment (MUST) Trial--lessons for comparative effectiveness trials.

PubMed

Holbrook, Janet T; Kempen, John H; Prusakowski, Nancy A; Altaweel, Michael M; Jabs, Douglas A

2011-12-01

Randomized clinical trials (RCTs) are an important component of comparative effectiveness (CE) research because they are the optimal design for head-to-head comparisons of different treatment options. To describe decisions made in the design of the Multicenter Uveitis Steroid Treatment (MUST) Trial to ensure that the results would be widely generalizable. Review of design and implementation decisions and their rationale for the trial. The MUST Trial is a multicenter randomized controlled CE trial evaluating a novel local therapy (intraocular fluocinolone acetonide implant) versus the systemic therapy standard of care for noninfectious uveitis. Decisions made in protocol design in order to broaden enrollment included allowing patients with very poor vision and media opacity to enroll and including clinical sites outside the United States. The treatment protocol was designed to follow standard care. The primary outcome, visual acuity, is important to patients and can be evaluated in all eyes with uveitis. Other outcomes include patient-reported visual function, quality of life, and disease and treatment related complications. The trial population is too small for subgroup analyses that are of interest and the trial is being conducted at tertiary medical centers. CE trials require greater emphasis on generalizability than many RCTs but otherwise face similar challenges for design choices as any RCT. The increase in heterogeneity in patients and treatment required to ensure generalizability can be balanced with a rigorous approach to implementation, outcome assessment, and statistical design. This approach requires significant resources that may limit implementation in many RCTs, especially in clinical practice settings.

An open prospective single cohort multicenter study evaluating the novel, tapered, conical connection implants supporting single crowns in the anterior and premolar maxilla: interim 1-year results.

PubMed

Fügl, Alexander; Zechner, Werner; Pozzi, Alessandro; Heydecke, Guido; Mirzakhanian, Christine; Behneke, Nikolaus; Behneke, Alexandra; Baer, Russell A; Nölken, Robert; Gottesman, Edward; Colic, Snjezana

2017-07-01

The aim of this multicenter prospective clinical study was to evaluate anodized tapered implants with a conical connection and integrated platform shifting placed in the anterior and premolar maxilla. The study enrolled patients requiring single-tooth restorations in healed sites of maxillary anterior and premolar teeth. All implants were immediately temporized. Clinical and radiographic evaluations were conducted at implant insertion, 6 months, and 1 year. Outcome measures included bone remodeling, cumulative survival rate (CSR), success rate, soft-tissue health and esthetics, and patient satisfaction. Bone remodeling and pink esthetic score were analyzed using Wilcoxon signed-rank tests. CSR was calculated using life table analysis. Other soft-tissue outcomes were analyzed using sign tests. Out of 97 enrolled patients (102 implants), 87 patients (91 implants) completed the 1-year visit. Marginal bone remodeling was -0.85 ± 1.36 mm. After the expected initial bone loss, a mean bone gain of 0.11 ± 1.05 mm was observed between 6 months and 1 year. The CSR was 99.0%, and the cumulative success rate was 97.0%. Partial or full papilla was observed at 30.8% of sites at baseline, 87.2% at 6 months, and 90.5% at 1 year. Soft-tissue response, esthetics, and patient satisfaction all improved during the study period. Bone gain was observed following the expected initial bone loss, and soft-tissue outcomes improved suggesting favorable tissue response using anodized tapered conical connection implants. Rapid stabilization of bone remodeling and robust papilla regeneration indicate favorable tissue healing promoted by the conical connection, platform-shift design. clinicaltrials.gov NCT02175550.

Appropriateness guidelines and predictive rules to select patients for upper endoscopy: a nationwide multicenter study.

PubMed

Buri, Luigi; Hassan, Cesare; Bersani, Gianluca; Anti, Marcello; Bianco, Maria Antonietta; Cipolletta, Livio; Di Giulio, Emilio; Di Matteo, Giovanni; Familiari, Luigi; Ficano, Leonardo; Loriga, Pietro; Morini, Sergio; Pietropaolo, Vincenzo; Zambelli, Alessandro; Grossi, Enzo; Intraligi, Marco; Buscema, Massimo

2010-06-01

Selecting patients appropriately for upper endoscopy (EGD) is crucial for efficient use of endoscopy. The objective of this study was to compare different clinical strategies and statistical methods to select patients for EGD, namely appropriateness guidelines, age and/or alarm features, and multivariate and artificial neural network (ANN) models. A nationwide, multicenter, prospective study was undertaken in which consecutive patients referred for EGD during a 1-month period were enrolled. Before EGD, the endoscopist assessed referral appropriateness according to the American Society for Gastrointestinal Endoscopy (ASGE) guidelines, also collecting clinical and demographic variables. Outcomes of the study were detection of relevant findings and new diagnosis of malignancy at EGD. The accuracy of the following clinical strategies and predictive rules was compared: (i) ASGE appropriateness guidelines (indicated vs. not indicated), (ii) simplified rule (>or=45 years or alarm features vs. <45 years without alarm features), (iii) logistic regression model, and (iv) ANN models. A total of 8,252 patients were enrolled in 57 centers. Overall, 3,803 (46%) relevant findings and 132 (1.6%) new malignancies were detected. Sensitivity, specificity, and area under the receiver-operating characteristic curve (AUC) of the simplified rule were similar to that of the ASGE guidelines for both relevant findings (82%/26%/0.55 vs. 88%/27%/0.52) and cancer (97%/22%/0.58 vs. 98%/20%/0.58). Both logistic regression and ANN models seemed to be substantially more accurate in predicting new cases of malignancy, with an AUC of 0.82 and 0.87, respectively. A simple predictive rule based on age and alarm features is similarly effective to the more complex ASGE guidelines in selecting patients for EGD. Regression and ANN models may be useful in identifying a relatively small subgroup of patients at higher risk of cancer.

Telmisartan combined with probucol effectively reduces urinary protein in patients with type 2 diabetes: A randomized double-blind placebo-controlled multicenter clinical study.

PubMed

Zhu, Hanyu; Chen, Xiangmei; Cai, Guangyan; Zheng, Ying; Liu, Moyan; Liu, Wenhu; Yao, Hebin; Wang, Yaping; Li, Wenge; Wu, Hua; Lun, Lide; Zhang, Jianrong; Guan, Xiaohong; Yin, Shinan; Zhuang, Xiaoming; Li, Jijun; Liu, Yanjun; Zhou, Chunhua

2016-09-01

Persistent proteinuria is an important factor contributing to the progression of diabetic nephropathy. The present randomized double-blind placebo-controlled multicenter clinical study evaluated the efficacy and safety of telmisartan combined with the antioxidant probucol in reducing urinary protein levels in patients with type 2 diabetes (T2D). Patients with T2D and 24-h proteinuria 0.5-3 g were enrolled in the study and randomly assigned to one of two groups: a telmisartan or a probucol + telmisartan group. Both groups were given telmisartan 80 mg q.d. for 48 weeks. The probucol + telmisartan group was given probucol 500 mg b.i.d. for the first 24 weeks, with the dosage then reduced to 250 mg b.i.d. for the remaining 24 weeks. The telmisartan group was given probucol placebo. In all, 160 patients were enrolled in the present study. The 24-h proteinuria levels were significantly reduced in the probucol + telmisartan compared with telmisartan group. For patients with baseline 24-h proteinuria levels <1.0 g, both treatments resulted in significant reductions in 24-h proteinuria levels after 48 weeks treatment. However, in patients with baseline 24-h proteinuria levels ≥1.0 g, 24-h proteinuria levels after 48 weeks treatment were only reduced in the probucol + telmisartan group. There was no significant difference between the two groups for either adverse cardiovascular or other events. In patients with diabetic nephropathy, probucol combined with telmisartan more effectively reduces urinary protein levels than telmisartan alone. © 2015 The Authors. Journal of Diabetes published by Wiley Publishing Asia Pty Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine.

Soluble intercellular adhesion molecule-1 and clinical outcomes in patients with acute lung injury

PubMed Central

Eisner, Mark D.; Parsons, Polly E.; Thompson, B. Taylor; Conner, Edward R.; Matthay, Michael A.; Ware, Lorraine B.

2009-01-01

Objective To determine if levels of soluble intercellular adhesion molecule-1 (sICAM-1), a marker of alveolar epithelial and endothelial injury, differ in patients with hydrostatic pulmonary edema and acute lung injury (ALI) and are associated with clinical outcomes in patients with ALI. Design, setting, and participants Measurement of sICAM-1 levels in (1) plasma and edema fluid from 67 patients with either hydrostatic pulmonary edema or ALI enrolled in an observational, prospective single center study, and (2) in plasma from 778 patients with ALI enrolled in a large multi-center randomized controlled trial of ventilator strategy. Results In the single-center study, levels of sICAM-1 were significantly higher in both edema fluid and plasma (median 938 and 545 ng/ml, respectively) from ALI patients compared to hydrostatic edema patients (median 384 and 177 ng/ml, P < 0.03 for both comparisons). In the multi-center study, higher plasma sICAM-1 levels were associated with poor clinical outcomes in both unadjusted and multivariable models. Subjects with ALI whose plasma sICAM-1 levels increased over the first 3 days of the study had a higher risk of death, after adjusting for other important predictors of outcome (odds ratio 1.48; 95% CI 1.03–2.12, P = 0.03). Conclusions Both plasma and edema fluid levels of sICAM-1 are higher in patients with ALI than in patients with hydrostatic pulmonary edema. Higher plasma sICAM-1 levels and increasing sICAM-1 levels over time are associated with poor clinical outcomes in ALI. Measurement of sICAM-1 levels may be useful for identifying patients at highest risk of poor outcomes from ALI. PMID:18670758

The DENALI Trial: an interim analysis of a prospective, multicenter study of the Denali retrievable inferior vena cava filter.

PubMed

Stavropoulos, S William; Sing, Ronald F; Elmasri, Fakhir; Silver, Mitchell J; Powell, Alex; Lynch, Frank C; Aal, Ahmed Kamel Abdel; Lansky, Alexandra J; Settlage, Richard A; Muhs, Bart E

2014-10-01

To assess safety and effectiveness of a nitinol retrievable inferior vena cava (IVC) filter in patients who require caval interruption to protect against pulmonary embolism (PE). Two hundred patients with temporary indications for an IVC filter were enrolled in this prospective, multicenter clinical study. Patients undergoing filter implantation were to be followed for 2 years or for 30 days after filter retrieval. At the time of the present interim report, all 200 patients had been enrolled in the study, and 160 had undergone a retrieval attempt or been followed to 6 months with their filter in place. Primary study endpoints included technical and clinical success of filter placement and retrieval. Patients were also evaluated for recurrent PE, new or worsening deep vein thrombosis, and filter migration, fracture, penetration, and tilt. Clinical success of placement was achieved in 94.5% of patients (172 of 182), with a one-sided lower limit of the 95% confidence interval of 90.1%. Technical success rate of filter placement was 99.5%. Technical success rate of retrieval was 97.3%; 108 filters were retrieved in 111 attempts. In two cases, the filter apex could not be engaged with a snare, and one device was engaged but could not be removed. Filter retrievals occurred at a mean indwell time of 165 days (range, 5-632 d). There were no instances of filter fracture, migration, or tilt greater than 15° at the time of retrieval or 6-month follow-up. In this interim report, the nitinol retrievable IVC filter provided protection against pulmonary embolism, and the device could be retrieved with a low rate of complications. Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.

The Advanced Glaucoma Intervention Study (AGIS): 3. Baseline characteristics of black and white patients.

PubMed

1998-07-01

The purpose of this report is to examine the differences at baseline in demographic, medical, and ophthalmic characteristics between blacks and whites enrolled in the Advanced Glaucoma Intervention Study (AGIS), a multicenter, randomized, clinical trial. Multicenter, randomized, controlled trial. A total of 332 black patients (451 eyes), 249 white patients (325 eyes), and 10 patients of other races (13 eyes) with open-angle glaucoma that could not be controlled by medical therapy alone participated. There was no intervention performed. The investigators compare the baseline demographic, medical, and ophthalmic characteristics of black and white patients, adjusting the comparisons for age and gender. Blacks in the study were younger than whites and had more systemic hypertension and diabetes than whites. The visual field defects of blacks on average were substantially more severe than those of whites. Intraocular pressures and visual acuity scores were similar in the two groups. Blacks were more hyperopic and had relatively fewer disk rim hemorrhages than whites. The findings of the current study concur with those of previous clinical studies of open-angle glaucoma that visual field defects are more severe in blacks than whites.

Association between moderate-to-severe diarrhea in young children in the global enteric multicenter study (GEMS) and types of handwashing materials used by caretakers in Mirzapur, Bangladesh.

PubMed

Baker, Kelly K; Dil Farzana, Fahmida; Ferdous, Farzana; Ahmed, Shahnawaz; Kumar Das, Sumon; Faruque, A S G; Nasrin, Dilruba; Kotloff, Karen L; Nataro, James P; Kolappaswamy, Krishnan; Levine, Myron M

2014-07-01

Handwashing practices among caretakers of case and control children < 5 years of age enrolled in the Global Enteric Multicenter Study in Mirzapur, Bangladesh were characterized and analyzed for association with moderate-to-severe diarrhea. Soap or detergent ownership was common, yet 48% of case and 47.7% of control caretakers also kept ashes for handwashing, including 36.8% of the wealthiest households. Soap, detergent, and ash were used for multiple hygiene purposes and were kept together at handwashing areas. Caretakers preferred soap for handwashing, but frequently relied on ash, or a detergent/ash mixture, as a low-cost alternative. Moderate-to-severe diarrhea was equally likely for children of caretakers who kept soap versus those who kept ash (matched OR = 0.91; 0.62-1.32). Contact with ash and water reduced concentrations of bacterial enteropathogens, without mechanical scrubbing. Thus, washing hands with ash is a prevalent behavior in Mirzapur and may help diminish transmission of diarrheal pathogens to children. © The American Society of Tropical Medicine and Hygiene.

Association between Moderate-to-Severe Diarrhea in Young Children in the Global Enteric Multicenter Study (GEMS) and Types of Handwashing Materials Used by Caretakers in Mirzapur, Bangladesh

PubMed Central

Baker, Kelly K.; Dil Farzana, Fahmida; Ferdous, Farzana; Ahmed, Shahnawaz; Kumar Das, Sumon; Faruque, A. S. G.; Nasrin, Dilruba; Kotloff, Karen L.; Nataro, James P.; Kolappaswamy, Krishnan; Levine, Myron M.

2014-01-01

Handwashing practices among caretakers of case and control children < 5 years of age enrolled in the Global Enteric Multicenter Study in Mirzapur, Bangladesh were characterized and analyzed for association with moderate-to-severe diarrhea. Soap or detergent ownership was common, yet 48% of case and 47.7% of control caretakers also kept ashes for handwashing, including 36.8% of the wealthiest households. Soap, detergent, and ash were used for multiple hygiene purposes and were kept together at handwashing areas. Caretakers preferred soap for handwashing, but frequently relied on ash, or a detergent/ash mixture, as a low-cost alternative. Moderate-to-severe diarrhea was equally likely for children of caretakers who kept soap versus those who kept ash (matched OR = 0.91; 0.62–1.32). Contact with ash and water reduced concentrations of bacterial enteropathogens, without mechanical scrubbing. Thus, washing hands with ash is a prevalent behavior in Mirzapur and may help diminish transmission of diarrheal pathogens to children. PMID:24778193

Inter-ethnic marriages and severity of coronary artery disease: A multicenter study of Arabian Gulf States

PubMed Central

Daoulah, Amin; Al-kaabi, Salem; Lotfi, Amir; Al-Murayeh, Mushabab; Nasseri, S Ali; Ahmed, Waleed; Al-Otaibi, Salah N; Alama, Mohamed N; Elkhateeb, Osama E; Plotkin, Amy J; Malak, Majed M; Alshali, Khalid; Hamzi, Mohamed; Al Khunein, Saleh; Abufayyah, Mohammed; Alsheikh-Ali, Alawi A

2017-01-01

AIM To assess the association of inter-ethnic vs intra-ethnic marriage with severity of coronary artery disease (CAD) in men undergoing angiography. METHODS We conducted a prospective multicenter, multi-ethnic, cross sectional observational study at five hospitals in Saudi Arabia and the United Arab Emirates, in which we used logistic regression analysis with and without adjustment for baseline differences. RESULTS Data were collected for 1068 enrolled patients undergoing coronary angiography for clinical indications during the period of April 1st, 2013 to March 30th, 2014. Ethnicities of spouses were available only for male patients. Of those enrolled, 687 were married men and constituted the cohort for the present analysis. Intra-ethnic marriages were reported in 70% and inter-ethnic marriages in 30%. After adjusting for baseline differences, inter-ethnic marriage was associated with lower odds of having significant CAD [adjusted odds ratio 0.52 (95%CI: 0.33, 0.81)] or multi-vessel disease (MVD) [adjusted odds ratio 0.57 (95%CI: 0.37, 0.86)]. The adjusted association with left main disease showed a similar trend, but was not statistically significant [adjusted odds ratio 0.74 (95%CI: 0.41, 1.32)]. The association between inter-ethnic marriage and the presence of significant CAD and MVD was not modified by number of concurrent wives (P interaction > 0.05 for both). CONCLUSION Among married men undergoing coronary angiography, inter-ethnic, as compared to intra-ethnic, marriage is associated with lower odds of significant CAD and MVD. PMID:28515856

Distinct Molecular Phenotypes of Direct vs Indirect ARDS in Single-Center and Multicenter Studies

PubMed Central

Janz, David R.; Bernard, Gordon R.; May, Addison K.; Kangelaris, Kirsten N.; Matthay, Michael A.; Ware, Lorraine B.

2015-01-01

BACKGROUND: ARDS is a heterogeneous syndrome that encompasses lung injury from both direct and indirect sources. Direct ARDS (pneumonia, aspiration) has been hypothesized to cause more severe lung epithelial injury than indirect ARDS (eg, nonpulmonary sepsis); however, this hypothesis has not been well studied in humans. METHODS: We measured plasma biomarkers of lung epithelial and endothelial injury and inflammation in a single-center study of 100 patients with ARDS and severe sepsis and in a secondary analysis of 853 patients with ARDS drawn from a multicenter randomized controlled trial. Biomarker levels in patients with direct vs indirect ARDS were compared in both cohorts. RESULTS: In both studies, patients with direct ARDS had significantly higher levels of a biomarker of lung epithelial injury (surfactant protein D) and significantly lower levels of a biomarker of endothelial injury (angiopoietin-2) than those with indirect ARDS. These associations were robust to adjustment for severity of illness and ARDS severity. In the multicenter study, patients with direct ARDS also had lower levels of von Willebrand factor antigen and IL-6 and IL-8, markers of endothelial injury and inflammation, respectively. The prognostic value of the biomarkers was similar in direct and indirect ARDS. CONCLUSIONS: Direct lung injury in humans is characterized by a molecular phenotype consistent with more severe lung epithelial injury and less severe endothelial injury. The opposite pattern was identified in indirect lung injury. Clinical trials of novel therapies targeted specifically at the lung epithelium or endothelium may benefit from preferentially enrolling patients with direct and indirect ARDS, respectively. PMID:26033126

Distinct molecular phenotypes of direct vs indirect ARDS in single-center and multicenter studies.

PubMed

Calfee, Carolyn S; Janz, David R; Bernard, Gordon R; May, Addison K; Kangelaris, Kirsten N; Matthay, Michael A; Ware, Lorraine B

2015-06-01

ARDS is a heterogeneous syndrome that encompasses lung injury from both direct and indirect sources. Direct ARDS (pneumonia, aspiration) has been hypothesized to cause more severe lung epithelial injury than indirect ARDS (eg, nonpulmonary sepsis); however, this hypothesis has not been well studied in humans. We measured plasma biomarkers of lung epithelial and endothelial injury and inflammation in a single-center study of 100 patients with ARDS and severe sepsis and in a secondary analysis of 853 patients with ARDS drawn from a multicenter randomized controlled trial. Biomarker levels in patients with direct vs indirect ARDS were compared in both cohorts. In both studies, patients with direct ARDS had significantly higher levels of a biomarker of lung epithelial injury (surfactant protein D) and significantly lower levels of a biomarker of endothelial injury (angiopoietin-2) than those with indirect ARDS. These associations were robust to adjustment for severity of illness and ARDS severity. In the multicenter study, patients with direct ARDS also had lower levels of von Willebrand factor antigen and IL-6 and IL-8, markers of endothelial injury and inflammation, respectively. The prognostic value of the biomarkers was similar in direct and indirect ARDS. Direct lung injury in humans is characterized by a molecular phenotype consistent with more severe lung epithelial injury and less severe endothelial injury. The opposite pattern was identified in indirect lung injury. Clinical trials of novel therapies targeted specifically at the lung epithelium or endothelium may benefit from preferentially enrolling patients with direct and indirect ARDS, respectively.

Early Childhood Risk Factors for Decreased FEV1 at Age Six to Seven Years in Young Children with Cystic Fibrosis.

PubMed

Sanders, Don B; Emerson, Julia; Ren, Clement L; Schechter, Michael S; Gibson, Ronald L; Morgan, Wayne; Rosenfeld, Margaret

2015-08-01

There are limited objective measures of the severity of lung disease before children are able to routinely perform spirometry, generally at age 6 years. Identifying risk factors for reduced lung function at age 6 provides opportunities to intervene and slow the progression of cystic fibrosis (CF) lung disease. To evaluate early childhood predictors of lung function at age 6-7 in a large U.S. CF cohort in the current era of widespread early eradication therapy for Pseudomonas aeruginosa (P. aeruginosa). Participants were children with CF enrolled before age 4 in the Early Pseudomonas Infection Control (EPIC) Observational Study, a multicenter, longitudinal study that enrolled P. aeruginosa-negative children not exceeding 12 years of age. Linear regression was used to estimate the association between potential early childhood risk factors and the best FEV1% predicted at age 6-7 years. Four hundred and eighty-four children (of 1,797 enrolled in the EPIC Observational Study) met the eligibility criteria for this analysis. Mean (SD) age at enrollment was 2.0 (1.3) years. In a multivariable model adjusted for age at enrollment, the following risk factors were significantly associated with lower mean (95% confidence interval) FEV1% predicted at age 6-7: weight percentile less than 10% during the year of enrollment (-5.3 [-9.1, -1.5]), P. aeruginosa positive during the year of enrollment (-2.8 [-5.7, 0.0]), crackles or wheeze during the year of enrollment (-5.7 [-9.4, -1.9]), mother's education of high school or less (-4.2 [-7.3, -1.2]), and mother smoked during pregnancy (-4.4 [-8.8, 0.1]). In this large U.S. cohort, we identified several early childhood risk factors for lower FEV1 at age 6-7 years, most of which are modifiable. Clinical trial registered with www.clinicaltrials.gov (NCT00097773).

Developing future clinician scientists while supporting a research infrastructure.

PubMed

Holsti, Maija; Adelgais, Kathleen M; Willis, Leah; Jacobsen, Kammy; Clark, Edward B; Byington, Carrie L

2013-04-01

Supporting clinical research is a national priority. Clinician scientists are rare and clinical trials in academic medical centers (AMC) often fail to meet enrollment goals. Undergraduate students interested in biomedical careers often lack opportunities to perform clinical research. Describe an innovative undergraduate course that supports clinical research in an AMC. The course, Clinical Research Methods and Practice, offers undergraduate students the opportunity to learn clinical research through didactic and practical experiences. The students in turn support clinician scientists' conduct of clinical studies in an AMC. Clinician scientists receive research support and participate in mentoring sessions for students. Over seven semesters, 128 students have assisted in 21 clinical studies located in outpatient and inpatient units of two hospitals. Students identified and screened eligible patients, collected clinical data, assisted in obtaining informed consent, and transported specimens. Many of the clinician scientists have met their enrollment goals and several have been top-enrollers in multicenter clinical trials as a result of student support. The Clinical Research Methods and Practice class addresses barriers to clinical research in AMC. This may be a model for institutions committed to mentoring students early in their career and to developing infrastructures for clinical research. © 2013 Wiley Periodicals, Inc.

Diagnostic performance of computed tomography coronary angiography (from the Prospective National Multicenter Multivendor EVASCAN Study).

PubMed

Gueret, Pascal; Deux, Jean-François; Bonello, Laurent; Sarran, Anthony; Tron, Christophe; Christiaens, Luc; Dacher, Jean-Nicolas; Bertrand, David; Leborgne, Laurent; Renard, Cedric; Caussin, Christophe; Cluzel, Philippe; Helft, Gerard; Crochet, Dominique; Vernhet-Kovacsik, Hélène; Chabbert, Valérie; Ferrari, Emile; Gilard, Martine; Willoteaux, Serge; Furber, Alain; Barone-Rochette, Gilles; Jankowski, Adrien; Douek, Philippe; Mousseaux, Elie; Sirol, Marc; Niarra, Ralph; Chatellier, Gilles; Laissy, Jean-Pierre

2013-02-15

Computed tomographic coronary angiography (CTCA) has been proposed as a noninvasive test for significant coronary artery disease (CAD), but only limited data are available from prospective multicenter trials. The goal of this study was to establish the diagnostic accuracy of CTCA compared to coronary angiography (CA) in a large population of symptomatic patients with clinical indications for coronary imaging. This national, multicenter study was designed to prospectively evaluate stable patients able to undergo CTCA followed by conventional CA. Data from CTCA and CA were analyzed in a blinded fashion at central core laboratories. The main outcome was the evaluation of patient-, vessel-, and segment-based diagnostic performance of CTCA to detect or rule out significant CAD (≥50% luminal diameter reduction). Of 757 patients enrolled, 746 (mean age 61 ± 12 years, 71% men) were analyzed. They underwent CTCA followed by CA 1.7 ± 0.8 days later using a 64-detector scanner. The prevalence of significant CAD in native coronary vessels by CA was 54%. The rate of nonassessable segments by CTCA was 6%. In a patient-based analysis, sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of CTCA were 91%, 50%, 68%, 83%, 1.82, and 0.18, respectively. The strongest predictors of false-negative results on CTCA were high estimated pretest probability of CAD (odds ratio [OR] 1.97, p <0.001), male gender (OR 1.5, p <0.002), diabetes (OR 1.5, p <0.0001), and age (OR 1.2, p <0.0001). In conclusion, in this large multicenter study, CTCA identified significant CAD with high sensitivity. However, in routine clinical practice, each patient should be individually evaluated, and the pretest probability of obstructive CAD should be taken into account when deciding which method, CTCA or CA, to use to diagnose its presence and severity. Copyright © 2013 Elsevier Inc. All rights reserved.

China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS): A new, prospective, multicenter, randomized controlled trial in China

PubMed Central

Gao, Peng; Zhao, Zhenwei; Wang, Daming; Wu, Jian; Cai, Yiling; Li, Tianxiao; Wu, Wei; Shi, Huaizhang; He, Weiwen; Zhu, Fengshui; Ling, Feng

2015-01-01

Background Patients with symptomatic stenosis of intradural arteries are at high risk for subsequent stroke. Since the SAMMPRIS trial, stenting is no longer recommended as primary treatment; however, the results of this trial, its inclusion criteria and its center selection received significant criticism and did not appear to reflect our experience regarding natural history nor treatment complications rate. As intracranial atherosclerosis (ICAS) is the most common cause for stroke in Asian countries, we are hereby proposing a refined prospective, randomized, multicenter study in an Asian population with strictly defined patient and participating center inclusion criteria. Methods The China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS) trial is an ongoing, government-funded, prospective, multicenter, randomized trial. It recruits patients with recent TIA or stroke caused by 70%–99% stenosis of a major intracranial artery. Patients with previous stroke related to perforator ischemia will not be included. Only high-volume centers with a proven track record will enroll patients as determined by a lead-in phase. Patients will be randomized (1:1) to best medical therapy alone or medical therapy plus stenting. Primary endpoints are any stroke or death within 30 days after enrollment or after any revascularization procedure of the qualifying lesion during follow-up, or stroke in the territory of the symptomatic intracranial artery beyond 30 days. The CASSISS trial will be conducted in eight sites in China with core imaging lab review at a North American site and aims to have a sample size of 380 participants (stenting, 190; medical therapy, 190). Recruitment is expected to be finished by December 2016. Patients will be followed for at least three years. The trial is scheduled to complete in 2019. Conclusion In the proposed trial, certain shortcomings of SAMMPRIS including patient and participating center selection will be addressed. The present manuscript outlines the rationale and design of the study. We estimate that this trial will allow for a critical reappraisal of the role of intracranial stenting for selected patients in high-volume centers. PMID:25934656

Adversity and Syndemic Production Among Men Participating in the Multicenter AIDS Cohort Study: A Life-Course Approach

PubMed Central

Lim, Sin How; Plankey, Michael W.; Chmiel, Joan S.; Guadamuz, Thomas T.; Kao, Uyen; Shoptaw, Steven; Carrico, Adam; Ostrow, David; Stall, Ron

2013-01-01

Objectives. We tested a theory of syndemic production among men who have sex with men (MSM) using data from a large cohort study. Methods. Participants were 1551 men from the Multicenter AIDS Cohort Study enrolled at 4 study sites: Baltimore, Maryland–Washington, DC; Chicago, Illinois; Los Angeles, California; and Pittsburgh, Pennsylvania. Participants who attended semiannual visits from April 1, 2008, to March 31, 2009, completed an additional survey that captured data about events throughout their life course thought to be related to syndemic production. Results. Using multivariate analysis, we found that the majority of life-course predictor variables (e.g., victimization, internalized homophobia) were significantly associated with both the syndemic condition and the component psychosocial health outcomes (depressive symptoms, stress, stimulant use, sexual compulsivity, intimate partner violence). A nested negative binomial analysis showed that the overall life course significantly explained variability in the syndemic outcomes (χ2 = 247.94; P < .001; df = 22). Conclusions. We identified life-course events and conditions related to syndemic production that may help to inform innovative interventions that will effectively disentangle interconnecting health problems and promote health among MSM. PMID:23153154

Multicenter Randomized Controlled Trial on Duration of Therapy for Thrombosis in Children and Young Adults (Kids-DOTT): Pilot/Feasibility Phase Findings

PubMed Central

Goldenberg, N.A.; Abshire, T.; Blatchford, P.J.; Fenton, L.Z.; Halperin, J.L.; Hiatt, W.R.; Kessler, C.M.; Kittelson, J.M.; Manco-Johnson, M.J.; Spyropoulos, A.C.; Steg, P.G.; Stence, N.V.; Turpie, A.G.G.; Schulman, S.

2015-01-01

BACKGROUND Randomized controlled trials (RCTs) in pediatric venous thromboembolism (VTE) treatment have been challenged by unsubstantiated design assumptions and/or poor accrual. Pilot/feasibility (P/F) studies are critical to future RCT success. METHODS Kids-DOTT is a multicenter RCT investigating non-inferiority of a 6-week (shortened) vs. 3-month (conventional) duration of anticoagulation in patients <21 years old with provoked venous thrombosis. Primary efficacy and safety endpoints are symptomatic recurrent VTE at 1 year and anticoagulant-related, clinically-relevant bleeding. In the P/F phase, 100 participants were enrolled in an open, blinded endpoint, parallel-cohort RCT design. RESULTS No eligibility violations or randomization errors occurred. Of enrolled patients, 69% were randomized, 3% missed the randomization window, and 28% were followed in pre-specified observational cohorts for completely occlusive thrombosis or persistent antiphospholipid antibodies. Retention at 1 year was 82%. Inter-observer agreement between local vs. blinded central determination of venous occlusion by imaging at 6 weeks post-diagnosis was strong (κ-statistic=0.75; 95% confidence interval [CI] 0.48–1.0). Primary efficacy and safety event rates were 3.3% (95% CI 0.3–11.5%) and 1.4% (0.03–7.4%). CONCLUSIONS The P/F phase of Kids-DOTT has demonstrated validity of vascular imaging findings of occlusion as a randomization criterion, and defined randomization, retention, and endpoint rates to inform the fully-powered RCT. PMID:26118944

Skeletal involvement in Gaucher disease: An observational multicenter study of prognostic factors in the Argentine Gaucher disease patients.

PubMed

Drelichman, Guillermo; Fernández Escobar, Nicolás; Basack, Nora; Aversa, Luis; Larroude, María Silvia; Aguilar, Gabriela; Szlago, Marina; Schenone, Andrea; Fynn, Alcyra; Cuello, María Fernanda; Aznar, Marcela; Fernández, Ramiro; Ruiz, Alba; Reichel, Paola; Guelbert, Norberto; Robledo, Hugo; Watman, Nora; Bolesina, Moira; Elena, Graciela; Veber, S Ernesto; Pujal, Graciela; Galván, Graciela; Chain, Juan José; Arizo, Adriana; Bietti, Julieta; Bar, Daniel; Dragosky, Marta; Marquez, Marisa; Feldman, Leonardo; Muller, Katja; Zirone, Sandra; Buchovsky, Greogorio; Lanza, Victoria; Sanabria, Alba; Fernández, Ignacio; Jaureguiberry, Rossana; Contte, Marcelo; Barbieri María, Angie; Maro, Alejandra; Zárate, Graciela; Fernández, Gabriel; Rapetti, María Cristina; Donato, Hugo; Degano, Adriana; Kantor, Gustavo; Albina, Roberto; Á Lvarez Bollea, María; Brun, María; Bacciedoni, Viviana; Del Río, Francis; Soberón, Bárbara; Boido, Nazario; Schweri, Maya; Borchichi, Sandra; Welsh, Victoria; Corrales, Marcela; Cedola, Alejandra; Carvani, Analía; Diez, Blanca; Richard, Lucía; Baduel, Ccecilia; Nuñez, Gabriela; Colimodio, Rubén; Barazzutti, Lucía; Medici, Hugo; Meschengieser, Susana; Damiani, Germán; Nucifora, María; Girardi, Beatriz; Gómez, Sergio; Papucci, Maura; Verón, David; Quiroga, Luis; Carro, Gustavo; De Ambrosio, Patricia; Ferro, José; Pujol, Marcelo; Castella, Cristina Cabral; Franco, Liliana; Nisnovich, Gisela; Veloso, María; Pacheco, Isabel; Savarino, Mario; Marino, Andrés; Saavedra, José Luis

2016-10-01

Patients with Gaucher type 1 (GD1) throughout Argentina were enrolled in the Argentine bone project to evaluate bone disease and its determinants. We focused on presence and predictors of bone lesions (BL) and their relationship to therapeutic goals (TG) with timing and dose of enzyme replacement therapy (ERT). A total of 124 patients on ERT were enrolled in a multi-center study. All six TG were achieved by 82% of patients: 70.1% for bone pain and 91.1% for bone crisis. However, despite the fact that bone TGs were achieved, residual bone disease was present in 108 patients on ERT (87%) at time 0. 16% of patients showed new irreversible BL (bone infarcts and avascular osteonecrosis) despite ERT, suggesting that they appeared during ERT or were not detected at the moment of diagnosis. We observed 5 prognostic factors that predicted a higher probability of being free of bone disease: optimal ERT compliance; early diagnosis; timely initiation of therapy; ERT initiation dose ≥45 UI/kg/EOW; and the absence of history of splenectomy. Skeletal involvement was classified into 4 major phenotypic groups according to BL: group 1 (12.9%) without BL; group 2 (28.2%) with reversible BL; group 3 (41.9%) with reversible BL and irreversible chronic BL; and group 4 (16.9%) with acute irreversible BL. Our study identifies prognostic factors for achieving best therapeutic outcomes, introduces new risk stratification for patients and suggests the need for a redefinition of bone TG. Am. J. Hematol. 91:E448-E453, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Characteristics and Causes for Non-Accrued Clinical Research (NACR) at an Academic Medical Institution

PubMed Central

Tice, Debra G.; Carroll, Kelly A.; Bhatt, Karishma H.; Belknap, Steven M.; Mai, David; Gipson, Heather J.; West, Dennis P.

2013-01-01

Background The impact of non-accrued clinical research (NACR) represents an important economic burden that is under consideration as the U.S. Department of Health and Human Services looks into reforming the regulations governing IRB review. NACR refers to clinical research projects that fail to enroll subjects. A delineation of the issues surrounding NACR is expected to enhance subject accrual and to minimize occurrence of NACR. The authors assessed demographics, characteristics, and reasons for NACR at an academic medical center, including time trends, funding source, research team (principal investigator, department), IRB resource utilization (IRB level of review, number of required IRB reviews, initial IRB turn-around time, and duration of NACR). Methods The authors analyzed data from 848 clinical research study closures during 2010 and 2011 to determine proportion, incidence, and characteristics of NACR. Studies with subject enrollment during the same time period were used as a comparative measure. Results Data from 704 (83.0%) study closures reported enrollment of 1 or more subjects while 144 (17.0 %) reported NACR (zero enrollment). PI-reported reasons for NACR included: 32 (22.2%) contract or funding issues; 43 (30.0%) insufficient study-dedicated resources; 41 (28.4%) recruitment issues; 17 (11.8%) sponsor-initiated study closure and 11 (7.6%) were “other/reason unreported”. Conclusions NACR is not uncommon, affecting about one in six clinical research projects in the study population and reported to be more common in some other institutions. The complex and fluid nature of research conduct, non-realistic enrollment goals, and delays in both the approval and/or accrual processes contribute to NACR. Results suggest some simple strategies that investigators and institutions may use to reduce NACR, including careful feasibility assessment, reduction of institutional delays, and prompt initiation of subject accrual for multi-center studies using competitive enrollment. Institutional action to support investigators in the conduct clinical research is also encouraged to reduce likelihood of NACR. PMID:23671544

Characteristics and Causes for Non-Accrued Clinical Research (NACR) at an Academic Medical Institution.

PubMed

Tice, Debra G; Carroll, Kelly A; Bhatt, Karishma H; Belknap, Steven M; Mai, David; Gipson, Heather J; West, Dennis P

2013-06-01

The impact of non-accrued clinical research (NACR) represents an important economic burden that is under consideration as the U.S. Department of Health and Human Services looks into reforming the regulations governing IRB review. NACR refers to clinical research projects that fail to enroll subjects. A delineation of the issues surrounding NACR is expected to enhance subject accrual and to minimize occurrence of NACR. The authors assessed demographics, characteristics, and reasons for NACR at an academic medical center, including time trends, funding source, research team (principal investigator, department), IRB resource utilization (IRB level of review, number of required IRB reviews, initial IRB turn-around time, and duration of NACR). The authors analyzed data from 848 clinical research study closures during 2010 and 2011 to determine proportion, incidence, and characteristics of NACR. Studies with subject enrollment during the same time period were used as a comparative measure. Data from 704 (83.0%) study closures reported enrollment of 1 or more subjects while 144 (17.0 %) reported NACR (zero enrollment). PI-reported reasons for NACR included: 32 (22.2%) contract or funding issues; 43 (30.0%) insufficient study-dedicated resources; 41 (28.4%) recruitment issues; 17 (11.8%) sponsor-initiated study closure and 11 (7.6%) were "other/reason unreported". NACR is not uncommon, affecting about one in six clinical research projects in the study population and reported to be more common in some other institutions. The complex and fluid nature of research conduct, non-realistic enrollment goals, and delays in both the approval and/or accrual processes contribute to NACR. Results suggest some simple strategies that investigators and institutions may use to reduce NACR, including careful feasibility assessment, reduction of institutional delays, and prompt initiation of subject accrual for multi-center studies using competitive enrollment. Institutional action to support investigators in the conduct clinical research is also encouraged to reduce likelihood of NACR.

GHPSS multicenter Italian survey: smoking prevalence, knowledge and attitudes, and tobacco cessation training among third-year medical students.

PubMed

Saulle, Rosella; Bontempi, Claudio; Baldo, Vincenzo; Boccia, Giovanni; Bonaccorsi, Guglielmo; Brusaferro, Silvio; Donato, Francesco; Firenze, Alberto; Gregorio, Pasquale; Pelissero, Gabriele; Sella, Alberto; Siliquini, Roberta; Boccia, Antonio; La Torre, Giuseppe

2013-01-01

Healthcare professionals have an important role to play both as advisers - influencing smoking cessation - and as role models. The aims of this study were to examine smoking prevalence, knowledge and attitudes among Italian university students attending medical schools using the Global Health Professions Student Survey (GHPSS) approach. A multicenter cross-sectional study was conducted among University students of 9 Italian medical schools (age ranging between 19 and 29 years). The GHPSS questionnaire was self-administered. A logistic regression model was used to identify possible factors associated with tobacco smoking status. Data were analyzed with the software SPSS 19.0 for Windows. Seven hundred thirty medical students (response rate 100%) were enrolled. The prevalence of current smokers was 20.4% (males 22.4%, females 19.1%). Of the total sample, 87.7% believed that health professionals should receive specific training in techniques to quit smoking, and 65% believed that health professionals had a role in giving advice or information about smoking cessation. However, 89.4% answered that they had not received specific training on smoking cessation techniques. Multivariate analysis showed that students belonging to universities in southern Italy were more likely to be smokers (OR = 2.00; 95% CI: 1.03-3.97). This Italian multicenter survey found that one fifth of future medical doctors are smokers. There is a need to adopt a standard undergraduate curriculum containing comprehensive tobacco prevention and cessation training to improve their effectiveness as role models.

Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies.

PubMed

Harrison, Taylor; Miyahara, Sachiko; Lee, Anthony; Evans, Scott; Bastow, Barbara; Simpson, David; Gilron, Ian; Dworkin, Robert; Daar, Eric S; Wieclaw, Linda; Clifford, David B

2013-07-01

There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared with placebo. This study was a phase II, randomized, double-blind, placebo-controlled, four-period crossover multicenter study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary. A total of 15 patients were enrolled from eight study sites and eight patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared with placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study dropout. Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed. Wiley Periodicals, Inc.

Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies

PubMed Central

Harrison, Taylor; Miyahara, Sachiko; Lee, Anthony; Evans, Scott; Bastow, Barbara; Simpson, David; Gilron, Ian; Dworkin, Robert; Daar, Eric S.; Wieclaw, Linda; Clifford, David B.

2014-01-01

Objective There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared to placebo. Design This study was a phase II, randomized, double blind, placebo-controlled, four-period crossover multi-center study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary. Results A total of 15 patients were enrolled from 8 study sites and 8 patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared to placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study drop-out. Conclusions Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed. PMID:23565581

Results of the combined U.S. Multicenter Pivotal Study and the Continuing Access Study of the Nit-Occlud PDA device for percutaneous closure of patent ductus arteriosus.

PubMed

Moore, John W; Greene, Jessica; Palomares, Salvadore; Javois, Alexander; Owada, Carl Y; Cheatham, John P; Hoyer, Mark H; Jones, Thomas K; Levi, Daniel S

2014-12-01

This study aimed to compare the efficacy and safety of the Nit-Occlud PDA device (PFM Medical, Cologne, Germany) to benchmarks designed as objective performance criteria (OPC). The Nit-Occlud PDA is a nitinol coil-type patent ductus arteriosus (PDA) occluder with a reverse cone configuration, which is implanted using a controlled delivery system. Patients with <4-mm minimum diameter PDA were prospectively enrolled in the Pivotal and the Continuing Access Studies from 15 sites in the United States and were followed up for 12 months post-procedure. Investigator-reported outcomes were compared to OPC including a composite success criterion, efficacy criteria of successful closure (clinical and echocardiographic), and safety criteria incidence of adverse events (serious and of total). The Pivotal Study enrolled patients between November 1, 2002 and October 31, 2005, and the Continuing Access Study enrolled additional patients between September 1, 2006 and October 31, 2007. A total of 357 patients were enrolled, and 347 had successful device implantations. After 12 months, 96.8% had complete echocardiographic closure (OPC = 85%) and 98.1% had clinical closure (OPC = 95%). There were no deaths or serious adverse events (OPC = 1%). The total adverse event rate was 4.7% (OPC = 6%). Composite success was 95.1% in the study patients (OPC = 80%). Closure of small- and medium-sized PDA with the Nit-Occlud PDA is effective and safe when compared with OPC. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Aripiprazole for Irritability in Asian Children and Adolescents with Autistic Disorder: A 12-Week, Multinational, Multicenter, Prospective Open-Label Study.

PubMed

Kim, Hyo-Won; Park, Eun-Jin; Kim, Ji-Hoon; Boon-Yasidhi, Vitharon; Tarugsa, Jariya; Reyes, Alexis; Manalo, Stella; Joung, Yoo-Sook

2018-04-24

We investigated the effectiveness and tolerability of aripiprazole in the treatment of irritability in Asian children and adolescents (6-17 years) with autistic disorder in a 12-week, multinational, multicenter, open-label study. Sixty-seven subjects (10.0 ± 3.1 years old, 52 boys) were enrolled and treated with flexibly dosed aripiprazole for 12 weeks (mean dose, 5.1 ± 2.5 mg; range 2-15 mg). Aripiprazole significantly reduced the mean caregiver-rated scores for the Irritability, Lethargy/Social Withdrawal, Stereotypy, Hyperactivity, and Inappropriate Speech subscales of the Aberrant Behavior Checklist from baseline to week 12 (p < 0.001 for all subscales). Clinician-rated Clinical Global Impression Severity of Illness scale score also improved from baseline through week 12 (p < 0.001). The most common adverse event was weight gain and no serious adverse event related to aripiprazole treatment was noted. Our results suggest that aripiprazole is effective and generally tolerable in the treatment of irritability in Asian children and adolescents with autistic disorder. Further studies with larger sample sizes and longer treatment durations are required.

Establishment of an Italian chronic migraine database: a multicenter pilot study.

PubMed

Barbanti, Piero; Fofi, L; Cevoli, S; Torelli, P; Aurilia, C; Egeo, G; Grazzi, L; D'Amico, D; Manzoni, G C; Cortelli, P; Infarinato, F; Vanacore, N

2018-05-01

To optimize chronic migraine (CM) ascertainment and phenotype definition, provide adequate clinical management and health care procedures, and rationalize economic resources allocation, we performed an exploratory multicenter pilot study aimed at establishing a CM database, the first step for developing a future Italian CM registry. We enrolled 63 consecutive CM patients in four tertiary headache centers screened with face-to-face interviews using an ad hoc dedicated semi-structured questionnaire gathering detailed information on life-style, behavioral and socio-demographic factors, comorbidities, and migraine features before and after chronicization and healthcare resource use. Our pilot study provided useful insights revealing that CM patients (1) presented in most cases symptoms of peripheral trigeminal sensitization, a relatively unexpected feature which could be useful to unravel different CM endophenotypes and to predict trigeminal-targeted treatments' responsiveness; (2) had been frequently admitted to emergency departments; (3) had undergone, sometime repeatedly, unnecessary or inappropriate investigations; (4) got rarely illness benefit exemption or disability allowance only. We deem that the expansion of the database-shortly including many other Italian headache centers-will contribute to more precisely outline CM endophenotypes, hence improving management, treatment, and economic resource allocation, ultimately reducing CM burden on both patients and health system.

The Fukuoka Kidney disease Registry (FKR) Study: design and methods.

PubMed

Tanaka, Shigeru; Ninomiya, Toshiharu; Fujisaki, Kiichiro; Yoshida, Hisako; Nagata, Masaharu; Masutani, Kosuke; Tokumoto, Masanori; Mitsuiki, Koji; Hirakata, Hideki; Fujimi, Satoru; Kiyohara, Yutaka; Kitazono, Takanari; Tsuruya, Kazuhiko

2017-06-01

Chronic kidney disease (CKD) is an established independent risk factor for progression to end-stage renal disease (ESRD) and incidence of cardiovascular disease (CVD). The onset and progression of CKD are associated with both genetic predisposition and various lifestyle-related factors, but little is known about the influence of genetic-environmental interactions on the incidence of ESRD or CVD in patients with CKD. The Fukuoka Kidney disease Registry (FKR) Study is designed as one of the largest prospective, multicenter, observational cohort studies in non-dialysis dependent CKD patients. The FKR Study aims to enroll approximately 5000 individuals at multiple clinical centers and follow them for up to at least 5 years. At baseline, subjects enrolled in the FKR Study will fill out extensive lifestyle-related questionnaires. Further, their health status and treatments will be monitored annually through a research network of nephrology centers. Blood and urine samples, including DNA/RNA, will be collected at the time of enrolment and every 5-years follow-up. The FKR Study will provide many insights into the onset and progression of CKD, which will suggest hypothesis-driven interventional clinical trials aimed at reducing the burden of CKD. The features of the FKR Study may also facilitate innovative research to identify and validate novel risk factors, including genetic susceptibility and biomarkers, using biomaterials by high-throughput omics technologies.

A multi-center, randomized, double blind placebo-controlled trial of estrogens to prevent Alzheimer’s disease and loss of memory in women: design and baseline characteristics

PubMed Central

Sano, Mary; Jacobs, Diane; Andrews, Howard; Bell, Karen; Graff-Radford, Neill; Lucas, John; Rabins, Peter; Bolla, Karen; Tsai, Wei-Yan; Cross, Peter; Andrews, Karen; Costa, Rosann; Luo, Xiaodong

2012-01-01

Background Observational studies and small clinical trials suggested that hormone replacement therapy (HRT) decreases risk of cognitive loss and Alzheimer’s disease (AD) in postmenopausal women and may have value in primary prevention. Purpose A clinical trial was designed to determine if HRT delays AD or memory loss. This report describes the rationale and original design of the trial and details extensive modifications that were required to respond to unanticipated findings that emerged from other studies during the course of the trial. Methods The trial was designed as a multi-center, placebo-controlled primary prevention trial for women 65 years of age or older with a family history of dementia. Recruitment from local sites was supplemented by centralized efforts to use names of Medicare beneficiaries. Inclusion criteria included good general health and intact memory functioning. Participants were randomized to HRT or placebo in a 1:1 ratio. Assignment was stratified by hysterectomy status and site. The primary outcomes were incident AD and memory decline on neuropsychological testing. Results Enrollment began in March 1998. In response to the Women’s Health Initiative (WHI) May 2002 report of increased incidence of heart disease, stroke, pulmonary embolism, and breast cancer among women randomized to HRT, participants were re-consented with a revised consent form. Procedural modifications, including discontinuation of study medication and a modification of the planned primary outcome based on a final enrollment below the target enrollment (N = 477), were enacted in response to the subsequent WHI Memory Study report of increased risk of dementia and poorer cognitive function with HRT. The mean length of treatment exposure prior to discontinuation was 2.14 years. Participants’ mean age at baseline was 72.8; mean education was 14.2 years. Minority participation was 19% and 34% had a hysterectomy. The study continues to follow these participants for a total of 5 years blind to the original medication assignment. Limitations Results reported from the WHI during the course of this study mandated extensive procedural modifications, including discontinuing recruitment before completion and halting study medication. Alternative strategies for study redesign that were considered are discussed. PMID:18827045

SUMMIT (Serially Unified Multicenter Multiple Sclerosis Investigation): creating a repository of deeply phenotyped contemporary multiple sclerosis cohorts.

PubMed

Bove, Riley; Chitnis, Tanuja; Cree, Bruce Ac; Tintoré, Mar; Naegelin, Yvonne; Uitdehaag, Bernard Mj; Kappos, Ludwig; Khoury, Samia J; Montalban, Xavier; Hauser, Stephen L; Weiner, Howard L

2017-08-01

There is a pressing need for robust longitudinal cohort studies in the modern treatment era of multiple sclerosis. Build a multiple sclerosis (MS) cohort repository to capture the variability of disability accumulation, as well as provide the depth of characterization (clinical, radiologic, genetic, biospecimens) required to adequately model and ultimately predict a patient's course. Serially Unified Multicenter Multiple Sclerosis Investigation (SUMMIT) is an international multi-center, prospectively enrolled cohort with over a decade of comprehensive follow-up on more than 1000 patients from two large North American academic MS Centers (Brigham and Women's Hospital (Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB; BWH)) and University of California, San Francisco (Expression/genomics, Proteomics, Imaging, and Clinical (EPIC))). It is bringing online more than 2500 patients from additional international MS Centers (Basel (Universitätsspital Basel (UHB)), VU University Medical Center MS Center Amsterdam (MSCA), Multiple Sclerosis Center of Catalonia-Vall d'Hebron Hospital (Barcelona clinically isolated syndrome (CIS) cohort), and American University of Beirut Medical Center (AUBMC-Multiple Sclerosis Interdisciplinary Research (AMIR)). We provide evidence for harmonization of two of the initial cohorts in terms of the characterization of demographics, disease, and treatment-related variables; demonstrate several proof-of-principle analyses examining genetic and radiologic predictors of disease progression; and discuss the steps involved in expanding SUMMIT into a repository accessible to the broader scientific community.

Evaluating the use of fibrin glue for sealing low-output enterocutaneous fistulas: study protocol for a randomized controlled trial.

PubMed

Wu, Xiuwen; Ren, Jianan; Wang, Gefei; Wang, Jianzhong; Wang, Feng; Fan, Yueping; Li, Yuanxin; Han, Gang; Zhou, Yanbing; Song, Xiaofei; Quan, Bin; Yao, Min; Li, Jieshou

2015-10-07

The management of an enterocutaneous fistula poses a significant challenge to surgeons and is often associated with a costly hospital stay and long-term discomfort. The use of fibrin glue in the fistula tract has been shown to promote closure of low output enterocutaneous fistulas. Our previous nonrandomized study demonstrated that autologous platelet-rich fibrin glue treatment significantly decreased time to fistula closure and promoted closure rates. However, there are several limitations in the study, which may lead to bias in our conclusion. Thus, a multicenter, randomized, controlled clinical trial is required. The study is designed as a randomized, open-label, three-arm, multicenter study in nine Chinese academic hospitals for evaluating the efficacy and safety of fibrin glue for sealing low-output fistulas. An established number of 171 fistula patients will undergo prospective random assignment to autologous fibrin glue, commercial porcine fibrin sealants or drainage cessation (1:1:1). The primary endpoint is fistula closure time (defined as the interval between the day of enrollment and day of fistula closure) during the 14-day treatment period. To our knowledge, this is the first study to evaluate the safety and efficacy of both autologous and commercial fibrin glue sealing for patients with low-output volume fistulas. NCT01828892 . Registration date: April 2013.

The use of PriMatrix, a fetal bovine acellular dermal matrix, in healing chronic diabetic foot ulcers: a prospective multicenter study.

PubMed

Kavros, Steven J; Dutra, Timothy; Gonzalez-Cruz, Renier; Liden, Brock; Marcus, Belinda; McGuire, James; Nazario-Guirau, Luis

2014-08-01

The objective of this multicenter study was to prospectively evaluate the healing outcomes of chronic diabetic foot ulcers (DFUs) treated with PriMatrix (TEI Biosciences, Boston, Massachusetts), a fetal bovine acellular dermal matrix. Inclusion criteria required the subjects to have a chronic DFU that ranged in area from 1 to 20 cm² and failed to heal more than 30% during a 2-week screening period when treated with moist wound therapy. For qualifying subjects, PriMatrix was secured into a clean, sharply debrided wound; dressings were applied to maintain a moist wound environment, and the DFU was pressure off-loaded. Wound area measurements were taken weekly for up to 12 weeks, and PriMatrix was reapplied at the discretion of the treating physician. A total of 55 subjects were enrolled at 9 US centers with 46 subjects progressing to study completion. Ulcers had been in existence for an average of 286 days, and initial mean ulcer area was 4.34 cm². Of the subjects completing the study, 76% healed by 12 weeks with a mean time to healing of 53.1 ± 21.9 days. The mean number of applications for these healed wounds was 2.0 ± 1.4, with 59.1% healing with a single application of PriMatrix and 22.9% healing with 2 applications. For subjects not healed by 12 weeks, the average wound area reduction was 71.4%. The results of this multicenter prospective study demonstrate that the use of PriMatrix integrated with standard-of-care therapy is a successful treatment regimen to heal DFUs.

Surgical outcomes of robot-assisted rectal cancer surgery using the da Vinci Surgical System: a multi-center pilot Phase II study.

PubMed

Tsukamoto, Shunsuke; Nishizawa, Yuji; Ochiai, Hiroki; Tsukada, Yuichiro; Sasaki, Takeshi; Shida, Dai; Ito, Masaaki; Kanemitsu, Yukihide

2017-12-01

We conducted a multi-center pilot Phase II study to examine the safety of robotic rectal cancer surgery performed using the da Vinci Surgical System during the introduction period of robotic rectal surgery at two institutes based on surgical outcomes. This study was conducted with a prospective, multi-center, single-arm, open-label design to assess the safety and feasibility of robotic surgery for rectal cancer (da Vinci Surgical System). The primary endpoint was the rate of adverse events during and after robotic surgery. The secondary endpoint was the completion rate of robotic surgery. Between April 2014 and July 2016, 50 patients were enrolled in this study. Of these, 10 (20%) had rectosigmoid cancer, 17 (34%) had upper rectal cancer, and 23 (46%) had lower rectal cancer; six underwent high anterior resection, 32 underwent low anterior resection, 11 underwent intersphincteric resection, and one underwent abdominoperineal resection. Pathological stages were Stage 0 in 1 patient, Stage I in 28 patients, Stage II in 7 patients and Stage III in 14 patients. Pathologically complete resection was achieved in all patients. There was no intraoperative organ damage or postoperative mortality. Eight (16%) patients developed complications of all grades, of which 2 (4%) were Grade 3 or higher, including anastomotic leakage (2%) and conversion to open surgery (2%). The present study demonstrates the feasibility and safety of robotic rectal cancer surgery, as reflected by low morbidity and low conversion rates, during the introduction period. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

The morbidity and associated risk factors of cancer in chronic liver disease patients with diabetes mellitus: a multicenter field survey.

PubMed

Kawaguchi, Takumi; Kohjima, Motoyuki; Ichikawa, Tatsuki; Seike, Masataka; Ide, Yasushi; Mizuta, Toshihiko; Honda, Koichi; Nakao, Kazuhiko; Nakamuta, Makoto; Sata, Michio

2015-03-01

Diabetes mellitus is associated with various cancers; however, little is known of the relationship between cancer and diabetes in chronic liver disease (CLD) patients. The aim of this study is to investigate the morbidity and associated factors of cancer, including the use of anti-diabetics, in CLD patients with diabetes. We performed a multicenter survey in 2012 and 478 CLD patients with diabetes were enrolled (age 64.3 ± 12.1 years, female/male 187/291). A frequency analysis of cancer and antidiabetic use was performed. Independent factors for cancer were analyzed using logistic regression and decision-tree analysis. The morbidity of cancer was 33.3%. Hepatocellular carcinoma (HCC) and extra-hepatic cancer were diagnosed in 24.7 and 11.3% of enrolled patients, respectively. The frequency of antidiabetic use was 66.5%. Of prescribed antidiabetics, 39% were dipeptidyl-peptidase 4 inhibitors; however, their use was not significantly associated with cancer. In contrast, the use of exogenous insulin (OR 2.21; 95% CI 1.16-4.21, P = 0.0165) and sulfonylurea (OR 2.08; 95% CI 1.05-3.97, P = 0.0353) were independently associated with HCC and extra-hepatic cancer, respectively. In decision-tree analysis, exogenous insulin and sulfonylurea were also identified as a divergence factor for HCC and extra-hepatic cancer, respectively. We found a high morbidity of not only HCC, but also extra-hepatic cancer in CLD patients with diabetes. We also showed a possible association between the use of antidiabetics and the morbidity of cancer. Thus, a large-scale cohort study is needed to establish a therapeutic strategy for diabetes to suppress carcinogenesis in CLD patients.

Respiratory Syncytial Virus Genomic Load and Disease Severity Among Children Hospitalized With Bronchiolitis: Multicenter Cohort Studies in the United States and Finland

PubMed Central

Hasegawa, Kohei; Jartti, Tuomas; Mansbach, Jonathan M.; Laham, Federico R.; Jewell, Alan M.; Espinola, Janice A.; Piedra, Pedro A.; Camargo, Carlos A.

2015-01-01

Background. We investigated whether children with a higher respiratory syncytial virus (RSV) genomic load are at a higher risk of more-severe bronchiolitis. Methods. Two multicenter prospective cohort studies in the United States and Finland used the same protocol to enroll children aged <2 years hospitalized for bronchiolitis and collect nasopharyngeal aspirates. By using real-time polymerase chain reaction analysis, patients were classified into 3 genomic load status groups: low, intermediate, and high. Outcome measures were a length of hospital stay (LOS) of ≥3 days and intensive care use, defined as admission to the intensive care unit or use of mechanical ventilation. Results. Of 2615 enrolled children, 1764 (67%) had RSV bronchiolitis. Children with a low genomic load had a higher unadjusted risk of having a length of stay of ≥3 days (52%), compared with children with intermediate and those with high genomic loads (42% and 51%, respectively). In a multivariable model, the risk of having a length of stay of ≥3 days remained significantly higher in the groups with intermediate (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.20–1.69) and high (OR, 1.58; 95% CI, 1.29–1.94) genomic loads. Similarly, children with a high genomic load had a higher risk of intensive care use (20%, compared with 15% and 16% in the groups with low and intermediate genomic loads, respectively). In a multivariable model, the risk remained significantly higher in the group with a high genomic load (OR, 1.43; 95% CI, 1.03–1.99). Conclusion. Children with a higher RSV genomic load had a higher risk for more-severe bronchiolitis. PMID:25425699

Safety and Efficacy of Rocuronium With Sugammadex Reversal Versus Succinylcholine in Outpatient Surgery-A Multicenter, Randomized, Safety Assessor-Blinded Trial.

PubMed

Soto, Roy; Jahr, Jonathan S; Pavlin, Janet; Sabo, Daniel; Philip, Beverly K; Egan, Talmage D; Rowe, Everton; de Bie, Joris; Woo, Tiffany

Complex surgical procedures are increasingly performed in an outpatient setting, with emphasis on rapid recovery and case turnover. In this study, the combination of rocuronium for neuromuscular blockade (NMB) reversed by single-dose sugammadex was compared with succinylcholine followed by spontaneous recovery in outpatient surgery. This multicenter, randomized, safety assessor-blinded study enrolled adults undergoing a short elective outpatient surgical procedure requiring NMB and tracheal intubation. Patients were randomized to NMB with either rocuronium 0.6 mg/kg for tracheal intubation with incremental doses of rocuronium 0.15 mg/kg and subsequent reversal with sugammadex 4.0 mg/kg at 1-2 posttetanic counts or succinylcholine 1.0 mg/kg for intubation with spontaneous recovery. The primary efficacy end point was the time from sugammadex administration to recovery of the train-of-four ratio to 0.9; for succinylcholine, time from administration to recovery of the first twitch (T1) to 90% was assessed. From 167 patients enrolled, 150 received treatment. The all-subjects-treated population comprised 70 patients in the rocuronium-sugammadex group and 80 in the succinylcholine group. Geometric mean (95% confidence interval) time from the start of sugammadex administration to recovery of the train-of-four ratio to 0.9 was 1.8 (1.6-2.0) minutes. Geometric mean (95% confidence interval) time from succinylcholine administration to recovery of T1 to 90% was 10.8 (10.1-11.5) minutes. Health outcome variables were similar between the groups. Adverse events were reported in 87.1% and 93.8% of patients for rocuronium-sugammadex and succinylcholine, respectively. In conclusion, rocuronium for intubation followed by sugammadex for reversal of NMB offers a viable treatment option in outpatient surgery without prolonging recovery duration or jeopardizing safety.

Development of quality control and instrumentation performance metrics for diffuse optical spectroscopic imaging instruments in the multi-center clinical environment

NASA Astrophysics Data System (ADS)

Keene, Samuel T.; Cerussi, Albert E.; Warren, Robert V.; Hill, Brian; Roblyer, Darren; Leproux, AnaÑ--s.; Durkin, Amanda F.; O'Sullivan, Thomas D.; Haghany, Hosain; Mantulin, William W.; Tromberg, Bruce J.

2013-03-01

Instrument equivalence and quality control are critical elements of multi-center clinical trials. We currently have five identical Diffuse Optical Spectroscopic Imaging (DOSI) instruments enrolled in the American College of Radiology Imaging Network (ACRIN, #6691) trial located at five academic clinical research sites in the US. The goal of the study is to predict the response of breast tumors to neoadjuvant chemotherapy in 60 patients. In order to reliably compare DOSI measurements across different instruments, operators and sites, we must be confident that the data quality is comparable. We require objective and reliable methods for identifying, correcting, and rejecting low quality data. To achieve this goal, we developed and tested an automated quality control algorithm that rejects data points below the instrument noise floor, improves tissue optical property recovery, and outputs a detailed data quality report. Using a new protocol for obtaining dark-noise data, we applied the algorithm to ACRIN patient data and successfully improved the quality of recovered physiological data in some cases.

THE 6-MINUTE WALK TEST AND OTHER CLINICAL ENDPOINTS IN DUCHENNE MUSCULAR DYSTROPHY: RELIABILITY, CONCURRENT VALIDITY, AND MINIMAL CLINICALLY IMPORTANT DIFFERENCES FROM A MULTICENTER STUDY

PubMed Central

McDonald, Craig M; Henricson, Erik K; Abresch, R Ted; Florence, Julaine; Eagle, Michelle; Gappmaier, Eduard; Glanzman, Allan M; Spiegel, Robert; Barth, Jay; Elfring, Gary; Reha, Allen; Peltz, Stuart W

2013-01-01

Introduction: An international clinical trial enrolled 174 ambulatory males ≥5 years old with nonsense mutation Duchenne muscular dystrophy (nmDMD). Pretreatment data provide insight into reliability, concurrent validity, and minimal clinically important differences (MCIDs) of the 6-minute walk test (6MWT) and other endpoints. Methods: Screening and baseline evaluations included the 6-minute walk distance (6MWD), timed function tests (TFTs), quantitative strength by myometry, the PedsQL, heart rate–determined energy expenditure index, and other exploratory endpoints. Results: The 6MWT proved feasible and reliable in a multicenter context. Concurrent validity with other endpoints was excellent. The MCID for 6MWD was 28.5 and 31.7 meters based on 2 statistical distribution methods. Conclusions: The ratio of MCID to baseline mean is lower for 6MWD than for other endpoints. The 6MWD is an optimal primary endpoint for Duchenne muscular dystrophy (DMD) clinical trials that are focused therapeutically on preservation of ambulation and slowing of disease progression. Muscle Nerve 48: 357–368, 2013 PMID:23674289

Randomized, Multicenter Study of Gefitinib Dose-escalation in Advanced Non-small-cell Lung Cancer Patients Achieved Stable Disease after One-month Gefitinib Treatment

PubMed Central

Xue, Cong; Hong, Shaodong; Li, Ning; Feng, Weineng; Jia, Jun; Peng, Jiewen; Lin, Daren; Cao, Xiaolong; Wang, Siyang; Zhang, Weimin; Zhang, Hongyu; Dong, Wei; Zhang, Li

2015-01-01

There is no consensus on the optimal treatment for patients with advanced non-small-cell lung cancer (NSCLC) and stable disease (SD) after gefitinib therapy. This randomized, open-label, multicenter study aimed to explore whether dose-escalation of gefitinib would improve response and survival in NSCLC patients who achieved SD after one-month of standard gefitinib dosage. Between May 2009 and January 2012, 466 patients were enrolled and 100 eligible patients were randomized (1:1) to receive either a higher dose (500 mg/d; H group) or to continue standard dose (250 mg/d; S group) of gefitinib. Objective response rate (ORR) was similar between the two groups (12.5% vs 12.5%, p = 1.000). There were no significant differences regarding progression-free survival (PFS) and overall survival (OS) between both arms (H group vs S group: median PFS, 5.30 months vs 6.23 months, p = 0.167; median OS, 13.70 months vs 18.87 months, p = 0.156). Therefore, dose-escalation of gefitinib does not confer a response or survival advantage in patients who achieve SD with one month of standard-dose gefitinib treatment. PMID:26216071

Multiple pregnancy, short cervix, part-time worker, steroid use, low educational level and male fetus are risk factors for preterm birth in Japan: a multicenter, prospective study.

PubMed

Shiozaki, Arihiro; Yoneda, Satoshi; Nakabayashi, Masao; Takeda, Yoshiharu; Takeda, Satoru; Sugimura, Motoi; Yoshida, Koyo; Tajima, Atsushi; Manabe, Mami; Akagi, Kozo; Nakagawa, Shoko; Tada, Katsuhiko; Imafuku, Noriaki; Ogawa, Masanobu; Mizunoe, Tomoya; Kanayama, Naohiro; Itoh, Hiroaki; Minoura, Shigeki; Ogino, Mitsuharu; Saito, Shigeru

2014-01-01

To examine the relationship between preterm birth and socioeconomic factors, past history, cervical length, cervical interleukin-8, bacterial vaginosis, underlying diseases, use of medication, employment status, sex of the fetus and multiple pregnancy. In a multicenter, prospective, observational study, 1810 Japanese women registering their future delivery were enrolled at 8⁺⁰ to 12⁺⁶ weeks of gestation. Data on cervical length and delivery were obtained from 1365 pregnant women. Multivariate logistic regression analysis was performed. Short cervical length, steroid use, multiple pregnancy and male fetus were risk factors for preterm birth before 34 weeks of gestation. Multiple pregnancy, low educational level, short cervical length and part-timer were risk factors for preterm birth before 37 weeks of gestation. Multiple pregnancy and cervical shortening at 20-24 weeks of gestation was a stronger risk factor for preterm birth. Any pregnant woman being part-time employee or low educational level, having a male fetus and requiring steroid treatment should be watched for the development of preterm birth. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

A Prospective Multi-Center Observational Study of Children Hospitalized with Diarrhea in Ho Chi Minh City, Vietnam

PubMed Central

Thompson, Corinne N.; Phan, My V. T.; Hoang, Nguyen Van Minh; Minh, Pham Van; Vinh, Nguyen Thanh; Thuy, Cao Thu; Nga, Tran Thi Thu; Rabaa, Maia A.; Duy, Pham Thanh; Dung, Tran Thi Ngoc; Phat, Voong Vinh; Nga, Tran Vu Thieu; Tu, Le Thi Phuong; Tuyen, Ha Thanh; Yoshihara, Keisuke; Jenkins, Claire; Duong, Vu Thuy; Phuc, Hoang Le; Tuyet, Pham Thi Ngoc; Ngoc, Nguyen Minh; Vinh, Ha; Chinh, Nguyen Tran; Thuong, Tang Chi; Tuan, Ha Manh; Hien, Tran Tinh; Campbell, James I.; Chau, Nguyen Van Vinh; Thwaites, Guy; Baker, Stephen

2015-01-01

We performed a prospective multicenter study to address the lack of data on the etiology, clinical and demographic features of hospitalized pediatric diarrhea in Ho Chi Minh City (HCMC), Vietnam. Over 2,000 (1,419 symptomatic and 609 non-diarrheal control) children were enrolled in three hospitals over a 1-year period in 2009–2010. Aiming to detect a panel of pathogens, we identified a known diarrheal pathogen in stool samples from 1,067/1,419 (75.2%) children with diarrhea and from 81/609 (13.3%) children without diarrhea. Rotavirus predominated in the symptomatic children (664/1,419; 46.8%), followed by norovirus (293/1,419; 20.6%). The bacterial pathogens Salmonella, Campylobacter, and Shigella were cumulatively isolated from 204/1,419 (14.4%) diarrheal children and exhibited extensive antimicrobial resistance, most notably to fluoroquinolones and third-generation cephalosporins. We suggest renewed efforts in generation and implementation of policies to control the sale and prescription of antimicrobials to curb bacterial resistance and advise consideration of a subsidized rotavirus vaccination policy to limit the morbidity due to diarrheal disease in Vietnam. PMID:25802437

Effectiveness and predictors of success of noninvasive ventilation during H1N1 pandemics: a multicenter study.

PubMed

Nicolini, A; Tonveronachi, E; Navalesi, P; Antonelli, M; Valentini, I; Melotti, R M; Pigna, A; Carrassi, A; Righini, P; Ferrari Bravo, M; Pelosi, P; Nicoli, F; Cosentini, R; Vaschetto, R; Faenza, S; Nava, S

2012-12-01

The use of non-invasive ventilation (NIV) in acute hypoxemic respiratory failure (AHRF) due to H1N1 virus infection is controversial. In this multicenter study we aimed to assess the efficacy of NIV in avoiding endotracheal intubation (ETI) and to identify predictors of success or failure. In this prospective multicenter study, 98 patients with new pulmonary infiltrate(s) sustained by H1N1 virus and a PaO(2)/FiO2<300 were eligible for study; 38/98 required immediate ETI, while the others received NIV as a first line therapy; 13/60 patients failed NIV and were intubated after 5.8+5.5 hours from enrolment. The remaining 47/60 patients were successfully ventilated with NIV. Hospital mortality was significantly higher in those patients who failed NIV vs. those who succeeded (53.8% vs. 2.1%; OR=0.52, P<0.001). ETI was associated with higher number of infectious complications, mainly sepsis and septic shock. The OR of having one of these events in the NIV failure group vs. NIV success was 16.7, P<0.001. According to logistic regression model, a SAPS II>29 and a PaO(2)/FIO(2)≤127 at admission and PaO2/FIO(2)≤149 after 1 hr of NIV were independently associated with the need for ETI. The early application of NIV, with the aim to avoid invasive ventilation, during the H1N1 pandemics was associated with an overall success rate of 47/98 (48%). Patients presenting at admission with an high SAPS II score and a low PaO(2)/FiO(2) ratio and/or unable to promptly correct gas exchange are at high risk of intubation and mortality.

Implementation of clinical practice guidelines for ventilator-associated pneumonia: a multicenter prospective study.

PubMed

Sinuff, Tasnim; Muscedere, John; Cook, Deborah J; Dodek, Peter M; Anderson, William; Keenan, Sean P; Wood, Gordon; Tan, Richard; Haupt, Marilyn T; Miletin, Michael; Bouali, Redouane; Jiang, Xuran; Day, Andrew G; Overvelde, Janet; Heyland, Daren K

2013-01-01

Ventilator-associated pneumonia is an important cause of morbidity and mortality in critically ill patients. Evidence-based clinical practice guidelines for the prevention, diagnosis, and treatment of ventilator-associated pneumonia may improve outcomes, but optimal methods to ensure implementation of guidelines in the intensive care unit are unclear. Hence, we determined the effect of educational sessions augmented with reminders, and led by local opinion leaders, as strategies to implement evidence-based ventilator-associated pneumonia guidelines on guideline concordance and ventilator-associated pneumonia rates. Two-year prospective, multicenter, time-series study conducted between June 2007 and December 2009. Eleven ICUs (ten in Canada, one in the United States); five academic and six community ICUs. At each site, 30 adult patients mechanically ventilated >48 hrs were enrolled during four data collection periods (baseline, 6, 15, and 24 months). Guideline recommendations for the prevention, diagnosis, and treatment of ventilator-associated pneumonia were implemented using a multifaceted intervention (education, reminders, local opinion leaders, and implementation teams) directed toward the entire multidisciplinary ICU team. Clinician exposure to the intervention was assessed at 6, 15, and 24 months after the introduction of this intervention. The main outcome measure was aggregate concordance with the 14 ventilator-associated pneumonia guideline recommendations. One thousand three hundred twenty patients were enrolled (330 in each study period). Clinician exposure to the multifaceted intervention was high and increased during the study: 86.7%, 93.3%, 95.8%, (p < .001), as did aggregate concordance (mean [SD]): 50.7% (6.1), 54.4% (7.1), 56.2% (5.9), 58.7% (6.7) (p = .007). Over the study period, ventilator-associated pneumonia rates decreased (events/330 patients): 47 (14.2%), 34 (10.3%), 38 (11.5%), 29 (8.8%) (p = .03). A 2-yr multifaceted intervention to enhance ventilator-associated pneumonia guideline uptake was associated with a significant increase in guideline concordance and a reduction in ventilator-associated pneumonia rates.

The success of opening single chronic total occlusion lesions to improve myocardialviabilitytrial (SOS-COMEDY): Study protocol of a prospective multicenter study.

PubMed

Huang, Rongchong; Song, Xiantao; Zhang, Haishan; Tian, Wen; Huang, Zheng; Zhang, Xingwei; Yang, Junqing; Zhang, Dongfeng; Wu, Jian; Zhong, Lei; Ting, Henry H

2018-04-01

Success of opening single (SOS)-comedy is a prospective multicenter study to compare the improvement in the decrease of myocardial viability by percutaneous coronary intervention (PCI) with that by optimal medical therapy (OMT) alone in patients with chronic total occlusion (CTO) of a single coronary artery. The risks and the benefits of both options (PCI and OMT) were listed in a CTO decision aid (DA). Eligible participants detected by invasive coronary angiography (ICA) or coronary computed tomography angiography (CCTA) were divided into PCI or OMT groups according to patients' choice after shared-decision making process with DA. Participants will undergo positron emission tomography/computed tomography (PET/CT), cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE), and proceed to ICA and revascularization if possible. Blinded core laboratory interpretation will be performed for ICA, CCTA, PET/CT, CMR, and TTE. All participants will be followed up for 12 months. The primary endpoint is the improvement to the decrease of myocardial viability from baseline assessed with the use of PET/CT after 12-month follow-up. All of the patients are appropriately consented before enrolling in this study, which has been approved by the Ethics Committee. Results of SOS-COMEDY will be helpful to develop a strategy for single CTO patients.

EWOLUTION: Design of a registry to evaluate real-world clinical outcomes in patients with AF and high stroke risk-treated with the WATCHMAN left atrial appendage closure technology.

PubMed

Boersma, Lucas V A; Schmidt, Boris; Betts, Tim R; Sievert, Horst; Tamburino, Corrado; Teiger, Emmanuel; Stein, Kenneth M; Bergmann, Martin W

2016-09-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and the rate of ischemic stroke attributed to non-valvular AF is estimated at 5% per year. Several multi-center studies established left atrial appendage closure as a safe and effective alternative to oral anticoagulation, but there is a need for additional real world data. The purpose of this observational, prospective, single-arm, multicenter clinical study is to compile real-world clinical outcome data for WATCHMAN™ LAA (left atrial appendage) Closure Technology. One thousand subjects at up to 70 institutions in Europe, the Middle East, and Russia will be enrolled. Patients will be followed for 2 years after WATCHMAN implantation, according to standard medical practice. Primary endpoints include procedural and long-term data including stroke/embolism, bleeding, and death. This article presents the background of the LAAC device and describes the design of the study. Results for peri-procedural analyses are expected toward the end of 2015; long-term follow-up data are expected in the latter half of 2017. The EWOLUTION study will formally expand knowledge of LAA closure into a broader real world setting. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Associations among depression severity, painful physical symptoms, and social and occupational functioning impairment in patients with major depressive disorder: a 3-month, prospective, observational study.

PubMed

Harada, Eiji; Satoi, Yoichi; Kuga, Atsushi; Tokuoka, Hirofumi; Kikuchi, Toshiaki; Watanabe, Koichiro; Alev, Levent; Mimura, Masaru

2017-01-01

To investigate associations among depression severity, painful physical symptoms (PPS), and social and occupational functioning impairment in patients with major depressive disorder (MDD) who had achieved complete remission (CR) or partial remission (PR) after acute treatment. This was a 12-week, multicenter, prospective, observational study. Patients with MDD treated with an antidepressant medication for the previous 12 weeks (±3 weeks) who had achieved CR (defined as a 17-item Hamilton Rating Scale for Depression [HAM-D17] score ≤7) or PR (HAM-D17 score ≥8 and ≤18) were enrolled. Depression severity, PPS, and impairment in social and occupational functioning were assessed using the HAM-D17, the Brief Pain Inventory (Short Form) (BPI-SF), and the Social and Occupational Functioning Assessment Scale (SOFAS), respectively, at enrollment (Week 12) and after 12 weeks (Week 24). Overall, 323 Japanese patients with MDD were enrolled (CR n=158, PR n=165) and 288 patients completed the study (CR n=139, PR n=149). HAM-D17 and SOFAS scores were strongly and negatively correlated at enrollment (Week 12; P <0.0001) and Week 24 ( P <0.0001). A weak negative correlation between the BPI-SF and SOFAS was observed at Week 24 ( P =0.0011), but not at enrollment ( P =0.164). Remission status at enrollment (CR or PR) was associated with achieving normal social and occupational functioning (SOFAS score ≥80) at Week 24 in patients who had not achieved normal social and occupational functioning (SOFAS score <80) at enrollment (CR vs PR, OR=0.05 [95% CIs 0.01-0.18], P <0.0001). A greater proportion of patients with CR and no PPS at enrollment achieved SOFAS scores ≥80 at Week 24 than those with CR and PPS. Our results suggest that treating both depressive symptoms and PPS is important for achieving a normal level of functioning on a long-term basis in patients with MDD.

Association of prehospitalization aspirin therapy and acute lung injury: results of a multicenter international observational study of at-risk patients.

PubMed

Kor, Daryl J; Erlich, Jason; Gong, Michelle N; Malinchoc, Michael; Carter, Rickey E; Gajic, Ognjen; Talmor, Daniel S

2011-11-01

To evaluate the association between prehospitalization aspirin therapy and incident acute lung injury in a heterogeneous cohort of at-risk medical patients. This is a secondary analysis of a prospective multicenter international cohort investigation. Multicenter observational study including 20 US hospitals and two hospitals in Turkey. Consecutive, adult, nonsurgical patients admitted to the hospital with at least one major risk factor for acute lung injury. None. Baseline characteristics and acute lung injury risk factors/modifiers were identified. The presence of aspirin therapy and the propensity to receive this therapy were determined. The primary outcome was acute lung injury during hospitalization. Secondary outcomes included intensive care unit and hospital mortality and intensive care unit and hospital length of stay. Twenty-two hospitals enrolled 3855 at-risk patients over a 6-month period. Nine hundred seventy-six (25.3%) were receiving aspirin at the time of hospitalization. Two hundred forty (6.2%) patients developed acute lung injury. Univariate analysis noted a reduced incidence of acute lung injury in those receiving aspirin therapy (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.46-0.90; p = .010). This association was attenuated in a stratified analysis based on deciles of aspirin propensity scores (Cochran-Mantel-Haenszel pooled OR, 0.70; 95% CI, 0.48-1.03; p = .072). After adjusting for the propensity to receive aspirin therapy, no statistically significant associations between prehospitalization aspirin therapy and acute lung injury were identified; however, a prospective clinical trial to further evaluate this association appears warranted.

Multicenter Randomized Trial of Robot-Assisted Rehabilitation for Chronic Stroke: Methods and Entry Characteristics for VA ROBOTICS

PubMed Central

Lo, Albert C.; Guarino, Peter; Krebs, Hermano I.; Volpe, Bruce T.; Bever, Christopher T.; Duncan, Pamela W.; Ringer, Robert J.; Wagner, Todd H.; Richards, Lorie G.; Bravata, Dawn M.; Haselkorn, Jodie K.; Wittenberg, George F.; Federman, Daniel G.; Corn, Barbara H.; Maffucci, Alysia D.; Peduzzi, Peter

2017-01-01

Background Chronic upper extremity impairment due to stroke has significant medical, psychosocial, and financial consequences, but few studies have examined the effectiveness of rehabilitation therapy during the chronic stroke period. Objective To test the safety and efficacy of the MIT-Manus robotic device for chronic upper extremity impairment following stroke. Methods The VA Cooperative Studies Program initiated a multicenter, randomized, controlled trial in November 2006 (VA ROBOTICS). Participants with upper extremity impairment ≥6 months poststroke were randomized to robot-assisted therapy (RT), intensive comparison therapy (ICT), or usual care (UC). RT and ICT consisted of three 1-hour treatment sessions per week for 12 weeks. The primary outcome was change in the Fugl-Meyer Assessment upper extremity motor function score at 12 weeks relative to baseline. Secondary outcomes included the Wolf Motor Function Test and the Stroke Impact Scale. Results A total of 127 participants were randomized: 49 to RT, 50 to ICT, and 28 to UC. The majority of participants were male (96%), with a mean age of 65 years. The primary stroke type was ischemic (85%), and 58% of strokes occurred in the anterior circulation. Twenty percent of the participants reported a stroke in addition to their index stroke. The average time from the index stroke to enrollment was 56 months (range, 6 months to 24 years). The mean Fugl-Meyer score at entry was 18.9. Conclusions VA ROBOTICS demonstrates the feasibility of conducting multicenter clinical trials to rigorously test new rehabilitative devices before their introduction to clinical practice. The results are expected in early 2010. PMID:19541917

Dosimetric characterization of small fields using a plastic scintillator detector: A large multicenter study.

PubMed

Mancosu, Pietro; Pasquino, Massimo; Reggiori, Giacomo; Masi, Laura; Russo, Serenella; Stasi, Michele

2017-09-01

In modern radiation therapy accurate small fields dosimetry is a challenge and its standardization is fundamental to harmonize delivered dose in different institutions. This study presents a multicenter characterization of MLC-defined small field for Elekta and Varian linear accelerators. Measurements were performed using the Exradin W1 plastic scintillator detector. The project enrolled 24 Italian centers. Each center performed Tissue Phantom Ratio (TPR), in-plane and cross-plane dose profiles of 0.8×0.8cm 2 field, and Output Factor (OF) measurements for square field sizes ranging from 0.8 to 10cm. Set-up conditions were 10cm depth in water phantom at SSD 90cm. Measurements were performed using two twin Exradin W1 plastic scintillator detectors (PSD) correcting for the Cerenkov effect as proposed by the manufacturer. Data analysis from 12 Varian and 12 Elekta centers was performed. Measurements of 7 centers were not included due to cable problems. TPR measurements showed standard deviations (SD)<1%; SD<0.4mm for the profile penumbra was obtained, while FWHM measurements showed SD<0.5mm. OF measurements showed SD<1.5% for field size greater than 2×2cm 2 . Median OFs values were in agreement with the recent bibliography. High degree of consistency was registered for all the considered parameters. This work confirmed the importance of multicenter dosimetric intercomparison. W1 PSD could be considered as a good candidate for small field measurements. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Comparison of 3 biodegradable polymer and durable polymer-based drug-eluting stents in all-comers (BIO-RESORT): rationale and study design of the randomized TWENTE III multicenter trial.

PubMed

Lam, Ming Kai; Sen, Hanim; Tandjung, Kenneth; van Houwelingen, K Gert; de Vries, Arie G; Danse, Peter W; Schotborgh, Carl E; Scholte, Martijn; Löwik, Marije M; Linssen, Gerard C M; Ijzerman, Maarten J; van der Palen, Job; Doggen, Carine J M; von Birgelen, Clemens

2014-04-01

To evaluate the safety and efficacy of 2 novel drug-eluting stents (DES) with biodegradable polymer-based coatings versus a durable coating DES. BIO-RESORT is an investigator-initiated, prospective, patient-blinded, randomized multicenter trial in 3540 Dutch all-comers with various clinical syndromes, requiring percutaneous coronary interventions (PCI) with DES implantation. Randomization (stratified for diabetes mellitus) is being performed in a 1:1:1 ratio between ORSIRO sirolimus-eluting stent with circumferential biodegradable coating, SYNERGY everolimus-eluting stent with abluminal biodegradable coating, and RESOLUTE INTEGRITY zotarolimus-eluting stent with durable coating. The primary endpoint is the incidence of the composite endpoint target vessel failure at 1 year, consisting of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. Power calculation assumes a target vessel failure rate of 8.5% with a 3.5% non-inferiority margin, giving the study a power of 85% (α level .025 adjusted for multiple testing). The impact of diabetes mellitus on post-PCI outcome will be evaluated. The first patient was enrolled on December 21, 2012. BIO-RESORT is a large, prospective, randomized, multicenter trial with three arms, comparing two DES with biodegradable coatings versus a reference DES with a durable coating in 3540 all-comers. The trial will provide novel insights into the clinical outcome of modern DES and will address the impact of known and so far undetected diabetes mellitus on post-PCI outcome. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

Baseline Morbidity in 2,990 Adult African Volunteers Recruited to Characterize Laboratory Reference Intervals for Future HIV Vaccine Clinical Trials

PubMed Central

Stevens, Wendy; Kamali, Anatoli; Karita, Etienne; Anzala, Omu; Sanders, Eduard J.; Jaoko, Walter; Kaleebu, Pontiano; Mulenga, Joseph; Dally, Len; Fast, Pat; Gilmour, Jill; Farah, Bashir; Birungi, Josephine; Hughes, Peter; Manigart, Olivier; Stevens, Gwynn; Yates, Sarah; Thomson, Helen; von Lieven, Andrea; Krebs, Marietta; Price, Matt A.; Stoll-Johnson, Lisa; Ketter, Nzeera

2008-01-01

Background An understanding of the health of potential volunteers in Africa is essential for the safe and efficient conduct of clinical trials, particularly for trials of preventive technologies such as vaccines that enroll healthy individuals. Clinical safety laboratory values used for screening, enrolment and follow-up of African clinical trial volunteers have largely been based on values derived from industrialized countries in Europe and North America. This report describes baseline morbidity during recruitment for a multi-center, African laboratory reference intervals study. Methods Asymptomatic persons, aged 18–60 years, were invited to participate in a cross-sectional study at seven sites (Kigali, Rwanda; Masaka and Entebbe, Uganda; Kangemi, Kenyatta National Hospital and Kilifi, Kenya; and Lusaka, Zambia). Gender equivalency was by design. Individuals who were acutely ill, pregnant, menstruating, or had significant clinical findings were not enrolled. Each volunteer provided blood for hematology, immunology, and biochemistry parameters and urine for urinalysis. Enrolled volunteers were excluded if found to be positive for HIV, syphilis or Hepatitis B and C. Laboratory assays were conducted under Good Clinical Laboratory Practices (GCLP). Results and Conclusions Of the 2990 volunteers who were screened, 2387 (80%) were enrolled, and 2107 (71%) were included in the analysis (52% men, 48% women). Major reasons for screening out volunteers included abnormal findings on physical examination (228/603, 38%), significant medical history (76, 13%) and inability to complete the informed consent process (73, 13%). Once enrolled, principle reasons for exclusion from analysis included detection of Hepatitis B surface antigen (106/280, 38%) and antibodies against Hepatitis C (95, 34%). This is the first large scale, multi-site study conducted to the standards of GCLP to describe African laboratory reference intervals applicable to potential volunteers in clinical trials. Approximately one-third of all potential volunteers screened were not eligible for analysis; the majority were excluded for medical reasons. PMID:18446196

Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

PubMed Central

2013-01-01

Introduction Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. Conclusions Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. Trial registration ClinicalTrials.gov number NCT01209169. PMID:23388612

Testing prospectively the effectiveness and safety of paclitaxel-eluting stents in over 1000 very high-risk patients: design, baseline characteristics, procedural data and in-hospital outcomes of the multicenter Taxus in Real-life Usage Evaluation (TRUE) Study.

PubMed

Biondi-Zoccai, Giuseppe G L; Sangiorgi, Giuseppe M; Antoniucci, David; Grube, Eberhard; Di Mario, Carlo; Reimers, Bernard; Tamburino, Corrado; Agostoni, Pierfrancesco; Cosgrave, John; Colombo, Antonio

2007-05-02

Paclitaxel-eluting stents (PES) have been proved effective in randomized trials enrolling highly selected patients. Yet, given the uncertainty concerning results of PES implantation in very high-risk patients and lesions, we designed a prospective multicenter registry, the Taxus in Real-life Usage Evaluation (TRUE) Study. STUDY DESIGN, PATIENT CHARACTERISTICS AND IN-HOSPITAL OUTCOMES: Consecutive patients undergoing PES implantation were enrolled provided that the target lesion treated with PES was an unprotected left main (ULM), a true bifurcation, a chronic total occlusion (CTO), a long lesion (>28 mm), located in a small vessel (<2.75 mm), or the patient had diabetes mellitus. Clinical events will be adjudicated at 1, 7 and 12 months, with 4- to 8-month angiographic follow-up. The primary end-point will be the 7-month occurrence of major adverse cardiovascular events (MACE, i.e. the composite of cardiac death, non-fatal myocardial infarction [MI], coronary artery bypass grafting [CABG] and percutaneous target vessel revascularization [TVR]). To date, patient enrollment has been completed reaching the target of 1065 subjects. These included 322 (30.2%) diabetics, 115 (10.8%) subjects undergoing PES implantation for ULM, 229 (21.5%) in a bifurcation, 191 (17.9%) in a CTO, 430 (40.4%) in a small vessel, and 289 (27.1%) in a long lesion. An average of 1.5+/-0.6 vessels and 2.0+/-1.0 lesions were treated per patient, with 2.0+/-1.2 PES implanted per patient, and a 46+/-30 mm total PES length per patient. In-hospital MACE occurred in 39 (3.7%) patients, with 2 (0.2%) cardiac deaths, 32 (3.0%) MI, 5 (0.5%) TVR, no CABG, and 4 (0.4%) acute stent thromboses. Despite the availability of randomized trials, only carefully designed and prospective registries can provide timely and accurate assessment of the risk-benefit profile of PES in very high-risk patients. Indeed, the TRUE Study, including as much as 115 ULM and 229 bifurcation interventions, should give important insights into the outcome of PES in such an unprecedented and challenging context.

Randomized, multicenter study: on-demand versus continuous maintenance treatment with esomeprazole in patients with non-erosive gastroesophageal reflux disease.

PubMed

Bayerdörffer, Ekkehard; Bigard, Marc-Andre; Weiss, Werner; Mearin, Fermín; Rodrigo, Luis; Dominguez Muñoz, Juan Enrique; Grundling, Hennie; Persson, Tore; Svedberg, Lars-Erik; Keeling, Nanna; Eklund, Stefan

2016-04-14

Most patients with gastroesophageal reflux disease experience symptomatic relapse after stopping acid-suppressive medication. The aim of this study was to compare willingness to continue treatment with esomeprazole on-demand versus continuous maintenance therapy for symptom control in patients with non-erosive reflux disease (NERD) after 6 months. This multicenter, open-label, randomized, parallel-group study enrolled adults with NERD who were heartburn-free after 4 weeks' treatment with esomeprazole 20 mg daily. Patients received esomeprazole 20 mg daily continuously or on-demand for 6 months. The primary variable was discontinuation due to unsatisfactory treatment. On-demand treatment was considered non-inferior if the upper limit of the one-sided 95 % confidence interval (CI) for the difference between treatments was <10 %. Of 877 patients enrolled, 598 were randomized to maintenance treatment (continuous: n = 297; on-demand: n = 301). Discontinuation due to unsatisfactory treatment was 6.3 % for on-demand and 9.8 % for continuous treatment (difference -3.5 % [90 % CI: -7.1 %, 0.2 %]). In total, 82.1 and 86.2 % of patients taking on-demand and continuous therapy, respectively, were satisfied with the treatment of heartburn and regurgitation symptoms, a secondary variable (P = NS). Mean study drug consumption was 0.41 and 0.91 tablets/day, respectively. Overall, 5 % of the on-demand group developed reflux esophagitis versus none in the continuous group (P < 0.0001). The Gastrointestinal Symptom Rating Scale Reflux dimension was also improved for continuous versus on-demand treatment. Esomeprazole was well tolerated. In terms of willingness to continue treatment, on-demand treatment with esomeprazole 20 mg was non-inferior to continuous maintenance treatment and reduced medication usage in patients with NERD who had achieved symptom control with initial esomeprazole treatment. ClinicalTrials.gov identifier (NCT number): NCT02670642 ; Date of registration: December 2015.

The Adult Respiratory Distress Syndrome Cognitive Outcomes Study

PubMed Central

Christie, Jason D.; Lanken, Paul N.; Biester, Rosette C.; Thompson, B. Taylor; Bellamy, Scarlett L.; Localio, A. Russell; Demissie, Ejigayehu; Hopkins, Ramona O.; Angus, Derek C.

2012-01-01

Rationale: Cognitive and psychiatric morbidity is common and potentially modifiable after acute lung injury (ALI). However, practical measures of neuropsychological function for use in multicenter trials are lacking. Objectives: To determine whether a validated telephone-based neuropsychological test battery is feasible in a multicenter trial. To determine the frequency and risk factors for long-term neuropsychological impairment. Methods: As an adjunct study to the Acute Respiratory Distress Syndrome Clinical Trials Network Fluid and Catheter Treatment Trial, we assessed neuropsychological function at 2 and 12 months post–hospital discharge. Measurements and Main Results: Of 406 eligible survivors, we approached 261 to participate and 213 consented. We tested 122 subjects at least once, including 102 subjects at 12 months. Memory, verbal fluency, and executive function were impaired in 13% (12 of 92), 16% (15 of 96), and 49% (37 of 76) of long-term survivors. Long-term cognitive impairment was present in 41 of the 75 (55%) survivors who completed cognitive testing. Depression, post-traumatic stress disorder, or anxiety was present in 36% (37 of 102), 39% (40 of 102), and 62% (63 of 102) of long-term survivors. Enrollment in a conservative fluid-management strategy (P = 0.005) was associated with cognitive impairment and lower partial pressure of arterial oxygen during the trial was associated with cognitive (P = 0.02) and psychiatric impairment (P = 0.02). Conclusions: Neuropsychological function can be assessed by telephone in a multicenter trial. Long-term neuropsychological impairment is common in survivors of ALI. Hypoxemia is a risk factor for long-term neuropsychological impairment. Fluid management strategy is a potential risk factor for long-term cognitive impairment; however, given the select population studied and an unclear mechanism, this finding requires confirmation. PMID:22492988

Prevalence and Outcomes in Patients Undergoing Reintubation After Anterior Cervical Spine Surgery: Results From the AOSpine North America Multicenter Study on 8887 Patients.

PubMed

Nagoshi, Narihito; Fehlings, Michael G; Nakashima, Hiroaki; Tetreault, Lindsay; Gum, Jeffrey L; Smith, Zachary A; Hsu, Wellington K; Tannoury, Chadi A; Tannoury, Tony; Traynelis, Vincent C; Arnold, Paul M; Mroz, Thomas E; Gokaslan, Ziya L; Bydon, Mohamad; De Giacomo, Anthony F; Jobse, Bruce C; Massicotte, Eric M; Riew, K Daniel

2017-04-01

A multicenter, retrospective cohort study. To evaluate clinical outcomes in patients with reintubation after anterior cervical spine surgery. A total of 8887 patients undergoing anterior cervical spine surgery were enrolled in the AOSpine North America Rare Complications of Cervical Spine Surgery study. Patients with or without complications after surgery were included. Demographic and surgical information were collected for patients with reintubation. Patients were evaluated using a variety of assessment tools, including the modified Japanese Orthopedic Association scale, Nurick score, Neck Disability Index, and Short Form-36 Health Survey. Nine cases of postoperative reintubation were identified. The total prevalence of this complication was 0.10% and ranged from 0% to 0.59% across participating institutions. The time to development of airway symptoms after surgery was within 24 hours in 6 patients and between 5 and 7 days in 3 patients. Although 8 patients recovered, 1 patient died. At final follow-up, patients with reintubation did not exhibit significant and meaningful improvements in pain, functional status, or quality of life. Although the prevalence of reintubation was very low, this complication was associated with adverse clinical outcomes. Clinicians should identify their high-risk patients and carefully observe them for up to 2 weeks after surgery.

Identifying neuropathic pain in patients with multiple sclerosis: a cross-sectional multicenter study using highly specific criteria.

PubMed

Solaro, Claudio; Cella, M; Signori, Alessio; Martinelli, Vittorio; Radaelli, Marta; Centonze, D; Sica, F; Grasso, M G; Clemenzi, A; Bonavita, S; Esposito, S; Patti, F; D'Amico, E; Cruccu, G; Truini, A

2018-04-01

Pain is a common and heterogeneous complication of multiple sclerosis (MS). In this multicenter, cross sectional study, we aimed at investigating the prevalence of pain in MS using highly specific criteria for distinguishing the different types of pain. After a structured interview, in patients with pain, clinical examination and DN4 questionnaire were used for distinguishing neuropathic and nociceptive pain. In subjects with neuropathic pain, the Neuropathic Pain Symptom Inventory was used for differentiating neuropathic pain symptoms. We enrolled 1249 participants (832 F, 417 M, mean age 33.9 years, mean disease duration 8 years, mean EDSS 3.2); based on clinical evaluation and DN4 score 429 patients (34.34%) were classified with pain (470 pain syndromes): 286 nociceptive pain syndromes and 184 neuropathic pain syndromes. Multivariate analysis showed that pain was associated with age, gender and disease severity and that neuropathic pain was distinctly associated with EDSS. Our study, providing definite information on the prevalence, characteristics and variables associated with neuropathic pain due to MS, shows that a more severe disease course is associated with a higher risk of neuropathic pain. Our findings might, therefore, provide a basis for improving the clinical management of this common MS complication.

Recent effectiveness of proton pump inhibitors for severe reflux esophagitis: the first multicenter prospective study in Japan.

PubMed

Mizuno, Hideki; Matsuhashi, Nobuyuki; Sakaguchi, Masahiro; Inoue, Syuji; Nakada, Koji; Higuchi, Kazuhide; Haruma, Ken; Joh, Takashi

2015-11-01

Proton pump inhibitors are the first-line treatment for reflux esophagitis. Because severe reflux esophagitis has very low prevalence in Japan, little is known about the effectiveness of proton pump inhibitors in these patients. This prospective multicenter study assessed the effectiveness of proton pump inhibitors for severe reflux esophagitis in Japan. Patients with modified Los Angeles grade C or D reflux esophagitis were treated with daily omeprazole (10 or 20 mg), lansoprazole (15 or 30 mg), or rabeprazole (10, 20, or 40 mg) for 8 weeks. Healing was assessed endoscopically, with questionnaires administered before and after treatment to measure the extent of reflux and dyspepsia symptoms. Factors affecting healing rates, including patient characteristics and endoscopic findings, were analyzed. Of the 115 patients enrolled, 64 with grade C and 19 with grade D reflux esophagitis completed the study. The healing rate was 67.5% (56/83), with 15 of the other 27 patients (55.6%) improving to grade A or B. No patient characteristic or endoscopic comorbidity was significantly associated with healing rate. Reflux and dyspepsia symptoms improved significantly with treatment. The low healing rate suggests the need of endoscopic examination to assess healing of reflux esophagitis at the end of therapy. (UMIN000005271).

Serum reference interval of ARCHITECT alpha-fetoprotein in healthy Chinese Han adults: Sub-analysis of a prospective multi-center study.

PubMed

Yan, Cunling; Yang, Jia; Wei, Lianhua; Hu, Jian; Song, Jiaqi; Wang, Xiaoqin; Han, Ruilin; Huang, Ying; Zhang, Wei; Soh, Andrew; Beshiri, Agim; Fan, Zhuping; Zheng, Yijie; Chen, Wei

2018-02-01

Alpha-fetoprotein (AFP) has been widely used in clinical practice for decades. However, large-scale survey of serum reference interval for ARCHITECT AFP is still absent in Chinese population. This study aimed to measure serum AFP levels in healthy Chinese Han subjects, which is a sub-analysis of an ongoing prospective, cross-sectional, multi-center study (ClinicalTrials.gov Identifier: NCT03047603). This analysis included a total of 530 participants (41.43±12.14years of age on average, 48.49% males), enrolled from 5 regional centers. Serum AFP level was measured by ARCHITECT immunoassay. Statistical analysis was performed using SAS 9.4 and R software. AFP distribution did not show significant correlation with age or sex. The overall median and interquartile range of AFP was 2.87 (2.09, 3.83) ng/mL. AFP level did not show a trend of increasing with age. The new reference interval was 2.0-7.07ng/mL (LOQ- 97.5th percentiles). The reference interval for ARCHITECT AFP is updated with the data of adequate number of healthy Han adults. This new reference interval is more practical and applicable in Chinese adults. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Energy and Protein in Critically Ill Patients with AKI: A Prospective, Multicenter Observational Study Using Indirect Calorimetry and Protein Catabolic Rate.

PubMed

Sabatino, Alice; Theilla, Miriam; Hellerman, Moran; Singer, Pierre; Maggiore, Umberto; Barbagallo, Maria; Regolisti, Giuseppe; Fiaccadori, Enrico

2017-07-26

The optimal nutritional support in Acute Kidney Injury (AKI) still remains an open issue. The present study was aimed at evaluating the validity of conventional predictive formulas for the calculation of both energy expenditure and protein needs in critically ill patients with AKI. A prospective, multicenter, observational study was conducted on adult patients hospitalized with AKI in three different intensive care units (ICU). Nutrient needs were estimated by different methods: the Guidelines of the European Society of Parenteral and Enteral Nutrition (ESPEN) for both calories and proteins, the Harris-Benedict equation, the Penn-State and Faisy-Fagon equations for energy. Actual energy and protein needs were repeatedly measured by indirect calorimetry (IC) and protein catabolic rate (PCR) until oral nutrition start, hospital discharge or renal function recovery. Forty-two patients with AKI were enrolled, with 130 IC and 123 PCR measurements obtained over 654 days of artificial nutrition. No predictive formula was precise enough, and Bland-Altman plots wide limits of agreement for all equations highlight the potential to under- or overfeed individual patients. Conventional predictive formulas may frequently lead to incorrect energy and protein need estimation. In critically ill patients with AKI an increased risk for under- or overfeeding is likely when nutrient needs are estimated instead of measured.

Relationship between medication synchronization and antiretroviral adherence.

PubMed

Ghassemi, Emily; Smith, Jennifer; Owens, Laura; Herring, Charles; Holland, Melissa

2018-06-12

To compare antiretroviral adherence (measured as the proportion of days covered [PDC]) and change in viral load in insured, HIV-infected, adult outpatients enrolled and not enrolled in a medication synchronization program. This was a multicenter, retrospective, pilot cohort study. Fifty-eight insured, HIV-infected, outpatients at least 18 years of age receiving antiretroviral therapy (ART) for at least 3 months as of August 2015 were included. PDC, viral load, PDC dichotomized into adherent or nonadherent, and viral load dichotomized into detectable or undetectable were collected for each patient. Study data were compared in those with (enrolled) and without (not enrolled or control) medication synchronization. The study end points were analyzed between the 2 groups retrospectively after 3 months. PDC in patients undergoing medication synchronization was significantly higher than in control patients: mean ± SD 96 ± 9% versus 71 ± 27%, respectively (P < 0.0001). The medication synchronization group was also more likely to be adherent to ART than the control group (odds ratio 10.67, 95% confidence interval 2.63-43.31). In the medication synchronization group, 75.9% of patients had an undetectable baseline viral load, and 83.3% had an undetectable viral load at study completion. In the control group, 62.1% and 64.7% had an undetectable viral load at baseline and completion, respectively. No statistically significant change in viral load was observed between groups (P = 0.34). In insured, HIV-infected, adult outpatients, implementation of a medication synchronization program was associated with improved ART adherence. Future studies are needed to better assess the impact of medication synchronization on clinical outcomes. Copyright © 2018 American Pharmacists Association®. All rights reserved.

Czech multicenter research database of severe COPD

PubMed Central

Novotna, Barbora; Koblizek, Vladimir; Zatloukal, Jaromir; Plutinsky, Marek; Hejduk, Karel; Zbozinkova, Zuzana; Jarkovsky, Jiri; Sobotik, Ondrej; Dvorak, Tomas; Safranek, Petr

2014-01-01

Purpose Chronic obstructive pulmonary disease (COPD) has been recognized as a heterogeneous, multiple organ system-affecting disorder. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) places emphasis on symptom and exacerbation management. The aim of this study is examine the course of COPD and its impact on morbidity and all-cause mortality of patients, with respect to individual phenotypes and GOLD categories. This study will also evaluate COPD real-life patient care in the Czech Republic. Patients and methods The Czech Multicentre Research Database of COPD is projected to last for 5 years, with the aim of enrolling 1,000 patients. This is a multicenter, observational, and prospective study of patients with severe COPD (post-bronchodilator forced expiratory volume in 1 second ≤60%). Every consecutive patient, who fulfils the inclusion criteria, is asked to participate in the study. Patient recruitment is done on the basis of signed informed consent. The study was approved by the Multicentre Ethical Committee in Brno, Czech Republic. Results The objective of this paper was to outline the methodology of this study. Conclusion The establishment of the database is a useful step in improving care for COPD subjects. Additionally, it will serve as a source of data elucidating the natural course of COPD, comorbidities, and overall impact on the patients. Moreover, it will provide information on the diverse course of the COPD syndrome in the Czech Republic. PMID:25419124

PRIMARY IMMUNE DEFICIENCY TREATMENT CONSORTIUM (PIDTC) UPDATE

PubMed Central

Griffith, Linda M.; Cowan, Morton J.; Notarangelo, Luigi D.; Kohn, Donald B.; Puck, Jennifer M.; Shearer, William T.; Burroughs, Lauri M.; Torgerson, Troy R.; Decaluwe, Hélène; Haddad, Elie

2016-01-01

The Primary Immune Deficiency Treatment Consortium (PIDTC) is a collaboration of 41 North American centers studying therapy for rare primary immune deficiency diseases (PID) including Severe Combined Immune Deficiency (SCID), Wiskott-Aldrich syndrome (WAS) and chronic granulomatous disease (CGD). An additional 3 European centers have partnered with the PIDTC to study CGD. Natural history protocols of the PIDTC analyze outcomes of treatment for rare PID in multicenter longitudinal retrospective, prospective and cross-sectional studies. Since 2009, participating centers have enrolled over 800 subjects on PIDTC protocols for SCID, and enrollment on the studies in WAS and CGD is underway. Four pilot projects have been funded and 12 junior investigators have received fellowship awards. Important publications of the consortium describe outcomes of hematopoietic cell transplantation (HCT) for SCID during 2000–2009, diagnostic criteria for SCID, and the pilot project of newborn screening (NBS) for SCID in the Navajo Nation. The PIDTC Annual Scientific Workshops provide an opportunity to strengthen collaborations with junior investigators, patient advocacy groups and international colleagues. Funded by the NIAID and ORDR, NCATS, the PIDTC has recently received renewal for another 5 years. Here, we review accomplishments of the group, projects underway, highlights of recent workshops and challenges for the future. PMID:27262745

Comparison of the Performance Between Sepsis-1 and Sepsis-3 in ICUs in China: A Retrospective Multicenter Study.

PubMed

Cheng, Baoli; Li, Zhongwang; Wang, Jingya; Xie, Guohao; Liu, Xu; Xu, Zhipeng; Chu, Lihua; Zhao, Jialian; Yao, Yongming; Fang, Xiangming

2017-09-01

The definition of sepsis was updated to sepsis-3 in February 2016. However, the performance of the previous and new definition of sepsis remains unclear in China. This was a retrospective multicenter study in six intensive care unit (ICUs) from five university-affiliated hospitals to compare the performance between sepsis-1 and sepsis-3 in China. From May 1, 2016 to June 1, 2016, 496 patients were enrolled consecutively. Data were extracted from the electronic clinical records. We evaluated the performance of sepsis-1 and sepsis-3 by measuring the area under the receiver operating characteristic curves (AUROC) to predict 28-day mortality rates. Of 496 enrolled patients, 186 (37.5%) were diagnosed with sepsis according to sepsis-1, while 175 (35.3%) fulfilled the criteria of sepsis-3. The AUROC of systemic inflammatory response syndrome (SIRS) is significantly smaller than that of sequential organ failure assessment (SOFA) (0.55 [95% confidence interval, 0.46-0.64] vs. 0.69 (95% confidence interval, 0.61-0.77], P = 0.008) to predict 28-day mortality rates of infected patients. Moreover, 5.9% infected patients (11 patients) were diagnosed as sepsis according to sepsis-1 but not to sepsis-3. The APACHE II, SOFA scores, and mortality rate of the 11 patients were significantly lower than of patients whose sepsis was defined by both the previous and new criteria (8.6±3.5 vs. 16.3±6.2, P =  < 0.001; 1 (0-1) vs. 6 (4-8), P = <0.001; 0.0 vs. 33.1%, P = 0.019). In addition, the APACHE II, length of stay in ICU, and 28-day mortality rate of septic patients rose gradually corresponding with the raise in SOFA score (but not the SIRS score). Sepsis-3 performed better than sepsis-1 in the study samples in ICUs in China.

Compatibility of Biosimilar Filgrastim with Cytotoxic Chemotherapy during the Treatment of Malignant Diseases (VENICE): A Prospective, Multicenter, Non-Interventional, Longitudinal Study.

PubMed

Fruehauf, Stefan; Otremba, Burkhard; Stötzer, Oliver; Rudolph, Christine

2016-11-01

Febrile neutropenia (FN) is a serious and frequent complication of cytotoxic chemotherapy. Biosimilar filgrastim (Nivestim™, Hospira Inc, A Pfizer Company, Lake Forest, IL, USA) is a granulocyte-colony stimulating factor licensed for the treatment of neutropenia and FN induced by myelosuppressive chemotherapy. The primary goal of this VENICE study (ClinicalTrials.gov identifier, NCT01627990) was to observe the tolerability, safety and efficacy of biosimilar filgrastim in patients receiving cancer chemotherapy. This was a prospective, multicenter, non-interventional, longitudinal study. Consenting adult patients with solid tumors or hematologic malignancies for whom cytotoxic chemotherapy and treatment with biosimilar filgrastim was planned were enrolled. Among the enrolled patients (N = 386), 81% were female, with a median age (range) of 61 (22-92) years, with 39% >65 years old. Most patients (n = 338; 88%) had solid tumors and the remainder (n = 49; 13%) had hematological malignancies. The majority of the patients (64%) received biosimilar filgrastim as primary prophylaxis and 36% as secondary prophylaxis. At the follow-up visits, for the majority of patients (95.6%) there had been no change in chemotherapy dose due to FN. For two patients (0.5%) the chemotherapy was discontinued due to FN and for four patients (1.0%) the chemotherapy dose was reduced due to FN. For the majority of patients (96.9%) the chemotherapy cycle following the first biosimilar filgrastim treatment was not delayed due to FN. For 3 patients (0.8%), the chemotherapy was delayed following the first biosimilar filgrastim treatment. Less than one-third (29.8%) of the patients experienced ≥1 adverse event that was at least potentially related to biosimilar filgrastim treatment. Biosimilar filgrastim was effective and well-tolerated in both the primary and secondary prophylactic setting in patients undergoing chemotherapy for solid tumors and hematological malignancies. ClinicalTrials.gov identifier, NCT01627990. Hospira Inc, A Pfizer Company, Lake Forest, IL, USA.

Efficacy and safety of non-suture dural closure using a novel dural substitute consisting of polyglycolic acid felt and fibrin glue to prevent cerebrospinal fluid leakage-A non-controlled, open-label, multicenter clinical trial.

PubMed

Terasaka, Shunsuke; Taoka, Toshiaki; Kuroda, Satoshi; Mikuni, Nobutaka; Nishi, Toru; Nakase, Hiroyuki; Fujii, Yukihiko; Hayashi, Yasuhiko; Murata, Jun-Ichi; Kikuta, Ken-Ichiro; Kuroiwa, Toshihiko; Shimokawa, Sachie; Houkin, Kiyohiro

2017-05-01

The objective of this study is to evaluate the efficacy and safety of non-suture dural closure using a novel dural substitute (GM111) consisting of polyglycolic acid felt with a fibrin-glue-coated area commensurate in size with the dural defect. This was a non-controlled, open-label, multicenter clinical trial. The efficacy evaluation endpoints were (1) GM111's intra-operative capability to close dural defects and (2) prevention of cerebrospinal fluid (CSF) leakage and subcutaneous CSF retention throughout the postoperative period (evaluated by diagnostic imaging). Patients meeting the following three preoperative and two intra-operative selection criteria were enrolled: (1) between 12 and <75 years of age; (2) the dura is surmised to be defective and in need of reconstruction; (3) informed written consent was obtained from the patient; (4) the surgical wound is class 1; and (5) the size of duraplasty is ≥0.2 cm 2 to <100 cm 2 . Sixty patients were enrolled. The craniotomy site was supratentorial in 77.2%, infratentorial in 12.3% and sellar in 10.5%. The GM111 prosthesis size ranged from 0.24 to 42 cm 2 . To evaluate the efficacy, intra-operative closure was confirmed by Valsalva's maneuver, water infusion, etc., in all patients. CSF leakage and subcutaneous CSF retention throughout the postoperative period were found in four patients. Adverse events for which a causal relationship with GM111 could not be ruled out occurred in 8.8% of the patients. There were no instances of postoperative infection due to GM111. GM111 showed good closure capability and safety when used for non-suture dural closure.

Efficacy of a pentavalent human-bovine reassortant rotavirus vaccine against rotavirus gastroenteritis among American Indian children.

PubMed

Grant, Lindsay R; Watt, James P; Weatherholtz, Robert C; Moulton, Lawrence H; Reid, Raymond; Santosham, Mathuram; O'Brien, Katherine L

2012-02-01

Before the widespread use of rotavirus vaccines, rotavirus was a leading cause of gastroenteritis among children. Navajo and White Mountain Apache children suffer a disproportionate burden of severe rotavirus disease compared with the general U.S. population. We enrolled Navajo and White Mountain Apache infants in a multicenter, double-blind, placebo-controlled trial of pentavalent human-bovine reassortant rotavirus vaccine (PRV). Subjects received 3 doses of vaccine or placebo at 4 to 10 week intervals, with the first dose given between 6 and 12 weeks of age. Gastroenteritis episodes were identified by active surveillance. Disease severity was determined by a standardized scoring system. There were 509 and 494 randomized children who received vaccine and placebo, respectively. Among placebo recipients, the incidence of rotavirus gastroenteritis was 34.2 episodes/100 child-years (95% confidence interval [95% CI]: 25.8-38.9) versus 8.1 episodes/100 child-years (95% CI: 5.4-12.5) in the vaccine group. The percentage of rotavirus episodes caused by serotypes G1, G2, and G3 was 72.3%, 23.4%, and 2.1%, respectively. There were no severe rotavirus episodes among vaccinees and 4 among placebo recipients. PRV was 77.1% (95% CI: 59.7-87.6), 89.5% (95% CI: 65.9-97.9), and 82.9% (95% CI: 61.1-93.6) effective against G1-G4 rotavirus disease, severe and moderate rotavirus disease combined, and outpatient visits for rotavirus disease, respectively. The risk of adverse events was similar for the vaccine and placebo groups. PRV was highly effective in preventing rotavirus disease and related health care utilization in these American Indian infants. Vaccine efficacy and immunogenicity were similar to the overall study population enrolled in the multicenter trial.

Toward evidence-based diagnosis of myocarditis in children and adolescents: Rationale, design, and first baseline data of MYKKE, a multicenter registry and study platform.

PubMed

Messroghli, Daniel R; Pickardt, Thomas; Fischer, Marcus; Opgen-Rhein, Bernd; Papakostas, Konstantin; Böcker, Dorothée; Jakob, André; Khalil, Markus; Mueller, Goetz C; Schmidt, Florian; Kaestner, Michael; Udink Ten Cate, Floris E A; Wagner, Robert; Ruf, Bettina; Kiski, Daniela; Wiegand, Gesa; Degener, Franziska; Bauer, Ulrike M M; Friede, Tim; Schubert, Stephan

2017-05-01

The aim of this registry is to provide data on age-related clinical features of suspected myocarditis and to create a study platform allowing for deriving diagnostic criteria and, at a later stage, testing therapeutic interventions in patients with myocarditis. After an initial 6-month pilot phase, MYKKE was opened in June 2014 as a prospective multicenter registry for patients from pediatric heart centers, university hospitals, and community hospitals with pediatric cardiology wards in Germany. Inclusion criteria consisted of age<18 years and hospitalization for suspected myocarditis as leading diagnosis at the discretion of the treating physician. By December 31, 2015, fifteen centers across Germany were actively participating and had enrolled 149 patients. Baseline data reveal 2 age peaks (<2 years, >12 years), show higher proportions of males, and document a high prevalence of severe disease courses in pediatric patients with suspected myocarditis. Severe clinical courses and early adverse events were more prevalent in younger patients and were related to severely impaired leftventricular ejection fraction at initial presentation. MYKKE represents a multicenter registry and research platform for children and adolescents with suspected myocarditis that achieve steady recruitment and generate a wide range of real-world data on clinical course, diagnostic workup, and treatment of this group of patients. The baseline data reveal the presence of 2 age peaks and provide important insights into the severity of disease in children with suspected myocarditis. In the future, MYKKE might facilitate interventional substudies by providing an established collaborating network using common diagnostic approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment of iron deficiency and anemia in pregnant women: an observational French study.

PubMed

Harvey, Thierry; Zkik, Asmaa; Auges, Marie; Clavel, Thierry

2016-01-01

We explored the prevalence and management of iron deficiency and anemia among pregnant women in France. In this prospective, observational, multicenter registry study, randomly selected investigators (gynecologists/obstetricians/midwives registered in the CEGEDIM(®) database) assessed pregnant women presenting for a consultation. Participants completed a questionnaire at study inclusion. A total of 1506 patients were enrolled by 95 investigators. Overall, investigators estimated a moderate or significant risk of iron deficiency in almost 60% of women. The overall prevalence of anemia (15.8%) increased with longer pregnancy duration. Medication (mainly iron-based) was prescribed to 57.3% of patients. In French clinical practice, the estimated risk of iron deficiency and prevalence of anemia during pregnancy align with expectations and are managed according to national/international recommendations.

Predictors of Relapse after Discontinuing Systemic Treatment in Childhood Autoimmune Chronic Uveitis.

PubMed

Simonini, Gabriele; Bracaglia, Claudia; Cattalini, Marco; Taddio, Andrea; Brambilla, Alice; De Libero, Cinzia; Pires Marafon, Denise; Caputo, Roberto; Cimaz, Rolando

2017-06-01

To identify clinical predictors of relapse in childhood autoimmune chronic uveitis after stopping systemic treatment. A retrospective, multicenter, cohort study. Ninety-four children in remission, receiving no treatments and with at least a 6-month followup, were enrolled. A higher probability of maintaining remission after discontinuing treatment was shown in idiopathic compared with juvenile idiopathic arthritis uveitis (Mantel-Cox chi-square = 23.21) if inactivity had been obtained within 6 months from starting systemic treatment (Mantel-Cox chi-square = 24.17) and by antitumor necrosis factor-α treatment (Mantel-Cox chi-square = 6.43). Type of disease, time, and type of systemic therapy to achieve inactivity predict different duration of uveitis remission after treatment withdrawal.

Nutritional status affects treatment tolerability and survival in metastatic colorectal cancer patients: results of an AGEO prospective multicenter study.

PubMed

Barret, Maximilien; Malka, David; Aparicio, Thomas; Dalban, Cécile; Locher, Christophe; Sabate, Jean-Marc; Louafi, Samy; Mansourbakht, Touraj; Bonnetain, Franck; Attar, Alain; Taieb, Julien

2011-01-01

The possible impact of malnutrition on the tolerability and efficacy of modern chemotherapy regimens for metastatic colorectal cancer (mCRC) is unclear. In this prospective, cross-sectional, multicenter study, we collected demographic, oncological and nutritional data for all consecutive mCRC patients during a 14-day period in eight hospitals. Nutritional status was assessed with the nutritional risk index (NRI), and patients were classified as severely malnourished when NRI was <83.5; drug-induced toxicities were evaluated using the National Cancer Institute Common Toxicity Criteria (version 3.0). Survival times were calculated from the date of the nutritional assessment. We enrolled 114 mCRC patients (median age: 65 years, range: 22-92; WHO performance status 0/1/2/3: 21/54/21/4%) of whom 88% had at least 2 metastatic sites and 49% were receiving chemotherapy as first-line treatment. Malnutrition was diagnosed in 65% of the patients and was severe in 19%. Severe malnutrition was associated with more adverse effects following chemotherapy (p = 0.01) and with shorter median overall survival (14.0 vs. 36.2 months in non-/moderately malnourished patients, p = 0.02). In mCRC patients, severe malnutrition is associated with greater chemotherapy toxicity and reduced overall survival. Copyright © 2012 S. Karger AG, Basel.

A multicenter, randomized, controlled clinical trial evaluating the use of dehydrated human amnion/chorion membrane allografts and multilayer compression therapy vs. multilayer compression therapy alone in the treatment of venous leg ulcers.

PubMed

Serena, Thomas E; Carter, Marissa J; Le, Lam T; Sabo, Matthew J; DiMarco, Daniel T

2014-01-01

Venous leg ulcers produce significant clinical and economic burdens on society and often require advanced wound therapy. The purpose of this multicenter, randomized, controlled study is to evaluate the safety and efficacy of one or two applications of dehydrated human amnion/chorion membrane allograft and multilayer compression therapy vs. multilayer compression therapy alone in the treatment of venous leg ulcers. The primary study outcome was the proportion of patients achieving 40% wound closure at 4 weeks. Of the 84 participants enrolled, 53 were randomized to receive allograft and 31 were randomized to the control group of multilayer compression therapy alone. At 4 weeks, 62% in the allograft group and 32% in the control group showed a greater than 40% wound closure (p = 0.005), thus showing a significant difference between the allograft-treated groups and the multilayer compression therapy alone group at the 4-week surrogate endpoint. After 4 weeks, wounds treated with allograft had reduced in size a mean of 48.1% compared with 19.0% for controls. Venous leg ulcers treated with allograft had a significant improvement in healing at 4 weeks compared with multilayer compression therapy alone. © 2014 by the Wound Healing Society.

Chronic gastritis in China: a national multi-center survey

PubMed Central

2014-01-01

Background Chronic gastritis is one of the most common findings at upper endoscopy in the general population, and chronic atrophic gastritis is epidemiologically associated with the occurrence of gastric cancer. However, the current status of diagnosis and treatment of chronic gastritis in China is unclear. Methods A multi-center national study was performed; all patients who underwent diagnostic upper endoscopy for evaluation of gastrointestinal symptoms from 33 centers were enrolled. Data including sex, age, symptoms and endoscopic findings were prospectively recorded. Results Totally 8892 patients were included. At endoscopy, 4389, 3760 and 1573 patients were diagnosed to have superficial gastritis, erosive gastritis, and atrophic gastritis, respectively. After pathologic examination, it is found that atrophic gastritis, intestinal metaplasia and dysplasia were prevalent, which accounted for 25.8%, 23.6% and 7.3% of this patient population. Endoscopic features were useful for predicting pathologic atrophy (PLR = 4.78), but it was not useful for predicting erosive gastritis. Mucosal-protective agents and PPI were most commonly used medications for chronic gastritis. Conclusions The present study suggests non-atrophic gastritis is the most common endoscopic finding in Chinese patients with upper GI symptoms. Precancerous lesions, including atrophy, intestinal metaplasia and dysplasia are prevalent in Chinese patients with chronic gastritis, and endoscopic features are useful for predicting pathologic atrophy. PMID:24502423

Chronic gastritis in China: a national multi-center survey.

PubMed

Du, Yiqi; Bai, Yu; Xie, Pei; Fang, Jingyuan; Wang, Xiaozhong; Hou, Xiaohua; Tian, Dean; Wang, Chengdang; Liu, Yandi; Sha, Weihong; Wang, Bangmao; Li, Yanqing; Zhang, Guoliang; Li, Yan; Shi, Ruihua; Xu, Jianming; Li, Youming; Huang, Minghe; Han, Shengxi; Liu, Jie; Ren, Xu; Xie, Pengyan; Wang, Zhangliu; Cui, Lihong; Sheng, Jianqiu; Luo, Hesheng; Wang, Zhaohui; Zhao, Xiaoyan; Dai, Ning; Nie, Yuqiang; Zou, Yiyou; Xia, Bing; Fan, Zhining; Chen, Zhitan; Lin, Sanren; Li, Zhao-Shen

2014-02-07

Chronic gastritis is one of the most common findings at upper endoscopy in the general population, and chronic atrophic gastritis is epidemiologically associated with the occurrence of gastric cancer. However, the current status of diagnosis and treatment of chronic gastritis in China is unclear. A multi-center national study was performed; all patients who underwent diagnostic upper endoscopy for evaluation of gastrointestinal symptoms from 33 centers were enrolled. Data including sex, age, symptoms and endoscopic findings were prospectively recorded. Totally 8892 patients were included. At endoscopy, 4389, 3760 and 1573 patients were diagnosed to have superficial gastritis, erosive gastritis, and atrophic gastritis, respectively. After pathologic examination, it is found that atrophic gastritis, intestinal metaplasia and dysplasia were prevalent, which accounted for 25.8%, 23.6% and 7.3% of this patient population. Endoscopic features were useful for predicting pathologic atrophy (PLR = 4.78), but it was not useful for predicting erosive gastritis. Mucosal-protective agents and PPI were most commonly used medications for chronic gastritis. The present study suggests non-atrophic gastritis is the most common endoscopic finding in Chinese patients with upper GI symptoms. Precancerous lesions, including atrophy, intestinal metaplasia and dysplasia are prevalent in Chinese patients with chronic gastritis, and endoscopic features are useful for predicting pathologic atrophy.

Effect of Kangfuxin Solution on Chemo/Radiotherapy-Induced Mucositis in Nasopharyngeal Carcinoma Patients: A Multicenter, Prospective Randomized Phase III Clinical Study

PubMed Central

Luo, Yangkun; Feng, Mei; Fan, Zixuan; Zhu, Xiaodong; Jin, Feng; Li, Rongqing; Wu, Jingbo; Yang, Xia; Jiang, Qinghua; Bai, Hongfang; Huang, Yecai; Lang, Jinyi

2016-01-01

Objective. To evaluate the efficacy and safety of Kangfuxin Solution, a pure Chinese herbal medicine, on mucositis induced by chemoradiotherapy in nasopharyngeal carcinoma patients. Methods. A randomized, parallel-group, multicenter clinical study was performed. A total of 240 patients were randomized to receive either Kangfuxin Solution (test group) or compound borax gargle (control group) during chemoradiotherapy. Oral mucositis, upper gastrointestinal mucositis, and oral pain were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and the Verbal Rating Scale (VRS). Results. Of 240 patients enrolled, 215 were eligible for efficacy analysis. Compared with the control group, the incidence and severity of oral mucositis in the test group were significantly reduced (P = 0.01). The time to different grade of oral mucositis occurrence (grade 1, 2, or 3) was longer in test group (P < 0.01), and the accumulated radiation dose was also higher in test group comparing to the control group (P < 0.05). The test group showed lower incidence of oral pain and gastrointestinal mucositis than the control group (P < 0.01). No significant adverse events were observed. Conclusion. Kangfuxin Solution demonstrated its superiority to compound borax gargle on mucositis induced by chemoradiotherapy. Its safety is acceptable for clinical application. PMID:27375766

Clinical Profile, Etiology, and Treatment of Chronic Pancreatitis in North American Women: Analysis of a Large Multicenter Cohort.

PubMed

Romagnuolo, Joseph; Talluri, Jyothsna; Kennard, Elizabeth; Sandhu, Bimaljit S; Sherman, Stuart; Cote, Gregory A; Al-Kaade, Samer; Gardner, Timothy B; Gelrud, Andres; Lewis, Michele D; Forsmark, Christopher E; Guda, Nalini M; Conwell, Darwin L; Banks, Peter A; Muniraj, Thiruvengadam; Wisniewski, Stephen R; Tian, Ye; Wilcox, C Mel; Anderson, Michelle A; Brand, Randall E; Slivka, Adam; Whitcomb, David C; Yadav, Dhiraj

2016-08-01

Historically, chronic pancreatitis (CP) was considered a disease of alcoholic males, but recent data suggest its etiology to be complex. To better understand CP in women, we compared data on women and men with CP in a large, prospectively ascertained multicenter US cohort. Patients with CP enrolled in the NAPS2 Continuation and Validation study were studied. Information on demographics, etiology, risk factors, phenotype, and treatment(s) used was obtained from detailed questionnaires completed by the patients and physicians. Of 521 cases, 45% were women. Women were significantly (P < 0.05) less likely to have alcohol etiology (30% vs 58.5%) and more likely to have nonalcoholic etiologies (idiopathic, 32% vs 18%; obstructive, 12% vs 2.4%; genetic, 12.8% vs 7.3%). Demographics, pain experience, morphologic findings, exocrine and endocrine insufficiency, CP-related disability, and use of medical therapies were mostly similar in both sexes. Sphincterotomy (biliary, 33% vs 24%; pancreatic, 38% vs 28%; P < 0.05) was performed more frequently in women, whereas cyst/pseudocyst operations were more common in men (6.6 vs 2.6%, P = 0.02). Most CP cases in women are from nonalcoholic etiologies. In contrast to many other chronic diseases, clinical phenotype of CP is determined by the disease and is independent of sex.

A prospective, multi-center study of the chocolate balloon in femoropopliteal peripheral artery disease: The Chocolate BAR registry.

PubMed

Mustapha, Jihad A; Lansky, Alexandra; Shishehbor, Mehdi; Miles McClure, John; Johnson, Sarah; Davis, Thomas; Makam, Prakash; Crowder, William; Konstantino, Eitan; Attaran, Robert R

2018-05-01

The Chocolate BAR study is a prospective multicenter post-market registry designed to evaluate the safety and performance of the Chocolate percutaneous transluminal angioplasty balloon catheter in a broad population with symptomatic peripheral arterial disease. The primary endpoint is acute procedural success (defined as ≤30% residual stenosis without flow-limiting dissection); secondary long-term outcomes include freedom from target lesion revascularization (TLR), major unplanned amputation, survival, and patency. A total of 262 patients (290 femoropopliteal lesions) were enrolled at 30 US centers between 2012 and 2014. The primary endpoint of procedure success was achieved in 85.1% of cases, and freedom from stenting occurred in 93.1%. Bail out stenting by independent adjudication occurred in 1.6% of cases and there were no flow limiting dissections. There was mean improvement of 2.1 Rutherford classes (±1.5) at 12-months, with 78.5% freedom from TLR, 97.2% freedom from major amputation, and 93.3% freedom from all-cause mortality. Core Lab adjudicated patency was 64.1% at 12 months. Use of the Chocolate balloon in an "all-comers" population achieved excellent procedural outcomes with low dissection rates and bailout stent use. © 2018 Wiley Periodicals, Inc.

Effective symptomatic treatment for severe and intractable pruritus associated with severe burn-induced hypertrophic scars: A prospective, multicenter, controlled trial.

PubMed

Wu, Jun; Xu, Rui; Zhan, Rixing; Luo, Gaoxing; Niu, Xihua; Liu, Yi; Lee, Benjamin Tak-Kwong; Flury, Meinrad; Wong, Chun-Ho; Fok, Manson; Lau, Johnson Yiu-Nam

2016-08-01

Burn-induced hypertrophic scars are disfiguring and can be associated with severe and intractable pruritus. No effective treatment modalities are currently available for symptomatic control of pruritus for most patients. We assessed the effect of the Antipruritic Hydrogel (CQ-01) in the symptomatic treatment of severe and intractable pruritus associated with burn-induced hypertrophic scars in a prospective, multicenter, controlled trial. A pilot study was conducted in healthy adult volunteers to identify the most appropriate hydrogel formulation. A selected preparation called Chongqing No. 1 (CQ-01; a guar gum-based hydrogel impregnated with peppermint oil, menthol, and methyl salicylate by a nanoemulsion), showed an excellent symptomatic relief in an exploratory study in 2 patients with intractable pruritus. A statistically powered, prospective, multicenter, controlled study was then conducted in 74 patients to evaluate the efficacy and safety of a 24-h application of CQ-01 compared to a gel control and a negative control on three separate areas in each patient. Symptom assessment was based on our visual analog JW scale (ranging from 0 to 100) at baseline and various time points up to 7 days after application. Follow-up studies were conducted to determine the reproducibility of CQ-01 in repeated applications. Of the 74 enrolled subjects, the only observed adverse event was skin irritation reported in 6 patients (8%) and resolved shortly after gel removal. Compared to the baseline, the gauze negative control had a mean JW score reduction of 7; while the gel control and CQ-01 had a drop of 18 (p<0.001) and 36 (p<0.001), respectively. The CQ-01 clinical effect was significant for up to 3 days and waned slowly from 3 to 7 days. There was no statistical correlation between the treatment response and any of the demographic, patient or burn-related factors. Further studies showed a trend that repeated applications might be more effective, suggesting the absence of tachyphylaxis. This prospective, multicenter, controlled study showed that this novel hydrogel CQ-01 is safe and provides significant symptomatic relief for severe and intractable pruritus associated with hypertrophic scars, an unmet medical need for these patients. This effect is independent of the etiology of the burn trauma, extent of the scarring, and duration of the scar formation. Copyright © 2016. Published by Elsevier Ltd.

A multicenter, randomized, controlled trial of osteopathic manipulative treatment on preterms.

PubMed

Cerritelli, Francesco; Pizzolorusso, Gianfranco; Renzetti, Cinzia; Cozzolino, Vincenzo; D'Orazio, Marianna; Lupacchini, Mariacristina; Marinelli, Benedetta; Accorsi, Alessandro; Lucci, Chiara; Lancellotti, Jenny; Ballabio, Silvia; Castelli, Carola; Molteni, Daniela; Besana, Roberto; Tubaldi, Lucia; Perri, Francesco Paolo; Fusilli, Paola; D'Incecco, Carmine; Barlafante, Gina

2015-01-01

Despite some preliminary evidence, it is still largely unknown whether osteopathic manipulative treatment improves preterm clinical outcomes. The present multi-center randomized single blind parallel group clinical trial enrolled newborns who met the criteria for gestational age between 29 and 37 weeks, without any congenital complication from 3 different public neonatal intensive care units. Preterm infants were randomly assigned to usual prenatal care (control group) or osteopathic manipulative treatment (study group). The primary outcome was the mean difference in length of hospital stay between groups. A total of 695 newborns were randomly assigned to either the study group (n= 352) or the control group (n=343). A statistical significant difference was observed between the two groups for the primary outcome (13.8 and 17.5 days for the study and control group respectively, p<0.001, effect size: 0.31). Multivariate analysis showed a reduction of the length of stay of 3.9 days (95% CI -5.5 to -2.3, p<0.001). Furthermore, there were significant reductions with treatment as compared to usual care in cost (difference between study and control group: 1,586.01€; 95% CI 1,087.18 to 6,277.28; p<0.001) but not in daily weight gain. There were no complications associated to the intervention. Osteopathic treatment reduced significantly the number of days of hospitalization and is cost-effective on a large cohort of preterm infants.

Prevalence and Outcomes in Patients Undergoing Reintubation After Anterior Cervical Spine Surgery: Results From the AOSpine North America Multicenter Study on 8887 Patients

PubMed Central

Nagoshi, Narihito; Nakashima, Hiroaki; Tetreault, Lindsay; Gum, Jeffrey L.; Smith, Zachary A.; Hsu, Wellington K.; Tannoury, Chadi A.; Tannoury, Tony; Traynelis, Vincent C.; Arnold, Paul M.; Mroz, Thomas E.; Gokaslan, Ziya L.; Bydon, Mohamad; De Giacomo, Anthony F.; Jobse, Bruce C.; Massicotte, Eric M.; Riew, K. Daniel

2017-01-01

Study Design: A multicenter, retrospective cohort study. Objective: To evaluate clinical outcomes in patients with reintubation after anterior cervical spine surgery. Methods: A total of 8887 patients undergoing anterior cervical spine surgery were enrolled in the AOSpine North America Rare Complications of Cervical Spine Surgery study. Patients with or without complications after surgery were included. Demographic and surgical information were collected for patients with reintubation. Patients were evaluated using a variety of assessment tools, including the modified Japanese Orthopedic Association scale, Nurick score, Neck Disability Index, and Short Form-36 Health Survey. Results: Nine cases of postoperative reintubation were identified. The total prevalence of this complication was 0.10% and ranged from 0% to 0.59% across participating institutions. The time to development of airway symptoms after surgery was within 24 hours in 6 patients and between 5 and 7 days in 3 patients. Although 8 patients recovered, 1 patient died. At final follow-up, patients with reintubation did not exhibit significant and meaningful improvements in pain, functional status, or quality of life. Conclusions: Although the prevalence of reintubation was very low, this complication was associated with adverse clinical outcomes. Clinicians should identify their high-risk patients and carefully observe them for up to 2 weeks after surgery. PMID:28451501

Cerebral Oximetry Monitoring to Maintain Normal Cerebral Oxygen Saturation during High-risk Cardiac Surgery: A Randomized Controlled Feasibility Trial.

PubMed

Deschamps, Alain; Hall, Richard; Grocott, Hilary; Mazer, C David; Choi, Peter T; Turgeon, Alexis F; de Medicis, Etienne; Bussières, Jean S; Hudson, Christopher; Syed, Summer; Seal, Doug; Herd, Stuart; Lambert, Jean; Denault, André; Deschamps, Alain; Mutch, Alan; Turgeon, Alexis; Denault, Andre; Todd, Andrea; Jerath, Angela; Fayad, Ashraf; Finnegan, Barry; Kent, Blaine; Kennedy, Brent; Cuthbertson, Brian H; Kavanagh, Brian; Warriner, Brian; MacAdams, Charles; Lehmann, Christian; Fudorow, Christine; Hudson, Christopher; McCartney, Colin; McIsaac, Dan; Dubois, Daniel; Campbell, David; Mazer, David; Neilpovitz, David; Rosen, David; Cheng, Davy; Drapeau, Dennis; Dillane, Derek; Tran, Diem; Mckeen, Dolores; Wijeysundera, Duminda; Jacobsohn, Eric; Couture, Etienne; de Medicis, Etienne; Alam, Fahad; Abdallah, Faraj; Ralley, Fiona E; Chung, Frances; Lellouche, Francois; Dobson, Gary; Germain, Genevieve; Djaiani, George; Gilron, Ian; Hare, Gregory; Bryson, Gregory; Clarke, Hance; McDonald, Heather; Roman-Smith, Helen; Grocott, Hilary; Yang, Homer; Douketis, James; Paul, James; Beaubien, Jean; Bussières, Jean; Pridham, Jeremy; Armstrong, J N; Parlow, Joel; Murkin, John; Gamble, Jonathan; Duttchen, Kaylene; Karkouti, Keyvan; Turner, Kim; Baghirzada, Leyla; Szabo, Linda; Lalu, Manoj; Wasowicz, Marcin; Bautista, Michael; Jacka, Michael; Murphy, Michael; Schmidt, Michael; Verret, Michaël; Perrault, Michel-Antoine; Beaudet, Nicolas; Buckley, Norman; Choi, Peter; MacDougall, Peter; Jones, Philip; Drolet, Pierre; Beaulieu, Pierre; Taneja, Ravi; Martin, Rene; Hall, Richard; George, Ronald; Chun, Rosa; McMullen, Sarah; Beattie, Scott; Sampson, Sonia; Choi, Stephen; Kowalski, Stephen; McCluskey, Stuart; Syed, Summer; Boet, Sylvain; Ramsay, Tim; Saha, Tarit; Mutter, Thomas; Chowdhury, Tumul; Uppal, Vishal; Mckay, William

2016-04-01

Cerebral oxygen desaturation during cardiac surgery has been associated with adverse perioperative outcomes. Before a large multicenter randomized controlled trial (RCT) on the impact of preventing desaturations on perioperative outcomes, the authors undertook a randomized prospective, parallel-arm, multicenter feasibility RCT to determine whether an intervention algorithm could prevent desaturations. Eight Canadian sites randomized 201 patients between April 2012 and October 2013. The primary outcome was the success rate of reversing cerebral desaturations below 10% relative to baseline in the intervention group. Anesthesiologists were blinded to the cerebral saturation values in the control group. Intensive care unit personnel were blinded to cerebral saturation values for both groups. Secondary outcomes included the area under the curve of cerebral desaturation load, enrolment rates, and a 30-day follow-up for adverse events. Cerebral desaturations occurred in 71 (70%) of the 102 intervention group patients and 56 (57%) of the 99 control group patients (P = 0.04). Reversal was successful in 69 (97%) of the intervention group patients. The mean cerebral desaturation load (SD) in the operating room was smaller for intervention group patients compared with control group patients (104 [217] %.min vs. 398 [869] %.min, mean difference, -294; 95% CI, -562 to -26; P = 0.03). This was also true in the intensive care unit (P = 0.02). There were no differences in adverse events between the groups. Study sites were successful in reversal of desaturation, patient recruitment, randomization, and follow-up in cardiac surgery, supporting the feasibility of conducting a large multicenter RCT.

Realizing effectiveness across continents with hydroxyurea: Enrollment and baseline characteristics of the multicenter REACH study in Sub-Saharan Africa.

PubMed

McGann, Patrick T; Williams, Thomas N; Olupot-Olupot, Peter; Tomlinson, George A; Lane, Adam; Luís Reis da Fonseca, José; Kitenge, Robert; Mochamah, George; Wabwire, Ham; Stuber, Susan; Howard, Thad A; McElhinney, Kathryn; Aygun, Banu; Latham, Teresa; Santos, Brígida; Tshilolo, Léon; Ware, Russell E

2018-08-01

Despite its well-described safety and efficacy in the treatment of sickle cell anemia (SCA) in high-income settings, hydroxyurea remains largely unavailable in sub-Saharan Africa, where more than 75% of annual SCA births occur and many comorbidities exist. Realizing Effectiveness Across Continents with Hydroxyurea (REACH, ClinicalTrials.gov NCT01966731) is a prospective, Phase I/II open-label trial of hydroxyurea designed to evaluate the feasibility, safety, and benefits of hydroxyurea treatment for children with SCA in four sub-Saharan African countries. Following comprehensive training of local research teams, REACH was approved by local Ethics Committees and achieved full enrollment ahead of projections with 635 participants enrolled over a 30-month period, despite half of families living >12 km from their clinical site. At enrollment, study participants (age 5.4 ± 2.4 years) had substantial morbidity, including a history of vaso-occlusive pain (98%), transfusion (68%), malaria (85%), and stroke (6%). Significant differences in laboratory characteristics were noted across sites, with lower hemoglobin concentrations (P < .01) in Angola (7.2 ± 1.0 g/dL) and the DRC (7.0 ± 0.9 g/dL) compared to Kenya (7.4 ± 1.1 g/dL) and Uganda (7.5 ± 1.1 g/dL). Analysis of known genetic modifiers of SCA demonstrated a high frequency of α-thalassemia (58.4% with at least a single α-globin gene deletion) and G6PD deficiency (19.7% of males and 2.4% of females) across sites. The CAR β-globin haplotype was present in 99% of participants. The full enrollment to REACH confirms the feasibility of conducting high-quality SCA research in Africa; this study will provide vital information to guide safe and effective dosing of hydroxyurea for children with SCA living in Africa. © 2018 Wiley Periodicals, Inc.

Lung-protective Ventilation in Patients with Brain Injury: A Multicenter Cross-sectional Study and Questionnaire Survey in China

PubMed Central

Luo, Xu-Ying; Hu, Ying-Hong; Cao, Xiang-Yuan; Kang, Yan; Liu, Li-Ping; Wang, Shou-Hong; Yu, Rong-Guo; Yu, Xiang-You; Zhang, Xia; Li, Bao-Shan; Ma, Zeng-Xiang; Weng, Yi-Bing; Zhang, Heng; Chen, De-Chang; Chen, Wei; Chen, Wen-Jin; Chen, Xiu-Mei; Du, Bin; Duan, Mei-Li; Hu, Jin; Huang, Yun-Feng; Jia, Gui-Jun; Li, Li-Hong; Liang, Yu-Min; Qin, Bing-Yu; Wang, Xian-Dong; Xiong, Jian; Yan, Li-Mei; Yang, Zheng-Ping; Dong, Chen-Ming; Wang, Dong-Xin; Zhan, Qing-Yuan; Fu, Shuang-Lin; Zhao, Lin; Huang, Qi-Bing; Xie, Ying-Guang; Huang, Xiao-Bo; Zhang, Guo-Bin; Xu, Wang-Bin; Xu, Yuan; Liu, Ya-Ling; Zhao, He-Ling; Sun, Rong-Qing; Sun, Ming; Cheng, Qing-Hong; Qu, Xin; Yang, Xiao-Feng; Xu, Ming; Shi, Zhong-Hua; Chen, Han; He, Xuan; Yang, Yan-Lin; Chen, Guang-Qiang; Sun, Xiu-Mei; Zhou, Jian-Xin

2016-01-01

Background: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. Methods: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. Results: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0–8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5–6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. Conclusions: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. Trial Registration: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073. PMID:27411450

Gender indexing in publications of clinical trials: 1991-2008.

PubMed

Drye, Lea T; Meinert, Jill L; Meinert, Curtis L

2010-12-01

In 1993 Congress passed the NIH Revitalization Act, which instructed the Director of the NIH to ensure that phase III clinical trials are 'designed and carried out in a manner sufficient to provide for a valid analysis of whether the variables being studied in the trial affect females or members of minority groups, as the case may be, differently than other subjects in the trial.' The purpose of this article is to track the PubMed indexing of gender in clinical trial publications since 1991 with a view toward assessing the impact of the legislation on the number of gender specific trials. We searched PubMed for full-length publications from years 1991 to 2008 of research on humans indexed as publication type 'clinical trial', 'randomized clinical trial' and multicenter randomized trial ('multicenter study' AND 'randomized clinical trial'), and counted the number of trials indexed as male-only, female-only, male and female, and gender unknown in PubMed. The majority of trial publications were indexed in PubMed as including both genders. The proportion of publications indexed as including both genders has increased while the number of publications not indexed with respect to gender and the number of publications indexed as male-only have decreased. In 2005, approximately 13% of NIH expenditures were for female specific or related research compared to 6% for male specific or related research. The proportion of clinical trial publications that were indexed in PubMed as including females began to increase before the legislation so it is difficult to conclude that changes in the number of female-only or male-only trials are due to the legislation. PubMed listings do not include gender enrollment, so female and male enrollment totals could not be compared. The NIH policy should be rewritten to be made gender neutral to bring it in line with the principle of justice as embodied in the Belmont Report.

Risk Factors for Malnutrition among Older Adults in the Emergency Department: A Multicenter Study.

PubMed

Burks, Collin E; Jones, Christopher W; Braz, Valerie A; Swor, Robert A; Richmond, Natalie L; Hwang, Kay S; Hollowell, Allison G; Weaver, Mark A; Platts-Mills, Timothy F

2017-08-01

Among older adults, malnutrition is common, often missed by healthcare providers, and influences recovery from illness or injury. To identify modifiable risk factors associated with malnutrition in older patients. Prospective cross-sectional multicenter study. 3 EDs in the South, Northeast, and Midwest. Non-critically ill, English-speaking adults aged ≥65 years. Random time block sampling was used to enroll patients. The ED interview assessed malnutrition using the Mini Nutritional Assessment Short-Form. Food insecurity and poor oral health were assessed using validated measures. Other risk factors examined included depressive symptoms, limited mobility, lack of transportation, loneliness, and medication side effects, qualified by whether the patient reported the risk factor affected their diet. The population attributable risk proportion (PARP) for malnutrition was estimated for each risk factor. In our sample (n = 252), the prevalence of malnutrition was 12%. Patient characteristics associated with malnutrition included not having a college degree, being admitted to the hospital, and residence in an assisted living facility. Of the risk factors examined, the PARPs for malnutrition were highest for poor oral health (54%; 95% CI 16%, 78%), food insecurity (14%; 95% CI 3%, 31%), and lack of transportation affecting diet (12%; 95% CI 3%, 28%). Results of this observational study identify multiple modifiable factors associated with the problem of malnutrition in older adults. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

A prospective multicenter study on self-expandable metallic stents as a bridge to surgery for malignant colorectal obstruction in Japan: efficacy and safety in 312 patients.

PubMed

Saito, Shuji; Yoshida, Shuntaro; Isayama, Hiroyuki; Matsuzawa, Takeaki; Kuwai, Toshio; Maetani, Iruru; Shimada, Mamoru; Yamada, Tomonori; Tomita, Masafumi; Koizumi, Koichi; Hirata, Nobuto; Kanazawa, Hideki; Enomoto, Toshiyuki; Sekido, Hitoshi; Saida, Yoshihisa

2016-09-01

Endoscopic stenting with a self-expandable metallic stent (SEMS) is a widely accepted procedure for malignant colonic obstruction. The Colonic Stent Safe Procedure Research Group conducted the present prospective feasibility study. Our objectives were to estimate the safety and feasibility of SEMS placement as a bridge to surgery (BTS) for malignant colorectal obstruction. We conducted a prospective, observational, single-arm, multicenter clinical trial from March 2012 to October 2013. Each patient was treated with an uncovered WallFlex enteral colonic stent. Patients were followed up until discharge after surgery. A total of 518 consecutive patients were enrolled in this study. The cohort intended for BTS consisted of 312 patients (61 %), and the stent could be released in 305 patients. Technical and clinical success rates were 98 and 92 %, respectively. Elective surgery was performed in 297 patients, and emergency surgery was performed in eight patients for the treatment of complications. The overall preoperative complication rate was 7.2 %. Major complications, including perforation, occurred in 1.6 %, persistent colonic obstruction occurred in 1.0 %, and stent migration occurred in 1.3 % patients. The median time from SEMS to surgery was 16 days. Silent perforations were observed in 1.3 %. Open and laparoscopic surgery was performed in 121 and 184 patients, respectively. The tumor could be resected in 297 patients. The primary anastomosis rate was 92 %. The rate of anastomotic leakage was 4 %, and the overall stoma creation rate was 10 %. The median duration of hospitalization following surgery was 12 days. Overall postoperative morbidity and mortality rates were 16 and 0.7 %, respectively. This largest, multicenter, prospective study demonstrates the feasibility of SEMS placement as a BTS for malignant colorectal obstruction. SEMS serves as a safe and effective BTS with acceptable stoma creation and complication rates in patients with acute malignant colonic obstruction.

Verteporfin therapy in age-related macular degeneration (VAM): an open-label multicenter photodynamic therapy study of 4,435 patients.

PubMed

Bessler, Neil M

2004-08-01

To provide broad clinical experience and to gather safety data on photodynamic therapy with verteporfin (Visudyne, Novartis AG, Basel, Switzerland), also termed verteporfin therapy, in patients with predominantly classic subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The Verteporfin in Age-related Macular Degeneration (VAM) Study was designed to provide expanded access to verteporfin therapy after beneficial results for these cases were reported but before regulatory approval in North America. This open-label multicenter study from September 1999 through June 2000 enrolled among 222 centers patients 50 years or older in the United States, or 40 years or older in Canada, with age-related macular degeneration and subfoveal CNV with a lesion composition that was predominantly classic CNV on fluorescein angiography. Corrected visual acuity with habitual eyewear in the office setting was 20/40 to 20/200, inclusive. All patients received verteporfin therapy and returned for follow-up every 3 months. At those follow-up examinations, additional courses of treatment were recommended if any fluorescein leakage from CNV was identified. Safety information was collected from patient self-reporting, questioning (in person and by telephone), and physician evaluation. Safety was assessed by evaluating the effect of treatment on corrected distance visual acuity and by evaluating adverse events. A total of 4,435 patients were enrolled of whom 4,051 (91%) completed the study after receiving 6,701 treatments. Most patients received only one treatment in VAM before regulatory approval of verteporfin in the United States and Canada. Three hundred patients (6.8%) experienced an adverse event considered by the treating ophthalmologist to be associated with treatment, including 115 (2.6%) with abnormal or decreased vision, of whom 25 (0.6%) experienced acute severe visual acuity decrease, and 14 (0.3%) with transient infusion-related back pain. Patients were advised to avoid exposure to direct sunlight for 24 hours; however, after verteporfin administration only 2 (0.05%) reported a photosensitivity reaction. An additional course of verteporfin therapy was administered to 1,739 of 2,314 patients (75.2%) who had a month 3 examination that was not their close-out visit and 177 of 266 (66.5%) who had a month 6 examination that was not their close-out visit. Verteporfin therapy exhibited no additional or new safety concerns. The therapy associated with a low incidence of adverse events when expanded access was provided in a large, open-label, multicenter study, including a low incidence (0.05%) of reported photosensitivity reactions despite a short photosensitivity protection period (24 hours) following verteporfin administration.

The interaction between equipoise and logistics in clinical trials: A case study.

PubMed

Warshaw, Meredith G; Carey, Vincent J; McFarland, Elizabeth J; Dawson, Liza; Abrams, Elaine; Melvin, Ann; Fairlie, Lee; Spiegel, Hans; Jay, Jonathan; Agwu, Allison L

2017-06-01

Equipoise is usually discussed as an ethical issue in clinical trials. However, it also has practical implications. Clinical equipoise is usually construed to mean uncertainty or disagreement among the expert clinician community. However, an individual physician's sense of equipoise may vary by location, based on the local standard of care or availability of specific treatment options, and these differences can affect providers' willingness to enroll participants into clinical trials. There are also logistical barriers to enrollment in international trials due to prolonged timelines for approvals by government agencies and ethical review boards. A multinational clinical trial of bridging strategies for treatment of non-adherent HIV-infected youth, experienced differing perceptions of equipoise due to disparities in availability of treatment options by country. Unfortunately, the countries with most demand for the trial were those where the approval process was most delayed, and the study was closed early due to slow accrual. When planning multicenter clinical trials, it is important to take into account heterogeneity among research sites and try to anticipate differences in equipoise and logistical factors between sites, in order to plan to address these issues at the design stage.

The MANGUA Project: A Population-Based HIV Cohort in Guatemala

PubMed Central

García, Juan Ignacio; Samayoa, Blanca; Sabidó, Meritxell; Prieto, Luis Alberto; Nikiforov, Mikhail; Pinzón, Rodolfo; Santa Marina de León, Luis Roberto; Ortiz, José Fernando; Ponce, Ernesto; Mejía, Carlos Rodolfo; Arathoon, Eduardo; Casabona, Jordi; Study Group, The Mangua Cohort

2015-01-01

Introduction. The MANGUA cohort is an ongoing multicenter, observational study of people living with HIV/AIDS in Guatemala. The cohort is based on the MANGUA application which is an electronic database to capture essential data from the medical records of HIV patients in care. Methods. The cohort enrolls HIV-positive adults ≥16 years of age. A predefined set of sociodemographic, behavioral, clinical, and laboratory data are registered at entry to the cohort study. Results. As of October 1st, 2012, 21 697 patients had been included in the MANGUA cohort (median age: 33 years, 40.3% female). At enrollment 74.1% had signs of advanced HIV infection and only 56.3% had baseline CD4 cell counts. In the first 12 months after starting antiretroviral treatment 26.9% (n = 3938) of the patients were lost to the program. Conclusions. The implementation of a cohort of HIV-positive patients in care in Guatemala is feasible and has provided national HIV indicators to monitor and evaluate the HIV epidemic. The identified percentages of late presenters and high rates of LTFU will help the Ministry to target their current efforts in improving access to diagnosis and care. PMID:26425365

Design characteristics of the Corrona Japan rheumatoid arthritis registry.

PubMed

Yamanaka, Hisashi; Kishimoto, Mitsumasa; Pappas, Dimitrios A; Greenberg, Jeffrey D; Kremer, Joel M; Tanaka, Yoshiya

2018-01-01

The primary objective is to prospectively study the comparative safety and effectiveness of older and newer classes of nonbiologic DMARDs (Disease-modifying antirheumatic drugs), biologic DMARDs and targeted synthetic therapies approved for rheumatoid arthritis (RA) in a real-world patient population in Japan. Prospective, multicenter, noninterventional, observational study across geographic distribution of both private and public institutions for patients with RA who are newly prescribed one of the following medications: (1) methotrexate; (2) anti-TNF biologic DMARDs; (3) non-TNF biologic DMARDs; and (4) approved JAK inhibitors at the time of enrollment into the registry. Target enrollment is currently 2000 subjects. Baseline and follow-up data on patient demographics, medical history, disease activity, laboratory results, comorbidities, hospitalizations, and targeted safety events are obtained via Physician and Patient Questionnaires. Fifty sites are anticipated to participate with 40 sites ethics committee (EC) approved at the time of submission consisting of 23% clinics, 21% private academic hospitals, 29% private mid-sized to large hospitals, 15% national academic hospitals, and 12% national hospitals. The Corrona Japan RA Registry will provide real-world evidence from both private and public institutions on the comparative effectiveness and safety of recently approved RA therapies in Japan.

The MANGUA Project: A Population-Based HIV Cohort in Guatemala.

PubMed

García, Juan Ignacio; Samayoa, Blanca; Sabidó, Meritxell; Prieto, Luis Alberto; Nikiforov, Mikhail; Pinzón, Rodolfo; Santa Marina de León, Luis Roberto; Ortiz, José Fernando; Ponce, Ernesto; Mejía, Carlos Rodolfo; Arathoon, Eduardo; Casabona, Jordi; Study Group, The Mangua Cohort

2015-01-01

Introduction. The MANGUA cohort is an ongoing multicenter, observational study of people living with HIV/AIDS in Guatemala. The cohort is based on the MANGUA application which is an electronic database to capture essential data from the medical records of HIV patients in care. Methods. The cohort enrolls HIV-positive adults ≥16 years of age. A predefined set of sociodemographic, behavioral, clinical, and laboratory data are registered at entry to the cohort study. Results. As of October 1st, 2012, 21 697 patients had been included in the MANGUA cohort (median age: 33 years, 40.3% female). At enrollment 74.1% had signs of advanced HIV infection and only 56.3% had baseline CD4 cell counts. In the first 12 months after starting antiretroviral treatment 26.9% (n = 3938) of the patients were lost to the program. Conclusions. The implementation of a cohort of HIV-positive patients in care in Guatemala is feasible and has provided national HIV indicators to monitor and evaluate the HIV epidemic. The identified percentages of late presenters and high rates of LTFU will help the Ministry to target their current efforts in improving access to diagnosis and care.

Triangular Titanium Implants for Minimally Invasive Sacroiliac Joint Fusion: 2-Year Follow-Up from a Prospective Multicenter Trial.

PubMed

Duhon, Bradley S; Bitan, Fabien; Lockstadt, Harry; Kovalsky, Don; Cher, Daniel; Hillen, Travis

2016-01-01

Sacroiliac joint (SIJ) dysfunction is an underdiagnosed condition. Several published cohorts have reported favorable mid-term outcomes after SIJ fusion using titanium implants placed across the SIJ. Herein we report long-term (24-month) results from a prospective multicenter clinical trial. One hundred and seventy-two subjects at 26 US sites with SI joint dysfunction were enrolled and underwent minimally invasive SI joint fusion with triangular titanium implants. Subjects underwent structured assessments preoperatively and at 1, 3, 6, 12, 18 and 24 months postoperatively, including SIJ pain ratings (0-100 visual analog scale), Oswestry Disability Index (ODI), Short Form-36 (SF-36), EuroQOL-5D (EQ-5D), and patient satisfaction. Adverse events were collected throughout follow-up. All participating patients underwent a high-resolution pelvic CT scan at 1 year. Mean subject age was 50.9 years and 69.8% were women. SIJ pain was present for an average of 5.1 years prior to surgical treatment. SIJ pain decreased from 79.8 at baseline to 30.4 at 12 months and remained low at 26.0 at 24 months (p<.0001 for change from baseline). ODI decreased from 55.2 at baseline to 31.5 at 12 months and remained low at 30.9 at 24 months (p<.0001 for change from baseline). Quality of life (SF-36 and EQ-5D) improvements seen at 12 months were sustained at 24 months. The proportion of subjects taking opioids for SIJ or low back pain decreased from 76.2% at baseline to 55.0% at 24 months (p <.0001). To date, 8 subjects (4.7%) have undergone one or more revision SIJ surgeries. 7 device-related adverse events occurred. CT scan at one year showed a high rate (97%) of bone adherence to at least 2 implants on both the iliac and sacral sides with modest rates of bone growth across the SIJ. In this study of patients with SIJ dysfunction, minimally invasive SI joint fusion using triangular titanium implants showed marked improvements in pain, disability and quality of life at 2 years. Imaging showed that bone apposition to implants was common but radiographic evidence of intraarticular fusion within the joint may take more than 1 year in many patients. This prospective multicenter clinical trial was approved by local or regional IRBs at each center prior to first patient enrollment. Informed consent with IRB-approved study-specific consent forms was obtained from all patients prior to participation.

Triangular Titanium Implants for Minimally Invasive Sacroiliac Joint Fusion: 2-Year Follow-Up from a Prospective Multicenter Trial

PubMed Central

Bitan, Fabien; Lockstadt, Harry; Kovalsky, Don; Cher, Daniel; Hillen, Travis

2016-01-01

Background Sacroiliac joint (SIJ) dysfunction is an underdiagnosed condition. Several published cohorts have reported favorable mid-term outcomes after SIJ fusion using titanium implants placed across the SIJ. Herein we report long-term (24-month) results from a prospective multicenter clinical trial. Methods One hundred and seventy-two subjects at 26 US sites with SI joint dysfunction were enrolled and underwent minimally invasive SI joint fusion with triangular titanium implants. Subjects underwent structured assessments preoperatively and at 1, 3, 6, 12, 18 and 24 months postoperatively, including SIJ pain ratings (0-100 visual analog scale), Oswestry Disability Index (ODI), Short Form-36 (SF-36), EuroQOL-5D (EQ-5D), and patient satisfaction. Adverse events were collected throughout follow-up. All participating patients underwent a high-resolution pelvic CT scan at 1 year. Results Mean subject age was 50.9 years and 69.8% were women. SIJ pain was present for an average of 5.1 years prior to surgical treatment. SIJ pain decreased from 79.8 at baseline to 30.4 at 12 months and remained low at 26.0 at 24 months (p<.0001 for change from baseline). ODI decreased from 55.2 at baseline to 31.5 at 12 months and remained low at 30.9 at 24 months (p<.0001 for change from baseline). Quality of life (SF-36 and EQ-5D) improvements seen at 12 months were sustained at 24 months. The proportion of subjects taking opioids for SIJ or low back pain decreased from 76.2% at baseline to 55.0% at 24 months (p <.0001). To date, 8 subjects (4.7%) have undergone one or more revision SIJ surgeries. 7 device-related adverse events occurred. CT scan at one year showed a high rate (97%) of bone adherence to at least 2 implants on both the iliac and sacral sides with modest rates of bone growth across the SIJ. Conclusions In this study of patients with SIJ dysfunction, minimally invasive SI joint fusion using triangular titanium implants showed marked improvements in pain, disability and quality of life at 2 years. Imaging showed that bone apposition to implants was common but radiographic evidence of intraarticular fusion within the joint may take more than 1 year in many patients. This prospective multicenter clinical trial was approved by local or regional IRBs at each center prior to first patient enrollment. Informed consent with IRB-approved study-specific consent forms was obtained from all patients prior to participation. PMID:27162715

Clinical and Biological Predictors of Plasma Levels of Soluble RAGE in Critically Ill Patients: Secondary Analysis of a Prospective Multicenter Observational Study.

PubMed

Pranal, Thibaut; Pereira, Bruno; Berthelin, Pauline; Roszyk, Laurence; Godet, Thomas; Chabanne, Russell; Eisenmann, Nathanael; Lautrette, Alexandre; Belville, Corinne; Blondonnet, Raiko; Cayot, Sophie; Gillart, Thierry; Skrzypczak, Yvan; Souweine, Bertrand; Bouvier, Damien; Blanchon, Loic; Sapin, Vincent; Constantin, Jean-Michel; Jabaudon, Matthieu

2018-01-01

Although soluble forms of the receptor for advanced glycation end products (RAGE) have been recently proposed as biomarkers in multiple acute or chronic diseases, few studies evaluated the influence of usual clinical and biological parameters, or of patient characteristics and comorbidities, on circulating levels of soluble RAGE in the intensive care unit (ICU) setting. To determine, among clinical and biological parameters that are usually recorded upon ICU admission, which variables, if any, could be associated with plasma levels of soluble RAGE. Data for this ancillary study were prospectively obtained from adult patients with at least one ARDS risk factor upon ICU admission enrolled in a large multicenter observational study. At ICU admission, plasma levels of total soluble RAGE (sRAGE) and endogenous secretory (es)RAGE were measured by duplicate ELISA and baseline patient characteristics, comorbidities, and usual clinical and biological indices were recorded. After univariate analyses, significant variables were used in multivariate, multidimensional analyses. 294 patients were included in this ancillary study, among whom 62% were admitted for medical reasons, including septic shock (11%), coma (11%), and pneumonia (6%). Although some variables were associated with plasma levels of RAGE soluble forms in univariate analysis, multidimensional analyses showed no significant association between admission parameters and baseline plasma sRAGE or esRAGE. We found no obvious association between circulating levels of soluble RAGE and clinical and biological indices that are usually recorded upon ICU admission. This trial is registered with NCT02070536.

A Multi-Center Diabetes Eye Screening Study in Community Settings: Study Design and Methodology.

PubMed

Murchison, Ann P; Friedman, David S; Gower, Emily W; Haller, Julia A; Lam, Byron L; Lee, David J; McGwin, Gerald; Owsley, Cynthia; Saaddine, Jinan; Insight Study Group

2016-01-01

Diabetes is the leading cause of new cases of blindness among adults aged 20-74 years within the United States. The Innovative Network for Sight Research group (INSIGHT) designed the Diabetic Eye Screening Study (DESS) to examine the feasibility and short-term effectiveness of non-mydriatic diabetic retinopathy (DR) screening for adults with diabetes in community-based settings. Study enrollment began in December 2011 at four sites: an internal medicine clinic at a county hospital in Birmingham, Alabama; a Federally-qualified community healthcare center in Miami-Dade County, Florida; a university-affiliated outpatient pharmacy in Philadelphia, Pennsylvania; and a medical home in Winston-Salem, North Carolina. People 18 years or older with previously diagnosed diabetes were offered free DR screening using non-mydriatic retinal photography that was preceded by a brief questionnaire addressing demographic information and previous eye care use. Visual acuity was also measured for each eye. Images were evaluated at a telemedicine reading center by trained evaluators using the National Health System DR grading classification. Participants and their physicians were sent screening report results and telephoned for a follow-up survey 3 months post-screening to determine whether participants had sought follow-up comprehensive eye care and their experiences with the screening process. Target enrollment at each site was a minimum of 500 persons. Three of the four sites met this enrollment goal. The INSIGHT/DESS is intended to establish the feasibility and short-term effectiveness of DR screening using non-mydriatic retinal photography in persons with diabetes who seek services in community-based clinic and pharmacy settings.

Functional recovery following critical illness in children: the "wee-cover" pilot study.

PubMed

Choong, Karen; Al-Harbi, Samah; Siu, Katie; Wong, Katie; Cheng, Ji; Baird, Burke; Pogorzelski, David; Timmons, Brian; Gorter, Jan-Willem; Thabane, Lehana; Khetani, Mary

2015-05-01

To determine the feasibility of conducting a longitudinal prospective study to evaluate functional recovery and predictors of impaired functional recovery in critically ill children. Prospective pilot study. Single-center PICU at McMaster Children's Hospital, Hamilton, Canada. Children aged 12 months to 17 years, with at least one organ dysfunction, limited mobility or bed rest during the first 48 hours of PICU admission, and a minimum 48-hour PICU length of stay, were eligible. Patients transferred from a neonatal ICU prior to ever being discharged home, already mobilizing well or at baseline functional status at time of screening, with an English language barrier, and prior enrollment into this study, were excluded. None. The primary outcome was feasibility, as defined by the ability to screen, enroll eligible patients, and execute the study procedures and measurements on participants. Secondary outcomes included functional status at baseline, 3 and 6 months, PICU morbidity, and mortality. Functional status was measured using the Pediatric Evaluation of Disability Inventory and the Participation and Environment Measure for Children and Youth. Thirty-three patients were enrolled between October 2012 and April 2013. Consent rate was 85%, and follow-up rates were 93% at 3 months and 71% at 6 months. We were able to execute the study procedures and measurements, demonstrating feasibility of conducting a future longitudinal study. Functional status deteriorated following critical illness. Recovery appears to be influenced by baseline health or functional status and severity of illness. Longitudinal research is needed to understand how children recover after a critical illness. Our results suggest factors that may influence the recovery trajectory and were used to inform the methodology, outcomes of interest, and appropriate sample size of a larger multicenter study evaluating functional recovery in this population.

Standardized Methods for Enhanced Quality and Comparability of Tuberculous Meningitis Studies.

PubMed

Marais, Ben J; Heemskerk, Anna D; Marais, Suzaan S; van Crevel, Reinout; Rohlwink, Ursula; Caws, Maxine; Meintjes, Graeme; Misra, Usha K; Mai, Nguyen T H; Ruslami, Rovina; Seddon, James A; Solomons, Regan; van Toorn, Ronald; Figaji, Anthony; McIlleron, Helen; Aarnoutse, Robert; Schoeman, Johan F; Wilkinson, Robert J; Thwaites, Guy E

2017-02-15

Tuberculous meningitis (TBM) remains a major cause of death and disability in tuberculosis-endemic areas, especially in young children and immunocompromised adults. Research aimed at improving outcomes is hampered by poor standardization, which limits study comparison and the generalizability of results. We propose standardized methods for the conduct of TBM clinical research that were drafted at an international tuberculous meningitis research meeting organized by the Oxford University Clinical Research Unit in Vietnam. We propose a core dataset including demographic and clinical information to be collected at study enrollment, important aspects related to patient management and monitoring, and standardized reporting of patient outcomes. The criteria proposed for the conduct of observational and intervention TBM studies should improve the quality of future research outputs, can facilitate multicenter studies and meta-analyses of pooled data, and could provide the foundation for a global TBM data repository.

Aortic stenosis is a risk factor for all-cause mortality in patients on dialysis: a multicenter prospective cohort analysis.

PubMed

Inaguma, Daijo; Sasakawa, Yuji; Suzuki, Noriko; Ito, Eri; Takahashi, Kazuo; Hayashi, Hiroki; Koide, Shigehisa; Hasegawa, Midori; Yuzawa, Yukio

2018-04-03

Aortic stenosis (AS) is common in patients on dialysis as well as in the general population. AS leads to difficulty with dialysis therapy because of unstable conditions such as intradialytic hypotension due to low cardiac output. However, the precise morbidity rates and risk factors of AS in patients on dialysis are unknown. Moreover, there are no large-scale observational studies regarding the association between AS in patients on dialysis and mortality. Therefore, we will investigate whether morbidity of AS in patients on dialysis is associated with mortality. This is a multicenter prospective cohort analysis in the Tokai region of Japan. The 75 participating centers in this study will enroll approximately 2400 patients during 12 months, with or without AS. We started enrollment in July 2017 and will follow patents until June 2023. Transthoracic echocardiography will be performed to evaluate aortic valve. Parameters used for evaluation of aortic valve are mean pressure gradient between left ventricle and ascending aorta, aortic valve area, and maximum aortic jet velocity. We will diagnose AS using the criteria based on the 2014 American Heart Association/ American College of Cardiology Guideline. We will also perform transthoracic echocardiography at 12, 24, 36, 48, and 60 months. Survival prognosis and CV events will be determined at the end of June 2019, 2020, 2021, 2022, and 2023. Development of AS will be also evaluated as new onset or annual change in AS parameters. We will classify patients based on the presence or absence of AS and the stages of AS and will compare outcomes. Study outcomes will include the following: 1) all-cause mortality rates; 2) incidence of cardiovascular (CV) events; 3) CV-related mortality rates; 4) infection-related mortality rates; 5) new onset or development of AS. We will consider the following hypotheses in this study, among others: The prevalence of AS is higher in dialysis patients; new onset and development of AS are associated with factors that are specific for dialysis, such as hyperphosphatemia, hyperparathyroidism, and medication; and outcomes in AS patients are poorer than in patients without AS at baseline. UMIN000026756 , Registered March 29 2017.

Clinical trial design and rationale of the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) investigational device exemption clinical study protocol.

PubMed

Heatley, Gerald; Sood, Poornima; Goldstein, Daniel; Uriel, Nir; Cleveland, Joseph; Middlebrook, Don; Mehra, Mandeep R

2016-04-01

The HeartMate 3 left ventricular assist system (LVAS; St. Jude Medical, Inc., formerly Thoratec Corporation, Pleasanton, CA) was recently introduced into clinical trials for durable circulatory support in patients with medically refractory advanced-stage heart failure. This centrifugal, fully magnetically levitated, continuous-flow pump is engineered with the intent to enhance hemocompatibility and reduce shear stress on blood elements, while also possessing intrinsic pulsatility. Although bridge-to-transplant (BTT) and destination therapy (DT) are established dichotomous indications for durable left ventricular assist device (LVAD) support, clinical practice has challenged the appropriateness of these designations. The introduction of novel LVAD technology allows for the development of clinical trial designs to keep pace with current practices. The prospective, randomized Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) clinical trial aims to evaluate the safety and effectiveness of the HeartMate 3 LVAS by demonstrating non-inferiority to the HeartMate II LVAS (also St. Jude Medical, Inc.). The innovative trial design includes patients enrolled under a single inclusion and exclusion criteria , regardless of the intended use of the device, with outcomes ascertained in the short term (ST, at 6 months) and long term (LT, at 2 years). This adaptive trial design includes a pre-specified safety phase (n = 30) analysis. The ST cohort includes the first 294 patients and the LT cohort includes the first 366 patients for evaluation of the composite primary end-point of survival to transplant, recovery or LVAD support free of debilitating stroke (modified Rankin score >3), or re-operation to replace the pump. As part of the adaptive design, an analysis by an independent statistician will determine whether sample size adjustment is required at pre-specified times during the study. A further 662 patients will be enrolled to reach a total of 1,028 patients for evaluation of the secondary end-point of pump replacement at 2 years. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

A Multicenter, Randomized, Controlled Trial of Osteopathic Manipulative Treatment on Preterms

PubMed Central

Cerritelli, Francesco; Pizzolorusso, Gianfranco; Renzetti, Cinzia; Cozzolino, Vincenzo; D’Orazio, Marianna; Lupacchini, Mariacristina; Marinelli, Benedetta; Accorsi, Alessandro; Lucci, Chiara; Lancellotti, Jenny; Ballabio, Silvia; Castelli, Carola; Molteni, Daniela; Besana, Roberto; Tubaldi, Lucia; Perri, Francesco Paolo; Fusilli, Paola; D’Incecco, Carmine; Barlafante, Gina

2015-01-01

Background Despite some preliminary evidence, it is still largely unknown whether osteopathic manipulative treatment improves preterm clinical outcomes. Materials and Methods The present multi-center randomized single blind parallel group clinical trial enrolled newborns who met the criteria for gestational age between 29 and 37 weeks, without any congenital complication from 3 different public neonatal intensive care units. Preterm infants were randomly assigned to usual prenatal care (control group) or osteopathic manipulative treatment (study group). The primary outcome was the mean difference in length of hospital stay between groups. Results A total of 695 newborns were randomly assigned to either the study group (n= 352) or the control group (n=343). A statistical significant difference was observed between the two groups for the primary outcome (13.8 and 17.5 days for the study and control group respectively, p<0.001, effect size: 0.31). Multivariate analysis showed a reduction of the length of stay of 3.9 days (95% CI -5.5 to -2.3, p<0.001). Furthermore, there were significant reductions with treatment as compared to usual care in cost (difference between study and control group: 1,586.01€; 95% CI 1,087.18 to 6,277.28; p<0.001) but not in daily weight gain. There were no complications associated to the intervention. Conclusions Osteopathic treatment reduced significantly the number of days of hospitalization and is cost-effective on a large cohort of preterm infants. PMID:25974071

Antihypertensive effect of a fixed-dose combination of losartan/hydrochlorothiazide in patients with uncontrolled hypertension: a multicenter study.

PubMed

Hosoya, Tatsuo; Kuriyama, Satoru; Ohno, Iwao; Kawamura, Tetsuya; Ogura, Makoto; Ikeda, Masato; Ishikawa, Masahiro; Hayashi, Fumihiro; Kanai, Tatsuya; Tomonari, Haruo; Soejima, Michimasa; Akaba, Kiyoaki; Tokudome, Goro; Endo, S; Fukui, A; Gomi, H; Hamaguchi, A; Hanaoka, K; Hara, Y; Hara, Y; Hasegawa, T; Hayakawa, H; Hikida, M; Hirano, K; Horiguchi, M; Hosoya, M; Ichida, K; Imai, T; Ishii, T; Ishikawa, H; Kameda, C; Kasai, T; Kobayashi, A; Kobayashi, H; Kurashige, M; Kusama, Y; Maezawa, H; Maezawa, Y; Maruyama, Y; Matsuda, H; Matsuo, N; Matsuo, T; Miura, Y; Miyajima, M; Miyakawa, M; Miyazaki, Y; Mizuguchi, M; Nakao, M; Nokano, H; Ohkido, I; Ohtsuka, Y; Okada, K; Okamoto, H; Okonogi, H; Saikawa, H; Saito, H; Sekiguchi, C; Suetsugu, Y; Sugano, N; Suzuki, T; Suzuki, T; Takahashi, H; Takahashi, Y; Takamizawa, S; Takane, K; Morita, T; Takazoe, K; Tanaka, H; Tanaka, S; Terawaki, H; Toyoshima, R; Tsuboi, N; Udagawa, T; Ueda, H; Ueda, Y; Uetake, M; Unemura, S; Utsunomiya, M; Utsunomiya, Y; Yamada, T; Yamada, Y; Yamaguchi, Y; Yamamoto, H; Yokoo, T; Yokoyama, K; Yonezawa, H; Yoshida, H; Yoshida, M; Yoshizawa, T

2012-04-01

Achieving adequate blood pressure (BP) control often requires more than one antihypertensive agent. The purpose of this study was to determine whether a fixed-dose formulation of losartan (LOS) plus hydrochlorothiazide (HCTZ) (LOS/HCTZ) is effective in achieving a greater BP lowering in patients with uncontrolled hypertension. The study was a prospective, multicenter, observational trial exploring the antihypertensive effect of a single tablet of LOS 50 mg/HCTZ 12.5 mg. A total of 228 patients whose BP had previously been treated with more than one antihypertensive agents without having achieved BP goal below 130/80 mmHg enrolled in the study. A significant decrease in systolic and diastolic BP was observed in both clinic and home measurement after switching from the previous treatment to LOS/HCTZ. There was a significant decrease in both B-type natriuretic peptide (BNP) and urinary albumin creatinine (Cr) excretion ratio (ACR), especially in patients with elevated values. In contrast, there was a significant increase in serum Cr concentration in conjunction with a decrease in estimated glomerular filtration rate (eGFR). Overall serum uric acid (UA) concentration increased, whereas in patients with hyperuricemia there was a significant reduction in this value. Switching to LOS/HCTZ provides a greater reduction in clinic and home BP in patients with uncontrolled hypertension. This combination therapy may lead to cardio-, reno protection and improve UA metabolism.

Baseline data from a multicenter, 5-year, prospective cohort study of Japanese age-related macular degeneration: an AMD2000 report.

PubMed

Tsujikawa, Akitaka; Akagi-Kurashige, Yumiko; Yuzawa, Mitsuko; Ishibashi, Tatsuro; Nakanishi, Hideo; Nakatani, Eiji; Teramukai, Satoshi; Fukushima, Masanori; Yoshimura, Nagahisa

2018-03-01

To report research participants' baseline characteristics in the AMD2000 study, a prospective, multicenter, 5-year, observational cohort study of Japanese age-related macular degeneration (AMD). The characteristics were determined using multimodal imaging. Patients with AMD were recruited at 18 clinical sites in Japan between April 2006 and March 2009. Each patient underwent a complete ophthalmic examination, including measurement of best-corrected visual acuity (Landolt chart), indirect ophthalmoscopy, slit-lamp biomicroscopy with a contact lens, optical coherence tomography imaging, fundus photography, and fluorescein and indocyanine green angiography. Four hundred sixty participants (326 men [70.9%]) were included in the study. At enrollment, 131 eyes (28.5%) had hard drusen and 125 eyes (27.2%) had soft drusen in the macular area. A total of 455 eyes (98.9%) were diagnosed as having wet AMD, and 5 eyes (1.1%), as having dry AMD. Of the 455 eyes with wet AMD, 209 eyes (45.4%) had typical AMD, 228 eyes (49.6%) had polypoidal choroidal vasculopathy (PCV), and 18 eyes (3.9%) had retinal angiomatous proliferation. The size of choroidal neovascularization (CNV) was significantly smaller with indocyanine green angiography than with fluorescein angiography (P < 0.001). Poor baseline visual acuity was associated with cystoid macular edema, older age, scar, extrafoveal macular edema, subfoveal CNV, large branching vascular network, and hard exudates. Japanese patients with AMD are predominantly male, lack drusen, and have a high rate of PCV.

Multimodal treatment with primary single-agent epirubicin in operable breast cancer: 5-year experience of the Michelangelo Cooperative Group.

PubMed

Bonadonna, G; Zambetti, M; Bumma, C; Donadio, M; Bolognesi, A; Robustelli Della Cuna, G; Ambrosini, G; Lelli, G; Mansutti, M; Verderio, P; Valagussa, P

2002-07-01

To assess the efficacy of primary single-agent epirubicin (120 mg/m(2) every 3 weeks for three cycles) in reducing tumor burden in operable breast cancer >or=2.5 cm in largest diameter at diagnosis and its effect on the rate of conservative surgery. A total of 319 eligible patients, who were all candidates for mastectomy, were enrolled on to a multicenter prospective non-randomized study. Tumor response was assessed clinically and pathologically. Relapse-free and overall survival were assessed on major prognostic variables. After primary epirubicin, complete disappearance of invasive neoplastic cells accounted for only 2.6% of patients, but 40% of patients had their primary tumor downstaged to

Multicenter clinical trials in sepsis: understanding the big picture and building a successful operation at your hospital.

PubMed

Dellinger, R Phillip; Schorr, Christa; Trzeciak, Stephen

2011-03-01

Only through adequately designed and adequately conducted clinical trials can new treatments be found for the benefit of the septic patient. Over the past 20 years, tens of thousands of patients have been enrolled in sepsis clinical trials with little success. These efforts, however, have not been without worth. Much has been learned and the knowledge gained has changed our approach to trial design in this very difficult field. Animal studies are better designed to match the clinical picture of severe sepsis. Phase II studies are more carefully engineered to answer questions about the most suitable target population and end points. Trial conduct likely benefits from use of CROs and a CCC. The future of clinical trials may include more standardization of sepsis management across investigative sites. Before the decision is made to become an investigative site in a multicenter industry-sponsored clinical trial in sepsis or severe sepsis, it is important to recognize what is required to succeed. Once these key-to-success elements are in place, members of the investigative team are more likely to realize the satisfaction and career growth from becoming a successful site. The most professional satisfaction comes from the knowledge of contributing to original science in the field of the sepsis. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparison of Clinical Characteristics among Subtypes of Visual Symptoms in Patients with Transient Ischemic Attack: Analysis of the PROspective Multicenter registry to Identify Subsequent cardiovascular Events after TIA (PROMISE-TIA) Registry.

PubMed

Tanaka, Koji; Uehara, Toshiyuki; Kimura, Kazumi; Okada, Yasushi; Hasegawa, Yasuhiro; Tanahashi, Norio; Suzuki, Akifumi; Nakagawara, Jyoji; Arii, Kazumasa; Nagahiro, Shinji; Ogasawara, Kuniaki; Uchiyama, Shinichiro; Matsumoto, Masayasu; Iihara, Koji; Toyoda, Kazunori; Minematsu, Kazuo

2018-06-01

A transient visual symptom (TVS) is a clinical manifestation of transient ischemic attack (TIA). The aim of this study was to investigate differences in clinical characteristics among subtypes of TVS using multicenter TIA registry data. Patients with TIA visiting within 7 days of onset were prospectively enrolled from 57 hospitals between June 2011 and December 2013. Clinical characteristics were compared between patients with 3 major subtypes of TVS (transient monocular blindness [TMB], homonymous lateral hemianopia [HLH], and diplopia). Of 1365 patients, 106 (7.8%) had TVS, including 40 TMB (38%), 34 HLH (32%), 17 diplopia (16%), and 15 others/unknown (14%). Ninety-one patients with 1 of the 3 major subtypes of TVS were included. Symptoms persisted on arrival in 12 (13%) patients. Isolated TVS was significantly more common in TMB than in HLH and diplopia (88%, 62%, and 0%, respectively; P < .001). Duration of symptoms was shorter in patients with TMB than those with HLH (P = .004). The ABCD 2 score was significantly lower in patients with TMB compared with those with HLH and diplopia (median 2 [interquartile range 2-3] versus 3 [2-4] and 4 [2-5], respectively; P = .005). Symptomatic extracranial internal carotid artery stenosis or occlusion was seen in 14 (16%) patients, and was more frequent in TMB than in HLH and diplopia (28%, 9%, and 0%, respectively; P = .015). TVS was an uncommon symptom in our TIA multicenter cohort. Some differences in clinical characteristics were found among subtypes of TVS. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Treatment benefit and the risk of suicidality in multicenter, randomized, controlled trials of sertraline in children and adolescents.

PubMed

March, John S; Klee, Brian J; Kremer, Charlotte M E

2006-01-01

The aim of this study was to examine the balance between the benefits of treatment and the risk of suicidality in children and adolescents in multicenter, randomized, controlled trials of sertraline versus placebo. The published literature was searched for multicenter, randomized, placebo-controlled trials of sertraline for pediatric mental disorders. Four trials were identified: Two (pooled) in pediatric major depressive disorder (MDD; Wagner 2003) and two in obsessive-compulsive disorder (OCD; March et al. 1998; POTS Team 2004). Using intent-to-treat (ITT) analysis populations, the authors calculated the number needed to treat (NNT) for response and remission and the number needed to harm (NNH) for suicidality, and their ratio, for each clinical trial. NNTs ranged from 2 to 10, indicating clinically meaningful benefits. Benefit was greater for OCD than for MDD, and for adolescents as compared with children in MDD. No age effect was apparent for OCD. Suicidality was reported in 8 patients (5 assigned to sertraline and 3 assigned to placebo). All but 1 (a placebo-treated patient in the Pfizer OCD trial) were enrolled in the sertraline MDD trial. The NNH for suicidality in MDD was 64. Treatment emergent suicidality was more common in children (NNH 28.7) than in adolescents (NNH 706.3). Because no patient developed suicidality in sertraline-treated OCD patients, the NNH for sertraline in OCD approaches infinity. With the stipulation that doctor and patient preferences necessarily play a critical role in the choice of treatment, NNT to NNH ratios indicate a positive benefit-to-risk ratio for sertraline in adolescents with MDD and in patients of all ages with OCD.

Blood lipid profiles and factors associated with dyslipidemia assessed by a point-of-care testing device in an outpatient setting: A large-scale cross-sectional study in Southern China.

PubMed

Zhang, Pei-dong; He, Lin-yun; Guo, Yang; Liu, Peng; Li, Gong-xin; Wang, Li-zi; Liu, Ying-feng

2015-06-01

To promote the concept of POCT and to investigate dyslipidemia in Guangzhou, China, we performed a study examining blood lipids assessed by POCT and reported factors associated with dyslipidemia. This multicenter, cross-sectional study enrolled outpatients from 9 Guangzhou hospitals from May through September 2013. After informed consent was obtained, the following information was collected: age; gender; the presence of diabetes mellitus, obesity, and hypertension as well as current use of cigarettes or alcohol. Patients were asked to fast for 8h before the blood examination performed on a POCT device, the CardioChek PA. Of 4012 patients enrolled (1544 males, 2468 females; mean age 60.35±9.41 years), 1993 (49.7%) patients had dyslipidemia, but only 101 (5.1%) took statins. The multivariate tests of associations between demographic variables, comorbidities, and the risk of having dyslipidemia found that the significant predictors of dyslipidemia were male gender, age ≥60 years, being a current smoker or alcohol drinker, and hypertension. Most dyslipidemia patients in Guangzhou remain untreated. POCT in China is feasible, and its widespread use might improve dyslipidemia awareness, treatment and control. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Granulocyte-Monocyte Apheresis in Steroid-Dependent, Azathioprine-Intolerant/Resistant Moderate Ulcerative Colitis: A Prospective Multicenter Study

PubMed Central

Imperiali, Gianni; Terpin, Maria Maddalena; Beverina, Ivo; Bortoli, Aurora; Devani, Massimo; Viganò, Chiara

2017-01-01

Background Granulocyte-monocyte apheresis has been proposed for the treatment of ulcerative colitis, although it is limited by costs and variability of results. Aim To assess effectiveness of granulocyte-monocyte apheresis in patients with steroid-dependent, azathioprine-intolerant/resistant moderate ulcerative colitis. Methods Consecutive patients fulfilling inclusion criteria were prospectively enrolled, treated by apheresis, and followed up for 12 months. The primary end point of the study was steroid-free clinical remission at 12 months, with no need for biologic therapy or surgery. Results From January to December 2013, 33 patients were enrolled. After one year of follow-up, 12 (36%) patients had clinical remission, were steroid-free, and had no need for biological therapy or surgery; 3 (9%) cases showed a clinical response (but not clinical remission). Moreover, 12 (36%) patients required biologic therapy, 4 (12%) underwent colectomy, and in the other 2 (6%) a reduction, but not withdrawal, of steroid dose was achieved. Conclusions Our study shows that a standard course of granulocyte-monocyte apheresis is associated with a 36% steroid-free clinical remission in patients with steroid-dependent, azathioprine-intolerant or resistant moderate ulcerative colitis. Apheresis might represent an alternative to biologic therapy or surgery in this specific subgroup of patients. This trial is registered with Clinicaltrial.gov NCT03189888. PMID:29403531

Acute-on-Chronic Liver Failure in China: Rationale for Developing a Patient Registry and Baseline Characteristics.

PubMed

Gu, Wen-Yi; Xu, Bao-Yan; Zheng, Xin; Chen, Jinjun; Wang, Xian-Bo; Huang, Yan; Gao, Yan-Hang; Meng, Zhong-Ji; Qian, Zhi-Ping; Liu, Feng; Lu, Xiao-Bo; Shang, Jia; Li, Hai; Wang, Shao-Yang; Sun, Xin; Li, Hai

2018-05-14

Definitions and descriptions of acute-on-chronic liver failure (ACLF) vary between Western and Eastern types, and alcoholism and hepatitis B virus(HBV) are the main etiologies, respectively. To determine whether there are unified diagnostic criteria and common treatment programs for different etiologies of ACLF, a multicenter prospective cohort with the same inclusion criteria and disease indicators as those used in the European CANONIC (Chronic liver failure-ACLF in Cirrhosis) study is urgently needed in Asia, where the prevalence of HBV is high. Fourteen nationwide liver centers from tertiary university hospitals in China were included, and 2,600 hospitalized patients with chronic liver disease (both cirrhotic and non-cirrhotic) of various etiologies with acute decompensation or acute hepatic injury were continuously recruited from January 2015 to December 2016. Data were collected during hospitalization and continuous follow-ups were performed once a month until 36 months after hospital discharge. A multicenter prospective cohort of 2,600 patients was designed (NCT no. NCT02457637). Of these patients, 71.5% had HBV-related disease, 1,833 had cirrhotic disease, and 767 had non-cirrhotic disease. The numbers and proportions of enrolled patients from each participating center and the baseline characteristics of the patients with or without cirrhosis are presented.

A pilot study on the randomization of inferior vena cava filter placement for venous thromboembolism prophylaxis in high-risk trauma patients.

PubMed

Rajasekhar, Anita; Lottenberg, Lawrence; Lottenberg, Richard; Feezor, Robert J; Armen, Scott B; Liu, Huazhi; Efron, Philip A; Crowther, Mark; Ang, Darwin

2011-08-01

Placement of prophylactic inferior vena cava filters (pIVCFs) for the prevention of pulmonary embolism (PE) in high-risk trauma patients (HRTPs) are widely practiced despite the lack of Level I data supporting this use. We report the 2-year interim analysis of the Filters in Trauma pilot study. This is a single institution, prospective randomized controlled pilot feasibility study in a Level I trauma center. HRTPs were identified for pIVCF placement by the Eastern Association for the Surgery of Trauma guidelines. From November 2008 to November 2010, HRTPs were enrolled and randomized to either pIVCF or no pIVCF. All patients received pharmacologic prophylaxis when safe. Primary outcomes included feasibility objectives and secondary outcomes were incidence of PE, deep vein thrombosis (DVT), and death. Thirty-four of 38 enrolled patients were eligible for analysis. The baseline sociodemographic characteristics were balanced between the both groups. Results of the feasibility objectives included: time from admission to enrollment (mean, 47.4 hours ± 22.0 hours), time from enrollment to randomization (mean, 4.8 hours ± 9.1 hours), time from randomization to IVCF placement (mean, 16.9 hours ± 9.2 hours), adherence to weekly compression ultrasound within first month (IVCF group = 44.4%; non-IVCF group = 62.5%), and 1-month clinical follow-up (IVCF group = 83.3%; non-IVCF group = 100%). At 6-month follow-up, one PE in the nonfilter group and one DVT in the filter group had occurred. One non-PE-related death occurred in the filter group. Barriers to enrollment included inability to obtain informed consent due to patient refusal or no next of kin identified and delayed notification of eligibility status. Our pilot study demonstrates for the first time that a randomized controlled trial evaluating the efficacy of pIVCFs in trauma patients is feasible. This pilot data will be used to inform the design of a multicenter randomized controlled trial to determine the incidence of PE and DVT in HRTPs receiving pIVCFs versus no pIVCF.

Effect of Contract Research Organization Bureaucracy in Clinical Trial Management: A Model From Lung Cancer.

PubMed

Gobbini, Elisa; Pilotto, Sara; Pasello, Giulia; Polo, Valentina; Di Maio, Massimo; Arizio, Francesca; Galetta, Domenico; Petrillo, Patrizia; Chiari, Rita; Matocci, Roberta; Di Costanzo, Alessandro; Di Stefano, Teresa Severina; Aglietta, Massimo; Cagnazzo, Celeste; Sperduti, Isabella; Bria, Emilio; Novello, Silvia

2018-03-01

Contract research organization (CRO) support is largely included in clinical trial management, although its effect in terms of time savings and benefit has not yet been quantified. We performed a retrospective multicenter analysis of lung cancer trials to explore differences in term of trial activation timelines and accrual for studies with and without CRO involvement. Results regarding study timelines from feasibility data to first patient enrollment were collected from 7 Italian thoracic oncology departments. The final accruals (screened/enrolled patients) are reported. We considered CRO/sponsor-administered and CRO-free trials according to who was responsible for the management of the crucial setup phases. Of 113 trials, 62 (54.9%) were CRO-administered, 34 (30.1%) were sponsor-administered, and 17 (15.0%) were CRO-free. The median time from feasibility invitation to documentation obtainment was 151 days in the CRO-administered trials versus 128 in the sponsor-administered and 120 in the CRO-free trials. The time from document submission to contract signature was 142 days in the CRO-administered versus 128 in the sponsor-administered and 132 in the CRO-free trials. The time from global accrual opening to first patient enrollment was 247 days for the CRO-administered versus 194 in the sponsor-administered and 151 in the CRO-free trials. No significant differences were observed in terms of the median overall timeline: 21 months in the CRO-administered, 15 in the sponsor-administered, and 18 months in the CRO-free studies (P = .29). Although no statistically significant differences were identified, the results of our analysis support the idea that bureaucratic procedures might require more time in CRO-administered trials than in sponsor-administered and CRO-free studies. This bureaucratic delay could negatively affect Italian patients' screening and enrollment compared with other countries. Copyright © 2017 Elsevier Inc. All rights reserved.

Safety and effectiveness of minimally invasive sacroiliac joint fusion in women with persistent post-partum posterior pelvic girdle pain: 12-month outcomes from a prospective, multi-center trial.

PubMed

Capobianco, Robyn; Cher, Daniel

2015-01-01

Postpartum posterior pelvic girdle pain (PPGP) affects nearly 20 % of women who experience back pain in the peripartum period. The sacroiliac joint is a source of this pain in 75 % of women with persistent PPGP. A subset of women will fail to obtain acceptable pain relief from the current array of non-surgical treatment options. The purpose of this study is to assess the safety and effectiveness of minimally invasive sacroiliac (SI) joint fusion in women with chronic SI joint dysfunction whose pain began in the peri-partum period whose symptoms were recalcitrant to non-surgical management. A sub-group analysis of subjects with sacroiliac joint disruption and/or degenerative sacroiliitis enrolled in a prospective, multi-center trial of SI joint fusion was performed. Subjects with PPGP were identified and compared with women without PPGP and with men. Of 172 enrolled subjects, 52 were male, 100 were females without PPGP and 20 females had PPGP. PPGP subjects were significantly younger (43.3 years, vs. 52.8 for females without PPGP and 50.5 for men, p = 0.002). There were no differences in any other demographic or baseline clinical measure. Women with PPGP experienced a significant improvement in pain (-51 mm on VAS), function (-20.6 pts on ODI) and quality of life (SF-36 PCS +10.4, MCS +7.2, EQ-5D +0.31) at 12 months after surgery. These improvements were characteristic of the overall study results; no difference was detected between sub-groups. The sacroiliac joint can be a source of pain in women with persistent PPGP and should be investigated as a pain generator. In this study, women with carefully diagnosed chronic SI joint pain from PPGP recalcitrant to conservative therapies experienced clinically beneficially improvements in pain, disability and quality of life after minimally invasive SI joint fusion using a series of triangular porous plasma spray coated implants.

OpT2mise: a randomized controlled trial to compare insulin pump therapy with multiple daily injections in the treatment of type 2 diabetes-research design and methods.

PubMed

Aronson, Ronnie; Cohen, Ohad; Conget, Ignacio; Runzis, Sarah; Castaneda, Javier; de Portu, Simona; Lee, Scott; Reznik, Yves

2014-07-01

In insulin-requiring type 2 diabetes patients, current insulin therapy approaches such as basal-alone or basal-bolus multiple daily injections (MDI) have not consistently provided achievement of optimal glycemic control. Previous studies have suggested a potential benefit of continuous subcutaneous insulin infusion (CSII) in these patients. The OpT2mise study is a multicenter, randomized, trial comparing CSII with MDI in a large cohort of subjects with evidence of persistent hyperglycemia despite previous MDI therapy. Subjects were enrolled into a run-in period for optimization of their MDI insulin regimen. Subjects showing persistent hyperglycemia (glycated hemoglobin [HbA1c] ≥8% and ≤12%) were then randomly assigned to CSII or continuing an MDI regimen for a 6-month phase followed by a single crossover of the MDI arm, switching to CSII. The primary end point is the between-group difference in mean change in HbA1c from baseline to 6 months. Secondary end points include change in mean 24-h glucose values, area under the curve and time spent in hypoglycemia and hyperglycemia, measures of glycemic excursions, change in postprandial hyperglycemia, and evaluation of treatment satisfaction. Safety end points include hypoglycemia, hospital admissions, and emergency room visits. When subject enrollment was completed in May 2013, 495 subjects had been enrolled in the study. The study completion for the primary end point is expected in January 2014. OpT2mise will represent the largest studied homogeneous cohort of type 2 diabetes patients with persistent hyperglycemia despite optimized MDI therapy. OpT2mise will help define the role of CSII in insulin intensification and define its safety, rate of hypoglycemia, patient adherence, and patient satisfaction.

Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen M; Alothman, Adel; Balkhy, Hanan H; Al-Dawood, Abdulaziz; AlJohani, Sameera; Al Harbi, Shmeylan; Kojan, Suleiman; Al Jeraisy, Majed; Deeb, Ahmad M; Assiri, Abdullah M; Al-Hameed, Fahad; AlSaedi, Asim; Mandourah, Yasser; Almekhlafi, Ghaleb A; Sherbeeni, Nisreen Murad; Elzein, Fatehi Elnour; Memon, Javed; Taha, Yusri; Almotairi, Abdullah; Maghrabi, Khalid A; Qushmaq, Ismael; Al Bshabshe, Ali; Kharaba, Ayman; Shalhoub, Sarah; Jose, Jesna; Fowler, Robert A; Hayden, Frederick G; Hussein, Mohamed A

2018-01-30

It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality. This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018. ClinicalTrials.gov, ID: NCT02845843 . Registered on 27 July 2016.

Follicular Lymphoma in the United States: First Report of the National LymphoCare Study

PubMed Central

Friedberg, Jonathan W.; Taylor, Michael D.; Cerhan, James R.; Flowers, Christopher R.; Dillon, Hildy; Farber, Charles M.; Rogers, Eric S.; Hainsworth, John D.; Wong, Elaine K.; Vose, Julie M.; Zelenetz, Andrew D.; Link, Brian K.

2009-01-01

Purpose Optimal therapy of follicular lymphoma (FL) is not defined. We analyzed a large prospective cohort study to identify current demographics and patterns of care of FL in the United States. Patients and Methods The National LymphoCare Study is a multicenter, longitudinal, observational study designed to collect information on treatment regimens and outcomes for patients with newly diagnosed FL in the United States. Patients were enrolled between 2004 and 2007. There is no study-specific prescribed treatment regimen or intervention. Results Two thousand seven hundred twenty-eight subjects were enrolled at 265 sites, including the 80% of patients enrolled from nonacademic sites. Using the Follicular Lymphoma International Prognostic Index (FLIPI), three distinct groups independent of histologic grade could be defined. Initial therapeutic strategy was: observation, 17.7%; rituximab monotherapy, 13.9%; clinical trial 6.1%; radiation therapy, 5.6%; chemotherapy only, 3.2%; chemotherapy plus rituximab, 51.9%. Chemotherapy plus rituximab regimens were: rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone, 55.0%; rituximab plus cyclophosphamide, vincristine, and prednisone, 23.1%; rituximab plus fludarabine based, 15.5%; other, 6.4%. The choice to initiate therapy rather than observe was associated with age, FLIPI, stage, and grade (P < .01). Significant differences in treatment (P < .01) across regions of the United States were noted. Contrary to practice guidelines, treatment of stage I FL frequently omits radiation therapy. Conclusion Widely disparate therapeutic approaches are utilized for FL. Initial therapy is deferred in a small subset of patients. There is no single standard of care for the treatment of de novo FL, although antibody use is ubiquitous when therapy is initiated. These disparate approaches to the initial care of patients with FL render a heterogeneous group of patients at relapse. PMID:19204203

The pediatric heart network: meeting the challenges to multicenter studies in pediatric heart disease

PubMed Central

Burns, Kristin M.; Pemberton, Victoria L.; Pearson, Gail D.

2017-01-01

Purpose of review Because of the relatively small numbers of pediatric patients with congenital heart disease cared for in any individual center, there is a significant need for multicenter clinical studies to validate new medical or surgical therapies. The Pediatric Heart Network (PHN), with 15 years of experience in multicenter clinical research, has tackled numerous challenges when conducting multicenter studies. Recent findings This review describes the challenges encountered and the strategies employed to conduct high-quality, collaborative research in pediatric cardiovascular disease. Summary Sharing lessons learned from the PHN can provide guidance to investigators interested in conducting pediatric multicenter studies. PMID:26196261

FTY720 and everolimus in de novo renal transplant patients at risk for delayed graft function: results of an exploratory one-yr multicenter study.

PubMed

Tedesco-Silva, H; Lorber, M I; Foster, C E; Sollinger, H W; Mendez, R; Carvalho, D B; Shapiro, R; Rajagopalan, P R; Mayer, H; Slade, J; Kahan, B D

2009-01-01

This exploratory, multicenter, open-label study evaluated the efficacy and safety of FTY720, as a part of an immunosuppressive regimen, in combination with everolimus and steroids in de novo renal transplant recipients at increased risk of delayed graft function (DGF). Patients received FTY720 (5 mg) and everolimus (4 mg) 2-12 h pre-transplantation, followed by 2.5 mg/d FTY720 and concentration-controlled everolimus (4-8 ng/mL) post-transplant for 12 months. Induction therapy was prohibited. After enrollment of 56 of the planned 200 patients between 2000 and 2002, the recruitment was terminated. The primary endpoint, rate of graft loss, or death at three months was 15.4% and the biopsy-confirmed acute rejection was 42.3%. Death or graft loss at 12 months in the DGF and non-DGF arms was 36.0% and 25.9%, respectively. The mean estimated creatinine clearance at three months was 63 and 55 mL/min in the non-DGF and DGF groups, respectively, while at 12 months it was 56 mL/min in both the groups. Although there was no comparator arm, the results from this exploratory study (compared with data from other phases II and III trials) indicated no apparent benefits of FTY720-based regimens for prevention of acute rejection and preservation of renal function in renal transplant recipients at high risk of DGF.

Clinical effect of intratympanic dexamethasone injection in acute unilateral tinnitus: A prospective, placebo-controlled, multicenter study.

PubMed

Lee, Hyun-Jin; Kim, Min-Beom; Yoo, Shin-Young; Park, Shi Nae; Nam, Eui-Cheol; Moon, In Seok; Lee, Ho-Ki

2018-01-01

The purpose of this study was to investigate the effectiveness of intratympanic dexamethasone injection (ITDI) in acute tinnitus of presumed cochlear origin. A prospective, randomized, placebo-controlled, double-blinded, multicenter study. Between August 2013 and December 2015, 54 patients with unilateral tinnitus were enrolled at four different centers. Patients were assigned either to an ITDI (n = 27) or an intratympanic normal saline injection (ITNI; n = 27) group through block randomization. Intratympanic injections were administered four times over 2 weeks. At 4 weeks after initial injection, we analyzed the improvement rates of tinnitus using the tinnitus handicap Inventory (THI) and visual analogue scale (VAS) for loudness, awareness, and annoyance. We defined improvement as the reduction of more than 7 points or of more than 20% in the final THI score compared to the initial THI score. The initial mean hearing thresholds and VAS and THI scores of the two groups did not differ significantly. At 4 weeks after initial injection, the mean VAS and THI scores of both groups had significantly reduced. However, the improvement rate did not differ significantly between the groups (ITDI, 51.9%; ITNI, 59.3%). The results indicate that ITDI might not be more effective than ITNI for the treatment of acute unilateral tinnitus. Therefore, ITDI should not be considered as the main treatment for patients presenting with acute tinnitus as the primary symptom. 1b. Laryngoscope, 128:184-188, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Mixed membership trajectory models of cognitive impairment in the multicenter AIDS cohort study.

PubMed

Molsberry, Samantha A; Lecci, Fabrizio; Kingsley, Lawrence; Junker, Brian; Reynolds, Sandra; Goodkin, Karl; Levine, Andrew J; Martin, Eileen; Miller, Eric N; Munro, Cynthia A; Ragin, Ann; Sacktor, Ned; Becker, James T

2015-03-27

The longitudinal trajectories that individuals may take from a state of normal cognition to HIV-associated dementia are unknown. We applied a novel statistical methodology to identify trajectories to cognitive impairment, and factors that affected the 'closeness' of an individual to one of the canonical trajectories. The Multicenter AIDS Cohort Study (MACS) is a four-site longitudinal study of the natural and treated history of HIV disease among gay and bisexual men. Using data from 3892 men (both HIV-infected and HIV-uninfected) enrolled in the neuropsychology substudy of the MACS, a Mixed Membership Trajectory Model (MMTM) was applied to capture the pathways from normal cognitive function to mild impairment to severe impairment. MMTMs allow the data to identify canonical pathways and to model the effects of risk factors on an individual's 'closeness' to these trajectories. First, we identified three distinct trajectories to cognitive impairment: 'normal aging' (low probability of mild impairment until age 60); 'premature aging' (mild impairment starting at age 45-50); and 'unhealthy' (mild impairment in 20s and 30s) profiles. Second, clinically defined AIDS, and not simply HIV disease, was associated with closeness to the premature aging trajectory, and, third, hepatitis-C infection, depression, race, recruitment cohort and confounding conditions all affected individual's closeness to these trajectories. These results provide new insight into the natural history of cognitive dysfunction in HIV disease and provide evidence for a potential difference in the pathophysiology of the development of cognitive impairment based on trajectories to impairment.

Complications of Microwave Ablation for Liver Tumors: Results of a Multicenter Study

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

Livraghi, Tito, E-mail: lalivra@tin.it; Meloni, Franca, E-mail: meloni@yahoo.it; Solbiati, Luigi, E-mail: lusolbia@tin.it

2012-08-15

Purpose: New technologies for microwave ablation (MWA) have been conceived, designed to achieve larger areas of necrosis compared with radiofrequency ablation (RFA). The purpose of this study was to report complications by using this technique in patients with focal liver cancer. Methods: Members of 14 Italian centers used a 2.45-GMHz generator delivering energy through a cooled miniature-choke MW antenna and a standardized protocol for follow-up. They completed a questionnaire regarding number and type of deaths, major and minor complications and side effects, and likelihood of their relationship to the procedure. Enrollment included 736 patients with 1.037 lesions: 522 had hepatocellularmore » carcinoma with cirrhosis, 187 had metastases predominantly from colorectal cancer, and 27 had cholangiocellular carcinoma. Tumor size ranged from 0.5 to 10 cm. In 13 centers, the approach used was percutaneous, in 4 videolaparoscopic, and in 3 laparotomic. Results: No deaths were reported. Major complications occurred in 22 cases (2.9%), and minor complications in 54 patients (7.3%). Complications of MWA do not differ from those RFA, both being based on the heat damage. Conclusion: Results of this multicenter study confirmed those of single-center experiences, indicating that MWA is a safe procedure, with no mortality and a low rate of major complications. The low rate of complications was probably due to precautions adopted, knowing in advance possible risk conditions, on the basis of prior RFA experience.« less

Candida infective endocarditis.

PubMed

Baddley, J W; Benjamin, D K; Patel, M; Miró, J; Athan, E; Barsic, B; Bouza, E; Clara, L; Elliott, T; Kanafani, Z; Klein, J; Lerakis, S; Levine, D; Spelman, D; Rubinstein, E; Tornos, P; Morris, A J; Pappas, P; Fowler, V G; Chu, V H; Cabell, C

2008-07-01

Candida infective endocarditis (IE) is uncommon but often fatal. Most epidemiologic data are derived from small case series or case reports. This study was conducted to explore the epidemiology, treatment patterns, and outcomes of patients with Candida IE. We compared 33 Candida IE cases to 2,716 patients with non-fungal IE in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS). Patients were enrolled and the data collected from June 2000 until August 2005. We noted that patients with Candida IE were more likely to have prosthetic valves (p < 0.001), short-term indwelling catheters (p < 0.0001), and have healthcare-associated infections (p < 0.001). The reasons for surgery differed between the two groups: myocardial abscess (46.7% vs. 22.2%, p = 0.026) and persistent positive blood cultures (33.3% vs. 9.9%, p = 0.003) were more common among those with Candida IE. Mortality at discharge was higher in patients with Candida IE (30.3%) when compared to non-fungal cases (17%, p = 0.046). Among Candida patients, mortality was similar in patients who received combination surgical and antifungal therapy versus antifungal therapy alone (33.3% vs. 27.8%, p = 0.26). New antifungal drugs, particularly echinocandins, were used frequently. These multi-center data suggest distinct epidemiologic features of Candida IE when compared to non-fungal cases. Indications for surgical intervention are different and mortality is increased. Newer antifungal treatment options are increasingly used. Large, multi-center studies are needed to help better define Candida IE.

Candida Infective Endocarditis

PubMed Central

Baddley, John W.; Benjamin, Daniel K.; Patel, Mukesh; Miró, José; Athan, Eugene; Barsic, Bruno; Bouza, Emilio; Clara, Liliana; Elliott, Tom; Kanafani, Zeina; Klein, John; Lerakis, Stamatios; Levine, Donald; Spelman, Denis; Rubinstein, Ethan; Tornos, Pilar; Morris, Arthur J.; Pappas, Paul; Fowler, Vance G.; Chu, Vivian H.; Cabell, Christopher

2009-01-01

Purpose Candida infective endocarditis (IE) is uncommon but often fatal. Most epidemiologic data are derived from small case series or case reports. This study was conducted to explore epidemiology, treatment patterns, and outcomes of patients with Candida IE. Methods We compared 33 Candida IE cases to 2716 patients with non-fungal IE in the International Collaboration on Endocarditis - Prospective Cohort Study. Patients were enrolled and data collected from June 2000 until August 2005. Results Patients with Candida IE were more likely to have prosthetic valves (p<0.001), short term indwelling catheters (p<0.0001), and have healthcare-associated infection (p<0.001). Reasons for surgery differed between the two groups: myocardial abscess (46.7% vs. 22.2% p=0.026) and persistent positive blood cultures (33.3% vs. 9.9%, p=0.003) were more common among those with Candida IE. Mortality at discharge was higher in patients with Candida IE (30.3%) when compared to non-fungal cases (17%, p=0.046). Among Candida patients, mortality was similar in patients who received combination surgical and antifungal therapy versus antifungal therapy alone (33.3% vs. 27.8%, p=0.26). New antifungal drugs, particularly echinocandins, were used frequently. Conclusions These multi-center data suggest distinct epidemiologic features of Candida IE when compared to non-fungal cases. Indications for surgical intervention are different and mortality is increased. Newer antifungal treatment options are increasingly used. Large, multi-center studies are needed to help better define Candida IE. PMID:18283504

Validation of the Ottawa Knee Rule in children: a multicenter study.

PubMed

Bulloch, Blake; Neto, Gina; Plint, Amy; Lim, Rodrick; Lidman, Per; Reed, Martin; Nijssen-Jordan, Cheri; Tenenbein, Milton; Klassen, Terry P; Bhargava, Ravi

2003-07-01

The main objective of this study was to determine the sensitivity and specificity of the Ottawa Knee Rules when they were applied to children. The secondary objective was to determine post hoc whether use of the rules would reduce the number of knee radiographs ordered. This prospective, multicenter validation study included children aged 2 to 16 years who presented to the emergency department with a knee injury sustained in the preceding 7 days. Children were assessed for the variables comprising the Ottawa Knee Rules, and physicians ordered radiographs at their discretion. A positive outcome was defined as any fracture. A negative outcome was defined as children who did not have a fracture on radiograph or, if no radiograph was obtained, were asymptomatic after 14 days. A total of 750 children were enrolled. The mean age was 11.8+/-3.1 years, and 443 (58.7%) were male patients. Seventy children had fractures. Radiography was performed for 670 children, whereas 80 children had only a structured telephone interview. The Ottawa Knee Rules were 100% sensitive (95% confidence interval [CI] 94.9% to 100%), with a specificity of 42.8% (95% CI 39.1% to 46.5%). Only 460 children would have required a radiograph if radiographs had been performed according to the Ottawa Knee Rules, which would have resulted in an absolute reduction of 209 (31.2%) radiographs. The Ottawa Knee Rules are valid in children and have the potential to decrease the use of radiography in children with knee injuries.

The association between the miRNA-146a rs2910164 C>G polymorphism and Kawasaki disease in a southern Chinese population.

PubMed

Zhang, Li; Wang, Jinxin; Che, Di; Wang, Yanfei; Rong, Xing; Pi, Lei; Xu, Yufen; Li, Wei; Huang, Ping; Chu, Maoping; Gu, Xiaoqiong

2018-06-14

miRNA-146a plays a critical role in innate immune and inflammatory responses. Kawasaki disease involves immune-mediated inflammatory responses, which lead to vascular endothelial injury. However, there has been no study on the association between the miRNA-146a rs2910164 C>G polymorphism and Kawasaki disease risk. We enrolled 532 Kawasaki disease patients and 623 healthy controls from a southern Chinese population, and the miRNA-146a rs2910164 C>G polymorphism was genotyped by the TaqMan method. There was no evidence that this polymorphism was associated with Kawasaki disease. Stratified analysis also showed no significant association. This study indicates that the miRNA-146a rs2910164 C>G polymorphism may not be associated with Kawasaki disease in a southern Chinese population. Larger, multicenter studies are needed to confirm our conclusions. ©2018 The Author(s).

Effectiveness of adjuvant radiotherapy in patients with oropharyngeal and floor of mouth squamous cell carcinoma and concomitant histological verification of singular ipsilateral cervical lymph node metastasis (pN1-state)--a prospective multicenter randomized controlled clinical trial using a comprehensive cohort design.

PubMed

Moergel, Maximilian; Jahn-Eimermacher, Antje; Krummenauer, Frank; Reichert, Torsten E; Wagner, Wilfried; Wendt, Thomas G; Werner, Jochen A; Al-Nawas, Bilal

2009-12-23

Modern radiotherapy plays an important role in therapy of advanced head and neck carcinomas. However, no clinical studies have been published addressing the effectiveness of postoperative radiotherapy in patients with small tumor (pT1, pT2) and concomitant ipsilateral metastasis of a single lymph node (pN1), which would provide a basis for a general treatment recommendation. The present study is a non-blinded, prospective, multi-center randomized controlled trial (RCT). As the primary clinical endpoint, overall-survival in patients receiving postoperative radiation therapy vs. patients without adjuvant therapy following curative intended surgery is compared. The aim of the study is to enroll 560 adult males and females for 1:1 randomization to one of the two treatment arms (irradiation/no irradiation). Since patients with small tumor (T1/T2) but singular lymph node metastasis are rare and the amount of patients consenting to randomization is not predictable in advance, all patients rejecting randomization will be treated as preferred and enrolled in a prospective observational study (comprehensive cohort design) after giving informed consent. This observational part of the trial will be performed with maximum consistency to the treatment and observation protocol of the RCT. Because the impact of patient preference for a certain treatment option is not calculable, parallel design of RCT and observational study may provide a maximum of evidence and efficacy for evaluation of treatment outcome. Secondary clinical endpoints are as follows: incidence and time to tumor relapse (locoregional relapse, lymph node involvement and distant metastatic spread), Quality of life as reported by EORTC (QLQ-C30 with H&N 35 module), and time from operation to orofacial rehabilitation. All tumors represent a homogeneous clinical state and therefore additional investigation of protein expression levels within resection specimen may serve for establishment of surrogate parameters of patient outcome. The inherent challenges of a rare clinical condition (pN1) and two substantially different therapy arms would limit the practicality of a classical randomized study. The concept of a Comprehensive Cohort Design combines the preference of a randomized study, with the option of careful data interpretation within an observational study. ClinicalTrials.gov: NCT00964977.

Subclinical atherosclerosis and history of cardiovascular events in Italian patients with rheumatoid arthritis: Results from a cross-sectional, multicenter GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study.

PubMed

Ruscitti, Piero; Margiotta, Domenico Paolo Emanuele; Macaluso, Federica; Iacono, Daniela; D'Onofrio, Francesca; Emmi, Giacomo; Atzeni, Fabiola; Prete, Marcella; Perosa, Federico; Sarzi-Puttini, Piercarlo; Emmi, Lorenzo; Cantatore, Francesco Paolo; Triolo, Giovanni; Afeltra, Antonella; Giacomelli, Roberto; Valentini, Gabriele

2017-10-01

Several studies have pointed out a significant association between rheumatoid arthritis (RA) and accelerated atherosclerosis. At the best of our knowledge, no such study has been carried out in a large Italian series and, in this study, we aimed to investigate the prevalence of both subclinical atherosclerosis and history of cardiovascular events (CVEs), in patients consecutively admitted from January 1, 2015 to December 31, 2015 to Rheumatology Units throughout the whole Italy.Centers members of GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) were invited to enrol patients consecutively admitted from January 1, 2015 to December 31, 2015 and satisfying American College of Rheumatology/ European League Against Rheumatism criteria for RA and to investigate each of them for: traditional cardiovascular risk factors: sex, age, smoking habit, total cholesterol, triglycerides, glycaemia, high blood pressure, metabolic syndrome (MS), type 2 diabetes (T2D); RA features: disease duration as assessed from the first symptom, disease activity as evaluated by DAS28, radiographic damage as assessed by hands and feet x-ray, and previous joint surgery; prevalence of both subclinical atherosclerosis and history of CVEs.Eight centers participated to the study. From January 1, 2015 to December 31, 2015, the 1176 patients, who had been investigated for all the items, were enrolled in the study. They were mostly women (80.52%), with a median age of 60 years (range, 18-91 years), a median disease duration of 12 years (range, 0.8-25 years), seropositive in 69.21%. Nineteen percent were in remission; 17.51% presented low disease activity; 39.45% moderate disease activity; 22.61% high disease activity.Eighty-two patients (6.9%) had a history for CVEs (58 myocardial infarction, 38 heart failure, 10 ischemic transitory attack, and 7 stroke). This figure appears to be lower than that reported worldwide (8.5%). After excluding the 82 patients with a history of CV events, subclinical atherosclerosis was detected in 16% of our patients, (176 patients), a figure lower than that reported worldwide (32.7%) and in previous Italian studies.This is the first Italian multicenter study on subclinical and clinical atherosclerosis in patients with RA. We pointed out a low prevalence of both subclinical atherosclerosis and history of CV events.

Insulin resistance is associated with depression risk in polycystic ovary syndrome.

PubMed

Greenwood, Eleni A; Pasch, Lauri A; Cedars, Marcelle I; Legro, Richard S; Eisenberg, Esther; Huddleston, Heather G

2018-06-13

To test the hypothesis that insulin resistance is associated with depression risk in polycystic ovary syndrome (PCOS). Secondary analysis of data from a multicenter randomized trial. Multicenter university-based clinical practices. Seven hundred thirty-eight women with PCOS by modified Rotterdam criteria seeking pregnancy enrolled in a randomized clinical trial comparing clomiphene citrate versus letrozole. The Primary Care Evaluation of Mental Disorders Patient Health Questionnaire was self-administered to identify depression using a validated algorithm at enrollment. Demographic and anthropometric data were collected, and serum assays were performed. Insulin resistance was estimated using the homeostatic model of insulin resistance (HOMA-IR), with a cutoff of >2.2 considered abnormal. Demographic, endocrine, and metabolic parameters associated with depression. In a univariate logistic regression analysis, elevated HOMA-IR was associated with 2.3-fold increased odds of depression (odds ratio [OR] = 2.32; 95% confidence interval [CI], 1.28-4.21). This association remained significant after controlling for age and body mass index (adjusted OR [aOR] = 2.23; 95% CI, 1.11-4.46) and in a model including additional potential confounders (aOR = 2.03; 95% CI, 1.00-4.16). Insulin resistance has a strong and independent association with depression in PCOS and may serve as a physiologic mediator. Our findings corroborate a growing body of evidence linking insulin resistance to depressed mood. The association between insulin resistance and depressed mood warrants further investigation to elucidate mechanisms and identify potential therapeutic targets. Copyright © 2018 American Society for Reproductive Medicine. All rights reserved.

Once-monthly injection of paliperidone palmitate in patients with recently diagnosed and chronic schizophrenia: a post-hoc comparison of efficacy and safety.

PubMed

Si, Tianmei; Zhuo, Jianmin; Turkoz, Ibrahim; Mathews, Maju; Tan, Wilson; Feng, Yu

2017-12-01

The use of long-acting injectable antipsychotics in recently diagnosed schizophrenia remains less explored. We evaluated the efficacy and safety of paliperidone palmitate once-monthly (PP1M) treatment in adult patients with recently diagnosed vs. chronic schizophrenia. These post-hoc analyses included two multicenter studies. Study 1 (NCT01527305) enrolled recently diagnosed (≤5 years) and chronic (>5 years) patients; Study 2 (NCT01051531) enrolled recently diagnosed patients only. Recently diagnosed patients were further sub-grouped into ≤2 years or 2-5 years. The primary efficacy endpoint was the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score. In Study 1, 41.5% patients had recent diagnosis (≤2 years: 56.8%; 2-5 years: 43.2%); 58.5% had chronic schizophrenia. In Study 2, 52.8% and 47.2% patients were grouped into ≤2 years and 2-5 years, respectively. PANSS total score showed significantly greater improvement in patients with recently diagnosed vs. chronic schizophrenia. Similar results were obtained for PANSS responder rate, improvements in PANSS, and CGI-S scores. PP1M was efficacious in both recently diagnosed and chronic schizophrenia, with the benefits being more pronounced in patients with recently diagnosed schizophrenia. This adds to growing evidence recommending long-acting antipsychotic interventions at early stages of schizophrenia.

The impact of wire caliber on ERCP outcomes: a multicenter randomized controlled trial of 0.025-inch and 0.035-inch guidewires.

PubMed

Bassan, Milan S; Sundaralingam, Praka; Fanning, Scott B; Lau, James; Menon, Jayaram; Ong, Evan; Rerknimitr, Rungsun; Seo, Dong-Wan; Teo, Eng Kiong; Wang, Hsiu-Po; Reddy, D Nageshwar; Goh, Khean Lee; Bourke, Michael J

2018-06-01

Wire-guided biliary cannulation has been demonstrated to improve cannulation rates and reduce post-ERCP pancreatitis (PEP), but the impact of wire caliber has not been studied. This study compares successful cannulation rates and ERCP adverse events by using a 0.025-inch and 0.035-inch guidewire. A randomized, single blinded, prospective, multicenter trial at 9 high-volume tertiary-care referral centers in the Asia-Pacific region was performed. Patients with an intact papilla and conventional anatomy who did not have malignancy in the head of the pancreas or ampulla and were undergoing ERCP were recruited. ERCP was performed by using a standardized cannulation algorithm, and patients were randomized to either a 0.025-inch or 0.035-inch guidewire. The primary outcomes of the study were successful wire-guided cannulation and the incidence of PEP. Overall successful cannulation and ERCP adverse events also were studied. A total of 710 patients were enrolled in the study. The primary wire-guided biliary cannulation rate was similar in 0.025-inch and 0.035-inch wire groups (80.7% vs 80.3%; P = .90). The rate of PEP between the 0.025-inch and the 0.035-inch wire groups did not differ significantly (7.8% vs 9.3%; P = .51). No differences were noted in secondary outcomes. Similar rates of successful cannulation and PEP were demonstrated in the use of 0.025-inch and 0.035-inch guidewires. (Clinical trial registration number: NCT01408264.). Copyright © 2018. Published by Elsevier Inc.

Outcome after one year of upper airway stimulation for obstructive sleep apnea in a multicenter German post-market study.

PubMed

Steffen, Armin; Sommer, J Ulrich; Hofauer, Benedikt; Maurer, Joachim T; Hasselbacher, Katrin; Heiser, Clemens

2018-02-01

Upper airway stimulation (UAS) of the hypoglossal nerve has been implemented in the routine clinical practice for patients with moderate-to-severe obstructive sleep apnea (OSA) who could not adhere to continuous positive airway pressure. This study reports objective and patient-reported outcome after 12 months of implantation. Multicenter prospective single-arm study. Consecutive patients who received the UAS system (Inspire Medical Systems, Inc., Minneapolis, Minnesota, Maple Grove, MN, U.S.A.) were enrolled in three German centers. Key study exclusion criteria included body mass index > 35 kg/m 2 , apnea-hypopnea index (AHI) < 15 or > 65, or complete concentric collapse at the soft palate during sedated endoscopy. Data collection at 6- and 12-month visit include home sleep test and patient-reported outcome measures. Among the total of 60 participants, the median AHI reduced from 28.6 to 9.5 from baseline to 12 months. Patient-reported outcome measured in Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire both improved significantly from baseline to 12 months. The average usage time was 39.1 ± 14.9 hours per week among all participants based on recordings by the implanted device. One patient requested a removal of the device for cosmetic and other personal reasons and was completed without sequelae. This study supported that UAS is a safe and effective treatment option for patients with OSA in routine clinical practice. 4. Laryngoscope, 128:509-515, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Clinical and Biological Predictors of Plasma Levels of Soluble RAGE in Critically Ill Patients: Secondary Analysis of a Prospective Multicenter Observational Study

PubMed Central

Pranal, Thibaut; Pereira, Bruno; Berthelin, Pauline; Roszyk, Laurence; Chabanne, Russell; Eisenmann, Nathanael; Lautrette, Alexandre; Belville, Corinne; Blondonnet, Raiko; Gillart, Thierry; Skrzypczak, Yvan; Souweine, Bertrand; Bouvier, Damien; Constantin, Jean-Michel

2018-01-01

Rationale Although soluble forms of the receptor for advanced glycation end products (RAGE) have been recently proposed as biomarkers in multiple acute or chronic diseases, few studies evaluated the influence of usual clinical and biological parameters, or of patient characteristics and comorbidities, on circulating levels of soluble RAGE in the intensive care unit (ICU) setting. Objectives To determine, among clinical and biological parameters that are usually recorded upon ICU admission, which variables, if any, could be associated with plasma levels of soluble RAGE. Methods Data for this ancillary study were prospectively obtained from adult patients with at least one ARDS risk factor upon ICU admission enrolled in a large multicenter observational study. At ICU admission, plasma levels of total soluble RAGE (sRAGE) and endogenous secretory (es)RAGE were measured by duplicate ELISA and baseline patient characteristics, comorbidities, and usual clinical and biological indices were recorded. After univariate analyses, significant variables were used in multivariate, multidimensional analyses. Measurements and Main Results 294 patients were included in this ancillary study, among whom 62% were admitted for medical reasons, including septic shock (11%), coma (11%), and pneumonia (6%). Although some variables were associated with plasma levels of RAGE soluble forms in univariate analysis, multidimensional analyses showed no significant association between admission parameters and baseline plasma sRAGE or esRAGE. Conclusions We found no obvious association between circulating levels of soluble RAGE and clinical and biological indices that are usually recorded upon ICU admission. This trial is registered with NCT02070536. PMID:29861796

Multicenter cohort study on association of genotypes with prospective sports concussion: methods, lessons learned, and recommendations.

PubMed

Terrell, Thomas R; Bostick, Roberd; Barth, Jeffrey; Sloane, Richard; Cantu, Robert C; Bennett, Ellen; Galloway, Leslie; Laskowitz, Daniel; Erlanger, Dave; McKeag, Doug; Valentine, Verle; Nichols, Gregory

2017-01-01

Approximately 3.8 million sports related TBIs occur per year. Genetic variation may affect both TBI risk and post-TBI clinical outcome. Limited research has focused on genetic risk for concussion among athletes. We describe the design, methods, and baseline characteristics of this prospective cohort study designed to investigate a potential association between genetic polymorphisms of apolipoprotein E gene, APOE promoter G-219T, and Tau gene exon 6 polymorphisms (Ser53 Pro and Hist47Tyr) with: 1) the risk of prospective concussion; 2) concussion severity; and 3) postconcussion neurocognitive recovery. The prospective cohort study included a final population of 2947 college, high school, and professional athletes. Baseline data collection included a concussion/medical history questionnaire, neuropsychological (NP) testing, and genetic sampling for the genetic polymorphisms. Data collection on new concussions experienced utilized post-concussion history/mental status form, Lovell post-concussion symptom score, Standardized Assessment of Concussion (SAC) and/or the Sports Concussion Assessment Tool (SCAT)-1/SCAT-2, and post-concussion NP testing. This paper is focused on discussing the important methodological considerations, organizational challenges and lessons learned in the completion of a multi-center prospective cohort study. A total of 3740 subjects enrolled, with a total of 335 concussions experienced. Of critical importance to the success of a study of this type is to successfully recruit committed institutions with qualified local study personnel, obtain "buy-in" from study sites, and cultivate strong working relationships with study sites. The use of approved incentives may improve study site recruitment, enhance retention, and enhance compliance with study protocols. Future publications will detail the specific findings of this study. Collaborative research is very likely needed given the nature of this study population.

Prospective, non-interventional, multicenter study of the intraocular pressure-lowering effects of prostaglandin analog/prostamide-containing therapies in previously treated patients with open-angle glaucoma or ocular hypertension

PubMed Central

Tamçelik, Nevbahar; Izgi, Belgin; Temel, Ahmet; Yildirim, Nilgun; Okka, Mehmet; Özcan, Altan; Yüksel, Nurşen; Elgin, Ufuk; Altan, Çiğdem; Ozer, Baris

2017-01-01

Objective The objective of this study was to assess the intraocular pressure (IOP)-lowering efficacy, tolerability, safety, and usage patterns of prostaglandin analog/prostamide (PGA/P)-containing topical ocular hypotensives in ocular hypertension (OHT) and primary open-angle glaucoma in the Turkish clinical setting. Methods This non-interventional, multicenter study enrolled previously treated patients who failed to achieve target IOP (or experienced unacceptable adverse events [AEs]) and were prescribed a PGA/P-containing IOP-lowering agent. Treatment was initiated at baseline (V1), and patients returned at weeks 4–6 (V2) and 8–12 (V3). The primary efficacy measure was the change in IOP from baseline at V3 in each eye. The secondary measures were physician’s assessment of IOP-lowering efficacy, patients (%) reaching target IOP determined at V1, hyperemia score, physician and patient assessment of study treatment tolerability at V3, and AE frequency/severity. A subgroup analysis of patients receiving the most common study treatment was conducted. All analyses were performed using the safety population (patients who received one or more doses and had any data available). Results Of 358 enrolled patients, 60.6% had primary open-angle glaucoma, 29.9% had secondary open-angle glaucoma (protocol amendment), and 13.1% had OHT; 13 patients had multiple diagnoses. At V3, the mean IOP change from baseline was ≥−4.2 mmHg (≥21.1%). IOP met or was lower than the target in 81.7% of patients, 95% exhibited none to mild conjunctival hyperemia (most common AE), and tolerability was rated good/very good by >91.1% of patients and physicians. The results were similar in patients who received the most common study treatment, bimatoprost 0.03%/timolol 0.5% (bim/tim; n=310). Conclusion PGA/P-containing medications, including bim/tim, significantly reduced IOP in previously treated patients with open-angle glaucoma or OHT; most reached their target IOP or an IOP even lower than their target and reported good/very good tolerability. PGA/P-containing medications such as bim/tim should be considered as a safe, effective therapeutic option for Turkish patients who exhibit poor response, tolerance, or adherence to their previous therapy. PMID:28458511

Early Enteral Nutrition in Burns: Compliance With Guidelines and Associated Outcomes in a Multicenter Study

PubMed Central

Mosier, Michael J.; Pham, Tam N.; Klein, Matthew B.; Gibran, Nicole S.; Arnoldo, Brett D.; Gamelli, Richard L.; Tompkins, Ronald G.; Herndon, David N.

2013-01-01

Early nutritional support is an essential component of burn care to prevent ileus, stress ulceration, and the effects of hypermetabolism. The American Burn Association practice guidelines state that enteral feedings should be initiated as soon as practical. The authors sought to evaluate compliance with early enteral nutrition (EN) guidelines, associated complications, and hospitalization outcomes in a prospective multicenter observational study. They conducted a retrospective review of mechanically ventilated burn patients enrolled in the prospective observational multicenter study “Inflammation and the Host Response to Injury.” Timing of initiation of tube feedings was recorded, with early EN defined as being started within 24 hours of admission. Univariate and multivariate analyses were performed to distinguish barriers to initiation of EN and the impact of early feeding on development of multiple organ dysfunction syndrome, infectious complications, days on mechanical ventilation, intensive care unit (ICU) length of stay, and survival. A total of 153 patients met study inclusion criteria. The cohort comprised 73% men, with a mean age of 41 ± 15 years and a mean %TBSA burn of 46 ± 18%. One hundred twenty-three patients (80%) began EN in the first 24 hours and 145 (95%) by 48 hours. Age, sex, inhalation injury, and full-thickness burn size were similar between those fed by 24 hours vs after 24 hours, except for higher mean Acute Physiology and Chronic Health Evaluation II scores (26 vs 23, P = .03) and smaller total burn size (44 vs 54% TBSA burn, P = .01) in those fed early. There was no significant difference in rates of hyperglycemia, abdominal compartment syndrome, or gastrointestinal bleeding between groups. Patients fed early had shorter ICU length of stay (adjusted hazard ratio 0.57, P = 0.03, 95% confidence interval 0.35–0.94) and reduced wound infection risk (adjusted odds ratio 0.28, P = 0.01, 95% confidence interval 0.10–0.76). The investigators have found early EN to be safe, with no increase in complications and a lower rate of wound infections and shorter ICU length of stay. Across institutions, there has been high compliance with early EN as part of the standard operating procedure in this prospective multicenter observational trial. The investigators advocate that initiation of EN by 24 hours be used as a formal recommendation in nutrition guidelines for severe burns, and that nutrition guidelines be actively disseminated to individual burn centers to permit a change in practice. PMID:21116188

Multicenter Trial of Sentinel Node Biopsy for Breast Cancer Using Both Technetium Sulfur Colloid and Isosulfan Blue Dye

PubMed Central

Tafra, Lorraine; Lannin, Donald R.; Swanson, Melvin S.; Van Eyk, Jason J.; Verbanac, Kathryn M.; Chua, Arlene N.; Ng, Peter C.; Edwards, Maxine S.; Halliday, Bradford E.; Henry, C. Alan; Sommers, Linda M.; Carman, Claire M.; Molin, Melinda R.; Yurko, John E.; Perry, Roger R.; Williams, Robert

2001-01-01

Objective To determine the factors associated with false-negative results on sentinel node biopsy and sentinel node localization (identification rate) in patients with breast cancer enrolled in a multicenter trial using a combination technique of isosulfan blue with technetium sulfur colloid (Tc99). Summary Background Data Sentinel node biopsy is a diagnostic test used to detect breast cancer metastases. To test the reliability of this method, a complete lymph node dissection must be performed to determine the false-negative rate. Single-institution series have reported excellent results, although one multicenter trial reported a false-negative rate as high as 29% using radioisotope alone. A multicenter trial was initiated to test combined use of Tc99 and isosulfan blue. Methods Investigators (both private-practice and academic surgeons) were recruited after attending a course on the technique of sentinel node biopsy. No investigator participated in a learning trial before entering patients. Tc99 and isosulfan blue were injected into the peritumoral region. Results Five hundred twenty-nine patients underwent 535 sentinel node biopsy procedures for an overall identification rate in finding a sentinel node of 87% and a false-negative rate of 13%. The identification rate increased and the false-negative rate decreased to 90% and 4.3%, respectively, after investigators had performed more than 30 cases. Univariate analysis of tumor showed the poorest success rate with older patients and inexperienced surgeons. Multivariate analysis identified both age and experience as independent predictors of failure. However, with older patients, inexperienced surgeons, and patients with five or more metastatic axillary nodes, the false-negative rate was consistently greater. Conclusions This multicenter trial, from both private practice and academic institutions, is an excellent indicator of the general utility of sentinel node biopsy. It establishes the factors that play an important role (patient age, surgical experience, tumor location) and those that are irrelevant (prior surgery, tumor size, Tc99 timing). This widens the applicability of the technique and identifies factors that require further investigation. PMID:11141225

Levetiracetam for the treatment of alcohol withdrawal syndrome: a multicenter, prospective, randomized, placebo-controlled trial.

PubMed

Richter, Christoph; Hinzpeter, Axel; Schmidt, Folkhard; Kienast, Thorsten; Preuss, Ulrich W; Plenge, Thomas; Heinz, Andreas; Schaefer, Martin

2010-12-01

Treatment of alcohol withdrawal syndrome (AWS) with benzodiazepines is limited by risk of abuse, intoxication, respiratory problems, and liver toxicity. Alternatives such as carbamazepine and valproate may also have safety problems, such as hepatotoxicity or central nervous adverse effects. We therefore investigated the safety and efficacy of levetiracetam (LV), a newer antiepileptic with a potentially favorable adverse-effect profile, for the treatment of AWS. One hundred six patients were enrolled in a prospective, randomized, double-blind, multicenter, placebo-controlled trial. Levetiracetam was administered in a fixed dose schedule over 6 days. Diazepam was added when symptom triggered as rescue medication. Severity of the AWS was measured with the AWS and Clinical Institute Withdrawal Assessment Scale. Although tolerability and safety data were similar in the LV group when compared with placebo, the total daily and weekly dose of diazepam as rescue medication and the severity of alcohol withdrawal symptoms did not differ significantly between groups. Our data so far do not support an additional effect of LV on the reduction of alcohol withdrawal symptoms.

The Lipid-Rich Plaque Study of vulnerable plaques and vulnerable patients: Study design and rationale.

PubMed

Waksman, Ron; Torguson, Rebecca; Spad, Mia-Ashley; Garcia-Garcia, Hector; Ware, James; Wang, Rui; Madden, Sean; Shah, Priti; Muller, James

2017-10-01

It has been hypothesized that the outcome post-PCI could be improved by the detection and subsequent treatment of vulnerable patients and lipid-rich vulnerable coronary plaques (LRP). A near-infrared spectroscopy (NIRS) catheter capable of detecting LRP is being evaluated in The Lipid-Rich Plaque Study. The LRP Study is an international, multicenter, prospective cohort study conducted in patients with suspected coronary artery disease (CAD) who underwent cardiac catheterization with possible ad hoc PCI for an index event. Patient level and plaque level events were detected by follow-up in the subsequent 2 years. Enrollment began in February 2014 and was completed in March 2016; a total of 1,562 patients were enrolled. Adjudication of new coronary event occurrence and de novo culprit lesion location during the 2-year follow-up is performed by an independent clinical end-points committee (CEC) blinded to NIRS-IVUS findings. The first analysis of the results will be performed when at least 20 de novo events have occurred for which follow-up angiographic data and baseline NIRS-IVUS measurements are available. It is expected that results of the study will be announced in 2018. The LRP Study will test the hypotheses that NIRS-IVUS imaging to detect LRP in patients can identify vulnerable patients and vulnerable plaques. Identification of vulnerable patients will assist future studies of novel systemic therapies; identification of localized vulnerable plaques would enhance future studies of possible preventive measures. Copyright © 2017 Elsevier Inc. All rights reserved.

Biomarker-driven trial in metastatic pancreas cancer: feasibility in a multicenter study of saracatinib, an oral Src inhibitor, in previously treated pancreatic cancer.

PubMed

Arcaroli, John; Quackenbush, Kevin; Dasari, Arvind; Powell, Rebecca; McManus, Martine; Tan, Aik-Choon; Foster, Nathan R; Picus, Joel; Wright, John; Nallapareddy, Sujatha; Erlichman, Charles; Hidalgo, Manuel; Messersmith, Wells A

2012-10-01

Src tyrosine kinases are overexpressed in pancreatic cancers, and the oral Src inhibitor saracatinib has shown antitumor activity in preclinical models of pancreas cancer. We performed a CTEP-sponsored Phase II clinical trial of saracatinib in previously treated pancreas cancer patients, with a primary endpoint of 6-month survival. A Simon MinMax two-stage phase II design was used. Saracatinib (175 mg/day) was administered orally continuously in 28-day cycles. In the unselected portion of the study, 18 patients were evaluable. Only two (11%) patients survived for at least 6 months, and three 6-month survivors were required to move to second stage of study as originally designed. The study was amended as a biomarker-driven trial (leucine rich repeat containing protein 19 [LRRC19] > insulin-like growth factor-binding protein 2 [IGFBP2] "top scoring pairs" polymerase chain reaction [PCR] assay, and PIK3CA mutant) based on preclinical data in a human pancreas tumor explant model. In the biomarker study, archival tumor tissue or fresh tumor biopsies were tested. Biomarker-positive patients were eligible for the study. Only one patient was PIK3CA mutant in a 3' untranslated region (UTR) portion of the gene. This patient was enrolled in the study and failed to meet the 6-month survival endpoint. As the frequency of biomarker-positive patients was very low (<3%), the study was closed. Although we were unable to conclude whether enriching for a subset of second/third line pancreatic cancer patients treated with a Src inhibitor based on a biomarker would improve 6-month survival, we demonstrate that testing pancreatic tumor samples for a biomarker-driven, multicenter study in metastatic pancreas cancer is feasible.

A multicenter, open-label, 52-week study of 2% rebamipide (OPC-12759) ophthalmic suspension in patients with dry eye.

PubMed

Kinoshita, Shigeru; Awamura, Saki; Nakamichi, Norihiro; Suzuki, Hiroyuki; Oshiden, Kazuhide; Yokoi, Norihiko

2014-03-01

To investigate the efficacy and safety of 2% rebamipide ophthalmic suspension administered 4 times daily for 52 weeks in patients with dry eye. Multicenter (17 sites), open-label, single-arm study. A total of 154 patients with dry eye were enrolled in this study. After a 2-week screening period, patients received 2% rebamipide, instilled as 1 drop in each eye, 4 times daily for 52 weeks. The signs and symptoms measures were assessed at baseline, at weeks 2 and 4, and at every 4 weeks thereafter. The objective signs were fluorescein corneal staining score, lissamine green conjunctival staining score, and tear film break-up time, while subjective symptoms were dry eye-related ocular symptoms (foreign body sensation, dryness, photophobia, eye pain, and blurred vision). The safety variable was the occurrence of adverse events. For all objective signs and subjective symptoms, the scores significantly improved at week 2 compared with baseline (P < .001, paired t test). Interestingly, further improvements of those scores were observed at every visit up to week 52. No deaths were reported, yet serious adverse events that were not thought to be drug related were observed in 6 patients. The incidence of any of the adverse events did not markedly increase throughout the 52-week treatment period. The results of this study show that 2% rebamipide is effective in improving both the objective signs and subjective symptoms of dry eye patients for at least 52 weeks. In addition, 2% rebamipide treatment was generally well tolerated. Copyright © 2014. Published by Elsevier Inc.

Treatment of scabies with 5% permethrin cream: results of a German multicenter study.

PubMed

Hamm, Henning; Beiteke, Ulrike; Höger, Peter H; Seitz, Cornelia S; Thaci, Diamant; Sunderkötter, Cord

2006-05-01

Until recently, no prescription drug containing permethrin for the therapy of scabies was available on the German market.Therefore, a 5% permethrin cream formulation (InfectoScab 5%) was tested in a single-arm multi-center study including adults and children from 3 months of age with proven scabies. On day 0, patients were treated once with permethrin cream in the study center. Control examinations including dermatoscopy were performed on day 14+/-2 and on day 28+/-3. Patients who were not considered cured or who had contact to individuals with untreated scabies received one further treatment with permethrin cream on day 14+/-2. Itching and local tolerability of the cream were documented in patients' diaries. Side effects were assessed by history, skin inspection and evaluation of patients' notes. 106 patients in 13 centers were enrolled in the study. Their mean age was 29.2 years (range, 141 days to 71.9 years); 34% of them were children or adolescents. 78.3% of patients were either severely (3 body sites) or very severely (4-5 sites) affected. The cure rate on day 28+/-3 was 95.1% (95% confidence interval, 91.0-99.3%). Pruritus declined markedly and continuously. In general, the cream was well tolerated; side effects were almost invariably mild. Our results support the efficacy and safety of 5% permethrin cream in adults, children and infants suffering from scabies. These results have contributed to the approval of InfectoScab 5% in Germany for the treatment of scabies in October 2004.

Effects of nebivolol and atenolol on central aortic pressure in hypertensive patients: a multicenter, randomized, double-blind study.

PubMed

Redón, Josep; Pascual-Izuel, Jose M; Rodilla, Enrique; Vicente, Antonio; Oliván, Josefina; Bonet, Josep; Torguet, Josep Pere; Calaforra, Oscar; Almirall, Jaume

2014-06-01

The main objective was to compare the mean change in augmentation index of hypertensive patients treated with nebivolol or atenolol. Multicenter, double-blind randomized study conducted in six Spanish centers. We enrolled outpatients between the ages of 40 and 65 years with mild or moderate essential hypertension (systolic blood pressure, SBP ≥ 140 mmHg to ≤ 179 mmHg and diastolic blood pressure, DBP ≥ 90 mmHg to ≤ 109 mmHg after a 2-week run-in placebo period). Patients received nebivolol 5 mg or atenolol 50 mg once daily. At week 3, atenolol could be titrated up to 100 mg qd for non-responders. Additionally, patients not achieving normal blood pressure after 6 weeks could be treated with 25 mg hydrochlorothiazide. Follow-up visits were at 3, 6 and 10 weeks. The final study population of 138 patients (58% men; median age 52.6 years, range 40-67 years) was randomized into two groups of 69 patients each. Baseline characteristics of the two groups were similar. At the screening visit, 69% presented with mild hypertension. Nebivolol modified the mean augmentation index to a lesser extent than atenolol after 10 weeks (mean difference 3.1%, 95% CI 0.55-5.69; p = 0.027). A higher proportion of patients in the atenolol group required a diuretic. Reductions in central aortic pressure and peripheral arterial pressure were similar for both treatment groups. The study confirms that nebivolol produces a less pronounced impact on augmentation index than atenolol.

Clinical outcome of renal artery stenting for hypertension and chronic kidney disease up to 12 months in the J-RAS Study – prospective, single-arm, multicenter clinical study.

PubMed

Fujihara, Masahiko; Yokoi, Yoshiaki; Abe, Takaaki; Soga, Yoshimitsu; Yamashita, Takehiro; Miyashita, Yusuke; Nakamura, Masato; Yokoi, Hiroyoshi; Ito, Sadayoshi

2015-01-01

Atherosclerotic renal artery stenosis (ARAS) causes renovascular hypertension (HTN) and impairs renal function, leading to chronic kidney disease (CKD). The J-RAS study was a prospective, multicenter study to assess the clinical outcome of renal artery stenting for up to 1 year in Japanese patients with ARAS. One hundred and forty-nine patients were enrolled between November 2010 and January 2013. The patients were classified into an HTN (n=121) group and a CKD (n=108) group in the primary analysis. The primary efficacy endpoints were change in blood pressure for the HTN group and change in estimated glomerular filtration rate (eGFR) for the CKD group at 1 months. The primary safety endpoint was freedom from major cardiovascular or renal events at 12 months. In the HTN group, the mean systolic blood pressure (SBP) significantly decreased from 161.6 ± 21 mmHg at baseline to 137.0 ± 21 mmHg (P<0.0001). In the CKD group, there was no significant difference in eGFR from 40.7 ± 10 ml·min(-1)·1.73 m(-2)at baseline to 40.8 ± 13 ml·min(-1)·1.73 m(-2)(P=0.32). The primary safety endpoint was 89.4% at 12 months. In the J-RAS trial, significant SBP reduction was seen in the HTN group, and stabilization of renal function in the CKD group. Renal artery stenting for ARAS is safe and effective in Japanese patients.

Alkalinized lidocaine and heparin provide immediate relief of pain and urgency in patients with interstitial cystitis.

PubMed

Parsons, C Lowell; Zupkas, Paul; Proctor, Jeffrey; Koziol, James; Franklin, Amie; Giesing, Dennis; Davis, Edward; Lakin, Charles M; Kahn, Bruce S; Garner, William J

2012-01-01

It has been reported in an open-label study that the combination of alkalinized lidocaine and heparin can immediately relieve the symptoms of urinary urgency, frequency, and pain associated with interstitial cystitis (IC). This combination has also been reported to relieve pain associated with sex in patients with IC. The aim of this study was to corroborate these findings in a multicenter setting. The study design was a multicenter prospective, double-blind, crossover, placebo-controlled trial. Each participant met all of the clinical National Institute of Diabetes and Digestive and Kidney Diseases criteria (excluding cystoscopy) for IC. Each patient received drug and control, in random order, within 48 hours of enrolling in the study. The primary outcome measure was percent change in pain score (11-point analog pain scale) 12 hours after receiving the drug or control. Secondary measures were the global assessment response (GAR) of symptoms and 12-hour average urgency reduction determined from 11-point urgency scales. Eighteen (18) patients completed the trial. The average reduction of pain over 12 hours was 21% for control and 42% for active drug (P = 0.0363). GAR was 13% for control and 50% for drug (P = 0.0137). Average urgency reduction was 13% for control and 35% for drug (P = 0.0328). The combination of alkalinized lidocaine and heparin provides up to 12 hours of relief from urgency and pain associated with IC. This combination provides significant immediate relief of symptoms for patients with IC. © 2011 International Society for Sexual Medicine.

Effectiveness of intra-articular injections of sodium hyaluronate-chondroitin sulfate in knee osteoarthritis: a multicenter prospective study.

PubMed

Rivera, Fabrizio; Bertignone, Luca; Grandi, Giancarlo; Camisassa, Roberto; Comaschi, Guido; Trentini, Diego; Zanone, Marco; Teppex, Giuseppe; Vasario, Gabriele; Fortina, Giorgio

2016-03-01

Intra-articular injection of hyaluronic acid is a well-established therapy for the treatment of knee osteoarthritis. The aim of the study was to assess the effectiveness and safety of the use of Arthrum HCS(®) (40 mg hyaluronic acid and 40 mg chondroitin sulfate in 2 mL). This was an open, multicenter, prospective study. Men or women over 40 years of age with documented knee osteoarthritis and WOMAC subscore A (severity of pain) ≥25 were enrolled. They received three weekly intra-articular injections of sodium hyaluronate 2 % and chondroitin sulfate 2 % in combination. WOMAC subscore A was assessed at 1, 3 and 6 months after the last injection. One hundred and twelve patients were included (women, 66 %). The mean (SD) WOMAC subscore A decreased from 52.1 (15.2) at inclusion to 20.5 (19.7) at month 6 (P < 0.0001). The mean subscore was already significantly decreased 1 month after the last injection at 25.7 (P < 0.0001). Pain relief and consumption of analgesic drugs, both assessed with visual analogic scale (VAS), consistently decreased. The investigators were satisfied/very satisfied as regards the therapeutic effectiveness of sodium hyaluronate-chondroitin sulfate in reducing pain (77 %), improving mobility (78 %) and reducing the consumption of analgesics (74 %). Only one adverse effect was reported by one patient (knee tumefaction). These results suggest that intra-articular injections of Arthrum HCS(®) (sodium hyaluronate plus chondroitin sulfate) in patients with knee osteoarthritis are efficient and safe. These results should be confirmed in a randomized controlled study. IV.

Validating the Western Trauma Association algorithm for managing patients with anterior abdominal stab wounds: a Western Trauma Association multicenter trial.

PubMed

Biffl, Walter L; Kaups, Krista L; Pham, Tam N; Rowell, Susan E; Jurkovich, Gregory J; Burlew, Clay Cothren; Elterman, J; Moore, Ernest E

2011-12-01

The optimal management of stable patients with anterior abdominal stab wounds (AASWs) remains a matter of debate. A recent Western Trauma Association (WTA) multicenter trial found that exclusion of peritoneal penetration by local wound exploration (LWE) allowed immediate discharge (D/C) of 41% of patients with AASWs. Performance of computed tomography (CT) scanning or diagnostic peritoneal lavage (DPL) did not improve the D/C rate; however, these tests led to nontherapeutic (NONTHER) laparotomy (LAP) in 24% and 31% of cases, respectively. An algorithm was proposed that included LWE, followed by either D/C or admission for serial clinical assessments, without further imaging or invasive testing. The purpose of this study was to evaluate the safety and efficacy of the algorithm in providing timely interventions for significant injuries. A multicenter, institutional review board-approved study enrolled patients with AASWs. Management was guided by the WTA AASW algorithm. Data on the presentation, evaluation, and clinical course were recorded prospectively. Two hundred twenty-two patients (94% men, age, 34.7 years ± 0.3 years) were enrolled. Sixty-two (28%) had immediate LAP, of which 87% were therapeutic (THER). Three (1%) died and the mean length of stay (LOS) was 6.9 days. One hundred sixty patients were stable and asymptomatic, and 81 of them (51%) were managed entirely per protocol. Twenty (25%) were D/C'ed from the emergency department after (-) LWE, and 11 (14%) were taken to the operating room (OR) for LAP when their clinical condition changed. Two (2%) of the protocol group underwent NONTHER LAP, and no patient experienced morbidity or mortality related to delay in treatment. Seventy-nine (49%) patients had deviations from protocol. There were 47 CT scans, 11 DPLs, and 9 laparoscopic explorations performed. In addition to the laparoscopic procedures, 38 (48%) patients were taken to the OR based on test results rather than a change in the patient's clinical condition; 17 (45%) of these patients had a NONTHER LAP. Eighteen (23%) patients were D/C'ed from the emergency department. The LOS was no different among patients who had immediate or delayed LAP. Mean LOS after NONTHER LAP was 3.6 days ± 0.8 days. The WTA proposed algorithm is designed for cost-effectiveness. Serial clinical assessments can be performed without the added expense of CT, DPL, or laparoscopy. Patients requiring LAP generally manifest early in their course, and there does not appear to be any morbidity related to a delay to OR. These data validate this approach and should be confirmed in a larger number of patients to more convincingly evaluate the algorithm's safety and cost-effectiveness compared with other approaches.

A universal definition of ARDS: the PaO2/FiO2 ratio under a standard ventilatory setting--a prospective, multicenter validation study.

PubMed

Villar, Jesús; Pérez-Méndez, Lina; Blanco, Jesús; Añón, José Manuel; Blanch, Lluís; Belda, Javier; Santos-Bouza, Antonio; Fernández, Rosa Lidia; Kacmarek, Robert M

2013-04-01

The PaO2/FiO2 is an integral part of the assessment of patients with acute respiratory distress syndrome (ARDS). The American-European Consensus Conference definition does not mandate any standardization procedure. We hypothesized that the use of PaO2/FiO2 calculated under a standard ventilatory setting within 24 h of ARDS diagnosis allows a more clinically relevant ARDS classification. We studied 452 ARDS patients enrolled prospectively in two independent, multicenter cohorts treated with protective mechanical ventilation. At the time of ARDS diagnosis, patients had a PaO2/FiO2 ≤ 200. In the derivation cohort (n = 170), we measured PaO2/FiO2 with two levels of positive end-expiratory pressure (PEEP) (≥ 5 and ≥ 10 cmH2O) and two levels of FiO2 (≥ 0.5 and 1.0) at ARDS onset and 24 h later. Dependent upon PaO2 response, patients were reclassified into three groups: mild (PaO2/FiO2 > 200), moderate (PaO2/FiO2 101-200), and severe (PaO2/FiO2 ≤ 100) ARDS. The primary outcome measure was ICU mortality. The standard ventilatory setting that reached the highest significance difference in mortality among these categories was tested in a separate cohort (n = 282). The only standard ventilatory setting that identified the three PaO2/FiO2 risk categories in the derivation cohort was PEEP ≥ 10 cmH2O and FiO2 ≥ 0.5 at 24 h after ARDS onset (p = 0.0001). Using this ventilatory setting, patients in the validation cohort were reclassified as having mild ARDS (n = 47, mortality 17 %), moderate ARDS (n = 149, mortality 40.9 %), and severe ARDS (n = 86, mortality 58.1 %) (p = 0.00001). Our method for assessing PaO2/FiO2 greatly improved risk stratification of ARDS and could be used for enrolling appropriate ARDS patients into therapeutic clinical trials.

A multicenter, observational study of lanreotide depot/autogel (LAN) in patients with acromegaly in the United States: 2-year experience from the SODA registry.

PubMed

Salvatori, Roberto; Gordon, Murray B; Woodmansee, Whitney W; Ioachimescu, Adriana G; Carver, Don W; Mirakhur, Beloo; Cox, David; Molitch, Mark E

2017-12-01

This analysis evaluates the 2-year effectiveness and safety of lanreotide depot/autogel (LAN), as well as treatment convenience and acromegaly symptom relief, from the Somatuline ® Depot for Acromegaly (SODA) registry, a post-marketing, open-label, observational, multicenter, United States registry study. Patients with acromegaly treated with LAN were eligible for enrollment. Demographics, LAN dose, extended dosing interval (EDI) (interval of injections ≥42 days), insulin-like growth factor 1 (IGF-1), growth hormone (GH), glycated hemoglobin, adverse events (AEs), injection convenience, and symptom data were collected. As of September 29, 2014, 241 patients were enrolled in SODA. IGF-1 levels below age- and gender-adjusted upper normal limit (ULN) were achieved in 71.2% at month (M) 12 and 74.4% at M24; GH ≤2.5 µg/L in 83.3% at M12 and 80.0% at M24; GH <1.0 µg/L in 61.7% at M12 and 61.4% at M24. Both IGF-1 < ULN and GH ≤2.5 µg/L were achieved in 65.0% at M12 and 54.8% at M24; both IGF-1 < ULN and GH < 1.0 µg/L were achieved in 51.7 and 42.9% at M12 and M24, respectively. EDI regimen was 5.0% at baseline and 12.0% at M24. At M24, acromegaly symptoms appeared stable or improved. The most common AE was arthralgia (25.7%). Among 106 serious AEs reported by 42 patients, 10 were deemed related to therapy in 9 patients. At M24, 73.1% of patients rated LAN as convenient. SODA indicates 2-year biochemical control with majority of patients achieving both IGF-1 < ULN and GH ≤2.5 µg/L. LAN was generally well tolerated with no new or unexpected safety signals reported during the observation period. clinicaltrials.gov Clinical Trial Identifier: NCT00686348.

Epidemiology, Seasonality and Factors Associated with Rotavirus Infection among Children with Moderate-to-Severe Diarrhea in Rural Western Kenya, 2008–2012: The Global Enteric Multicenter Study (GEMS)

PubMed Central

Omore, Richard; Tate, Jacqueline E.; O’Reilly, Ciara E.; Ayers, Tracy; Williamson, John; Moke, Feny; Schilling, Katie A.; Awuor, Alex O.; Jaron, Peter; Ochieng, John B.; Oundo, Joseph; Parashar, Umesh D.; Parsons, Michele B.; Bopp, Cheryl C.; Nasrin, Dilruba; Farag, Tamer H.; Kotloff, Karen L.; Nataro, James P.; Panchalingam, Sandra; Levine, Myron M.; Laserson, Kayla F.; Nuorti, J. Pekka; Mintz, Eric D.; Breiman, Robert F.

2016-01-01

Objective To evaluate factors associated with rotavirus diarrhea and to describe severity of illness among children <5 years old with non-dysenteric, moderate-to-severe diarrhea (MSD) in rural western Kenya. Methods We analyzed data from children <5 years old with non-dysenteric MSD enrolled as cases in the Global Enteric Multicenter Study (GEMS) in Kenya. A non-dysenteric MSD case was defined as a child with ≥3 loose stools in 24 hrs. and one or more of the following: sunken eyes, skin tenting, intravenous rehydration, or hospitalization, who sought care at a sentinel health center within 7 days of illness onset. Rotavirus antigens in stool samples were detected by ELISA. Demographic and clinical information was collected at enrollment and during a single follow-up home visit at approximately 60 days. We analyzed diarrhea severity using a GEMS 17 point numerical scoring system adapted from the Vesikari score. We used logistic regression to evaluate factors associated with rotavirus infection. Results From January 31, 2008 to September 30, 2012, among 1,637 (92%) non-dysenteric MSD cases, rotavirus was detected in stools of 245 (15.0%). Rotavirus-positive compared with negative cases were: younger (median age, 8 vs. 13 months; p<0.0001), had more severe illness (median severity score, 9 vs 8; p<0.0001) and had to be hospitalized more frequently (37/245 [15.1%] vs. 134/1,392 [9.6%]), p <0.013). Independent factors associated with rotavirus infection included age 0–11 months old (aOR = 5.29, 95% CI 3.14–8.89) and presenting with vomiting ≥3 times/24hrs (aOR = 2.58, 95% CI [1.91–3.48]). Rotavirus was detected more commonly in warm and dry months than in the cool and rainy months (142/691 [20%] vs 70/673 [10%]) p<0.0001). Conclusions Diarrhea caused by rotavirus is associated with severe symptoms leading to hospitalization. Consistent with other settings, infants had the greatest burden of disease. PMID:27494517

Safety and tolerability of pasireotide long-acting release in acromegaly-results from the acromegaly, open-label, multicenter, safety monitoring program for treating patients who have a need to receive medical therapy (ACCESS) study.

PubMed

Fleseriu, Maria; Rusch, Elisha; Geer, Eliza B

2017-01-01

Pasireotide long-acting release is a somatostatin analog that is indicated for treatment of patients with acromegaly. This analysis documents the safety of pasireotide long-acting release in patients with acromegaly enrolled in the ACCESS trial (ClinicalTrials.gov identifier: NCT01995734). ACCESS is an open-label, multicenter, single-arm, expanded-treatment protocol designed to provide patients access to pasireotide long-acting release pending regulatory approval. Patients received pasireotide long-acting release 40 mg administered intramuscularly every 28 days. The primary outcome was the proportion of patients having a treatment-emergent grade ≥3 or serious adverse event. Efficacy data were not collected. Forty-four adult patients with active acromegaly were enrolled in the study for an average of 37.6 weeks (range, 4-70 weeks). Twenty-five grade ≥3 treatment-emergent adverse events were reported in 11 patients (25.0 %), 3 of whom (27.3 %) experienced grade ≥3 hyperglycemia. In patients treated with pasireotide long-acting release for ≥3 months (n = 42), mean glycated hemoglobin and fasting plasma glucose levels increased significantly from 5.9 % and 100.4 mg/dL at baseline to 6.8 % and 135.9 mg/dL at 3 months, respectively. Ten patients (22.7 %) were treated with pasireotide long-acting release for ≥15 months, after which mean glycated hemoglobin and fasting plasma glucose levels were 6.3 % and 123 mg/dL, respectively. Twenty-one patients (48 %) initiated antidiabetic medication. Grade ≥3 adverse events (primary outcome) were reported in 25.0 % of acromegaly patients treated with pasireotide long-acting release in a clinical setting. Hyperglycemia-related adverse events were reported in 45.5 % of patients, but were typically manageable, supporting the role of pasireotide long-acting release as a safe treatment option for acromegaly patients.

Point-of-care washing of allogeneic red blood cells for the prevention of transfusion-related respiratory complications (WAR-PRC): a protocol for a multicenter randomised clinical trial in patients undergoing cardiac surgery

PubMed Central

Warner, Matthew A; Welsby, Ian J; Norris, Phillip J; Silliman, Christopher C; Armour, Sarah; Wittwer, Erica D; Santrach, Paula J; Meade, Laurie A; Liedl, Lavonne M; Nieuwenkamp, Chelsea M; Douthit, Brian; van Buskirk, Camille M; Schulte, Phillip J; Kor, Daryl J

2017-01-01

Introduction The transfusion-related respiratory complications, transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO), are leading causes of transfusion-related morbidity and mortality. At present, there are no effective preventive strategies with red blood cell (RBC) transfusion. Although mechanisms remain incompletely defined, soluble biological response modifiers (BRMs) within the RBC storage solution may play an important role. Point-of-care (POC) washing of allogeneic RBCs may remove these BRMs, thereby mitigating their impact on post-transfusion respiratory complications. Methods and analysis This is a multicenter randomised clinical trial of standard allogeneic versus washed allogeneic RBC transfusion for adult patients undergoing cardiac surgery testing the hypothesis that POC RBC washing is feasible, safe, and efficacious and will reduce recipient immune and physiologic responses associated with transfusion-related respiratory complications. Relevant clinical outcomes will also be assessed. This investigation will enrol 170 patients at two hospitals in the USA. Simon’s two-stage design will be used to assess the feasibility of POC RBC washing. The primary safety outcomes will be assessed using Wilcoxon Rank-Sum tests for continuous variables and Pearson chi-square test for categorical variables. Standard mixed modelling practices will be employed to test for changes in biomarkers of lung injury following transfusion. Linear regression will assess relationships between randomised group and post-transfusion physiologic measures. Ethics and dissemination Safety oversight will be conducted under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained by the DSMB as well as the institutional review boards at each institution prior to enrolling the first study participant. This study aims to provide important information regarding the feasibility of POC washing of allogeneic RBCs and its potential impact on ameliorating post-transfusion respiratory complications. Additionally, it will inform the feasibility and scientific merit of pursuing a more definitive phase II/III clinical trial. Registration ClinicalTrials.gov registration number is NCT02094118 (Pre-results). PMID:28821525

Relationship between patient characteristics and treatment allocation for patients with personality disorders.

PubMed

van Manen, Janine G; Andrea, Helene; van den Eijnden, Ellen; Meerman, Anke M M A; Thunnissen, Moniek M; Hamers, Elisabeth F M; Huson, Nelleke; Ziegler, Uli; Stijnen, Theo; Busschbach, Jan J V; Timman, Reinier; Verheul, Roel

2011-10-01

Within a large multi-center study in patients with personality disorders, we investigated the relationship between patient characteristics and treatment allocation. Personality pathology, symptom distress, treatment history, motivational factors, and sociodemographics were measured at intake in 923 patients, who subsequently enrolled in short-term or long-term outpatient, day hospital, or inpatient psychotherapy for personality pathology. Logistic regressions were used to examine the predictors of allocation decisions. We found a moderate relationship (R(2) = 0.36) between patient characteristics and treatment setting, and a weak relationship (R(2) = 0.18) between patient characteristics and treatment duration. The most prominent predictors for setting were: symptom distress, cluster C personality pathology, level of identity integration, treatment history, motivation, and parental responsibility. For duration the most prominent predictor was age. We conclude from this study that, in addition to pathology and motivation factors, sociodemographics and treatment history are related to treatment allocation in clinical practice.

Exploration of the Influence of Childhood Trauma, Combat Exposure, and the Resilience Construct on Depression and Suicidal Ideation among U.S. Iraq/Afghanistan era Military Personnel and Veterans

PubMed Central

Youssef, Nagy A.; Green, Kimberly T.; Dedert, Eric A.; Hertzberg, Jeffrey S.; Calhoun, Patrick S.; Dennis, Michelle F.; Beckham, Jean C.

2013-01-01

OBJECTIVES This study evaluated the effect of childhood trauma exposure and the role of resilience on both depressive symptoms and suicidal ideation. METHODS 1488 military personnel and veterans, who served after September 2001, were evaluated for depressive, suicidal, and PTSD symptoms, combat exposure, childhood trauma exposure, and resiliency. Participants were enrolled as part of an ongoing multicenter study. Outcome measures were depressive symptoms and suicidal ideation. RESULTS After controlling for the effects of combat exposure and PTSD, results revealed that childhood trauma exposures were significantly associated with depressive symptoms and suicidal ideation. In addition, resilience was negatively associated with depressive symptoms and suicidal ideation, suggesting a potential protective effect. CONCLUSION These findings suggest that evaluation of childhood trauma is important in the clinical assessment and treatment of depressive symptoms and suicidal ideation among military personnel and veterans. PMID:23614484

Treat-early and treat-mild: role of fast vs. slow escalation of headaches.

PubMed

Ng-Mak, D S; Ma, L; Hu, X H; Chen, Y-T

2009-04-01

This prospective, multi-center, observational study aimed to examine patients' early treatment decision process. Specifically, we assessed if the association between mild headache pain at treatment initiation and early treatment differed by the speed of headache escalation. Patients (n = 168) were instructed to collect information on their headache experience during the study period via an electronic diary over 30 consecutive days after enrollment. At the time of treatment, patients who treated early were 2.3 times as likely to experience mild headache pain as those who treated late. Controlling for the effect of escalation of headache, patients who treated early were three times as likely to report mild headache pain at dosing as those who treated late. The interaction between fast escalation of headache and mild pain was not statistically significant. Early treatment is associated with mild pain, regardless of the speed of headache escalation.

Early-life gut microbiome and egg allergy.

PubMed

Fazlollahi, M; Chun, Y; Grishin, A; Wood, R A; Burks, A W; Dawson, P; Jones, S M; Leung, D Y M; Sampson, H A; Sicherer, S H; Bunyavanich, S

2018-07-01

Gut microbiota may play a role in egg allergy. We sought to examine the association between early-life gut microbiota and egg allergy. We studied 141 children with egg allergy and controls from the multicenter Consortium of Food Allergy Research study. At enrollment (age 3 to 16 months), fecal samples were collected, and clinical evaluation, egg-specific IgE measurement, and egg skin prick test were performed. Gut microbiome was profiled by 16S rRNA sequencing. Analyses for the primary outcome of egg allergy at enrollment, and the secondary outcomes of egg sensitization at enrollment and resolution of egg allergy by age 8 years, were performed using Quantitative Insights into Microbial Ecology, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States, and Statistical Analysis of Metagenomic Profiles. Compared to controls, increased alpha diversity and distinct taxa (PERMANOVA P = 5.0 × 10 -4 ) characterized the early-life gut microbiome of children with egg allergy. Genera from the Lachnospiraceae, Streptococcaceae, and Leuconostocaceae families were differentially abundant in children with egg allergy. Predicted metagenome functional analyses showed differential purine metabolism by the gut microbiota of egg-allergic subjects (Kruskal-Wallis P adj  = 0.021). Greater gut microbiome diversity and genera from Lachnospiraceae and Ruminococcaceae were associated with egg sensitization (PERMANOVA P = 5.0 × 10 -4 ). Among those with egg allergy, there was no association between early-life gut microbiota and egg allergy resolution by age 8 years. The distinct early-life gut microbiota in egg-allergic and egg-sensitized children identified by our study may point to targets for preventive or therapeutic intervention. © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

BRIM-P: A phase I, open-label, multicenter, dose-escalation study of vemurafenib in pediatric patients with surgically incurable, BRAF mutation-positive melanoma.

PubMed

Chisholm, Julia C; Suvada, Jozef; Dunkel, Ira J; Casanova, Michela; Zhang, Weijiang; Ritchie, Natasha; Choi, YounJeong; Park, Jane; Das Thakur, Meghna; Simko, Stephen; Wan Rachel Tam, Nga; Ferrari, Andrea

2018-05-01

Vemurafenib, a selective inhibitor of BRAF kinase, is approved for the treatment of adult stage IIIc/IV BRAF V600 mutation-positive melanoma. We conducted a phase I, open-label, dose-escalation study in pediatric patients aged 12-17 years with this tumor type (NCT01519323). Patients received vemurafenib orally until disease progression. Dose escalation was conducted using a 3 + 3 design. Patients were monitored for dose-limiting toxicities (DLTs) during the first 28 days of treatment to determine the maximum tolerated dose (MTD). Safety/tolerability, tumor response, and pharmacokinetics were evaluated. Six patients were enrolled (720 mg twice daily [BID], n = 3; 960 mg BID [n = 3]). The study was terminated prematurely due to low enrollment. No DLTs were observed; thus, the MTD could not be determined. All patients experienced at least one adverse event (AE); the most common were diarrhea, headache, photosensitivity, rash, nausea, and fatigue. Three patients experienced serious AEs, one patient developed secondary cutaneous malignancies, and five patients died following disease progression. Mean steady-state plasma concentrations of vemurafenib following 720 mg and 960 mg BID dosing were similar or higher, respectively, than in adults. There were no objective responses. Median progression-free survival and overall survival were 4.4 months (95% confidence interval [CI] = 2.7-5.2) and 8.1 months (95% CI = 5.1-12.0), respectively. A recommended and effective dose of vemurafenib for patients aged 12-17 years with metastatic or unresectable melanoma was not identified. Extremely low enrollment in this trial highlights the importance of considering the inclusion of adolescents with adult cancers in adult trials. © 2018 Wiley Periodicals, Inc.

Strategies in maintenance for patients receiving long-term therapy (SIMPLE): a study of MMX mesalamine for the long-term maintenance of quiescent ulcerative colitis.

PubMed

Kane, Sunanda; Katz, Seymour; Jamal, M Mazen; Safdi, Michael; Dolin, Ben; Solomon, Dory; Palmen, Mary; Barrett, Karen

2012-06-01

This was a phase IV, multicenter, open-label, 12-14-month study to assess clinical recurrence in patients with ulcerative colitis (UC) who received maintenance treatment with MMX Multi Matrix System (MMX) mesalamine. A secondary outcome was the relationship between long-term efficacy and adherence. Patients with quiescent UC (no rectal bleeding; 0-1 bowel movements more than normal per day) were enrolled directly into a 12-month maintenance phase of the study during which they received MMX mesalamine 2.4 g/day given once daily (QD). Patients with active, mild-to-moderate UC at screening were enrolled into a 2-month acute phase; those who achieved quiescence could continue into the maintenance phase. The primary endpoint was clinical recurrence at Month 6. Of the 290 patients enrolled, 208 entered the maintenance phase; 152 directly and 56 via the acute phase. Following 6 and 12 months of treatment, 76.5% and 64.4% of evaluable patients, respectively, were recurrence-free. The majority of evaluable patients at Month 6 (81.6%) and Month 12 (79.4%) in the maintenance phase were ≥ 80% adherent to MMX mesalamine. At Month 6, clinical recurrence was observed in 20.6% of patients who were ≥ 80% adherent and 36.1% of patients with <80% adherence (P = 0.05 [post-hoc chi-square analysis]); 31.2% and 52.5% at Month 12 (P = 0.01 [post-hoc chi-square analysis]). MMX mesalamine 2.4 g/day QD is effective for maintaining quiescence in patients with UC. Furthermore, adherence to prescribed treatment yielded lower rates of clinical recurrence. Continued education regarding the importance of long-term 5-aminosalicylic acid therapy is warranted. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

Pharmacokinetics and Pharmacodynamics of Piperacillin-Tazobactam in 42 Patients Treated with Concomitant CRRT

PubMed Central

Bauer, Seth R.; Salem, Charbel; Connor, Michael J.; Groszek, Joseph; Taylor, Maria E.; Wei, Peilin; Tolwani, Ashita J.

2012-01-01

Summary Background and objectives Current recommendations for piperacillin-tazobactam dosing in patients receiving continuous renal replacement therapy originate from studies with relatively few patients and lower continuous renal replacement therapy doses than commonly used today. This study measured the pharmacokinetic and pharmacodynamic characteristics of piperacillin-tazobactam in patients treated with continuous renal replacement therapy using contemporary equipment and prescriptions. Design, setting, participants, & measurements A multicenter prospective observational study in the intensive care units of two academic medical centers was performed, enrolling patients with AKI or ESRD receiving piperacillin-tazobactam while being treated with continuous renal replacement therapy. Pregnant women, children, and patients with end stage liver disease were excluded from enrollment. Plasma and continuous renal replacement therapy effluent samples were analyzed for piperacillin and tazobactam levels using HPLC. Pharmacokinetic and pharmacodynamic parameters were calculated using standard equations. Multivariate analyses were used to examine the association of patient and continuous renal replacement therapy characteristics with piperacillin pharmacokinetic parameters. Results Forty-two of fifty-five subjects enrolled had complete sampling. Volume of distribution (median=0.38 L/kg, intraquartile range=0.20 L/kg) and elimination rate constants (median=0.104 h−1, intraquartile range=0.052 h−1) were highly variable, and clinical parameters could explain only a small fraction of the large variability in pharmacokinetic parameters. Probability of target attainment for piperacillin was 83% for total drug but only 77% when the unbound fraction was considered. Conclusions There is significant patient to patient variability in pharmacokinetic/pharmacodynamic parameters in patients receiving continuous renal replacement therapy. Many patients did not achieve pharmacodynamic targets, suggesting that therapeutic drug monitoring might optimize therapy. PMID:22282479

Patient-centered recruitment and retention for a randomized controlled study.

PubMed

Chhatre, Sumedha; Jefferson, Ashlie; Cook, Ratna; Meeker, Caitlin R; Kim, Ji Hyun; Hartz, Kayla Marie; Wong, Yu-Ning; Caruso, Adele; Newman, Diane K; Morales, Knashawn H; Jayadevappa, Ravishankar

2018-03-27

Recruitment and retention strategies for patient-centered outcomes research are evolving and research on the subject is limited. In this work, we present a conceptual model of patient-centered recruitment and retention, and describe the recruitment and retention activities and related challenges in a patient-centered comparative effectiveness trial. This is a multicenter, longitudinal randomized controlled trial in localized prostate cancer patients. We recruited 743 participants from three sites over 15 months period (January 2014 to March 2015), and followed them for 24 months. At site 1, of the 773 eligible participants, 551 (72%) were enrolled. At site 2, 34 participants were eligible and 23 (68%) enrolled. Of the 434 eligible participants at site 3, 169 (39%) enrolled. We observed that strategies related to the concepts of trust (e.g., physician involvement, ensuring protection of information), communication (e.g., brochures and pamphlets in physicians' offices, continued contact during regular clinic visits and calling/emailing assessment), attitude (e.g., emphasizing the altruistic value of research, positive attitude of providers and research staff), and expectations (e.g., full disclosure of study requirements and time commitment, update letters) facilitated successful patient recruitment and retention. A stakeholders' advisory board provided important input for the recruitment and retention activities. Active engagement, reminders at the offices, and personalized update letters helped retention during follow-up. Usefulness of telephone recruitment was site specific and, at one site, the time requirement for telephone recruitment was a challenge. We have presented multilevel strategies for successful recruitment and retention in a clinical trial using a patient-centered approach. Our strategies were flexible to accommodate site-level requirements. These strategies as well as the challenges can aid recruitment and retention efforts of future large-scale, patient-centered research studies. Clinicaltrials.gov , ID: NCT02032550 . Registered on 22 November 2013.

Multicenter phase II study of apatinib in non-triple-negative metastatic breast cancer.

PubMed

Hu, Xichun; Cao, Jun; Hu, Wenwei; Wu, Changping; Pan, Yueyin; Cai, Li; Tong, Zhongsheng; Wang, Shusen; Li, Jin; Wang, Zhonghua; Wang, Biyun; Chen, Xiaoyu; Yu, Hao

2014-11-07

Apatinib is a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2). This study was conducted to assess the efficacy and safety of apatinib in patients with non-triple-negative metastatic breast cancer who had received prior chemotherapy for their metastatic disease. This multicenter, open-label, single arm study enrolled patients with non-triple-negative breast cancer, pretreated with anthracycline, taxanes and capecitabine, and who failed in the metastatic setting at least 1 and at most 4 prior chemotherapy regimens and at least one endocrine drug for hormone receptor-positive patients as well as at least one anti-Her2 drug for Her2-positive patients. The primary end point of this study was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. Apatinib was administered as 500 mg daily on days 1 through 28 of each 4-week cycle. 38 patients were enrolled with a median age of 49 years (range, 35 to 62 years) and received apatinib for a median of 4 cycles (range from 0 to 10 cycles). 18 (47.4%) patients experienced dose reduction during treatment. The median relative dose intensity (relative to assigned dose for each cycle) was 82% (range, 45.0% to 100.0%). Median follow-up time was 10.1 months. Median PFS of all 38 patients was 4.0 months (95% confidence interval (CI), 2.8 m - 5.2 m). 36 patients were eligible for efficacy analysis. ORR was 16.7% (6/36). DCR was 66.7% (24/36). Median OS was 10.3 months (95% CI, 9.1 m - 11.6 m). The most common grade 3/4 treatment-related AEs were hypertension (20.5%), hand-foot syndrome (10.3%), and proteinuria (5.1%). Of three possibly drug-related SAEs recorded in the study, 2 (3.4%) deaths occurred within 28 days of last treatment and were both considered to be the result of disease progression. The other one was grade 2 diarrhea needing hospitalization. Apatinib exhibited objective efficacy in heavily pretreated, metastatic non-triple-negative breast cancer with manageable toxicity, and it might be better to be tested in breast cancer with high angiogenesis dependency. ClinicalTrials.gov: NCT01653561.

The Use of Poly-4-Hydroxybutyrate (P4HB) Scaffold in the Ptotic Breast: A Multicenter Clinical Study.

PubMed

Adams, William P; Baxter, Richard; Glicksman, Caroline; Mast, Bruce A; Tantillo, Michael; Van Natta, Bruce W

2018-04-06

Mastopexy and reduction mammaplasty are often limited by the patient's poor native soft tissue quality, resulting in ptosis recurrence and loss of rejuvenated surgical results. Surgical scaffolds and acellular dermal matrices are used in these procedures to provide physical and mechanical stabilization of weakened or compromised tissue. GalaFLEX scaffold, made from poly-4-hydroxybutyrate (P4HB), is a next-generation product for soft tissue reinforcement that resorbs gradually while aiding tissue regeneration to achieve excellent outcomes. To assess the clinical performance of GalaFLEX scaffold in soft tissue reinforcement during elective mastopexy and reduction mammaplasty. This multicenter, single-arm, observational study assessed product performance and outcomes of GalaFLEX scaffold when used in breast surgery. Outcomes included ptosis correction and maintenance, associated adverse events, patient and surgeon satisfaction, and mammographic and ultrasound imaging evaluation. At 6 centers in the US, 62 of 69 enrolled patients were treated. Of this population, 89.7% had successful ptosis correction and maintenance at 1 year, with high patient and surgeon satisfaction for breast shape, droop/sag of the breast, and maintenance of results at 1 year. There were 5 adverse events deemed related to the device (8.0%), including nerve pain, breast swelling, ptosis, and 2 instances of asymmetry. GalaFLEX scaffold safely and successfully supports and elevates breast tissue in mastopexy and reduction mammaplasty, with maintained support at 1 year. Surgeon and patient satisfaction were high. No mammogram or ultrasound interference was detected.

77 FR 12598 - Notice Correction; A Multi-Center International Hospital-Based Case-Control Study of Lymphoma in...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Notice Correction; A Multi-Center International Hospital-Based Case-Control Study of Lymphoma in Asia (AsiaLymph) (NCI) The Federal... project titled, ``A multi-center international hospital-based case-control study of lymphoma in Asia (Asia...

Parvovirus B19 Infection in Children With Arterial Ischemic Stroke.

PubMed

Fullerton, Heather J; Luna, Jorge M; Wintermark, Max; Hills, Nancy K; Tokarz, Rafal; Li, Ying; Glaser, Carol; DeVeber, Gabrielle A; Lipkin, W Ian; Elkind, Mitchell S V

2017-10-01

Case-control studies suggest that acute infection transiently increases the risk of childhood arterial ischemic stroke. We hypothesized that an unbiased pathogen discovery approach utilizing MassTag-polymerase chain reaction would identify pathogens in the blood of childhood arterial ischemic stroke cases. The multicenter international VIPS study (Vascular Effects of Infection in Pediatric Stroke) enrolled arterial ischemic stroke cases, and stroke-free controls, aged 29 days through 18 years. Parental interview included questions on recent infections. In this pilot study, we used MassTag-polymerase chain reaction to test the plasma of the first 161 cases and 34 controls enrolled for a panel of 28 common bacterial and viral pathogens. Pathogen DNA was detected in no controls and 14 cases (8.7%): parvovirus B19 (n=10), herpesvirus 6 (n=2), adenovirus (n=1), and rhinovirus 6C (n=1). Parvovirus B19 infection was confirmed by serologies in all 10; infection was subclinical in 8. Four cases with parvovirus B19 had underlying congenital heart disease, whereas another 5 had a distinct arteriopathy involving a long-segment stenosis of the distal internal carotid and proximal middle cerebral arteries. Using MassTag-polymerase chain reaction, we detected parvovirus B19-a virus known to infect erythrocytes and endothelial cells-in some cases of childhood arterial ischemic stroke. This approach can generate new, testable hypotheses about childhood stroke pathogenesis. © 2017 American Heart Association, Inc.

Drug-induced acute liver failure: results of a U.S. multicenter, prospective study.

PubMed

Reuben, Adrian; Koch, David G; Lee, William M

2010-12-01

Acute liver failure (ALF) due to drug-induced liver injury (DILI), though uncommon, is a concern for both clinicians and patients. The Acute Liver Failure Study Group has prospectively collected cases of all forms of acute liver failure since 1998. We describe here cases of idiosyncratic DILI ALF enrolled during a 10.5-year period. Data were collected prospectively, using detailed case report forms, from 1198 subjects enrolled at 23 sites in the United States, all of which had transplant services. A total of 133 (11.1%) ALF subjects were deemed by expert opinion to have DILI; 81.1% were considered highly likely, 15.0% probable, and 3.8% possible. Subjects were mostly women (70.7%) and there was overrepresentation of minorities for unclear reasons. Over 60 individual agents were implicated, the most common were antimicrobials (46%). Transplant-free (3-week) survival was poor (27.1%), but with highly successful transplantation in 42.1%, overall survival was 66.2%. Transplant-free survival in DILI ALF is determined by the degree of liver dysfunction, specifically baseline levels of bilirubin, prothrombin time/international normalized ratio, and Model for End-Stage Liver Disease scores. DILI is an uncommon cause of ALF that evolves slowly, affects a disproportionate number of women and minorities, and shows infrequent spontaneous recovery, but transplantation affords excellent survival. Copyright © 2010 American Association for the Study of Liver Diseases.

Immunogenicity and safety of the new reduced-dose tetanus-diphtheria vaccine in healthy Korean adolescents: A comparative active control, double-blind, randomized, multicenter phase III study.

PubMed

Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Kim, Sang Yong; Kim, Jong-Hyun; Kim, Hyun-Hee; Lee, Kyung-Yil; Kim, Hwang Min; Choi, Young Youn; Ma, Sang Hyuk; Kim, Chun Soo; Kim, Dong Ho; Ahn, Dong Ho; Kang, Jin Han

2017-04-01

A new reduced-dose tetanus-diphtheria (Td) vaccine was developed in Korea, and phase I and II clinical trials were successfully undertaken. We conducted this double-blind, randomized, multicenter phase III clinical trial to assess the immunogenicity and safety of the new Td vaccine. Healthy adolescents 11-12 years of age were enrolled and randomized to receive the new Td vaccine (study group) or a commercially available Td vaccine (control group). Blood samples were collected prior to and 4 weeks after the vaccination. Between the study and control groups, seroprotection rate, booster response, and geometric mean titer of antibodies against diphtheria and tetanus toxoids were compared after the vaccination. All solicited and unsolicited adverse events and serious adverse events during the 6-week study period were monitored. A total of 164 adolescents received vaccination, and 156 of them were evaluated to assess immunogenicity. The seroprotection rate and geometric mean titer for antibodies against diphtheria were significantly higher in the study group, whereas those against tetanus were significantly higher in the control group. However, all seroprotection rates against diphtheria and tetanus in the study and control groups were high: 100% against diphtheria and tetanus in the study group, and 98.7% against diphtheria and 100% against tetanus in the control group. No significant differences in the frequency of solicited and unsolicited adverse events were observed between the two vaccine groups. The new Td vaccine is highly immunogenic and safe, and this new Td vaccine can be effectively used for preventing diphtheria and tetanus. Copyright © 2015. Published by Elsevier B.V.

Rationale, Design, and Methodology of the APOLLON trial: A comPrehensive, ObservationaL registry of heart faiLure with midrange and preserved ejectiON fraction.

PubMed

Özlek, Bülent; Özlek, Eda; Çelik, Oğuzhan; Çil, Cem; Doğan, Volkan; Tekinalp, Mehmet; Zencirkıran Ağuş, Hicaz; Kahraman, Serkan; Ösken, Altuğ; Rencüzoğulları, İbrahim; Tanık, Veysel Ozan; Bekar, Lütfü; Çakır, Mustafa Ozan; Kaya, Bedri Caner; Tibilli, Hakan; Çelik, Yunus; Başaran, Özcan; Mert, Kadir Uğur; Sevinç, Samet; Demirci, Erkan; Dondurmacı, Engin; Biteker, Murat

2018-05-01

Although almost half of chronic heart failure (HF) patients have mid-range (HFmrEF) and preserved left-ventricular ejection fraction (HFpEF), no studies have been carried out with these patients in our country. This study aims to determine the demographic characteristics and current status of the clinical background of HFmrEF and HFpEF patients in a multicenter trial. A comPrehensive, ObservationaL registry of heart faiLure with mid range and preserved ejectiON fraction (APOLLON) trial will be an observational, multicenter, and noninterventional study conducted in Turkey. The study population will include 1065 patients from 12 sites in Turkey. All data will be collected at one point in time and the current clinical practice will be evaluated (ClinicalTrials.gov number NCT03026114). We will enroll all consecutive patients admitted to the cardiology clinics who were at least 18 years of age and had New York Heart Association class II, III, or IV HF, elevated brain natriuretic peptide levels within the last 30 days, and an left ventricular ejection fraction (LVEF) of at least 40%. Patients fulfilling the exclusion criteria will not be included in the study. Patients will be stratified into two categories according to LVEF: mid-range EF (HFmrEF, LVEF 40%-49%) and preserved EF (HFpEF, LVEF ≥50%). Regional quota sampling will be performed to ensure that the sample was representative of the Turkish population. Demographic, lifestyle, medical, and therapeutic data will be collected by this specific survey. The APOLLON trial will be the largest and most comprehensive study in Turkey evaluating HF patients with a LVEF ≥40% and will also be the first study to specifically analyze the recently designated HFmrEF category.

Whole-exome sequencing for RH genotyping and alloimmunization risk in children with sickle cell anemia

PubMed Central

Flanagan, Jonathan M.; Vege, Sunitha; Luban, Naomi L. C.; Brown, R. Clark; Ware, Russell E.; Westhoff, Connie M.

2017-01-01

RH genes are highly polymorphic and encode the most complex of the 35 human blood group systems. This genetic diversity contributes to Rh alloimmunization in patients with sickle cell anemia (SCA) and is not avoided by serologic Rh-matched red cell transfusions. Standard serologic testing does not distinguish variant Rh antigens. Single nucleotide polymorphism (SNP)–based DNA arrays detect many RHD and RHCE variants, but the number of alleles tested is limited. We explored a next-generation sequencing (NGS) approach using whole-exome sequencing (WES) in 27 Rh alloimmunized and 27 matched non-alloimmunized patients with SCA who received chronic red cell transfusions and were enrolled in a multicenter study. We demonstrate that WES provides a comprehensive RH genotype, identifies SNPs not interrogated by DNA array, and accurately determines RHD zygosity. Among this multicenter cohort, we demonstrate an association between an altered RH genotype and Rh alloimmunization: 52% of Rh immunized vs 19% of non-immunized patients expressed variant Rh without co-expression of the conventional protein. Our findings suggest that RH allele variation in patients with SCA is clinically relevant, and NGS technology can offer a comprehensive alternative to targeted SNP-based testing. This is particularly relevant as NGS data becomes more widely available and could provide the means for reducing Rh alloimmunization in children with SCA. PMID:29296782

Safety and Tolerance Evaluation of Milk Fat Globule Membrane-Enriched Infant Formulas: A Randomized Controlled Multicenter Non-Inferiority Trial in Healthy Term Infants

PubMed Central

Billeaud, Claude; Puccio, Giuseppe; Saliba, Elie; Guillois, Bernard; Vaysse, Carole; Pecquet, Sophie; Steenhout, Philippe

2014-01-01

OBJECTIVE This multicenter non-inferiority study evaluated the safety of infant formulas enriched with bovine milk fat globule membrane (MFGM) fractions. METHODS Healthy, full-term infants (n = 119) age ≤14 days were randomized to standard infant formula (control), standard formula enriched with a lipid-rich MFGM fraction (MFGM-L), or standard formula enriched with a protein-rich MFGM fraction (MFGM-P). Primary outcome was mean weight gain per day from enrollment to age 4 months (non-inferiority margin: −3.0 g/day). Secondary (length, head circumference, tolerability, morbidity, adverse events) and exploratory (phospholipids, metabolic markers, immune markers) outcomes were also evaluated. RESULTS Weight gain was non-inferior in the MFGM-L and MFGM-P groups compared with the control group. Among secondary and exploratory outcomes, few between-group differences were observed. Formula tolerance rates were high (>94%) in all groups. Adverse event and morbidity rates were similar across groups except for a higher rate of eczema in the MFGM-P group (13.9% vs control [3.5%], MFGM-L [1.4%]). CONCLUSION Both MFGM-enriched formulas met the primary safety endpoint of non-inferiority in weight gain and were generally well tolerated, although a higher rate of eczema was observed in the MFGM-P group. PMID:25452707

Performance assessment of diffuse optical spectroscopic imaging instruments in a 2-year multicenter breast cancer trial

NASA Astrophysics Data System (ADS)

Leproux, Anaïs; O'Sullivan, Thomas D.; Cerussi, Albert; Durkin, Amanda; Hill, Brian; Hylton, Nola; Yodh, Arjun G.; Carp, Stefan A.; Boas, David; Jiang, Shudong; Paulsen, Keith D.; Pogue, Brian; Roblyer, Darren; Yang, Wei; Tromberg, Bruce J.

2017-12-01

We present a framework for characterizing the performance of an experimental imaging technology, diffuse optical spectroscopic imaging (DOSI), in a 2-year multicenter American College of Radiology Imaging Network (ACRIN) breast cancer study (ACRIN-6691). DOSI instruments combine broadband frequency-domain photon migration with time-independent near-infrared (650 to 1000 nm) spectroscopy to measure tissue absorption and reduced scattering spectra and tissue hemoglobin, water, and lipid composition. The goal of ACRIN-6691 was to test the effectiveness of optically derived imaging endpoints in predicting the final pathologic response of neoadjuvant chemotherapy (NAC). Sixty patients were enrolled over a 2-year period at participating sites and received multiple DOSI scans prior to and during 3- to 6-month NAC. The impact of three sources of error on accuracy and precision, including different operators, instruments, and calibration standards, was evaluated using a broadband reflectance standard and two different solid tissue-simulating optical phantoms. Instruments showed <0.0010 mm-1 (10.3%) and 0.06 mm-1 (4.7%) deviation in broadband absorption and reduced scattering, respectively, over the 2-year duration of ACRIN-6691. These variations establish a useful performance criterion for assessing instrument stability. The proposed procedures and tests are not limited to DOSI; rather, they are intended to provide methods to characterize performance of any instrument used in translational optical imaging.

Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge.

PubMed

Elli, Luca; Tomba, Carolina; Branchi, Federica; Roncoroni, Leda; Lombardo, Vincenza; Bardella, Maria Teresa; Ferretti, Francesca; Conte, Dario; Valiante, Flavio; Fini, Lucia; Forti, Edoardo; Cannizzaro, Renato; Maiero, Stefania; Londoni, Claudio; Lauri, Adriano; Fornaciari, Giovanni; Lenoci, Nicoletta; Spagnuolo, Rocco; Basilisco, Guido; Somalvico, Francesco; Borgatta, Bruno; Leandro, Gioacchino; Segato, Sergio; Barisani, Donatella; Morreale, Gaetano; Buscarini, Elisabetta

2016-02-08

Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS.

Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge

PubMed Central

Elli, Luca; Tomba, Carolina; Branchi, Federica; Roncoroni, Leda; Lombardo, Vincenza; Bardella, Maria Teresa; Ferretti, Francesca; Conte, Dario; Valiante, Flavio; Fini, Lucia; Forti, Edoardo; Cannizzaro, Renato; Maiero, Stefania; Londoni, Claudio; Lauri, Adriano; Fornaciari, Giovanni; Lenoci, Nicoletta; Spagnuolo, Rocco; Basilisco, Guido; Somalvico, Francesco; Borgatta, Bruno; Leandro, Gioacchino; Segato, Sergio; Barisani, Donatella; Morreale, Gaetano; Buscarini, Elisabetta

2016-01-01

Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS. PMID:26867199

In-hospital management and outcome of patients on warfarin undergoing coronary stent implantation: results of the multicenter, prospective WARfarin and coronary STENTing (WAR-STENT) registry.

PubMed

Rubboli, Andrea; Sciahbasi, Alessandro; Briguori, Carlo; Saia, Francesco; Palmieri, Cataldo; Moroni, Luigi Andrea; Calabrò, Paolo; Leone, Antonio Maria; Franco, Nicoletta; Valgimigli, Marco; Varani, Elisabetta; Santi, Michela; Pasqualini, Paola; Capecchi, Alessandro; Piccalò, Giacomo; Margheri, Massimo; di Pasquale, Giuseppe; Galvani, Marcello; Bolognese, Leonardo; Gonzini, Lucio; Maggioni, Aldo Pietro

2013-04-01

The in-hospital management of patients on warfarin undergoing coronary stent implantation (PCI-S) is variable, and the in-hospital outcome incompletely defined. To determine the adherence to the current recommendations, and the incidence of adverse events, we carried out the prospective, multicenter, observational WARfarin and coronary STENTing (WAR-STENT) registry (ClinicalTrials.gov identifier NCT00722319). All consecutive patients on warfarin undergoing PCI-S at 37 Italian centers were enrolled and followed for 12 months. Outcome measures were: major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, need for urgent revascularization, stroke, and venous thromboembolism, and major and minor bleeding. In this paper, we report the in-hospital findings. Out of the 411 patients enrolled, 92% were at non-low (ie, moderate or high) thromboembolic risk. The radial approach and bare-metal stents were used in 61% and 60% of cases, respectively. Drug-eluting stents were essentially reserved to patients with diabetes, which in turn, significantly predicted the implantation of drug-eluting stents (odds ratio [OR], 2.02; 95% confidence interval [CI], 1.29-3.17; P=.002). The in-hospital MACE and major bleeding rates were 2.7% and 2.1%, respectively. At discharge, triple therapy (TT) of warfarin, aspirin, and clopidogrel was prescribed to 76% of patients. Prescription of TT was significantly more frequent in the non-low thromboembolic risk group. Non-low thromboembolic risk, in turn, was a significant predictor of TT prescription (OR, 11.2; 95% CI, 4.83-26.3; P<.0001). In conclusion, real-world warfarin patients undergoing PCI-S are largely managed according to the current recommendations. As a consequence, the risk of in-hospital MACE and major bleedings appears limited and acceptable.

A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation.

PubMed

Stevens, R B; Wrenshall, L E; Miles, C D; Farney, A C; Jie, T; Sandoz, J P; Rigley, T H; Osama Gaber, A

2016-06-01

A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit anti-thymocyte globulin induction (SD-rATG) showed improved efficacy compared with conventional divided-dose (DD-rATG) administration. The present multicenter, double-blind/double-dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD-rATG versus DD-rATG induction for noninferiority in early (7-day) safety and tolerability. Ninety-five patients (randomized 1:1) received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD-rATG induction to be noninferior to DD-rATG induction in early tolerability and equivalent in 12-month safety. (Clinical Trials.gov #NCT00906204.). © Copyright 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of the American Society of Transplantation and the American Society of Transplant Surgeons.

Methodologic issues in terminating enrollment of a subgroup of patients in a multicenter randomized trial.

PubMed

Lee, Shing M; Wise, Robert; Sternberg, Alice L; Tonascia, James; Piantadosi, Steven

2004-01-01

The National Emphysema Treatment Trial (NETT) was a multicenter randomized controlled trial comparing medical treatment plus lung-volume-reduction surgery (LVRS) to medical treatment alone for the treatment of severe emphysema. The primary outcomes specified for the trial were mortality from all causes and change in functional status as indicated by the change in maximum exercise capacity measured two years after randomization. A secondary objective of the trial was to define criteria to identify subgroups of patients at risk of harm or benefit from LVRS. Stopping guidelines for safety and efficacy based on 30-day mortality and a combination of overall mortality and functional status at two years were specified at the inception of the trial. Although specific subgroups of patients likely to benefit were not identified in advance, several clinical factors were specified as likely to be important in defining subgroups with differential outcome. In May 2001, with 40% of expected deaths accrued, the Data and Safety Monitoring Board determined that a subgroup of patients was at significantly higher risk of 30-day mortality from LVRS without counterbalancing evidence of functional benefit, and recommended that the protocol be modified to exclude further randomization of such patients. The trial's sponsor, the National Heart, Lung and Blood Institute, accepted the recommendation, which was rapidly communicated to participating clinics. This paper describes the operational aspects of identification of the subgroup and implementation of the recommendation to continue the trial, but to terminate enrollment of new patients in the subgroup. These aspects include notification of the investigators, the institutional review boards, the Research Group, the patients and the medical community. We also describe the repercussions of the publication and the misinterpretations of the results based on media coverage.

Survival in infants treated with sebelipase Alfa for lysosomal acid lipase deficiency: an open-label, multicenter, dose-escalation study.

PubMed

Jones, Simon A; Rojas-Caro, Sandra; Quinn, Anthony G; Friedman, Mark; Marulkar, Sachin; Ezgu, Fatih; Zaki, Osama; Gargus, J Jay; Hughes, Joanne; Plantaz, Dominique; Vara, Roshni; Eckert, Stephen; Arnoux, Jean-Baptiste; Brassier, Anais; Le Quan Sang, Kim-Hanh; Valayannopoulos, Vassili

2017-02-08

Infants presenting with lysosomal acid lipase deficiency have marked failure to thrive, diarrhea, massive hepatosplenomegaly, anemia, rapidly progressive liver disease, and death typically in the first 6 months of life; the only available potential treatment has been hematopoietic stem cell transplantation, which is associated with high morbidity and mortality in this population. The study objective was to evaluate safety and efficacy (including survival) of enzyme replacement with sebelipase alfa in infants with lysosomal acid lipase deficiency. This is an ongoing multicenter, open-label, phase 2/3 study conducted in nine countries. The study enrolled infants with growth failure prior to 6 months of age with rapidly progressive lysosomal acid lipase deficiency; they received once-weekly doses of sebelipase alfa initiated at 0.35 mg/kg with intrapatient dose escalation up to 5 mg/kg. The main outcome of interest is survival to 12 months and survival beyond 24 months of age. Nine patients were enrolled; median age at baseline was 3.0 months (range 1.1-5.8 months). Sixty-seven percent (exact 95% CI 30%-93%) of sebelipase alfa-treated infants survived to 12 months of age compared with 0% (exact 95% CI 0%-16%) for a historical control group (n = 21). Patients who survived to age 12 months exhibited improvements in weight-for-age, reductions in markers of liver dysfunction and hepatosplenomegaly, and improvements in anemia and gastrointestinal symptoms. Three deaths occurred early (first few months of life), two patients died because of advanced disease, and a third patient died following complications of non-protocol-specified abdominal paracentesis. A fourth death occurred at 15 months of age and was related to other clinical conditions. The five surviving patients have survived to age ≥24 months with continued sebelipase alfa treatment; all have displayed marked improvement in growth parameters and liver function. Serious adverse events considered related to sebelipase alfa were reported in one of the nine infants (infusion reaction: tachycardia, pallor, chills, and pyrexia). Most infusion-associated reactions were mild and non-serious. Sebelipase alfa markedly improved survival with substantial clinically meaningful improvements in growth and other key disease manifestations in infants with rapidly progressive lysosomal acid lipase deficiency TRIAL REGISTRATION: Clinicaltrials.gov NCT01371825 . Registered 9 June 2011.

The LIBERTY study: Design of a prospective, observational, multicenter trial to evaluate the acute and long-term clinical and economic outcomes of real-world endovascular device interventions in treating peripheral artery disease.

PubMed

Adams, George L; Mustapha, Jihad; Gray, William; Hargus, Nick J; Martinsen, Brad J; Ansel, Gary; Jaff, Michael R

2016-04-01

Most peripheral artery disease (PAD) clinical device trials are supported by commercial manufacturers and designed for regulatory device approval, with extensive inclusion/exclusion criteria to support homogeneous patient populations. High-risk patients with advanced disease, including critical limb ischemia (CLI), are often excluded leading to difficulty in translating trial results into real-world clinical practice. As a result, physicians have no direct guidance regarding the use of endovascular devices. There is a need for objectively assessed studies to evaluate clinical, functional, and economic outcomes in PAD patient populations. LIBERTY is a prospective, observational, multicenter study sponsored by Cardiovascular Systems Inc (St Paul, MN) to evaluate procedural and long-term clinical and economic outcomes of endovascular device interventions in patients with symptomatic lower extremity PAD. Approximately 1,200 patients will be enrolled and followed up to 5 years: 500 patients in the "Claudicant Rutherford 2-3" arm, 600 in the "CLI Rutherford 4-5" arm, and 100 in the "CLI Rutherford 6" arm. The study will use 4 core laboratories for independent analysis and will evaluate the following: procedural and lesion success, rates of major adverse events, duplex ultrasound interpretations, wound status, quality of life, 6-minute walk test, and economic analysis. The LIBERTY Patient Risk Score(s) will be developed as a clinical predictor of outcomes to provide guidance for interventions in this patient population. LIBERTY will investigate real-world PAD patients treated with endovascular revascularization with rigorous study guidelines and independent oversight of outcomes. This study will provide observational, all-comer patient clinical data to guide future endovascular therapy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The role of hemodialysis machines dedication in reducing Hepatitis C transmission in the dialysis setting in Iran: A multicenter prospective interventional study

PubMed Central

Shamshirsaz, Alireza Abdollah; Kamgar, Mohammad; Bekheirnia, Mir Reza; Ayazi, Farzam; Hashemi, Seyed Reza; Bouzari, Navid; Habibzadeh, Mohammad Reza; Pourzahedgilani, Nima; Broumand, Varshasb; Shamshirsaz, Amirhooshang Abdollah; Moradi, Maziyar; Borghei, Mehrdad; Haghighi, Niloofar Nobakht; Broumand, Behrooz

2004-01-01

Background Hepatitis C virus (HCV) infection is a significant problem among patients undergoing maintenance hemodialysis (HD). We conducted a prospective multi-center study to evaluate the effect of dialysis machine separation on the spread of HCV infection. Methods Twelve randomly selected dialysis centers in Tehran, Iran were randomly divided into two groups; those using dedicated machines (D) for HCV infected individuals and those using non-dedicated HD machines (ND). 593 HD cases including 51 HCV positive (RT-PCR) cases and 542 HCV negative patients were enrolled in this study. The prevalence of HCV infection in the D group was 10.1% (range: 4.6%– 13.2%) and it was 7.1% (range: 4.2%–16.8%) in the ND group. During the study conduction 5 new HCV positive cases and 169 new HCV negative cases were added. In the D group, PCR positive patients were dialyzed on dedicated machines. In the ND group all patients shared the same machines. Results In the first follow-up period, the incidence of HCV infection was 1.6% and 4.7% in the D and ND group respectively (p = 0.05). In the second follow-up period, the incidence of HCV infection was 1.3% in the D group and 5.7% in the ND group (p < 0.05). Conclusions In this study the incidence of HCV in HD patients decreased by the use of dedicated HD machines for HCV infected patients. Additional studies may help to clarify the role of machine dedication in conjunction with application of universal precautions in reducing HCV transmission. PMID:15469615

Immunogenicity and safety assessment of a trivalent, inactivated split influenza vaccine in Korean children: Double-blind, randomized, active-controlled multicenter phase III clinical trial.

PubMed

Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Lee, Soo Young; Kim, Hyun-Hee; Kim, Jong-Hyun; Lee, Kyung-Yil; Ma, Sang Hyuk; Park, Joon Soo; Kim, Hwang Min; Kim, Chun Soo; Kim, Dong Ho; Choi, Young Youn; Cha, Sung-Ho; Hong, Young Jin; Kang, Jin Han

2015-01-01

A multicenter, double-blind, randomized, active-control phase III clinical trial was performed to assess the immunogenicity and safety of a trivalent, inactivated split influenza vaccine. Korean children between the ages of 6 months and 18 y were enrolled and randomized into a study (study vaccine) or a control vaccine group (commercially available trivalent, inactivated split influenza vaccine) in a 5:1 ratio. Antibody responses were determined using hemagglutination inhibition assay, and post-vaccination immunogenicity was assessed based on seroconversion and seroprotection rates. For safety assessment, solicited local and systemic adverse events up to 28 d after vaccination and unsolicited adverse events up to 6 months after vaccination were evaluated. Immunogenicity was assessed in 337 and 68 children of the study and control groups. In the study vaccine group, seroconversion rates against influenza A/H1N1, A/H3N2, and B strains were 62.0% (95% CI: 56.8-67.2), 53.4% (95% CI: 48.1-58.7), and 54.9% (95% CI: 48.1-60.2), respectively. The corresponding seroprotection rates were 95.0% (95% CI: 92.6-97.3), 93.8% (95% CI: 91.2-96.4), and 95.3% (95% CI: 93.0-97.5). The lower 95% CI limits of the seroconversion and seroprotection rates were over 40% and 70%, respectively, against all strains. Seroconversion and seroprotection rates were not significantly different between the study and control vaccine groups. Furthermore, the frequencies of adverse events were not significantly different between the 2 vaccine groups, and no serious vaccination-related adverse events were noted. In conclusion, the study vaccine exhibited substantial immunogenicity and safety in Korean children and is expected to be clinically effective.

Next-generation narrow band imaging system for colonic polyp detection: a prospective multicenter randomized trial.

PubMed

Horimatsu, Takahiro; Sano, Yasushi; Tanaka, Shinji; Kawamura, Takuji; Saito, Shoichi; Iwatate, Mineo; Oka, Shiro; Uno, Koji; Yoshimura, Kenichi; Ishikawa, Hideki; Muto, Manabu; Tajiri, Hisao

2015-07-01

Previous studies have yielded conflicting results on the colonic polyp detection rate with narrow-band imaging (NBI) compared with white-light imaging (WLI). We compared the mean number of colonic polyps detected per patient for NBI versus WLI using a next-generation NBI system (EVIS LUCERA ELITE; Olympus Medical Systems) used with standard-definition (SD) colonoscopy and wide-angle (WA) colonoscopy. this study is a 2 × 2 factorial, prospective, multicenter randomized controlled trial. this study was conducted at five academic centers in Japan. patients were allocated to one of four groups: (1) WLI with SD colonoscopy (H260AZI), (2) NBI with SD colonoscopy (H260AZI), (3) WLI with WA colonoscopy (CF-HQ290), and (4) NBI with WA colonoscopy (CF-HQ290). the mean numbers of polyps detected per patient were compared between the four groups: WLI with/without WA colonoscopy and NBI with/without WA colonoscopy. Of the 454 patients recruited, 431 patients were enrolled. The total numbers of polyps detected by WLI with SD, NBI with SD, WLI with WA, and NBI with WA were 164, 176, 188, and 241, respectively. The mean number of polyps detected per patient was significantly higher in the NBI group than in the WLI group (2.01 vs 1.56; P = 0.032). The rate was not higher in the WA group than in the SD group (1.97 vs 1.61; P = 0.089). Although WA colonoscopy did not improve the polyp detection, next-generation NBI colonoscopy represents a significant improvement in the detection of colonic polyps.

The frailty in elderly patients receiving cardiac interventional procedures (FRASER) program: rational and design of a multicenter prospective study.

PubMed

Campo, Gianluca; Pavasini, Rita; Maietti, Elisa; Tonet, Elisabetta; Cimaglia, Paolo; Scillitani, Giulia; Bugani, Giulia; Serenelli, Matteo; Zaraket, Fatima; Balla, Cristina; Trevisan, Filippo; Biscaglia, Simone; Sassone, Biagio; Galvani, Marcello; Ferrari, Roberto; Volpato, Stefano

2017-10-01

Frailty has become a high-priority issue in cardiovascular medicine because of the aging of cardiovascular patients. Simple and reproducible tools to assess frailty in elderly patients are clearly on demand. Their application may help physicians in the selection of invasive and medical treatments and in the timing and modality of the follow-up. The frailty in elderly patients receiving cardiac interventional procedures (FRASER) program is designed with the aim to validate the use of the short physical performance battery (SPPB) as prognostic tools in patients admitted to hospital for acute coronary syndrome (ACS). The FRASER program is a multicenter prospective study involving 4 Italian cardiology units. The FRASER program enrolls only patients aged ≥70 years. The core of the FRASER program includes patients admitted to hospital for ACS. The aims are (1) to describe SPPB distribution before hospital discharge and (2) to investigate the prognostic role of SPPB score. The primary outcome is a composite of 1-year all-cause mortality and hospital readmission for any cause. Ancillary analyses will be focused on different study populations (patients hospitalized for arrhythmias or acute heart failure or symptomatic severe aortic stenosis) and on different tools to assess frailty (multidimensional prognostic index, clinical frailty score, grip strength). The FRASER program will fill critical gaps in the knowledge regarding the link between frailty, cardiovascular disease, interventional procedures and outcome and will help physicians in the generation of a more personalized risk assessment and in the identification of potential targets for interventions.

A Prospective, Single Arm, Multi-site, Clinical Evaluation of a Nonradioactive Surgical Guidance Technology for the Location of Nonpalpable Breast Lesions during Excision.

PubMed

Cox, Charles E; Russell, Scott; Prowler, Vanessa; Carter, Ebonie; Beard, Abby; Mehindru, Ankur; Blumencranz, Peter; Allen, Kathleen; Portillo, Michael; Whitworth, Pat; Funk, Kristi; Barone, Julie; Norton, Denise; Schroeder, Jerome; Police, Alice; Lin, Erin; Combs, Freddie; Schnabel, Freya; Toth, Hildegard; Lee, Jiyon; Anglin, Beth; Nguyen, Minh; Canavan, Lynn; Laidley, Alison; Warden, Mary Jane; Prati, Ronald; King, Jeff; Shivers, Steven C

2016-10-01

This study was a multicenter evaluation of the SAVI SCOUT(®) breast localization and surgical guidance system using micro-impulse radar technology for the removal of nonpalpable breast lesions. The study was designed to validate the results of a recent 50-patient pilot study in a larger multi-institution trial. The primary endpoints were the rates of successful reflector placement, localization, and removal. This multicenter, prospective trial enrolled patients scheduled to have excisional biopsy or breast-conserving surgery of a nonpalpable breast lesion. From March to November 2015, 154 patients were consented and evaluated by 20 radiologists and 16 surgeons at 11 participating centers. Patients had SCOUT(®) reflectors placed up to 7 days before surgery, and placement was confirmed by mammography or ultrasonography. Implanted reflectors were detected by the SCOUT(®) handpiece and console. Presence of the reflector in the excised surgical specimen was confirmed radiographically, and specimens were sent for routine pathology. SCOUT(®) reflectors were successfully placed in 153 of 154 patients. In one case, the reflector was placed at a distance from the target that required a wire to be placed. All 154 lesions and reflectors were successfully removed during surgery. For 101 patients with a preoperative diagnosis of cancer, 86 (85.1 %) had clear margins, and 17 (16.8 %) patients required margin reexcision. SCOUT(®) provides a reliable and effective alternative method for the localization and surgical excision of nonpalpable breast lesions using no wires or radioactive materials, with excellent patient, radiologist, and surgeon acceptance.

CERAMENT treatment of fracture defects (CERTiFy): protocol for a prospective, multicenter, randomized study investigating the use of CERAMENT™ BONE VOID FILLER in tibial plateau fractures

PubMed Central

2014-01-01

Background Bone graft substitutes are widely used for reconstruction of posttraumatic bone defects. However, their clinical significance in comparison to autologous bone grafting, the gold-standard in reconstruction of larger bone defects, still remains under debate. This prospective, randomized, controlled clinical study investigates the differences in pain, quality of life, and cost of care in the treatment of tibia plateau fractures-associated bone defects using either autologous bone grafting or bioresorbable hydroxyapatite/calcium sulphate cement (CERAMENT™|BONE VOID FILLER (CBVF)). Methods/Design CERTiFy (CERament™ Treatment of Fracture defects) is a prospective, multicenter, controlled, randomized trial. We plan to enroll 136 patients with fresh traumatic depression fractures of the proximal tibia (types AO 41-B2 and AO 41-B3) in 13 participating centers in Germany. Patients will be randomized to receive either autologous iliac crest bone graft or CBVF after reduction and osteosynthesis of the fracture to reconstruct the subchondral bone defect and prevent the subsidence of the articular surface. The primary outcome is the SF-12 Physical Component Summary at week 26. The co-primary endpoint is the pain level 26 weeks after surgery measured by a visual analog scale. The SF-12 Mental Component Summary after 26 weeks and costs of care will serve as key secondary endpoints. The study is designed to show non-inferiority of the CBVF treatment to the autologous iliac crest bone graft with respect to the physical component of quality of life. The pain level at 26 weeks after surgery is expected to be lower in the CERAMENT bone void filler treatment group. Discussion CERTiFy is the first randomized multicenter clinical trial designed to compare quality of life, pain, and cost of care in the use of the CBVF and the autologous iliac crest bone graft in the treatment of tibia plateau fractures. The results are expected to influence future treatment recommendations. Trial registration number ClinicalTrials.gov: NCT01828905 PMID:24606670

Multicenter prospective randomized phase II study of antimicrobial prophylaxis in low-risk patients undergoing colon surgery.

PubMed

Shimizu, Junzo; Ikeda, Kimimasa; Fukunaga, Mutsumi; Murata, Kohei; Miyamoto, Atsushi; Umeshita, Koji; Kobayashi, Tetsuro; Monden, Morito

2010-10-01

Postoperative antimicrobial therapy is generally administered as standard prophylaxis against postoperative infection, despite a lack of sufficient evidence for its usefulness. This study was a phase II study to evaluate the necessity of postoperative antibiotic prophylaxis in patients undergoing a colectomy. Patients received 1 g cefmetazole or flomoxef immediately after anesthetic induction, every 3 h during surgery, and then later once again on the next day. They were randomly assigned to receive either cefmetazole or flomoxef. Ninety-one patients were enrolled in the study. A surgical site infection (SSI) occurred in 7.7% (7/91) of patients. All cases were superficial incisional infections. When comparing the two drugs, SSI occurred in 8.3% (4/48) of patients treated with cefmetazole and in 7.0% (3/43) treated with flomoxef, showing no significant difference (P > 0.99). Antimicrobial prophylaxis was well tolerated when used on the day of a colectomy and once again on the next day.

Prospective, multicenter French study evaluating the clinical impact of the Breast Cancer Intrinsic Subtype-Prosigna® Test in the management of early-stage breast cancers.

PubMed

Hequet, Delphine; Callens, Céline; Gentien, David; Albaud, Benoit; Mouret-Reynier, Marie-Ange; Dubot, Coraline; Cottu, Paul; Huchon, Cyrille; Zilberman, Sonia; Berseneff, Helene; Foa, Cyril; Salmon, Rémy; Roulot, Aurélie; Lerebours, Florence; Salomon, Anne; Ghali, Nadeem; Morel, Pascale; Li, Qianyi; Cayre, Anne; Guinebretière, Jean-Marc; Hornberger, John; Penault-Llorca, Frédérique; Rouzier, Roman

2017-01-01

The Prosigna® breast cancer prognostic gene signature assay identifies a gene-expression profile that permits the classification of tumors into subtypes and gives a score for the risk of recurrence (ROR) at 10 years. The primary objective of this multicenter study was to evaluate the impact of Prosigna's assay information on physicians' adjuvant treatment decisions in patients with early-stage breast cancer. Secondary objectives were to assess confidence of practitioners in their therapeutic recommendations before and after the added information provided by the Prosigna assay; and to evaluate the emotional state of patients before and after the Prosigna test results. Consecutive patients with invasive early-stage breast cancer were enrolled in a prospective, observational, multicenter study carried out in 8 hospitals in France. The Prosigna test was carried out on surgical specimens using the nCounter® Analysis System located at the Institut Curie. Both before and after receiving the Prosigna test results, physicians completed treatment confidence questionnaires and patients completed questionnaires concerning their state of anxiety, the difficulties felt in face of the therapy and quality of life. Information was also collected at 6 months regarding the physicians' opinion on the test results and the patients' degree of anxiety, difficulties with therapy and quality of life. Between March 2015 and January 2016, 8 study centers in France consecutively enrolled 210 postmenopausal women with estrogen receptor (ER) positive, human epidermal growth hormone-2 (HER-2) negative, and node negative tumors, either stage 1 or stage 2. Intrinsic tumor subtypes as assessed by the Prosigna test were 114 (58.2%) Luminal A, 79 (40.3%) Luminal B, 1 (0.5%) HER-2 enriched (HER-2E), and 2 (1.0%) basal-like. Before receiving the Prosigna test results, physicians categorized tumor subtypes based on immunohistochemistry (IHC) as Luminal A in 126 (64%) patients and Luminal B in 70 (36%) patients, an overall discordance rate of 25%. The availability of Prosigna assay results was significantly associated with the likelihood of change in treatment recommendations, with 34 patients (18%) having their treatment plan changed from Adjuvant Chemotherapy to No Adjuvant Chemotherapy or vice versa (p<0.001, Fisher's exact test). Prosigna test results also decreased patients' anxiety about the chosen adjuvant therapy, and improved emotional well-being and measures of personal perceptions of uncertainty. The results of this prospective decision impact study are consistent with 2 previous, identically designed studies carried out in Spain and Germany. The availability of Prosigna test results increased the confidence of treating physicians in their adjuvant treatment decisions, and led to an 18% change in chemotherapy treatment plan (from Adjuvant Chemotherapy to No Adjuvant Chemotherapy or vice versa). Prosigna testing decreased anxiety and improved measures of health-related quality of life in patients facing adjuvant therapy. The 25% discordance between Prosigna test and IHC subtyping underlines the importance of molecular testing for optimal systemic therapy indications in early breast cancer.

Prospective, multicenter French study evaluating the clinical impact of the Breast Cancer Intrinsic Subtype-Prosigna® Test in the management of early-stage breast cancers

PubMed Central

Callens, Céline; Gentien, David; Albaud, Benoit; Mouret-Reynier, Marie-Ange; Dubot, Coraline; Cottu, Paul; Huchon, Cyrille; Zilberman, Sonia; Berseneff, Helene; Foa, Cyril; Salmon, Rémy; Roulot, Aurélie; Lerebours, Florence; Salomon, Anne; Ghali, Nadeem; Morel, Pascale; Li, Qianyi; Cayre, Anne; Guinebretière, Jean-Marc; Hornberger, John; Penault-Llorca, Frédérique; Rouzier, Roman

2017-01-01

Purpose The Prosigna® breast cancer prognostic gene signature assay identifies a gene-expression profile that permits the classification of tumors into subtypes and gives a score for the risk of recurrence (ROR) at 10 years. The primary objective of this multicenter study was to evaluate the impact of Prosigna’s assay information on physicians’ adjuvant treatment decisions in patients with early-stage breast cancer. Secondary objectives were to assess confidence of practitioners in their therapeutic recommendations before and after the added information provided by the Prosigna assay; and to evaluate the emotional state of patients before and after the Prosigna test results. Methods Consecutive patients with invasive early-stage breast cancer were enrolled in a prospective, observational, multicenter study carried out in 8 hospitals in France. The Prosigna test was carried out on surgical specimens using the nCounter® Analysis System located at the Institut Curie. Both before and after receiving the Prosigna test results, physicians completed treatment confidence questionnaires and patients completed questionnaires concerning their state of anxiety, the difficulties felt in face of the therapy and quality of life. Information was also collected at 6 months regarding the physicians’ opinion on the test results and the patients’ degree of anxiety, difficulties with therapy and quality of life. Results Between March 2015 and January 2016, 8 study centers in France consecutively enrolled 210 postmenopausal women with estrogen receptor (ER) positive, human epidermal growth hormone-2 (HER-2) negative, and node negative tumors, either stage 1 or stage 2. Intrinsic tumor subtypes as assessed by the Prosigna test were 114 (58.2%) Luminal A, 79 (40.3%) Luminal B, 1 (0.5%) HER-2 enriched (HER-2E), and 2 (1.0%) basal-like. Before receiving the Prosigna test results, physicians categorized tumor subtypes based on immunohistochemistry (IHC) as Luminal A in 126 (64%) patients and Luminal B in 70 (36%) patients, an overall discordance rate of 25%. The availability of Prosigna assay results was significantly associated with the likelihood of change in treatment recommendations, with 34 patients (18%) having their treatment plan changed from Adjuvant Chemotherapy to No Adjuvant Chemotherapy or vice versa (p<0.001, Fisher’s exact test). Prosigna test results also decreased patients’ anxiety about the chosen adjuvant therapy, and improved emotional well-being and measures of personal perceptions of uncertainty. Conclusions The results of this prospective decision impact study are consistent with 2 previous, identically designed studies carried out in Spain and Germany. The availability of Prosigna test results increased the confidence of treating physicians in their adjuvant treatment decisions, and led to an 18% change in chemotherapy treatment plan (from Adjuvant Chemotherapy to No Adjuvant Chemotherapy or vice versa). Prosigna testing decreased anxiety and improved measures of health-related quality of life in patients facing adjuvant therapy. The 25% discordance between Prosigna test and IHC subtyping underlines the importance of molecular testing for optimal systemic therapy indications in early breast cancer. PMID:29045452

A multicenter study on the health-related quality of life of cataract patients: baseline data.

PubMed

Yamada, Masakazu; Mizuno, Yoshinobu; Miyake, Yozo

2009-09-01

This study examines the impact of cataracts on health-related quality of life (HR-QOL) and health events in the older population. The study population consisted of 439 unoperated cataract patients aged 60 years or older who visited any of the facilities affiliated with the Cataract Survey Group of the National Hospital Organization of Japan, which has been conducting a prospective multicenter cohort study on cataract patients. HR-QOL of the patients was assessed using the Japanese version of Visual Function Questionnaire-25 (VFQ-25) and the 8-Item Short-Form Health Survey (SF-8). The health condition and health events of the patients were also investigated. The average age of the 439 patients enrolled (126 men and 313 women) was 73.0 +/- 7.1 years. There were 323 patients with comorbidities (73.6%), 81 of whom (23.7%) felt it was hard to visit the hospital owing to their visual impairment. In the previous year, 74 patients (16.9%) had experienced a fall and 14 (3.2%) had been in a traffic accident. Of those, 43.2% and 8.3% respectively answered that the falls and the accident could have been triggered by their visual impairment. When the patients were classified according to visual acuity, most of the VFQ-25 subscale scores declined significantly with decreasing visual acuity, whereas the SF-8 scores showed no significant change. The participants of this study were patients with unoperated cataract, and thus the decline of HR-QOL was modest. The survey of health events, however, revealed that the visual constraint has a certain impact on the daily lives of the older population.

Design and rationale of the ANALYZE ST study: a prospective, nonrandomized, multicenter ST monitoring study to detect acute coronary syndrome events in implantable cardioverter-defibrillator patients.

PubMed

Gibson, C Michael; Krucoff, Mitchell; Kirtane, Ajay J; Rao, Sunil V; Mackall, Judith A; Matthews, Ray; Saba, Samir; Waksman, Ron; Holmes, David

2014-10-01

In the setting of ST-segment elevation myocardial infarction, timely restoration of normal blood flow is associated with improved myocardial salvage and survival. Despite improvements in door-to-needle and door-to-balloon times, there remains an unmet need with respect to improved symptom-to-door times. A prior report of an implanted device to monitor ST-segment deviation demonstrated very short times to reperfusion among patients with an acute coronary syndrome (ACS) with documented thrombotic occlusion. The goal of the ANALYZE ST study is to evaluate the safety and effectiveness of a novel ST-segment monitoring feature using an existing implantable cardioverter-defibrillator (ICD) among patients with known coronary artery disease. The ANALYZE ST study is a prospective, nonrandomized, multicenter, pivotal Investigational Device Exemption study enrolling 5,228 patients with newly implanted ICD systems for standard clinical indications who also have a documented history of coronary artery disease. Patients will be monitored for 48 months, during which effectiveness of the device for the purpose of early detection of cardiac injury will be evaluated by analyzing the sensitivity of the ST monitoring feature to identify clinical ACS events. In addition, the safety of the ST monitoring feature will be evaluated through the assessment of the percentage of patients for which monitoring produces a false-positive event over the course of 12 months. The ANALYZE ST trial is testing the hypothesis that the ST monitoring feature in the Fortify ST ICD system (St. Jude Medical, Inc., St. Paul, MN) (or other ICD systems with the ST monitoring feature) will accurately identify patients with clinical ACS events. Copyright © 2014 Mosby, Inc. All rights reserved.

A Multicenter Phase I/II Study of the BCNU Implant (Gliadel ® Wafer) for Japanese Patients with Malignant Gliomas

PubMed Central

AOKI, Tomokazu; NISHIKAWA, Ryo; SUGIYAMA, Kazuhiko; NONOGUCHI, Naosuke; KAWABATA, Noriyuki; MISHIMA, Kazuhiko; ADACHI, Jun-ichi; KURISU, Kaoru; YAMASAKI, Fumiyuki; TOMINAGA, Teiji; KUMABE, Toshihiro; UEKI, Keisuke; HIGUCHI, Fumi; YAMAMOTO, Tetsuya; ISHIKAWA, Eiichi; TAKESHIMA, Hideo; YAMASHITA, Shinji; ARITA, Kazunori; HIRANO, Hirofumi; YAMADA, Shinobu; MATSUTANI, Masao

2014-01-01

Carmustine (BCNU) implants (Gliadel® Wafer, Eisai Inc., New Jersey, USA) for the treatment of malignant gliomas (MGs) were shown to enhance overall survival in comparison to placebo in controlled clinical trials in the United States and Europe. A prospective, multicenter phase I/II study involving Japanese patients with MGs was performed to evaluate the efficacy, safety, and pharmacokinetics of BCNU implants. The study enrolled 16 patients with newly diagnosed MGs and 8 patients with recurrent MGs. After the insertion of BCNU implants (8 sheets maximum, 61.6 mg BCNU) into the removal cavity, various chemotherapies (including temozolomide) and radiotherapies were applied. After placement, overall and progression-free survival rates and whole blood BCNU levels were evaluated. In patients with newly diagnosed MGs, the overall survival rates at 12 months and 24 months were 100.0% and 68.8%, and the progression-free survival rate at 12 months was 62.5%. In patients with recurrent MGs, the progression-free survival rate at 6 months was 37.5%. There were no grade 4 or higher adverse events noted due to BCNU implants, and grade 3 events were observed in 5 of 24 patients (20.8%). Whole blood BCNU levels reached a peak of 19.4 ng/mL approximately 3 hours after insertion, which was lower than 1/600 of the peak BCNU level recorded after intravenous injections. These levels decreased to less than the detection limit (2.00 ng/mL) after 24 hours. The results of this study involving Japanese patients are comparable to those of previous studies in the United States and Europe. PMID:24739422

Efficacy of the 308-nm excimer laser for treatment of psoriasis: results of a multicenter study.

PubMed

Feldman, Steven R; Mellen, Beverly G; Housman, Tamara Salam; Fitzpatrick, Richard E; Geronemus, Roy G; Friedman, Paul M; Vasily, David B; Morison, Warwick L

2002-06-01

Our purpose was to demonstrate the efficacy of the 308-nm excimer laser for treatment of psoriasis. This study was a multicenter open trial from 5 dermatology practices (one university-based and 4 private practices). Up to 30 patients per center with stable mild to moderate plaque-type psoriasis constituted the study population. Patients received 308-nm ultraviolet B doses to affected areas. The initial dose was based on multiples of a predetermined minimal erythema dose. Subsequent doses were based on the response to treatment. Treatments were scheduled twice weekly for a total of 10 treatments. The main outcome measure was 75% clearing of the target plaque. Time to clearing was analyzed by Kaplan-Meier methods, accounting for truncated observations. One hundred twenty-four patients were enrolled in the study, and 80 completed the entire protocol. The most common reason for exiting from the study was noncompliance. Of the patients who met the protocol requirements of 10 treatments or clearing, 72% (66/92) achieved at least 75% clearing in an average of 6.2 treatments. Eighty-four percent of patients (95% confidence interval [CI], 79%-87%) reached improvement of 75% or better after 10 or fewer treatments. Fifty percent of patients (95% CI, 35%-61%) reached improvement of 90% or better after 10 or fewer treatments. Common side effects included erythema, blisters, hyperpigmentation, and erosions, but they were well tolerated. Monochromatic 308-nm excimer laser treatment appears to be effective and safe for psoriasis. It requires fewer patient visits than conventional phototherapy, and, unlike those treatments, the laser targets only the affected areas of the skin, sparing the surrounding uninvolved skin.

A multi-center study on the regenerative effects of erythropoietin in burn and scalding injuries: study protocol for a randomized controlled trial.

PubMed

Günter, Christina Irene; Bader, Augustinus; Dornseifer, Ulf; Egert, Silvia; Dunda, Sebastian; Grieb, Gerrit; Wolter, Thomas; Pallua, Norbert; von Wild, Tobias; Siemers, Frank; Mailänder, Peter; Thamm, Oliver; Ernert, Carsten; Steen, Michael; Sievers, Reiner; Reichert, Bert; Rahmanian-Schwarz, Afshin; Schaller, Hans; Hartmann, Bernd; Otte, Max; Kehl, Victoria; Ohmann, Christian; Jelkmann, Wolfgang; Machens, Hans-Günther

2013-05-03

Although it was initially assumed that erythropoietin (EPO) was a hormone that only affected erythropoiesis, it has now been proposed that EPO plays an additional key role in the regulation of acute and chronic tissue damage. This is a large, prospective, randomized, double-blind, multi-center study, funded by the German Federal Ministry of Education and Research, and fully approved by the designated ethics committee. The trial, which is to investigate the effects of EPO in severely burned patients, is in its recruitment phase and is being carried out in 13 German burn care centers. A total of 150 patients are to be enrolled to receive study medication every other day for 21 days (EPO 150 IU/kg body weight or placebo). A follow-up of one year is planned. The primary endpoint of this study is the time until complete re-epithelialization of a defined skin graft donor site is reached. Furthermore, clinical parameters such as wound healing, scar formation (using the Vancouver scar scale), laboratory values, quality of life (SF-36), angiogenic effects, and gene- and protein-expression patterns are to be determined. The results will be carefully evaluated for gender differences. We are seeking new insights into the mechanisms of wound healing in thermally injured patients and more detailed information about the role EPO plays, specifically in these complex interactions. We additionally expect that the biomimetic effects of EPO will be useful in the treatment of acute thermal dermal injuries. EudraCT Number: 2006-002886-38, Protocol Number: 0506, ISRCT Number: http://controlled-trials.com/ISRCTN95777824/ISRCTN95777824.

Update on the MRI Core of the Alzheimer's Disease Neuroimaging Initiative

PubMed Central

Jack, Clifford R; Bernstein, Matt A; Borowski, Bret J; Gunter, Jeffrey L; Fox, Nick C; Thompson, Paul M; Schuff, Norbert; Krueger, Gunnar; Killiany, Ronald J; DeCarli, Charles S; Dale, Anders M; Weiner, Michael W

2010-01-01

Functions of the ADNI MRI core fall into three categories: (1) those of the central MRI core lab at Mayo Clinic, Rochester, Minnesota, needed to generate high quality MRI data in all subjects at each time point; (2) those of the funded ADNI MRI core imaging analysis groups responsible for analyzing the MRI data, and (3) the joint function of the entire MRI core in designing and problem solving MR image acquisition, pre-processing and analyses methods. The primary objective of ADNI was and continues to be improving methods for clinical trials in Alzheimer's disease. Our approach to the present (“ADNI-GO”) and future (“ADNI-2”, if funded) MRI protocol will be to maintain MRI methodological consistency in previously enrolled “ADNI-1” subjects who are followed longitudinally in ADNI-GO and ADNI-2. We will modernize and expand the MRI protocol for all newly enrolled ADNI-GO and ADNI-2 subjects. All newly enrolled subjects will be scanned at 3T with a core set of three sequence types: 3D T1-weighted volume, FLAIR, and a long TE gradient echo volumetric acquisition for micro hemorrhage detection. In addition to this core ADNI-GO and ADNI-2 protocol, we will perform vendor specific pilot sub-studies of arterial spin labeling perfusion, resting state functional connectivity and diffusion tensor imaging. One each of these sequences will be added to the core protocol on systems from each MRI vendor. These experimental sub-studies are designed to demonstrate the feasibility of acquiring useful data in a multi-center (but single vendor) setting for these three emerging MRI applications. PMID:20451869

Efficacy and safety of golimumab in Indian patients with rheumatoid arthritis: Subgroup data from GO-MORE study.

PubMed

Pal, Sarvajeet; Veeravalli, Sarath Chandra Mouli; Das, Siddharth Kumar; Shobha, Vineeta; Uppuluri, Ramakrishna Rao; Dharmanand, B G; Nadkar, Milind; Hsia, Elizabeth; Fei, Kaiyin; Yao, Ruji; Khalifa, Ahmed

2016-11-01

To conduct a subgroup analysis of GO-MORE trial Part 1, comparing efficacy and safety of add-on subcutaneous golimumab therapy in rheumatoid arthritis (RA) patients enrolled from and outside India. GO-MORE was an open-label, multicenter, prospective trial of add-on golimumab in biologic-naïve RA patients, having active disease despite being on conventional DMARD regimen(s). Part 1 of the study was chosen as the focus of this subgroup analysis because a substantial number of Indian patients (106) were enrolled compared to no Indian patients in Part 2. The primary efficacy outcome was proportion of patients achieving good to moderate DAS28-ESR (Disease Activity Score of 28 joints calculated using erythrocyte sedimentation rate) European League Against Rheumatism (EULAR) response at month 6. Efficacy evaluable population comprised of 105 and 3175 patients from India and outside India, respectively. Safety analysis included 106 patients enrolled from India and 3251 from outside India. A higher proportion of Indian patients had a high disease activity as measured by DAS28 ESR than outside India patients. At month 6, the proportion of Indian and non-Indian patients achieving DAS28-ESR, DAS28 - C-reactive protein, simplified disease activity index (SDAI) remission, and EuroQoL Quality-of-Life Questionnaire (EQ-5D) scores were comparable. Incidence of all adverse events was lower in Indian patients. There were no deaths, cases of tuberculosis or malignancy reported in the patients from India at month 6. The efficacy and safety results with add-on golimumab were consistent between RA patients from India and outside India, despite high baseline disease activity in the Indian patients. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Update on the magnetic resonance imaging core of the Alzheimer's disease neuroimaging initiative.

PubMed

Jack, Clifford R; Bernstein, Matt A; Borowski, Bret J; Gunter, Jeffrey L; Fox, Nick C; Thompson, Paul M; Schuff, Norbert; Krueger, Gunnar; Killiany, Ronald J; Decarli, Charles S; Dale, Anders M; Carmichael, Owen W; Tosun, Duygu; Weiner, Michael W

2010-05-01

Functions of the Alzheimer's Disease Neuroimaging Initiative (ADNI) magnetic resonance imaging (MRI) core fall into three categories: (1) those of the central MRI core laboratory at Mayo Clinic, Rochester, Minnesota, needed to generate high quality MRI data in all subjects at each time point; (2) those of the funded ADNI MRI core imaging analysis groups responsible for analyzing the MRI data; and (3) the joint function of the entire MRI core in designing and problem solving MR image acquisition, pre-processing, and analyses methods. The primary objective of ADNI was and continues to be improving methods for clinical trials in Alzheimer's disease. Our approach to the present ("ADNI-GO") and future ("ADNI-2," if funded) MRI protocol will be to maintain MRI methodological consistency in the previously enrolled "ADNI-1" subjects who are followed up longitudinally in ADNI-GO and ADNI-2. We will modernize and expand the MRI protocol for all newly enrolled ADNI-GO and ADNI-2 subjects. All newly enrolled subjects will be scanned at 3T with a core set of three sequence types: 3D T1-weighted volume, FLAIR, and a long TE gradient echo volumetric acquisition for micro hemorrhage detection. In addition to this core ADNI-GO and ADNI-2 protocol, we will perform vendor-specific pilot sub-studies of arterial spin-labeling perfusion, resting state functional connectivity, and diffusion tensor imaging. One of these sequences will be added to the core protocol on systems from each MRI vendor. These experimental sub-studies are designed to demonstrate the feasibility of acquiring useful data in a multicenter (but single vendor) setting for these three emerging MRI applications. Copyright 2010 The Alzheimer

Rationale and design of a prospective study of the clinical significance of atrial arrhythmias detected by implanted device diagnostics: the TRENDS study.

PubMed

Glotzer, Taya V; Daoud, Emile G; Wyse, D George; Singer, Daniel E; Holbrook, Reece; Pruett, Khadeeja; Smith, Kenneth; Hilker, Christopher E

2006-01-01

Sustained atrial fibrillation (AF) is a common risk factor for stroke. While intermittent AF also appears to pose a substantial stroke risk, the quantitative relationship between the percentage of time spent in AF and stroke risk is poorly specified and "intermittent" AF is not the same as paroxysmal AF. Improved assessment of the impact of AF burden on stroke risk will allow more targeted and safer use of antithrombotic therapy. The primary objective of this study is to determine if AT/AF (all device detected atrial tachyarrhythmias, including atrial flutter, atrial fibrillation, and atrial tachycardia) burden over a 30 day period is an independent predictor of the occurrence of ischemic stroke, transient ischemic attack (TIA) and/or systemic embolism in subjects not receiving anticoagulation therapy. TRENDS is a prospective, post-market, non-randomized, multicenter study designed to enroll 3100 subjects who have an independent Class I/II indication for cardiac rhythm device implantation and who have demographic features suggestive of an increased risk for thromboembolic complications related to AT/AF. All implanted devices will have the ability to collect long-term AT/AF burden trending data and will be equivalently programmed to ensure consistent data collection. All subjects will be followed with device interrogations every 3 months and clinic visits every 6 months for 1 year. Subjects with a documented history of AT/AF prior to enrollment and those who develop AT/AF during the 12-month follow-up will be followed until the last subject enrolled in the study has completed their 24-month follow-up. The results of the TRENDS study should help clarify the implications of data retrieved from an implantable device with regard to the risk for thromboembolic complications from atrial arrhythmias, even in the absence of symptoms.

Cross-sectional multicenter study of patients with urea cycle disorders in the United States.

PubMed

Tuchman, Mendel; Lee, Brendan; Lichter-Konecki, Uta; Summar, Marshall L; Yudkoff, Marc; Cederbaum, Stephen D; Kerr, Douglas S; Diaz, George A; Seashore, Margaretta R; Lee, Hye-Seung; McCarter, Robert J; Krischer, Jeffrey P; Batshaw, Mark L

2008-08-01

Inherited urea cycle disorders comprise eight disorders (UCD), each caused by a deficiency of one of the proteins that is essential for ureagenesis. We report on a cross-sectional investigation to determine clinical and laboratory characteristics of patients with UCD in the United States. The data used for the analysis was collected at the time of enrollment of individuals with inherited UCD into a longitudinal observation study. The study has been conducted by the Urea Cycle Disorders Consortium within the Rare Diseases Clinical Research Network (RDCRN) funded by the National Institutes of Health. One-hundred eighty-three patients were enrolled into the study. Ornithine transcarbamylase (OTC) deficiency was the most frequent disorder (55%), followed by argininosuccinic aciduria (16%) and citrullinemia (14%). Seventy-nine percent of the participants were white (16% Latinos), and 6% were African American. Intellectual and developmental disabilities were reported in 39% with learning disabilities (35%) and half had abnormal neurological examination. Sixty-three percent were on a protein restricted diet, 37% were on Na-phenylbutyrate and 5% were on Na-benzoate. Forty-five percent of OTC deficient patients were on L-citrulline, while most patients with citrullinemia (58%) and argininosuccinic aciduria (79%) were on L-arginine. Plasma levels of branched-chain amino acids were reduced in patients treated with ammonia scavenger drugs. Plasma glutamine levels were higher in proximal UCD and in neonatal type disease. The RDCRN allows comprehensive analyses of rare inherited UCD, their frequencies and current medical practices.

Cross-Sectional Multi-Center Study of Patients with Urea Cycle Disorders in the United States

PubMed Central

Tuchman, Mendel; Lee, Brendan; Lichter-Konecki, Uta; Summar, Marshall L.; Yudkoff, Marc; Cederbaum, Stephen D.; Kerr, Douglas S.; Diaz, George A.; Seashore, Margaretta R.; Lee, Hye-Seung; McCarter, Robert J.; Krischer, Jeffrey P.; Batshaw, Mark L.

2008-01-01

Inherited urea cycle disorders comprise eight disorders (UCD), each caused by a deficiency of one of the protein that is essential for ureagenesis. We report on a cross sectional investigation to determine clinical and laboratory characteristics of patients with UCD in the United States. The data used for the analysis was collected at the time of enrollment of individuals with inherited UCD into a longitudinal observation study. The study has been conducted by the Urea Cycle Disorders Consortium (UCDC) within the Rare Diseases Clinical Research Network (RDCRN) funded by the National Institutes of Health. One hundred eighty three patients were enrolled into the study. Ornithine transcarbamylase (OTC) deficiency was the most frequent disorder (55%), followed by argininosuccinic aciduria (17%) and citrullinemia (11%). 79% of the participants were white (16% Latinos), and 6% were African American. Intellectual and developmental disabilities were reported in 39% with learning disabilities (35%) and half had abnormal neurological examination. 63% were on a protein restricted diet, 37% were on Na-phenylbutyrate and 5% were on Na-benzoate. 45% of OTC deficient patients were on L-citrulline, while most patients with citrullinemia (58%) and argininosuccinic (79%) were on L-arginine. Plasma levels of branched-chain amino acids were reduced in patients treated with ammonia scavenger drugs. Plasma glutamine levels were higher in proximal UCD disorders and in the neonatal type disease. The RDCRN allows comprehensive analyses of rare inherited UCD, their frequencies and current medical practices. PMID:18562231

Study Design and Interim Outcomes of Guangzhou Institute of Respiratory Disease COPD Biobank.

PubMed

Lu, Wenju; Zheng, Zeguang; Chen, Xindong; Tan, Hui; Wang, Jian; Zhang, Zili; Zheng, Jinping; Chen, Rongchang; Zhang, Chenting; Xu, Xiaoming; Chen, Yuqin; Yang, Quan; Xiong, Mingmei; Guo, Meihua; Zhou, Qipeng; Tang, Chun; Wang, Yingfeng; Ye, Jinmei; Li, Defu; Shu, Jiaze; Tan, Shu; Xu, Chuyi; Wang, Yan; Lai, Ning; Yang, Kai; Lu, Jiachun; Ran, Pixin; Zhong, Nanshan

2016-01-01

GIRD COPD Biobank is a multicenter observational study blood-based database with local characteristics, in order to investigate the causes, risk factors, pathogenesis, prevalence patterns and trends of COPD and promote new pathogenic insights in China. We enrolled 855 clinically COPD patients and 660 controls with normal lung function. Extensive data collection has been undertaken with questionnaires, clinical measurements, and collection and storage of blood specimens, following Standard Operating Procedures (SOP). All surveys had similar quality controls, supervisions, and training of the investigator team. Since September 2010, a total of 1515 subjects (1116 [73.7%] males; 855 [56.4%] diagnosed with COPD) were enrolled. Analyses of the design and interim results of the GIRD COPD Biobank Study identified patients with COPD were older, lower educational level, a longer history of pack-year smoking, less in kitchen fan usage, X-ray exposure, and history of disease (P < 0.01 for all); Most of the COPD subjects belonged to moderately severe or worse, stratified according to Global Lung Function Initiative (GLI); COPD patients had relatively more co-morbidities than controls; Environmental hazard exposures might be the main contributors to the reported respiratory symptoms; Cold air, haze, and influenza acted the top three factors to induce respiratory symptoms in both COPD cases and controls. The GIRD COPD Biobank Study has the potential to provide substantial novel insights into the genetics, biomarkers, environmental and lifestyle aspects of COPD. It is expected to provide new insights for pathogenesis and the long-term progression of COPD.

Effectiveness of adjuvant radiotherapy in patients with oropharyngeal and floor of mouth squamous cell carcinoma and concomitant histological verification of singular ipsilateral cervical lymph node metastasis (pN1-state) - A prospective multicenter randomized controlled clinical trial using a comprehensive cohort design

PubMed Central

2009-01-01

Background Modern radiotherapy plays an important role in therapy of advanced head and neck carcinomas. However, no clinical studies have been published addressing the effectiveness of postoperative radiotherapy in patients with small tumor (pT1, pT2) and concomitant ipsilateral metastasis of a single lymph node (pN1), which would provide a basis for a general treatment recommendation. Methods/Design The present study is a non-blinded, prospective, multi-center randomized controlled trial (RCT). As the primary clinical endpoint, overall-survival in patients receiving postoperative radiation therapy vs. patients without adjuvant therapy following curative intended surgery is compared. The aim of the study is to enroll 560 adult males and females for 1:1 randomization to one of the two treatment arms (irradiation/no irradiation). Since patients with small tumor (T1/T2) but singular lymph node metastasis are rare and the amount of patients consenting to randomization is not predictable in advance, all patients rejecting randomization will be treated as preferred and enrolled in a prospective observational study (comprehensive cohort design) after giving informed consent. This observational part of the trial will be performed with maximum consistency to the treatment and observation protocol of the RCT. Because the impact of patient preference for a certain treatment option is not calculable, parallel design of RCT and observational study may provide a maximum of evidence and efficacy for evaluation of treatment outcome. Secondary clinical endpoints are as follows: incidence and time to tumor relapse (locoregional relapse, lymph node involvement and distant metastatic spread), Quality of life as reported by EORTC (QLQ-C30 with H&N 35 module), and time from operation to orofacial rehabilitation. All tumors represent a homogeneous clinical state and therefore additional investigation of protein expression levels within resection specimen may serve for establishment of surrogate parameters of patient outcome. Conclusion The inherent challenges of a rare clinical condition (pN1) and two substantially different therapy arms would limit the practicality of a classical randomized study. The concept of a Comprehensive Cohort Design combines the preference of a randomized study, with the option of careful data interpretation within an observational study. Trial registration ClinicalTrials.gov: NCT00964977 PMID:20028566

Multicenter clinical trial on a permanent hair dye containing paratoluenediamine.

PubMed

Foti, Caterina; Balato, Nicola; Cristaudo, Antonio; Patruno, Cataldo; Pigatto, Paolo; Ambrifi, Marina; Bufano, Tamara; Damiani, Giovanni; De Rocco, Mariagrazia; Diani, Marco; Napolitano, Maddalena; Romita, Paolo

2018-08-01

Adverse reactions to hair dyes are frequent and usually caused by sensitization to paraphenylenediamine (PPD). The aim of the study was to evaluate the tolerability of a PPD-free permanent hair dye (Shine On, BioNike, Milan, Italy) containing paratoluenediamine (PTD) in a group of subjects sensitized to PPD. The trial, which carried out at four dermatology centers, included subjects sensitized to PPD that turned out negative to patch testing to PTD. The subjects underwent to an open test consisting in the application of two hair dye colors of the product under examination. Finally, subjects who were negative upon the open test were offered to undergo the usage test with the dye, with dermatological evaluations carried out 48 and 96 hours after product application. Sixty subjects were enrolled. They underwent the open test with two shades of dyes: "color 1 - black," the dye color with the highest concentration of color intermediates, and "color 7.3 - golden blonde," the dye color with the highest number of chemically different color intermediates. No reactions occurred with "color 7.3 - golden blonde," while 3 cases (3 out of 60) showed erythema and edema reactions to color 1. The hair dye usage test was negative for all the 21 subjects that were enrolled. The hair dye evaluated in this study (Shine On, BioNike) can be a valid alternative for subjects sensitized to PPD.

The role of HIV infection in the etiology and epidemiology of diarrheal disease among children aged 0-59 months in Manhiça district, Rural Mozambique.

PubMed

Acácio, Sozinho; Nhampossa, Tacilta; Quintó, Llorenç; Vubil, Delfino; Sacoor, Charfudin; Kotloff, Karen; Farag, Tamer; Dilruba, Nasrin; Macete, Eusebio; Levine, Myron M; Alonso, Pedro; Mandomando, Inácio; Bassat, Quique

2018-05-28

Diarrhea is an important health problem among HIV-infected patients. This study evaluates the role of HIV on the epidemiology, etiology and severity of diarrheal disease among children. The Global Enteric Multicenter Study enrolled children with moderate-to-severe (MSD) and less severe (LSD) diarrhea between December 2007 and November 2012. One to three controls for MSD cases and one per LSD case were enrolled and matched by age, sex and neighborhood. All children were tested for HIV. Clinical, anthropometric data and stools were collected. A follow-up was performed at 60 days. 214 MSD cases and 418 controls, together with 349 LSD cases and 214 controls were tested. HIV prevalence among MSD cases was 25% (4% for matched controls) and 6% among LSD cases (6% among matched controls). HIV-infected children were more likely to have MSD (OR=5.6, p< 0.0001). Mortality rates were higher among HIV-infected children compared with uninfected (34 vs. 5 per 1000 children-weeks at risk; p=0.0039). Cryptosporidium, Giardia, EAEC (aatA only) were more prevalent among HIV-infected MSD-cases than uninfected ones. HIV is an important risk factor for MSD. The high mortality rate implies that children with MSD should be screened for HIV and managed accordingly. Copyright © 2018. Published by Elsevier Ltd.

Waon Therapy for Managing Chronic Heart Failure　- Results From a Multicenter Prospective Randomized WAON-CHF Study.

PubMed

Tei, Chuwa; Imamura, Teruhiko; Kinugawa, Koichiro; Inoue, Teruo; Masuyama, Tohru; Inoue, Hiroshi; Noike, Hirofumi; Muramatsu, Toshihiro; Takeishi, Yasuchika; Saku, Keijiro; Harada, Kazumasa; Daida, Hiroyuki; Kobayashi, Youichi; Hagiwara, Nobuhisa; Nagayama, Masatoshi; Momomura, Shinichi; Yonezawa, Kazuya; Ito, Hiroshi; Gojo, Satoshi; Akaishi, Makoto; Miyata, Masaaki; Ohishi, Mitsuru

2016-01-01

Waon therapy improves heart failure (HF) symptoms, but further evidence in patients with advanced HF remains uncertain. In 19 institutes, we prospectively enrolled hospitalized patients with advanced HF, who had plasma levels of B-type natriuretic peptide (BNP) >500 pg/ml on admission and BNP >300 pg/ml regardless of more than 1 week of medical therapy. Enrolled patients were randomized into Waon therapy or control groups. Waon therapy was performed once daily for 10 days with a far infrared-ray dry sauna maintained at 60℃ for 15 min, followed by bed rest for 30 min covered with a blanket. The primary endpoint was the ratio of BNP before and after treatment. In total, 76 Waon therapy and 73 control patients (mean age 66 years, men 61%, mean plasma BNP 777 pg/ml) were studied. The groups differed only in body mass index and the frequency of diabetes. The plasma BNP, NYHA classification, 6-min walk distance (6MWD), and cardiothoracic ratio significantly improved only in the Waon therapy group. Improvements in NYHA classification, 6MWD, and cardiothoracic ratio were significant in the Waon therapy group, although the change in plasma BNP did not reach statistical significance. No serious adverse events were observed in either group. Waon therapy, a holistic soothing warmth therapy, showed clinical advantages in safety and efficacy among patients with advanced HF.

Ranitidine is associated with infections, necrotizing enterocolitis, and fatal outcome in newborns.

PubMed

Terrin, Gianluca; Passariello, Annalisa; De Curtis, Mario; Manguso, Francesco; Salvia, Gennaro; Lega, Laura; Messina, Francesco; Paludetto, Roberto; Canani, Roberto Berni

2012-01-01

Gastric acidity is a major nonimmune defense mechanism against infections. The objective of this study was to investigate whether ranitidine treatment in very low birth weight (VLBW) infants is associated with an increased risk of infections, necrotizing enterocolitis (NEC), and fatal outcome. Newborns with birth weight between 401 and 1500 g or gestational age between 24 and 32 weeks, consecutively observed in neonatal intensive care units, were enrolled in a multicenter prospective observational study. The rates of infectious diseases, NEC, and death in enrolled subjects exposed or not to ranitidine were recorded. We evaluated 274 VLBW infants: 91 had taken ranitidine and 183 had not. The main clinical and demographic characteristics did not differ between the 2 groups. Thirty-four (37.4%) of the 91 children exposed to ranitidine and 18 (9.8%) of the 183 not exposed to ranitidine had contracted infections (odds ratio 5.5, 95% confidence interval 2.9-10.4, P < .001). The risk of NEC was 6.6-fold higher in ranitidine-treated VLBW infants (95% confidence interval 1.7-25.0, P = .003) than in control subjects. Mortality rate was significantly higher in newborns receiving ranitidine (9.9% vs 1.6%, P = .003). Ranitidine therapy is associated with an increased risk of infections, NEC, and fatal outcome in VLBW infants. Caution is advocated in the use of this drug in neonatal age.

Clinical and demographic factors associated with urinary tract infection in young febrile infants.

PubMed

Zorc, Joseph J; Levine, Deborah A; Platt, Shari L; Dayan, Peter S; Macias, Charles G; Krief, William; Schor, Jeffrey; Bank, David; Shaw, Kathy N; Kuppermann, Nathan

2005-09-01

Previous research has identified clinical predictors for urinary tract infection (UTI) to guide urine screening in febrile children <24 months of age. These studies have been limited to single centers, and few have focused on young infants who may be most at risk for complications if a UTI is missed. The objective of this study was to identify clinical and demographic factors associated with UTI in febrile infants who are < or =60 days of age using a prospective multicenter cohort. We conducted a multicenter, prospective, cross-sectional study during consecutive bronchiolitis seasons. All febrile (> or =38 degrees C) infants who were < or =60 days of age and seen at any of 8 pediatric emergency departments from October through March 1999-2001 were eligible. Clinical appearance was evaluated using the Yale Observation Scale. UTI was defined as growth of a known bacterial pathogen from a catheterized specimen at a level of (1) > or =50000 cfu/mL or (2) > or =10000 cfu/mL in association with a positive dipstick test or urinalysis. We used bivariate tests and multiple logistic regression to identify demographic and clinical factors that were associated with the likelihood of UTI. A total of 1025 (67%) of 1513 eligible patients were enrolled; 9.0% of enrolled infants received a diagnosis of UTI. Uncircumcised male infants had a higher rate of UTI (21.3%) compared with female (5.0%) and circumcised male (2.3%) infants. Infants with maximum recorded temperature of > or =39 degrees C had a higher rate of UTI (16.3%) than other infants (7.2%). After multivariable adjustment, UTI was associated with being uncircumcised (odds ratio: 10.4; bias-corrected 95% confidence interval: 4.7-31.4) and maximum temperature (odds ratio: 2.4 per degrees C; 95% confidence interval: 1.5-3.6). Factors that were reported previously to be associated with risk for UTI in infants and toddlers, such as white race and ill appearance, were not significantly associated with risk for UTI in this cohort of young infants. Being uncircumcised and height of fever were associated with UTI in febrile infants who were < or =60 days of age. Uncircumcised male infants were at particularly high risk and may warrant a different approach to screening and management.

Smartphone ECG for evaluation of ST-segment elevation myocardial infarction (STEMI): Design of the ST LEUIS International Multicenter Study.

PubMed

Barbagelata, Alejandro; Bethea, Charles F; Severance, Harry W; Mentz, Robert J; Albert, David; Barsness, Gregory W; Le, Viet T; Anderson, Jeffrey L; Bunch, T Jared; Yanowitz, Frank; Chisum, Benjamin; Ronnow, Brianna S; Muhlestein, Joseph B

In patients experiencing an ST-elevation myocardial infarction (STEMI), rapid diagnosis and immediate access to reperfusion therapy leads to optimal clinical outcomes. The rate-limiting step in STEMI diagnosis is the availability and performance of a 12-lead ECG. Recent technology has provided access to a reliable means of obtaining an ECG reading through a smartphone application (app) that works with an attachment providing all 12-leads of a standard ECG system. The ST LEUIS study was designed to validate the smartphone ECG app and its ability to accurately assess the presence or absence of STEMI in patients presenting with chest pain compared with the gold standard 12-lead ECG. We aimed to support the diagnostic utility of smartphone technology to provide a timely diagnosis and treatment of STEMI. The study will take place over 12months at five institutions. Approximately 60 patients will be enrolled per institution, for a total recruitment of 300 patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Early mortality in children with acute lymphoblastic leukemia in a developing country: the role of malnutrition at diagnosis. A multicenter cohort MIGICCL study.

PubMed

Martín-Trejo, Jorge Alfonso; Núñez-Enríquez, Juan Carlos; Fajardo-Gutiérrez, Arturo; Medina-Sansón, Aurora; Flores-Lujano, Janet; Jiménez-Hernández, Elva; Amador-Sanchez, Raquel; Peñaloza-Gonzalez, José Gabriel; Alvarez-Rodriguez, Francisco Javier; Bolea-Murga, Victoria; Espinosa-Elizondo, Rosa Martha; de Diego Flores-Chapa, José; Pérez-Saldivar, Maria Luisa; Rodriguez-Zepeda, María Del Carmen; Dorantes-Acosta, Elisa María; Núñez-Villegas, Nora Nancy; Velazquez-Aviña, Martha Margarita; Torres-Nava, José Refugio; Reyes-Zepeda, Nancy Carolina; González-Bonilla, César Raúl; Flores-Villegas, Luz Victoria; Rangel-López, Angélica; Rivera-Luna, Roberto; Paredes-Aguilera, Rogelio; Cárdenas-Cardós, Rocío; Martínez-Avalos, Armando; Gil-Hernández, Ana Elena; Duarte-Rodríguez, David Aldebarán; Mejía-Aranguré, Juan Manuel

2017-04-01

The role of malnutrition at diagnosis as a predictor of early mortality in Mexican leukemia children remains controversial. The objective of present study was to investigate whether malnutrition was a predictor of early mortality during the first year of treatment in Mexican acute lymphoblastic leukemia (ALL) children through the first population-based study. A total of 794 newly diagnosed ALL pediatric patients from public hospitals of Mexico City were enrolled. A multivariate Cox proportional hazards regression model was constructed and adjusted by patient's age at diagnosis, gender, hospital of treatment, and socioeconomic status. Early mortality was high (12.1%) and malnutrition by different indicators was not associated with mortality at induction phase and at 6th month; a high risk of dying (RR = 2.08; 95% CI: 1.08-4.01) was observed in the group of malnourished children with a high-risk ALL.

[Diagnostic value of quantitative cultures of endotracheal aspirate in ventilator-associated pneumonia: a multicenter study].

PubMed

Valencia Arango, M; Torres Martí, A; Insausti Ordeñana, J; Alvarez Lerma, F; Carrasco Joaquinet, N; Herranz Casado, M; Tirapu León, J P

2003-09-01

To study the validity of quantitative cultures of tracheal aspirate (TA) in comparison with the plugged telescoping catheter (PTC) for the diagnosis of mechanical ventilator-associated pneumonia. Prospective multicenter study enrolling patients undergoing mechanical ventilation for longer than 72 hours. TA samples were collected from patients with suspected ventilator-associated pneumonia, followed by PTC sampling. Quantitative cultures were performed on all samples. Patients were classified according to the presence or not of pneumonia, based on clinical and radiologic criteria, clinical course and autopsy findings. The cutoff points were > or = 103 colony-forming units (cfu)/mL for PTC cultures; the TA cutoffs analyzed were > or = 105 and > or = 106 cfu/mL. Of the 120 patients studied, 84 had diagnoses of pneumonia and 36 did not (controls). The sensitivity values for TA > or = 106, TA > or = 105, and PTC, respectively, were 54% (95% confidence interval [CI], 42%-64%), 71% (95% CI, 60%-81%), and 68% (95% CI, 57%-78%). The specificity values were 75% (95% CI, 58%-88%), 58% (95% CI, 41%-74%), and 75% (95% CI, 58%-88%), respectively. Staphylococcus aureus was the microorganism most frequently isolated in both TA and PTC samples, followed in frequency by Pseudomomonas aeruginosa in TA samples and Haemophilus influenzae in PTC samples. No significant differences were found between the sensitivity of TA > or = 105 and that of PTC, nor between the specificities of TA > or = 106 and PTC. No differences in the specificities of PTC and TA were found when a TA cutoff of > or = 106 cfu/ml was used. Moreover, at a cutoff of > or = 105 the sensitivity of TA was not statistically different from that of PTC. Quantitative cultures of TA can be considered acceptable for the diagnosis of ventilator-associated pneumonia.

Early usage of Bakri postpartum balloon in the management of postpartum hemorrhage: a large prospective, observational multicenter clinical study in South China.

PubMed

Wang, Dongyu; Xu, Shuqia; Qiu, Xiwen; Zhu, Caixia; Li, Zhuyu; Wang, Zilian; Hou, Hongying; Gao, Yu; Wang, Xiaoyi; He, Ping; Qin, Yiwei; Liu, Lihua

2017-12-18

To evaluate the success rate and protocol of the Bakri balloon for postpartum hemorrhage (PPH) in the course of a prospective observational multicenter cohort study in South China. At 20 hospitals in South China, women with postpartum bleeding who failed to respond to the first-line conservative management and received the Bakri balloon were recruited for the study. Maternal characteristics, PPH characteristics, PPH management and outcomes in regard to the Bakri balloon use were recorded. A total of 472 women had a Bakri balloon tamponade and 407 (86.23%) women were enrolled (67 after vaginal delivery and 340 either during or after cesarean delivery). The success rate of the Bakri balloon in this study was 91.65% (373/407 women). During vaginal deliveries, the group with a hemorrhage >2000 mL before balloon insertion had significantly more blood loss (551.67±635.17 mL vs. 242.06±313.69 mL, P=0.039) and lower maternal hemoglobin (73±21.77 g/L vs. 92.06±19.60 g/L, P=0.029) after using Bakri balloon than the group with a hemorrhage <1000 mL. Similar data were found during cesarean deliveries. The blood loss before and after balloon insertion were significantly higher in the Bakri balloon failure group (1700±1429.88 mL before and 1209.58±1139.72 mL after using the balloon) than those in the success group [918±493.92 mL before (P=0.002) and 266.57±361.60 mL after using the balloon (P=0.001)]. Rapid diagnosis or prognosis of PPH, in combination with early usage of the Bakri postpartum balloon is more effective for the management of PPH.

Health-related quality of life assessment in people with multiple sclerosis and their family caregivers. A multicenter study in Catalonia (Southern Europe)

PubMed Central

Aymerich, Marta; Guillamón, Imma; Jovell, Albert J

2009-01-01

Objectives: To measure the health-related quality of life (HRQoL) of multiple sclerosis (MS) patients and their caregivers, and to assess which factors can best describe HRQoL. Methods: A cross-sectional multicenter study of nine hospitals enrolled MS patients and their caregivers who attended outpatient clinics consecutively. The instruments used were the SF-36 for patients and the SF-12 and GHQ-12 for caregivers. Classification and regression tree analysis was used to analyze the explanatory factors of HRQoL. Results: A total of 705 patients (mean age 40.4 years, median Expanded Disability Status Scale 2.5, 77.8% with relapsing-remitting MS) and 551 caregivers (mean age 45.4 years) participated in the study. MS patients had significantly lower HRQoL than in the general population (physical SF-36: 39.9; 95% confidence interval [CI]: 39.1–40.6; mental SF-36: 44.4; 95% CI: 43.5–45.3). Caregivers also presented lower HRQoL than general population, especially in its mental domain (mental SF-12: 46.4; 95% CI: 45.5–47.3). Moreover, according to GHQ-12, 27% of caregivers presented probable psychological distress. Disability and co-morbidity in patients, and co-morbidity and employment status in caregivers, were the most important explanatory factors of their HRQoL. Conclusions: Not only the HRQoL of patients with MS, but also that of their caregivers, is indeed notably affected. Caregivers’ HRQoL is close to population of chronic illness even that the patients sample has a mild clinical severity and that caregiving role is a usual task in the study context. PMID:19936174

MAGNETIC VT study: a prospective, multicenter, post-market randomized controlled trial comparing VT ablation outcomes using remote magnetic navigation-guided substrate mapping and ablation versus manual approach in a low LVEF population.

PubMed

Di Biase, Luigi; Tung, Roderick; Szili-Torok, Tamás; Burkhardt, J David; Weiss, Peter; Tavernier, Rene; Berman, Adam E; Wissner, Erik; Spear, William; Chen, Xu; Neužil, Petr; Skoda, Jan; Lakkireddy, Dhanunjaya; Schwagten, Bruno; Lock, Ken; Natale, Andrea

2017-04-01

Patients with ischemic cardiomyopathy (ICM) are prone to scar-related ventricular tachycardia (VT). The success of VT ablation depends on accurate arrhythmogenic substrate localization, followed by optimal delivery of energy provided by constant electrode-tissue contact. Current manual and remote magnetic navigation (RMN)-guided ablation strategies aim to identify a reentry circuit and to target a critical isthmus through activation and entrainment mapping during ongoing tachycardia. The MAGNETIC VT trial will assess if VT ablation using the Niobe™ ES magnetic navigation system results in superior outcomes compared to a manual approach in subjects with ischemic scar VT and low ejection fraction. This is a randomized, single-blind, prospective, multicenter post-market study. A total of 386 subjects (193 per group) will be enrolled and randomized 1:1 between treatment with the Niobe ES system and treatment via a manual procedure at up to 20 sites. The study population will consist of patients with ischemic cardiomyopathy with left ventricular ejection fraction (LVEF) of ≤35% and implantable cardioverter defibrillator (ICD) who have sustained monomorphic VT. The primary study endpoint is freedom from any recurrence of VT through 12 months. The secondary endpoints are acute success; freedom from any VT at 1 year in a large-scar subpopulation; procedure-related major adverse events; and mortality rate through 12-month follow-up. Follow-up will consist of visits at 3, 6, 9, and 12 months, all of which will include ICD interrogation. The MAGNETIC VT trial will help determine whether substrate-based ablation of VT with RMN has clinical advantages over manual catheter manipulation. Clinicaltrials.gov identifier: NCT02637947.

An open-label, multicenter, flexible dose study to evaluate the efficacy and safety of Viagra (sildenafil citrate) in Korean men with erectile dysfunction and arterial hypertension who are taking antihypertensive agents.

PubMed

Park, Hyun Jun; Park, Nam Cheol; Shim, Hong Bang; Park, Jong Kwan; Lee, Sung Won; Park, Kwangsung; Kim, Sae Woong; Moon, Ki Hak; Lee, Dong Hyeon; Yoon, Sang Jin

2008-10-01

Erectile dysfunction (ED) is common among men taking antihypertensive agents to control blood pressure. We evaluated the efficacy and safety of sildenafil citrate in men with ED taking antihypertensive agents. A total of 198 male subjects, aged 20 years and older were enrolled. This study was conducted for 10 weeks as an open-label, multicenter and flexible dose trial with a 2-week screening period and an 8-week treatment phase. Subjects were asked to complete Event Log Worksheets, as well as the International Index of Erectile Function (IIEF) and the Global Efficacy Assessment Questions (GEAQ) questionnaires during the study period. The average age among the 167 subjects who completed the study was 55.8 (31.7 to 77.1). The scores for questions 3 and 4 of IIEF improved from 2.3 and 1.8 at baseline to 3.7 and 3.4 at week 4 and 3.8 and 3.4 at week 8, respectively. There were 86.3% of the patients reported improved erectile function at week 8; 88.3% of the patients reported improved ability to achieve sexual intercourse at week 8. There were no significant differences observed in the responses to questions 3 and 4 of IIEF and GEAQ by the number of antihypertensive agents taken. The adverse events were facial flushing (20.1%), headache (11.7%), palpitation (5.0%), rhinitis (2.8%), URI (2.8%), dizziness (2.2%), dyspnea (2.2%), and nausea (1.7%). Sildenafil citrate is an effective treatment for ED; it is safe and well tolerated by patients with ED taking multiple antihypertensive agents for arterial hypertension.

[The efficacy and safety of cefixime and amoxicillin/clavulanate in the treatment of asymptomatic bacteriuria in pregnant women: a randomized, prospective, multicenter study].

PubMed

Rafal'skiĭ, V V; Dovgan', E V; Kozyrev, Iu V; Gustovarova, T A; Khlybova, S V; Novoselova, A V; Filippenko, N G; Likhikh, D G

2013-01-01

The study was aimed to the evaluation of efficacy and safety of cefixime and amoxicillin/clavulanate in the treatment of asymptomatic bacteriuria in pregnant women. A prospective, multicenter, randomized study that included 112 pregnant women with asymptomatic bacteriuria was performed. 58 women were randomized in group 1 (cefixime [suprax solutab] 400 mg 1 time a day, 7 days), 54 women were included in group 2 (amoxicillin/clavulanate [amoksiklav] 625 mg 3 times a day, 7 days). The average age of the patients in group 1 was 25.2 +/- 6.6; in group 2--26.6 +/- 5.8 years. Physical examination, evaluation of complaints, collection of data on adverse reactions, and bacteriological analysis of urine were performed after enrollment in the study at visit 2 (day 10 +/- 1) and 3 (day 35 +/- 2). Comparable effectiveness of cefixime and amoxicillin/clavulanate in the treatment of asymptomatic bacteriuria in pregnant women was found. Eradication of the pathogen and sustained bacteriological response were observed in 94.8 and 92.7% of women treated with cefixime, and in 98.2 and 92.5% of women treated with amoxicillin/clavulanate, respectively (P > 0.05). At the same time, the use of amoxicillin/clavulanate compared with cefixime significantly higher was followed by the development of adverse reactions (13% and 1.7; respectively; P = 0.02). Seven-day courses of cefixime at a dose 400 mg 1 time a day and amoxicillin/clavulanate at a dose of 625 mg 3 times a day are high-effective treatment regimens for asymptomatic bacteriuria in pregnant women in Russia. The use of amoxicillin/clavulanate is significantly more often accompanied by the development of adverse reactions compared with cefixime.

Long-Term Omalizumab Treatment: A Multicenter, Real-Life, 5-Year Trial.

PubMed

Yorgancıoğlu, Arzu; Öner Erkekol, Ferda; Mungan, Dilşad; Erdinç, Münevver; Gemicioğlu, Bilun; Özşeker, Zeynep Ferhan; Bayrak Değirmenci, Papatya; Naycı, Sibel; Çilli, Aykut; Erdenen, Füsun; Kırmaz, Cengiz; Ediger, Dane; Yalçın, Arzu Didem; Büyüköztürk, Suna; Öztürk, Sami; Güleç, Mustafa; Işık, Sacide Rana; Kalyoncu, Ali Fuat; Göksel, Özlem; Aydın, Ömür; Havlucu, Yavuz; Baloğlu Ar, İdilhan; Erdoğdu, Ahmet

2018-05-17

Omalizumab has demonstrated therapeutic benefits both in controlled clinical trials and real-life studies. However, research concerning the long-term effects and tolerability of omalizumab is needed. The main objective of this study was to evaluate the effectiveness and tolerability of treatment with omalizumab for up to 5 years. A multicenter, retrospective, chart-based study was carried out to compare documented exacerbations, hospitalizations, systemic steroid requirement, FEV1, and asthma control test (ACT) results during 1 year prior to omalizumab treatment versus at 1, 3, and 5 years of treatment. Adverse events and reasons for discontinuation were also recorded at each time point. Four hundred and sixty-five patients were enrolled in the study. Outcome variables had improved after the 1st year and were sustained after the 3rd and 5th years of treatment with omalizumab. Omalizumab treatment reduced the asthma exacerbation rate by 71.3% (p < 0.001) at 1 year, 64.3% (p < 0.001) at 3 years, and 54.8% (p = 0.002) at 5 years. The hospitalization rate also decreased; by the 5th year of the treatment no patients were hospitalized. ACT results had also improved significantly: 12 (p < 0.001) at 1 year, 12 (p < 0.001) at 3 years, and 12 (p = 0.002) at 5 years. Overall, 12.7% of patients reported adverse events (most of these were mild-to-moderate) and the overall dropout rate was 9.0%. Omalizumab had a significant effect on asthma outcomes and this effect was maintained over 5 years. The drug was found to be generally safe and treatment compliance was good. © 2018 S. Karger AG, Basel.

The prognostic significance of atrial fibrillation in heart failure with preserved ejection function: insights from KaRen, a prospective and multicenter study.

PubMed

Bosseau, Christian; Donal, Erwan; Lund, Lars H; Oger, Emmanuel; Hage, Camilla; Mulak, Geneviève; Daubert, Jean-Claude; Linde, Cecilia

2017-06-01

The prognostic value of atrial fibrillation (AF) in heart failure with preserved ejection fraction (HFPEF) remains controversial. We sought to study the prognostic value of AF in a prospective cohort and to characterize the HFPEF patients with AF. KaRen was a prospective, multicenter, international, observational study intended to characterize HFPEF; 538 patients presenting with an acute decompensated cardiac failure and a left ventricular EF > 45% were included. EKG and echocardiogram performed 4-8 week following the index hospitalization were analyzed in core centers. Clinical and echocardiographic characteristics of patients in sinus rhythm vs. with documented AF at enrolment (decompensated HF), upon their 4-8-week visit (in presumed stable clinical condition) and according to patients' cardiac history, were compared. The primary study endpoint was death from any cause or first hospitalization for decompensated heart failure (HF). A total of 413 patients (32% in AF) were analyzed, with a mean follow-up period of 28 months. The patients were primarily elderly individuals (mean age: 76.2 years), with a slight female predominance and a high prevalence of non-cardiovascular comorbidities. The baseline echocardiographic characteristics and the natriuretic peptide levels were indicative of a more severe heart condition among the patients with AF. However, the patients with AF exhibited a similar survival-free interval compared with the patients in sinus rhythm. In this elderly HFPEF population with a high prevalence of non-cardiovascular comorbidities, the presence of AF was not associated with a worse prognosis despite impaired clinical and echocardiographic features.ClinicalTrials.gov: NCT00774709.

The Efficacy and Safety of HA IDF Plus (with Lidocaine) Versus HA IDF (Without Lidocaine) in Nasolabial Folds Injection: A Randomized, Multicenter, Double-Blind, Split-Face Study.

PubMed

Lee, Jong-Hun; Kim, Seok-Hwan; Park, Eun-Soo

2017-04-01

Injection-related pain of dermal fillers is a consistent and bothersome problem for patients undergoing soft tissue augmentation. Reducing the pain could improve overall patient satisfaction. The purpose of this study was to compare the pain relief, efficacy, and safety of HA IDF plus containing lidocaine with HA IDF without lidocaine during correction of nasolabial folds (NLFs). Sixty-two subjects were enrolled in a randomized, multicenter, double-blind, split-face study of HA IDF plus and HA IDF for NLF correction. For split-face study, HA IDF plus was injected to one side of NLF, and HA IDF was injected to the other side. The first evaluation variable was the injection site pain measured using a 100-mm visual analogue scale (VAS). The second evaluation variables included the global aesthetic improvement scale, wrinkle severity rating scale, and adverse events. Immediately after injection, 91.94% of subjects experienced at least 10 mm decrease in VAS scores at the side injected with HA IDF plus compared with HA IDF, and the rate of subjects is statistically significant. The two fillers were not significantly different in safety profile or wrinkle correction during the follow-up visit. HA IDF plus significantly reduced the injection-related pain during NLFs correction compared with HA IDF without altering clinical outcomes or safety. Both HA IDF plus and HA IDF were considerably tolerated and most adverse reactions were mild and transient. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Acceptance of living liver donation among medical students: A multicenter stratified study from Spain

PubMed Central

Ríos, Antonio; López-Navas, Ana Isabel; López-López, Ana Isabel; Gómez, Francisco Javier; Iriarte, Jorge; Herruzo, Rafael; Blanco, Gerardo; Llorca, Francisco Javier; Asunsolo, Angel; Sánchez-Gallegos, Pilar; Gutiérrez, Pedro Ramón; Fernández, Ana; de Jesús, María Teresa; Martínez-Alarcón, Laura; Lana, Alberto; Fuentes, Lorena; Hernández, Juan Ramón; Virseda, Julio; Yelamos, José; Bondía, José Antonio; Hernández, Antonio Miguel; Ayala, Marco Antonio; Ramírez, Pablo; Parrilla, Pascual

2016-01-01

AIM: To analyze the attitude of Spanish medical students toward living liver donation (LLD) and to establish which factors have an influence on this attitude. METHODS: Study type: A sociological, interdisciplinary, multicenter and observational study. Study population: Medical students enrolled in Spain (n = 34000) in the university academic year 2010-2011. Sample size: A sample of 9598 students stratified by geographical area and academic year. Instrument used to measure attitude: A validated questionnaire (PCID-DVH RIOS) was self-administered and completed anonymously. Data collection procedure: Randomly selected medical schools. The questionnaire was applied to each academic year at compulsory sessions. Statistical analysis: Student´s t test, χ2 test and logistic regression analysis. RESULTS: The completion rate was 95.7% (n = 9275). 89% (n = 8258) were in favor of related LLD, and 32% (n = 2937) supported unrelated LLD. The following variables were associated with having a more favorable attitude: (1) age (P = 0.008); (2) sex (P < 0.001); (3) academic year (P < 0.001); (4) geographical area (P = 0.013); (5) believing in the possibility of needing a transplant oneself in the future (P < 0.001); (6) attitude toward deceased donation (P < 0.001); (7) attitude toward living kidney donation (P < 0.001); (8) acceptance of a donated liver segment from a family member if one were needed (P < 0.001); (9) having discussed the subject with one's family (P < 0.001) and friends (P < 0.001); (10) a partner's opinion about the subject (P < 0.001); (11) carrying out activities of an altruistic nature; and (12) fear of the possible mutilation of the body after donation (P < 0.001). CONCLUSION: Spanish medical students have a favorable attitude toward LLD. PMID:27433093

A randomized study comparing outcomes of stapled and hand-sutured anastomoses in patients undergoing open gastrointestinal surgery.

PubMed

Chandramohan, S M; Gajbhiye, Raj Narenda; Agwarwal, Anil; Creedon, Erin; Schwiers, Michael L; Waggoner, Jason R; Tatla, Daljit

2013-08-01

Although stapling is an alternative to hand-suturing in gastrointestinal surgery, recent trials specifically designed to evaluate differences between the two in surgery time, anastomosis time, and return to bowel activity are lacking. This trial compared the outcomes of the two in subjects undergoing open gastrointestinal surgery. Adult subjects undergoing emergency or elective surgery requiring a single gastric, small, or large bowel anastomosis were enrolled into this open-label, prospective, randomized, interventional, parallel, multicenter, controlled trial. Randomization was assigned in a 1:1 ratio between the hand-sutured group (n = 138) and the stapled group (n = 142). Anastomosis time, surgery time, and time to bowel activity were collected and compared as primary endpoints. A total of 280 subjects were enrolled from April 2009 to September 2010. Only the time of anastomosis was significantly different between the two arms: 17.6 ± 1.90 min (stapled) and 20.6 ± 1.90 min (hand-sutured). This difference was deemed not clinically or economically meaningful. Safety outcomes and other secondary endpoints were similar between the two arms. Mechanical stapling is faster than hand-suturing for the construction of gastrointestinal anastomoses. Apart from this, stapling and hand-suturing are similar with respect to the outcomes measured in this trial.

Classification and possible bacterial infection in outpatients with eczema and dermatitis in China

PubMed Central

Wang, Xin; Shi, Xiao-Dong; Li, Lin-Feng; Zhou, Ping; Shen, Yi-Wei

2017-01-01

Abstract Little is known about the classification and bacterial infection in outpatients with eczema and dermatitis in China. To investigate the prevalence of eczema and dermatitis in outpatients of dermatology clinics in China, examine classification and proportion of common types of dermatitis and the possible bacterial infection, and analyze the possible related factors. Outpatients with eczema or dermatitis from 39 tertiary hospitals of 15 provinces in mainland China from July 1 to September 30, 2014, were enrolled in this cross-sectional and multicenter study. Among 9393 enrolled outpatients, 636 patients (6.7%) were excluded because of incomplete information. The leading subtypes of dermatitis were unclassified eczema (35.5%), atopic dermatitis (13.4%), irritant dermatitis (9.2%), and widespread eczema (8.7%). Total bacterial infection rate was 52.3%, with widespread eczema, stasis dermatitis, and atopic dermatitis being the leading three (65.7%, 61.8%, and 61.4%, respectively). Clinically very likely bacterial infection has a significant positive correlation with disease duration, history of allergic disease, history of flexion dermatitis, and severe itching. Atopic dermatitis has become a common subtype of dermatitis in China. Secondary bacterial infection is common in all patients with dermatitis, and more attentions should be paid on this issue in other type of dermatitis apart from atopic dermatitis. PMID:28858126

Impact of registration on clinical trials on infection risk in pediatric acute myeloid leukemia.

PubMed

Dix, David; Aplenc, Richard; Bowes, Lynette; Cellot, Sonia; Ethier, Marie-Chantal; Feusner, Jim; Gillmeister, Biljana; Johnston, Donna L; Lewis, Victor; Michon, Bruno; Mitchell, David; Portwine, Carol; Price, Victoria; Silva, Mariana; Stobart, Kent; Yanofsky, Rochelle; Zelcer, Shayna; Beyene, Joseph; Sung, Lillian

2016-04-01

Little is known about the impact of enrollment on therapeutic clinical trials on adverse event rates. Primary objective was to describe the impact of clinical trial registration on sterile site microbiologically documented infection for children with newly diagnosed acute myeloid leukemia (AML). We conducted a multicenter cohort study that included children aged ≤18 years with de novo AML. Primary outcome was microbiologically documented sterile site infection. Infection rates were compared between those registered and not registered on clinical trials. Five hundred seventy-four children with AML were included of which 198 (34.5%) were registered on a therapeutic clinical trial. Overall, 400 (69.7%) had at least one sterile site microbiologically documented infection. In multiple regression, registration on clinical trials was independently associated with a higher risk of microbiologically documented sterile site infection [adjusted odds ratio (OR) 1.24, 95% confidence interval (CI) 1.01-1.53; p = 0.040] and viridans group streptococcal infection (OR 1.46, 95% CI 1.08-1.98; p = 0.015). Registration on trials was not associated with Gram-negative or invasive fungal infections. Children with newly diagnosed AML enrolled on clinical trials have a higher risk of microbiologically documented sterile site infection. This information may impact on supportive care practices in pediatric AML. © 2015 UICC.

A Large Multicenter Experience With Endoscopic Suturing for Management of Gastrointestinal Defects and Stent Anchorage in 122 Patients: A Retrospective Review.

PubMed

Sharaiha, Reem Z; Kumta, Nikhil A; DeFilippis, Ersilia M; Dimaio, Christopher J; Gonzalez, Susana; Gonda, Tamas; Rogart, Jason; Siddiqui, Ali; Berg, Paul S; Samuels, Paul; Miller, Larry; Khashab, Mouen A; Saxena, Payal; Gaidhane, Monica R; Tyberg, Amy; Teixeira, Julio; Widmer, Jessica; Kedia, Prashant; Loren, David; Kahaleh, Michel; Sethi, Amrita

2016-01-01

To describe a multicenter experience using an endoscopic suturing device for management of gastrointestinal (GI) defects and stent anchorage. Endoscopic closure of GI defects including perforations, fistulas, and anastomotic leaks as well as stent anchorage has improved with technological advances. An endoscopic suturing device (OverStitch; Apollo Endosurgery Inc.) has been used. Retrospective study of consecutive patients who underwent endoscopic suturing for management of GI defects and/or stent anchorage were enrolled between March 2012 and January 2014 at multiple academic medical centers. Data regarding demographic information and outcomes including long-term success were collected. One hundred and twenty-two patients (mean age, 52.6 y; 64.2% females) underwent endoscopic suturing at 8 centers for stent anchorage (n=47; 38.5%), fistulas (n=40; 32.7%), leaks (n=15; 12.3%), and perforations (n=20; 16.4%). A total of 44.2% underwent prior therapy and 97.5% achieved technical success. Immediate clinical success was achieved in 79.5%. Long-term clinical success was noted in 78.8% with mean follow-up of 68 days. Clinical success was 91.4% in stent anchorage, 93% in perforations, 80% in fistulas, but only 27% in anastomotic leak closure. Endoscopic suturing for management of GI defects and stent anchoring is safe and efficacious. Stent migration after stent anchoring was reduced compared with published data. Long-term success without further intervention was achieved in the majority of patients. The role of endoscopic suturing for repair of anastomotic leaks remains unclear given limited success in this retrospective study.

Efficacy of Levofloxacin in the Treatment of BK Viremia: A Multicenter, Double-Blinded, Randomized, Placebo-Controlled Trial

PubMed Central

Lee, Belinda T.; Gabardi, Steven; Grafals, Monica; Hofmann, R. Michael; Akalin, Enver; Aljanabi, Aws; Mandelbrot, Didier A.; Adey, Deborah B.; Heher, Eliot; Fan, Pang-Yen; Conte, Sarah; Dyer-Ward, Christine

2014-01-01

Background and objectives BK virus reactivation in kidney transplant recipients can lead to progressive allograft injury. Reduction of immunosuppression remains the cornerstone of treatment for active BK infection. Fluoroquinolone antibiotics are known to have in vitro antiviral properties, but the evidence for their use in patients with BK viremia is inconclusive. The objective of the study was to determine the efficacy of levofloxacin in the treatment of BK viremia. Design, setting, participants, & measurements Enrollment in this prospective, multicenter, double-blinded, placebo-controlled trial occurred from July 2009 to March 2012. Thirty-nine kidney transplant recipients with BK viremia were randomly assigned to receive levofloxacin, 500 mg daily, or placebo for 30 days. Immunosuppression in all patients was adjusted on the basis of standard clinical practices at each institution. Plasma BK viral load and serum creatinine were measured monthly for 3 months and at 6 months. Results At the 3-month follow-up, the percentage reductions in BK viral load were 70.3% and 69.1% in the levofloxacin group and the placebo group, respectively (P=0.93). The percentage reductions in BK viral load were also equivalent at 1 month (58% versus and 67.1%; P=0.47) and 6 months (82.1% versus 90.5%; P=0.38). Linear regression analysis of serum creatinine versus time showed no difference in allograft function between the two study groups during the follow-up period. Conclusions A 30-day course of levofloxacin does not significantly improve BK viral load reduction or allograft function when used in addition to overall reduction of immunosuppression. PMID:24482066

Efficacy of levofloxacin in the treatment of BK viremia: a multicenter, double-blinded, randomized, placebo-controlled trial.

PubMed

Lee, Belinda T; Gabardi, Steven; Grafals, Monica; Hofmann, R Michael; Akalin, Enver; Aljanabi, Aws; Mandelbrot, Didier A; Adey, Deborah B; Heher, Eliot; Fan, Pang-Yen; Conte, Sarah; Dyer-Ward, Christine; Chandraker, Anil

2014-03-01

BK virus reactivation in kidney transplant recipients can lead to progressive allograft injury. Reduction of immunosuppression remains the cornerstone of treatment for active BK infection. Fluoroquinolone antibiotics are known to have in vitro antiviral properties, but the evidence for their use in patients with BK viremia is inconclusive. The objective of the study was to determine the efficacy of levofloxacin in the treatment of BK viremia. Enrollment in this prospective, multicenter, double-blinded, placebo-controlled trial occurred from July 2009 to March 2012. Thirty-nine kidney transplant recipients with BK viremia were randomly assigned to receive levofloxacin, 500 mg daily, or placebo for 30 days. Immunosuppression in all patients was adjusted on the basis of standard clinical practices at each institution. Plasma BK viral load and serum creatinine were measured monthly for 3 months and at 6 months. At the 3-month follow-up, the percentage reductions in BK viral load were 70.3% and 69.1% in the levofloxacin group and the placebo group, respectively (P=0.93). The percentage reductions in BK viral load were also equivalent at 1 month (58% versus and 67.1%; P=0.47) and 6 months (82.1% versus 90.5%; P=0.38). Linear regression analysis of serum creatinine versus time showed no difference in allograft function between the two study groups during the follow-up period. A 30-day course of levofloxacin does not significantly improve BK viral load reduction or allograft function when used in addition to overall reduction of immunosuppression.

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

Mimura, Hidefumi, E-mail: mimura@marianna-u.ac.jp; Arai, Yasuaki, E-mail: arai-y3111@mvh.biglobe.ne.jp; Yamakado, Koichiro, E-mail: yama@clin.medic.mie-u.ac.jp

PurposeThis multicenter phase I/II study evaluated the safety, feasibility, and initial efficacy of radiofrequency ablation (RFA) for small malignant renal tumors.MethodsThirty-three patients were enrolled in the study. A single session of RFA was performed in patients with a renal tumor of 1–3 cm in greatest diameter, with the exception of lesions adjacent to the renal hilum. The primary endpoint was the safety of renal RFA, and the secondary endpoints were its feasibility and initial efficacy for local control, as well as the incidence and grade of adverse events. Clinical efficacy was evaluated by CT scans within 1 week and at a furthermore » 4 weeks after the procedure using the criteria adapted from the Response Evaluation Criteria in Solid Tumors.ResultsThe RFA procedure was completed in 100 % (95 % confidence interval [CI] 89–100 %) of all 33 patients. There were no severe adverse events (0 % [95 % CI 0–11 %]). Among the 33 patients, a complete response, partial response, progressive disease, and stable disease were seen in 28 (85 %), 0 (0 %), one (3 %), and one (3 %) patient(s), respectively, with a tumor response rate of 85 % [95 % CI 68–95 %]). Three patients (9 %), including one ineligible patient (3 %), were not evaluable. Out of 30 evaluable patients, a complete response was achieved in 28 (93 %).ConclusionThe current multicenter trial revealed that RFA is a safe, feasible, and effective treatment for small malignant renal tumors in patients who are not candidates for surgery.« less

Prognostic factors of liver cirrhosis mortality after a first episode of spontaneous bacterial peritonitis. A multicenter study.

PubMed

Melcarne, Luigi; Sopeña, Julia; Martínez-Cerezo, Francisco José; Vergara, Mercedes; Miquel, Mireia; Sánchez-Delgado, Jordi; Dalmau, Blai; Machlab, Salvador; Portilla, Dustin; González-Padrón, Yonaisy; Real Álvarez, Mónica; Carpintero, Chantal; Casas, Meritxell

2018-02-01

Spontaneous bacterial peritonitis is an infectious complication with a negative impact on survival of patients with cirrhosis. To analyze the short- and long-term survival after a first episode of bacterial peritonitis and the associated prognostic factors. This was a retrospective, multicenter study of patients admitted to hospital for spontaneous bacterial peritonitis between 2008 and 2013. Independent variables related to mortality were analyzed by logistic regression. The prognostic power of the Child Pugh Score, the Model for End-Stage Liver Disease (MELD) and the Charlson index was analyzed by ROC curve. A total of 159 patients were enrolled, 72% were males with a mean age of 63.5 years and a mean MELD score of 19 (SD ± 9.5). Mortality at 30 and 90 days and one and two years was 21%, 31%, 55% and 69%, respectively. Hepatic encephalopathy (p = 0.008, OR 3.5, 95% CI 1.4-8.8) and kidney function (p = 0.026, OR 2.7, 95% CI 1.13-16.7) were independent factors for short- and long-term mortality. MELD was a good marker of short- and long-term survival (area under the curve [AUC] 0.7: 95% CI 1.02-1.4). The Charlson index was related to long-term mortality (AUC 0.68: 95% CI 0.6-0.77). Short- and long-term mortality of spontaneous bacterial peritonitis is still high. The main prognostic factors for mortality are impairment of liver and kidney function. MELD and the Charlson index are good markers of survival.

Equine-derived bone mineral matrix for maxillary sinus floor augmentation: a clinical, radiographic, histologic, and histomorphometric case series.

PubMed

Nevins, Myron; Heinemann, Friedhelm; Janke, Ulrich W; Lombardi, Teresa; Nisand, David; Rocchietta, Isabella; Santoro, Giacomo; Schupbach, Peter; Kim, David M

2013-01-01

The objective of this proof-of-principle multicenter case series was to examine the bone regenerative potential of a newly introduced equine-derived bone mineral matrix (Equimatrix) to provide human sinus augmentation for the purpose of implant placement in the posterior maxilla. There were 10 patients requiring 12 maxillary sinus augmentations enrolled in this study. Histologic results at 6 months demonstrated abundant amounts of vital new bone in intimate contact with residual graft particles. Active bridging between residual graft particles with newly regenerated bone was routinely observed in intact core specimens. A mean value of 23.4% vital bone formation was observed at 6 months. This compared favorably with previous results using xenografts to produce bone in the maxillary sinus for the purpose of dental implant placement. Both the qualitative and quantitative results of this case series suggest comparable bone regenerative results at 6 months to bovine-derived xenografts.

[Quadruple regimens using domestically manufactured drugs in gastritis and duodenal ulcer patients for Helicobacter pylori eradication: a perspective, multicenter, randomized controlled trial].

PubMed

Gao, Wen; Hu, Fulian; Cheng, Hong; Wang, Huahong; Yang, Yunsheng; Liang, Hao; Zhang, Shutian; Meng, Fandong; Cui, Meihua; Wei, Hong; Sheng, Jianqiu; An, Hejuan J; Jiang, Bo; Chen, Ye; Li, Yanqing; Zuo, Xiuli; Gong, Jun; Zhao, Ping; Dong, Lei; Wang, Bangmao; Jiang, Kai; Zhang, Guiying; Li, Jiansheng; Zhao, Ye; Gao, Hengjun; Yang, Li

2016-01-26

To observe the effects and safety of quadruple regimens including domestically manufactured rabeprazole used as first line/initial therapy for Helicobacter pylori(H.pylori) eradication in gastritis and duodenal ulcer patients, and to investigate the effects of extended use of bismuth after the quadruple therapy on eradication of H. pylori. From January to August 2013, 430 patients with chronic gastritis or duodenal ulcer who were confirmed as H. pylori positive in gastroscopy for upper gastrointestinal symptoms were enrolled from 12 centers in China for initial treatment using quadruple regimens for H. pylori eradication. The study was a prospective, multicenter, randomized double-blinded double-dummy parallel-controlled clinical trial. The 310 chronic gastritis patients were divided into 2 groups: group A1 was given quadruple regime (rabeprazole+ amoxicillin+ clarithromycin+ bismuth potassium citrate) for 10 days followed by bismuth-placebo for 21 days; group A2 was given the quadruple regimen for 10 days and then bismuth potassium citrate for 21 days. The duodenal ulcer patients were given the quadruple for 10 days, then rabeprazole for 14 days. All the patients took (13)C urea breath test to detect H. pylori 28 days after medicine withdrawal. Altogether 428 cases were enrolled and 404 completed the trial. The total eradication rate in the chronic gastritis patients was 85.1% (262/308, intention-to-treat (ITT)analysis), which was 81.7% (125/153, ITT) in the A1 group and 88.4% (137/155, ITT) in the A2 group; the eradication rate in the duodenal ulcer patients was 85.8% (103/120, ITT). No severe adverse effects were reported. The symptoms (pain, burning sensation, reflux, belching, nausea, and vomiting) improvement status was similar among A1 and A2 groups. The quadruple regimen using rabeprazole manufactured in China and administered for 10 days as first line/initial therapy in chronic gastritis and duodenal ulcer patients could achieve good H. pylori eradication rate. The extended use of bismuth after 10-day quadruple regimen might further improve the eradication rate. The regimens containing proton-pump inhibitor and bismuth may be well tolerated and safe in clinical application.

Mediterranean diet adherence and synergy with acute myocardial infarction and its determinants: A multicenter case-control study in Italy.

PubMed

La Torre, Giuseppe; Saulle, Rosella; Di Murro, Francesca; Siliquini, Roberta; Firenze, Alberto; Maurici, Massimo; Mannocci, Alice; Colamesta, Vittoria; Barillà, Francesco; Ferrante, Fabio; Agati, Luciano

2018-01-01

Cardiovascular diseases are the leading causes of mortality and morbidity in Western countries. The possible synergistic effect of poor adherence to a Mediterranean diet (MD) and other risk factors for acute myocardial infarction (AMI) such as hypertension, cholesterol, ever smoker, BMI> 25, diabetes, has not been deeply studied. Case-control study. Patients with first AMI and controls from four tertiary referral Italian centers were screened for enrolment. Dietary information was collected through a questionnaire and a MD adherence score was calculated. Physical activity and smoking habits were also registered. The Synergy Index was calculated according to Rothman. 127 cases and 173 controls were enrolled. The analysis was conducted using a dichotomous variable for the MD score with values ≥7 representing good adherence. Multivariate analysis showed the following variables associated to AMI: ever smoker (OR = 2.08), diabetes (OR = 1.42), hypertension (OR = 2.08), hypercholesterolemia (OR = 2.47), BMI> 25 (OR = 1.99), while a protective effect emerged both in subjects scoring > 7 on the MD score (OR = 0.55) and in subjects resident of Southern Italy (OR = 0.38). A synergistic effect does exist between poor adherence to the MD and the following risk factors: hypertension, hypercholesterolemia, BMI >25, diabetes and being a resident in central and northern Italy. Synergy between heart disease risk factors and MD underlines the need to enlarge the list of known modifiable cardiovascular risk factors to include and promote adherence to Mediterranean dietary habits.

Clinical outcomes and nadir prostate-specific antigen (PSA) according to initial PSA levels in primary androgen deprivation therapy for metastatic prostate cancer.

PubMed

Kitagawa, Yasuhide; Ueno, Satoru; Izumi, Kouji; Kadono, Yoshifumi; Mizokami, Atsushi; Hinotsu, Shiro; Akaza, Hideyuki; Namiki, Mikio

2016-03-01

To investigate the clinical outcomes of metastatic prostate cancer patients and the relationship between nadir prostate-specific antigen (PSA) levels and different types of primary androgen deprivation therapy (PADT). This study utilized data from the Japan Study Group of Prostate Cancer registry, which is a large, multicenter, population-based database. A total of 2982 patients treated with PADT were enrolled. Kaplan-Meier analysis was used to compare progression-free survival (PFS) and overall survival (OS) in patients treated using combined androgen blockade (CAB) and non-CAB therapies. The relationships between nadir PSA levels and PADT type according to initial serum PSA levels were also investigated. Among the 2982 enrolled patients, 2101 (70.5 %) were treated with CAB. Although CAB-treated patients had worse clinical characteristics, their probability of PFS and OS was higher compared with those treated with a non-CAB therapy. These results were due to a survival benefit with CAB in patients with an initial PSA level of 500-1000 ng/mL. Nadir PSA levels were significantly lower in CAB patients than in non-CAB patients with comparable initial serum PSA levels. A small survival benefit for CAB in metastatic prostate cancer was demonstrated in a Japanese large-scale prospective cohort study. The clinical significance of nadir PSA levels following PADT was evident, but the predictive impact of PSA nadir on OS was different between CAB and non-CAB therapy.

Pancreatitis, very early compared with normal start of enteral feeding (PYTHON trial): design and rationale of a randomised controlled multicenter trial

PubMed Central

2011-01-01

Background In predicted severe acute pancreatitis, infections have a negative effect on clinical outcome. A start of enteral nutrition (EN) within 24 hours of onset may reduce the number of infections as compared to the current practice of starting an oral diet and EN if necessary at 3-4 days after admission. Methods/Design The PYTHON trial is a randomised controlled, parallel-group, superiority multicenter trial. Patients with predicted severe acute pancreatitis (Imrie-score ≥ 3 or APACHE-II score ≥ 8 or CRP > 150 mg/L) will be randomised to EN within 24 hours or an oral diet and EN if necessary, after 72 hours after hospital admission. During a 3-year period, 208 patients will be enrolled from 20 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of mortality or infections (bacteraemia, infected pancreatic or peripancreatic necrosis, pneumonia) during hospital stay or within 6 months following randomisation. Secondary endpoints include other major morbidity (e.g. new onset organ failure, need for intervention), intolerance of enteral feeding and total costs from a societal perspective. Discussion The PYTHON trial is designed to show that a very early (< 24 h) start of EN reduces the combined endpoint of mortality or infections as compared to the current practice of an oral diet and EN if necessary at around 72 hours after admission for predicted severe acute pancreatitis. Trial Registration ISRCTN: ISRCTN18170985 PMID:21392395

Multicenter clinical study on the treatment of children's tic disorder with Qufeng Zhidong Recipe.

PubMed

Wu, Min; Xiao, Guang-hua; Yao, Min; Zhang, Jian-ming; Zhang, Xin; Zhou, Ya-bing; Zhang, Jing-yan; Wang, Shu-xia; Ma, Bo; Chen, Yan-ping

2009-08-01

To assess the effect and adverse reaction of Qufeng Zhidong Recipe (QZR) in treating children's tic disorder (TD). With multicenter randomized parallel open-controlled method adopted, the patients enrolled were assigned to two groups, 41 cases in the Chinese medicine (CM) group and 40 in the Western medicine (WM) group. They were treated by QZR and haloperidol plus trihexyphenidyl respectively for 12 weeks as one course. In total, two courses of treatment were given. The curative effect and adverse reactions were evaluated by scoring with Yale Global Tic Severity Scale (YGTSS), Traditional Chinese Medicine Syndrome Scale (TCMSS), and Treatment Emergent Symptom Scale (TESS), as well as results of laboratory examinations. After one course of treatment, the markedly effective rate in the CM and the WM group was 14.6% and 17.5%, respectively, and the total effective rate 43.9% and 47.5%, respectively, which showed insignificant difference between groups (P>0.05). However, after two courses of treatment, markedly effective rate in them was 73.2% and 7.5%, and the total effective rate was 100.0% and 57.5%, both showing significant differences between groups (P<0.05). Besides, the adverse reactions occurred in the CM group was less than that in the WM group obviously. QZR has definite curative effect with no apparent adverse reaction in treating TD, and it can obviously improve the symptoms and signs and upgrade the quality of life and learning capacities in such patients.

Multicenter comparison of two clinical decision rules for the use of radiography in acute, high-risk knee injuries.

PubMed

Seaberg, D C; Yealy, D M; Lukens, T; Auble, T; Mathias, S

1998-07-01

Two separate clinical decision rules, one developed in Ottawa and the other in Pittsburgh, for the use of radiography in acute knee injuries have been previously validated and published. In this study, the rules were prospectively validated and compared in a new set of patients. A prospective, blinded, multicenter trial was conducted in the emergency departments of three urban teaching hospitals. A convenience sample of 934 patients with knee pain requiring radiographs was enrolled. A standardized data form was completed for each patient, comprising the 10 clinical variables included in the two rules. Standard knee radiographs were then taken in each patient. The rules were interpreted by the primary investigator on the basis of the data sheet and the final radiologist radiograph reading. In the 745 patients in whom the Pittsburgh rules could be applied there were 91 fractures (12.2%). The use of the Pittsburgh rule missed one fracture, yielding a sensitivity of 99% (95% confidence interval [CI], 94% to 100%); the specificity was 60% (95% CI, 56% to 64%). The Ottawa inclusion criteria were met by 750 patients, with 87 fractures (11.6%). The Ottawa rule missed three fractures, for a sensitivity of 97% (95% CI, 90% to 99%); specificity was 27% (95% CI, 23% to 30%). Prospective validation and comparison found the Pittsburgh rule for knee radiographs to be more specific without loss of sensitivity compared with the Ottawa rule.

An international, multicenter phase II trial of bortezomib in patients with hepatocellular carcinoma.

PubMed

Kim, George P; Mahoney, Michelle R; Szydlo, Daniel; Mok, Tony S K; Marshke, Robert; Holen, Kyle; Picus, Joel; Boyer, Michael; Pitot, Henry C; Rubin, Joseph; Philip, Philip A; Nowak, Anna; Wright, John J; Erlichman, Charles

2012-02-01

Bortezomib (PS-341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitin-proteasome pathway. This phase II study evaluated the activity and tolerability of bortezomib in unresectable hepatocellular carcinoma (HCC) patients. The primary endpoint was confirmed tumor response rate (RR) with secondary endpoints including duration of response, time to disease progression, survival and toxicity. Treatment consisted of bortezomib, 1.3 mg/m2 IV bolus on days 1, 4, 8, and 11 of each 21-day treatment cycle. Eligibility included: no prior systemic chemotherapy, ECOG PS 0-2, Child-Pugh A or B, preserved hematologic, hepatic and neurologic function; prior liver-directed therapy was permitted. Thirty-five patients enrolled and received a median of 2 cycles of treatment (range 1-12). Overall, 24 and 4 patients had a maximum severity of grade 3 and 4 adverse events (AEs), respectively. No treatment related deaths occurred. Only thrombocytopenia (11%) was seen in greater than 10% of patients. One patient achieved a partial response, lasting 13 weeks during treatment and progressed 11.6 months later; two patients received treatment for greater than 6 months. Median time-to-progression was 1.6 months and median survival was 6.0 months. This international, multicenter trial evaluated bortezomib as monotherapy in unresectable HCC patients. And, despite the lack of significant activity, this report serves as a baseline clinical experience for the development of future dual biologic approaches including bortezomib.

An international, multicenter phase II trial of bortezomib in patients with hepatocellular carcinoma

PubMed Central

Kim, George P.; Mahoney, Michelle R.; Szydlo, Daniel; Mok, Tony S. K.; Marshke, Robert; Holen, Kyle; Picus, Joel; Boyer, Michael; Pitot, Henry C.; Rubin, Joseph; Philip, Philip A.; Nowak, Anna; Wright, John J.; Erlichman, Charles

2013-01-01

Summary Background and Rationale Bortezomib (PS-341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitinproteasome pathway. This phase II study evaluated the activity and tolerability of bortezomib in unresectable hepatocellular carcinoma (HCC) patients. Methods The primary endpoint was confirmed tumor response rate (RR) with secondary endpoints including duration of response, time to disease progression, survival and toxicity. Treatment consisted of bortezomib, 1.3 mg/m2 IV bolus on days 1, 4, 8, and 11 of each 21-day treatment cycle. Eligibility included: no prior systemic chemotherapy, ECOG PS 0-2, Child-Pugh A or B, preserved hematologic, hepatic and neurologic function; prior liver-directed therapy was permitted. Results Thirty-five patients enrolled and received a median of 2 cycles of treatment (range 1–12). Overall, 24 and 4 patients had a maximum severity of grade 3 and 4 adverse events (AEs), respectively. No treatment related deaths occurred. Only thrombocytopenia (11%) was seen in greater than 10% of patients. One patient achieved a partial response, lasting 13 weeks during treatment and progressed 11.6 months later; two patients received treatment for greater than 6 months. Median time-to-progression was 1.6 months and median survival was 6.0 months. Conclusions This international, multicenter trial evaluated bortezomib as monotherapy in unresectable HCC patients. And, despite the lack of significant activity, this report serves as a baseline clinical experience for the development of future dual biologic approaches including bortezomib. PMID:20839030

Haemophilia utilization group study - Part Va (HUGS Va): design, methods and baseline data.

PubMed

Zhou, Z-Y; Wu, J; Baker, J; Curtis, R; Forsberg, A; Huszti, H; Koerper, M; Lou, M; Miller, R; Parish, K; Riske, B; Shapiro, A; Ullman, M; Johnson, K

2011-09-01

To describe the study design, procedures and baseline characteristics of the Haemophilia Utilization Group Study - Part Va (HUGS Va), a US multi-center observational study evaluating the cost of care and burden of illness in persons with factor VIII deficiency. Patients with factor VIII level ≤ 30%, age 2-64 years, receiving treatment at one of six federally supported haemophilia treatment centres (HTCs) were enrolled in the study. Participants completed an initial interview including questions on socio-demographical characteristics, health insurance status, co-morbidities, access to care, haemophilia treatment regimen, factor utilization, self-reported joint pain and motion limitation and health-related quality of life. A periodic follow-up survey collected data regarding time lost from usual activities, disability days, health care utilization and outcomes of care. HTC clinicians documented participants' baseline clinical characteristics and pharmacy dispensing records for 2 years. Between July 2005 and July 2007, 329 participants were enrolled. Average age was 9.7 years for children and 33.5 years for adults; two-thirds had severe haemophilia. The distributions of age, marital status, education level and barriers to haemophilia care were relatively consistent across haemophilic severity categories. Differences were found in participants' employment status, insurance status and income. Overall, children with haemophilia had quality of life scores comparable to healthy counterparts. Adults had significantly lower physical functioning than the general US population. As one of the largest economic studies of haemophilia care, HUGS Va will provide detailed information regarding the burden of illness and health care utilization in the US haemophilia A population. © 2011 Blackwell Publishing Ltd.

Study protocol title: a prospective cohort study of low back pain

PubMed Central

2013-01-01

Background Few prospective cohort studies of workplace low back pain (LBP) with quantified job physical exposure have been performed. There are few prospective epidemiological studies for LBP occupational risk factors and reported data generally have few adjustments for many personal and psychosocial factors. Methods/design A multi-center prospective cohort study has been incepted to quantify risk factors for LBP and potentially develop improved methods for designing and analyzing jobs. Due to the subjectivity of LBP, six measures of LBP are captured: 1) any LBP, 2) LBP ≥ 5/10 pain rating, 3) LBP with medication use, 4) LBP with healthcare provider visits, 5) LBP necessitating modified work duties and 6) LBP with lost work time. Workers have thus far been enrolled from 30 different employment settings in 4 diverse US states and performed widely varying work. At baseline, workers undergo laptop-administered questionnaires, structured interviews, and two standardized physical examinations to ascertain demographics, medical history, psychosocial factors, hobbies and physical activities, and current musculoskeletal disorders. All workers’ jobs are individually measured for physical factors and are videotaped. Workers are followed monthly for the development of low back pain. Changes in jobs necessitate re-measure and re-videotaping of job physical factors. The lifetime cumulative incidence of low back pain will also include those with a past history of low back pain. Incident cases will exclude prevalent cases at baseline. Statistical methods planned include survival analyses and logistic regression. Discussion Data analysis of a prospective cohort study of low back pain is underway and has successfully enrolled over 800 workers to date. PMID:23497211

Study protocol title: a prospective cohort study of low back pain.

PubMed

Garg, Arun; Hegmann, Kurt T; Moore, J Steven; Kapellusch, Jay; Thiese, Matthew S; Boda, Sruthi; Bhoyr, Parag; Bloswick, Donald; Merryweather, Andrew; Sesek, Richard; Deckow-Schaefer, Gwen; Foster, James; Wood, Eric; Sheng, Xiaoming; Holubkov, Richard

2013-03-07

Few prospective cohort studies of workplace low back pain (LBP) with quantified job physical exposure have been performed. There are few prospective epidemiological studies for LBP occupational risk factors and reported data generally have few adjustments for many personal and psychosocial factors. A multi-center prospective cohort study has been incepted to quantify risk factors for LBP and potentially develop improved methods for designing and analyzing jobs. Due to the subjectivity of LBP, six measures of LBP are captured: 1) any LBP, 2) LBP ≥ 5/10 pain rating, 3) LBP with medication use, 4) LBP with healthcare provider visits, 5) LBP necessitating modified work duties and 6) LBP with lost work time. Workers have thus far been enrolled from 30 different employment settings in 4 diverse US states and performed widely varying work. At baseline, workers undergo laptop-administered questionnaires, structured interviews, and two standardized physical examinations to ascertain demographics, medical history, psychosocial factors, hobbies and physical activities, and current musculoskeletal disorders. All workers' jobs are individually measured for physical factors and are videotaped. Workers are followed monthly for the development of low back pain. Changes in jobs necessitate re-measure and re-videotaping of job physical factors. The lifetime cumulative incidence of low back pain will also include those with a past history of low back pain. Incident cases will exclude prevalent cases at baseline. Statistical methods planned include survival analyses and logistic regression. Data analysis of a prospective cohort study of low back pain is underway and has successfully enrolled over 800 workers to date.

Baseline Lower Urinary Tract Symptoms in Patients Enrolled in LURN: A Prospective, Observational Cohort Study.

PubMed

Cameron, Anne P; Lewicky-Gaupp, Christina; Smith, Abigail R; Helfand, Brian T; Gore, John L; Clemens, J Quentin; Yang, Claire C; Siddiqui, Nazema Y; Lai, H Henry; Griffith, James W; Andreev, Victor P; Liu, Gang; Weinfurt, Kevin; Amundsen, Cindy L; Bradley, Catherine S; Kusek, John W; Kirkali, Ziya

2018-04-01

We described and compared the frequency and type of lower urinary tract symptoms reported by men and women at the time that they were recruited from urology and urogynecology clinics into the Symptoms of Lower Urinary Tract Dysfunction Research Network multicenter, prospective, observational cohort study. At 6 research sites treatment seeking men and women were enrolled who reported any lower urinary tract symptoms at a frequency more than rarely during the last month on the LUTS (Lower Urinary Tract Symptoms) Tool. At baseline the study participants underwent a standardized clinical evaluation and completed validated questionnaires. Urological tests were performed, including pelvic/rectal examination, post-void residual urine measurement and urinalysis. A total of 545 women and 519 men were enrolled in the study. Mean ± SD age was 58.8 ± 14.1 years. At baseline nocturia, frequency and a sensation of incomplete emptying were similar in men and women but men experienced more voiding symptoms (90% vs 85%, p = 0.007) and women reported more urgency (85% vs 66%, p <0.001). Women also reported more of any type of urinary incontinence than men (82% vs 51% p <0.001), which was mixed incontinence in 57%. Only 1% of men reported stress incontinence but they had other urinary incontinence, including post-void dribbling in 44% and urgency incontinence in 46%. Older participants had higher odds of reporting symptoms of nocturia and urgency. In this large, treatment seeking cohort of men and women lower urinary tract symptoms varied widely by gender and age. Men reported more voiding symptoms and nonstress or urgency urinary incontinence while women reported more incontinence overall and urgency. Older participants had greater odds of urgency and nocturia. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Multicenter Prospective Clinical Series Evaluating Radiofrequency Ablation in the Treatment of Painful Spine Metastases

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

Bagla, Sandeep, E-mail: sandeep.bagla@gmail.com; Sayed, Dawood; Smirniotopoulos, John

BackgroundRadiofrequency ablation (RFA) of vertebral body metastases (VBM) has been reported as safe and effective in retrospective studies. This single-arm prospective multicenter clinical study evaluates RFA in the treatment of painful VBM.MethodsFifty patients with VBM were prospectively enrolled during a 13-month period at eight US centers under an IRB-approved study. Percutaneous RFA was performed under imaging guidance with cement augmentation at the discretion of the operator. Pain, disability and quality of life were evaluated at baseline, prior to discharge, days 3, 7, 30 and 90 using the Numerical Pain Rating Scale, Oswestry Disability Index (ODI), the Functional Assessment of Cancermore » Therapy-General 7 (FACT-G7) and Functional Assessment of Cancer Therapy Quality-of-Life Measurement in Patients with Bone Pain (FACT-BP). Adverse events were monitored throughout this time interval.ResultsTwenty-six male and 24 female patients (mean age 61.0) underwent 69 treatments (30 thoracic and 39 lumbar). Cement augmentation was performed in 96 % of reported levels. Significant improvement in mean scores for pain, disability and cancer-specific health-related quality of life from baseline to all time intervals was seen. NRPS improved from 5.9 to 2.1 (p < 0.0001). ODI improved from 52.9 to 37.0 (p < 0.08). FACT-G7 improved form 10.9 to 16.2 (p = 0.0001). FACT-BP improved from 22.6 to 38.9 (p < 0.001). No complications related to the procedure were reported.ConclusionRFA with cement augmentation safely and effectively reduces pain and disability rapidly, while increasing quality of life in patients suffering from vertebral body metastases.« less

Assessment of coronary artery calcium by chest CT compared with EKG-gated cardiac CT in the multicenter AIDS cohort study.

PubMed

Chandra, Divay; Gupta, Aman; Leader, Joseph K; Fitzpatrick, Meghan; Kingsley, Lawrence A; Kleerup, Eric; Haberlen, Sabina A; Budoff, Matthew J; Witt, Mallory; Post, Wendy S; Sciurba, Frank C; Morris, Alison

2017-01-01

Individuals with HIV are at increased risk for coronary artery disease (CAD). Early detection of subclinical CAD by assessment of coronary artery calcium (CAC) may help risk stratify and prevent CAD events in these individuals. However, the current standard to quantify CAC i.e. Agatston scoring requires EKG-gated cardiac CT imaging. To determine if the assessment of CAC using non-EKG-gated chest CT and the Weston scoring system is a useful surrogate for Agatston scores in HIV-infected and HIV-uninfected individuals. CAC was assessed by both the Weston and Agatston score in 108 men enrolled in the Multicenter AIDS Cohort Study. Participants were 55.2 (IQR 50.4; 59.9) years old and 62 (57.4%) were seropositive for HIV. Inter-observer agreement (rs = 0.94, κ = 90.0%, p<0.001, n = 21) and intra-observer agreement (rs = 0.95, κ = 95.2%, p<0.001, n = 97) for category of Weston score were excellent. Weston scores were associated with similar CAD risk factors as Agatston scores (age, race, HDL cholesterol level, all p<0.05) in our cohort. There was excellent correlation (rs = 0.92, p<0.001) and agreement (κw = 0.77, p<0.001) between Weston and Agatston scores. This study is the first to examine calcium scoring using chest CT in HIV-infected individuals and to independently validate the Weston score as a surrogate for the Agatston score. In clinical or research settings where EKG-gated cardiac CT is not feasible for the assessment of coronary calcium, Weston scoring by using chest CT should be considered.

Discordance of physician clinical judgment vs. pneumonia severity index (PSI) score to admit patients with low risk community-acquired pneumonia: a prospective multicenter study.

PubMed

Marcos, Pedro J; Restrepo, Marcos I; González-Barcala, Francisco J; Soni, Nilam J; Vidal, Iria; Sanjuàn, Pilar; Llinares, Diego; Ferreira-Gonzalez, Lucía; Rábade, Carlos; Otero-González, Isabel; Marcos, Pedro; Verea-Hernando, Héctor

2017-06-01

The relationship between clinical judgment and the pneumonia severity index (PSI) score in deciding the site of care for patients with community-acquired pneumonia (CAP) has not been well investigated. The objective of the study was to determine the clinical factors that influence decision-making to hospitalize low-risk patients (PSI ≤2) with CAP. An observational, prospective, multicenter study of consecutive CAP patients was performed at five hospitals in Spain. Patients admitted with CAP and a PSI ≤2 were identified. Admitting physicians completed a patient-specific survey to identify the clinical factors influencing the decision to admit a patient. The reason for admission was categorized into 1 of 6 categories. We also assessed whether the reason for admission was associated with poorer clinical outcomes [intensive care unit (ICU) admission, 30-day mortality or readmission]. One hundred and fifty-five hospitalized patients were enrolled. Two or more reasons for admission were seen in 94 patients (60.6%), including abnormal clinical test results (60%), signs of clinical deterioration (43.2%), comorbid conditions (28.4%), psychosocial factors (28.4%), suspected H1N1 pneumonia (20.6%), and recent visit to the emergency department (ED) in the past 2 weeks (7.7%). Signs of clinical deterioration and abnormal clinical test results were associated with poorer clinical outcomes (P<0.005). Low-risk patients with CAP and a PSI ≤2 are admitted to the hospital for multiple reasons. Abnormal clinical test results and signs of clinical deterioration are two specific reasons for admission that are associated with poorer clinical outcomes in low risk CAP patients.

Previous cerebrovascular disease is an important predictor of clinical outcomes in elderly patients with percutaneous coronary interventions: The Nobori-Biolimus eluting stent prospective multicenter 1-year observational registry in South Korea

PubMed Central

Kim, Yong Hoon; Her, Ae-Young; Kim, Byeong-Keuk; Shin, Dong-Ho; Kim, Jung-Sun; Ko, Young-Guk; Choi, Donghoon; Hong, Myeong-Ki; Jang, Yangsoo

2017-01-01

Objective: The appropriate selection of elderly patients for revascularization has become increasingly important because these subsets of patients are more likely to experience a major cardiac or cerebrovascular event—percutaneous coronary intervention (PCI). The objective of this study was to determine important independent risk factor for predicting clinical outcomes in the elderly patients after successful PCI, particularly in a series of South Korean population. Methods: This study is prospective, multicenter, observational cross-sectional study. A total of 1,884 consecutive patients who underwent successful PCI with Nobori® Biolimus A9-eluting stents were enrolled between April 2010 and December 2012. They were divided into two groups according to the age: patients <75 years old (younger patient group) and ≥75 years old (elderly patient group). The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE) at 1-year after index PCI. Results: The 1-year cumulative incidence of MACCE (12.9% vs. 4.3%, p<0.001) and total death (7.1% vs. 1.5%, p<0.001) was significantly higher in the elderly group than in younger group. Previous cerebrovascular disease was significantly correlated with MACCE in elderly patients 1-year after PCI (hazard ratio, 2.804; 95% confidence interval, 1.290–6.093 p=0.009). Conclusion: Previous cerebrovascular disease is important independent predictor of the MACCE in elderly patients at 1-year after PCI with Nobori® Biolimus A9-eluting stents especially in a series of South Korean population. Therefore, careful PCI with intensive monitoring and management can improve major clinical outcomes after successful PCI in elderly patients with previous cerebrovascular disease compared with younger patients. PMID:28554989

Depression and Cognitive Impairment in Peritoneal Dialysis: A Multicenter Cross-sectional Study.

PubMed

Dong, Jie; Pi, Hai-Chen; Xiong, Zu-Ying; Liao, Jin-Lan; Hao, Li; Liu, Gui-Ling; Ren, Ye-Ping; Wang, Qin; Duan, Li-Ping; Zheng, Zhao-Xia

2016-01-01

Depression and cognitive impairment have been identified as independent risk factors for mortality in peritoneal dialysis (PD) patients. The relationship between depression and global and specific cognitive functions in PD patients was investigated in this study. Multicenter cross-sectional study. 458 clinically stable patients, drawn from 5 PD units, who performed PD for at least 3 months were enrolled. Depression, defined as depression severity index score > 0.5 using the Zung Self-rating Depression Scale. Global and specific cognitive impairment. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), Trail-Making Test forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skills, and language ability. Prevalences of depression and cognitive impairment evaluated by the 3MS were 52% and 28.4%, respectively. Patients with mild or moderate/severe depression had higher prevalences of general cognitive impairment, executive dysfunction, and impaired immediate and delayed memory. After adjusting for demographics, comorbid conditions, and clinical parameters, depression scores were independently associated with lower 3MS scores, lower immediate and delayed memory and language ability scores, and longer completion times of Trails A and B. Even mild depression was independently associated with higher risk for cognitive impairment, executive dysfunction, and impaired immediate and delayed memory after multivariable adjustments. The causal relationship between depression and cognitive impairment could not be determined, and the potential copathogenesis behind depression and cognitive impairment was not fully investigated. Even mild depression is closely associated with global and specific cognitive impairment in PD patients. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

First-line disease-modifying drugs in relapsing-remitting multiple sclerosis: an Italian real-life multicenter study on persistence.

PubMed

Ferraro, Diana; Camera, Valentina; Baldi, Eleonora; Vacchiano, Veria; Curti, Erica; Guareschi, Angelica; Malagù, Susanna; Montepietra, Sara; Strumia, Silvia; Santangelo, Mario; Caniatti, Luisa; Foschi, Matteo; Lugaresi, Alessandra; Granella, Franco; Pesci, Ilaria; Motti, Luisa; Neri, Walter; Immovilli, Paolo; Montanari, Enrico; Vitetta, Francesca; Simone, Anna Maria; Sola, Patrizia

2018-04-12

The introduction of oral disease-modifying drugs (DMDs) in addition to the available, injectable, ones for relapsing-remitting multiple sclerosis (RRMS) could be expected to improve medication persistence due to a greater acceptability of the route of administration. The aim of the study was to compare the proportion of patients discontinuing injectable DMDs (interferon beta 1a/1b, pegylated interferon, glatiramer acetate) with those discontinuing oral DMDs (dimethylfumarate and teriflunomide) during an observation period of at least 12 months. Secondary aims were to compare the time to discontinuation and the reasons for discontinuation between the two groups and to explore the demographic and clinical factors associated with DMD discontinuation. In this prospective, multi-center, real-life observational study, patients commencing any first-line DMD between 1 January 2015 and 31 July 2016 were enrolled and followed up for at least 12 months or until the drug was discontinued. Of the 520 included patients, 262 (49.6%) started an injectable and 258 (50.4%) an oral DMD. There was no difference in the proportion of patients on oral (n = 62, 24%) or on injectable (n = 60, 23%) DMDs discontinuing treatment, the most frequent reason being adverse events/side-effects. Higher baseline Expanded Disability Status Scale (EDSS) scores and younger age increased the odds of treatment withdrawal. Time to treatment discontinuation was not different between the two groups and was not influenced by the initiated DMD (oral versus injectable), even after adjustment for baseline differences. The route of administration alone (i.e. oral versus injectable) was not a significant predictor of persistence with first-line DMDs in RRMS.

An open-label, randomized, multicenter study of the safety, tolerability, and immunogenicity of quadrivalent human papillomavirus (types 6/11/16/18) vaccine given concomitantly with diphtheria, tetanus, pertussis, and poliomyelitis vaccine in healthy adolescents 11 to 17 years of age.

PubMed

Vesikari, Timo; Van Damme, Pierre; Lindblad, Niklas; Pfletschinger, Ulrich; Radley, David; Ryan, Desmond; Vuocolo, Scott; Haupt, Richard M; Guris, Dalya

2010-04-01

GARDASIL/SILGARD is a quadrivalent human papillomavirus (HPV) vaccine with activity against HPV 6/11/16/18. In many countries, GARDASIL is recommended for routine use among adolescents at the same age as other vaccines. In this study, we evaluated the immunogenicity and safety of GARDASIL administered concomitantly with REPEVAX (diphtheria, tetanus, acellular pertussis, and poliomyelitis vaccine). This was an open-label, randomized, multicenter study. We enrolled males (n = 260) and females (n = 583) aged 11 to 17 years. All subjects received a 0.5 mL dose of GARDASIL at day 1, month 2, and month 6, and a 0.5 mL dose of REPEVAX either on day 1 (opposite limb from GARDASIL) or at month 1. Antibody levels for all vaccine components were measured. We monitored systemic and injection-site adverse experiences (AEs) and serious adverse experiences. Immune response for all GARDASIL antigens following concomitant administration of the vaccines was demonstrated noninferior to nonconcomitant administration. Seroconversion for HPV 6, 11, 16, and 18 was >99.7% in both concomitant and nonconcomitant vaccination groups. For REPEVAX, noninferiority of immune response was established for diphtheria, tetanus, and all polio and pertussis antigens. Concomitant administration of the 2 vaccines was generally well-tolerated, although there was a small increase in headache and injection-site swelling in the concomitant group. Overall, concomitant administration of GARDASIL and REPEVAX was generally well-tolerated and did not interfere with the immune response to either vaccine. Concomitant administration of vaccines would minimize the number of visits required to deliver each vaccine individually.

Primary limited lumbar discectomy with an annulus closure device: one-year clinical and radiographic results from a prospective, multi-center study.

PubMed

Lequin, Michiel B; Barth, Martin; Thomė, Claudius; Bouma, Gerrit J

2012-12-01

Discectomy as a treatment for herniated lumbar discs results in outcomes after surgery that are not uniformly positive. Surgeons face the dilemma between limited nucleus removal which is associated with a higher risk of recurrence, or more aggressive nucleus removal which may lead to disc height loss and persistent back-pain. annulus closure devices may allow for the benefits of limited nucleus removal without the increased risk of recurrence. This is an interim report of an ongoing 24-month post-marketing study of the Barricaid® annulus closure device, consisting of a flexible polymer mesh that blocks the defect, held in place by a titanium bone anchor. We prospectively enrolled 45 patients at four hospitals, and implanted the Barricaid® after a limited discectomy. annulus defect size and volume of removed nucleus were recorded. Reherniations were reported, pain and function were monitored and imaging was performed at regular intervals during 24 months of follow-up. At 12 months postsurgery, pain and function were significantly improved, comparing favorably to reported results from limited discectomy. Disc height has been well maintained. One reherniation has occurred (2.4%), which was associated with a misplaced device. No device fracture, subsidence or migration has been observed. The use of an annulus closure device may provide a reduction in reherniation rate for lumbar discectomy patients with large annulus defects who are at the greatest risk of recurrence. Using such a device should provide the surgeon increased confidence in minimizing nucleus removal, which, in turn, may preserve disc height and biomechanics, reducing degeneration and associated poor clinical outcomes in the long-term. A randomized multicenter study evaluating limited discectomy with and without the Barricaid® is currently underway, and will provide a higher level of evidence.

Assessment of coronary artery calcium by chest CT compared with EKG-gated cardiac CT in the multicenter AIDS cohort study

PubMed Central

Chandra, Divay; Gupta, Aman; Leader, Joseph K.; Fitzpatrick, Meghan; Kingsley, Lawrence A.; Kleerup, Eric; Haberlen, Sabina A.; Budoff, Matthew J.; Witt, Mallory; Post, Wendy S.; Sciurba, Frank C.; Morris, Alison

2017-01-01

Rationale Individuals with HIV are at increased risk for coronary artery disease (CAD). Early detection of subclinical CAD by assessment of coronary artery calcium (CAC) may help risk stratify and prevent CAD events in these individuals. However, the current standard to quantify CAC i.e. Agatston scoring requires EKG-gated cardiac CT imaging. Objective To determine if the assessment of CAC using non-EKG-gated chest CT and the Weston scoring system is a useful surrogate for Agatston scores in HIV-infected and HIV-uninfected individuals. Methods and measurements CAC was assessed by both the Weston and Agatston score in 108 men enrolled in the Multicenter AIDS Cohort Study. Results Participants were 55.2 (IQR 50.4; 59.9) years old and 62 (57.4%) were seropositive for HIV. Inter-observer agreement (rs = 0.94, κ = 90.0%, p<0.001, n = 21) and intra-observer agreement (rs = 0.95, κ = 95.2%, p<0.001, n = 97) for category of Weston score were excellent. Weston scores were associated with similar CAD risk factors as Agatston scores (age, race, HDL cholesterol level, all p<0.05) in our cohort. There was excellent correlation (rs = 0.92, p<0.001) and agreement (κw = 0.77, p<0.001) between Weston and Agatston scores. Conclusions This study is the first to examine calcium scoring using chest CT in HIV-infected individuals and to independently validate the Weston score as a surrogate for the Agatston score. In clinical or research settings where EKG-gated cardiac CT is not feasible for the assessment of coronary calcium, Weston scoring by using chest CT should be considered. PMID:28453572

Efficacy and safety of febuxostat for prevention of tumor lysis syndrome in patients with malignant tumors receiving chemotherapy: a phase III, randomized, multi-center trial comparing febuxostat and allopurinol.

PubMed

Tamura, Kazuo; Kawai, Yasukazu; Kiguchi, Toru; Okamoto, Masataka; Kaneko, Masahiko; Maemondo, Makoto; Gemba, Kenichi; Fujimaki, Katsumichi; Kirito, Keita; Goto, Tetsuya; Fujisaki, Tomoaki; Takeda, Kenji; Nakajima, Akihiro; Ueda, Takanori

2016-10-01

Control of serum uric acid (sUA) levels is very important during chemotherapy in patients with malignant tumors, as the risks of tumor lysis syndrome (TLS) and renal events are increased with increasing levels of sUA. We investigated the efficacy and safety of febuxostat, a potent non-purine xanthine oxidase inhibitor, compared with allopurinol for prevention of hyperuricemia in patients with malignant tumors, including solid tumors, receiving chemotherapy in Japan. An allopurinol-controlled multicenter, open-label, randomized, parallel-group comparative study was carried out. Patients with malignant tumors receiving chemotherapy, who had an intermediate risk of TLS or a high risk of TLS and were not scheduled to be treated with rasburicase, were enrolled and then randomized to febuxostat (60 mg/day) or allopurinol (300 or 200 mg/day). All patients started to take the study drug 24 h before chemotherapy. The primary objective was to confirm the non-inferiority of febuxostat to allopurinol based on the area under the curve (AUC) of sUA for a 6-day treatment period. Forty-nine and 51 patients took febuxostat and allopurinol, respectively. sUA decreased over time after initiation of study treatment. The least squares mean difference of the AUC of sUA between the treatment groups was -33.61 mg h/dL, and the 95 % confidence interval was -70.67 to 3.45, demonstrating the non-inferiority of febuxostat to allopurinol. No differences were noted in safety outcomes between the treatment groups. Febuxostat demonstrated an efficacy and safety similar to allopurinol in patients with malignant tumors receiving chemotherapy. http://www.clinicaltrials.jp ; Identifier: JapicCTI-132398.

Multicenter Prospective Clinical Series Evaluating Radiofrequency Ablation in the Treatment of Painful Spine Metastases.

PubMed

Bagla, Sandeep; Sayed, Dawood; Smirniotopoulos, John; Brower, Jayson; Neal Rutledge, J; Dick, Bradley; Carlisle, James; Lekht, Ilya; Georgy, Bassem

2016-09-01

Radiofrequency ablation (RFA) of vertebral body metastases (VBM) has been reported as safe and effective in retrospective studies. This single-arm prospective multicenter clinical study evaluates RFA in the treatment of painful VBM. Fifty patients with VBM were prospectively enrolled during a 13-month period at eight US centers under an IRB-approved study. Percutaneous RFA was performed under imaging guidance with cement augmentation at the discretion of the operator. Pain, disability and quality of life were evaluated at baseline, prior to discharge, days 3, 7, 30 and 90 using the Numerical Pain Rating Scale, Oswestry Disability Index (ODI), the Functional Assessment of Cancer Therapy-General 7 (FACT-G7) and Functional Assessment of Cancer Therapy Quality-of-Life Measurement in Patients with Bone Pain (FACT-BP). Adverse events were monitored throughout this time interval. Twenty-six male and 24 female patients (mean age 61.0) underwent 69 treatments (30 thoracic and 39 lumbar). Cement augmentation was performed in 96 % of reported levels. Significant improvement in mean scores for pain, disability and cancer-specific health-related quality of life from baseline to all time intervals was seen. NRPS improved from 5.9 to 2.1 (p < 0.0001). ODI improved from 52.9 to 37.0 (p < 0.08). FACT-G7 improved form 10.9 to 16.2 (p = 0.0001). FACT-BP improved from 22.6 to 38.9 (p < 0.001). No complications related to the procedure were reported. RFA with cement augmentation safely and effectively reduces pain and disability rapidly, while increasing quality of life in patients suffering from vertebral body metastases.

Lung Ultrasound-Implemented Diagnosis of Acute Decompensated Heart Failure in the ED: A SIMEU Multicenter Study.

PubMed

Pivetta, Emanuele; Goffi, Alberto; Lupia, Enrico; Tizzani, Maria; Porrino, Giulio; Ferreri, Enrico; Volpicelli, Giovanni; Balzaretti, Paolo; Banderali, Alessandra; Iacobucci, Antonello; Locatelli, Stefania; Casoli, Giovanna; Stone, Michael B; Maule, Milena M; Baldi, Ileana; Merletti, Franco; Cibinel, Gian Alfonso; Baron, Paolo; Battista, Stefania; Buonafede, Giuseppina; Busso, Valeria; Conterno, Andrea; Del Rizzo, Paola; Ferrera, Patrizia; Pecetto, Paolo Fascio; Moiraghi, Corrado; Morello, Fulvio; Steri, Fabio; Ciccone, Giovannino; Calasso, Cosimo; Caserta, Mimma A; Civita, Marina; Condo', Carmen; D'Alessandro, Vittorio; Del Colle, Sara; Ferrero, Stefania; Griot, Giulietta; Laurita, Emanuela; Lazzero, Alberto; Lo Curto, Francesca; Michelazzo, Marianna; Nicosia, Vincenza; Palmari, Nicola; Ricchiardi, Alberto; Rolfo, Andrea; Rostagno, Roberto; Bar, Fabrizio; Boero, Enrico; Frascisco, Mauro; Micossi, Ilaria; Mussa, Alessandro; Stefanone, Valerio; Agricola, Renzo; Cordero, Gabriele; Corradi, Federica; Runzo, Cristina; Soragna, Aldo; Sciullo, Daniela; Vercillo, Domenico; Allione, Attilio; Artana, Nicoletta; Corsini, Fabrizio; Dutto, Luca; Lauria, Giuseppe; Morgillo, Teresa; Tartaglino, Bruno; Bergandi, Daniela; Cassetta, Ilaria; Masera, Clotilde; Garrone, Mario; Ghiselli, Gianluca; Ausiello, Livia; Barutta, Letizia; Bernardi, Emanuele; Bono, Alessia; Forno, Daniela; Lamorte, Alessandro; Lison, Davide; Lorenzati, Bartolomeo; Maggio, Elena; Masi, Ilaria; Maggiorotto, Matteo; Novelli, Giulia; Panero, Francesco; Perotto, Massimo; Ravazzoli, Marco; Saglio, Elisa; Soardo, Flavia; Tizzani, Alessandra; Tizzani, Pietro; Tullio, Mattia; Ulla, Marco; Romagnoli, Elisa

2015-07-01

Lung ultrasonography (LUS) has emerged as a noninvasive tool for the differential diagnosis of pulmonary diseases. However, its use for the diagnosis of acute decompensated heart failure (ADHF) still raises some concerns. We tested the hypothesis that an integrated approach implementing LUS with clinical assessment would have higher diagnostic accuracy than a standard workup in differentiating ADHF from noncardiogenic dyspnea in the ED. We conducted a multicenter, prospective cohort study in seven Italian EDs. For patients presenting with acute dyspnea, the emergency physician was asked to categorize the diagnosis as ADHF or noncardiogenic dyspnea after (1) the initial clinical assessment and (2) after performing LUS ("LUS-implemented" diagnosis). All patients also underwent chest radiography. After discharge, the cause of each patient's dyspnea was determined by independent review of the entire medical record. The diagnostic accuracy of the different approaches was then compared. The study enrolled 1,005 patients. The LUS-implemented approach had a significantly higher accuracy (sensitivity, 97% [95% CI, 95%-98.3%]; specificity, 97.4% [95% CI, 95.7%-98.6%]) in differentiating ADHF from noncardiac causes of acute dyspnea than the initial clinical workup (sensitivity, 85.3% [95% CI, 81.8%-88.4%]; specificity, 90% [95% CI, 87.2%-92.4%]), chest radiography alone (sensitivity, 69.5% [95% CI, 65.1%-73.7%]; specificity, 82.1% [95% CI, 78.6%-85.2%]), and natriuretic peptides (sensitivity, 85% [95% CI, 80.3%-89%]; specificity, 61.7% [95% CI, 54.6%-68.3%]; n = 486). Net reclassification index of the LUS-implemented approach compared with standard workup was 19.1%. The implementation of LUS with the clinical evaluation may improve accuracy of ADHF diagnosis in patients presenting to the ED. Clinicaltrials.gov; No.: NCT01287429; URL: www.clinicaltrials.gov.

Impact of daily supplementation of Spirulina platensis on the immune system of naïve HIV-1 patients in Cameroon: a 12-months single blind, randomized, multicenter trial.

PubMed

Ngo-Matip, Marthe-Elise; Pieme, Constant Anatole; Azabji-Kenfack, Marcel; Moukette, Bruno Moukette; Korosky, Emmanuel; Stefanini, Philippe; Ngogang, Jeanne Yonkeu; Mbofung, Carl Moses

2015-07-21

Micronutrient deficiencies occur early in Human Immunodeficiency Virus (HIV) infections they have reverse effects on the nutritional status. The diet supplementation with a natural nutraceutical rich in proteins and micronutrient like Spirulina platensis, may be effective and efficient in delaying HIV disease progression by frequently reported improvement in immune response. A prospective single-blind, randomized, multicenter study conducted on 320 HIV-1 ARV-naïve participants for 12 months. Participants received either S. platensis supplementation and standard care or standard care and local balanced diet without S. platenis. Selected hematological and biochemical as well as CD4 count cells, viral load copies were assessed at three separate times. Among the 169 ART-naïve participants enrolled in the study, the female was mostly represented (67.1%). The significant increase of CD4 count cells (596.32-614.92 cells count) and significant decrease of viral load levels (74.7 × 10(3)-30.87 × 10(3) copies/mL) of the patients who received a supplementation of S. platensis was found after 6 months of treatment. Haemoglobin level was also significantly higher in the same group while the fasting blood glucose concentration decreased after 12 months compared to control. A daily supplementation with S. platensis to diet combined with a reasonable balanced diet has significantly increased the CD4 cells and reduced the viral load after 6 months. Further studies are recommended among a large specific group of people infected by the HIV in order to investigate the mechanisms involved on the effect of S. platensis on immune system.

Bendamustine in Combination With Gemcitabine and Vinorelbine Is an Effective Regimen As Induction Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma: Final Results of a Multicenter Phase II Study.

PubMed

Santoro, Armando; Mazza, Rita; Pulsoni, Alessandro; Re, Alessandro; Bonfichi, Maurizio; Zilioli, Vittorio Ruggero; Salvi, Flavia; Merli, Francesco; Anastasia, Antonella; Luminari, Stefano; Annechini, Giorgia; Gotti, Manuel; Peli, Annalisa; Liberati, Anna Marina; Di Renzo, Nicola; Castagna, Luca; Giordano, Laura; Carlo-Stella, Carmelo

2016-09-20

This multicenter, open-label, phase II study evaluated the combination of bendamustine, gemcitabine, and vinorelbine (BeGEV) as induction therapy before autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (HL). Patients with HL who were refractory to or had relapsed after one previous chemotherapy line were eligible. The primary end point was complete response (CR) rate after four cycles of therapy. Secondary end points were: overall response rate, stem-cell mobilization activity, and toxicity. Progression-free and overall survival were also evaluated. In total, 59 patients were enrolled. After four cycles of therapy, 43 patients (73%) achieved CR, and six (10%) achieved partial response, for an overall response rate of 83%. The most common grade 3 to 4 nonhematologic toxicities included febrile neutropenia (n = 7) and infection (n = 4). Regarding hematologic toxicities, grade 3 to 4 thrombocytopenia and neutropenia were each experienced by eight patients (13.5%). CD34+ cells were successfully harvested in 55 of 57 evaluable patients, and 43 of 49 responding patients underwent ASCT. With a median follow-up of 29 months, the 2-year progression-free and overall survival rates for the total population were 62.2% and 77.6%, respectively. The same figures for patients undergoing autograft were 80.8% and 89.3%, respectively. This phase II study demonstrates that BeGEV is an effective salvage regimen able to induce CR in a high proportion of patients with relapsed or refractory HL before ASCT. These data provide a strong rationale for further development of the BeGEV regimen. © 2016 by American Society of Clinical Oncology.

Unique characteristics and failure patterns of metaplastic breast cancer in contrast to invasive ductal carcinoma: a retrospective multicenter case-control study (KROG 13-07).

PubMed

Yu, Jeong Il; Choi, Doo Ho; Huh, Seung Jae; Ahn, Sung Ja; Lee, Ji Shin; Shin, Kyung Hwan; Kwon, Youngmee; Kim, Yong Bae; Suh, Chang-Ok; Kim, Jin Hee; Cho, Jihyoung; Kim, In Ah; Lee, Jong Hoon; Park, Won

2015-04-01

This retrospective study was performed to investigate the need for management modification in MBC according to evaluation of characteristics and failure patterns compared with IDC. We performed this multicenter study taking MBC and randomly assigned IDC cases matched for age (± 3 years), pathologic stage (T and N), locoregional treatment methods (surgery with or without radiation therapy), and period of treatment (± 6 months) that occurred from January 1999 to November 2011 in the 6 institutions of the Korean Radiation Oncology Group. A total of 144 female MBC patients were enrolled. The median follow-up was 51 months (range, 1-186 months). The rates of positivity for estrogen receptor (P < .001), progesterone receptor (P < .001), and HER2 (P = .007) were significantly lower in MBC patients. During follow-up, recurrence developed in 22 (15.3%) MBC and 6 (4.2%) IDC patients (P = .002). The median time to recurrence of MBC and IDC was 15 months and 24 months, respectively. Most instances of recurrence in MBC developed in the triple-negative (TN) subgroup (TN-MBC). In particular, locoregional recurrence developed exclusively in the TN-MBC subgroup. In the TN-MBC subgroup, the number of risk factors (pT2-3, N1-3) was related to significant differences in overall survival (P = .001) and recurrence-free survival (P < .001). The MBC patients had a higher rate of TN, poorer differentiation, and a higher recurrence rate than did the IDC patients. Considering the unique characteristics and failure patterns, it is necessary to modify the current management guidelines for MBC. Copyright © 2015 Elsevier Inc. All rights reserved.

Multicenter phase II study of apatinib treatment for metastatic gastric cancer after failure of second-line chemotherapy.

PubMed

Ruan, Hanguang; Dong, Junlin; Zhou, Xueliang; Xiong, Juan; Wang, Hua; Zhong, Xiaoming; Cao, Xiaolong

2017-11-28

Apatinib is a tyrosine kinase inhibitor and vascular endothelial growth factor receptor 2 (VEGFR-2) targeted drug. A phase I clinical trial showed that this agent has antitumor activity in Chinese patients with metastatic gastric cancer (mGC). The aim of this study was to investigate the safety and efficacy of apatinib treatment in patients with mGC. This was an open-label, multicenter, single-arm study involving four institutions in China. We enrolled 42 patients from March 2015 to October 2015 who experienced tumor progression after second-line chemotherapy and had no other treatment options that clearly conferred a survival benefit. Oral apatinib (850 mg daily) was administered within 30 min of eating breakfast, lunch, or dinner on days 1 through 28 of each 4-week cycle. The median progression-free survival (PFS) time and median overall survival (OS) time were 4.0 months (95% CI, 2.85-5.15) and 4.50 months (95% CI, 4.03-4.97), respectively. The disease control rate (DCR) and objective response rate (ORR) were, respectively, 78.57% and 9.52% after 2 cycles and 57.14% and 19.05% after 4 cycles. The main adverse events (AEs) were secondary hypertension, elevated aminotransferase, and hand-foot syndrome, with incidences of 35.71%, 45.24%, and 40.48%, respectively. The most common grade 3 to 4 AEs were secondary hypertension and elevated aminotransferase, with incidences of 7.14% each. Apatinib is effective and safe in heavily pretreated patients with mGC who fail to respond to two or more prior chemotherapy regimens. Toxicities were tolerable or could be clinically managed.

Effectiveness of Physical Therapy in Treating Atraumatic Full Thickness Rotator Cuff Tears. A Multicenter Prospective Cohort Study

PubMed Central

Kuhn, John E.; Dunn, Warren R.; Sanders, Rosemary; An, Qi; Baumgarten, Keith M.; Bishop, Julie Y.; Brophy, Robert H.; Carey, James L.; Holloway, Brian G.; Jones, Grant L.; Ma, C. Benjamin; Marx, Robert G.; McCarty, Eric C.; Poddar, Sourav K.; Smith, Matthew V.; Spencer, Edwin E.; Vidal, Armando F.; Wolf, Brian R.; Wright, Rick W.

2013-01-01

Purpose To assess the effectiveness of a specific non-operative physical therapy program in treating atraumatic full thickness rotator cuff tears using a multicenter prospective cohort study design. Methods Patients with atraumatic full thickness rotator cuff tears who consented to enroll provided data via questionnaire on demographics, symptom characteristics, co-morbidities, willingness to undergo surgery, and patient related outcome assessments (SF-12, ASES, WORC, SANE score, Shoulder Activity Scale). Physicians recorded physical examination and imaging data. Patients began a physical therapy program developed from a systematic review of the literature and returned for evaluation at 6 and 12 weeks. At those visits patients could chose one of three courses: 1.) Cured (no formal follow up scheduled), 2.) Improved (continue therapy with scheduled reassessment in 6 weeks), or 3.) No better (offered surgery). Patients were contacted by telephone at 1 and 2 years to determine if they had undergone surgery since their last visit. A Wilcoxon signed rank test with continuity correction was used to compare initial, 6 week, and 12 week outcome scores. Results The cohort consists of 452 patients. Patient reported outcomes improved significantly at 6 and 12 weeks. Patients elected to undergo surgery less than 25% of the time. Patients who decided to have surgery generally did so between 6 and 12 weeks, and few had surgery between 3 and 24 months. Conclusion Non-operative treatment using this physical therapy protocol is effective for treating atraumatic full thickness rotator cuff tears in approximately 75% of patients followed for two years. Level of evidence Level IV, Case Series, Treatment Study PMID:23540577

Optical Coherence Tomography Substudy of A Prospective Multicenter Randomized Post-Market Trial to Assess the Safety and Effectiveness of the Firehawk™ Rapamycin Target Eluting Cobalt Chromium Coronary Stent System for the Treatment of Atherosclerotic Lesions: TARGET All Comers.

PubMed

Baumbach, Andreas; Lansky, Alexandra J; Onuma, Yoshi; Asano, Taku; Johnson, Thomas; Anderson, Richard; Kiemeneij, Ferdinand; Zheng, Ming; Van Royen, Niels; Slagboom, Ton; Vlachojannis, Georg; Xu, Bo; Serruys, Patrick; Wijns, William

2018-06-12

Durable polymer drug-eluting stents (DP DES) may contribute to persistent inflammation, delayed endothelial healing and subsequent late DES thrombosis. The aim of this Optical Coherence Tomography (OCT) sub-study was to compare healing and neointimal coverage of a novel bioabsorbable polymer sirolimus-eluting stent (FIREHAWK®) (BP DES) versus the DP DES (XIENCE) at 90 days in an all comers patient population. The TARGET All Comers study is a prospective multicenter randomised post-market trial of 1656 patients randomised 1:1 to FIREHAWK or XIENCE at 21 centers in 10 European countries. The TARGET OCT sub-study enrolled 36 consecutive patients with 52 lesions at 6 centers proficient in OCT. Follow-up OCT was performed at 3 months or prior to revascularisation when occurring before the 3-month window. The substudy was designed for non-inferiority of the primary endpoint of neointimal thickness. At follow-up, the mean neointimal thickness by OCT (52 lesions, Firehawk, n=24; Xience, n=28), was not significantly different between groups (Firehawk 75.5μm vs Xience V 82.3 μm) meeting the primary endpoint of non-inferiority (Pnoninferiority<0.001). The percentage of stent strut coverage was high in both groups (strut level: 99.9% ± 0.3 vs 100% ± 0.1, p=0.26), and the proportion of malapposed struts (1.0±1.6% vs. 1.2±2.0%, p=0.51) was low in both groups. Based on OCT, the FIREHAWK BP DES has a similar healing response 3 months after implantation compared to the DP DES, with near complete strut coverage, moderate neointima formation and minimal strut malapposition.

A prospective multicenter study of microbiologically defined infections in pediatric cancer patients with fever and neutropenia: Swiss Pediatric Oncology Group 2003 fever and neutropenia study.

PubMed

Agyeman, Philipp; Kontny, Udo; Nadal, David; Leibundgut, Kurt; Niggli, Felix; Simon, Arne; Kronenberg, Andreas; Frei, Reno; Escobar, Hugo; Kühne, Thomas; Beck-Popovic, Maja; Bodmer, Nicole; Ammann, Roland A

2014-09-01

Fever and neutropenia (FN) often complicate anticancer treatment and can be caused by potentially fatal infections. Knowledge of pathogen distribution is paramount for optimal patient management. Microbiologically defined infections (MDI) in pediatric cancer patients presenting with FN by nonmyeloablative chemotherapy enrolled in a prospective multicenter study were analyzed. Effectiveness of empiric antibiotic therapy in FN episodes with bacteremia was assessed taking into consideration recently published treatment guidelines for pediatric patients with FN. MDI were identified in a minority (22%) of pediatric cancer patients with FN. In patients with, compared with patients without MDI, fever [median, 5 (interquartile range: 3-8) vs. 2 (interquartile range: 1-3) days, P < 0.001] and hospitalization [10 (6-14) vs. 5 (3-8) days, P < 0.001] lasted longer, transfer to the intensive care unit was more likely [13 of 95 (14%) vs. 7 of 346 (2.0%), P < 0.001], and antibiotics were given longer [10 (7-14) vs. 5 (4-7) days, P < 0.001]. Empiric antibiotic therapy in FN episodes with bacteremia was highly effective if not only intrinsic and reported antimicrobial susceptibilities were considered but also the purposeful omission of coverage for coagulase-negative staphylococci and enterococci was taken into account [81% (95% confidence interval: 68-90) vs. 96.6% (95% confidence interval: 87-99.4), P = 0.004]. MDI were identified in a minority of FN episodes but they significantly affected management and the clinical course of pediatric cancer patients. Compliance with published guidelines was associated with effectiveness of empiric antibiotic therapy in FN episodes with bacteremia.

New Factors Predicting Delayed Graft Function: a Multi-Center Cohort Study of Kidney Donation After Brain Death Followed by Circulatory Death.

PubMed

Sun, Qipeng; Huang, Zhengyu; Zhou, Honglan; Lin, Minzhuan; Hua, Xuefeng; Hong, Liangqing; Na, Ning; Cai, Ruiming; Wang, Gang; Sun, Qiquan

2018-05-30

Delayed graft function (DGF) is a common complication following kidney transplantation adversely affecting graft outcomes. Donation after brain death followed by circulatory death (DBCD), a novel donation pattern, is expected to correlate with high incidence of DGF. However, little information is available about factors associated with DGF in DBCD. A total of 383 kidney transplants from DBCD donation in three institutions were enrolled. Associations of DGF with the clinical characteristics of recipients and donors were quantified. In this retrospective multi-center study, the incidence of DGF was 19.3%. Lower incidence of DGF was found in recipients for whom antithymocyte globulin was used for induction (p < 0.05), which was an independent protective factor against DGF (odds ratio [OR] = 0.48; 95% CI 0.27-0.86). Two novel explicative variables were recognized as independent risk factors, including use of vasoactive drugs (OR = 3.15; 95% CI 1.39-7.14) and cardiopulmonary resuscitation (OR = 2.51; 95% CI 1.05-6.00), which contributed significantly to increased risk of DGF (p < 0.05). Prolonged warm ischemia time (> 18 min; OR = 2.42; 95% CI 1.36-4.32), was also predictive of DGF in DBCD. A prediction model was developed and achieved an area under the curve of 0.89 in predicting DGF when combined with reported parameters. The novel factors, confirmed for the first time in our study, will help to improve risk prediction of DGF and to determine optimal interventions to prevent DGF in clinical practice. © 2018 The Author(s). Published by S. Karger AG, Basel.

Efficacy of Magnesium Trihydrate of Ursodeoxycholic Acid and Chenodeoxycholic Acid for Gallstone Dissolution: A Prospective Multicenter Trial.

PubMed

Hyun, Jong Jin; Lee, Hong Sik; Kim, Chang Duck; Dong, Seok Ho; Lee, Seung-Ok; Ryu, Ji Kon; Lee, Don Haeng; Jeong, Seok; Kim, Tae Nyeun; Lee, Jin; Koh, Dong Hee; Park, Eun Taek; Lee, In-Seok; Yoo, Byung Moo; Kim, Jin Hong

2015-07-01

Cholecystectomy is necessary for the treatment of symptomatic or complicated gallbladder (GB) stones, but oral litholysis with bile acids is an attractive alternative therapeutic option for asymptomatic or mildly symptomatic patients. This study was conducted to evaluate the efficacy of magnesium trihydrate of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on gallstone dissolution and to investigate improvements in gallstone-related symptoms. A prospective, multicenter, phase 4 clinical study to determine the efficacy of orally administered magnesium trihydrate of UDCA and CDCA was performed from January 2011 to June 2013. The inclusion criteria were GB stone diameter ≤15 mm, GB ejection fraction ≥50%, radiolucency on plain X-ray, and asymptomatic/mildly symptomatic patients. The patients were prescribed one capsule of magnesium trihydrate of UDCA and CDCA at breakfast and two capsules at bedtime for 6 months. The dissolution rate, response rate, and change in symptom score were evaluated. A total of 237 subjects were enrolled, and 195 subjects completed the treatment. The dissolution rate was 45.1% and the response rate was 47.2% (92/195) after 6 months of administration of magnesium trihydrate of UDCA and CDCA. Only the stone diameter was significantly associated with the response rate. Both the symptom score and the number of patients with symptoms significantly decreased regardless of stone dissolution. Adverse events necessitating discontinuation of the drug, surgery, or endoscopic management occurred in 2.5% (6/237) of patients. Magnesium trihydrate of UDCA and CDCA is a well-tolerated bile acid that showed similar efficacy for gallstone dissolution and improvement of gallstone-related symptoms as that shown in previous studies.

Sunitinib in relapsed or refractory diffuse large B-cell lymphoma: a clinical and pharmacodynamic phase II multicenter study of the NCIC Clinical Trials Group.

PubMed

Buckstein, Rena; Kuruvilla, John; Chua, Neil; Lee, Christina; Macdonald, David A; Al-Tourah, Abdulwahab J; Foo, Alison H; Walsh, Wendy; Ivy, S Percy; Crump, Michael; Eisenhauer, Elizabeth A

2011-05-01

There are limited effective therapies for most patients with relapsed diffuse large B-cell lymphoma (DLBCL). We conducted a phase II trial of the multi-targeted vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, sunitinib, 37.5 mg given orally once daily in adult patients with relapsed or refractory DLBCL. Of 19 enrolled patients, 17 eligible patients were evaluable for toxicity and 15 for response. No objective responses were seen and nine patients achieved stable disease (median duration 3.4 months). As a result, the study was closed at the end of the first stage. Grades 3-4 neutropenia and thrombocytopenia were observed in 29% and 35%, respectively. There was no relationship between change in circulating endothelial cell numbers (CECs) and bidimensional tumor burden over time. Despite some activity in solid tumors, sunitinib showed no evidence of response in relapsed/refractory DLBCL and had greater than expected hematologic toxicity.

Sunitinib in relapsed or refractory diffuse large B-cell lymphoma: a clinical and pharmacodynamic phase II multicenter study of the NCIC Clinical Trials Group

PubMed Central

Buckstein, Rena; Kuruvilla, John; Chua, Neil; Lee, Christina; Macdonald, David A; Al-Tourah, Abdulwahab J; Foo, Alison H; Walsh, Wendy; Ivy, S Percy; Crump, Michael; Eisenhauer, Elizabeth A

2011-01-01

There are limited effective therapies for most patients with relapsed diffuse large B-cell lymphoma (DLBCL). We conducted a phase II trial of the multi-targeted vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, sunitinib, 37.5 mg given orally once daily in adult patients with relapsed or refractory DLBCL. Of 19 enrolled patients, 17 eligible patients were evaluable for toxicity and 15 for response. No objective responses were seen and nine patients achieved stable disease (median duration 3.4 months). As a result, the study was closed at the end of the first stage. Grades 3—4 neutropenia and thrombocytopenia were observed in 29% and 35%, respectively. There was no relationship between change in circulating endothelial cell numbers (CECs) and bidimensional tumor burden over time. Despite some activity in solid tumors, sunitinib showed no evidence of response in relapsed/refractory DLBCL and had greater than expected hematologic toxicity. PMID:21463120

Differential Effects of Antiepileptic Drugs on Neonatal Outcomes

PubMed Central

Pennell, P.B.; Klein, A.M.; Browning, N.; Baker, G.A.; Clayton-Smith, J.; Kalayjian, L.A.; Liporace, J.D.; Privitera, M.; Crawford, T.; Loring, D.W.; Meador, K.J.

2012-01-01

Offspring of women with epilepsy (WWE) on AEDs are at increased risks for major congenital malformations and reduced cognition. They may be at risk for other adverse neonatal outcomes. WWE on carbamazepine (CBZ), lamotrigine (LTG), phenytoin (PHT), or valproate (VPA) monotherapy were enrolled in a prospective, observational, multicenter study of the neurodevelopmental effects of AEDs. The odds ratio for small for gestational age (SGA) was higher for VPA vs. PHT, VPA vs. LTG, and CBZ vs. PHT. Microcephaly rates were elevated to 12% for all newborns and 12-months-old, but normalized by age 24-months. Reduced Apgar scores occurred more frequently in the VPA and PHT groups at 1 minute, but scores were near normal in all groups at 5 minutes. This study demonstrates increased risks for being born SGA in the VPA and CBZ groups, and transiently reduced Apgar scores in the VPA and PHT groups. Differential risks amongst the AEDs can help inform decisions about AED selection for women during childbearing years. PMID:22749607

Prospective research on infants with mild encephalopathy: the PRIME study.

PubMed

Prempunpong, C; Chalak, L F; Garfinkle, J; Shah, B; Kalra, V; Rollins, N; Boyle, R; Nguyen, K-A; Mir, I; Pappas, A; Montaldo, P; Thayyil, S; Sánchez, P J; Shankaran, S; Laptook, A R; Sant'Anna, G

2018-01-01

To determine short-term outcomes of infants with evidence of hypoxia-ischemia at birth and classified as mild neonatal encephalopathy (NE) at <6 h of age. Prospective multicenter study. Mild NE was defined as ⩾1 abnormal category in modified Sarnat score. Primary outcome was any abnormality on early amplitude integrated electroencephalogram (aEEG) or seizures, abnormal brain magnetic resonance imaging (MRI) or neurological exam at discharge. A total of 54/63 (86%) of enrolled infants had data on components of the primary outcome, which was abnormal in 28/54 (52%): discontinuous aEEG (n=4), MRI (n=9) and discharge exam (n=22). Abnormal tone and/or incomplete Moro were the most common findings. MRI abnormalities were confined to cerebral cortex but two infants had basal ganglia and/or thalamus involvement. The 18 to 24 months follow-up is ongoing. A larger than expected proportion of mild NE infants with abnormal outcomes was observed. Future research should evaluate safety and efficacy of neuroprotection for mild NE.

Effects of ethinyl estradiol and ibuprofen compared to placebo on endometrial bleeding, cervical mucus and the postcoital test in levonorgestrel subcutaneous implant users.

PubMed

Archer, David F; Philput, Christine B; Levine, Adam S; Cullins, Vanessa; Stovall, Thomas G; Bacon, Janice; Weber, Margaret E

2008-08-01

The study was conducted to evaluate ethinyl estradiol (EE) or ibuprofen (IBU) compared to placebo (PL) on spotting and bleeding (S/B) and a postcoital test (PCT) in women using the levonorgestrel subcutaneous implant. Women experiencing excessive S/B were enrolled in a multicenter prospective randomized study using EE, IBU or PL. Duration of S/B and a PCT were evaluated. Statistical analysis used a general linear model procedure with Duncan's multiple range tests for individual variables. One hundred seven women were evaluated, and there was no difference in the duration of bleeding among the three therapies, while the mean number of spotting days were 1.8 for EE and 2.8 for PL (p=.04). There was no effect of IBU on S/B. No effect on cervical mucus or sperm was found between treatments. There was a decrease in spotting but no effect on bleeding with EE compared to PL.

Efficacy of a non-hormonal treatment, BRN-01, on menopausal hot flashes: a multicenter, randomized, double-blind, placebo-controlled trial.

PubMed

Colau, Jean-Claude; Vincent, Stéphane; Marijnen, Philippe; Allaert, François-André

2012-09-01

Homeopathic medicines have a place among the non-hormonal therapies for the treatment of hot flashes during the menopause. The objective of this study was to evaluate the efficacy of the non-hormonal treatment BRN-01 in reducing hot flashes in menopausal women. This was a multicenter, randomized, double-blind, placebo-controlled study carried out between June 2010 and July 2011. The study was conducted in 35 active centers in France (gynecologists in private practice). One hundred and eight menopausal women, ≥ 50 years of age, were enrolled in the study. The eligibility criteria included menopause for <24 months and ≥ 5 hot flashes per day with a significant negative effect on the women's professional and/or personal life. Treatment was either BRN-01 tablets, a registered homeopathic medicine containing Actaea racemosa (4 centesimal dilutions [4CH]), Arnica montana (4CH), Glonoinum (4CH), Lachesis mutus (5CH), and Sanguinaria canadensis (4CH), or identical placebo tablets, prepared by Laboratoires Boiron according to European Pharmacopoeia standards. Oral treatment (2 to 4 tablets per day) was started on day 3 after study enrollment and was continued for 12 weeks. The main outcome measure was the hot flash score (HFS) compared before, during, and after treatment. Secondary outcome criteria were the quality of life (QoL) [measured using the Hot Flash Related Daily Interference Scale (HFRDIS)], severity of symptoms (measured using the Menopause Rating Scale), evolution of the mean dosage, and compliance. All adverse events (AEs) were recorded. One hundred and one women were included in the final analysis (intent-to-treat population: BRN-01, n = 50; placebo, n = 51). The global HFS over the 12 weeks, assessed as the area under the curve (AUC) adjusted for baseline values, was significantly lower in the BRN-01 group than in the placebo group (mean ± SD 88.2 ± 6.5 versus 107.2 ± 6.4; p = 0.0411). BRN-01 was well tolerated; the frequency of AEs was similar in the two treatment groups, and no serious AEs were attributable to BRN-01. BRN-01 seemed to have a significant effect on the HFS, compared with placebo. According to the results of this clinical trial, BRN-01 may be considered a new therapeutic option with a safe profile for hot flashes in menopausal women who do not want or are not able to take hormone replacement therapy or other recognized treatments for this indication. Trial registration number (EudraCT): 2009-016959-21.

Guaifenesin has no effect on sputum volume or sputum properties in adolescents and adults with acute respiratory tract infections.

PubMed

Hoffer-Schaefer, Agathe; Rozycki, Henry J; Yopp, Melissa A; Rubin, Bruce K

2014-05-01

Guaifenesin (glyceryl guaiacolate ether [GGE]) has been studied as a cough suppressant and as an expectorant; however, published studies to date have failed to find a consistent benefit. An 8-day multi-center clinical trial was conducted to study the effect of two 600-mg extended-release GGE tablets twice daily for 1 week on cold symptoms, sputum volume, and properties in adolescents and adults with productive cough from an acute respiratory tract infection (RTI). The study enrolled 378 subjects (GGE, n = 188; and placebo, n = 190) who were otherwise healthy and had an RTI for up to 5 days before enrollment. Subjects suffered from at least 2 of 3 symptoms of cough, thickened mucus, and chest congestion. A total of 151 GGE and 144 control subjects completed the full protocol. Single-sputum samples were collected from each subject on days 1, 3, 4, and 8 of the study. The rheology and interfacial tension of sputum were measured, and 24-h collected samples from days 1 and 4 were analyzed for total volume and hydration. Symptoms in both the GGE and placebo groups improved to a similar degree over time. There were no significant differences between the GGE and placebo groups for sputum volume (P = .41), percent solids (P = .69), interfacial tension (P = .88), elasticity (P = .71), viscosity (P = .45), or mechanical impedance (P = .75). The recommended dose of GGE had no measurable effect on sputum volume or properties and is unlikely to be an expectorant or mucolytic when used to treat acute RTI. (ClinicalTrials.gov registration NCT01046136.).

A single-arm clinical trial of a 48-hour intravenous N-acetylcysteine protocol for treatment of acetaminophen poisoning.

PubMed

Heard, K; Rumack, B H; Green, J L; Bucher-Bartelson, B; Heard, S; Bronstein, A C; Dart, R C

2014-06-01

Acetylcysteine prevents hepatic injury when administered soon after acetaminophen overdose. The most commonly used treatment protocols are a 72-hour oral and a 21-hour intravenous (IV) protocol. Between 1984 and 1994, 409 patients were enrolled in a study to describe the outcomes of patients who were treated using a 48-hour IV protocol. In 1991, an interim analysis reported the first 223 patients. The objective of this manuscript is to report the rates of hepatotoxicity and adverse events occurring during a 48-hour IV acetylcysteine protocol in the entire 409 patient cohort. This was a multicenter, single-arm, open-label clinical trial enrolling patients who presented with a toxic serum acetaminophen concentration within 24 h of acute acetaminophen ingestion. Patients were treated with 140 mg/kg loading dose followed by 70 mg/kg every 4 h for 12 doses. Serum aminotransferase activities were measured every 8 h during the protocol, and adverse events were recorded. The primary outcome was the percentage of subjects who developed hepatotoxicity defined as a peak serum aminotransferase greater than 1000 IU/L. Four hundred and nine patients were enrolled, and 309 met inclusion for the outcome analysis. The overall percentage of patients developing hepatotoxicity was 18.1%, and 3.4% of patients treated within 10 h developed hepatotoxicity. One acetaminophen-related death occurred in a patient treated at 22 h. Adverse events occurred in 28.9% of enrolled subjects; the most common adverse events were nausea, vomiting, and flushing, and no events were rated as serious by the investigator. Acetaminophen-overdosed patients treated with IV acetylcysteine administered as 140 mg/kg loading dose followed by 70 mg/kg every 4 h for 12 doses had a low rate of hepatotoxicity and few adverse events. This protocol delivers a higher dose of acetylcysteine which may be useful in selected cases involving very large overdoses.

Prevalence and impact of active and passive cigarette smoking in acute respiratory distress syndrome.

PubMed

Hsieh, S Jean; Zhuo, Hanjing; Benowitz, Neal L; Thompson, B Taylor; Liu, Kathleen D; Matthay, Michael A; Calfee, Carolyn S

2014-09-01

Cigarette smoke exposure has recently been found to be associated with increased susceptibility to trauma- and transfusion-associated acute respiratory distress syndrome. We sought to determine 1) the incidence of cigarette smoke exposure in a diverse multicenter sample of acute respiratory distress syndrome patients and 2) whether cigarette smoke exposure is associated with severity of lung injury and mortality in acute respiratory distress syndrome. Analysis of the Albuterol for the Treatment of Acute Lung Injury and Omega Acute Respiratory Distress Syndrome Network studies. Acute Respiratory Distress Syndrome Network hospitals. Three hundred eighty-one patients with acute respiratory distress syndrome. None. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol, a validated tobacco-specific marker, was measured in urine samples from subjects enrolled in two National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network randomized controlled trials. Urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol levels were consistent with active smoking in 36% of acute respiratory distress syndrome patients and with passive smoking in 41% of nonsmokers (vs 20% and 40% in general population, respectively). Patients with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol levels in the active smoking range were younger and had a higher incidence of alcohol misuse, fewer comorbidities, lower severity of illness, and less septic shock at enrollment compared with patients with undetectable 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol levels. Despite this lower severity of illness, the severity of lung injury did not significantly differ based on biomarker-determined smoking status. Cigarette smoke exposure was not significantly associated with death after adjusting for differences in age, alcohol use, comorbidities, and severity of illness. In this first multicenter study of biomarker-determined cigarette smoke exposure in acute respiratory distress syndrome patients, we found that active cigarette smoke exposure was significantly more prevalent among acute respiratory distress syndrome patients compared to population averages. Despite their younger age, better overall health, and lower severity of illness, smokers by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol had similar severity of lung injury as patients with undetectable 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. These findings suggest that active cigarette smoking may increase susceptibility to acute respiratory distress syndrome in younger, healthier patients.

Point-of-care washing of allogeneic red blood cells for the prevention of transfusion-related respiratory complications (WAR-PRC): a protocol for a multicenter randomised clinical trial in patients undergoing cardiac surgery.

PubMed

Warner, Matthew A; Welsby, Ian J; Norris, Phillip J; Silliman, Christopher C; Armour, Sarah; Wittwer, Erica D; Santrach, Paula J; Meade, Laurie A; Liedl, Lavonne M; Nieuwenkamp, Chelsea M; Douthit, Brian; van Buskirk, Camille M; Schulte, Phillip J; Carter, Rickey E; Kor, Daryl J

2017-08-18

The transfusion-related respiratory complications, transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO), are leading causes of transfusion-related morbidity and mortality. At present, there are no effective preventive strategies with red blood cell (RBC) transfusion. Although mechanisms remain incompletely defined, soluble biological response modifiers (BRMs) within the RBC storage solution may play an important role. Point-of-care (POC) washing of allogeneic RBCs may remove these BRMs, thereby mitigating their impact on post-transfusion respiratory complications. This is a multicenter randomised clinical trial of standard allogeneic versus washed allogeneic RBC transfusion for adult patients undergoing cardiac surgery testing the hypothesis that POC RBC washing is feasible, safe, and efficacious and will reduce recipient immune and physiologic responses associated with transfusion-related respiratory complications. Relevant clinical outcomes will also be assessed. This investigation will enrol 170 patients at two hospitals in the USA. Simon's two-stage design will be used to assess the feasibility of POC RBC washing. The primary safety outcomes will be assessed using Wilcoxon Rank-Sum tests for continuous variables and Pearson chi-square test for categorical variables. Standard mixed modelling practices will be employed to test for changes in biomarkers of lung injury following transfusion. Linear regression will assess relationships between randomised group and post-transfusion physiologic measures. Safety oversight will be conducted under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained by the DSMB as well as the institutional review boards at each institution prior to enrolling the first study participant. This study aims to provide important information regarding the feasibility of POC washing of allogeneic RBCs and its potential impact on ameliorating post-transfusion respiratory complications. Additionally, it will inform the feasibility and scientific merit of pursuing a more definitive phase II/III clinical trial. ClinicalTrials.gov registration number is NCT02094118 (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.

Galectin 3 complements BNP in risk stratification in acute heart failure.

PubMed

Fermann, Gregory J; Lindsell, Christopher J; Storrow, Alan B; Hart, Kimberly; Sperling, Matthew; Roll, Susan; Weintraub, Neal L; Miller, Karen F; Maron, David J; Naftilan, Allen J; McPherson, John A; Sawyer, Douglas B; Christenson, Robert; Collins, Sean P

2012-12-01

Galectin 3 (G3) is a mediator of fibrosis and remodeling in heart failure. Patients diagnosed with and treated for Acute Heart Failure Syndromes were prospectively enrolled in the Decision Making in Acute Decompensated Heart Failure multicenter trial. Patients with a higher G3 had a history of renal disease, a lower heart rate and acute kidney injury. They also tended to have a history of HF and 30-day adverse events compared with B-type natriuretic peptide. In Acute Heart Failure Syndromes, G3 levels do not provide prognostic value, but when used complementary to B-type natriuretic peptide, G3 is associated with renal dysfunction and may predict 30-day events.

Long-Term Follow Up of Patients with Mild-to-Moderate Alzheimer's Disease Treated with Bapineuzumab in a Phase III, Open-Label, Extension Study.

PubMed

Salloway, Stephen P; Sperling, Reisa; Fox, Nick C; Sabbagh, Marwan N; Honig, Lawrence S; Porsteinsson, Anton P; Rofael, Hany; Ketter, Nzeera; Wang, Daniel; Liu, Enchi; Carr, Stephen; Black, Ronald S; Brashear, H Robert

2018-06-08

A 3-year extension of two Phase III parent studies of intravenous (IV) bapineuzumab in patients with mild-to-moderate Alzheimer's disease dementia (apolipoprotein (APOE) ɛ4 carriers and noncarriers) is summarized. The primary and secondary objectives were to evaluate the long-term safety, tolerability, and maintenance of efficacy of bapineuzumab. A multicenter study in patients who had participated in double-blind placebo-controlled parent studies. Patients enrolled in the extension study were assigned to receive IV infusions of bapineuzumab (0.5 or 1.0 mg/kg) every 13 weeks until termination but were blinded to whether they had received bapineuzumab or placebo in the parent studies. A total of 1,462 (688 were APOEɛ4 carriers and 774 were noncarriers) patients were enrolled. Extension-onset adverse events occurred in >81% of the patients in each dose group. Fall, urinary tract infection, agitation, and ARIA-E occurred in ≥10% of participants. The incidence proportion of ARIA-E was higher among carriers and noncarriers who received bapineuzumab for the first time in the extension study (11.8% and 5.4%, respectively) versus those who were previously exposed in the parent studies (5.1% and 1.3%, respectively). After 6 to 12 months exposure to bapineuzumab IV in the extension study, similar deterioration of cognition and function occurred with no significant differences between the dose groups. Infusion of bapineuzumab 0.5 or 1.0 mg/kg every 13 weeks for up to 3 years was generally well tolerated, with a safety and tolerability profile similar to that in previous studies.

Safety, tolerability and efficacy of lixisenatide as monotherapy in Japanese patients with type 2 diabetes mellitus: An open-label, multicenter study.

PubMed

Seino, Yutaka; Terauchi, Yasuo; Wang, Xiangling; Watanabe, Daisuke; Niemoeller, Elisabeth

2018-01-01

To assess the overall safety of lixisenatide monotherapy in Japanese patients with type 2 diabetes mellitus. Patients with type 2 diabetes mellitus, previously treated with ≤1 oral antidiabetic drug, were enrolled in an uncontrolled, open-label, single-arm study over 24 and 52 weeks. Any oral antidiabetic drug treatment was stopped at the start of the 6-week run-in period. From baseline, patients received once-daily lixisenatide monotherapy (10 μg for 1 week, 15 μg for 1 week, 20 μg thereafter) for 52 weeks (first 140 patients enrolled) or 24 weeks (subsequently enrolled patients). The primary end-point was safety over 24 and 52 weeks. Secondary efficacy end-points included absolute change in glycated hemoglobin, fasting plasma glucose and bodyweight from baseline. Of 428 patients screened, 361 and 140 were treated for 24 and 52 weeks, respectively; 88.4 and 90.0% completed treatment. During the 24- and 52-week treatment periods, 268/361 (74.2%) and 117/140 (83.6%) patients, respectively, had treatment-emergent adverse events; the most frequently reported was nausea (33.2 and 31.4%, respectively). The risk of severe hypoglycemia was low; only one case was reported. Lixisenatide treatment resulted in a decrease in mean glycated hemoglobin A1c (-0.98 and -0.86%), fasting plasma glucose (-1.05 and -0.85 mmol/L), and bodyweight (-1.33 and -1.48 kg) for the 24- and 52-week treatment periods, respectively. Once-daily lixisenatide monotherapy was associated with a safety profile in line with the glucagon-like peptide-1 receptor agonist class, and improved glycemic control in Japanese patients with type 2 diabetes mellitus. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Safety and efficacy of first-line bevacizumab with chemotherapy in Asian patients with advanced nonsquamous NSCLC: results from the phase IV MO19390 (SAiL) study.

PubMed

Tsai, Chun-Ming; Au, Joseph Siu-kie; Chang, Gee-Chen; Cheng, Ashley Chi-kin; Zhou, Caicun; Wu, Yi-long

2011-06-01

First-line treatment with bevacizumab combined with chemotherapy has been shown to improve outcomes in patients with advanced, nonsquamous non-small cell lung cancer (NSNSCLC) in phase III clinical trials. SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a preplanned subanalysis of Asian patients enrolled in SAiL. Patients with untreated, locally advanced, metastatic or recurrent NSNSCLC received bevacizumab 7.5 or 15 mg/kg every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Eligibility criteria for SAiL permitted enrolment of a broad patient population. The primary end point was safety; secondary end points included time to disease progression and overall survival. The Asian intent-to-treat population comprised 314 of the 2212 patients enrolled in the SAiL trial. In the Asian subanalysis, patients received a median of nine cycles of bevacizumab, and the median follow-up was 16.4 months. The incidence of clinically significant adverse events (grade ≥3) of special interest was relatively low in this population (15.6% overall); proteinuria (7.6%), hypertension (4.8%), and bleeding (2.5%) were the most common. A total of five adverse events related to bevacizumab were reported as grade 5. Disease control rate was 94.1%, median time to disease progression was 8.3 months, and median overall survival was 18.9 months. The safety and efficacy of first-line bevacizumab-based treatment in Asian patients with advanced NSNSCLC is consistent with that demonstrated in phase III studies and in the overall SAiL population. There were no new safety signals.

Risk Behavior among Women enrolled in a Randomized Controlled Efficacy Trial of an Adenoviral Vector Vaccine to Prevent HIV Acquisition: the Step Study

PubMed Central

Novak, Richard M.; Metch, Barbara; Buchbinder, Susan; Cabello, Robinson; Donastorg, Yeycy; Figoroa, John-Peter; Adbul-Jauwad, Hend; Joseph, Patrice; Koenig, Ellen; Metzger, David; Sobieszycz, Magda; Tyndall, Mark; Zorilla, Carmen

2013-01-01

Objectives Report of risk behavior, HIV incidence, and pregnancy rates among women participating in the Step Study, a phase IIB trial of MRKAd5 HIV-1 gag/pol/nef vaccine in HIV-negative individuals who were at high risk of HIV-1. Design Prospective multicenter, double-blinded, placebo-controlled trial Methods Women were from North American (NA) and Caribbean and South America (CSA) sites. Risk behavior was collected at screening and 6-month intervals. Differences in characteristics between groups were tested with Chi-square, two-sided Fisher’s exact tests, and Wilcoxon rank sum tests. Generalized estimating equation models were used to assess behavioral change. Results Among 1134 enrolled women, the median number of male partners was 18; 73.8% reported unprotected vaginal sex, 15.9% unprotected anal sex and 10.8% evidence of a sexually transmitted infection in the 6 months prior to baseline. With 3344 person-years (p–y) of follow up, there were 15 incident HIV infections: incidence rate was 0.45 per 100/p-y (95% CI 0.25, 0.74). Crack cocaine use in both regions (relative risk [RR]=2.4 [1.7,3.3]) and in CSA, unprotected anal sex (RR=6.4 [3.8. 10.7]) and drug use (RR=4.1 [2.1, 8.0]) were baseline risk behaviors associated with HIV acquisition. There was a marked reduction in risk behaviors after study enrollment with some recurrence in unprotected vaginal sex. Of 963 non-sterilized women, 304 (31.6%) became pregnant. Conclusions Crack cocaine use and unprotected anal sex are important risk criteria to identify high-risk women for HIV efficacy trials. Pregnancy during the trial was a common occurrence and needs to be considered in trial planning for prevention trials in women. PMID:23807272

Effects of ATX-MS-1467 immunotherapy over 16 weeks in relapsing multiple sclerosis.

PubMed

Chataway, Jeremy; Martin, Keith; Barrell, Kevin; Sharrack, Basil; Stolt, Pelle; Wraith, David C

2018-03-13

To assess safety, tolerability, and efficacy of the antigen-specific immunotherapy ATX-MS-1467 in participants with relapsing multiple sclerosis using different treatment protocols to induce tolerance. Two open-label trials in adult participants with relapsing multiple sclerosis were conducted. Study 1 was a multicenter, phase 1b safety evaluation comparing intradermal (i.d.) (cohort 1) with subcutaneous (cohort 2) administration in 43 participants. Both cohorts received ATX-MS-1467 dosed at 25, 50, 100, 400, and 800 μg at 14-day intervals over 8 weeks, followed by 8 weeks with 4 additional 800-μg doses at 14-day intervals and 32 weeks off study medication. Study 2 was a phase 2a, multicenter, single-arm trial enrolling 37 participants. ATX-MS-1467 was titrated from 50 μg i.d. on day 1 to 200 μg on day 15 and 800 μg on day 29 followed by biweekly administration of 800 μg for 16 weeks and 16 weeks off study medication. Efficacy was evaluated on MRI parameters and clinical variables. Safety endpoints included treatment-emergent adverse events and injection-site reactions. In study 1, there was a significant decrease in new/persisting T1 gadolinium-enhanced (GdE) lesions in cohort 1 from baseline to week 16, returning to baseline values at week 48. In study 2, the number of T1 GdE lesions were significantly reduced on treatment and remained reduced at study completion. Safety results were unremarkable in both studies. Relatively slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions and a sustained effect post treatment. Further trials of ATX-MS-1467 are warranted. This work provides Class IV evidence that for patients with relapsing multiple sclerosis, slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions. © 2018 American Academy of Neurology.

Clinical evaluation of XaraColl(®), a bupivacaine-collagen implant, for postoperative analgesia in two multicenter, randomized, double-blind, placebo-controlled pilot studies.

PubMed

Cusack, Susan L; Jaros, Mark; Kuss, Michael; Minkowitz, Harold S; Winkle, Peter; Hemsen, Lisa

2012-01-01

XaraColl(®), a collagen-based implant that delivers bupivacaine to the site of surgical trauma, is under development for postoperative analgesia. Because of differing patient attitudes to postoperative pain control and the inability to assess baseline pain, standard clinical methods for evaluating analgesic efficacy are compromised and justify application of novel integrated approaches. We conducted two independent, multicenter, double-blind, placebo-controlled studies in men undergoing unilateral inguinal hernioplasty by open laparotomy to evaluate the safety and efficacy of XaraColl at different doses (100 mg and 200 mg of bupivacaine hydrochloride; study 1 and 2, respectively). Enrolled patients (50 in study 1 and 53 in study 2) were randomized to receive active or placebo implants in a 1:1 ratio. Postoperative pain intensity and use of supplementary opioid medication were recorded through 72 hours. Safety was assessed through 30 days. The principal efficacy variables were the summed pain intensity (SPI), total use of opioid analgesia (TOpA), and an integrated endpoint (I-SPI-TOpA). Each variable was analyzed at 24, 48, and 72 hours after implantation. A pooled analysis of both studies was also performed retrospectively. Through 24 and 48 hours, XaraColl-treated patients experienced significantly less pain in study 1 (P < 0.001 and P = 0.012, respectively) whereas they took significantly less opioid analgesia in study 2 (P = 0.004 and P = 0.042, respectively). Over the same time intervals in the pooled analysis, treated patients experienced both significantly less pain (P < 0.001 and P = 0.006, respectively) and took significantly less opioid analgesia (P = 0.001 and P = 0.024, respectively). The I-SPI-TOpA endpoint that combined both SPI and TOpA demonstrated a significant treatment effect through 72 hours in the pooled analysis (P = 0.021). XaraColl offers great potential for improving the management of postoperative pain and warrants further investigation in definitive clinical trials.

The WISTAH hand study: A prospective cohort study of distal upper extremity musculoskeletal disorders

PubMed Central

2012-01-01

Background Few prospective cohort studies of distal upper extremity musculoskeletal disorders have been performed. Past studies have provided somewhat conflicting evidence for occupational risk factors and have largely reported data without adjustments for many personal and psychosocial factors. Methods/design A multi-center prospective cohort study was incepted to quantify risk factors for distal upper extremity musculoskeletal disorders and potentially develop improved methods for analyzing jobs. Disorders to analyze included carpal tunnel syndrome, lateral epicondylalgia, medial epicondylalgia, trigger digit, deQuervain’s stenosing tenosynovitis and other tendinoses. Workers have thus far been enrolled from 17 different employment settings in 3 diverse US states and performed widely varying work. At baseline, workers undergo laptop administered questionnaires, structured interviews, two standardized physical examinations and nerve conduction studies to ascertain demographic, medical history, psychosocial factors and current musculoskeletal disorders. All workers’ jobs are individually measured for physical factors and are videotaped. Workers are followed monthly for the development of musculoskeletal disorders. Repeat nerve conduction studies are performed for those with symptoms of tingling and numbness in the prior six months. Changes in jobs necessitate re-measure and re-videotaping of job physical factors. Case definitions have been established. Point prevalence of carpal tunnel syndrome is a combination of paraesthesias in at least two median nerve-served digits plus an abnormal nerve conduction study at baseline. The lifetime cumulative incidence of carpal tunnel syndrome will also include those with a past history of carpal tunnel syndrome. Incident cases will exclude those with either a past history or prevalent cases at baseline. Statistical methods planned include survival analyses and logistic regression. Discussion A prospective cohort study of distal upper extremity musculoskeletal disorders is underway and has successfully enrolled over 1,000 workers to date. PMID:22672216

The WISTAH hand study: a prospective cohort study of distal upper extremity musculoskeletal disorders.

PubMed

Garg, Arun; Hegmann, Kurt T; Wertsch, Jacqueline J; Kapellusch, Jay; Thiese, Matthew S; Bloswick, Donald; Merryweather, Andrew; Sesek, Richard; Deckow-Schaefer, Gwen; Foster, James; Wood, Eric; Kendall, Richard; Sheng, Xiaoming; Holubkov, Richard

2012-06-06

Few prospective cohort studies of distal upper extremity musculoskeletal disorders have been performed. Past studies have provided somewhat conflicting evidence for occupational risk factors and have largely reported data without adjustments for many personal and psychosocial factors. A multi-center prospective cohort study was incepted to quantify risk factors for distal upper extremity musculoskeletal disorders and potentially develop improved methods for analyzing jobs. Disorders to analyze included carpal tunnel syndrome, lateral epicondylalgia, medial epicondylalgia, trigger digit, deQuervain's stenosing tenosynovitis and other tendinoses. Workers have thus far been enrolled from 17 different employment settings in 3 diverse US states and performed widely varying work. At baseline, workers undergo laptop administered questionnaires, structured interviews, two standardized physical examinations and nerve conduction studies to ascertain demographic, medical history, psychosocial factors and current musculoskeletal disorders. All workers' jobs are individually measured for physical factors and are videotaped. Workers are followed monthly for the development of musculoskeletal disorders. Repeat nerve conduction studies are performed for those with symptoms of tingling and numbness in the prior six months. Changes in jobs necessitate re-measure and re-videotaping of job physical factors. Case definitions have been established. Point prevalence of carpal tunnel syndrome is a combination of paraesthesias in at least two median nerve-served digits plus an abnormal nerve conduction study at baseline. The lifetime cumulative incidence of carpal tunnel syndrome will also include those with a past history of carpal tunnel syndrome. Incident cases will exclude those with either a past history or prevalent cases at baseline. Statistical methods planned include survival analyses and logistic regression. A prospective cohort study of distal upper extremity musculoskeletal disorders is underway and has successfully enrolled over 1,000 workers to date.

The evaluation of a new apheresis device for automated red blood cell exchange procedures in patients with sickle cell disease.

PubMed

Quirolo, Keith; Bertolone, Salvatore; Hassell, Kathryn; Howard, Thomas; King, Karen E; Rhodes, Diane K; Bill, Jerry

2015-04-01

The Spectra Optia apheresis system (SO), a blood component separator, can be used to perform red blood cell exchange (RBCX) procedures for the transfusion management of sickle cell disease (SCD) in adults and children. This study was designed to evaluate the performance of the SO RBCX protocols (exchange and depletion/exchange) in patients with SCD. Patients with SCD and a need for an RBCX procedure as part of a chronic program or as a single procedure were enrolled in this multicenter, single-arm, open-label study. The primary goal of the study was to confirm that the predicted percentage of the patient's original RBCs remaining at the end of the procedure (FCRp) reflects the actual cell fraction remaining, as measured by %HbS (FCRa). Secondary endpoints included ability of the SO to achieve the desired final hematocrit (Hct) and device-related serious adverse events (SAEs). Seventy-two patients 12 years of age or older were enrolled in the study; 60 were evaluable. The ratio of FCRa to FCRp after the RBCX procedure was 0.90, well within the prespecified range of 0.75 to 1.25. The SO was able to achieve the desired final Hct in the evaluable population. The safety profile was favorable, and no patients had an SAE or unexpected adverse device effect or withdrew from the procedure or treatment due to an adverse event. The SO performed effectively and safely for both the RBCX procedure and the RBCX depletion/exchange procedure. © 2014 AABB.

Improving the antidepressant efficacy of transcranial magnetic stimulation: Maximizing the number of stimulations and treatment location in treatment resistant depression

PubMed Central

McDonald, William M.; Durkalski, Valerie; Ball, Edward R.; Holtzheimer, Paul E.; Pavlicova, Martina; Lisanby, Sarah H.; Avery, David; Anderson, Berry S.; Nahas, Ziad; Zarkowski, Paul; Sackeim, Harold A.; George, Mark S.

2015-01-01

Objective To assess the efficacy of increasing the number of fast left repetitive transcranial magnetic stimulations (rTMS) (10 Hz @ 120% of motor threshold (MT) over the left dorsolateral prefrontal cortex (DLPFC)) needed to achieve remission in treatment resistant depression (TRD). And, to determine if patients who do not remit to fast left will remit using slow right rTMS (1 Hz @ 120% MT over the right DLPFC). Method Patients were part of a multicenter sham controlled trial investigating the efficacy of fast left rTMS 1. Patients who failed to meet minimal response criteria in the sham controlled study could enroll in this open fast left rTMS study for an additional 3- 6 weeks. Patients who failed to remit to fast left could switch to slow right rTMS for up to four additional weeks. The final outcome measure was remission, defined as a HAM-D score of ≤ 3 or two consecutive HAM-D scores less than 10. Results Forty-three of 141 (30.5%) patients who enrolled in the open phase study eventually met criteria for remission. Patients who remitted during fast left treatment received a mean of 26 active treatments (90,000 pulses). 26% of patients who failed fast left remitted during slow right treatment. Conclusion The total number of rTMS stimulations needed to achieve remission in TRD may be higher than is used in most studies. TRD patients who do not respond to fast left rTMS may remit to slow right rTMS or additional rTMS stimulations. PMID:21898711

Persistent lipid abnormalities in patients treated with statins: Portuguese results of the Dyslipidemia International Study (DYSIS).

PubMed

da Silva, P Marques; Cardoso, S Massano

2011-01-01

Cardiovascular disease (CVD) is the leading cause of death and one of the most important causes of morbidity in Western societies. Dyslipidemia is an important risk factor for CVD and effective treatment significantly reduces cardiovascular risk. To evaluate the prevalence and type of persistent lipid abnormalities in patients treated with statins. The Dyslipidemia International Study (DYSIS) was a multicenter, epidemiologic cross-sectional study conducted in 12 European countries and Canada. Patients > or = 45 years old, treated with statins for at least three months during the enrolment period from April 2008 to February 2009, were sequentially enrolled. This study presents the results for the Portuguese population. In Portugal, 916 patients were recruited in 125 centers; mean age was 64.1 +/- 9.9 years and 47.1% were women. Most patients (66.7%) presented high cardiovascular risk. The most frequently used statin was simvastatin (55.9%; dose 21.3 +/- 6.2 mg/day) and only 15.3% of the patients were simultaneously taking other lipid-lowering agents. In most patients, LDL (62.9%; n = 883) and total cholesterol (68%; n = 883) were not at the target levels recommended by the European Society of Cardiology (ESC). It was also found that 22% of patients presented lower HDL values than those recommended and that 39% presented high triglyceride levels. LDL outside the target range was the most common abnormality, both when assessed separately and when combined with low HDL and high triglycerides. The number of patients with lipid abnormalities was very significant, especially for LDL, considering that all were under statin therapy.

Prognostic study of cardiac events in Japanese high risk hemodialysis patients using I-BMIPP-SPECT: B-SAFE study design.

PubMed

Hasebe, Naoyuki; Moroi, Masao; Nishimura, Masato; Hara, Kazuhiro; Hase, Hiroki; Hashimoto, Akiyoshi; Kumita, Shinichiro; Haze, Kazuo; Momose, Mitsuru; Nagai, Yoji; Sugimoto, Tokuichiro; Kusano, Eiji; Akiba, Takashi; Nakata, Tomoaki; Nishimura, Tsunehiko; Tamaki, Nagara; Kikuchi, Kenjiro

2008-12-01

Cardiovascular disease is the leading cause of morbidity and mortality in patients undergoing hemodialysis. Such patients frequently develop complications such as asymptomatic coronary artery disease (CAD). Accordingly, CAD must ideally be diagnosed at an early stage to improve prognosis. Although myocardial perfusion single photon emission computed tomography (SPECT) is valuable for diagnosing CAD, the stress test is not always applicable to patients on hemodialysis. Thus, we proposed a multicenter, prospective cohort study called "B-SAFE" to investigate the applicability of resting (123)I-labeled beta-methyl-iodophenylpentadecanoic acid ((123)I-BMIPP)-SPECT will be used to diagnose cardiac disease and evaluate the prognosis of hemodialysis patients by imaging myocardial fatty acid metabolism. B-SAFE began enrolling patients from June 2006 at 48 facilities. We performed (123)I-BMIPP-SPECT on 702 hemodialysis patients with risk factors for CAD until 30 November 2007 and plan to follow up for three years. The primary endpoints will be cardiac death and sudden death. This study should end in 2010.

Stakeholders' views on data sharing in multicenter studies.

PubMed

Mazor, Kathleen M; Richards, Allison; Gallagher, Mia; Arterburn, David E; Raebel, Marsha A; Nowell, W Benjamin; Curtis, Jeffrey R; Paolino, Andrea R; Toh, Sengwee

2017-09-01

To understand stakeholders' views on data sharing in multicenter comparative effectiveness research studies and the value of privacy-protecting methods. Semistructured interviews with five US stakeholder groups. We completed 11 interviews, involving patients (n = 15), researchers (n = 10), Institutional Review Board and regulatory staff (n = 3), multicenter research governance experts (n = 2) and healthcare system leaders (n = 4). Perceptions of the benefits and value of research were the strongest influences toward data sharing; cost and security risks were primary influences against sharing. Privacy-protecting methods that share summary-level data were acknowledged as being appealing, but there were concerns about increased cost and potential loss of research validity. Stakeholders were open to data sharing in multicenter studies that offer value and minimize security risks.

Interlaboratory quality control of total HIV-1 DNA load measurement for multicenter reservoir studies.

PubMed

Gantner, Pierre; Mélard, Adeline; Damond, Florence; Delaugerre, Constance; Dina, Julia; Gueudin, Marie; Maillard, Anne; Sauné, Karine; Rodallec, Audrey; Tuaillon, Edouard; Plantier, Jean-Christophe; Rouzioux, Christine; Avettand-Fenoel, Véronique

2017-11-01

Viral reservoirs represent an important barrier to HIV cure. Accurate markers of HIV reservoirs are needed to develop multicenter studies. The aim of this multicenter quality control (QC) was to evaluate the inter-laboratory reproducibility of total HIV-1-DNA quantification. Ten laboratories of the ANRS-AC11 working group participated by quantifying HIV-DNA with a real-time qPCR assay (Biocentric) in four samples (QCMD). Good reproducibility was found between laboratories (standard deviation ≤ 0.2 log 10 copies/10 6 PBMC) for the three positive QC that were correctly classified by each laboratory (QC1

A standardized stepwise drug treatment algorithm for depression reduces direct treatment costs in depressed inpatients - Results from the German Algorithm Project (GAP3).

PubMed

Ricken, Roland; Wiethoff, Katja; Reinhold, Thomas; Stamm, Thomas J; Baghai, Thomas C; Fisher, Robert; Seemüller, Florian; Brieger, Peter; Cordes, Joachim; Laux, Gerd; Hauth, Iris; Möller, Hans-Jürgen; Heinz, Andreas; Bauer, Michael; Adli, Mazda

2018-03-01

In a previous single center study we found that a standardized drug treatment algorithm (ALGO) was more cost effective than treatment as usual (TAU) for inpatients with major depression. This report aimed to determine whether this promising initial finding could be replicated in a multicenter study. Treatment costs were calculated for two time periods: the study period (from enrolment to exit from study) and time in hospital (from enrolment to hospital discharge) based on daily hospital charges. Cost per remitted patient during the study period was considered as primary outcome. 266 patients received ALGO and 84 received TAU. For the study period, ALGO costs were significantly lower than TAU (ALGO: 7 848 ± 6 065 €; TAU: 10 033 ± 7 696 €; p = 0.04). For time in hospital, costs were not different (ALGO: 14 734 ± 8 329 €; TAU: 14 244 ± 8 419 €; p = 0.617). Remission rates did not differ for the study period (ALGO: 57.9%, TAU: 50.0%; p=0.201). Remission rates were greater in ALGO (83.3%) than TAU (66.2%) for time in hospital (p = 0.002). Cost per remission was lower in ALGO (13 554 ± 10 476 €) than TAU (20 066 ± 15 391 €) for the study period (p < 0.001) and for time in hospital (ALGO: 17 582 ± 9 939 €; TAU: 21 516 ± 12 718 €; p = 0.036). Indirect costs were not assessed. Different dropout rates in TAU and ALGO complicated interpretation. Treatment algorithms enhance the cost effectiveness of the care of depressed inpatients, which replicates our prior results in an independent sample. Copyright © 2017. Published by Elsevier B.V.

Challenges of post-authorization safety studies: Lessons learned and results of a French study of fentanyl buccal tablet.

PubMed

Gavrielov-Yusim, Natalie; Bidollari, Ilda; Kaplan, Sigal; Bartov, Netta

2018-05-01

Recruiting and retaining participants in real-world studies that collect primary data are challenging. This article illustrates these challenges using a post-authorization safety study (PASS) to assess adverse events (AEs) experienced with fentanyl buccal tablet (FBT) over 3 months of treatment. This was an observational, prospective, multicenter study in France conducted over 1 year. The study employed primary data collection in FBT-treated patients and their treating physicians via a site qualification questionnaire and patient log completed by physicians and a questionnaire and pain diary completed by patients. Strategies to increase participation included reminders, newsletters, frequent follow-up telephone calls, and reducing the extent of data collected. Of the 1118 physicians contacted who returned the participation form or responded to a telephone call, only 128 expressed willingness to participate. Key reasons for non-participation were lack of interest (69.7%) and FBT not being used in practice by the contacted physician (25.1%). Overall, 224 patients were screened by 31 physicians, and 97 were enrolled. Key reasons for patient non-inclusion were unwillingness or inability to complete the patient AE diary or questionnaire (40.9% [52/127]) and patients' decision (33.9% [43/127]). Despite efforts to increase participation, enrollment in this study was low. Recruitment and retention methods are limited in their capacity to optimally execute a primary data collection in a PASS. For a PASS to provide reliable and valid information on medication use, involvement from health care agencies, regulators, and pharmaceutical companies is needed to establish their importance, drive study participation, and reduce patient withdrawal. Copyright © 2017 John Wiley & Sons, Ltd.

Fecal containment in bedridden patients: economic impact of 2 commercial bowel catheter systems.

PubMed

Kowal-Vem, Areta; Poulakidas, Stathis; Barnett, Barbara; Conway, Deborah; Culver, Daniel; Ferrari, Michelle; Potenza, Bruce; Koenig, Michael; Mah, John; Majewski, Mary; Morris, Linda; Powers, Jan; Stokes, Elizabeth; Tan, Michael; Salstrom, Sara-Jane; Zaletel, Cindy; Ambutas, Shirley; Casey, Kathleen; Stein, Jayne; DeSane, Mary; Berry, Kathy; Konz, Elizabeth C; Riemer, Michael R; Cullum, Malford E

2009-05-01

Fecal contamination is a major challenge in patients in acute/critical care settings that is associated with increased cost of care and supplies and with development of pressure ulcers, incontinence dermatitis, skin and soft tissue infections, and urinary tract infections. To assess the economic impact of fecal containment in bedridden patients using 2 different indwelling bowel catheters and to compare infection rates between groups. A multicenter, observational study was done at 12 US sites (7 that use catheter A, 5 that use catheter B). Patients were followed from insertion of an indwelling bowel catheter system until the patient left the acute/critical care unit or until 29 days after enrollment, whichever came first. Demographic data, frequency of bedding/dressing changes, incidence of infection, and Braden scores (risk of pressure ulcers) were recorded. The study included 146 bedridden patients (76 with catheter A, 70 with catheter B) who had similar Braden scores at enrollment. The rate of bedding/dressing changes per day differed significantly between groups (1.20 for catheter A vs 1.71 for catheter B; P = .004). According to a formula that accounted for personnel resources and laundry cycle costs, catheter A cost $13.94 less per patient per day to use than did catheter B. Catheter A was less likely than was catheter B to be removed during the observational period (P = .03). Observed infection rates were low. Catheter A may be more cost-effective than catheter B because it requires fewer unscheduled linen changes per patient day.

Human herpesvirus 8 and human herpesvirus 2 infections in prison population.

PubMed

Sarmati, L; Babudieri, S; Longo, B; Starnini, G; Carbonara, S; Monarca, R; Buonomini, A R; Dori, L; Rezza, G; Andreoni, M

2007-02-01

Incarcerated persons have high rates of infectious diseases. Few data on the prevalence of sexually transmitted diseases in prisoners are available. This multi-center cross-sectional study enrolled 973 inmates from eight Italian prisons. Demographic and behavioral data were collected using an anonymous standardized questionnaire and antibodies to HIV, HCV, HBV, HSV-2, and HHV-8 were detected in a blood sample obtained from each person at the time of the enrollment in the study. Two hundred and two out of the 973 subjects (20.7%) had antibodies against HHV-8. HHV-8-seropositive subjects were more likely to be older than 30 years with a higher educational level. HHV-8 infection was associated significantly with HBV (P < 0.001) and HSV-2 (P = 0.004) seropositivity and with previous imprisonments. Multivariate analysis showed that HHV-8 infection in Italian inmates was associated with HBV (P < 0.001) and HSV-2 (P = 0.002) seropositivity otherwise among foreigners inmates HHV-8 was significantly associated with HBV infection (P = 0.05). One hundred and eighty-six (21.2%) prisoners had anti-HSV-2 antibodies. At multivariate analysis HSV-2-positivity was significantly associated with HIV (P < 0.001) and HHV-8 infections (P = 0.003), whereas it was inversely associated with HCV infection (0.004). A relatively high seroprevalence of HHV-8 and HSV-2 among Italian prison inmates was found. The association of HHV-8 and HSV-2 infections suggest sexual transmission of these viruses among Italian prison inmates.

Suicidal risk among patients enrolled in methadone maintenance treatment: HCV status and implications for suicide prevention (ANRS Methaville).

PubMed

Michel, Laurent; Lions, Caroline; Maradan, Gwenaelle; Mora, Marion; Marcellin, Fabienne; Morel, Alain; Spire, Bruno; Roux, Perrine; Carrieri, Patrizia M

2015-10-01

Suicide is a critical issue among opioid users. The aim of this study was to assess the relationship between HCV status and suicidal risk in patients receiving methadone treatment. We used data from Methaville, a multicenter, pragmatic randomized trial designed to evaluate the feasibility of methadone induction in primary care compared with induction in specialized centers. Suicidal risk was assessed at enrollment and after one year of methadone treatment using the suicidality module in the MINI International Neuropsychiatric Interview. Socio-demographic characteristics, drug and alcohol consumption, behavioral and personality factors, history of drug use and health indicators were also assessed. A total of 195 individuals were enrolled from January 2009 to December 2010. Suicidal risk assessment was available at month 0 (M0) and M12 for 159 (72%) and 118 (73%) individuals, respectively. Forty-four (28%) were at risk of suicide at M0 and 17 (14%) at M12 (p=0.004). One patient attempted suicide by overdose during the one-year follow-up. The following three factors were associated with suicidal risk: hepatitis C virus (HCV) positive status (OR [95%CI]=17.25 [1.14-161.07]; p=0.04), receiving food assistance (OR [95%CI]=0.05 [0.00-1.05]; p=0.05) and a higher number of health problems (OR [95%CI]=1.24 [1.08-1.44]; p=0.003). Special attention should be given to HCV-positive patients through suicidal risk prevention strategies and routine suicide assessment as part of a comprehensive approach to prevention and care for opioid users. Our results represent a new and powerful argument for the expansion of access to HCV treatment to drug users with chronic infection. Copyright © 2015 Elsevier Inc. All rights reserved.

Plasma Septin9 versus fecal immunochemical testing for colorectal cancer screening: a prospective multicenter study.

PubMed

Johnson, David A; Barclay, Robert L; Mergener, Klaus; Weiss, Gunter; König, Thomas; Beck, Jürgen; Potter, Nicholas T

2014-01-01

Screening improves outcomes related to colorectal cancer (CRC); however, suboptimal participation for available screening tests limits the full benefits of screening. Non-invasive screening using a blood based assay may potentially help reach the unscreened population. To compare the performance of a new Septin9 DNA methylation based blood test with a fecal immunochemical test (FIT) for CRC screening. In this trial, fecal and blood samples were obtained from enrolled patients. To compare test sensitivity for CRC, patients with screening identified colorectal cancer (n = 102) were enrolled and provided samples prior to surgery. To compare test specificity patients were enrolled prospectively (n = 199) and provided samples prior to bowel preparation for screening colonoscopy. Plasma and fecal samples were analyzed using the Epi proColon and OC Fit-Check tests respectively. For all samples, sensitivity for CRC detection was 73.3% (95% CI 63.9-80.9%) and 68.0% (95% CI 58.2-76.5%) for Septin9 and FIT, respectively. Specificity of the Epi proColon test was 81.5% (95% CI 75.5-86.3%) compared with 97.4% (95% CI 94.1-98.9%) for FIT. For paired samples, the sensitivity of the Epi proColon test (72.2% -95% CI 62.5-80.1%) was shown to be statistically non-inferior to FIT (68.0%-95% CI 58.2-76.5%). When test results for Epi proColon and FIT were combined, CRC detection was 88.7% at a specificity of 78.8%. At a sensitivity of 72%, the Epi proColon test is non- inferior to FIT for CRC detection, although at a lower specificity. With negative predictive values of 99.8%, both methods are identical in confirming the absence of CRC. ClinicalTrials.gov NCT01580540.

The landscape of precision cancer medicine clinical trials in the United States.

PubMed

Roper, Nitin; Stensland, Kristian D; Hendricks, Ryan; Galsky, Matthew D

2015-05-01

Advances in tumor biology and multiplex genomic analysis have ushered in the era of precision cancer medicine. Little is currently known, however, about the landscape of prospective "precision cancer medicine" clinical trials in the U.S. We identified all adult interventional cancer trials registered on ClinicalTrials.gov between September 2005 and May 2013. Trials were classified as "precision cancer medicine" if a genomic alteration in a predefined set of 88 genes was required for enrollment. Baseline characteristics were ascertained for each trial. Of the initial 18,797 trials identified, 9094 (48%) were eligible for inclusion: 684 (8%) were classified as precision cancer medicine trials and 8410 (92%) were non-precision cancer medicine trials. Compared with non-precision cancer medicine trials, precision cancer medicine trials were significantly more likely to be phase II [RR 1.19 (1.10-1.29), p<0.001], multi-center [RR 1.18 (1.11-1.26), p<0.001], open-label [RR 1.04 (1.02-1.07), p=0.005] and involve breast [RR 4.03 (3.49-4.52), p<0.001], colorectal [RR 1.62 (1.22-2.14), p=0.002] and skin [RR 1.98 (1.55-2.54), p<0.001] cancers. Precision medicine trials required 38 unique genomic alterations for enrollment. The proportion of precision cancer medicine trials compared to the total number of trials increased from 3% in 2006 to 16% in 2013. The proportion of adult cancer clinical trials in the U.S. requiring a genomic alteration for enrollment has increased substantially over the past several years. However, such trials still represent a small minority of studies performed within the cancer clinical trials enterprise and include a small subset of putatively "actionable" alterations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Decompression Surgery Alone Versus Decompression Plus Fusion in Symptomatic Lumbar Spinal Stenosis: A Swiss Prospective Multicenter Cohort Study With 3 Years of Follow-up.

PubMed

Ulrich, Nils H; Burgstaller, Jakob M; Pichierri, Giuseppe; Wertli, Maria M; Farshad, Mazda; Porchet, François; Steurer, Johann; Held, Ulrike

2017-09-15

Retrospective analysis of a prospective, multicenter cohort study. To estimate the added effect of surgical fusion as compared to decompression surgery alone in symptomatic lumbar spinal stenosis patients with spondylolisthesis. The optimal surgical management of lumbar spinal stenosis patients with spondylolisthesis remains controversial. Patients of the Lumbar Stenosis Outcome Study with confirmed DLSS and spondylolisthesis were enrolled in this study. The outcomes of this study were Spinal Stenosis Measure (SSM) symptoms (score range 1-5, best-worst) and function (1-4) over time, measured at baseline, 6, 12, 24, and 36 months follow-up. In order to quantify the effect of fusion surgery as compared to decompression alone and number of decompressed levels, we used mixed effects models and accounted for the repeated observations in main outcomes (SSM symptoms and SSM function) over time. In addition to individual patients' random effects, we also fitted random slopes for follow-up time points and compared these two approaches with Akaike's Information Criterion and the chi-square test. Confounders were adjusted with fixed effects for age, sex, body mass index, diabetes, Cumulative Illness Rating Scale musculoskeletal disorders, and duration of symptoms. One hundred thirty-one patients undergoing decompression surgery alone (n = 85) or decompression with fusion surgery (n = 46) were included in this study. In the multiple mixed effects model the adjusted effect of fusion compared with decompression alone surgery on SSM symptoms was 0.06 (95% confidence interval: -0.16-0.27) and -0.07 (95% confidence interval: -0.25-0.10) on SSM function, respectively. Among the patients with degenerative lumbar spinal stenosis and spondylolisthesis our study confirms that in the two groups, decompression alone and decompression with fusion, patients distinctively benefited from surgical treatment. When adjusted for confounders, fusion surgery was not associated with a more favorable outcome in both SSM scores as compared to decompression alone surgery. 3.

Randomized, Double-Blind, Multicenter Phase 2 Study Comparing the Efficacy and Safety of Oral Solithromycin (CEM-101) to Those of Oral Levofloxacin in the Treatment of Patients with Community-Acquired Bacterial Pneumonia

PubMed Central

Oldach, David; Clark, Kay; Schranz, Jennifer; Das, Anita; Craft, J Carl; Scott, Drusilla; Jamieson, Brian D.

2013-01-01

Solithromycin, a new macrolide, and the first fluoroketolide in clinical development, with activity against macrolide-resistant bacteria, was tested in 132 patients with moderate to moderately severe community-acquired bacterial pneumonia (CABP) in a multicenter, double-blind, randomized phase 2 study. Patients were enrolled and randomized (1:1) to either 800 mg solithromycin orally (PO) on day 1, followed by 400 mg PO daily on days 2 to 5, or 750 mg levofloxacin PO daily on days 1 to 5. Efficacy outcome rates of clinical success at the test-of-cure visit 4 to 11 days after the last dose of study drug were comparable in the intent-to-treat (ITT) (84.6% for solithromycin versus 86.6% for levofloxacin) and microbiological-intent-to-treat (micro-ITT) (77.8% for solithromycin versus 71.4% for levofloxacin) populations. Early response success rates at day 3, defined as improvement in at least two cardinal symptoms of pneumonia, were also comparable (72.3% for solithromycin versus 71.6% for levofloxacin). More patients treated with levofloxacin than with solithromycin experienced treatment-emergent adverse events (TEAEs) during the study (45.6% versus 29.7%). The majority of TEAEs were mild or moderate gastrointestinal symptoms and included nausea (1.6% for solithromycin; 10.3% for levofloxacin), diarrhea (7.8% for solithromycin; 5.9% for levofloxacin), and vomiting (0% for solithromycin; 4.4% for levofloxacin). Six patients, all of whom received levofloxacin, discontinued the study drug due to an adverse event. Solithromycin demonstrated comparable efficacy and favorable safety relative to levofloxacin. These findings support a phase 3 study of solithromycin for the treatment of CABP. (This study has been registered at ClinicalTrials.gov under registration no. NCT01168713.) PMID:23507282

Randomized, double-blind, multicenter phase 2 study comparing the efficacy and safety of oral solithromycin (CEM-101) to those of oral levofloxacin in the treatment of patients with community-acquired bacterial pneumonia.

PubMed

Oldach, David; Clark, Kay; Schranz, Jennifer; Das, Anita; Craft, J Carl; Scott, Drusilla; Jamieson, Brian D; Fernandes, Prabhavathi

2013-06-01

Solithromycin, a new macrolide, and the first fluoroketolide in clinical development, with activity against macrolide-resistant bacteria, was tested in 132 patients with moderate to moderately severe community-acquired bacterial pneumonia (CABP) in a multicenter, double-blind, randomized phase 2 study. Patients were enrolled and randomized (1:1) to either 800 mg solithromycin orally (PO) on day 1, followed by 400 mg PO daily on days 2 to 5, or 750 mg levofloxacin PO daily on days 1 to 5. Efficacy outcome rates of clinical success at the test-of-cure visit 4 to 11 days after the last dose of study drug were comparable in the intent-to-treat (ITT) (84.6% for solithromycin versus 86.6% for levofloxacin) and microbiological-intent-to-treat (micro-ITT) (77.8% for solithromycin versus 71.4% for levofloxacin) populations. Early response success rates at day 3, defined as improvement in at least two cardinal symptoms of pneumonia, were also comparable (72.3% for solithromycin versus 71.6% for levofloxacin). More patients treated with levofloxacin than with solithromycin experienced treatment-emergent adverse events (TEAEs) during the study (45.6% versus 29.7%). The majority of TEAEs were mild or moderate gastrointestinal symptoms and included nausea (1.6% for solithromycin; 10.3% for levofloxacin), diarrhea (7.8% for solithromycin; 5.9% for levofloxacin), and vomiting (0% for solithromycin; 4.4% for levofloxacin). Six patients, all of whom received levofloxacin, discontinued the study drug due to an adverse event. Solithromycin demonstrated comparable efficacy and favorable safety relative to levofloxacin. These findings support a phase 3 study of solithromycin for the treatment of CABP. (This study has been registered at ClinicalTrials.gov under registration no. NCT01168713.).

Multicenter Trial of the VenaTech Convertible Vena Cava Filter.

PubMed

Hohenwalter, Eric J; Stone, James R; O'Moore, Paul V; Smith, Steven J; Selby, J Bayne; Lewandowski, Robert J; Samuels, Shaun; Kiproff, Paul M; Trost, David W; Madoff, David C; Handel, Jeremy; Gandras, Eric J; Vlahos, Athanasios; Rilling, William S

2017-10-01

To demonstrate rates of successful filter conversion and 6-month major device-related adverse events in subjects with converted caval filters. An investigational device exemption multicenter, prospective, single-arm study was performed at 11 sites enrolling 149 patients. The VenaTech Convertible Vena Cava Filter (B. Braun Interventional Systems, Inc, Bethlehem, Pennsylvania) was implanted in 149 patients with venous thromboembolism and contraindication to or failure of anticoagulation (n = 119), with high-risk trauma (n = 14), and for surgical prophylaxis (n = 16). When the patient was no longer at risk for pulmonary embolism as determined by clinical assessment, an attempt at filter conversion was made. Follow-up of converted patients (n = 93) was conducted at 30 days, 3 months, and 6 months after conversion. Patients who did not undergo a conversion attempt (n = 53) had follow-up at 6 months after implant. All implants were successful. One 7-day migration to the right atrium required surgical removal. Technical success rate for filter conversion was 92.7% (89/96). Mean time from placement to conversion was 130.7 days (range, 15-391 d). No major conversion-related events were reported. The mean conversion procedure time was 30.7 minutes (range, 7-135 min). There were 89 converted and 32 unconverted patients who completed 6-month follow-up with no delayed complications. The VenaTech Convertible filter has a high conversion rate and low 6-month device-related adverse event rate. Further studies are necessary to determine long-term safety and efficacy in both converted and unconverted patients. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

Early identification of patients at risk of acute lung injury: evaluation of lung injury prediction score in a multicenter cohort study.

PubMed

Gajic, Ognjen; Dabbagh, Ousama; Park, Pauline K; Adesanya, Adebola; Chang, Steven Y; Hou, Peter; Anderson, Harry; Hoth, J Jason; Mikkelsen, Mark E; Gentile, Nina T; Gong, Michelle N; Talmor, Daniel; Bajwa, Ednan; Watkins, Timothy R; Festic, Emir; Yilmaz, Murat; Iscimen, Remzi; Kaufman, David A; Esper, Annette M; Sadikot, Ruxana; Douglas, Ivor; Sevransky, Jonathan; Malinchoc, Michael

2011-02-15

Accurate, early identification of patients at risk for developing acute lung injury (ALI) provides the opportunity to test and implement secondary prevention strategies. To determine the frequency and outcome of ALI development in patients at risk and validate a lung injury prediction score (LIPS). In this prospective multicenter observational cohort study, predisposing conditions and risk modifiers predictive of ALI development were identified from routine clinical data available during initial evaluation. The discrimination of the model was assessed with area under receiver operating curve (AUC). The risk of death from ALI was determined after adjustment for severity of illness and predisposing conditions. Twenty-two hospitals enrolled 5,584 patients at risk. ALI developed a median of 2 (interquartile range 1-4) days after initial evaluation in 377 (6.8%; 148 ALI-only, 229 adult respiratory distress syndrome) patients. The frequency of ALI varied according to predisposing conditions (from 3% in pancreatitis to 26% after smoke inhalation). LIPS discriminated patients who developed ALI from those who did not with an AUC of 0.80 (95% confidence interval, 0.78-0.82). When adjusted for severity of illness and predisposing conditions, development of ALI increased the risk of in-hospital death (odds ratio, 4.1; 95% confidence interval, 2.9-5.7). ALI occurrence varies according to predisposing conditions and carries an independently poor prognosis. Using routinely available clinical data, LIPS identifies patients at high risk for ALI early in the course of their illness. This model will alert clinicians about the risk of ALI and facilitate testing and implementation of ALI prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT00889772).

One-year results of a prospective randomized, evaluator-blinded, multicenter study comparing TVT and TVT Secur.

PubMed

Andrada Hamer, Maria; Larsson, Per-Göran; Teleman, Pia; Bergqvist, Christina Eten; Persson, Jan

2013-02-01

The aim of this prospective randomized multicenter study was to compare retropubic tension-free vaginal tape (TVT) with TVT Secur in terms of efficacy and safety. We set out to enrol 280 stress urinary incontinent (SUI) women with a half-time interim analysis of short-term cure and adverse events. The short-term results have previously been published. Of the 133 randomized women, 125 underwent surgery, and 121 (TVT n = 61, TVT Secur n = 60) were available for follow-up 1 year postsurgery. No significant differences were found between groups regarding demographics or incontinence grade. One year after surgery, both subjective and objective cure rates were significantly lower for TVT Secur than for TVT (subjective cure: TVT 98 %, TVT Secur 80 %, p = 0.03; objective cure: TVT 94 %, TVT Secur 71 % for cough test, p = 0.01; TVT 76 %, TVT Secur 58 % for pad test, p = 0.05 ). Three major complications occurred in the TVT Secur group: one tape erosion into the urethra, one tape inadvertently placed into the bladder, and one immediate postoperative bleeding due to injury to the corona mortis. No major complications occurred in the TVT group. No significant differences were found between groups regarding peroperative bleeding, hospital stay, urge symptoms, residual urinary volume, subjective bladder emptying problems, postoperative urinary tract infections, and minor complications. The TVT Secur group used more antimuscarine medication after surgery than the TVT group (p = 0.03). Median time for surgery was 13 and 22 min for TVT Secur and TVT, respectively (p < 0.0001). The TVT Secur procedure had significantly inferior subjective and objective cure rates compared with the retropubic TVT procedure. Three serious adverse events occurred in the TVT Secur group. We therefore discourage further use of TVT Secur.

Immediate provisionalization in the esthetic zone: 1-year interim results from a prospective single-cohort multicenter study evaluating 3.0-mm-diameter tapered implants.

PubMed

Kolinski, Martin; Hess, Pablo; Leziy, Sonia; Friberg, Bertil; Bellucci, Gionata; Trisciuoglio, Davide; Wagner, Wilfried; Moergel, Maximilian; Pozzi, Alessandro; Wiltfang, Jörg; Behrens, Eleonore; Zechner, Werner; Vasak, Christoph; Weigl, Paul

2018-07-01

The aim of this interim analysis of a 5-year prospective multicenter study is to evaluate clinical and radiological performance of immediately provisionalized 3.0-mm-diameter tapered implants. Patients needing implant rehabilitation of maxillary lateral incisors or mandibular lateral and central incisors were treated with 3.0-mm-diameter implants placed in extraction or healed sites and immediately provisionalized. Clinical and radiographic examinations were performed at implant insertion, 6 months thereafter, and are ongoing. Marginal bone levels and changes, complications, the papilla, plaque, and bleeding indices, and the pink esthetic score (PES) were evaluated at each follow-up visit. Of 112 enrolled patients, 77 patients (91 implants) met the inclusion criteria. Seventy-one patients with 82 implants completed the 1-year follow-up. Three implants failed yielding a CSR of 96.7%. All failures occurred within the first 3 months after implant insertion. Marginal bone level changes from insertion to 6 months was - 0.57 ± 1.30 mm (n = 75) and from insertion to 12 months - 0.25 ± 1.38 mm (n = 72). Fifteen non-serious complications were recorded. Papilla index score and PES improved at the 1-year follow-up. Plaque formation and bleeding-on-probing showed no statistically significant differences between the 6-month and the 1-year visit. This 1-year analysis demonstrated high survival, stable bone levels, and healthy soft tissue with 3.0-mm-diameter implants. Narrow diameter implants are a safe and predictable treatment option in patients with limited bone volume and/or limited interdental space and eligible for immediate loading protocols.

Transfusion Requirement in Burn Care Evaluation (TRIBE): A Multicenter Randomized Prospective Trial of Blood Transfusion in Major Burn Injury.

PubMed

Palmieri, Tina L; Holmes, James H; Arnoldo, Brett; Peck, Michael; Potenza, Bruce; Cochran, Amalia; King, Booker T; Dominic, William; Cartotto, Robert; Bhavsar, Dhaval; Kemalyan, Nathan; Tredget, Edward; Stapelberg, Francois; Mozingo, David; Friedman, Bruce; Greenhalgh, David G; Taylor, Sandra L; Pollock, Brad H

2017-10-01

Our objective was to compare outcomes of a restrictive to a liberal red cell transfusion strategy in 20% or more total body surface area (TBSA) burn patients. We hypothesized that the restrictive group would have less blood stream infection (BSI), organ dysfunction, and mortality. Patients with major burns have major (>1 blood volume) transfusion requirements. Studies suggest that a restrictive blood transfusion strategy is equivalent to a liberal strategy. However, major burn injury is precluded from these studies. The optimal transfusion strategy in major burn injury is thus needed but remains unknown. This prospective randomized multicenter trial block randomized patients to a restrictive (hemoglobin 7-8 g/dL) or liberal (hemoglobin 10-11 g/dL) transfusion strategy throughout hospitalization. Data collected included demographics, infections, transfusions, and outcomes. Eighteen burn centers enrolled 345 patients with 20% or more TBSA burn similar in age, TBSA burn, and inhalation injury. A total of 7054 units blood were transfused. The restrictive group received fewer blood transfusions: mean 20.3 ± 32.7 units, median = 8 (interquartile range: 3, 24) versus mean 31.8 ± 44.3 units, median = 16 (interquartile range: 7, 40) in the liberal group (P < 0.0001, Wilcoxon rank sum). BSI incidence, organ dysfunction, ventilator days, and time to wound healing (P > 0.05) were similar. In addition, there was no 30-day mortality difference: 9.5% restrictive versus 8.5% liberal (P = 0.892, χ test). A restrictive transfusion strategy halved blood product utilization. Although the restrictive strategy did not decrease BSI, mortality, or organ dysfunction in major burn injury, these outcomes were no worse than the liberal strategy (Clinicaltrials.gov identifier NCT01079247).

One-Year Outcomes After Minor Stroke or High-Risk Transient Ischemic Attack: Korean Multicenter Stroke Registry Analysis.

PubMed

Park, Hong-Kyun; Kim, Beom Joon; Han, Moon-Ku; Park, Jong-Moo; Kang, Kyusik; Lee, Soo Joo; Kim, Jae Guk; Cha, Jae-Kwan; Kim, Dae-Hyun; Nah, Hyun-Wook; Park, Tai Hwan; Park, Sang-Soon; Lee, Kyung Bok; Lee, Jun; Hong, Keun-Sik; Cho, Yong-Jin; Lee, Byung-Chul; Yu, Kyung-Ho; Oh, Mi-Sun; Kim, Joon-Tae; Choi, Kang-Ho; Kim, Dong-Eog; Ryu, Wi-Sun; Choi, Jay Chol; Johansson, Saga; Lee, Su Jin; Lee, Won Hee; Lee, Ji Sung; Lee, Juneyoung; Bae, Hee-Joon

2017-11-01

Patients with minor ischemic stroke or transient ischemic attack are at high risk of recurrent stroke and vascular events, which are potentially disabling or fatal. This study aimed to evaluate contemporary subsequent vascular event risk after minor ischemic stroke or transient ischemic attack in Korea. Patients with minor ischemic stroke or high-risk transient ischemic attack admitted within 7 days of symptom onset were identified from a Korean multicenter stroke registry database. We estimated 3-month and 1-year event rates of the primary outcome (composite of stroke recurrence, myocardial infarction, or all-cause death), stroke recurrence, a major vascular event (composite of stroke recurrence, myocardial infarction, or vascular death), and all-cause death and explored differences in clinical characteristics and event rates according to antithrombotic strategies at discharge. Of 9506 patients enrolled in this study, 93.8% underwent angiographic assessment and 72.7% underwent cardiac evaluations; 25.1% had symptomatic stenosis or occlusion of intracranial arteries. At discharge, 95.2% of patients received antithrombotics (antiplatelet polytherapy, 37.1%; anticoagulation, 15.3%) and 86.2% received statins. The 3-month cumulative event rate was 5.9% for the primary outcome, 4.3% for stroke recurrence, 4.6% for a major vascular event, and 2.0% for all-cause death. Corresponding values at 1 year were 9.3%, 6.1%, 6.7%, and 4.1%, respectively. Patients receiving nonaspirin antithrombotic strategies or no antithrombotic agent had higher baseline risk profiles and at least 1.5× higher event rates for clinical event outcomes than those with aspirin monotherapy. Contemporary secondary stroke prevention strategies based on thorough diagnostic evaluation may contribute to the low subsequent vascular event rates observed in real-world clinical practice in Korea. © 2017 American Heart Association, Inc.

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.

Efficacy and Safety of Radiofrequency Ablation for Benign Thyroid Nodules: A Prospective Multicenter Study

PubMed Central

Jung, So Lyung; Lee, Jeong Hyun; Shong, Young Kee; Sung, Jin Yong; Kim, Kyu Sun; Lee, Ducky; Kim, Ji-hoon; Baek, Seon Mi; Sim, Jung Suk; Na, Dong Gyu

2018-01-01

Objective To assess the efficacy and safety of thyroid radiofrequency (RF) ablation for benign thyroid nodules by trained radiologists according to a unified protocol in a multi-center study. Materials and Methods From 2010 to 2011, 345 nodules from 345 patients (M:F = 43:302; mean age ± SD = 46.0 ± 12.7 years, range = 15–79) who met eligibility criteria were enrolled from five institutions. At pre-ablation, the mean volume was 14.2 ± 13.2 mL (1.1–80.8 mL). For 12 months or longer after treatment, 276 lesions, consisting of 248 solid and 28 predominantly cystic nodules, were followed. All operators performed RF ablation with a cool-tip RF system and two standard techniques (a transisthmic approach and the moving-shot technique). Volume reduction at 12 months after RF ablation (the primary outcome), therapeutic success, improvement of symptoms as well as of cosmetic problems, and complications were evaluated. Multiple linear regression analysis was applied to identify factors that were independently predictive of volume reduction. Results The mean volume reduction at 12 months was 80.3% (n = 276) and at the 24-, 36-, 48-, and 60-month follow-ups 84.3% (n = 198), 89.2% (n = 128), 91.9% (n = 57), and 95.3% (n = 6), respectively. Our therapeutic success was 97.8%. Both mean symptom and cosmetic scores showed significant improvements (p < 0.001). The rate of major complications was 1.0% (3/276). Solidity and applied energy were independent factors that predicted volume reduction. Conclusion Radiofrequency ablation performed by trained radiologists from multiple institutions using a unified protocol and similar devices was effective and safe for treating benign thyroid nodules. PMID:29354014

Multicenter Evaluation of Octreotide as Secondary Prophylaxis in Patients With Left Ventricular Assist Devices and Gastrointestinal Bleeding.

PubMed

Shah, Keyur B; Gunda, Sampath; Emani, Sitaramesh; Kanwar, Manreet K; Uriel, Nir; Colombo, Paolo C; Uber, Patricia A; Sears, Melissa L; Chuang, Joyce; Farrar, David J; Brophy, Donald F; Smallfield, George B

2017-11-01

Gastrointestinal (GI) bleeding is one of the most common complications after continuous-flow left ventricular assist device implantation. More than one third of patients with incident bleed go on to develop recurrent GI bleeding. Octreotide, a somatostatin analog, is proposed to reduce the risk of recurrent GI bleeding in this population. This multicenter, retrospective analysis evaluated 51 continuous-flow left ventricular assist device patients who received secondary prophylaxis with octreotide after their index GI bleed from 2009 to 2015. All patients had a hospitalization for GI bleed and received octreotide after discharge. Patient demographics, medical and medication history, and clinical characteristics of patients who rebled after receiving octreotide were compared with non-rebleeders. These data were also compared with matched historical control patients previously enrolled in the HMII (HeartMate II) clinical trials, none of whom received octreotide, to provide a context for the bleeding rates. Twelve patients (24%) who received secondary octreotide prophylaxis developed another GI bleed, whereas 39 (76%) did not. There were similar intergroup demographics; however, significantly more bleeders had a previous GI bleeding history before left ventricular assist device placement (33% versus 5%; P =0.02) and greater frequency of angiodysplasia confirmed during endoscopy (58% versus 23%; P =0.03). Fewer patients in this study experienced a recurrent GI bleed compared with a matched historical control group that did not receive octreotide (24% versus 43%; P =0.04). Patients with continuous-flow left ventricular assist device receiving secondary prophylaxis with octreotide had a significantly lower GI bleed recurrence compared with historical controls not treated with octreotide. Additional prospective studies are needed to confirm these data. © 2017 American Heart Association, Inc.

1-Hz rTMS in the treatment of tinnitus: A sham-controlled, randomized multicenter trial.

PubMed

Landgrebe, Michael; Hajak, Göran; Wolf, Stefan; Padberg, Frank; Klupp, Philipp; Fallgatter, Andreas J; Polak, Thomas; Höppner, Jacqueline; Haker, Rene; Cordes, Joachim; Klenzner, Thomas; Schönfeldt-Lecuona, Carlos; Kammer, Thomas; Graf, Erika; Koller, Michael; Kleinjung, Tobias; Lehner, Astrid; Schecklmann, Martin; Pöppl, Timm B; Kreuzer, Peter; Frank, Elmar; Langguth, Berthold

Chronic tinnitus is a frequent, difficult to treat disease with high morbidity. This multicenter randomized, sham-controlled trial investigated the efficacy and safety of 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied to the left temporal cortex in patients with chronic tinnitus. Tinnitus patients were randomized to receive 10 sessions of either real or sham 1-Hz-rTMS (2000 stimuli, 110% motor threshold) to the left temporal cortex. The primary outcome was the change in the sum score of the tinnitus questionnaire (TQ) of Goebel and Hiller from baseline to end of treatment. A total of 163 patients were enrolled in the study (real rTMS: 75; sham rTMS: 78). At day 12, the baseline mean of 43.1 TQ points in 71 patients assigned to real rTMS changed by -0.5 points; it changed by 0.5 points from a baseline of 42.1 in 75 patients randomized to sham rTMS (adjusted mean difference between groups: -1.0; 95.19% confidence interval: -3.2 to 1.2; p = 0.36). All secondary outcome measures including measures of depression and quality of life showed no significant differences either (p > 0.11). The number of participants with side-effects or adverse events did not differ between groups. Real 1-Hz-rTMS over the left temporal cortex was well tolerated but not superior compared with sham rTMS in improving tinnitus severity. These findings are in contrast to results from studies with smaller sample sizes and put the efficacy of this rTMS protocol for treatment of chronic tinnitus into question. Controlled Trials: http://www.isrctn.com/ISRCTN89848288. Copyright © 2017 Elsevier Inc. All rights reserved.

[Critical reading of reports of educational research in teachers of IMSS. Multicenter study].

PubMed

Leyva-González, Félix Arturo; Cacho-Salazar, Julio M; Degollado-Bardales, Lilia; Zavala-Arenas, Jesús Arturo; Angulo-Bernal, Sonia Elizabeth; Leyva-Salas, César Arturo; Orozco-Bisson, Gisele Victorine

2011-01-01

To determine the effect of an educational strategy promoting participation in the development of critical reading of educational research reports on professors of Educational Research and Teacher Education (CIEFD's). We performed an intervention study, multicenter professors (medical specialists) who enrolled in the courses: Diploma in teaching methodological level 1 and 2 (n = 46, n = 29, respectively) in the six CIEFD's (D.F. Siglo XXI, DF. La Raza, Nuevo León, Sonora, Puebla and Jalisco), in the period March to August 2007. A tool was built that assessed the variables critical appraisal of educational research reports, the construct validity, content and reliability was assessed by experts in education research. The educational strategy developed in the form of seminars, which were held three times a week in the Certification in teaching methodological level 1 and twice per week in the Certification Level 2 in teaching methodology duration per session: 6 h. The instrument was applied at the beginning and end of the course. In the two Graduates it was observed in the total group, an advance in the three indicators of critical reading, which was expressed with statistically significant differences; in the global score of the Diploma level 1 (final vs. initial measurement) the following mediums were observed: 36-67 (p = 0.0001); in the Diploma level 2, it was observed in its overall rating: 42-78 (p = 0.0001). This inquiry from the results observed some of theoretical approaches to mainstreaming participatory. An educational strategy promoting participation produced a breakthrough in the three indicators (to interpret, to judge and to formulate proposals) for critical reading of educational research reports.

Small field output factors evaluation with a microDiamond detector over 30 Italian centers.

PubMed

Russo, Serenella; Reggiori, Giacomo; Cagni, Elisabetta; Clemente, Stefania; Esposito, Marco; Falco, Maria Daniela; Fiandra, Christian; Giglioli, Francesca Romana; Marinelli, Marco; Marino, Carmelo; Masi, Laura; Pimpinella, Maria; Stasi, Michele; Strigari, Lidia; Talamonti, Cinzia; Villaggi, Elena; Mancosu, Pietro

2016-12-01

The aim of the study was a multicenter evaluation of MLC&jaws-defined small field output factors (OF) for different linear accelerator manufacturers and for different beam energies using the latest synthetic single crystal diamond detector commercially available. The feasibility of providing an experimental OF data set, useful for on-site measurements validation, was also evaluated. This work was performed in the framework of the Italian Association of Medical Physics (AIFM) SBRT working group. The project was subdivided in two phases: in the first phase each center measured OFs using their own routine detector for nominal field sizes ranging from 10×10cm 2 to 0.6×0.6cm 2 . In the second phase, the measurements were repeated in all centers using the PTW 60019 microDiamond detector. The project enrolled 30 Italian centers. Micro-ion chambers and silicon diodes were used for OF measurements in 24 and 6 centers respectively. Gafchromic films and TLDs were used for very small field OFs in 3 and 1 centers. Regarding the measurements performed with the user's detectors, OF standard deviations (SD) for field sizes down to 2×2cm 2 were in all cases <2.7%. In the second phase, a reduction of around 50% of the SD was obtained using the microDiamond detector. The measured values presented in this multicenter study provide a consistent dataset for OFs that could be a useful tool for improving dosimetric procedures in centers. The microDiamond data present a small variation among the centers confirming that this detector can contribute to improve overall accuracy in radiotherapy. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Fever Control Management Is Preferable to Mild Therapeutic Hypothermia in Traumatic Brain Injury Patients with Abbreviated Injury Scale 3-4: A Multi-Center, Randomized Controlled Trial.

PubMed

Hifumi, Toru; Kuroda, Yasuhiro; Kawakita, Kenya; Yamashita, Susumu; Oda, Yasutaka; Dohi, Kenji; Maekawa, Tsuyoshi

2016-06-01

In our prospective, multi-center, randomized controlled trial (RCT)-the Brain Hypothermia (B-HYPO) study-we could not show any difference on neurological outcomes in patients probably because of the heterogeneity in the severity of their traumatic condition. We therefore aimed to clarify and compare the effectiveness of the two therapeutic temperature management regimens in severe (Abbreviated Injury Scale [AIS] 3-4) or critical trauma patients (AIS 5). In the present post hoc B-HYPO study, we re-evaluated data based on the severity of trauma as AIS 3-4 or AIS 5 and compared Glasgow Outcome Scale score and mortality at 6 months by per-protocol analyses. Consequently, 135 patients were enrolled. Finally, 129 patients, that is, 47 and 31 patients with AIS 3-4 and 36 and 15 patients with AIS 5 were allocated to the mild therapeutic hypothermia (MTH) and fever control groups, respectively. No significant intergroup differences were observed with regard to age, gender, scores on head computed tomography (CT) scans, and surgical operation for traumatic brain injury (TBI), except for Injury Severity Score (ISS) in AIS 5. The fever control group demonstrated a significant reduction of TBI-related mortality compared with the MTH group (9.7% vs. 34.0%, p = 0.02) and an increase of favorable neurological outcomes (64.5% vs. 51.1%, p = 0.26) in patients with AIS 3-4, although the latter was not statistically significant. There was no difference in mortality or favorable outcome in patients with AIS 5. Fever control may be considered instead of MTH in patients with TBI (AIS 3-4).

Comparing the 12-month patency of low- versus high-pressure dilation in failing arteriovenous fistulae: A prospective multicenter trial (YOROI study).

PubMed

Wakamoto, Koki; Doi, Shigehiro; Nakashima, Ayumu; Kawai, Toru; Kyuden, Yasufumi; Naito, Takayuki; Asai, Mariko; Takahashi, Shunsuke; Murakami, Masaaki; Masaki, Takao

2018-03-01

This study was performed to investigate the effect of the balloon dilation pressure on the 12-month patency rate in patients with failed arteriovenous fistulas undergoing hemodialysis. In this multicenter, prospective, randomized trial, the 4-mm-diameter YOROI balloon was used for dilation of stenotic lesions. The balloons were inflated to a pressure of 8 atm (low-pressure group) or 30 atm to achieve complete expansion (high-pressure group). The 12-month patency rate after balloon angioplasty was analyzed by the Kaplan-Meier method and log-rank test and/or a Cox proportional hazard model. We also investigated the dilation pressure required to achieve complete expansion in the high-pressure group. In total, 71 patients were enrolled and allocated to either the low-pressure group (n = 34) or the high-pressure group (n = 37). The 12-month patency rates showed no significant difference between the low- and high-pressure groups (47% and 49%, respectively; p = 0.87). In the low-pressure group, the patency rate was not different between patients with complete dilation and residual stenosis (44% and 50%, respectively; p = 0.87). The Cox proportional hazard model revealed that the 12-month patency rate was associated with the stenosis diameter (hazard ratio 0.36; p = 0.001) and the presence of diabetes (hazard ratio 0.33; p = 0.018). Finally, the pressure required to achieve complete dilation was ≤20 atm in 76% of patients and ≤30 atm in 97% of patients. One patient required a dilation pressure of >30 atm. The patency rate does not differ between low-pressure dilation and high-pressure dilation.

Effect of Azilsartan on Day-to-Day Variability in Home Blood Pressure: A Prospective Multicenter Clinical Trial.

PubMed

Miyoshi, Toru; Suetsuna, Ryoji; Tokunaga, Naoto; Kusaka, Masayasu; Tsuzaki, Ryuichiro; Koten, Kazuya; Kunihisa, Kohno; Ito, Hiroshi

2017-07-01

The blood pressure variability (BPV) such as visit-to-visit, day-by-day, and ambulatory BPV has been also shown to be a risk of future cardiovascular events. However, the effects of antihypertensive therapy on BPV remain unclear. The purpose of this study was to evaluate the effect of azilsartan after switching from another angiotensin II receptor blocker (ARB) on day-to-day BPV in home BP monitoring. This prospective, multicenter, open-labeled, single-arm study included 28 patients undergoing treatment with an ARB, which was switched to azilsartan after enrollment. The primary outcome was the change in the mean of the standard deviation and the coefficient of variation of morning home BP for 5 consecutive days from baseline to the 24-week follow-up. The secondary outcome was the change in arterial stiffness measured by the cardio-ankle vascular index. The mean BPs in the morning and evening for 5 days did not statistically differ between baseline and 24 weeks. For the morning BP, the means of the standard deviations and coefficient of variation of the systolic BP were significantly decreased from 7.4 ± 3.6 mm Hg to 6.1 ± 3.2 mm Hg and from 5.4±2.7% to 4.6±2.3% (mean ± standard deviation, P = 0.04 and P = 0.04, respectively). For the evening BP, no significant change was observed in the systolic or diastolic BPV. The cardio-ankle vascular index significantly decreased from 8.3 ± 0.8 to 8.1 ± 0.8 (P = 0.03). Switching from another ARB to azilsartan reduced day-to-day BPV in the morning and improved arterial stiffness.

Effect of Azilsartan on Day-to-Day Variability in Home Blood Pressure: A Prospective Multicenter Clinical Trial

PubMed Central

Miyoshi, Toru; Suetsuna, Ryoji; Tokunaga, Naoto; Kusaka, Masayasu; Tsuzaki, Ryuichiro; Koten, Kazuya; Kunihisa, Kohno; Ito, Hiroshi

2017-01-01

Background The blood pressure variability (BPV) such as visit-to-visit, day-by-day, and ambulatory BPV has been also shown to be a risk of future cardiovascular events. However, the effects of antihypertensive therapy on BPV remain unclear. The purpose of this study was to evaluate the effect of azilsartan after switching from another angiotensin II receptor blocker (ARB) on day-to-day BPV in home BP monitoring. Methods This prospective, multicenter, open-labeled, single-arm study included 28 patients undergoing treatment with an ARB, which was switched to azilsartan after enrollment. The primary outcome was the change in the mean of the standard deviation and the coefficient of variation of morning home BP for 5 consecutive days from baseline to the 24-week follow-up. The secondary outcome was the change in arterial stiffness measured by the cardio-ankle vascular index. Results The mean BPs in the morning and evening for 5 days did not statistically differ between baseline and 24 weeks. For the morning BP, the means of the standard deviations and coefficient of variation of the systolic BP were significantly decreased from 7.4 ± 3.6 mm Hg to 6.1 ± 3.2 mm Hg and from 5.4±2.7% to 4.6±2.3% (mean ± standard deviation, P = 0.04 and P = 0.04, respectively). For the evening BP, no significant change was observed in the systolic or diastolic BPV. The cardio-ankle vascular index significantly decreased from 8.3 ± 0.8 to 8.1 ± 0.8 (P = 0.03). Conclusions Switching from another ARB to azilsartan reduced day-to-day BPV in the morning and improved arterial stiffness. PMID:28611863

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.

A State-of-the-Science Overview of Randomized Controlled Trials Evaluating Acute Management of Moderate-to-Severe Traumatic Brain Injury

PubMed Central

Synnot, Anneliese; Maas, Andrew I.; Menon, David K.; Cooper, D. James; Rosenfeld, Jeffrey V.; Gruen, Russell L.

2016-01-01

Abstract Moderate-to-severe traumatic brain injury (TBI) remains a major global challenge, with rising incidence, unchanging mortality and lifelong impairments. State-of-the-science reviews are important for research planning and clinical decision support. This review aimed to identify randomized controlled trials (RCTs) evaluating interventions for acute management of moderate/severe TBI, synthesize key RCT characteristics and findings, and determine their implications on clinical practice and future research. RCTs were identified through comprehensive database and other searches. Key characteristics, outcomes, risk of bias, and analysis approach were extracted. Data were narratively synthesized, with a focus on robust (multi-center, low risk of bias, n > 100) RCTs, and three-dimensional graphical figures also were used to explore relationships between RCT characteristics and findings. A total of 207 RCTs were identified. The 191 completed RCTs enrolled 35,340 participants (median, 66). Most (72%) were single center and enrolled less than 100 participants (69%). There were 26 robust RCTs across 18 different interventions. For 74% of 392 comparisons across all included RCTs, there was no significant difference between groups. Positive findings were broadly distributed with respect to RCT characteristics. Less than one-third of RCTs demonstrated low risk of bias for random sequence generation or allocation concealment, less than one-quarter used covariate adjustment, and only 7% employed an ordinal analysis approach. Considerable investment of resources in producing 191 completed RCTs for acute TBI management has resulted in very little translatable evidence. This may result from broad distribution of research effort, small samples, preponderance of single-center RCTs, and methodological shortcomings. More sophisticated RCT design, large multi-center RCTs in priority areas, increased focus on pre-clinical research, and alternatives to RCTs, such as comparative effectiveness research and precision medicine, are needed to fully realize the potential of acute TBI research to benefit patients. PMID:26711675

Postnatal Growth and Retinopathy of Prematurity Study: Rationale, Design, and Subject Characteristics.

PubMed

Binenbaum, Gil; Tomlinson, Lauren A

2017-02-01

Postnatal-growth-based predictive models demonstrate strong potential for improving the low specificity of retinopathy of prematurity (ROP) screening. Prior studies are limited by inadequate sample size. We sought to study a sufficiently large cohort of at-risk infants to enable development of a model with highly precise estimates of sensitivity for severe ROP. The Postnatal Growth and ROP (G-ROP) Study was a multicenter retrospective cohort study of infants at 30 North American hospitals during 2006-2012. A total of 65 G-ROP-certified abstractors submitted data to a secure, web-based database. Data included ROP examination findings, treatments, complications, daily weight measurements, daily oxygen supplementation, maternal/infant demographics, medical comorbidities, surgical events, and weekly nutrition. Data quality was monitored with system validation rules, data audits, and discrepancy algorithms. Of 11,261 screened infants, 8334 were enrolled, and 2927 had insufficient data due to transfer, discharge, or death. Of the enrolled infants, 90% (7483) had a known ROP outcome and were included in the study. Median birth weight was 1070 g (range 310-3000g) and mean gestational age 28 weeks (range 22-35 weeks). Severe ROP (Early Treatment of Retinopathy type 1 or 2) developed in 931 infants (12.5%). Successful incorporation of a predictive model into ROP screening requires confidence that it will capture cases of severe ROP. This dataset provides power to estimate sensitivity with half-confidence interval width of less than 0.5%, determined by the high number of severe ROP cases. The G-ROP Study represents a large, diverse cohort of at-risk infants undergoing ROP screening. It will facilitate evaluation of growth-based algorithms to improve efficiency of ROP screening.

Evaluation of synergistic effects of resynchronization therapy and a β-blocker up-titration strategy based on a predefined patient-management program: the RESTORE study.

PubMed

Palmisano, Pietro; Ammendola, Ernesto; D'Onofrio, Antonio; Accogli, Michele; Calò, Leonardo; Ruocco, Antonio; Rapacciuolo, Antonio; Del Giorno, Giuseppe; Bianchi, Valter; Malacrida, Maurizio; Valsecchi, Sergio; Gronda, Edoardo

2015-01-01

Prior studies have suggested that a substantial number of eligible heart failure (HF) patients fail to receive β-blocker therapy, or receive it at a suboptimal dose. The aim of this study is to assess the benefit of a predefined management program designed for β-blocker up-titration, evaluating the synergistic effect of cardiac resynchronization therapy (CRT) and β-blockers in a HF population. The Resynchronization Therapy and β-Blocker Titration (RESTORE) study is a prospective, case-control, multicenter cohort study designed to test the hypothesis that a β-blocker up-titration strategy based on a predefined management program maximizes the beneficial effect of CRT, increasing the number of patients reaching the target dose of β-blockers and improving their clinical outcome. All study patients receive an implantable defibrillator for CRT delivery in accordance with current guidelines. Enrollments started in December 2011 and are scheduled to end in December 2014. Approximately 250 consecutive patients will be prospectively enrolled in 6 Italian centers and followed up for 24 months after implantation. The primary endpoint is to demonstrate that CRT may allow titration of β-blockers until the optimal dose, or at least to the effective dose, in patients with HF. This study might provide important information about the benefit of a predefined management program for β-blocker up-titration in patients receiving CRT. Moreover, assessment of health-care utilization and the consumption of resources will allow estimating the potential utility of remote monitoring by means of an automated telemedicine system in facilitating the titration of β-blockers in comparison with a standard in-hospital approach. © 2015 Wiley Periodicals, Inc.

Factors Associated With Pressure Ulcers in Individuals With Spina Bifida

PubMed Central

Kim, Sunkyung; Ward, Elisabeth; Dicianno, Brad E.; Clayton, Gerald H.; Sawin, Kathleen J.; Beierwaltes, Patricia; Thibadeau, Judy

2015-01-01

Objective To describe factors associated with pressure ulcers in individuals with spina bifida (SB) enrolled in the National Spina Bifida Patient Registry (NSBPR). Design Unbalanced longitudinal multicenter cohort study. Setting Nineteen SB clinics. Participants Individuals with SB (N=3153) enrolled in 19 clinic sites that participate in the NSBPR. Interventions Not applicable. Main Outcome Measures Pressure ulcer status (yes/no) at the annual visit between 2009 and 2012. Results Of 3153 total participants, 19% (n=603) reported ulcers at their most recent annual clinic visit. Seven factors–level of lesion, wheelchair use, urinary incontinence, shunt presence, above the knee orthopedic surgery, recent surgery, and male sex–were significantly associated with the presence of pressure ulcers. Of these factors, level of lesion, urinary incontinence, recent surgery, and male sex were included in the final logistic regression model. The 3 adjusting variables–SB type, SB clinic, and age group–were significant in all analyses (all P<.001). Conclusions By adjusting for SB type, SB clinic, and age group, we found that 7 factors–level of lesion, wheelchair use, urinary incontinence, shunt presence, above the knee orthopedic surgery, recent surgery, and male sex–were associated with pressure ulcers. Identifying key factors associated with the onset of pressure ulcers can be incorporated into clinical practice in ways that prevent and enhance treatment of pressure ulcers in the population with SB. PMID:25796136

Thromboprophylaxis using combined intermittent pneumatic compression and pharmacologic prophylaxis versus pharmacologic prophylaxis alone in critically ill patients: study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen M; Alsolamy, Sami; Al-Dawood, Abdulaziz; Al-Omari, Awad; Al-Hameed, Fahad; Burns, Karen E A; Almaani, Mohammed; Lababidi, Hani; Al Bshabshe, Ali; Mehta, Sangeeta; Al-Aithan, Abdulsalam M; Mandourah, Yasser; Almekhlafi, Ghaleb; Finfer, Simon; Abdukahil, Sheryl Ann I; Afesh, Lara Y; Dbsawy, Maamoun; Sadat, Musharaf

2016-08-03

Venous thromboembolism (VTE) remains a common problem in critically ill patients. Pharmacologic prophylaxis is currently the standard of care based on high-level evidence from randomized controlled trials. However, limited evidence exists regarding the effectiveness of intermittent pneumatic compression (IPC) devices. The Pneumatic compREssion for preventing VENous Thromboembolism (PREVENT trial) aims to determine whether the adjunct use of IPC with pharmacologic prophylaxis compared to pharmacologic prophylaxis alone in critically ill patients reduces the risk of VTE. The PREVENT trial is a multicenter randomized controlled trial, which will recruit 2000 critically ill patients from over 20 hospitals in three countries. The primary outcome is the incidence of proximal lower extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the scans are blinded to intervention allocation, whereas the patients and caregivers are unblinded. The trial has 80 % power to detect a 3 % absolute risk reduction in proximal DVT from 7 to 4 %. The first patient was enrolled in July 2014. As of May 2015, a total of 650 patients have been enrolled from 13 centers in Saudi Arabia, Canada and Australia. The first interim analysis is anticipated in July 2016. We expect to complete recruitment by 2018. Clinicaltrials.gov: NCT02040103 (registered on 3 November 2013). Current controlled trials: ISRCTN44653506 (registered on 30 October 2013).

The Effectiveness of Silodosin for Nocturnal Polyuria in Elderly Men With Benign Prostatic Hyperplasia: A Multicenter Study.

PubMed

Kim, Young Won; Park, Jinsung; Chung, Hong; Kim, Hong-Wook; Kim, Hyung Joon; Jung, Jae Hung; Kim, Won Tae

2015-09-01

To investigate improvement in nocturia and nocturnal polyuria in nocturnal polyuria patients after silodosin administration by using a 3-day frequency volume chart. This was a prospective multicenter study. We enrolled nocturnal polyuria patients (nocturnal polyuria index [NPi]>0.33), aged ≥60 years, diagnosed with the 3-day frequency volume charts of patients with benign prostatic hyperplasia taking α-blockers. Of the 54 patients, 30 (55.6%) completed the study according to the study protocol (per-protocol group), and 24 dropped out (dropout group). Of the 24 patients in the dropout group, 5 withdrew consent due to side effects or lack of efficacy, 7 were lost to follow-up at 4 weeks, 8 were lost to follow-up at 12 weeks, and 4 dropped out due to failure to complete 3-day frequency volume charts at 12 weeks. In the per-protocol group, there was significant improvement in the International Prostate Symptom Score (IPSS), especially question numbers 1, 3, 4, 5, 6, 7, and the quality of life question (P=0.001, P=0.007, P<0.001, P=0.003, P=0.049, P<0.001, and P<0.001, respectively). The Leeds sleep evaluation questionnaire (LSEQ) score for the sleep question improved from 64.36 to 70.43 (P=0.039). The NPi reduced from 0.4005 to 0.3573 (P=0.027); however, in many cases, there was no improvement in nocturnal polyuria itself. In intention-to-treat analysis, there were significant improvements in IPSS and LSEQ in 45 patients. In elderly nocturnal polyuria patients, silodosin monotherapy exhibits good efficacy in improving nocturia and nocturnal polyuria; however, the mean NPi was still >0.33. Considering the high dropout rate of our study due to no implementation of 3-day frequency volume charts, prospective and large-scale studies are needed to confirm our results.

The Effectiveness of Silodosin for Nocturnal Polyuria in Elderly Men With Benign Prostatic Hyperplasia: A Multicenter Study

PubMed Central

Kim, Young Won; Park, Jinsung; Chung, Hong; Kim, Hong-Wook; Kim, Hyung Joon; Jung, Jae Hung; Kim, Won Tae

2015-01-01

Purpose: To investigate improvement in nocturia and nocturnal polyuria in nocturnal polyuria patients after silodosin administration by using a 3-day frequency volume chart. Methods: This was a prospective multicenter study. We enrolled nocturnal polyuria patients (nocturnal polyuria index [NPi]>0.33), aged ≥60 years, diagnosed with the 3-day frequency volume charts of patients with benign prostatic hyperplasia taking α-blockers. Of the 54 patients, 30 (55.6%) completed the study according to the study protocol (per-protocol group), and 24 dropped out (dropout group). Results: Of the 24 patients in the dropout group, 5 withdrew consent due to side effects or lack of efficacy, 7 were lost to follow-up at 4 weeks, 8 were lost to follow-up at 12 weeks, and 4 dropped out due to failure to complete 3-day frequency volume charts at 12 weeks. In the per-protocol group, there was significant improvement in the International Prostate Symptom Score (IPSS), especially question numbers 1, 3, 4, 5, 6, 7, and the quality of life question (P=0.001, P=0.007, P<0.001, P=0.003, P=0.049, P<0.001, and P<0.001, respectively). The Leeds sleep evaluation questionnaire (LSEQ) score for the sleep question improved from 64.36 to 70.43 (P=0.039). The NPi reduced from 0.4005 to 0.3573 (P=0.027); however, in many cases, there was no improvement in nocturnal polyuria itself. In intention-to-treat analysis, there were significant improvements in IPSS and LSEQ in 45 patients. Conclusions: In elderly nocturnal polyuria patients, silodosin monotherapy exhibits good efficacy in improving nocturia and nocturnal polyuria; however, the mean NPi was still >0.33. Considering the high dropout rate of our study due to no implementation of 3-day frequency volume charts, prospective and large-scale studies are needed to confirm our results. PMID:26620902

Open-label randomized multicenter selection study of once daily antiretroviral treatment regimen comparing ritonavir-boosted atazanavir to efavirenz with fixed-dose abacavir and lamivudine.

PubMed

Honda, Miwako; Ishisaka, Michiyo; Ishizuka, Naoki; Kimura, Satoshi; Oka, Shinichi

2011-01-01

The side-effects of anti-retroviral drugs are different between Japanese and Caucasian patients. Severe central nerve system (CNS) side-effects to efavirenz and low rate of hypersensitivity against abacavir characterize the Japanese. The objective of this study was to select a once daily regimen for further non-inferior study comparing the virological efficacy and safety of the first line once daily antiretroviral treatment regimens in the current HIV/AIDS guideline. The study design was a randomized, open label, multicenter, selection study. One arm was treated with efavirenz and the other with ritonavir-boosted atazanavir. A fixed-dose lamivudine plus abacavir were used in both arms. The primary endpoint was virologic success (viral load less than 50 copies/mL) rate at 48 weeks. Patients were followed-up to 96 weeks with safety as the secondary endpoint. Clinicaltrials.Gov (NCT00280969) and the University hospital Medical Information Network (UMIN000000243). A total of 71 participants were enrolled. Virologic success rates in both arms were similar at week 48 [efavirenz arm 28/36 (77.8%); atazanavir arm 27/35 (77.1%)], but were decreased at week 96 to 55.6% in the efavirenz arm and 68.8% in the atazanavir arm (p=0.33). At the 96-week follow-up, 52.8% of the EFV arm and 34.3% of the ATV/r arm reached total cholesterol more than 220 mg/dL and required treatment. None of the patients developed cardiovascular complications in this study by week 96. There was no significant difference in the efficacy of efavirenz and ritonavir-boosted atazanavir combined with lamivudine plus abacavir at 48 weeks. The evaluation of safety was extended to 96 weeks, which also showed no significant difference in both arms.

A multicenter randomized clinical trial of one-rod etonogestrel and two-rod levonorgestrel contraceptive implants with nonrandomized copper-IUD controls: methodology and insertion data.

PubMed

Meirik, Olav; Brache, Vivian; Orawan, Kiriwat; Habib, Ndema Abu; Schmidt, Johannes; Ortayli, Nuriye; Culwell, Kelly; Jackson, Emily; Ali, Moazzam

2013-01-01

Comparative data on etonogestrel and two-rod levonorgestrel contraceptive implants are lacking. A multicenter, open, parallel-group trial with random allocation of implants was performed. For every second implant user, an age-matched woman choosing an intrauterine device (IUD) (TCu380A) was admitted. Methods and data on implant/IUD insertion and 6-week follow-up are reported. A total of 2008 women were randomized to an implant, and 974 women were enrolled in the IUD group. Results from 997 etonogestrel implant users, 997 levonorgestrel implant users and 971 IUD users were analyzed. In the etonogestrel and levonorgestrel groups, respectively, mean insertion durations were 51 (SD 50.2) s and 88 (SD 60.8) s; complication rates at insertion were 0.8% and 0.2%; and at follow-up, 27.2% and 26.7% of women, respectively, had signs or symptoms at the insertion site. At follow-up within 6 weeks after insertion, all implants were in situ, while 2.1% of IUDs were expelled. Performance of etonogestrel and levonorgestrel implants at insertion and within the first 6 weeks is similar. Short-term (6 weeks) continuation rates appear higher for implants than TCu380A. Copyright © 2013 Elsevier Inc. All rights reserved.

Hospital outcomes of extremely low birth weight infants after introduction of donor milk to supplement mother's milk.

PubMed

Verd, Sergio; Porta, Roser; Botet, Francesc; Gutiérrez, Antonio; Ginovart, Gemma; Barbero, Ana Herranz; Ciurana, Anna; Plata, Isabel Iglesias

2015-04-01

This study evaluated the impact of an exclusive human milk diet to nourish extremely low birth weight infants in the neonatal intensive care unit. This multicenter pre-post retrospective study included all inborn infants <1,000 g admitted to four Level IV neonatal intensive care units either before or after implementing a donor human milk policy. The feeding protocol was unchanged in both periods. Collected data included maternal/infant demographics, infant clinical data, and enteral intake as mother's own milk, donor milk, and formula. Two hundred one infants were enrolled. Infant growth and other clinical outcomes were similar in both groups. Exposure to mother's own milk at discharge was not different. Median time in oxygen and duration of mechanical ventilation were significantly higher among formula-fed infants (63 versus 192 hours [p=0.046] and 24 versus 60 hours [p=0.016], respectively). Our results add evidence supporting the safety of donor milk. This study also found an association between exposure to formula in preterm infants and the requirement for respiratory support, a finding that warrants further investigation.

Ibrutinib for the treatment of mantle cell lymphoma.

PubMed

Herrera, Alex F; Jacobsen, Eric D

2014-11-01

Ibrutinib (PCI-32765)--a potent, covalent inhibitor of Bruton tyrosine kinase (BTK), an important kinase in the B-cell receptor signaling pathway--was recently approved by the FDA for the treatment of relapsed or refractory mantle cell lymphoma (MCL). The drug was granted accelerated approval based on the findings of an international, multicenter, single-arm phase II study that enrolled patients with relapsed or refractory MCL. In the study, ibrutinib (560 mg daily) was well tolerated as a single agent and resulted in an overall response rate of 68% and an estimated median response duration of 17.5 months. Ibrutinib's response rate and duration of response compare favorably with those for other novel agents approved for the treatment of relapsed or refractory MCL, while being less toxic than most chemotherapy or chemoimmunotherapy regimens. Ibrutinib is currently being studied in combination with chemoimmunotherapy, monoclonal antibody therapy, and novel agents in both the initial and the relapsed/refractory treatment settings. We review the mechanism of action, preclinical and clinical development, and the role of ibrutinib in the context of other available treatments. ©2014 American Association for Cancer Research.

Multiple-dose pharmacokinetics and safety of an ibuprofen-pseudoephedrine cold suspension in children.

PubMed

Gelotte, Cathy K; Prior, Mary Jane; Pendley, Charles; Zimmerman, Brenda; Lavins, Bernard J

2010-07-01

Two studies were conducted to characterize multiple-dose pharmacokinetics and potential drug interactions of ibuprofen and pseudoephedrine combined in a suspension and to evaluate safety of this combination in children with common cold, flu, or sinusitis. In the pharmacokinetic study, 24 healthy children aged 4-11 years were administered ibuprofen -pseudoephedrine suspension at 7.5 and 1.125 mg/kg, respectively, every 6 hours for 5 doses. Serial blood samples were drawn over 6 hours after final dose for assessment of steady-state pharmacokinetics. In the open-label, multicenter safety study, more than 100 children aged 2-11 years experiencing symptomatic rhinitis were enrolled. Ibuprofen -pseudoephedrine suspension was administered as needed at similar mg/kg doses every 6-8 hours for up to 3 days. Subjects enrolled in the pharmacokinetic study showed no accumulation of either drug; their weight-adjusted clearances were independent of age, and results were comparable with those from previous single-ingredient studies. For ibuprofen, oral clearance (Cl/F) was 77.5 + or - 16.4 mL/kg/h and volume of distribution (Vd/F) was 0.147 + or - 0.037 L/kg. For pseudoephedrine, Cl/F was 12.3 + or - 2.2 mL/kg/min and Vd/F was 2.52 + or - 0.47 L/kg. In the safety study, adverse events were reported for 18.4% of subjects; most were mild to moderate intensity. There was little difference in incidence of adverse events among different age and weight groups. In conclusion, administration of combined ibuprofen and pseudoephedrine in children demonstrated similar pharmacokinetics when compared with reports of the pharmacokinetics for the single-ingredient products, consistent with no apparent drug interactions. The combination suspension was generally well tolerated.

Distribution of respiratory syncytial virus subtypes A and B among infants presenting to the emergency department with lower respiratory tract infection or apnea.

PubMed

Jafri, Hasan S; Wu, Xionghua; Makari, Doris; Henrickson, Kelly J

2013-04-01

Respiratory syncytial virus (RSV), a leading viral respiratory pathogen worldwide, has 2 major subtypes, A and B. To describe the temporal and geographic distribution and parameters of disease severity associated with RSV A and B in the United States. A US multicenter active surveillance study was conducted in emergency departments (EDs) during 2 RSV seasons. Infants <1 year of age presenting to the ED with symptoms of lower respiratory tract infection or apnea were enrolled. RSV subtypes were detected in nasal swabs by reverse transcriptase polymerase chain reaction. Of 4248 patients enrolled, 4172 patients were evaluable; 32.4% of patients were positive for any RSV subtype in season 1 and 29.9% in season 2. RSV A and B were detected in each region studied. More patients presented to the ED with RSV A than with RSV B (853 [20.4%] versus 453 [10.9%], respectively); RSV A-positive patients were more likely to be admitted to the hospital or intensive care unit (47.7%, versus RSV B, 35.8%; P < 0.0001); hospitalized RSV A-positive patients were less likely to be prescribed antibiotics (32.4%, versus RSV B, 47.8%; P < 0.001). This is the largest epidemiologic study in EDs reporting trends in RSV subtypes. RSV subtypes A and B were documented in both seasons across all US regions studied and detected in September to May. The results of this study support suggestions from smaller studies that RSV A may be more virulent than RSV B; however, more quantitative assessments of disease severity are needed.

[Study of prognostic factors and prevalence of post-thrombotic syndrome in patients with deep vein thrombosis in Spain].

PubMed

Ordi, Josep; Salmerón, Luis; Acosta, Fernando; Camacho, Isabel; Marín, Núria

2016-01-15

The prevalence of post-thrombotic syndrome (PTS) in Spain is not known accurately at present. The main objective of this study was to determine the prevalence of PTS and the possible prognostic factors related to its development and impact on quality of life. This was an observational, multicenter, cross-sectional and retrospective study of patients who had suffered a deep vein thrombosis (DVT) between March 2010 and March 2011. The Villalta scale was applied as a standardized assessment of PTS at the enrollment visit. According to the score, distribution was: patients with PTS (score>4) and patients without PTS (score ≤4). Subsequently, DVT data and risk factors were collected retrospectively. The quality of life of patients was evaluated. In total 511 patients with DVT were enrolled, of which 7 patients were excluded as they did not meet the inclusion/exclusion criteria. The prevalence of PTS was 53%, with 56.2% having a mild character, 20.6% moderate, and 23.2% severe. The presence of risk factors for DVT including immobilization, hormonal therapy and obesity was significantly higher in patients with PTS than in patients without PTS. There were not significant differences in the location of the DVT. The perception of patients about their health was significantly worse in patients with DVT. The prevalence of PTS in patients with DVT is very high. The presence of risk factors for DVT clearly contributes to a greater predisposition to suffering PTS in an average time of 2 years. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Mediterranean diet adherence and synergy with acute myocardial infarction and its determinants: A multicenter case-control study in Italy

PubMed Central

Saulle, Rosella; Di Murro, Francesca; Siliquini, Roberta; Firenze, Alberto; Maurici, Massimo; Mannocci, Alice; Colamesta, Vittoria; Barillà, Francesco; Ferrante, Fabio; Agati, Luciano

2018-01-01

Background Cardiovascular diseases are the leading causes of mortality and morbidity in Western countries. The possible synergistic effect of poor adherence to a Mediterranean diet (MD) and other risk factors for acute myocardial infarction (AMI) such as hypertension, cholesterol, ever smoker, BMI> 25, diabetes, has not been deeply studied. Design Case-control study. Methods Patients with first AMI and controls from four tertiary referral Italian centers were screened for enrolment. Dietary information was collected through a questionnaire and a MD adherence score was calculated. Physical activity and smoking habits were also registered. The Synergy Index was calculated according to Rothman. Results 127 cases and 173 controls were enrolled. The analysis was conducted using a dichotomous variable for the MD score with values ≥7 representing good adherence. Multivariate analysis showed the following variables associated to AMI: ever smoker (OR = 2.08), diabetes (OR = 1.42), hypertension (OR = 2.08), hypercholesterolemia (OR = 2.47), BMI> 25 (OR = 1.99), while a protective effect emerged both in subjects scoring > 7 on the MD score (OR = 0.55) and in subjects resident of Southern Italy (OR = 0.38). A synergistic effect does exist between poor adherence to the MD and the following risk factors: hypertension, hypercholesterolemia, BMI >25, diabetes and being a resident in central and northern Italy. Conclusion Synergy between heart disease risk factors and MD underlines the need to enlarge the list of known modifiable cardiovascular risk factors to include and promote adherence to Mediterranean dietary habits. PMID:29543823

Efficacy and safety of an ascending-dose, extended-regimen levonorgestrel/ethinyl estradiol combined oral contraceptive.

PubMed

Portman, David J; Kaunitz, Andrew M; Howard, Brandon; Weiss, Herman; Hsieh, Jennifer; Ricciotti, Nancy

2014-04-01

To evaluate the efficacy and safety of an ascending-dose, extended-regimen (ADER) combined oral contraceptive consisting of levonorgestrel (LNG) 150 mcg/ethinyl estradiol (EE) 20 mcg for 42 days, LNG 150 mcg/EE 25 mcg for 21 days, LNG 150 mcg/EE 30 mcg for 21 days and EE 10 mcg for 7 days. This was a multicenter, open-label, phase 3, single-arm study. Sexually active women aged 18-40 years were enrolled and received ADER for up to 1 year (4 consecutive 91-day cycles). Participants kept diaries to record adherence, bleeding/spotting and other contraceptive use. Efficacy was measured using the Pearl Index and the life-table method; safety and tolerability were assessed through reported adverse events (AEs). A total of 3701 women were enrolled and 2144 completed the study. The Pearl Index was 3.19 [95% confidence interval (CI), 2.49-4.03], based on 70 pregnancies that occurred after ADER initiation and ≤ 7 days after the last LNG/EE or EE-only pill in women aged 18-35 years, excluding cycles in which another contraceptive method was used. Life-table pregnancy rate was 2.82% (95% CI, 2.23%-3.57%) for all users aged 18-35 years. Unscheduled bleeding/spotting decreased with increasing EE doses within each cycle and decreased after cycle 1. No unexpected AEs or changes in laboratory parameters were reported. This study demonstrated that ADER effectively prevented pregnancy with a favorable safety and tolerability profile. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Activity of IPI-504, a Novel Heat-Shock Protein 90 Inhibitor, in Patients With Molecularly Defined Non–Small-Cell Lung Cancer

PubMed Central

Sequist, Lecia V.; Gettinger, Scott; Senzer, Neil N.; Martins, Renato G.; Jänne, Pasi A.; Lilenbaum, Rogerio; Gray, Jhanelle E.; Iafrate, A. John; Katayama, Ryohei; Hafeez, Nafeeza; Sweeney, Jennifer; Walker, John R.; Fritz, Christian; Ross, Robert W.; Grayzel, David; Engelman, Jeffrey A.; Borger, Darrell R.; Paez, Guillermo; Natale, Ronald

2010-01-01

Purpose IPI-504 is a novel, water-soluble, potent inhibitor of heat-shock protein 90 (Hsp90). Its potential anticancer activity has been validated in preclinical in vitro and in vivo models. We studied the activity of IPI-504 after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy in patients with advanced, molecularly defined non–small-cell lung cancer (NSCLC). Patients and Methods Patients with advanced NSCLC, prior treatment with EGFR TKIs, and tumor tissue available for molecular genotyping were enrolled in this prospective, nonrandomized, multicenter, phase II study of IPI-504 monotherapy. The primary outcome was objective response rate (ORR). Secondary aims included safety, progression-free survival (PFS), and analysis of activity by molecular subtypes. Results Seventy-six patients were enrolled between December 2007 and May 2009 from 10 United States cancer centers. An ORR of 7% (five of 76) was observed in the overall study population, 10% (four of 40) in patients who were EGFR wild-type, and 4% (one of 28) in those with EGFR mutations. Although both EGFR groups were below the target ORR of 20%, among the three patients with an ALK gene rearrangement, two had partial responses and the third had prolonged stable disease (7.2 months, 24% reduction in tumor size). The most common adverse events included grades 1 and 2 fatigue, nausea, and diarrhea. Grade 3 or higher liver function abnormalities were observed in nine patients (11.8%). Conclusion IPI-504 has clinical activity in patients with NSCLC, particularly among patients with ALK rearrangements. PMID:20940188

One-Year Outcomes Following Directional Atherectomy of Infrapopliteal Artery Lesions: Subgroup Results of the Prospective, Multicenter DEFINITIVE LE Trial.

PubMed

Rastan, Aljoscha; McKinsey, James F; Garcia, Lawrence A; Rocha-Singh, Krishna J; Jaff, Michael R; Noory, Elias; Zeller, Thomas

2015-12-01

To report a subgroup analysis of the prospective, multicenter, single-arm DEFINITIVE LE trial to assess the effectiveness of directional atherectomy for the treatment of infrapopliteal artery lesions at 1 year. In the DEFINITIVE LE trial, follow-up assessments occurred up to 1 year postprocedure. Of the 800 patients enrolled, 145 subjects with 189 infrapopliteal lesions met the criteria for this analysis. Seventy (48.3%) and 75 (51.7%) patients were suffering critical limb ischemia (CLI) and intermittent claudication, respectively; 68.3% (99/145) had diabetes. The mean lesion length was 58±44 mm (all lesions); 20.2% were occluded. The primary endpoint for patients with claudication was duplex ultrasound-derived primary patency, while for subjects with CLI it was freedom from major amputation of the target limb at 1 year. Endpoints and adverse events were independently assessed. Procedure success (≤30% residual stenosis) was achieved in 84% of treated lesions. The 1-year primary patency rate was 84% (claudicants 89.6% and CLI patients 78%, p=0.11), and the freedom from major amputation rate was 97.1% (claudicants 100% and CLI 93.8%, p=0.03). In both claudication and CLI patients, significant improvements in Rutherford category and objective measures of walking distance and quality of life were seen at 1 year in comparison to baseline. This study demonstrates that directional atherectomy in infrapopliteal arteries results in promising technical and clinical results at 1 year for claudicant as well as CLI patients. © The Author(s) 2015.

Preoperative Short-Course Concurrent Chemoradiation Therapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer: A Phase 2 Multicenter Study (KROG 10-01)

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

Yeo, Seung-Gu; Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan; Oh, Jae Hwan

Purpose: A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer. Methods and Materials: Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m{sup 2}/day) and leucovorin (20 mg/m{sup 2}/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologicmore » downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity. Results: Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery. Conclusions: Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique.« less

A multi-center randomized controlled trial to compare a self-ligating bracket with a conventional bracket in a UK population: Part 1: Treatment efficiency.

PubMed

O'Dywer, Lian; Littlewood, Simon J; Rahman, Shahla; Spencer, R James; Barber, Sophy K; Russell, Joanne S

2016-01-01

To use a two-arm parallel trial to compare treatment efficiency between a self-ligating and a conventional preadjusted edgewise appliance system. A prospective multi-center randomized controlled clinical trial was conducted in three hospital orthodontic departments. Subjects were randomly allocated to receive treatment with either a self-ligating (3M SmartClip) or conventional (3M Victory) preadjusted edgewise appliance bracket system using a computer-generated random sequence concealed in opaque envelopes, with stratification for operator and center. Two operators followed a standardized protocol regarding bracket bonding procedure and archwire sequence. Efficiency of each ligation system was assessed by comparing the duration of treatment (months), total number of appointments (scheduled and emergency visits), and number of bracket bond failures. One hundred thirty-eight subjects (mean age 14 years 11 months) were enrolled in the study, of which 135 subjects (97.8%) completed treatment. The mean treatment time and number of visits were 25.12 months and 19.97 visits in the SmartClip group and 25.80 months and 20.37 visits in the Victory group. The overall bond failure rate was 6.6% for the SmartClip and 7.2% for Victory, with a similar debond distribution between the two appliances. No significant differences were found between the bracket systems in any of the outcome measures. No serious harm was observed from either bracket system. There was no clinically significant difference in treatment efficiency between treatment with a self-ligating bracket system and a conventional ligation system.

Financial management of large, multi-center trials in a challenging funding milieu.

PubMed

Lovegreen, Olivia; Riggs, Danielle; Staten, Myrlene A; Sheehan, Patricia; Pittas, Anastassios G

2018-05-03

Randomized clinical trials that have public health implications but no or low potential for commercial gain are predominantly funded by governmental (e.g., National Institutes of Health (NIH)) and not-for-profit organizations. Our objective was to develop an alternative clinical trial site funding model for judicious allocation of declining public research funds. In the Vitamin D and Type 2 Diabetes (D2d) study, an NIH-supported, large clinical trial testing the effect of vitamin D supplementation on incident diabetes in 2423 participants at high risk for diabetes, a hybrid financial management model for supporting collaborating clinical sites was developed and applied. The funding model employed two reimbursement components: Core (for study start-up and partial efforts throughout the study, ~40% of the total site budget), invoiced by sites, and Performance-Based Payments (for successful enrollment of participants and completion of follow-up visits, ~60% of the total site budget), automatically issued to the sites by the Coordinating Center based on actual recruitment and visits conducted. Underperforming sites transitioned to Performance-Based Payments only. Recruitment occurred from October 2013 through December 2016, requiring one additional year than the 2-year projection. Median enrollment at each site was 88 participants (range 29-318; 20 to 205% of the site target). At the end of year 1, study-wide recruitment was at 12% of the target (vs. 50% projected) and 12% of the total grant award was invested. The model constantly evaluated sites' needs and re-allocated resources to meet the study enrollment goal. If D2d had issued cost reimbursement subaward agreements and sites invoiced for their entire budget, 83% of the award would have been spent for all study activities over the first 4 years of the trial compared to 65% of the award spent (US$26M) under the hybrid model used by D2d. It is feasible to foster a hybrid financial management approach to steward limited available public funds for research in a dynamic and consistent way that does not compromise the trial's scientific integrity and ensures conservation of funds to complete recruitment and continue to follow up participants.

First human use of hybrid synthetic/biologic mesh in ventral hernia repair: a multicenter trial.

PubMed

Bittner, James G; El-Hayek, Kevin; Strong, Andrew T; LaPinska, Melissa Phillips; Yoo, Jin S; Pauli, Eric M; Kroh, Matthew

2018-03-01

Mesh options for reinforcement of ventral/incisional hernia (VIH) repair include synthetic or biologic materials. While each material has known advantages and disadvantages, little is understood about outcomes when these materials are used in combination. This multicenter study reports on the first human use of a novel synthetic/biologic hybrid mesh (Zenapro ® Hybrid Hernia Repair Device) for VIH repair. This prospective, multicenter post-market clinical trial enrolled consecutive adults who underwent elective VIH repair with hybrid mesh placed in the intraperitoneal or retromuscular/preperitoneal position. Patients were classified as Ventral Hernia Working Group (VHWG) grades 1-3 and had clean or clean-contaminated wounds. Outcomes of ventral and incisional hernia were compared using appropriate parametric tests. In all, 63 patients underwent VIH repair with hybrid mesh. Most were females (54.0%), had a mean age of 54.8 ± 10.9 years and mean body mass index of 34.5 ± 7.8 kg/m 2 , and classified as VHWG grade 2 (87.3%). Most defects were midline (92.1%) with a mean area of 106 ± 155 cm 2 . Cases were commonly classified as clean (92.1%) and were performed laparoscopically (60.3%). Primary fascial closure was achieved in 82.5% with 28.2% requiring component separation. Mesh location was frequently intraperitoneal (69.8%). Overall, 39% of patients available for follow-up at 12 months suffered surgical site events, which were generally more frequent after incisional hernia repair. Of these, seroma (23.7%) was most common, but few (8.5%) required procedural intervention. Other surgical site events that required procedural intervention included hematoma (1.7%), wound dehiscence (1.7%), and surgical site infection (3.4%). Recurrence rate was 6.8% (95% CI 2.2-16.6%) at 12-months postoperatively. Zenapro ® Hybrid Hernia Repair Device is safe and effective in VHWG grade 1-2 patients with clean wounds out to 12 months. Short-term outcomes and recurrence rate are acceptable. This hybrid mesh represents a novel option for reinforcement during VIH repair.

The Japan Statin Treatment Against Recurrent Stroke (J-STARS): A Multicenter, Randomized, Open-label, Parallel-group Study.

PubMed

Hosomi, Naohisa; Nagai, Yoji; Kohriyama, Tatsuo; Ohtsuki, Toshiho; Aoki, Shiro; Nezu, Tomohisa; Maruyama, Hirofumi; Sunami, Norio; Yokota, Chiaki; Kitagawa, Kazuo; Terayama, Yasuo; Takagi, Makoto; Ibayashi, Setsuro; Nakamura, Masakazu; Origasa, Hideki; Fukushima, Masanori; Mori, Etsuro; Minematsu, Kazuo; Uchiyama, Shinichiro; Shinohara, Yukito; Yamaguchi, Takenori; Matsumoto, Masayasu

2015-09-01

Although statin therapy is beneficial for the prevention of initial stroke, the benefit for recurrent stroke and its subtypes remains to be determined in Asian, in whom stroke profiles are different from Caucasian. This study examined whether treatment with low-dose pravastatin prevents stroke recurrence in ischemic stroke patients. This is a multicenter, randomized, open-label, blinded-endpoint, parallel-group study of patients who experienced non-cardioembolic ischemic stroke. All patients had a total cholesterol level between 4.65 and 6.21 mmol/L at enrollment, without the use of statins. The pravastatin group patients received 10 mg of pravastatin/day; the control group patients received no statins. The primary endpoint was the occurrence of stroke and transient ischemic attack (TIA), with the onset of each stroke subtype set to be one of the secondary endpoints. Although 3000 patients were targeted, 1578 patients (491 female, age 66.2 years) were recruited and randomly assigned to pravastatin group or control group. During the follow-up of 4.9 ± 1.4 years, although total stroke and TIA similarly occurred in both groups (2.56 vs. 2.65%/year), onset of atherothrombotic infarction was less frequent in pravastatin group (0.21 vs. 0.64%/year, p = 0.0047, adjusted hazard ratio 0.33 [95%CI 0.15 to 0.74]). No significant intergroup difference was found for the onset of other stroke subtypes, and for the occurrence of adverse events. Although whether low-dose pravastatin prevents recurrence of total stroke or TIA still needs to be examined in Asian, this study has generated a hypothesis that it may reduce occurrence of stroke due to larger artery atherosclerosis. This study was initially supported by a grant from the Ministry of Health, Labour and Welfare, Japan. After the governmental support expired, it was conducted in collaboration between Hiroshima University and the Foundation for Biomedical Research and Innovation.

Early rehabilitation for severe acquired brain injury in intensive care unit: multicenter observational study.

PubMed

Bartolo, Michelangelo; Bargellesi, Stefano; Castioni, Carlo A; Bonaiuti, Donatella; Antenucci, Roberto; Benedetti, Angelo; Capuzzo, Valeria; Gamna, Federica; Radeschi, Giulio; Citerio, Giuseppe; Colombo, Carolina; Del Casale, Laura; Recubini, Elena; Toska, Saimir; Zanello, Marco; D'Aurizio, Carlo; Spina, Tullio; Del Gaudio, Alredo; Di Rienzo, Filomena; Intiso, Domenico; Dallocchio, Giulia; Felisatti, Giovanna; Lavezzi, Susanna; Zoppellari, Roberto; Gariboldi, Valentina; Lorini, Luca; Melizza, Giovanni; Molinero, Guido; Mandalà, Giorgio; Pignataro, Amedeo; Montis, Andrea; Napoleone, Alessandro; Pilia, Felicita; Pisu, Marina; Semerjian, Monica; Pagliaro, Giuseppina; Nardin, Lorella; Scarponi, Federico; Zampolini, Mauro; Zava, Raffaele; Massetti, Maria A; Piccolini, Carlo; Aloj, Fulvio; Antonelli, Sergio; Zucchella, Chiara

2016-02-01

The increased survival after a severe acquired brain injury (sABI) raise the problem of making most effective the treatments in Intensive Care Unit (ICU)/Neurointensive Care Unit (NICU), also integrating rehabilitation care. Despite previous studies reported that early mobilization in ICU was effective in preventing complications and reducing hospital stay, few studies addressed the rehabilitative management of sABI patients in ICU/NICU. To collect clinical and functional data about the early rehabilitative management of sABI patients during ICU/NICU stay. Prospective, observational, multicenter study. Fourteen facilities supplied by intensive neurorehabilitation units and ICU/NICUs. Consecutive sABI patients admitted to ICU/NICU. Patients were evaluated at admission and then every 3-5 days. Clinical, functional and rehabilitative data, including Glasgow Coma Scale (GCS), Disability Rating Scale (DRS), The Rancho Los Amigos Levels of Cognitive Functioning Scale (LCF), Early Rehabilitation Barthel Index (ERBI), Glasgow Outcome scale (GOS) and Functional Independence Measure (FIM) were collected. One hundred and two patients (F/M 44/58) were enrolled. The mean duration of ICU stay was 24.7±13.9 days and the first rehabilitative evaluation occurred after 8.7±8.8 days. Regular postural changes and multijoint mobilization were prescribed in 63.7% and 64.7% cases, respectively. The mean session duration was 38±11.5 minutes. Swallowing evaluation was performed in 14.7% patients, psychological support was provided to 12.7% of patients' caregivers, while 17.6% received a psycho-educational intervention, and 28.4% were involved in interdisciplinary team meetings. The main discharge destinations were Severe Acquired Brain Injury rehabilitation units for 43.7%, intensive neurorehabilitation units for 20.7%. Data showed that early rehabilitation was not diffusely performed in sABI subjects in ICU/NICU and rehabilitative interventions were variable; one-third of subjects were not referred to dedicated rehabilitation unit at discharge. The study stresses the need to spread and implement a rehabilitative culture also for critical ill patients due to neurological diseases.

A novel hemostatic powder for upper gastrointestinal bleeding: a multicenter study (the "GRAPHE" registry).

PubMed

Haddara, Sami; Jacques, Jeremie; Lecleire, Stéphane; Branche, Julien; Leblanc, Sarah; Le Baleur, Yann; Privat, Jocelyn; Heyries, Laurent; Bichard, Philippe; Granval, Philippe; Chaput, Ulriikka; Koch, Stephane; Levy, Jonathan; Godart, Bruno; Charachon, Antoine; Bourgaux, Jean-François; Metivier-Cesbron, Elodie; Chabrun, Edouard; Quentin, Vincent; Perrot, Bastien; Vanbiervliet, Geoffroy; Coron, Emmanuel

2016-12-01

Background and study aims: The hemostatic powder TC-325 (Hemospray; Cook Medical, Winston-Salem, North Carolina, USA) has shown promising results in the treatment of upper gastrointestinal bleeding (UGIB) in expert centers in pilot studies. The aim of this study was to evaluate the feasibility and efficacy of TC-325 in a large prospective registry of use in routine practice. Patients and methods: The data of all patients treated with TC-325 were prospectively collected through a national registry. Outcomes were the immediate feasibility and efficacy of TC-325 application, as well as the rates of rebleeding at Day 8 and Day 30. Multivariate analysis was performed to determine predictive factors of rebleeding. Results: A total of 202 patients were enrolled and 64 endoscopists participated from 20 centers. TC-325 was used as salvage therapy in 108 patients (53.5 %). The etiology of bleeding was an ulcer in 75 patients (37.1 %), tumor in 61 (30.2 %), postendoscopic therapy in 35 (17.3 %), or other in 31 (15.3 %). Application of the hemostatic powder was found to be very easy or easy in 31.7 % and 55.4 %, respectively. The immediate efficacy rate was 96.5 %. Recurrence of UGIB was noted at Day 8 and Day 30 in 26.7 % and 33.5 %, respectively. Predictive factors of recurrence at Day 8 were melena at initial presentation and use of TC-325 as salvage therapy. Conclusion: These multicenter data confirmed the high rate of immediate hemostasis, excellent feasibility, and good safety profile of TC-325, which could become the treatment of choice in bleeding tumors or postendoscopic bleeding but not in bleeding ulcers where randomized studies are needed. ClinicalTrials.gov (NCT02595853). © Georg Thieme Verlag KG Stuttgart · New York.

Efficacy and safety of sequential use of everolimus in Japanese patients with advanced renal cell carcinoma after failure of first-line treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitor: a multicenter phase II clinical trial.

PubMed

Oyama, Masafumi; Sugiyama, Takayuki; Nozawa, Masahiro; Fujimoto, Kiyohide; Kishida, Takeshi; Kimura, Go; Tokuda, Noriaki; Hinotsu, Shiro; Shimozuma, Kojiro; Akaza, Hideyuki; Ozono, Seiichiro

2017-06-01

Many studies have shown the efficacy of everolimus after pretreatment with vascular endothelial growth factor receptor-tyrosine kinase inhibitors. We investigated the efficacy and safety of everolimus as a second-line treatment after the failure of vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy in Japanese patients with advanced renal cell carcinoma. This was an open-label, multicenter, phase II trial conducted in Japan through the central registration system. A total of 57  patients were enrolled. Patients were administered 10 mg of everolimus q.d. orally. The primary efficacy endpoint was progression-free survival achieved by administration of everolimus. The median progression-free survival of patients administered everolimus was 5.03 months (95% confidence interval: 3.70-6.20). The median overall survival was not reached. The objective response rate was 9.4% (95% confidence interval: 3.1-20.7). The progression-free survival in the group of <100% relative dose intensity was 6.70 months (95% confidence interval: 4.13-11.60), and that in the group of 100% relative dose intensity was 3.77 months (hazard ratio: 2.79, 95% confidence interval: 2.77-5.63). The commonly observed adverse events and laboratory abnormalities were stomatitis (49.1%), hypertriglyceridemia (26.4%), interstitial lung disease (26.4%), anemia (22.6%) and hypercholesterolemia (22.6%). The median progression-free survival was almost similar to that recorded in the RECORD-1 study, whereas prolongation of overall survival was observed in the present study compared with the RECORD-1 study. The treatment outcomes of first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy and second-line everolimus treatment in Japanese patients were successfully established in the present study. © The Author 2017. Published by Oxford University Press.

Galectin 3 complements BNP in risk stratification in acute heart failure

PubMed Central

Fermann, Gregory J.; Lindsell, Christopher J.; Storrow, Alan B.; Hart, Kimberly; Sperling, Matthew; Roll, Susan; Weintraub, Neal L.; Miller, Karen F.; Maron, David J.; Naftilan, Allen J.; Mcpherson, John A.; Sawyer, Douglas B.; Christenson, Robert; Collins, Sean P.

2013-01-01

Background Galectin 3 (G3) is a mediator of fibrosis and remodeling in heart failure. Methods Patients diagnosed with and treated for Acute Heart Failure Syndromes were prospectively enrolled in the Decision Making in Acute Decompensated Heart Failure multicenter trial. Results Patients with a higher G3 had a history of renal disease, a lower heart rate and acute kidney injury. They also tended to have a history of HF and 30-day adverse events compared with B-type natriuretic peptide. Conclusion In Acute Heart Failure Syndromes, G3 levels do not provide prognostic value, but when used complementary to B-type natriuretic peptide, G3 is associated with renal dysfunction and may predict 30-day events. PMID:22998064

Efficacy of sublingual specific immunotherapy in intermittent and persistent allergic rhinitis in children: an observational case-control study on 171 patients. The EFESO-children multicenter trial.

PubMed

Acquistapace, Franca; Agostinis, Fabio; Castella, Vincenzo; Kantar, Ahmad; Novembre, Elio; Perrone, Maria Rosaria; Pietrasanta, Michele; Sambugaro, Renato; Milani, Massimo

2009-11-01

Sublingual-specific immunotherapy (SLIT) is considered as a valid treatment of respiratory allergies. However, there are few data on large sample size regarding its clinical role in 'real life' in term of reduction of symptoms, rescue medications and prevention of asthma in patients suffering from allergic rhinitis (AR) especially in children. We performed a multicenter, case-control study to evaluate the effect of SLIT in children (age 6-18 yr) with intermittent or persistent AR. 171 children (27% girls and 73% boys) with AR due to seasonal or perennial allergens were enrolled in a multicenter case-control study. Cases (n = 90) were defined as patients with intermittent (64%) or persistent (36%) AR who were treated for at least two consecutive years with specific SLIT with the related allergen extracts (SLITone ALK-Abellò). Controls (n = 81) were defined as sex-age- and type of allergen matched AR children who were never treated with specific immunotherapy and had no asthmatic symptoms at the beginning of observation period. Main outcomes of the study were the rhinoconjunctivitis symptom score (SS) (sneezing, rhinorrea, nasal itch, congestion, ocular itch and watery eyes) with a ranging scale from 0 (=no symptoms) to 3 (=severe symptoms) and the medication score (MS) evaluating symptomatic drug intake (antihystamine and inhaled corticosteroids). SS and MS were evaluated at the end of the observational period in relation with the period, considering the last 12 months, in which patients suffered the highest symptoms levels (i.e., peak of relevant pollen season (seasonal AR) or during the period of maximum allergen exposure in case of perennial AR). Secondary outcome of the study was the development of asthma symptoms during the observation period. SS (mean +/- SD) was 4.5 +/- 2.5 in cases and 9.0 +/- 3.0 in controls (-50%) (p = 0.0001). MS (mean +/- SD) was 2.5 +/- 1.9 and 3.6 +/- 2.1 in the case and control groups, respectively (-31%) (p = 0.0001). At the end of the observation period asthma symptoms were present in 14 subjects in the case group (15%) and in 20 children (24%) in the control group (p = 0.13). New skin sensitizations appeared in 6% of cases (n = 2) and in 36% (n = 12) of the controls (p = 0.001). The EFESO trial shows that a 2-yr once daily SLIT treatment in children with intermittent or persistent AR is associated with lower symptom and medication scores in comparison with subjects treated with symptomatic drugs only.

Phase Ib study of the mitochondrial inhibitor ME-344 plus topotecan in patients with previously treated, locally advanced or metastatic small cell lung, ovarian and cervical cancers.

PubMed

Diamond, Jennifer R; Goff, Barbara; Forster, Martin D; Bendell, Johanna C; Britten, Carolyn D; Gordon, Michael S; Gabra, Hani; Waterhouse, David M; Poole, Mark; Ross Camidge, D; Hamilton, Erika; Moore, Kathleen M

2017-10-01

Background This multicenter, open-label, phase Ib study was designed to assess the safety, pharmacokinetics and preliminary efficacy of ME-344, a mitochondrial inhibitor, administered in combination with the topoisomerase I inhibitor, topotecan, in patients with previously treated, locally advanced or metastatic small cell lung (SCLC), ovarian and cervical cancers. Patients and methods In Part 1, patients received ME-344 10 mg/kg intravenously weekly on days 1, 8, 15 and 22 in combination with topotecan 4 mg/m 2 on days 1, 8, and 15 of a 28 day cycle. Cycles were repeated until disease progression or unacceptable toxicity. Patients were evaluated for dose-limiting toxicity (DLT) in cycle 1 and ME-344 pharmacokinetic samples were obtained. In Part 2, patients with locally advanced or metastatic SCLC and ovarian cancer were enrolled in expansion cohorts treated at the recommended phase II dose (RP2D) determined in Part 1. Results Fourteen patients were enrolled in Part 1 and no DLTs were observed. The RP2D of ME-344 in combination with topotecan was established as 10 mg/kg. In Part 2, 32 patients were enrolled. The most common treatment-emergent all-grade and grade 3/4 toxicities included fatigue (65.2%, 6.5%), neutropenia (56.5%, 43.5%) and thrombocytopenia (50%, 23.9%). One patient with recurrent ovarian cancer experienced a partial response by RECIST 1.1 and 21 patients achieved stable disease as best response. Conclusions The combination of ME-344 10 mg/kg weekly and topotecan 4 mg/m 2 was tolerable, however, the degree of anti-cancer activity does not support further investigation of the combination in unselected patients with SCLC, ovarian and cervical cancers.

Tailoring Outreach Efforts to Increase Primary Care Use Among Homeless Veterans: Results of a Randomized Controlled Trial.

PubMed

O'Toole, Thomas P; Johnson, Erin E; Borgia, Matthew L; Rose, Jennifer

2015-07-01

Homeless individuals often have significant unmet health care needs that are critical to helping them leave homelessness. However, engaging them in primary and mental health care services is often elusive and difficult to achieve. We aimed to increase health-seeking behavior and receipt of health care among homeless Veterans. This was a multi-center, prospective, community-based, two-by-two randomized controlled trial of homeless Veterans. Homeless Veterans not receiving primary care participated in the study. An outreach intervention that included a personal health assessment and brief intervention (PHA/BI), and/or a clinic orientation (CO) was implemented. We measured receipt of primary care within 4 weeks of study enrollment. Overall, 185 homeless Veterans were enrolled: the average age was 48.6 years (SD 10.8), 94.6% were male, 43.0% were from a minority population, 12.0% were unsheltered, 25.5% were staying in a dusk-to-dawn emergency shelter, 26.1% were in transitional housing, while 27.7% were in an unstable, doubled-up arrangement. At one month, 77.3% of the PHA/BI plus CO group accessed primary care and by 6 months, 88.7% had been seen in primary care. This was followed by the CO-only group, 50.0% of whom accessed care in the first 4 weeks, the PHI/BI-only arm at 41.0% and the Usual Care arm at 30.6%. Chi-squared tests by group were significant (p < 0.001) at both 4 weeks and 6 months. There was no difference in attitudes about care at baseline and 6 months or in use patterns once enrolled in care. Our findings suggest that treatment-resistant/avoidant homeless Veterans can be effectively engaged in primary and other clinical care services through a relatively low intensity, targeted and tailored outreach effort.

Factors Associated With Time to Site Activation, Randomization, and Enrollment Performance in a Stroke Prevention Trial.

PubMed

Demaerschalk, Bart M; Brown, Robert D; Roubin, Gary S; Howard, Virginia J; Cesko, Eldina; Barrett, Kevin M; Longbottom, Mary E; Voeks, Jenifer H; Chaturvedi, Seemant; Brott, Thomas G; Lal, Brajesh K; Meschia, James F; Howard, George

2017-09-01

Multicenter clinical trials attempt to select sites that can move rapidly to randomization and enroll sufficient numbers of patients. However, there are few assessments of the success of site selection. In the CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trials), we assess factors associated with the time between site selection and authorization to randomize, the time between authorization to randomize and the first randomization, and the average number of randomizations per site per month. Potential factors included characteristics of the site, specialty of the principal investigator, and site type. For 147 sites, the median time between site selection to authorization to randomize was 9.9 months (interquartile range, 7.7, 12.4), and factors associated with early site activation were not identified. The median time between authorization to randomize and a randomization was 4.6 months (interquartile range, 2.6, 10.5). Sites with authorization to randomize in only the carotid endarterectomy study were slower to randomize, and other factors examined were not significantly associated with time-to-randomization. The recruitment rate was 0.26 (95% confidence interval, 0.23-0.28) patients per site per month. By univariate analysis, factors associated with faster recruitment were authorization to randomize in both trials, principal investigator specialties of interventional radiology and cardiology, pre-trial reported performance >50 carotid angioplasty and stenting procedures per year, status in the top half of recruitment in the CREST trial, and classification as a private health facility. Participation in StrokeNet was associated with slower recruitment as compared with the non-StrokeNet sites. Overall, selection of sites with high enrollment rates will likely require customization to align the sites selected to the factor under study in the trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02089217. © 2017 American Heart Association, Inc.

Baseline Demographics, Safety, and Patient Acceptance of an Insertable Cardiac Monitor for Atrial Fibrillation Screening: The REVEAL-AF Study.

PubMed

Conti, Sergio; Reiffel, James A; Gersh, Bernard J; Kowey, Peter R; Wachter, Rolf; Halperin, Jonathan L; Kaplon, Rachelle E; Pouliot, Erika; Verma, Atul

2017-01-01

Given the high prevalence and risk of stroke associated with atrial fibrillation (AF), detection strategies have important public health implications. The ongoing prospective, single-arm, open-label, multicenter REVEAL AF trial is evaluating the incidence of previously undetected AF using an insertable cardiac monitor (ICM) in patients without prior AF or device implantation, but who could be at risk for AF due to their demographic characteristics, +/- non-specific but compatible symptoms. Enrollment required an elevated AF risk profile defined as CHADS2≥3 or CHADS 2 =2 plus one or more of the following: coronary artery disease, renal impairment, sleep apnea or chronic obstructive pulmonary disease. Exclusions included stroke or transient ischemic attack occurring in the previous year. Of 450 subjects screened, 399 underwent a device insertion attempt, and 395 were included in the final analysis (Reveal XT: n=122; Reveal LINQ: n=273; excluded: n=4). Participants were primarily identified by demographic characteristics and the presence of nonspecific symptoms, but without prior documentation of "overt" AF. The most common symptoms were palpitations (51%), dizziness/lightheadedness/pre-syncope (36%), and shortness of breath (36%). Over 100 subjects were enrolled in each pre-defined CHADS2 subgroup (2, 3 and ≥4). AF risk factors not included in the CHADS2 score were well represented (prevalence≥15%). Procedure and/or device related serious adverse events were low, with the miniaturized Reveal LINQ ICM having a more favorable safety profile than the predicate Reveal XT (all: n=13 [3.3%]; LINQ: n=6 [2.2%]; XT: n=7 [5.7%]). These data demonstrate that REVEAL AF was successful in enrolling its target population, high risk patients were willing to undergo ICM monitoring for AF screening, and ICM use in this group is becoming increasingly safe with advancements in technology. A clinically meaningful incidence of device detected AF in this study will inform clinical decisions regarding ICM use for AF screening in patients at risk.

Standardization of Clinical Assessment and Sample Collection Across All PERCH Study Sites

PubMed Central

Prosperi, Christine; Baggett, Henry C.; Brooks, W. Abdullah; Deloria Knoll, Maria; Hammitt, Laura L.; Howie, Stephen R. C.; Kotloff, Karen L.; Levine, Orin S.; Madhi, Shabir A.; Murdoch, David R.; O’Brien, Katherine L.; Thea, Donald M.; Awori, Juliet O.; Bunthi, Charatdao; DeLuca, Andrea N.; Driscoll, Amanda J.; Ebruke, Bernard E.; Goswami, Doli; Hidgon, Melissa M.; Karron, Ruth A.; Kazungu, Sidi; Kourouma, Nana; Mackenzie, Grant; Moore, David P.; Mudau, Azwifari; Mwale, Magdalene; Nahar, Kamrun; Park, Daniel E.; Piralam, Barameht; Seidenberg, Phil; Sylla, Mamadou; Feikin, Daniel R.; Scott, J. Anthony G.; O’Brien, Katherine L.; Levine, Orin S.; Knoll, Maria Deloria; Feikin, Daniel R.; DeLuca, Andrea N.; Driscoll, Amanda J.; Fancourt, Nicholas; Fu, Wei; Hammitt, Laura L.; Higdon, Melissa M.; Kagucia, E. Wangeci; Karron, Ruth A.; Li, Mengying; Park, Daniel E.; Prosperi, Christine; Wu, Zhenke; Zeger, Scott L.; Watson, Nora L.; Crawley, Jane; Murdoch, David R.; Brooks, W. Abdullah; Endtz, Hubert P.; Zaman, Khalequ; Goswami, Doli; Hossain, Lokman; Jahan, Yasmin; Ashraf, Hasan; Howie, Stephen R. C.; Ebruke, Bernard E.; Antonio, Martin; McLellan, Jessica; Machuka, Eunice; Shamsul, Arifin; Zaman, Syed M.A.; Mackenzie, Grant; Scott, J. Anthony G.; Awori, Juliet O.; Morpeth, Susan C.; Kamau, Alice; Kazungu, Sidi; Kotloff, Karen L.; Tapia, Milagritos D.; Sow, Samba O.; Sylla, Mamadou; Tamboura, Boubou; Onwuchekwa, Uma; Kourouma, Nana; Toure, Aliou; Madhi, Shabir A.; Moore, David P.; Adrian, Peter V.; Baillie, Vicky L.; Kuwanda, Locadiah; Mudau, Azwifarwi; Groome, Michelle J.; Baggett, Henry C.; Thamthitiwat, Somsak; Maloney, Susan A.; Bunthi, Charatdao; Rhodes, Julia; Sawatwong, Pongpun; Akarasewi, Pasakorn; Thea, Donald M.; Mwananyanda, Lawrence; Chipeta, James; Seidenberg, Phil; Mwansa, James; wa Somwe, Somwe; Kwenda, Geoffrey

2017-01-01

Abstract Background. Variable adherence to standardized case definitions, clinical procedures, specimen collection techniques, and laboratory methods has complicated the interpretation of previous multicenter pneumonia etiology studies. To circumvent these problems, a program of clinical standardization was embedded in the Pneumonia Etiology Research for Child Health (PERCH) study. Methods. Between March 2011 and August 2013, standardized training on the PERCH case definition, clinical procedures, and collection of laboratory specimens was delivered to 331 clinical staff at 9 study sites in 7 countries (The Gambia, Kenya, Mali, South Africa, Zambia, Thailand, and Bangladesh), through 32 on-site courses and a training website. Staff competency was assessed throughout 24 months of enrollment with multiple-choice question (MCQ) examinations, a video quiz, and checklist evaluations of practical skills. Results. MCQ evaluation was confined to 158 clinical staff members who enrolled PERCH cases and controls, with scores obtained for >86% of eligible staff at each time-point. Median scores after baseline training were ≥80%, and improved by 10 percentage points with refresher training, with no significant intersite differences. Percentage agreement with the clinical trainer on the presence or absence of clinical signs on video clips was high (≥89%), with interobserver concordance being substantial to high (AC1 statistic, 0.62–0.82) for 5 of 6 signs assessed. Staff attained median scores of >90% in checklist evaluations of practical skills. Conclusions. Satisfactory clinical standardization was achieved within and across all PERCH sites, providing reassurance that any etiological or clinical differences observed across the study sites are true differences, and not attributable to differences in application of the clinical case definition, interpretation of clinical signs, or in techniques used for clinical measurements or specimen collection. PMID:28575355

Multicenter study of combination DEP regimen as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis.

PubMed

Wang, Yini; Huang, Wenqiu; Hu, Liangding; Cen, Xinan; Li, Lihong; Wang, Jijun; Shen, Jianliang; Wei, Na; Wang, Zhao

2015-11-05

Hemophagocytic lymphohistiocytosis (HLH) is a refractory immune disorder with a significant risk of death. Although standard therapy has dramatically improved survival in HLH patients, approximately 30%, especially adults, show no response to current treatment strategies. This prospective study aimed to investigate the efficacy of liposomal doxorubicin treatment combined with etoposide and methylprednisolone (doxorubicin-etoposide-methylprednisolone; DEP) as a salvage therapy for adult refractory HLH. Adult patients who did not achieve at least partial response 2 weeks after initial standard HLH therapy were enrolled in this study between June 2013 and June 2014. Response to salvage therapy was assessed at 2 and 4 weeks after initiation of DEP therapy and patients were followed until death or until November 2014. Sixty-three refractory HLH patients were enrolled, including 29 cases of lymphoma-associated HLH, 22 cases of Epstein-Barr virus-associated HLH, and 4 cases of familial HLH. There were 8 cases with unknown underlying diseases. Seventeen cases (27.0%) achieved complete response and 31 cases (49.2%) achieved partial response. The overall response was 76.2% (48/63). Patients who showed no response to DEP died within 4 weeks after salvage therapy. Twenty-nine of the 48 patients who achieved partial or complete response survived to subsequent chemotherapy, allogenic hematopoietic stem cell transplantation, or splenectomy. Our study suggests that DEP regimen is an effective salvage regimen for adult refractory HLH, which can prolong patient survival as we continue to understand the responsible mechanisms and bridge the gap between HLH and its underlying diseases. This study was registered in the Chinese Clinical Trials Registry Platform (http://www.chictr.org.cn/) as ChiCTR-IPC-14005514. © 2015 by The American Society of Hematology.

Alosetron use in clinical practice: significant improvement in irritable bowel syndrome symptoms evaluated using the US Food and Drug Administration composite endpoint.

PubMed

Lacy, Brian E; Nicandro, Jean Paul; Chuang, Emil; Earnest, David L

2018-01-01

Alosetron is approved to treat women with severe IBS and diarrhea (IBS-D) who have failed standard therapy. In our study, we aimed to evaluate alosetron efficacy using new US Food and Drug Administration (FDA) endpoints and utilization in clinical practice. This prospective, open-label, multicenter, observational 12-week study evaluated women with severe IBS-D enrolled in the alosetron prescribing program. The coprimary FDA endpoints were changes from baseline in stool consistency and abdominal pain severity. Responders achieved a 30% decrease compared with baseline in weekly average of the worst abdominal pain in the past 24 h, and a 50% or greater reduction from baseline in the number of days/week with at least one stool of type 6 (mushy) or type 7 (watery) consistency. Secondary endpoints included changes from baseline in stool frequency, fecal urgency and fecal incontinence. Enrolled patients ( n = 192) were primarily White (90.6%), with a mean age of 44.5 years. Patient and physician rating of IBS severity was between moderate and severe (85.9% concordance, Spearman coefficient 0.429, p < 0.0001). Alosetron 0.5 mg twice daily (82.8%) was the most common dosing regimen. A total of 152 alosetron-treated patients completed the study. Of 105 fully evaluable patients, 45% met the FDA composite endpoint responder criteria for ⩾50% of the study period. Improvements in all individual symptoms were statistically significant compared with baseline. There were no serious adverse events, cases of colonic ischemia, or complications of constipation. In a clinical practice setting study, alosetron demonstrated treatment success using a rigorous FDA composite endpoint and also improved multiple other IBS symptoms, including fecal urgency and incontinence in women with severe IBS-D [ClinicalTrials.gov identifier: NCT01257477].

Prospective Observational Study of Implantable Cardioverter‐Defibrillators in Primary Prevention of Sudden Cardiac Death: Study Design and Cohort Description

PubMed Central

Cheng, Alan; Dalal, Darshan; Butcher, Barbara; Norgard, Sanaz; Zhang, Yiyi; Dickfeld, Timm; Eldadah, Zayd A.; Ellenbogen, Kenneth A.; Guallar, Eliseo; Tomaselli, Gordon F.

2013-01-01

Background Primary‐prevention implantable cardioverter‐defibrillators (ICDs) reduce total mortality in patients with severe left ventricular systolic function. However, only a minority of patients benefit from these devices. We designed the Prospective Observational Study of Implantable Cardioverter‐Defibrillators (PROSE‐ICD) to identify risk factors and enhance our understanding of the biological mechanisms that predispose to arrhythmic death in patients undergoing ICD implantation for primary prevention of sudden death. Methods and Results This is a multicenter prospective cohort study with a target enrollment of 1200 patients. The primary end point is ICD shocks for adjudicated ventricular tachyarrhythmias. The secondary end point is total mortality. All patients undergo a comprehensive evaluation including history and physical examination, signal‐averaged electrocardiograms, and blood sampling for genomic, proteomic, and metabolomic analyses. Patients are evaluated every 6 months and after every known ICD shock for additional electrocardiographic and blood sampling. As of December 2011, a total of 1177 patients have been enrolled with more nonwhite and female patients compared to previous randomized trials. A total of 143 patients have reached the primary end point, whereas a total of 260 patients died over an average follow‐up of 59 months. The PROSE‐ICD study represents a real‐world cohort of individuals with systolic heart failure receiving primary‐prevention ICDs. Conclusions Extensive electrophysiological and structural phenotyping as well as the availability of serial DNA and serum samples will be important resources for evaluating novel metrics for risk stratification and identifying patients at risk for arrhythmic sudden death. Clinical Trial Registration URL: http://clinicaltrials.gov/ Unique Identifier: NCT00733590. PMID:23525420

Clinical trial of nintedanib in patients with recurrent or metastatic salivary gland cancer of the head and neck: A multicenter phase 2 study (Korean Cancer Study Group HN14-01).

PubMed

Kim, Youjin; Lee, Su Jin; Lee, Ji Yun; Lee, Se-Hoon; Sun, Jong-Mu; Park, Keunchil; An, Ho Jung; Cho, Jae Yong; Kang, Eun Joo; Lee, Ha-Young; Kim, Jinsoo; Keam, Bhumsuk; Kim, Hye Ryun; Lee, Kyoung Eun; Choi, Moon Young; Lee, Ki Hyeong; Ahn, Myung-Ju

2017-06-01

Salivary gland cancers (SGCs) are uncommon and account for less than 5% of all head and neck cancers, but they are histologically heterogeneous. No specific therapy, including targeted agents, has consistently improved clinical outcomes in recurrent/metastatic SGC. Recent studies suggest that vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) play important roles in SGC. Nintedanib is a potent small-molecule, triple-receptor tyrosine kinase inhibitor (VEGFR1, VEGFR2, and VEGFR3; fibroblast growth factor receptor 1 [FGFR1], FGFR2, and FGFR3; and PDGFRα and PDGFRß). This study sought to determine the antitumor activity of nintedanib in patients with recurrent or metastatic SGC. This open-label, multicenter, phase 2, single-arm study was conducted at 11 hospitals in South Korea. Patients with pathologically confirmed recurrent and/or metastatic SGC for whom at least 1 line of systemic chemotherapy had failed were enrolled. Nintedanib was given orally at 200 mg twice a day until disease progression or unacceptable toxicity. The primary endpoint was the response rate. The secondary endpoints were progression-free survival, overall survival, toxicity, and the disease-control rate. The Simon 2-stage minimax design was used. The median age of the patients was 54 years, 60% were female, and 95% had an Eastern Cooperative Oncology Group performance status of 0 or 1. The majority of the patients had adenoid cystic carcinoma (65%), and 40% received at least 2 prior rounds of chemotherapy. After 20 patients were enrolled, the study was stopped because no responders were observed at stage I. There were no partial responses, but the disease-control rate was 75% (15 of 20). The median duration of stable disease was 8.2 months (range, 1.76-12.36 months). At the time of the data cutoff, with a median follow-up of 9.5 months, the median overall survival had not been reached, and the progression-free survival rate at 6 months was 60% (95% confidence interval, 0.34-0.79). Grade 3 adverse events included liver enzyme elevation (25%) and nausea/vomiting (5%). Four patients who required a dose reduction because of a grade 3 liver enzyme elevation showed no further grade 3 events. Single-agent nintedanib did not yield a partial response but did achieve a 75% disease-control rate with long-term stabilization in SGC patients. Because of the high rate and long duration of disease control with a good safety profile, further investigation is warranted. Cancer 2017;123:1958-1964. © 2017 American Cancer Society. © 2017 American Cancer Society.

SAFETY OF A CRM197-CONJUGATED HAEMOPHILUS INFLUENZAE TYPE B VACCINE IN KOREAN CHILDREN.

PubMed

Song, Hyoyoung; Bock, Hans; Guadagno, Alana; Costantini, Marco; Baehner, Frank; Kim, Yeon Ho; Ahn, Seung In; Son, Ki Hyuk; Yim, Dong-Seok

2015-07-01

Haemophilus influenzae type b (Hib) is a major cause of meningitis and pneumonia with high morbidity and mortality rates in young children. The introduction of effective and well-tolerated conjugate Hib vaccines, has nearly eradicated this disease in many countries. We investigated the safety of the Hib PRP-CRM197 vaccine in a multi-center post-marketing surveillance (PMS) study. Korean children (N = 764) aged 1-33 months were enrolled when receiving a routine primary immunization or a booster vaccine with Hib PRP-CRM197 and solicited and unsolicited adverse events (AEs) were recorded using a diary card for 7 and 28 days after each vaccination, respectively. In this study, AEs were reported by 66% of subjects but were generally mild, with 42% of subjects reporting solicited AEs and 46% reporting unsolicited AEs. Among the unsolicited AEs, 98% were determined to be unrelated to the study vaccine. The studied Hib PRP-CRM197 vaccine was well tolerated by the study group and found to have a similar safety profile to that reported in other clinical studies. This vaccine is suitable for routine immunization against Hib disease among Korean children. AEs due to this vaccine will continue to be monitored.

Epidemiology and outcomes associated with moderate to heavy Candida colonization during pregnancy. Vaginal Infections and Prematurity Study Group.

PubMed

Cotch, M F; Hillier, S L; Gibbs, R S; Eschenbach, D A

1998-02-01

Our purpose was to determine the risk factors, physical findings, microflora, and pregnancy outcome among pregnant women with moderate to heavy vaginal growth of Candida albicans and other Candida species. A multicenter cohort of 13,914 women were enrolled between 23 and 26 weeks' gestation. Women completed a questionnaire, underwent a physical examination, and had genital specimens taken for culture. A subset of 1459 women were reexamined during the third trimester. Pregnancy outcomes were recorded at delivery. The prevalence of moderate to heavy Candida colonization at midgestation was 10%. Colonized women, 83% of whom carried C. albicans, were more likely to be black or Hispanic, unmarried, a previous oral contraceptive user, and to manifest clinical signs indicative of Candida carriage. Candida colonization was positively associated with Trichomonas vaginalis, group B streptococci, and aerobic Lactobacillus and was not associated with adverse pregnancy outcome. These results suggest that Candida colonization is not associated with low birth weight or preterm delivery.

A randomized, double-blinded, placebo-controlled, multicenter trial, healing effect of rebamipide in patients with low-dose aspirin and/or non-steroidal anti-inflammatory drug induced small bowel injury.

PubMed

Kurokawa, Sei; Katsuki, Shinichi; Fujita, Tomoki; Saitoh, Yusuke; Ohta, Hidetoshi; Nishikawa, Kouji; Sato, Yasushi; Sato, Yasuhiro; Ohira, Koji; Yamada, Masataka; Kato, Mototsugu

2014-02-01

It is not clear what kind of drug is appropriate to heal NSAID-induced enteropathy. Several reports showed the preventive effect of prostaglandin analogue or inducer using healthy subjects who took NSAIDs. However there was no report for healing effect and for patients. The aim of this study was to evaluate the healing effect of rebamipide in patients with NSAIDs-induced enteropathy. In addition, we evaluated for nutritional parameter. This study was conducted as a randomized, double-blinded, placebo-controlled, multicenter trial. Study protocol was approved by each hospital's ethical committees. Patients with LDA and/or NSAID more than 3 months were enrolled. Patients with enteropathy were divided into the placebo and the rebamipide groups. Rebamipide 100 mg three times daily was administered during 4 weeks. Capsule endoscopies were performed at 0 and 4 week. The number of small intestinal ulcer and erosion were evaluated. Total protein was analyzed as nutritional parameter. Sixty one participants were completed this study. Change in number of small intestinal erosion in the rebamipide group was -2.5 ± 3.4, and 2.1 ± 3.9 in the placebo group (P < 0.0001). Change in number of small intestinal ulcer in the rebamipide group was -0.5 ± 1.6, and 0.1 ± 0.7 in the placebo group (P = 0.024). Change in serum total protein levels in the rebamipide group was 0.06 ± 0.36, and -0.27 ± 0.34 in the placebo group (P = 0.0005). Rebamipide has not only the healing effect for NSAIDs-induced enteropathy compared with placebo, but the improvement of nutritional condition. These results showed a tentative therapeutical strategy for chronic NSAIDs users.

Does the intragastric balloon have a predictive role in subsequent LAP-BAND(®) surgery? Italian multicenter study results at 5-year follow-up.

PubMed

Genco, Alfredo; Lorenzo, Michele; Baglio, Giovanni; Furbetta, Francesco; Rossi, Angelo; Lucchese, Marcello; Zappa, Marco A; Giardiello, Cristiano; Micheletto, Giancarlo; Bottari, Giorgio; Puglisi, Francesco; Montanari, Luca; Simona, Civitelli; Forestieri, Pietro

2014-01-01

The intragastric balloon has been reported to be a safe and effective tool for temporary weight loss. The aim of this study is the evaluation of the possible predictive role of intragastric balloon when used before laparoscopic adjustable gastric banding. A longitudinal multicenter study was conducted in patients with body mass index (BMI)>35 kg/m(2) who underwent gastric banding with the BioEnterics Intragastric Balloon (BIB). After balloon removal (6 mo), patients were allocated into 2 group according to their percentage of excess weight loss (%EWL): group>25 (%EWL>25%) and group<25 (%EWL<25%). Patients from both group underwent laparoscopic adjustable gastric banding (LAGB) 1-3 months after BIB removal. The LAP-BAND AP band was placed in all patients via pars flaccida. Weight loss parameters were considered in both groups. From January 2005 to December 2009, 1357 patients were enrolled in this study. Mean BMI at time of BIB positioning was 44.9±8.4 (range 29-82.5). After 6 months, at time of removal, mean BMI was 39.4±7.3. According to the cutoff, patients were allocated into group A (n = 699) and group B (n = 658). At this time the mean BMI was 36.4±6.4 and 42.7±6.9 (P = .001) in groups A and B, respectively. At 1-year follow-up from LAGB, mean BMI was 35.8±6.5 and 40.0±7.4 (P<.001) in groups A and B, respectively. This significant difference was confirmed at 3- and 5-year follow-ups. A similar pattern was observed with the %EWL. Satisfactory results with BIB are predictive of a positive outcome of LASB at 1, 3, and 5 years after the procedure, and poor results do not inevitably indicate a negative outcome for gastric banding. Copyright © 2014 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Impact of a Developmental Care Training Course on the Knowledge and Satisfaction of Health Care Professionals in Neonatal Units: A Multicenter Study.

PubMed

Mosqueda-Peña, Rocío; Lora-Pablos, David; Pavón-Muñoz, Abraham; Ureta-Velasco, Noelia; Moral-Pumarega, María Teresa; Pallás-Alonso, Carmen Rosa

2016-04-01

The impact of health-related continuing education courses on knowledge acquisition and clinical practice is infrequently evaluated, despite higher numbers of people enrolling in them. The majority of health care professionals working in neonatal intensive care units (NICUs) have received no training in developmental care (DC). The purpose of this study was to determine whether participation in a theoretical-practical course on DC had an effect on the degree of knowledge possessed by professionals in general terms and with respect to neonatal intensive care. The relationship between course satisfaction and knowledge acquisition was also studied. This was an observational multicenter study conducted in 20 neonatal units in Madrid. A pre- and post-course questionnaire evaluated both knowledge and satisfaction levels regarding the course on DC and the Newborn Individualized Developmental Care and Assessment Program (NIDCAP). We carried out a multivariate linear regression analysis to determine whether there was a correlation between knowledge gained and satisfaction level. A total of 566 professionals participated, with a 99% pre-course and a 90% post-course response rate. The mean rate of correct pre-course answers was 65%, while the mean rate of post-course correct answers was 81% (p < 0.001). Results were similar at all levels of neonatal care (Level I: 64% vs 80%; Level II: 64% vs. 83%; and 65% vs. 81%). Scores on a scale of satisfaction from 1 to 5 were high (averages of above 4 for all lectures and workshops). Pre-course knowledge scores, but not satisfaction, significantly influenced post-course knowledge (β 0.499; p < 0.01). Previous DC knowledge among Madrid health care professionals was similar, regardless of the level of neonatal care. Course attendance significantly improved the rate of correct answers. Although course satisfaction was high, there did not seem to be a correlation between knowledge gained and satisfaction. Copyright © 2016. Published by Elsevier B.V.

Multicenter Trial of Rivaroxaban for Early Discharge of Pulmonary Embolism From the Emergency Department (MERCURY PE): Rationale and Design.

PubMed

Singer, Adam J; Xiang, Jim; Kabrhel, Christopher; Merli, Gino J; Pollack, Charles; Tapson, Victor F; Wildgoose, Peter; Peacock, W Frank

2016-11-01

Traditionally, patients with pulmonary embolism (PE) are admitted from the emergency department and treated with low-molecular-weight heparin followed by warfarin. Several studies now demonstrate that it is possible to identify low-risk PE patients that can safely be treated as outpatients. The advent of the direct-acting oral anticoagulants such as rivaroxaban has made it easier than ever to manage patients outside of the hospital. This article describes the design of a randomized controlled trial aimed at testing the hypothesis that low-risk PE patients can be safely and effectively managed at home using rivaroxaban, resulting in fewer days of hospitalization than standard-of-care treatment. We have initiated a multicenter, open-label, randomized clinical trial in which low-risk adult PE patients (identified by the Hestia criteria) are randomized to outpatient management with oral rivaroxaban 15 mg twice daily for 21 days followed by 20 mg once daily for 90 days versus standard care, determined by the treating physician and based on local practices. The primary clinical endpoint will be the total number of inpatient hospital days (including the index admission) for venous thromboembolic or bleeding-related events during the first 30 days after randomization. A total of 150 subjects per group will provide 82% power to detect a difference of 1 day or greater in the primary outcome. Patient enrollment is ongoing at present in 45 of 60 planned sites. No interim analysis is planned and the study is being monitored by a data safety management board. The MERCURY PE study is designed to test the hypothesis that outpatient management of low-risk PE patients with rivaroxaban reduces the number of hospitalization days from venous thromboembolism and bleeding compared with standard care. This article describes the rationale and methodology for this study. © 2016 by the Society for Academic Emergency Medicine.

Sequential Therapy with Crizotinib and Alectinib in ALK-Rearranged Non-Small Cell Lung Cancer-A Multicenter Retrospective Study.

PubMed

Ito, Kentaro; Hataji, Osamu; Kobayashi, Hiroyasu; Fujiwara, Atsushi; Yoshida, Masamichi; D'Alessandro-Gabazza, Corina N; Itani, Hidetoshi; Tanigawa, Motoaki; Ikeda, Takuya; Fujiwara, Kentaro; Fujimoto, Hajime; Kobayashi, Tetsu; Gabazza, Esteban C; Taguchi, Osamu; Yamamoto, Nobuyuki

2017-02-01

Alectinib and crizotinib have been approved for the therapy of NSCLC caused by anaplastic lymphoma kinase gene (ALK) rearrangement. The effect of alectinib or crizotinib on overall survival (OS) in patients with ALK-rearranged NSCLC remains unknown. A multicenter retrospective study was conducted to compare OS between patients receiving alectinib and crizotinib and between patients treated with alectinib and those treated sequentially with crizotinib and then alectinib after crizotinib failure. The time to treatment failure (TTF), progression-free survival (PFS), and OS were compared. Sixty-one patients with ALK-rearranged NSCLC were enrolled. Forty-six patients were treated with anaplastic lymphoma kinase (ALK) inhibitors (31 with crizotinib, 28 with alectinib, and 13 with both ALK inhibitors). The response rate was 66.7% for the crizotinib-treated group and 80.8% for the alectinib-treated group. Among all patients, TTF and PFS were significantly prolonged in the alectinib-treated group compared with in the crizotinib-treated group. Subgroup analyses revealed significantly prolonged TTF for alectinib compared with crizotinib therapy in the ALK inhibitor-naive population. OS was significantly longer in the alectinib-treated group than in the crizotinib-treated group. The TTF and OS of patients treated sequentially with crizotinib and then with alectinib after crizotinib failure tended to be longer than those of patients treated with alectinib alone. Therapy with alectinib alone was significantly superior to therapy with crizotinib alone in terms of TTF, PFS, and OS, and sequential therapy with crizotinib and alectinib after crizotinib failure tended to provide a better OS benefit than did therapy with alectinib alone in patients with ALK-positive NSCLC. However, large-scale prospective studies are needed to confirm these observations. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Hospitalization for community-acquired febrile urinary tract infection: validation and impact assessment of a clinical prediction rule.

PubMed

Stalenhoef, Janneke E; van der Starre, Willize E; Vollaard, Albert M; Steyerberg, Ewout W; Delfos, Nathalie M; Leyten, Eliane M S; Koster, Ted; Ablij, Hans C; Van't Wout, Jan W; van Dissel, Jaap T; van Nieuwkoop, Cees

2017-06-06

There is a lack of severity assessment tools to identify adults presenting with febrile urinary tract infection (FUTI) at risk for complicated outcome and guide admission policy. We aimed to validate the Prediction Rule for Admission policy in Complicated urinary Tract InfeCtion LEiden (PRACTICE), a modified form of the pneumonia severity index, and to subsequentially assess its use in clinical practice. A prospective observational multicenter study for model validation (2004-2009), followed by a multicenter controlled clinical trial with stepped wedge cluster-randomization for impact assessment (2010-2014), with a follow up of 3 months. Paricipants were 1157 consecutive patients with a presumptive diagnosis of acute febrile UTI (787 in validation cohort and 370 in the randomized trial), enrolled at emergency departments of 7 hospitals and 35 primary care centers in the Netherlands. The clinical prediction rule contained 12 predictors of complicated course. In the randomized trial the PRACTICE included guidance on hospitalization for high risk (>100 points) and home discharge for low risk patients (<75 points), in the control period the standard policy regarding hospital admission was applied. Main outcomes were effectiveness of the clinical prediction rule, as measured by primary hospital admission rate, and its safety, as measured by the rate of low-risk patients who needed to be hospitalized for FUTI after initial home-based treatment, and 30-day mortality. A total of 370 patients were included in the randomized trial, 237 in the control period and 133 in the intervention period. Use of PRACTICE significantly reduced the primary hospitalization rate (from 219/237, 92%, in the control group to 96/133, 72%, in the intervention group, p < 0.01). The secondary hospital admission rate after initial outpatient treatment was 6% in control patients and 27% in intervention patients (1/17 and 10/37; p < 0.001). Although the proposed PRACTICE prediction rule is associated with a lower number of hospital admissions of patients presenting to the ED with presumptive febrile urinary tract infection, futher improvement is necessary to reduce the occurrence of secondary hospital admissions. NTR4480 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4480 , registered retrospectively 25 mrt 2014 (during enrollment of subjects).

Outcome of Treatment of Uveitic Macular Edema: The Multicenter Uveitis Steroid Treatment Trial 2-Year Results.

PubMed

Tomkins-Netzer, Oren; Lightman, Susan; Drye, Lea; Kempen, John; Holland, Gary N; Rao, Narsing A; Stawell, Richard J; Vitale, Albert; Jabs, Douglas A

2015-11-01

To evaluate the 2-year outcomes of uveitic macular edema. Longitudinal follow-up of a randomized cohort. At baseline, 148 eyes of 117 patients enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial had macular edema, and 134 eyes of 108 patients completed 2-year follow-up. Patients enrolled in the study were randomized to either systemic immunosuppression or intravitreal fluocinolone acetonide implant therapy. Macular edema was defined as thickening of the retina (center point thickness≥240 μm) on time-domain optical coherence tomography (OCT) of macula. Improvement in macular edema (≥20% reduction in central point thickness on OCT), resolution of macular edema (normalization of thickness on OCT), and best-corrected visual acuity (BCVA). Between randomization and 2-years' follow-up, 62% and 25% of eyes in the systemic and implant groups, respectively, received at least 1 supplemental regional corticosteroid injection. By 2-years' follow-up, macular edema improved in 71% of eyes and resolved in 60%. There were no differences between treatment groups in the proportion of eyes with macular edema improving (systemic therapy vs. implant, 65% vs. 77%; P=0.20) and resolving (52% vs. 68%; P=0.28), but eyes randomized to implant had more improvement in macular thickness (median decrease of 180 vs. 109 μm in the systemic therapy group; P=0.04). Eyes with baseline fluorescein angiographic leakage were more likely to improve than those without (76% vs. 58%; P=0.03). Overall, there was a mean 5-letter (1 line) improvement in BCVA at 2 years. Mean changes in BCVA from baseline at 2 years by macular edema response status were: resolution, +10 letters; improvement without resolution, +10 letters (P=0.92); little to no change, 6 letters (P=0.19); and worsening, -16 letters (worsening acuity; P=0.0003). About two thirds of eyes with uveitic macular edema were observed to experience improvement in the edema and visual acuity with implant or systemic treatment. Fluocinolone acetonide implant therapy was associated with a greater quantitative improvement in thickness. Fluorescein angiography leakage was associated with a greater likelihood of improvement in macular edema. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Serum Irisin Predicts Mortality Risk in Acute Heart Failure Patients.

PubMed

Shen, Shutong; Gao, Rongrong; Bei, Yihua; Li, Jin; Zhang, Haifeng; Zhou, Yanli; Yao, Wenming; Xu, Dongjie; Zhou, Fang; Jin, Mengchao; Wei, Siqi; Wang, Kai; Xu, Xuejuan; Li, Yongqin; Xiao, Junjie; Li, Xinli

2017-01-01

Irisin is a peptide hormone cleaved from a plasma membrane protein fibronectin type III domain containing protein 5 (FNDC5). Emerging studies have indicated association between serum irisin and many major chronic diseases including cardiovascular diseases. However, the role of serum irisin as a predictor for mortality risk in acute heart failure (AHF) patients is not clear. AHF patients were enrolled and serum was collected at the admission and all patients were followed up for 1 year. Enzyme-linked immunosorbent assay was used to measure serum irisin levels. To explore predictors for AHF mortality, the univariate and multivariate logistic regression analysis, and receiver-operator characteristic (ROC) curve analysis were used. To determine the role of serum irisin levels in predicting survival, Kaplan-Meier survival analysis was used. In this study, 161 AHF patients were enrolled and serum irisin level was found to be significantly higher in patients deceased in 1-year follow-up. The univariate logistic regression analysis identified 18 variables associated with all-cause mortality in AHF patients, while the multivariate logistic regression analysis identified 2 variables namely blood urea nitrogen and serum irisin. ROC curve analysis indicated that blood urea nitrogen and the most commonly used biomarker, NT-pro-BNP, displayed poor prognostic value for AHF (AUCs ≤ 0.700) compared to serum irisin (AUC = 0.753). Kaplan-Meier survival analysis demonstrated that AHF patients with higher serum irisin had significantly higher mortality (P<0.001). Collectively, our study identified serum irisin as a predictive biomarker for 1-year all-cause mortality in AHF patients though large multicenter studies are highly needed. © 2017 The Author(s). Published by S. Karger AG, Basel.

Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients.

PubMed

Beck, David E; Sweeney, W Brian; McCarter, Martin D

2014-12-01

Postoperative ileus is a significant clinical challenge lacking effective management strategies. Ghrelin-receptor stimulation has promotility effects in the upper and lower gastrointestinal tract. This proof-of-concept, phase 2, randomized study evaluated the safety and efficacy of the ghrelin-receptor agonist ipamorelin in the treatment of postoperative ileus following abdominal surgery (ClinicalTrials.gov NCT00672074). The design was a multicenter, double-blind, placebo-controlled, clinical trial. The settings include hospital inpatients. The patients were adults undergoing small and large bowel resection by open or laparoscopic surgery. The intervention was intravenous infusions of 0.03-mg/kg ipamorelin vs placebo twice daily, on postoperative day 1 to 7 or hospital discharge. Safety was assessed by monitoring adverse events and laboratory tests. The key efficacy endpoint was time from first dose of study drug to tolerance of a standardized solid meal. One hundred seventeen patients were enrolled, of whom 114 patients composed the safety and modified intent-to-treat populations. Demographic and disease characteristics were balanced between groups. Overall incidence of any treatment-emergent adverse events was 87.5 % in the ipamorelin group and 94.8 % in placebo group. Median time to first tolerated meal was 25.3 and 32.6 h in the ipamorelin and placebo groups, respectively (p = 0.15). This proof of concept study was small and enrolled patients with a broad range of underlying conditions. Ipamorelin 0.03-mg/kg twice daily for up to 7 days was well tolerated. There were no significant differences between ipamorelin and placebo in the key and secondary efficacy analyses.

Multicenter phase II trial of combination therapy with meloxicam, a cox-2 inhibitor, and natural interferon-alpha for metastatic renal cell carcinoma.

PubMed

Shinohara, Nobuo; Kumagai, Akira; Kanagawa, Kouichi; Maruyama, Satoru; Abe, Takashige; Sazawa, Ataru; Nonomura, Katsuya

2009-11-01

We conducted a Phase II trial to investigate the efficacy of combined therapy with meloxicam, a cyclooxygenase-2 inhibitor and natural interferon (IFN)-alpha in renal cell carcinoma patients with distant metastasis. The subjects of this study were patients with untreated renal cell carcinoma who were diagnosed from the results of imaging or pathological studies and who had measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST). Patients could be enrolled in the study irrespective of whether nephrectomy had been performed. Treatment involved the subcutaneous injection of natural IFN-alpha at 3 x 10(6) or 5 x 10(6) U three times weekly plus oral administration of meloxicam at 10 mg once daily. A total of 43 patients were enrolled in the present study, included 11 patients without nephrectomy, 23 patients with a high C-reactive protein (CRP) level and 23 patients with extrapulmonary metastasis. Four patients of complete response and 12 patients of partial response were confirmed, given an overall response rate of 37.2% (95% confidence interval, 23.0-53.3%). Stable disease for 6 months or longer was also obtained in 14 patients. The median time to progression was 14 months. Adverse events (AEs) observed were mainly flu-like symptoms due to cytokine. Although the Grade 3 or 4 AEs were fatigue, hepatic dysfunction, arthritis and gastric ulcer, all but one (gastric ulcer) were immediately improved by discontinuation of this combined therapy. The combination of meloxicam and natural IFN-alpha is considered to be an active regimen with tolerable toxicities as a first-line treatment of metastatic renal cell carcinoma.

Effect of Vitamin D Supplementation on Breast Cancer Biomarkers: CALGB 70806 (Alliance) Study Design and Baseline Data

PubMed Central

Apoe, Ogheneruona; Jung, Sin-Ho; Liu, Heshan; Seisler, Drew K; Charlamb, Jayne; Zekan, Patricia; Wang, Lili X.; Unzeitig, Gary W.; Garber, Judy; Marshall, James; Wood, Marie

2017-01-01

One in eight women will develop breast cancer over their lifetime with 230,000 women diagnosed in 2015. For this reason, breast cancer prevention efforts are essential. Vitamin D, with anticancer properties, may have a role in prevention of some cancers, including breast cancer. This report discusses the rationale, study protocol, and baseline data for a clinical trial of vitamin D and its effects on breast cancer biomarkers. This study was a randomized controlled trial designed to evaluate the effect of a fixed dose of vitamin D on specfic breast cancer biomarkers. Study participants were randomized to take either vitamin D or placebo for a period of 1 year. All participants had mammograms and blood drawn for serum biomarkers. A subset of participants underwent random periareolar fine needle aspiration to draw tissue for biomarkers. From January 2011 to December 2013, 300 premenopausal women, aged 59 or younger, were recruited from 41 institutions across the United States. A total of 102 women underwent random periareolar fine needle aspiration. The last subject completed the trial in January 2015. Baseline vitamin D levels for all participants ranged from 4–72 ng/mL, with 62% of participants being vitamin D deficient at enrollment (≥30 ng/mL or ≥75 nmo-l/L). The mean body mass index was 27.0 kg/m2 (range 15.1–53.6 kg/m2). 14% and 11.7% of participants were Hispanic or African American, respectively. Accrual and enrollment of participants is feasible for this type of multi-center prevention trial, and it can readily be carried out in a cooperative group setting. PMID:29081880

Endoscopic closure of persistent gastrocutaneous fistulae, after percutaneous endoscopic gastrostomy (PEG) tube placement, using the over-the-scope-clip system

PubMed Central

Changela, Kinesh; Culliford, Andrea; Duddempudi, Sushil; Krishnaiah, Mahesh; Anand, Sury

2015-01-01

Objectives: The Over-The-Scope-Clip (OTSC) has had an evolving role in endoscopic closure of gastrointestinal wall defects, in hemostasis of primary or postinterventional bleeding, and approximation of postbariatric surgery defects. Rapid and effective closure of gastrocutaneous (GC) fistulae using this device has been recently described in the literature. The aim of this study was to evaluate the technical feasibility, efficacy and safety of OTSC as an effective tool in the management of persistent GC fistulae secondary to a complication of percutaneous endoscopic gastrostomy (PEG) tube placement. Method: In this multicenter prospective observational study, we describe our experience with OTSC in the closure of persistent GC fistulas secondary to PEG tube placement. Patients with GC fistulas were sequentially enrolled with a mean age of 84 years. Primary treatment outcome was the immediate successful closure of GC fistula and resolution of leak. Secondary outcome was no recurrence of the fistula and leaks on follow up. Results: A total of 10 patients were enrolled over the study period. Mean age was 84.4 ± 8.75 years. The primary treatment outcome was achieved in all the patients undergoing this intervention. Secondary outcome was observed in 9/10 (90%) subjects. No procedural complications were reported. Larger fistulae (>2.5 cm) and those with significant fibrosis were more difficult to close with the OTSC system. The mean follow-up time after OTSC application was 43.7 ± 20.57 days. A limitation of this study was that there was no control group. Conclusions: OTSC application is a safe and effective endoscopic approach for the closure of persistent GC fistulae secondary to a complication of PEG tube placement. PMID:26136836

Endoscopic closure of persistent gastrocutaneous fistulae, after percutaneous endoscopic gastrostomy (PEG) tube placement, using the over-the-scope-clip system.

PubMed

Singhal, Shashideep; Changela, Kinesh; Culliford, Andrea; Duddempudi, Sushil; Krishnaiah, Mahesh; Anand, Sury

2015-07-01

The Over-The-Scope-Clip (OTSC) has had an evolving role in endoscopic closure of gastrointestinal wall defects, in hemostasis of primary or postinterventional bleeding, and approximation of postbariatric surgery defects. Rapid and effective closure of gastrocutaneous (GC) fistulae using this device has been recently described in the literature. The aim of this study was to evaluate the technical feasibility, efficacy and safety of OTSC as an effective tool in the management of persistent GC fistulae secondary to a complication of percutaneous endoscopic gastrostomy (PEG) tube placement. In this multicenter prospective observational study, we describe our experience with OTSC in the closure of persistent GC fistulas secondary to PEG tube placement. Patients with GC fistulas were sequentially enrolled with a mean age of 84 years. Primary treatment outcome was the immediate successful closure of GC fistula and resolution of leak. Secondary outcome was no recurrence of the fistula and leaks on follow up. A total of 10 patients were enrolled over the study period. Mean age was 84.4 ± 8.75 years. The primary treatment outcome was achieved in all the patients undergoing this intervention. Secondary outcome was observed in 9/10 (90%) subjects. No procedural complications were reported. Larger fistulae (>2.5 cm) and those with significant fibrosis were more difficult to close with the OTSC system. The mean follow-up time after OTSC application was 43.7 ± 20.57 days. A limitation of this study was that there was no control group. OTSC application is a safe and effective endoscopic approach for the closure of persistent GC fistulae secondary to a complication of PEG tube placement.

Characteristics of rheumatoid arthritis in Algeria: a multicenter study.

PubMed

Slimani, Samy; Abbas, Abdelmalek; Ben Ammar, Amina; Kebaili, Djemaa; Ali, El Hadi; Rahal, Fadia; Khamari, Mohamed Choukri; Baltache, Ayada; Khider, Imene; Chiheub, Riad; Khelif, Khireddine; Akbi, Sabrina; Rahmani, Salima; Dahou-Makhloufi, Chafia; Brahimi-Mazouni, Nadjia; Abtroun-Benmadi, Sabira; Ladjouze-Rezig, Aicha

2014-09-01

The aim of this study was to compare the epidemiology of rheumatoid arthritis (RA) in North Africa to that of Western countries. We have enrolled in a cross-sectional study all consecutive patients presenting with the diagnosis of RA according to the 1987 ACR criteria, and during a 5-month period, patients were included in 11 centers across northern Algeria. Demographics, clinical data, and health assessment questionnaires (HAQ) were collected for each patient. We have estimated means, standard deviations, and 95 % confidence intervals for all parameters. Of the 249 patients (213 females and 36 males) enrolled in the study, 10 (4 %) had juvenile onset of the disease. The mean age was 50.1 ± 14.5 years, and the mean duration of RA was 8.4 ± 7.8 years. In terms of comorbidities, 18.9 % of patients reported hypertension and 5.2 % had diabetes. The mean DAS28 at inclusion was 4.3 (95 % CI 4.1-4.5); 14.0 % were in remission (DAS28 ≤ 2.6). The mean HAQ score was 0.81 ± 0.82. Rheumatoid factor was positive in 78.5 % of cases, and anti-citrullinated protein/peptide antibodies, when measured, was positive in 69.0 % of cases. Seronegative patients were older and had a relatively less severe disease. For treatment, 89.7 % of patients were taking disease-modifying anti-rheumatic drugs and only 4 % were taking biologics (rituximab); 90.8 % of patients were taking glucocorticoids, and none of the patients satisfied the recommended calcium intake guidelines. RA in Algeria is more common in women. Compared to reports from Western countries, RA in Algeria appears to be less aggressive, with more dominant seronegative oligoarthritis forms. The remission rate is comparable to that of Western populations.

Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis: A Dose-Ranging Study

PubMed Central

Chavoustie, Steven E.; Jacobs, Mark; Reisman, Howard A.; Waldbaum, Arthur S.; Levy, Sharon F.; Hillier, Sharon L.; Nyirjesy, Paul

2015-01-01

Objective Metronidazole vaginal gel (MVG) 0.75% is a US Food and Drug Administration–approved, 5-day treatment for bacterial vaginosis (BV). This study tested the hypothesis that a shorter treatment course at a higher dose (MVG 1.3%) would yield similar efficacy to 5 days of MVG 0.75%. Materials and Methods This phase 2, multicenter, randomized, controlled, investigator-blinded, dose-ranging study enrolled women with a clinical diagnosis of BV. Patients were assigned to MVG 1.3% once daily for 1, 3, or 5 days or MVG 0.75% once daily for 5 days. The therapeutic cure rate, requiring clinical and bacteriological cure, at the end-of-study visit was determined for the per-protocol population. A Kaplan-Meier analysis was used to estimate median time-to-symptom resolution. Results In total, 255 women (mean age = 35 y) were enrolled. The per-protocol population included 189 patients. The therapeutic cure rate was higher in the 1-day (13/43, 30.2%), 3-day (12/48, 25.0%), and 5-day (16/49, 32.7%) MVG 1.3% groups versus the MVG 0.75% group (10/49, 20.4%). Median time-to-resolution of fishy odor was shorter in the 3 MVG 1.3% groups versus the MVG 0.75% group. The 5-day MVG 1.3% group had the lowest rate of symptom return. No clinically important differences were observed in adverse events across treatment groups; most events were mild or moderate in intensity and considered unrelated to treatment. Similar results were found in the modified intent-to-treat population. Conclusions Metronidazole vaginal gel 1.3% applied once daily for 1, 3, or 5 days showed similar efficacy, safety, and tolerability as MVG 0.75% once daily for 5 days. PMID:24983350

Safety and feasibility of pulmonary artery pressure-guided heart failure therapy: rationale and design of the prospective CardioMEMS Monitoring Study for Heart Failure (MEMS-HF).

PubMed

Angermann, Christiane E; Assmus, Birgit; Anker, Stefan D; Brachmann, Johannes; Ertl, Georg; Köhler, Friedrich; Rosenkranz, Stephan; Tschöpe, Carsten; Adamson, Philip B; Böhm, Michael

2018-05-19

Wireless monitoring of pulmonary artery (PA) pressures with the CardioMEMS HF™ system is indicated in patients with New York Heart Association (NYHA) class III heart failure (HF). Randomized and observational trials have shown a reduction in HF-related hospitalizations and improved quality of life in patients using this device in the United States. MEMS-HF is a prospective, non-randomized, open-label, multicenter study to characterize safety and feasibility of using remote PA pressure monitoring in a real-world setting in Germany, The Netherlands and Ireland. After informed consent, adult patients with NYHA class III HF and a recent HF-related hospitalization are evaluated for suitability for permanent implantation of a CardioMEMS™ sensor. Participation in MEMS-HF is open to qualifying subjects regardless of left ventricular ejection fraction (LVEF). Patients with reduced ejection fraction must be on stable guideline-directed pharmacotherapy as tolerated. The study will enroll 230 patients in approximately 35 centers. Expected duration is 36 months (24-month enrolment plus ≥ 12-month follow-up). Primary endpoints are freedom from device/system-related complications and freedom from pressure sensor failure at 12-month post-implant. Secondary endpoints include the annualized rate of HF-related hospitalization at 12 months versus the rate over the 12 months preceding implant, and health-related quality of life. Endpoints will be evaluated using data obtained after each subject's 12-month visit. The MEMS-HF study will provide robust evidence on the clinical safety and feasibility of implementing haemodynamic monitoring as a novel disease management tool in routine out-patient care in selected European healthcare systems. ClinicalTrials.gov; NCT02693691.

Randomized Controlled Trial of Pancreaticojejunostomy versus Stapler Closure of the Pancreatic Stump During Distal Pancreatectomy to Reduce Pancreatic Fistula.

PubMed

Kawai, Manabu; Hirono, Seiko; Okada, Ken-Ichi; Sho, Masayuki; Nakajima, Yoshiyuki; Eguchi, Hidetoshi; Nagano, Hiroaki; Ikoma, Hisashi; Morimura, Ryou; Takeda, Yutaka; Nakahira, Shin; Suzumura, Kazuhiro; Fujimoto, Jiro; Yamaue, Hiroki

2016-07-01

The aim of this study was to evaluate in a multicenter randomized controlled trial (RCT) whether pancreaticojejunostomy (PJ) of pancreatic stump decreases the incidence of pancreatic fistula after distal pancreatectomy (DP) compared with stapler closure. Several studies reported that PJ of pancreatic stump reduces the incidence of pancreatic fistula after DP. However, no RCT has confirmed the efficacy of PJ of pancreatic stump. One hundred thirty-six patients scheduled for DP were enrolled in this study between June 2011 and March 2014 at 6 high-volume surgical centers in Japan. Enrolled patients were randomized to either stapler closure or PJ. The primary endpoint was the incidence of pancreatic fistula based on the International Study Group on Pancreatic Fistula criteria. This RCT was registered with ClinicalTrials.gov (NCT01384617). Sixty-one patients randomized to stapler and 62 patients randomized to PJ were analyzed by intention-to-treat. Pancreatic fistula occurred in 23 patients (37.7%) in the stapler closure group and 24 (38.7%) in the PJ group (P = 0.332) in intention-to-treat analysis. The incidence of clinically relevant pancreatic fistula (grade B or C) was 16.4% for stapler closure and 9.7% for PJ (P = 0.201). Mortality was zero in both groups. In a subgroup analysis for thickness of pancreas greater than 12 mm, the incidence of clinically relevant pancreatic fistula occurred in 22.2% of the patients in the stapler closure group and in 6.2% of the PJ group (P = 0.080). PJ of the pancreatic stump during DP does not reduce pancreatic fistula compared with stapler closure.

Multicenter prospective evaluation of a new articulating 5-mm endoscopic linear stapler.

PubMed

Kuthe, Andreas; Haemmerle, Alexander; Ludwig, Kaja; Falck, Stephan; Hiller, Wolfgang; Mainik, Frederick; Freys, Stephan; Dubovoy, Lev; Jaehne, Joachim; Oldhafer, Karl

2016-05-01

The objective of this study was to evaluate the safety and efficacy of a novel 5-mm laparoscopic linear stapler in clinical gastrointestinal surgical applications. A prospective, single-arm study with an open enrollment of subjects requiring stapling of the gastrointestinal (GI) tract was performed. The study endpoints were the number of complications and technical failures associated with the use of a novel stapler when compared to similar events with conventional staplers as described in the medical literature. Seven centers enrolled 160 subjects, 150 of which were followed up to at least 30 days postoperatively. Intraoperative success: In 423 deployments, there were two staple line leaks and five staple line bleeds, all of which were intraoperatively resolved. In addition, incomplete staple lines were noted as a result of user error (n = 15) or device-related issues (n = 22), all of which were immediately resolved and none of which resulted in a complication or a change of the surgical procedure. Late outcomes: A total of 13 surgical complications in 160 patients were related to a GI transection or anastomosis, 12 of which related to a hand-sewn anastomosis or use of other commercially available staplers. One event (1/153, 0.065 %) on POD 1, involving bleeding of the staple line, was felt to be related to the use of the new stapler. The study confirmed that the new device was user-friendly (9 % incidence of problems firing the device), reliable (3 % device failures) and safe (<1 % complication rate related to the stapler). Based on these results, it would seem that this new 5-mm stapler is a safe and effective alternative to standard 12-mm staplers.

Randomized Controlled Trial of Pancreaticojejunostomy versus Stapler Closure of the Pancreatic Stump During Distal Pancreatectomy to Reduce Pancreatic Fistula

PubMed Central

Kawai, Manabu; Hirono, Seiko; Okada, Ken-ichi; Sho, Masayuki; Nakajima, Yoshiyuki; Eguchi, Hidetoshi; Nagano, Hiroaki; Ikoma, Hisashi; Morimura, Ryou; Takeda, Yutaka; Nakahira, Shin; Suzumura, Kazuhiro; Fujimoto, Jiro; Yamaue, Hiroki

2016-01-01

Objectives: The aim of this study was to evaluate in a multicenter randomized controlled trial (RCT) whether pancreaticojejunostomy (PJ) of pancreatic stump decreases the incidence of pancreatic fistula after distal pancreatectomy (DP) compared with stapler closure. Background: Several studies reported that PJ of pancreatic stump reduces the incidence of pancreatic fistula after DP. However, no RCT has confirmed the efficacy of PJ of pancreatic stump. Methods: One hundred thirty-six patients scheduled for DP were enrolled in this study between June 2011 and March 2014 at 6 high-volume surgical centers in Japan. Enrolled patients were randomized to either stapler closure or PJ. The primary endpoint was the incidence of pancreatic fistula based on the International Study Group on Pancreatic Fistula criteria. This RCT was registered with ClinicalTrials.gov (NCT01384617). Results: Sixty-one patients randomized to stapler and 62 patients randomized to PJ were analyzed by intention-to-treat. Pancreatic fistula occurred in 23 patients (37.7%) in the stapler closure group and 24 (38.7%) in the PJ group (P = 0.332) in intention-to-treat analysis. The incidence of clinically relevant pancreatic fistula (grade B or C) was 16.4% for stapler closure and 9.7% for PJ (P = 0.201). Mortality was zero in both groups. In a subgroup analysis for thickness of pancreas greater than 12 mm, the incidence of clinically relevant pancreatic fistula occurred in 22.2% of the patients in the stapler closure group and in 6.2% of the PJ group (P = 0.080). Conclusions: PJ of the pancreatic stump during DP does not reduce pancreatic fistula compared with stapler closure. PMID:26473652

A prospective approach to investigating the natural history of preclinical rheumatoid arthritis (RA) using first-degree relatives of probands with RA.

PubMed

Kolfenbach, Jason R; Deane, Kevin D; Derber, Lezlie A; O'Donnell, Colin; Weisman, Michael H; Buckner, Jane H; Gersuk, Vivian H; Wei, Shan; Mikuls, Ted R; O'Dell, James; Gregersen, Peter K; Keating, Richard M; Norris, Jill M; Holers, V Michael

2009-12-15

To describe a large, multicenter prospective cohort study of first-degree relatives (FDRs) of probands with rheumatoid arthritis (RA), and outline the use of such a study in investigating the natural history of RA development. A total of 1,058 FDRs, none of whom met the American College of Rheumatology criteria for RA, were enrolled in a prospective study investigating genetic and environmental influences on the development of RA-related autoimmunity. Demographic, epidemiologic, genetic, autoantibody, and physical examination data from the initial study enrollment visit were described for these FDRs, and the relationship was examined between genetic factors, autoantibodies, inflammation, and joint disease. Fifty-five percent of the FDRs had > or =1 copy of the shared epitope, 20% had > or =1 copy of the PTPN22 polymorphism, and approximately 16% were positive for rheumatoid factor (RF; including isotypes) and/or anti-cyclic citrullinated peptide antibody. IgM-RF positivity is associated with > or =1 tender joint on examination (odds ratio [OR] 2.50, 95% confidence interval [95% CI] 1.27-4.89; P < 0.01) and elevated C-reactive protein (CRP) levels (OR 5.31, 95% CI 1.45-19.52; P = 0.01). FDRs without RA demonstrate high prevalences of genetic risk factors and RA-related autoantibodies. Additionally, an RF association with tender joints and elevated CRP levels suggests that autoantibodies are a valid intermediate marker of RA-related autoimmunity in this cohort. This prospective FDR cohort will be a valuable resource for evaluating the relationship between genetic and epidemiologic factors and the development of RA-related autoimmunity.

Metronidazole vaginal gel 1.3% in the treatment of bacterial vaginosis: a dose-ranging study.

PubMed

Chavoustie, Steven E; Jacobs, Mark; Reisman, Howard A; Waldbaum, Arthur S; Levy, Sharon F; Hillier, Sharon L; Nyirjesy, Paul

2015-04-01

Metronidazole vaginal gel (MVG) 0.75% is a US Food and Drug Administration-approved, 5-day treatment for bacterial vaginosis (BV). This study tested the hypothesis that a shorter treatment course at a higher dose (MVG 1.3%) would yield similar efficacy to 5 days of MVG 0.75%. This phase 2, multicenter, randomized, controlled, investigator-blinded, dose-ranging study enrolled women with a clinical diagnosis of BV. Patients were assigned to MVG 1.3% once daily for 1, 3, or 5 days or MVG 0.75% once daily for 5 days. The therapeutic cure rate, requiring clinical and bacteriological cure, at the end-of-study visit was determined for the per-protocol population. A Kaplan-Meier analysis was used to estimate median time-to-symptom resolution. In total, 255 women (mean age = 35 y) were enrolled. The per-protocol population included 189 patients. The therapeutic cure rate was higher in the 1-day (13/43, 30.2%), 3-day (12/48, 25.0%), and 5-day (16/49, 32.7%) MVG 1.3% groups versus the MVG 0.75% group (10/49, 20.4%). Median time-to-resolution of fishy odor was shorter in the 3 MVG 1.3% groups versus the MVG 0.75% group. The 5-day MVG 1.3% group had the lowest rate of symptom return. No clinically important differences were observed in adverse events across treatment groups; most events were mild or moderate in intensity and considered unrelated to treatment. Similar results were found in the modified intent-to-treat population. Metronidazole vaginal gel 1.3% applied once daily for 1, 3, or 5 days showed similar efficacy, safety, and tolerability as MVG 0.75% once daily for 5 days.

STAR 3 randomized controlled trial to compare sensor-augmented insulin pump therapy with multiple daily injections in the treatment of type 1 diabetes: research design, methods, and baseline characteristics of enrolled subjects.

PubMed

Davis, Stephen N; Horton, Edward S; Battelino, Tadej; Rubin, Richard R; Schulman, Kevin A; Tamborlane, William V

2010-04-01

Sensor-augmented pump therapy (SAPT) integrates real-time continuous glucose monitoring (RT-CGM) with continuous subcutaneous insulin infusion (CSII) and offers an alternative to multiple daily injections (MDI). Previous studies provide evidence that SAPT may improve clinical outcomes among people with type 1 diabetes. Sensor-Augmented Pump Therapy for A1c Reduction (STAR) 3 is a multicenter randomized controlled trial comparing the efficacy of SAPT to that of MDI in subjects with type 1 diabetes. Subjects were randomized to either continue with MDI or transition to SAPT for 1 year. Subjects in the MDI cohort were allowed to transition to SAPT for 6 months after completion of the study. SAPT subjects who completed the study were also allowed to continue for 6 months. The primary end point was the difference between treatment groups in change in hemoglobin A1c (HbA1c) percentage from baseline to 1 year of treatment. Secondary end points included percentage of subjects with HbA1c < or =7% and without severe hypoglycemia, as well as area under the curve of time spent in normal glycemic ranges. Tertiary end points include percentage of subjects with HbA1c < or =7%, key safety end points, user satisfaction, and responses on standardized assessments. A total of 495 subjects were enrolled, and the baseline characteristics similar between the SAPT and MDI groups. Study completion is anticipated in June 2010. Results of this randomized controlled trial should help establish whether an integrated RT-CGM and CSII system benefits patients with type 1 diabetes more than MDI.

Long-term results of a sirolimus-eluting stent with biodegradable polymer (RAPSTROM™) in de novo coronary stenoses.

PubMed

Figini, Filippo; Manjunath, Chaman Nadish; Srinivas, Balaji Chandra; Sadananda, Kanvar Sarat; Sreedharan, Madhu; Fischer, Louie; Pillai, Ramakrishna; Varghese, Kiron; Gopal, Ajay K; Nagesh, Chamarajnagar Mahadevappa; Sheiban, Imad

2017-10-07

To report long-term results of a novel sirolimus-eluting stent with biodegradable polymer BACKGROUND: Newer generation drug-eluting stents are characterized by thin struts, improved platform design and highly biocompatible polymer carrying the antiproliferative drug. The RapstromTM stent, sharing these features, showed promising outcomes in preclinical models and in a first-in-man trial. The present study is a multicenter, non-randomized post-market registry, including patients with de novo coronary artery disease treated with implantation of one or more Rapstrom stents. Primary endpoint of the study was the rate of major adverse cardiac events (MACE) at three-year follow-up. 1073 patients were enrolled, with a high prevalence of diabetes (35%) and acute coronary syndrome at presentation (82%); at three-year follow up, MACE rate was 14.8%, with a low incidence of definite or probable stent thrombosis (0.75%). These data confirm the good clinical performance of the Rapstrom stent, supporting the concept that the combination of thin struts and biodegradable polymer is associated with positive clinical outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Prevalence of upper airway tumors and cysts among patients who snore.

PubMed

Suzuki, Masaaki; Saigusa, Hanako; Chiba, Shintaro; Hoshino, Tadahiko; Okamoto, Makito

2007-11-01

Sleep specialists usually do not pay much attention to the upper airway in patients who snore, because they can make the diagnosis of sleep-disordered breathing without performing nasopharyngeal endoscopy if they have the Epworth Sleepiness Scale scores and the results of polysomnography. The purpose of this study was to determine the prevalence of benign and malignant tumors and cysts in the upper airway in patients who snore. A retrospective multicenter trial was performed in 4 sleep laboratories. Adult male and female patients whose chief complaint on their first visit was witnessed snoring were enrolled in this study. All of the patients were evaluated by otolaryngologists using nasopharyngeal endoscopy to detect organic diseases in the upper airway. Among 2,923 patients, 2 patients had malignant tumors, 5 had benign tumors, and 2 had cysts in the upper airway. The prevalence of upper airway benign and malignant tumors and cysts among adult male and female patients was 0.24%. Routine detailed nasopharyngeal endoscopy should be carried out in each institution so as not to overlook organic diseases in the upper airway among patients who snore.

Multi-Center Biologic Assignment Trial Comparing Reduced Intensity Allogeneic Hematopoietic Cell Transplant to Hypomethylating Therapy or Best Supportive Care in Patients Aged 50-75 with Intermediate-2 and High Risk Myelodysplastic Syndrome Blood and Marrow Transplant Clinical Trials Network #1102 Study Rationale, Design and Methods

PubMed Central

Saber, Wael; Le Rademacher, Jennifer; Sekeres, Mikkael; Logan, Brent; Lewis, Moira; Mendizabal, Adam; Leifer, Eric; Appelbaum, Frederick R.; Horowitz, Mary M; Nakamura, Ryotaro; Cutler, Corey S.

2014-01-01

The introduction of reduced intensity conditioning regimens (RIC) made it possible to offer allogeneic hematopoietic cell transplantation (alloHCT) to older patients with myelodysplastic syndromes (MDS). However, the relative risks and benefits of alloHCT compared to novel non-transplant therapies continue to be the source of considerable uncertainty. We will perform a prospective biologic assignment trial to compare RIC alloHCT to non-transplant therapies based on donor availability. Primary outcome is 3-year overall survival. Secondary outcomes include leukemia-free survival, quality of life, and cost-effectiveness. Four hundred patients will be enrolled over roughly 3 years. Planned subgroup analyses will evaluate key biologic questions, such as the impact of age & response to hypomethylating agents on treatment effects. Findings from this study potentially may set a new standard of care for older MDS patients who are considered candidates for alloHCT. PMID:24972249

Impact of hydroxyurea on clinical events in the BABY HUG trial

PubMed Central

Files, Beatrice A.; Luo, Zhaoyu; Miller, Scott T.; Kalpatthi, Ram; Iyer, Rathi; Seaman, Phillip; Lebensburger, Jeffrey; Alvarez, Ofelia; Thompson, Bruce; Ware, Russell E.; Wang, Winfred C.

2012-01-01

The Pediatric Hydroxyurea Phase 3 Clinical Trial (BABY HUG) was a phase 3 multicenter, randomized, double-blind, placebo-controlled clinical trial of hydroxyurea in infants (beginning at 9-18 months of age) with sickle cell anemia. An important secondary objective of this study was to compare clinical events between the hydroxyurea and placebo groups. One hundred and ninety-three subjects were randomized to hydroxyurea (20 mg/kg/d) or placebo; there were 374 patient-years of on-study observation. Hydroxyurea was associated with statistically significantly lower rates of initial and recurrent episodes of pain, dactylitis, acute chest syndrome, and hospitalization; even infants who were asymptomatic at enrollment had less dactylitis as well as fewer hospitalizations and transfusions if treated with hydroxyurea. Despite expected mild myelosuppression, hydroxyurea was not associated with an increased risk of bacteremia or serious infection. These data provide important safety and efficacy information for clinicians considering hydroxyurea therapy for very young children with sickle cell anemia. This clinical trial is registered with the National Institutes of Health (NCT00006400, www.clinicaltrials.gov). PMID:22915643

Vitamin D levels are associated with gross motor function in amyotrophic lateral sclerosis.

PubMed

Paganoni, Sabrina; Macklin, Eric A; Karam, Chafic; Yu, Hong; Gonterman, Fernando; Fetterman, K Ashley; Cudkowicz, Merit; Berry, James; Wills, Anne-Marie

2017-10-01

The objective of this study was to determine whether serum vitamin D [25(OH)D] levels are associated with disease progression in amyotrophic lateral sclerosis (ALS). 25(OH)D was measured in subjects enrolled in a multicenter study for validation of ALS biomarkers. Baseline 25(OH)D levels were correlated with baseline ALSFRS-R scores. Average 25(OH)D levels from baseline and month 6 visits (seasonally asynchronous) were used to predict subsequent rate of change in ALSFRS-R from month 6 to month 18. Most subjects had either insufficient or deficient 25(OH)D levels. Lower 25(OH)D was associated with lower ALSFRS-R gross motor scores, but not lower ALSFRS-R total scores at baseline. Levels of 25(OH)D were not predictive of disease progression over the next 12 months. 25(OH)D was associated with baseline gross motor ALSFRS-R scores but did not predict the rate of disease progression. Vitamin D levels may reflect poor mobility in patients with ALS. Muscle Nerve, 2017 Muscle Nerve 56: 726-731, 2017. © 2017 Wiley Periodicals, Inc.

Sugarsquare, a Web-Based Patient Portal for Parents of a Child With Type 1 Diabetes: Multicenter Randomized Controlled Feasibility Trial

PubMed Central

Maas-Van Schaaijk, Nienke M; Sas, Theo C; Clement-de Boers, Agnes; Smallenbroek, Mischa; Nuboer, Roos; Noordam, Cees; Verhaak, Chris M

2017-01-01

Background Raising a child with type 1 diabetes (T1D) means combining the demands of the disease management with everyday parenting, which is associated with increased levels of distress. A Web-based patient portal, Sugarsquare, was developed to support parents, by providing online parent-professional communication, online peer support and online disease information. Objective The first aim of this study was to assess the feasibility of conducting a multicenter, randomized controlled trial in Dutch parents of a child with T1D. The second aim was to assess the feasibility of implementing Sugarsquare in clinical practice. Methods The parents of 105 children (N=105) with T1D below the age of 13 participated in a 6-month multicenter randomized controlled feasibility trial. They were randomly assigned to an experimental (n=54, usual care and Sugarsquare) or a control group (n=51, usual care). Attrition rates and user statistics were gathered to evaluate feasibility of the trial and implementation. To determine potential efficacy, the parenting stress index (PSI-SF) was assessed at baseline (T0) and after 6 months (T1). Results Of a potential population of parents of 445 children, 189 were willing to participate (enrollment refusal=57.5%, n=256), 142 filled in the baseline questionnaire (baseline attrition rate=25%, n=47), and 105 also filled in the questionnaire at T1 (post randomization attrition rate during follow-up=26%, n=32). As such, 24% of the potential population participated. Analysis in the experimental group (n=54) revealed a total of 32 (59%) unique users, divided into 12 (38%) frequent users, 9 (28%) incidental users, and 11 (34%) low-frequent users. Of the total of 44 professionals, 34 (77%) logged in, and 32 (73%) logged in repeatedly. Analysis of the user statistics in the experimental group further showed high practicability and integration in all users, moderate acceptability and demand in parents, and high acceptability and demand in health care professionals. Baseline parenting stress index scores were related to the parents’ frequency of logging on (ρ=.282, P=.03) and page-views (ρ=.304, P=.01). No significant differences in change in parenting stress between experimental and control group were found (F3,101=.49, P=.49). Conclusions The trial can be considered feasible, considering the average enrollment refusal rate, baseline attrition rate and postrandomization attrition rate, compared to other eHealth studies, although lower than hypothesized. Implementing Sugarsquare in clinical practice was partly feasible, given moderate demand and acceptability in parent users and lack of potential efficacy. Parents who reported higher levels of parenting stress used Sugarsquare more often than other parents, although Sugarsquare did not reduce parenting stress. These results indicate that Web-based interventions are a suitable way of providing parents of children with T1D with additional support. Future studies should determine how Sugarsquare could reduce parenting stress, for instance by adding targeted interventions. Factors potentially contributing to successful implementation are suggested. Trial Registration Nederlands Trial Register Number: NTR3643; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3643 (Archived by WebCite at http://www.webcitation.org/6qihOVCi6) PMID:28830853

Sugarsquare, a Web-Based Patient Portal for Parents of a Child With Type 1 Diabetes: Multicenter Randomized Controlled Feasibility Trial.

PubMed

Boogerd, Emiel; Maas-Van Schaaijk, Nienke M; Sas, Theo C; Clement-de Boers, Agnes; Smallenbroek, Mischa; Nuboer, Roos; Noordam, Cees; Verhaak, Chris M

2017-08-22

Raising a child with type 1 diabetes (T1D) means combining the demands of the disease management with everyday parenting, which is associated with increased levels of distress. A Web-based patient portal, Sugarsquare, was developed to support parents, by providing online parent-professional communication, online peer support and online disease information. The first aim of this study was to assess the feasibility of conducting a multicenter, randomized controlled trial in Dutch parents of a child with T1D. The second aim was to assess the feasibility of implementing Sugarsquare in clinical practice. The parents of 105 children (N=105) with T1D below the age of 13 participated in a 6-month multicenter randomized controlled feasibility trial. They were randomly assigned to an experimental (n=54, usual care and Sugarsquare) or a control group (n=51, usual care). Attrition rates and user statistics were gathered to evaluate feasibility of the trial and implementation. To determine potential efficacy, the parenting stress index (PSI-SF) was assessed at baseline (T0) and after 6 months (T1). Of a potential population of parents of 445 children, 189 were willing to participate (enrollment refusal=57.5%, n=256), 142 filled in the baseline questionnaire (baseline attrition rate=25%, n=47), and 105 also filled in the questionnaire at T1 (post randomization attrition rate during follow-up=26%, n=32). As such, 24% of the potential population participated. Analysis in the experimental group (n=54) revealed a total of 32 (59%) unique users, divided into 12 (38%) frequent users, 9 (28%) incidental users, and 11 (34%) low-frequent users. Of the total of 44 professionals, 34 (77%) logged in, and 32 (73%) logged in repeatedly. Analysis of the user statistics in the experimental group further showed high practicability and integration in all users, moderate acceptability and demand in parents, and high acceptability and demand in health care professionals. Baseline parenting stress index scores were related to the parents' frequency of logging on (ρ=.282, P=.03) and page-views (ρ=.304, P=.01). No significant differences in change in parenting stress between experimental and control group were found (F 3,101 =.49, P=.49). The trial can be considered feasible, considering the average enrollment refusal rate, baseline attrition rate and postrandomization attrition rate, compared to other eHealth studies, although lower than hypothesized. Implementing Sugarsquare in clinical practice was partly feasible, given moderate demand and acceptability in parent users and lack of potential efficacy. Parents who reported higher levels of parenting stress used Sugarsquare more often than other parents, although Sugarsquare did not reduce parenting stress. These results indicate that Web-based interventions are a suitable way of providing parents of children with T1D with additional support. Future studies should determine how Sugarsquare could reduce parenting stress, for instance by adding targeted interventions. Factors potentially contributing to successful implementation are suggested. Nederlands Trial Register Number: NTR3643; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3643 (Archived by WebCite at http://www.webcitation.org/6qihOVCi6). ©Emiel Boogerd, Nienke M Maas-Van Schaaijk, Theo C Sas, Agnes Clement-de Boers, Mischa Smallenbroek, Roos Nuboer, Cees Noordam, Chris M Verhaak. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 22.08.2017.

Economic evaluation of the randomized European Achalasia trial comparing pneumodilation with Laparoscopic Heller myotomy.

PubMed

Moonen, A; Busch, O; Costantini, M; Finotti, E; Tack, J; Salvador, R; Boeckxstaens, G; Zaninotto, G

2017-11-01

A recent multicenter randomized trial in achalasia patients has shown that pneumatic dilation resulted in equivalent relief of symptoms compared to laparoscopic Heller myotomy. Additionally, the cost of each treatment should be also taken in consideration. Therefore, the aim of the present study was to perform an economic analysis of the European achalasia trial. Patients with newly diagnosed achalasia were enrolled from to 2003 to 2008 in 14 centers in five European countries and were randomly assigned to either pneumatic dilation (PD) or laparoscopic Heller (LHM). The economic analysis was performed in the three centers in three different countries where most patients were enrolled (Amsterdam [NL], Leuven, [B] and Padova [I]) and then applied to all patients included in the study. The total raw costs of the two treatments per patient include the initial costs, the costs of complications, and the costs of retreatments. Two hundred and one patients, 107 (57 males and 50 females, mean age 46 CI: 43-49 years) were randomized to LHM and 94 (59 males and 34 females, mean age 46 CI 43-50 years) to PD. The total cost of PD per patient was quite comparable in the three different centers; €3397 in Padova, €3259 in Amsterdam and €3792 in Leuven. For LHM, the total costs per patient were highest in Amsterdam: €4488 in Padova, €6720 in Amsterdam, and €5856 in Leuven. In conclusion, the strategy of treating achalasia starting with PD appears the most economic approach, independent of the health system. © 2017 John Wiley & Sons Ltd.

Clinical classification of adult patients with chronic intestinal failure due to benign disease: An international multicenter cross-sectional survey.

PubMed

Pironi, Loris; Konrad, Denise; Brandt, Chrisoffer; Joly, Francisca; Wanten, Geert; Agostini, Federica; Chambrier, Cecile; Aimasso, Umberto; Zeraschi, Sarah; Kelly, Darlene; Szczepanek, Kinga; Jukes, Amelia; Di Caro, Simona; Theilla, Miriam; Kunecki, Marek; Daniels, Joanne; Serlie, Mireille; Poullenot, Florian; Wu, Jian; Cooper, Sheldon C; Rasmussen, Henrik H; Compher, Charlene; Seguy, David; Crivelli, Adriana; Pagano, Maria C; Hughes, Sarah-Jane; Guglielmi, Francesco W; Kozjek, Nada Rotovnik; Schneider, Stéphane M; Gillanders, Lyn; Ellegard, Lars; Thibault, Ronan; Matras, Przemysław; Zmarzly, Anna; Matysiak, Konrad; Van Gossum, Andrè; Forbes, Alastair; Wyer, Nicola; Taus, Marina; Virgili, Nuria M; O'Callaghan, Margie; Chapman, Brooke; Osland, Emma; Cuerda, Cristina; Sahin, Peter; Jones, Lynn; Lee, Andre D W; Bertasi, Valentino; Orlandoni, Paolo; Izbéki, Ferenc; Spaggiari, Corrado; Díez, Marta Bueno; Doitchinova-Simeonova, Maryana; Garde, Carmen; Serralde-Zúñiga, Aurora E; Olveira, Gabriel; Krznaric, Zeljko; Czako, Laszlo; Kekstas, Gintautas; Sanz-Paris, Alejandro; Jáuregui, Estrella Petrina; Murillo, Ana Zugasti; Schafer, Eszter; Arends, Jann; Suárez-Llanos, José P; Shaffer, Jon; Lal, Simon

2018-04-01

The aim of the study was to evaluate the applicability of the ESPEN 16-category clinical classification of chronic intestinal failure, based on patients' intravenous supplementation (IVS) requirements for energy and fluids, and to evaluate factors associated with those requirements. ESPEN members were invited to participate through ESPEN Council representatives. Participating centers enrolled adult patients requiring home parenteral nutrition for chronic intestinal failure on March 1st 2015. The following patient data were recorded though a structured database: sex, age, body weight and height, intestinal failure mechanism, underlying disease, IVS volume and energy need. Sixty-five centers from 22 countries enrolled 2919 patients with benign disease. One half of the patients were distributed in 3 categories of the ESPEN clinical classification. 9% of patients required only fluid and electrolyte supplementation. IVS requirement varied considerably according to the pathophysiological mechanism of intestinal failure. Notably, IVS volume requirement represented loss of intestinal function better than IVS energy requirement. A simplified 8 category classification of chronic intestinal failure was devised, based on two types of IVS (either fluid and electrolyte alone or parenteral nutrition admixture containing energy) and four categories of volume. Patients' IVS requirements varied widely, supporting the need for a tool to homogenize patient categorization. This study has devised a novel, simplified eight category IVS classification for chronic intestinal failure that will prove useful in both the clinical and research setting when applied together with the underlying pathophysiological mechanism of the patient's intestinal failure. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Epidemiology and outcomes of Clostridium difficile infection in allogeneic hematopoietic cell and lung transplant recipients.

PubMed

Dubberke, E R; Reske, K A; Olsen, M A; Bommarito, K; Cleveland, A A; Silveira, F P; Schuster, M G; Kauffman, C A; Avery, R K; Pappas, P G; Chiller, T M

2018-04-01

Clostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described. We performed a prospective, multicenter study of CDI within 365 days post-allogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12 weeks post-transplant and while hospitalized and contacted monthly up to 18 months post-transplantation. Six sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1 year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27 days vs 90 days; P = .037). CDI was associated with significantly higher mortality from 31 to 180 days post-index date among the allogeneic HCT recipients (Hazard ratio [HR] = 1.80; P = .007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180 days post-index date (HR = 4.7, P = .09). The epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate post-transplant period. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Etiology of Syncope and Unexplained Falls in Elderly Adults with Dementia: Syncope and Dementia (SYD) Study.

PubMed

Ungar, Andrea; Mussi, Chiara; Ceccofiglio, Alice; Bellelli, Giuseppe; Nicosia, Franco; Bo, Mario; Riccio, Daniela; Martone, Anna Maria; Guadagno, Livia; Noro, Gabriele; Ghidoni, Giulia; Rafanelli, Martina; Marchionni, Niccolò; Abete, Pasquale

2016-08-01

To investigate the etiology of transient loss of consciousness (T-LOC) suspected to be syncope and unexplained falls in elderly adults with dementia. Prospective, observational, multicenter study. Acute care wards, syncope units or centers for the diagnosis of dementia. Individuals aged 65 and older with a diagnosis of dementia and one or more episodes of T-LOC of a suspected syncopal nature or unexplained falls during the previous 3 months were enrolled. The causes of T-LOC suspected to be syncope and unexplained falls were evaluated using a simplified protocol based on European Society of Cardiology guidelines. Of 357 individuals enrolled, 181 (50.7%) had been referred for T-LOC suspected to be syncope, 166 (46.5%) for unexplained falls, and 10 (2.8%) for both. An initially suspected diagnosis of syncope was confirmed in 158 (87.3%), and syncope was identified as the cause of the event in 75 (45.2%) of those referred for unexplained falls. Orthostatic hypotension was the cause of the event in 117 of 242 (48.3%) participants with a final diagnosis of syncope. The simplified syncope diagnostic protocol can be used in elderly people with dementia referred for suspected syncope or unexplained falls. Unexplained falls may mask a diagnosis of syncope or pseudosyncope in almost 50% of cases. Given the high prevalence of orthostatic syncope in participants (~50%), a systematic reappraisal of drugs potentially responsible for orthostatic hypotension is warranted. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Population-Tailored Care for Homeless Veterans and Acute Care Use, Cost, and Satisfaction: A Prospective Quasi-Experimental Trial

PubMed Central

Johnson, Erin E.; Borgia, Matthew; Noack, Amy; Yoon, Jean; Gehlert, Elizabeth; Lo, Jeanie

2018-01-01

Introduction Although traditional patient-centered medical homes (PCMHs) are effective for patients with complex needs, it is unclear whether homeless-tailored PCMHs work better for homeless veterans. We examined the impact of enrollment in a Veterans Health Administration (VHA) homeless-tailored PCMH on health services use, cost, and satisfaction compared with enrollment in a traditional, nontailored PCMH. Methods We conducted a prospective, multicenter, quasi-experimental, single-blinded study at 2 VHA medical centers to assess health services use, cost, and satisfaction during 12 months among 2 groups of homeless veterans: 1) veterans receiving VHA homeless-tailored primary care (Homeless-Patient Aligned Care Team [H-PACT]) and 2) veterans receiving traditional primary care services (PACT). A cohort of 266 homeless veterans enrolled from June 2012 through January 2014. Results Compared with PACT patients, H-PACT patients had more social work visits (4.6 vs 2.7 visits) and fewer emergency department (ED) visits for ambulatory care-sensitive conditions (0 vs 0.2 visits); a significantly smaller percentage of veterans in H-PACT were hospitalized (23.1% vs 35.4%) or had mental health–related ED visits (34.1% vs 47.6%). We found significant differences in primary care provider–specific visits (H-PACT, 5.1 vs PACT, 3.6 visits), mental health care visits (H-PACT, 8.8 vs PACT, 13.4 visits), 30-day prescription drug fills (H-PACT, 40.5 vs PACT, 58.8 fills), and use of group therapy (H-PACT, 40.1% vs PACT, 53.7%). Annual costs per patient were significantly higher in the PACT group than the H-PACT group ($37,415 vs $28,036). In logistic regression model of acute care use, assignment to the H-PACT model was protective as was rating health “good” or better. Conclusion Homeless veterans enrolled in the population-tailored primary care approach used less acute care and costs were lower. Tailored-care models have implications for care coordination in the US Department of Veterans Affairs VA and community health systems. PMID:29451116

Predictors of Corneal Perforation or Need for Therapeutic Keratoplasty in Severe Fungal Keratitis: A Secondary Analysis of the Mycotic Ulcer Treatment Trial II.

PubMed

Prajna, N Venkatesh; Krishnan, Tiruvengada; Rajaraman, Revathi; Patel, Sushila; Shah, Ranjeet; Srinivasan, Muthiah; Das, Manoranjan; Ray, Kathryn J; Oldenburg, Catherine E; McLeod, Stephen D; Zegans, Michael E; Acharya, Nisha R; Lietman, Thomas M; Rose-Nussbaumer, Jennifer

2017-09-01

Identifying patients with infectious keratitis who are at risk of experiencing a poor outcome may be useful to allocate resources toward high-risk patients, particularly in resource-poor settings. To determine baseline patient and ulcer characteristics that predict a high risk of developing corneal perforation and/or the need to undergo therapeutic penetrating keratoplasty (TPK). This is a secondary analysis of Mycotic Ulcer Treatment Trial II, a multicenter, double-masked, placebo-controlled randomized clinical trial that enrolled 240 patients with smear-positive filamentous fungal corneal ulcers who enrolled between May 2010 and August 2015. Participants had a baseline visual acuity of 20/400 or worse and were randomized to receive oral voriconazole or a placebo (all participants received topical voriconazole, 1%). After 39 participants (16.3%) were enrolled, topical natamycin, 5%, was also added. The primary outcome of this secondary analysis was the rate of corneal perforation or the need to undergo TPK. The mean (SD) age at enrollment was 49 (13) years, 104 participants (43.3%) were women, and all were of Southeast Asian descent. The presence of hypopyon at baseline indicated 2.28 times the odds of the patient developing corneal perforation and/or needing TPK (95% CI, 1.18-4.40; P = .01). Study participants whose infiltrate involved the posterior one-third had a 71.4% risk of developing corneal perforation and/or needing TPK. For each 1-mm increase in the geometric mean of the infiltrate, there was 1.37 (95% CI, 1.12-1.67; P = .002) increased odds of developing perforation and/or needing TPK. Other clinical features such as visual acuity, baseline culture positivity, type of filamentous fungal organism and duration of symptoms, and demographic characteristics, such as sex and occupation, were not significant predictors in the multivariable regression analysis. These results suggest that risk stratification from baseline ulcer characteristics can identify those at highest risk for developing corneal perforation and/or needing TPK. clinicaltrials.gov Identifier: NCT00996736.

Design of the stenting and aggressive medical management for preventing recurrent stroke in intracranial stenosis trial.

PubMed

Chimowitz, Marc I; Lynn, Michael J; Turan, Tanya N; Fiorella, David; Lane, Bethany F; Janis, Scott; Derdeyn, Colin P

2011-01-01

Patients with recent transient ischemic attack (TIA) or stroke caused by 70% to 99% stenosis of a major intracranial artery are at high risk of recurrent stroke on usual medical management, suggesting the need for alternative therapies for this disease. The Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis trial is an ongoing, randomized, multicenter, 2-arm trial that will determine whether intracranial angioplasty and stenting adds benefit to aggressive medical management alone for preventing the primary endpoint (any stroke or death within 30 days after enrollment or after any revascularization procedure of the qualifying lesion during follow-up, or stroke in the territory of the symptomatic intracranial artery beyond 30 days) during a mean follow-up of 2 years in patients with recent TIA or stroke caused by 70% to 99% stenosis of a major intracranial artery. Aggressive medical management in both arms consists of aspirin 325 mg per day, clopidogrel 75 mg per day for 90 days after enrollment, intensive risk factor management primarily targeting systolic blood pressure <140 mm Hg (<130 mm Hg in diabetics) and low density cholesterol <70 mg/dL, and a lifestyle modification program. The sample size required to detect a 35% reduction in the rate of the primary endpoint from angioplasty and stenting based on the log-rank test with an alpha of 0.05, 80% power, and adjusting for a 2% loss to follow-up and 5% crossover from the medical to the stenting arm is 382 patients per group. Enrollment began in November 2008 and 451 patients have been enrolled as of March 31, 2011. This is the first randomized stroke prevention trial to compare angioplasty and stenting with medical therapy in patients with intracranial arterial stenosis and to incorporate intensive management of multiple risk factors and a lifestyle modification program in the study design. Hopefully, the results of the trial will lead to more effective therapy for this high-risk disease. Copyright © 2011 National Stroke Association. All rights reserved.

A Prospective, Multicenter Study to Compare a Disposable, High-fluid Capacity Underpad to Nonpermeable, Disposable, Reusable Containment Products on Incontinence-associated Dermatitis Rates Among Skilled Nursing Facility Residents.

PubMed

Motta, Glenda; Milne, Catherine T

2017-12-01

Due to the high prevalence of incontinence among skilled nursing facility (SNF) residents, incontinence-associated derma- titis (IAD) is a common occurrence. In addition, facility staff may mistakenly identify IAD as a pressure injury. A prospective, descriptive, multicenter study was conducted in 3 Connecticut facilities to evaluate the effect of substituting a disposable, high- uid capacity underpad for nonpermeable disposable and reusable containment products on the rate of IADs. Residents with and without IAD but with high IAD risk scores who were bed- or chairbound or ambulatory and used disposable nonpermeable briefs and underpads or reusable, laundered containment products when in bed longer than 2 hours were randomly enrolled and observed for a 4-week period. Facility staff were trained on the importance of differentiating between IAD and pressure injury; they substituted the study product (a disposable, high- uid capacity underpad) for all previously used containment products. Patient risk for IAD and skin condition were assessed using the Perineal Assessment Tool (PAT) and the Skin Condition Assessment Tool (SAT), respectively, at 5 time points: baseline, week 1, week 2, week 3, and week 4. The PAT is a 4-item instrument based conceptually on the 4 determinants in perineal skin breakdown; subscales are rated from 1 (least risk) to 3 (most risk), with a total score range of 4 to 12. The SAT is used to evaluate IAD speci cally, generating a cumulative severity score ranging from 0 to 3 on area of skin affected, degree of redness, and depth of ero- sion. Final data analysis was conducted on 40 residents: 25 had IAD present at enrollment and 15 were deemed high risk for developing IAD. Mean SAT scores in the 25 participants with IAD decreased with signi cance at week 1 (P = .0016), week 2 (P = .0023), week 3 (P = .0005), and week 4 (P <.0001). Baseline IAD severity scores averaged 3.3 ± 1.7. Overall IAD average severity scores in this group decreased from baseline mean of 3.3 ± 1.7 to 0.7 ± 1.4 at week 4 (P <.001). The 15 participants with intact, nondamaged skin at enrollment did not develop IAD from baseline to week 4, and PAT score risk levels decreased from high (7 or greater) to low (6 or less) as a result of a speci c reduction in the duration of irritant exposure category for 11 (73%) of this group of participants by week 4. PAT risk level scores for both IAD and non-IAD participants at baseline averaged 8.1 ± 1.4; after 4 weeks, they averaged 7.0 ± 1.5). Although change was not significant, results suggest the use of a disposable, high- uid capacity underpad improved SAT scores over time. IAD rates increased in each facility, but pressure injury incidence rates decreased for the study duration. Replacing a nonpermeable, reusable containment product with a disposable, high- uid capacity underpad when SNF residents are in bed longer than 2 hours may impact the severity of IAD and reduce its incidence. The inverse impact reported on IAD and pressure injury incidence rates 1 month after training suggest study educational efforts had a short-lasting effect. Future research is indicated to determine the most effective method to improve nurses' ability to identify and distinguish IAD from pressure injury in the SNF setting.

Formula Feeding Is Independently Associated With Acute Kidney Injury in Very Low Birth Weight Infants.

PubMed

Ginovart, Gemma; Gich, Ignasi; Verd, Sergio

2016-11-01

Successful strategies to prevent neonatal acute kidney injury are lacking. Nevertheless, it is well known that in breastfed babies the excretory needs of the kidney are low because the intake of most nutrients is just above the nutritional requirement. This study aimed to determine whether feeding type predicts acute kidney injury in the very low birth weight infant. One hundred and eighty-six infants were enrolled in this pre-post cohort study (114 infants were included in the only human milk-fed group and 72 in the formula-fed group). Routine biological markers of acute kidney injury were collected in both groups from birth to discharge. Compared with formula feeding, human milk feeding was associated with almost 80% lower odds of acute kidney injury (odds ratio [OR] = 0.2; 95% confidence interval [CI], 0.05-0.77). After confounding variables had been controlled for, formula feeding was independently associated with acute kidney injury in very low birth weight infants. The study showed that, at our institution, acute kidney injury in the neonatal period is frequently associated with the avoidable procedure of formula feeding. Further prospective multicenter studies are needed to determine the generality of this association.

Inter-ethnic variation of ocular traits-design and methodology of comparison study among American Caucasians, American Chinese and mainland Chinese.

PubMed

Wang, Dan Dan; Huang, Guo Fu; He, Ming Guang; Wu, Ling Ling; Lin, Shan

2011-03-01

To summarize the design and methodology of a multi-center study. With the existed ethnic differences of glaucoma, this survey will explore the differences with regard to anterior and posterior ocular segment parameters between Caucasians and Chinese. In this study, four cohorts including American Caucasians and American Chinese from San Francisco, southern mainland Chinese from Guangzhou, and northern mainland Chinese from Beijing were prospectively enrolled for a series of eye examinations and tests from May 2008 to December 2010. A total of 120 subjects including 15 of each gender in each age decade from 40s to 70s were recruited for each group. Data of the following tests were collected: a questionnaire eliciting systemic and ocular disease history, blood pressure, presenting and best corrected visual acuity, auto-refraction, Goldmann applanation tonometry, gonioscopy, A-scan, anterior segment optical coherence tomography (ASOCT), ultrasound biomicroscopy (UBM), visual field (VF), Heidelberg retinal tomography (HRT), OCT for optic nerve, and digital fundus photography. this study will provide insights to the etiologies of glaucoma especially PACG through inter-ethnic comparisons of relevant ocular anatomic and functional parameters.

Switch From Epoetin Beta to Darbepoetin Alfa Treatment of Anemia in Taiwanese Hemodialysis Patients: Dose Equivalence by Hemoglobin Stratification.

PubMed

Liao, Shang-Chih; Hung, Cheng-Chieh; Lee, Chien-Te; Lee, Chih-Hsiung; Lee, Chin-Chan; Lin, Chun-Liang; Sun, Chiao-Yin; Cheng, Ben-Chung; Yang, Chih-Chao; Wu, Chien-Hsing; Chen, Jin-Bor

2016-08-01

This multicenter study was designed to assess the hemoglobin (Hb) stability and conversion ratio of the switch from epoetin beta to darbepoetin alfa in Taiwanese hemodialysis (HD) patients. A total of 135 HD patients were enrolled and randomized with intravenous darbepoetin alfa or epoetin beta. The study duration was 24 weeks. Equivalent doses and conversion ratios were assessed with respect to Hb stratification: low Hb (≥8.0 g/dL to ≤10.0 g/dL) and high Hb (>10.0 g/dL to ≤11.0 g/dL). The results showed stable Hb levels in the study period. At week 24, the conversion ratio was higher for high Hb than low Hb (296.4 IU/dose epoetin beta: 1 µg/dose darbepoetin alfa. vs. 277.2 IU/dose epoetin beta: 1 µg/dose darbepoetin alfa). In conclusion, the conversion ratio in the present study was higher than 1 µg: 200 IU for darbepoetin alfa: epoetin for treating anemia in Taiwanese HD patients. © 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

A randomized trial of atropine vs patching for treatment of moderate amblyopia: follow-up at age 10 years.

PubMed

Repka, Michael X; Kraker, Raymond T; Beck, Roy W; Holmes, Jonathan M; Cotter, Susan A; Birch, Eileen E; Astle, William F; Chandler, Danielle L; Felius, Joost; Arnold, Robert W; Tien, D Robbins; Glaser, Stephen R

2008-08-01

To determine the visual acuity outcome at age 10 years for children younger than 7 years when enrolled in a treatment trial for moderate amblyopia. In a multicenter clinical trial, 419 children with amblyopia (visual acuity, 20/40-20/100) were randomized to patching or atropine eyedrops for 6 months. Two years after enrollment, a subgroup of 188 children entered long-term follow-up. Treatment after 6 months was at the discretion of the investigator; 89% of children were treated. Visual acuity at age 10 years with the electronic Early Treatment Diabetic Retinopathy Study test. Patching and atropine eyedrops produce comparable improvement in visual acuity that is maintained through age 10 years. The mean amblyopic eye acuity, measured in 169 patients, at age 10 years was 0.17 logMAR (logarithm of the minimum angle of resolution) (approximately 20/32), and 46% of amblyopic eyes had an acuity of 20/25 or better. Age younger than 5 years at entry into the randomized trial was associated with a better visual acuity outcome (P < .001). Mean amblyopic and sound eye visual acuities at age 10 years were similar in the original treatment groups (P = .56 and P = .80, respectively). At age 10 years, the improvement of the amblyopic eye is maintained, although residual amblyopia is common after treatment initiated at age 3 years to younger than 7 years. The outcome is similar regardless of initial treatment with atropine or patching.

Superior Rhythm Discrimination With the SmartShock Technology Algorithm　- Results of the Implantable Defibrillator With Enhanced Features and Settings for Reduction of Inaccurate Detection (DEFENSE) Trial.

PubMed

Oginosawa, Yasushi; Kohno, Ritsuko; Honda, Toshihiro; Kikuchi, Kan; Nozoe, Masatsugu; Uchida, Takayuki; Minamiguchi, Hitoshi; Sonoda, Koichiro; Ogawa, Masahiro; Ideguchi, Takeshi; Kizaki, Yoshihisa; Nakamura, Toshihiro; Oba, Kageyuki; Higa, Satoshi; Yoshida, Keiki; Tsunoda, Soichi; Fujino, Yoshihisa; Abe, Haruhiko

2017-08-25

Shocks delivered by implanted anti-tachyarrhythmia devices, even when appropriate, lower the quality of life and survival. The new SmartShock Technology ® (SST) discrimination algorithm was developed to prevent the delivery of inappropriate shock. This prospective, multicenter, observational study compared the rate of inaccurate detection of ventricular tachyarrhythmia using the SST vs. a conventional discrimination algorithm.Methods and Results:Recipients of implantable cardioverter defibrillators (ICD) or cardiac resynchronization therapy defibrillators (CRT-D) equipped with the SST algorithm were enrolled and followed up every 6 months. The tachycardia detection rate was set at ≥150 beats/min with the SST algorithm. The primary endpoint was the time to first inaccurate detection of ventricular tachycardia (VT) with conventional vs. the SST discrimination algorithm, up to 2 years of follow-up. Between March 2012 and September 2013, 185 patients (mean age, 64.0±14.9 years; men, 74%; secondary prevention indication, 49.5%) were enrolled at 14 Japanese medical centers. Inaccurate detection was observed in 32 patients (17.6%) with the conventional, vs. in 19 patients (10.4%) with the SST algorithm. SST significantly lowered the rate of inaccurate detection by dual chamber devices (HR, 0.50; 95% CI: 0.263-0.950; P=0.034). Compared with previous algorithms, the SST discrimination algorithm significantly lowered the rate of inaccurate detection of VT in recipients of dual-chamber ICD or CRT-D.

Multicenter Clinical Evaluation of the Alere i Respiratory Syncytial Virus Isothermal Nucleic Acid Amplification Assay.

PubMed

Hassan, Ferdaus; Hays, Lindsay M; Bonner, Aleta; Bradford, Bradley J; Franklin, Ruffin; Hendry, Phyllis; Kaminetsky, Jed; Vaughn, Michael; Cieslak, Kristin; Moffatt, Mary E; Selvarangan, Rangaraj

2018-03-01

The Alere i respiratory syncytial virus (RSV) assay is an isothermal nucleic acid amplification test capable of detecting RSV directly from respiratory specimens, with results being available in ≤13 min after test initiation. The objective of this study was to evaluate the performance characteristics of the Alere i RSV assay in a point-of-care setting by using direct nasopharyngeal (NP) swab specimens (direct NP) and nasopharyngeal swab specimens eluted and transported in viral transport medium (VTM NP). The study was a prospective, multicenter, clinical trial conducted at 9 sites across the United States to evaluate the clinical performance of the Alere i RSV assay with respiratory specimens obtained from both children (age, <18 years) and older adults (age, >60 years). The performance of the Alere i RSV assay was compared with that of the reference method, the Prodesse ProFlu+ real-time reverse transcriptase PCR (RT-PCR) assay. All specimens with discrepant test results were tested further by a second FDA-cleared PCR assay (the Verigene respiratory virus plus nucleic acid test; Luminex Inc., TX). A total of 554 subjects with signs and symptoms of respiratory infections were enrolled, and respiratory samples were collected in this study. In comparison with the ProFlu+ real-time RT-PCR, the overall sensitivity and specificity of Alere i RSV assay for the detection of RSV were 98.6% (95% confidence interval [CI], 94.4 to 99.7%) and 98.0% (95% CI, 95.8 to 99.1%), respectively, for direct NP and 98.6% (95% CI, 94.4 to 99.7%) and 97.8% (95% CI, 95.5 to 98.9%), respectively, for VTM NP. The Alere i RSV is a highly sensitive and specific molecular assay ideal for rapid RSV detection in patients in the point-of-care setting due to its minimal hands-on time and rapid result availability. Copyright © 2018 American Society for Microbiology.

Solitaire™ with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) trial: protocol for a randomized, controlled, multicenter study comparing the Solitaire revascularization device with IV tPA with IV tPA alone in acute ischemic stroke.

PubMed

Saver, Jeffrey L; Goyal, Mayank; Bonafe, Alain; Diener, Hans-Christoph; Levy, Elad I; Pereira, Vitor M; Albers, Gregory W; Cognard, Christophe; Cohen, David J; Hacke, Werner; Jansen, Olav; Jovin, Tudor G; Mattle, Heinrich P; Nogueira, Raul G; Siddiqui, Adnan H; Yavagal, Dileep R; Devlin, Thomas G; Lopes, Demetrius K; Reddy, Vivek; du Mesnil de Rochemont, Richard; Jahan, Reza

2015-04-01

Early reperfusion in patients experiencing acute ischemic stroke is critical, especially for patients with large vessel occlusion who have poor prognosis without revascularization. Solitaire™ stent retriever devices have been shown to immediately restore vascular perfusion safely, rapidly, and effectively in acute ischemic stroke patients with large vessel occlusions. The aim of the study was to demonstrate that, among patients with large vessel, anterior circulation occlusion who have received intravenous tissue plasminogen activator, treatment with Solitaire revascularization devices reduces degree of disability 3 months post stroke. The study is a global multicenter, two-arm, prospective, randomized, open, blinded end-point trial comparing functional outcomes in acute ischemic stroke patients who are treated with either intravenous tissue plasminogen activator alone or intravenous tissue plasminogen activator in combination with the Solitaire device. Up to 833 patients will be enrolled. Patients who have received intravenous tissue plasminogen activator are randomized to either continue with intravenous tissue plasminogen activator alone or additionally proceed to neurothrombectomy using the Solitaire device within six-hours of symptom onset. The primary end-point is 90-day global disability, assessed with the modified Rankin Scale (mRS). Secondary outcomes include mortality at 90 days, functional independence (mRS ≤ 2) at 90 days, change in National Institutes of Health Stroke Scale at 27 h, reperfusion at 27 h, and thrombolysis in cerebral infarction 2b/3 flow at the end of the procedure. Statistical analysis will be conducted using simultaneous success criteria on the overall distribution of modified Rankin Scale (Rankin shift) and proportions of subjects achieving functional independence (mRS 0-2). © 2015 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.

Comparative effect on platelet function of a fixed-dose aspirin and clopidogrel combination versus separate formulations in patients with coronary artery disease: A phase IV, multicenter, prospective, 4-week non-inferiority trial.

PubMed

Oh, Pyung Chun; Ahn, Taehoon; Kim, Dong Woon; Hong, Bum-Kee; Kim, Dong-Soo; Kwan, Jun; Choi, Cheol Ung; Yang, Yong-Mo; Bae, Jang Ho; Jung, Kyung Tae; Choi, Woong Gil; Jeon, Dong Woon; Cho, Deok Kyu; Pyun, Wook Bum; Cha, Kwang Soo; Cha, Tae-Joon; Chun, Kook Jin; Kim, Young Dae; Kim, Byung Soo; Kim, Doo-Il; Kim, Tae Ik

2016-01-01

The effect of aspirin and clopidogrel in a fixed-dose combination (FDC) on platelet function was compared with separate formulations in patients that had undergone percutaneous coronary intervention (PCI) with drug-eluting stent (DES). This was a phase IV, prospective, multicenter, single-arm, non-inferiority study. Patients that had taken aspirin 100 mg and clopidogrel 75 mg once daily as separate formulations for >6 months after PCI with DES were enrolled, and then switched to an aspirin/clopidogrel FDC once-daily for 4 weeks. Platelet reactivity was determined using the VerifyNow® P2Y12 assay at baseline (immediately prior to switching) and 4 weeks later. A total of 648 patients (the full-analysis population; age, 63.6±9.0 years; male, 76.5%) finished the study, and 565 (the per-protocol population) completed without protocol violations. In the per-protocol population, the % inhibitions of P2Y12 and ARU were not significantly different between baseline and after 4 weeks of FDC treatment (29.2±20.0% to 29.0±19.9%, P=0.708; 445.1±69.2 to 446.2±63.0, P=0.799, respectively) and the difference in P2Y12 inhibition observed did not exceed the predetermined limit of non-inferiority (95% CI, -0.9 to 1.3). In the full-analysis population, the % inhibitions of P2Y12, PRU, and ARU were not significantly changed after 4 weeks of FDC treatment. This study demonstrates that the efficacy of platelet inhibition by an aspirin/clopidogrel FDC was not inferior to that of separate aspirin and clopidogrel formulations in patients that had undergone PCI with DES. Copyright © 2015. Published by Elsevier Ireland Ltd.

Laparoscopic surgery for colorectal cancer is safe and has survival outcomes similar to those of open surgery in elderly patients with a poor performance status: subanalysis of a large multicenter case-control study in Japan.

PubMed

Niitsu, Hiroaki; Hinoi, Takao; Kawaguchi, Yasuo; Ohdan, Hideki; Hasegawa, Hirotoshi; Suzuka, Ichio; Fukunaga, Yosuke; Yamaguchi, Takashi; Endo, Shungo; Tagami, Soichi; Idani, Hitoshi; Ichihara, Takao; Watanabe, Kazuteru; Watanabe, Masahiko

2016-01-01

It remains controversial whether open or laparoscopic surgery should be indicated for elderly patients with colorectal cancer and a poor performance status. In those patients aged 80 years or older with Eastern Cooperative Oncology Group performance status score of 2 or greater who received elective surgery for stage 0 to stage III colorectal adenocarcinoma and had no concomitant malignancies and who were enrolled in a multicenter case-control study entitled "Retrospective study of laparoscopic colorectal surgery for elderly patients" that was conducted in Japan between 2003 and 2007, background characteristics and short-term and long-term outcomes for open surgery and laparoscopic surgery were compared. Of the 398 patients included, 295 underwent open surgery and 103 underwent laparoscopic surgery. There were no significant differences in the baseline characteristics between open surgery and laparoscopic surgery patients, except for previous abdominal surgery and TNM stage. The median operation duration was shorter with open surgery (open surgery, 153 min; laparoscopic surgery, 202 min; P < 0.001), and less blood loss occurred with laparoscopic surgery (median open surgery, 109 g; median laparoscopic surgery, 30 g; P < 0.001). An operation duration of 180 min or more (odds ratio, 1.97; 95 % confidence interval, 1.17-3.37; P = 0.011) and selection of laparoscopic surgery (odds ratio, 0.41; 95 % confidence interval, 0.22-0.75; P = 0.003) were statistically significant in the multivariate analysis for postoperative morbidity. Moreover, laparoscopic surgery did not result in an inferior overall survival rate compared with open surgery (log-rank test P = 0.289, 0.278, 0.346, 0.199, for all-stage, stage 0-I, stage II, and stage III disease, respectively). Laparoscopic surgery in elderly colorectal cancer patients with a poor performance status is safe and not inferior to open surgery in terms of overall survival.

Multicenter Phase II Trial of Temsirolimus and Bevacizumab in Pancreatic Neuroendocrine Tumors

PubMed Central

Hobday, Timothy J.; Qin, Rui; Reidy-Lagunes, Diane; Moore, Malcolm J.; Strosberg, Jonathan; Kaubisch, Andreas; Shah, Manisha; Kindler, Hedy Lee; Lenz, Heinz-Josef; Chen, Helen; Erlichman, Charles

2015-01-01

Purpose There are few effective therapies for pancreatic neuroendocrine tumors (PNETs). Recent placebo-controlled phase III trials of the mammalian target of rapamycin (mTOR) inhibitor everolimus and the vascular endothelial growth factor (VEGF)/platelet-derived growth factor receptor inhibitor sunitinib have noted improved progression-free survival (PFS). Preclinical studies have suggested enhanced antitumor effects with combined mTOR and VEGF pathway–targeted therapy. We conducted a clinical trial to evaluate combination therapy against these targets in PNETs. Patients and Methods We conducted a two-stage single-arm phase II trial of the mTOR inhibitor temsirolimus 25 mg intravenously (IV) once per week and the VEGF-A monoclonal antibody bevacizumab 10 mg/kg IV once every 2 weeks in patients with well or moderately differentiated PNETs and progressive disease by RECIST within 7 months of study entry. Coprimary end points were tumor response rate and 6-month PFS. Results A total of 58 patients were enrolled, and 56 patients were eligible for response assessment. Confirmed response rate (RR) was 41% (23 of 56 patients). PFS at 6 months was 79% (44 of 56). Median PFS was 13.2 months (95% CI, 11.2 to 16.6). Median overall survival was 34 months (95% CI, 27.1 to not reached). For evaluable patients, the most common grade 3 to 4 adverse events attributed to therapy were hypertension (21%), fatigue (16%), lymphopenia (14%), and hyperglycemia (14%). Conclusion The combination of temsirolimus and bevacizumab had substantial activity and reasonable tolerability in a multicenter phase II trial, with RR of 41%, well in excess of single targeted agents in patients with progressive PNETs. Six-month PFS was a notable 79% in a population of patients with disease progression by RECIST criteria within 7 months of study entry. On the basis of this trial, continued evaluation of combination mTOR and VEGF pathway inhibitors is warranted. PMID:25488966

The Barrel vascular reconstruction device for endovascular coiling of wide-necked intracranial aneurysms: a multicenter, prospective, post-marketing study.

PubMed

Gory, Benjamin; Blanc, Raphaël; Turjman, Francis; Berge, Jérôme; Piotin, Michel

2018-02-02

The Barrel vascular reconstruction device (Barrel VRD) is a novel stent with design features that allow endovascular coiling of wide-necked bifurcation aneurysms while preserving adjacent branches, without necessitating dual stent implantation. This study aimed to assess the safety and effectiveness of the Barrel VRD at 12-month follow-up. The Barrel VRD trial is a prospective, multicenter, observational post-marketing registry evaluating the use of the Barrel VRD for treatment of wide-necked bifurcation aneurysms. The primary effectiveness endpoint was successful aneurysm treatment measured by digital subtraction angiography with a Raymond-Roy occlusion grade of 1 or 2 in the absence of retreatment, parent artery stenosis (>50%), or target aneurysm rupture at 12 months. The primary safety endpoint was the absence of neurological death or major stroke at 12 months. Twenty patients were enrolled from December 2013 to December 2014. The device was implanted in 19 patients with 19 aneurysms (8 middle cerebral artery, 4 anterior communicating artery, 1 internal carotid artery terminus, 4 basilar artery aneurysms; mean dome height 5.7±1.91 mm; mean neck length 4.8±1.35 mm, mean dome-to-neck ratio 1.6±2.0). Coiling was performed in all cases. The primary effectiveness endpoint was achieved in 78.9% of subjects (15/19; 12 complete occlusions, 3 neck remnants), and the primary safety endpoint was 5.3% (1/19). This prospective study demonstrates that the Barrel VRD device resulted in ~80% occlusion rates and ~5% rates of neurological complications at 1 year after endovascular treatment of wide-necked bifurcation intracranial aneurysms. REGISTERED CLINICAL TRIAL: NCT02125097;Results. © 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.

[Pharmacotherapy of attention deficit hyperactivity disorder in children: the results of a multicenter double-blind placebo-controlled study of hopantenic acid].

PubMed

Zavadenko, N N; Suvorinova, N Yu; Vakula, I N; Malinina, E V; Kuzenkova, L M

To assess the efficacy and safety of hopantenic acid (pantogam) compared to placebo in the treatment of attention deficit hyperactivity disorder (ADHD) in children, aged from 6 to 12 years, during 4 month in the prospective multicenter comparative double-blind placebo-controlled study in parallel groups. One hundred patients enrolled in the safety assessment population were stratified into two equal pantogam and placebo groups. Eighty-nine patients who completed the study in according to the protocol were included in the efficacy assessment group: 45 in the pantogam group and 44 in the placebo group. Pantogam was administered in tablets (250 mg) in the therapeutic dose 30 mg/kg of body mass, divided into 2 doses, during 4 month. Patient's state was assessed by the total score on ADHD-DSM-IV, CGI-S WFIRS-P and results of the Toulouse-Piéron test for sustained attention. There was a trend towards an increase in the percentage of patients with positive changes (a decrease in the total ADHD-DSM-IV by ≥25%) in the end of the 3rd and 4th month in the pantogam group (treatment response was 66.7 and 68.9%, respectively) compared to the placebo group (treatment response was 52.3 and 61.4%, respectively). A significant decrease in disease severity assessed by the CGI-S was noted in the pantogam group compared to the placebo group. After 4 month of treatment with pantogam, the severity of functional disturbances was reduced by 4 out of 6 WFIRS-P domains: Family, School and learning, Child's self-concept and Risky activities. Pantogam improved the measures of sustained attention (accuracy and speed) in the Toulouse-Piéron test. The drug used in mean daily dose 30 mg/kg during 4 month had a favorable safety profile which did not differ from that of placebo.

Immediate transmucosal implant placement in molar extraction sites: a 12-month prospective multicenter cohort study.

PubMed

Cafiero, C; Annibali, S; Gherlone, E; Grassi, F R; Gualini, F; Magliano, A; Romeo, E; Tonelli, P; Lang, N P; Salvi, G E

2008-05-01

To assess the clinical and radiographic outcomes of immediate transmucosal placement of implants into molar extraction sockets. Twelve-month multicenter prospective cohort study. Following molar extraction, tapered implants with an endosseous diameter of 4.8 mm and a shoulder diameter of 6.5 mm were immediately placed into the sockets. Molars with evidence of acute periapical pathology were excluded. After implant placement and achievement of primary stability, flaps were repositioned and sutured allowing a non-submerged, transmucosal healing. Peri-implant marginal defects were treated according to the principles of guided bone regeneration (GBR) by means of deproteinized bovine bone mineral particles in conjunction with a bioresrobable collagen membrane. Standardized radiographs were obtained at baseline and 12 months thereafter. Changes in depth and width of the distance from the implant shoulder (IS) and from the alveolar crest (AC) to the bottom of the defect (BD) were assessed. Eighty-two patients (42 males and 40 females) were enrolled and followed for 12 months. They contributed with 82 tapered implants. Extraction sites displayed sufficient residual bone volume to allow primary stability of all implants. Sixty-four percent of the implants were placed in the areas of 36 and 46. GBR was used in conjunction with the placement of all implants. No post-surgical complications were observed. All implants healed uneventfully yielding a survival rate of 100% and healthy soft tissue conditions after 12 months. Radiographically, statistically significant changes (P<0.0001) in mesial and distal crestal bone levels were observed from baseline to the 12-month follow-up. The findings of this 12-month prospective cohort study showed that immediate transmucosal implant placement represented a predictable treatment option for the replacement of mandibular and maxillary molars lost due to reasons other than periodontitis including vertical root fractures, endodontic failures and caries.

Prevalence of externalized conductors in Riata and Riata ST silicone leads: results from the prospective, multicenter Riata Lead Evaluation Study.

PubMed

Hayes, David; Freedman, Roger; Curtis, Anne B; Niebauer, Mark; Neal Kay, G; Dinerman, Jay; Beau, Scott

2013-12-01

Following a class I recall of St. Jude Medical Riata/Riata ST silicone implantable cardioverter-defibrillator leads, we report on the phase I results of the Riata Lead Evaluation Study, a prospective, multicenter investigation to assess the prevalence of externalized conductors (ECs) and the electrical dysfunction in these leads. We enrolled patients previously implanted with Riata/Riata ST leads and performed cinefluoroscopy using multiple views. A physician panel adjudicated the images for the presence of EC. The prevalence of EC was stratified and compared by lead model and patient characteristics. Upon occurrence of a lead revision, another physician panel determined whether electrical dysfunction had occurred based on predefined criteria. Seven hundred seventy six patients with Riata/Riata ST silicone leads (8Fr/7Fr = 66.6%/33.4%; single-/dual-coil = 12.9%/87.1%) across 23 centers were analyzed. Implant duration was 4.8 ± 0.9 years for 7Fr and 6.5 ± 1.6 years for 8Fr leads (P <.001). The prevalence of EC was significantly lower in 7Fr compared with 8Fr leads for the entire study population (9.3% vs 24.2%, P < .001) and for leads implanted ≤6 years (9.4% vs 18.8%, P = .006). Other than lead size, there were no significant differences in lead, patient, or electrical characteristics between leads with and without EC. Over a period of 9.8 ± 2.0 months, the overall prevalence of electrical dysfunction was 1.3% (confidence interval 0.49%-2.1%), with only 3 of 10 cases occurring in leads with EC. Larger-diameter Riata leads were more prone to EC than smaller-diameter Riata ST leads. The prevalence of electrical dysfunction was not associated with EC. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Diagnostic Accuracy of Copeptin in the Differential Diagnosis of the Polyuria-polydipsia Syndrome: A Prospective Multicenter Study.

PubMed

Timper, Katharina; Fenske, Wiebke; Kühn, Felix; Frech, Nica; Arici, Birsen; Rutishauser, Jonas; Kopp, Peter; Allolio, Bruno; Stettler, Christoph; Müller, Beat; Katan, Mira; Christ-Crain, Mirjam

2015-06-01

The polyuria-polydipsia syndrome comprises primary polydipsia (PP) and central and nephrogenic diabetes insipidus (DI). Correctly discriminating these entities is mandatory, given that inadequate treatment causes serious complications. The diagnostic "gold standard" is the water deprivation test with assessment of arginine vasopressin (AVP) activity. However, test interpretation and AVP measurement are challenging. The objective was to evaluate the accuracy of copeptin, a stable peptide stoichiometrically cosecreted with AVP, in the differential diagnosis of polyuria-polydipsia syndrome. This was a prospective multicenter observational cohort study from four Swiss or German tertiary referral centers of adults >18 years old with the history of polyuria and polydipsia. A standardized combined water deprivation/3% saline infusion test was performed and terminated when serum sodium exceeded 147 mmol/L. Circulating copeptin and AVP levels were measured regularly throughout the test. Final diagnosis was based on the water deprivation/saline infusion test results, clinical information, and the treatment response. Fifty-five patients were enrolled (11 with complete central DI, 16 with partial central DI, 18 with PP, and 10 with nephrogenic DI). Without prior thirsting, a single baseline copeptin level >21.4 pmol/L differentiated nephrogenic DI from other etiologies with a 100% sensitivity and specificity, rendering a water deprivation testing unnecessary in such cases. A stimulated copeptin >4.9 pmol/L (at sodium levels >147 mmol/L) differentiated between patients with PP and patients with partial central DI with a 94.0% specificity and a 94.4% sensitivity. A stimulated AVP >1.8 pg/mL differentiated between the same categories with a 93.0% specificity and a 83.0% sensitivity. This study was limited by incorporation bias from including AVP levels as a diagnostic criterion. Copeptin is a promising new tool in the differential diagnosis of the polyuria-polydipsia syndrome, and a valid surrogate marker for AVP. Primary Funding Sources: Swiss National Science Foundation, University of Basel.

Association of day 4 cumulative fluid balance with mortality in critically ill patients with influenza: A multicenter retrospective cohort study in Taiwan.

PubMed

Chao, Wen-Cheng; Tseng, Chien-Hua; Chien, Ying-Chun; Sheu, Chau-Chyun; Tsai, Ming-Ju; Fang, Wen-Feng; Chen, Yu-Mu; Kao, Kuo-Chin; Hu, Han-Chung; Perng, Wann-Cherng; Yang, Kuang-Yao; Chen, Wei-Chih; Liang, Shinn-Jye; Wu, Chieh-Liang; Wang, Hao-Chien; Chan, Ming-Cheng

2018-01-01

Fluid balance is a fundamental management of patients with sepsis, and this study aimed to investigate the impact of cumulative fluid balance on critically ill patients with influenza admitted to an intensive care unit (ICU). This multicenter retrospective cohort study was conducted by the Taiwan Severe Influenza Research Consortium (TSIRC) which includes eight medical centers. Patients with virology-proven influenza infection admitted to ICUs between October 2015 and March 2016 were included for analysis. A total of 296 patients were enrolled (mean age: 61.4±15.6 years; 62.8% men), and 92.2% (273/296) of them required mechanical ventilation. In the survivors, the daily fluid balance was positive from day 1 to day 3, and then gradually became negative from day 4 to day 7, whereas daily fluid balance was continuously positive in the non-survivors. Using the cumulative fluid balance from day 1-4 as a cut-off point, we found that a negative cumulative day 1-4 fluid balance was associated with a lower 30-day mortality rate (log-rank test, P = 0.003). To evaluate the impact of shock on this association, we divided the patients into shock and non-shock groups. The positive correlation between negative day 1-4 fluid balance and mortality was significant in the non-shock group (log-rank test, P = 0.008), but not in the shock group (log-rank test, P = 0.396). In a multivariate Cox proportional hazard regression model adjusted for age, sex, cerebrovascular disease, and PaO2/FiO2, day 1-4 fluid balance was independently associated with a higher 30-day mortality rate (aHR 1.088, 95% CI: 1.007-1.174). A negative day 1-4 cumulative fluid balance was associated with a lower mortality rate in critically ill patients with influenza. Our findings indicate the critical role of conservative fluid strategy in the management of patients with complicated influenza.

Reduced duration of dual antiplatelet therapy using an improved drug-eluting stent for percutaneous coronary intervention of the left main artery in a real-world, all-comer population: Rationale and study design of the prospective randomized multicenter IDEAL-LM trial.

PubMed

Lemmert, Miguel E; Oldroyd, Keith; Barragan, Paul; Lesiak, Maciej; Byrne, Robert A; Merkulov, Evgeny; Daemen, Joost; Onuma, Yoshinobu; Witberg, Karen; van Geuns, Robert-Jan

2017-05-01

Continuous improvements in stent technology make percutaneous coronary intervention (PCI) a potential alternative to surgery in selected patients with unprotected left main coronary artery (uLMCA) disease. The optimal duration of dual antiplatelet therapy (DAPT) in these patients remains undetermined, and in addition, new stent designs using a bioabsorbable polymer might allow shorter duration of DAPT. IDEAL-LM is a prospective, randomized, multicenter study that will enroll 818 patients undergoing uLMCA PCI. Patients will be randomized in a 1:1 fashion to intravascular ultrasound-guided PCI with the novel everolimus-eluting platinum-chromium Synergy stent with a biodegradable polymer (Boston Scientific, Natick, MA) followed by 4 months of DAPT or the everolimus-eluting cobalt-chromium Xience stent (Abbott Vascular, Santa Clara, CA) followed by 12 months of DAPT. The total follow-up period will be 5 years. A subset of 100 patients will undergo optical coherence tomography at 3 months. The primary end point will be major adverse cardiovascular events (composite of all-cause mortality, myocardial infarction, and ischemia-driven target vessel revascularization) at 2 years. Secondary end points will consist of the individual components of the primary end point, procedural success, a device-oriented composite end point, stent thrombosis as per Academic Research Consortium criteria, and bleeding as per Bleeding Academic Research Consortium criteria. IDEAL-LM is designed to assess the safety and efficacy of the novel Synergy stent followed by 4 months of DAPT vs the Xience stent followed by 12 months of DAPT in patients undergoing uLMCA PCI. The study will provide novel insights regarding optimal treatment strategy for patients undergoing PCI of uLMCA disease (www.clinicaltrials.gov, NCT 02303717). Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Haemophilus influenzae type b as an important cause of culture-positive acute otitis media in young children in Thailand: a tympanocentesis-based, multi-center, cross-sectional study

PubMed Central

2014-01-01

Background Streptococcus pneumoniae (S. pneumoniae) and Haemophilus influenzae (H. influenzae) are considered major causes of bacterial acute otitis media (AOM) worldwide, but data from Asia on primary causes of AOM are limited. This tympanocentesis-based, multi-center, cross-sectional study assessed bacterial etiology and antimicrobial susceptibility of AOM in Thailand. Methods Children 3 to 59 months presenting with AOM (< 72 hours of onset) who had not received prescribed antibiotics, or subjects who received prescribed antibiotics but remained symptomatic after 48–72 hours (treatment failures), were eligible. Study visits were conducted from April 2008 to August 2009. Bacteria were identified from middle ear fluid collected by tympanocentesis or spontaneous otorrhea swab sampling (< 20% of cases). S. pneumoniae and H. influenzae serotypes were determined and antimicrobial resistance was also assessed. Results Of the 123 enrolled children, 112 were included in analysis and 48% of the 118 samples were positive for S. pneumoniae (23% (27/118)), H. influenzae (18% (21/118)), Moraxella catarrhalis (6% (7/118)) or Streptococcus pyogenes (3% (4/118)). The most common pneumococcal serotypes were 19F (26%) and 14 (22%). The majority of H. influenzae isolates were encapsulated (18/21), with 13 type b (Hib) representing 62% of all H. influenzae isolate or 11% of all samples (13/118), and there were only 3 non-typeable isolates. Despite high antibiotic resistance, amoxicillin/clavulanate susceptibility was high. No pneumococcal vaccine use was reported. Conclusions S. pneumoniae and H. influenzae, both frequently antibiotic resistant, were leading causes of bacterial AOM and there was an unexpectedly high burden of Hib in this population unvaccinated by any Hib conjugate vaccine. Conjugate vaccines effective against pneumococcus and H. influenzae could potentially reduce the burden of AOM in this population. PMID:24947736

REVIVE Trial: Retrograde Delivery of Autologous Bone Marrow in Patients With Heart Failure.

PubMed

Patel, Amit N; Mittal, Sanjay; Turan, Goekmen; Winters, Amalia A; Henry, Timothy D; Ince, Hueseyin; Trehan, Naresh

2015-09-01

Cell therapy is an evolving option for patients with end-stage heart failure and ongoing symptoms despite optimal medical therapy. Our goal was to evaluate retrograde bone marrow cell delivery in patients with either ischemic heart failure (IHF) or nonischemic heart failure (NIHF). This was a prospective randomized, multicenter, open-label study of the safety and feasibility of bone marrow aspirate concentrate (BMAC) infused retrograde into the coronary sinus. Sixty patients were stratified by IHF and NIHF and randomized to receive either BMAC infusion or control (standard heart failure care) in a 4:1 ratio. Accordingly, 24 subjects were randomized to the ischemic BMAC group and 6 to the ischemic control group. Similarly, 24 subjects were randomized to the nonischemic BMAC group and 6 to the nonischemic control group. All 60 patients were successfully enrolled in the study. The treatment groups received BMAC infusion without complications. The left ventricular ejection fraction in the patients receiving BMAC demonstrated significant improvement compared with baseline, from 25.1% at screening to 31.1% at 12 months (p=.007) in the NIHF group and from 26.3% to 31.1% in the IHF group (p=.035). The end-systolic diameter decreased significantly in the nonischemic BMAC group from 55.6 to 50.9 mm (p=.020). Retrograde BMAC delivery is safe. All patients receiving BMAC experienced improvements in left ventricular ejection fraction, but only those with NIHF showed improvements in left ventricular end-systolic diameter and B-type natriuretic peptide. These results provide the basis for a larger clinical trial in HF patients. This work is the first prospective randomized clinical trial using high-dose cell therapy delivered via a retrograde coronary sinus infusion in patients with heart failure. This was a multinational, multicenter study, and it is novel, translatable, and scalable. On the basis of this trial and the safety of retrograde coronary sinus infusion, there are three other trials under way using this route of delivery. ©AlphaMed Press.

A multicenter, randomized, double-blind clinical study to evaluate the efficacy and safety of a new monophasic hyaluronic acid filler with lidocaine 0.3% in the correction of nasolabial fold.

PubMed

Suh, Joon Hyuk; Oh, Chang Taek; Im, Song I; Lim, Jung Soo; Kim, Beom Joon; Lee, Jong Hun

2017-09-01

Many new brands of hyaluronic acid (HA) fillers are being introduced, but comparative research on the characteristics of similar products is limited. To test the efficacy, tolerability, and safety of a HA filler with lidocaine, Dermalax implant plus™ (Across), which is used for correcting nasolabial folds (NLFs), and to compare the performance of that of Restylane Sub-Q ® (Q-Med). A total of 52 subjects with visible NLFs were enrolled in this randomized, multicenter, patient/evaluator-blind, active-controlled, matched-pair clinical study. Each subject was injected with Dermalax implant plus™ in one NLF and Restylane Sub-Q ® in the other. All participants were reassessed for cosmetic changes at 2, 8, 12, 16, and 24 weeks. Wrinkle severity was rated using the 5-point Wrinkle Severity Rating Scale (WSRS). At week 24, the mean improvement in the WSRS compared to baseline was 1.06±0.54 for the PLUS side and 0.69±0.58 for the Sub-Q side (week 2: 1.67±0.58 and 1.21±0.67, week 8: 1.60±0.63 and 1.23±0.65, week 12: 1.58±0.61 and 1.15±0.61, week 16: 1.02±0.54 and 0.60±0.53). Average values of pain evaluated by self-assessment 100-mm VAS score within 30 minutes after the procedure in the PLUS and Sub-Q groups were 14.65±16.23 and 38.29±27.27, respectively. Both fillers were well tolerated, and adverse reactions were mild. We confirmed that the monophasic HA containing pre-incorporated lidocaine (PLUS) is not inferior to well-studied biphasic HA (Sub-Q) in correcting to severe nasolabial folds for 24 weeks and less painful than biphasic HA not containing lidocaine. © 2017 Wiley Periodicals, Inc.

A randomized, multi-center, open-label, phase III study of once-per-cycle DA-3031, a pegylated G-CSF, in comparison with daily filgrastim in patients receiving TAC chemotherapy for breast cancer.

PubMed

Park, K H; Lee, S; Park, J H; Kang, S Y; Kim, H Y; Park, I H; Park, Y H; Im, Y H; Lee, H J; Park, S; Lee, S I; Jung, K H; Kim, Y S; Seo, Jae Hong

2017-02-01

This multi-center, randomized, phase III study was conducted to demonstrate the non-inferiority of DA-3031 compared with daily filgrastim in patients during the first cycle of chemotherapy for breast cancer in terms of the duration of severe neutropenia (DSN). Seventy-four patients with breast cancer who were receiving combination chemotherapy with docetaxel, doxorubicin, and cyclophosphamide (TAC) were enrolled. All participants were randomized to receive either daily subcutaneous injections of filgrastim 100 μg/m 2 /day for up to 10 days or a single subcutaneous injection of DA-3031 at fixed doses of 6 mg on day 2 of each chemotherapy cycle. The mean duration of grade 4 (G4) neutropenia in cycle 1 was 2.08 ± 0.85 days for the filgrastim group and 2.28 ± 1.14 days for the DA-3031 group. The difference between groups was 0.2 ± 1.10 days (95 % confidence interval (CI) = -0.26, 0.66), which supported non-inferiority. No statistically significant differences were observed in nadir absolute neutrophil count (ANC) (154.34/mm 3 and 161.75/mm 3 for the filgrastim and DA-3031 groups, respectively; P = 0.8414) or in time to ANC recovery (10.03 ± 0.75 and 9.83 ± 1.56 days in the filgrastim and DA-3031 groups, respectively; P = 0.0611) during cycle 1. Serious AEs occurred in six (15.8 %) patients receiving filgrastim and in ten (27.8 %) patients receiving DA-3031; however, none was determined to be related to the study drug. DA-3031 and daily filgrastim are similar in regard to DSN and safety in breast cancer patients receiving TAC chemotherapy.

Adjuvant Chemoradiation for Gastric Cancer Using Epirubicin, Cisplatin, and 5-Fluorouracil Before and After Three-Dimensional Conformal Radiotherapy With Concurrent Infusional 5-Fluorouracil: A Multicenter Study of the Trans-Tasman Radiation Oncology Group

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

Leong, Trevor, E-mail: trevor.leong@petermac.or; Joon, Daryl Lim; Willis, David

Purpose: The INT0116 study has established postoperative chemoradiotherapy as the standard of care for completely resected gastric adenocarcinoma. However, the optimal chemoradiation regimen remains to be defined. We conducted a prospective, multicenter study to evaluate an alternative chemoradiation regimen that combines more current systemic treatment with modern techniques of radiotherapy delivery. Methods and Materials: Patients with adenocarcinoma of the stomach who had undergone an R0 resection were eligible. Adjuvant therapy consisted of one cycle of epirubicin, cisplatin, and 5-FU (ECF), followed by radiotherapy with concurrent infusional 5-FU, and then two additional cycles of ECF. Radiotherapy was delivered using precisely defined,more » multiple-field, three-dimensional conformal techniques. Results: A total of 54 assessable patients were enrolled from 19 institutions. The proportion of patients commencing Cycles 1, 2, and 3 of ECF chemotherapy were 100%, 81%, and 67% respectively. In all, 94% of patients who received radiotherapy completed treatment as planned. Grade 3/4 neutropenia occurred in 66% of patients with 7.4% developing febrile neutropenia. Most neutropenic episodes (83%) occurred in the post-radiotherapy period during cycles 2 and 3 of ECF. Grade 3/4 gastrointestinal toxicity occurred in 28% of patients. In all, 35% of radiotherapy treatment plans contained protocol deviations that were satisfactorily amended before commencement of treatment. At median follow-up of 36 months, the 3-year overall survival rate was estimated at 61.6%. Conclusions: This adjuvant regimen using ECF before and after three-dimensional conformal chemoradiation is feasible and can be safely delivered in a cooperative group setting. A regimen similar to this is currently being compared with the INT0116 regimen in a National Cancer Institute-sponsored, randomized Phase III trial.« less

Protocolized fluid therapy in brain-dead donors: The multi-center randomized MOnIToR trial

PubMed Central

Al-Khafaji, Ali; Elder, Michele; Lebovitz, Daniel J; Murugan, Raghavan; Souter, Michael; Stuart, Susan; Wahed, Abdus S.; Keebler, Ben; Dils, Dorrie; Mitchell, Stephanie; Shutterly, Kurt; Wilkerson, Dawn; Pearse, Rupert; Kellum, John A

2015-01-01

BACKGROUND Critical shortages of organs for transplantation jeopardize many lives. Observational data suggest that better fluid management for deceased organ donors could increase organ recovery. We conducted the first large multi-center randomized trial in brain-dead donors to determine whether protocolized fluid therapy increases organs transplanted. METHODS We randomly assigned donors to either protocolized or usual care in eight organ procurement organizations. A “protocol-guided fluid therapy” algorithm targeting cardiac index, mean arterial pressure and pulse pressure variation was used. Our primary outcome was the number of organs transplanted per donor and our primary analysis was intention-to-treat. Secondary analyses included: 1) modified intention-to-treat where only subjects able to receive the intervention were included, and 2) twelve-month survival in transplant recipients. The study was stopped early. RESULTS We enrolled 556 donors; 279 protocolized care, 277 usual care. Groups had similar characteristics at baseline. The study protocol could be implemented in 76% of subjects randomized to the intervention. There was no significant difference in mean number of organs transplanted per donor: 3.39 organs per donor, (95%CI: 3.14-3.63) with protocolized care, compared to usual care 3.29 (95%CI: 3.04-3.54) (mean difference, 0.1, 95%CI: -0.25 to 0.45; p=0.56). In modified intention-to-treat analysis the mean number of organs increased (3.52 organs per donor, 95%CI: 3.23-3.8) but was not statistically significant (mean difference, 0.23, 95%CI: -0.15-0.61; p=0.23). Among the 1430 recipients of organs from study subjects, with data available, 56 deaths (7.8%) occurred in the protocolized care arm and 56 (7.9%) in the usual care arm in the first year (Hazard Ratio: 0.97, p=0.86). CONCLUSIONS In brain-dead organ donors, protocol-guided fluid therapy compared to usual care may not increase the number of organs transplanted per donor. PMID:25583616

Impact of the Patient-Reported Outcomes Management Information System (PROMIS) upon the design and operation of multi-center clinical trials: a qualitative research study.

PubMed

Eisenstein, Eric L; Diener, Lawrence W; Nahm, Meredith; Weinfurt, Kevin P

2011-12-01

New technologies may be required to integrate the National Institutes of Health's Patient Reported Outcome Management Information System (PROMIS) into multi-center clinical trials. To better understand this need, we identified likely PROMIS reporting formats, developed a multi-center clinical trial process model, and identified gaps between current capabilities and those necessary for PROMIS. These results were evaluated by key trial constituencies. Issues reported by principal investigators fell into two categories: acceptance by key regulators and the scientific community, and usability for researchers and clinicians. Issues reported by the coordinating center, participating sites, and study subjects were those faced when integrating new technologies into existing clinical trial systems. We then defined elements of a PROMIS Tool Kit required for integrating PROMIS into a multi-center clinical trial environment. The requirements identified in this study serve as a framework for future investigators in the design, development, implementation, and operation of PROMIS Tool Kit technologies.

Impact of the Patient-Reported Outcomes Management Information System (PROMIS) upon the Design and Operation of Multi-center Clinical Trials: a Qualitative Research Study

PubMed Central

Diener, Lawrence W.; Nahm, Meredith; Weinfurt, Kevin P.

2013-01-01

New technologies may be required to integrate the National Institutes of Health’s Patient Reported Outcome Management Information System (PROMIS) into multi-center clinical trials. To better understand this need, we identified likely PROMIS reporting formats, developed a multi-center clinical trial process model, and identified gaps between current capabilities and those necessary for PROMIS. These results were evaluated by key trial constituencies. Issues reported by principal investigators fell into two categories: acceptance by key regulators and the scientific community, and usability for researchers and clinicians. Issues reported by the coordinating center, participating sites, and study subjects were those faced when integrating new technologies into existing clinical trial systems. We then defined elements of a PROMIS Tool Kit required for integrating PROMIS into a multi-center clinical trial environment. The requirements identified in this study serve as a framework for future investigators in the design, development, implementation, and operation of PROMIS Tool Kit technologies. PMID:20703765

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

Hoppe, Bradford S., E-mail: bhoppe@floridaproton.org; Henderson, Randal; Pham, Dat

Purpose: Proton therapy has been shown to reduce radiation dose to organs at risk (OAR) and could be used to safely escalate the radiation dose. We analyzed outcomes in a group of phase 2 study patients treated with dose-escalated proton therapy with concurrent chemotherapy for stage 3 non-small cell lung cancer (NSCLC). Methods and Materials: From 2009 through 2013, LU02, a phase 2 trial of proton therapy delivering 74 to 80 Gy at 2 Gy/fraction with concurrent chemotherapy for stage 3 NSCLC, was opened to accrual at our institution. Due to slow accrual and competing trials, the study was closed after justmore » 14 patients (stage IIIA, 9 patients; stage IIIB, 5 patients) were accrued over 4 years. During that same time period, 55 additional stage III patients were treated with high-dose proton therapy, including 7 in multi-institutional proton clinical trials, 4 not enrolled due to physician preference, and 44 who were ineligible based on strict entry criteria. An unknown number of patients were ineligible for enrollment due to insurance coverage issues and thus were treated with photon radiation. Median follow-up of surviving patients was 52 months. Results: Two-year overall survival and progression-free survival rates were 57% and 25%, respectively. Median lengths of overall survival and progression-free survival were 33 months and 14 months, respectively. There were no acute grade 3 toxicities related to proton therapy. Late grade 3 gastrointestinal toxicity and pulmonary toxicity each occurred in 1 patient. Conclusions: Dose-escalated proton therapy with concurrent chemotherapy was well tolerated with encouraging results among a small cohort of patients. Unfortunately, single-institution proton studies may be difficult to accrue and consideration for pragmatic and/or multicenter trial design should be considered when developing future proton clinical trials.« less

Prevalence of Fabry Disease in Young Patients with Stroke in Argentina.

PubMed

Reisin, Ricardo C; Mazziotti, Julieta; Cejas, Luciana León; Zinnerman, Alberto; Bonardo, Pablo; Pardal, Manuel Fernández; Martínez, Alejandra; Riccio, Patricia; Ameriso, Sebastián; Bendersky, Eduardo; Nofal, Pedro; Cairola, Patricia; Jure, Lorena; Sotelo, Andrea; Rozenfeld, Paula; Ceci, Romina; Casas-Parera, Ignacio; Sánchez-Luceros, Analía

2018-03-01

Fabry disease (FD) is an underdiagnosed cause of stroke in young adults, but the frequency of this association is largely unknown. We estimated the prevalence of FD in a nationwide cohort of young adults who had stroke and transient ischemic attack (TIA) in Argentina. This was a prospective, multicenter study of stroke and FD in young adults (18-55 years) conducted in Argentina between 2011 and 2015. Patients were enrolled if they had had a TIA or an ischemic or hemorrhagic stroke within the previous 180 days. FD was diagnosed by measuring α-galactosidase A activity (males) and through genetic studies (females). We enrolled 311 patients (54% men, mean age: 41 years). Ischemic events occurred in 89% of patients (80% infarcts, 9% TIA) and hemorrhagic strokes in 11%. One female (.3% of the total group, 1% of the cryptogenic ischemic strokes) had the pathogenic mutation c.888G>A/p.Met296Ile /Exon 6 on the GAL gene. Her only other manifestation of FD was angiokeratoma. Eighteen females had nonpathogenic intronic variations: c.-10C>T, c.-12G>A, or both. Two patients had the nonpathogenic mutation D313Y, while a third had the likely benign mutation S126G. FD was identified in 1 patient (.3%) in this first Latin American study. The patient presented with a late-onset oligo-symptomatic form of the disease. A large number of nonpathogenic mutations were present in our cohort, and it is essential that they not be mistaken for pathogenic mutations to avoid unnecessary enzyme replacement treatment. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

The Prevalence and Incidence of Epiretinal Membranes in Eyes With Inactive Extramacular CMV Retinitis

PubMed Central

Kozak, Igor; Vaidya, Vijay; Van Natta, Mark L.; Pak, Jeong W.; May, K. Patrick; Thorne, Jennifer E.

2014-01-01

Purpose. To determine the prevalence and incidence of epiretinal membranes (ERM) in eyes with inactive extramacular cytomegalovirus (CMV) retinitis in patients with acquired immune deficiency syndrome (AIDS). Methods. A case–control report from a longitudinal multicenter observational study by the Studies of the Ocular Complications of AIDS (SOCA) Research Group. A total of 357 eyes of 270 patients with inactive CMV retinitis and 1084 eyes of 552 patients with no ocular opportunistic infection (OOI) were studied. Stereoscopic views of the posterior pole from fundus photographs were assessed at baseline and year 5 visits for the presence of macular ERM. Generalized estimating equations (GEE) logistic regression was used to compare the prevalence and 5-year incidence of ERM in eyes with and without CMV retinitis at enrollment. Crude and adjusted logistic regression was performed adjusting for possible confounders. Main outcome measures included the prevalence, incidence, estimated prevalence, and incidence odds ratios. Results. The prevalence of ERM at enrollment was 14.8% (53/357) in eyes with CMV retinitis versus 1.8% (19/1084) in eyes with no OOI. The incidence of ERM at 5 years was 18.6% (16/86) in eyes with CMV retinitis versus 2.4% (6/253) in eyes with no OOI. The crude odds ratio (OR) (95% confidence interval, CI) for prevalence was 9.8 (5.5–17.5) (P < 0.01). The crude OR (95% CI) for incidence was 9.4 (3.2–27.9) (P < 0.01). Conclusions. A history of extramacular CMV retinitis is associated with increased prevalence and incidence of ERM formation compared to what is seen in eyes without ocular opportunistic infections in AIDS patients. PMID:24925880

Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial.

PubMed

Mahaffey, K W; Puma, J A; Barbagelata, N A; DiCarli, M F; Leesar, M A; Browne, K F; Eisenberg, P R; Bolli, R; Casas, A C; Molina-Viamonte, V; Orlandi, C; Blevins, R; Gibbons, R J; Califf, R M; Granger, C B

1999-11-15

The Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial was designed to test the hypothesis that adenosine as an adjunct to thrombolysis would reduce myocardial infarct size. Reperfusion therapy for acute myocardial infarction (MI) has been shown to reduce mortality, but reperfusion itself also may have deleterious effects. The AMISTAD trial was a prospective, open-label trial of thrombolysis with randomization to adenosine or placebo in 236 patients within 6 h of infarction onset. The primary end point was infarct size as determined by Tc-99 m sestamibi single-photon emission computed tomography (SPECT) imaging 6+/-1 days after enrollment based on multivariable regression modeling to adjust for covariates. Secondary end points were myocardial salvage index and a composite of in-hospital clinical outcomes (death, reinfarction, shock, congestive heart failure or stroke). In all, 236 patients were enrolled. Final infarct size was assessed in 197 (83%) patients. There was a 33% relative reduction in infarct size (p = 0.03) with adenosine. There was a 67% relative reduction in infarct size in patients with anterior infarction (15% in the adenosine group vs. 45.5% in the placebo group) but no reduction in patients with infarcts located elsewhere (11.5% for both groups). Patients randomized to adenosine tended to reach the composite clinical end point more often than those assigned to placebo (22% vs. 16%; odds ratio, 1.43; 95% confidence interval, 0.71 to 2.89). Many agents thought to attenuate reperfusion injury have been unsuccessful in clinical investigation. In this study, adenosine resulted in a significant reduction in infarct size. These data support the need for a large clinical outcome trial.

Twice-daily versus once-daily applications of pimecrolimus cream 1% for the prevention of disease relapse in pediatric patients with atopic dermatitis.

PubMed

Ruer-Mulard, Mireille; Aberer, Werner; Gunstone, Anthony; Kekki, Outi-Maria; López Estebaranz, Jose Luis; Vertruyen, André; Guettner, Achim; Hultsch, Thomas

2009-01-01

The aim of this study is to compare twice-daily and once-daily applications of pimecrolimus cream 1% for prevention of atopic dermatitis relapses in pediatric patients. This multicenter trial enrolled 300 outpatients aged 2 to 17 years, with mild-to-severe atopic dermatitis. The patients were initially treated with twice-daily topical pimecrolimus until complete clearance or for up to 6 weeks (open-label period). Those who achieved a decrease of at least 1 point in the Investigator's Global Assessment score were then randomized to double-blind treatment with pimecrolimus cream 1% either twice daily or once daily for up to 16 weeks. Study medication was discontinued during periods of disease remission (Investigator's Global Assessment = 0). The primary efficacy end point of the double-blind phase was disease relapse (worsening requiring topical corticosteroids or additional/alternative therapy and confirmed by Investigator's Global Assessment score > or = 3 and pruritus score > or = 2). Of the 300 patients enrolled in the study, 268 were randomized to treatment with pimecrolimus cream 1% either twice daily or once daily (n = 134 in each group). The relapse rate was lower in the twice-daily dose group (9.9%) than that in the once-daily dose group (14.7%), but analysis of the time to disease relapse, using a Cox proportional model to adjust for confounding variables, did not show a statistically significant difference between treatment arms (hazard ratio: 0.64; 95% CI: 0.31-1.30). Treatment of active atopic dermatitis lesions with pimecrolimus cream 1% twice daily, followed by the once-daily dosing regimen, was sufficient to prevent subsequent atopic dermatitis relapses over 16 weeks in pediatric patients.

The prevalence and incidence of epiretinal membranes in eyes with inactive extramacular CMV retinitis.

PubMed

Kozak, Igor; Vaidya, Vijay; Van Natta, Mark L; Pak, Jeong W; May, K Patrick; Thorne, Jennifer E

2014-06-12

To determine the prevalence and incidence of epiretinal membranes (ERM) in eyes with inactive extramacular cytomegalovirus (CMV) retinitis in patients with acquired immune deficiency syndrome (AIDS). A case-control report from a longitudinal multicenter observational study by the Studies of the Ocular Complications of AIDS (SOCA) Research Group. A total of 357 eyes of 270 patients with inactive CMV retinitis and 1084 eyes of 552 patients with no ocular opportunistic infection (OOI) were studied. Stereoscopic views of the posterior pole from fundus photographs were assessed at baseline and year 5 visits for the presence of macular ERM. Generalized estimating equations (GEE) logistic regression was used to compare the prevalence and 5-year incidence of ERM in eyes with and without CMV retinitis at enrollment. Crude and adjusted logistic regression was performed adjusting for possible confounders. Main outcome measures included the prevalence, incidence, estimated prevalence, and incidence odds ratios. The prevalence of ERM at enrollment was 14.8% (53/357) in eyes with CMV retinitis versus 1.8% (19/1084) in eyes with no OOI. The incidence of ERM at 5 years was 18.6% (16/86) in eyes with CMV retinitis versus 2.4% (6/253) in eyes with no OOI. The crude odds ratio (OR) (95% confidence interval, CI) for prevalence was 9.8 (5.5-17.5) (P < 0.01). The crude OR (95% CI) for incidence was 9.4 (3.2-27.9) (P < 0.01). A history of extramacular CMV retinitis is associated with increased prevalence and incidence of ERM formation compared to what is seen in eyes without ocular opportunistic infections in AIDS patients. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Characterizing the course of back pain after osteoporotic vertebral fracture: a hierarchical cluster analysis of a prospective cohort study.

PubMed

Toyoda, Hiromitsu; Takahashi, Shinji; Hoshino, Masatoshi; Takayama, Kazushi; Iseki, Kazumichi; Sasaoka, Ryuichi; Tsujio, Tadao; Yasuda, Hiroyuki; Sasaki, Takeharu; Kanematsu, Fumiaki; Kono, Hiroshi; Nakamura, Hiroaki

2017-09-23

This study demonstrated four distinct patterns in the course of back pain after osteoporotic vertebral fracture (OVF). Greater angular instability in the first 6 months after the baseline was one factor affecting back pain after OVF. Understanding the natural course of symptomatic acute OVF is important in deciding the optimal treatment strategy. We used latent class analysis to classify the course of back pain after OVF and identify the risk factors associated with persistent pain. This multicenter cohort study included 218 consecutive patients with ≤ 2-week-old OVFs who were enrolled at 11 institutions. Dynamic x-rays and back pain assessment with a visual analog scale (VAS) were obtained at enrollment and at 1-, 3-, and 6-month follow-ups. The VAS scores were used to characterize patient groups, using hierarchical cluster analysis. VAS for 128 patients was used for hierarchical cluster analysis. Analysis yielded four clusters representing different patterns of back pain progression. Cluster 1 patients (50.8%) had stable, mild pain. Cluster 2 patients (21.1%) started with moderate pain and progressed quickly to very low pain. Patients in cluster 3 (10.9%) had moderate pain that initially improved but worsened after 3 months. Cluster 4 patients (17.2%) had persistent severe pain. Patients in cluster 4 showed significant high baseline pain intensity, higher degree of angular instability, and higher number of previous OVFs, and tended to lack regular exercise. In contrast, patients in cluster 2 had significantly lower baseline VAS and less angular instability. We identified four distinct groups of OVF patients with different patterns of back pain progression. Understanding the course of back pain after OVF may help in its management and contribute to future treatment trials.

A prospective observational study to evaluate G-CSF usage in patients with solid tumors receiving myelosuppressive chemotherapy in Italian clinical oncology practice.

PubMed

Barni, S; Lorusso, V; Giordano, M; Sogno, G; Gamucci, T; Santoro, A; Passalacqua, R; Iaffaioli, V; Zilembo, N; Mencoboni, M; Roselli, M; Pappagallo, G; Pronzato, P

2014-01-01

Febrile neutropenia (FN) is a severe dose-limiting side effect of myelosuppressive chemotherapy in patients with solid tumors. Clinical practice guidelines recommend primary prophylaxis with G-CSF in patients with an overall ≥ 20 % risk of FN. AIOM Italian guidelines recommend starting G-CSF within 24-72 h after chemotherapy; for daily G-CSF, administration should continue until the absolute neutrophil count (ANC) is 1 × 10(9)/L post-nadir and should not be terminated after ANC increase in the early days of administration. The aim of this study was to assess guideline adherence in oncology practice in Italy. In this multicenter, prospective, observational study, patients were enrolled at the first G-CSF use in any cycle and were followed for two subsequent cycles (or until the end of chemotherapy if less than two additional cycles). Primary objective was to explore G-CSF use in Italian clinical practice; therefore, data were collected on the G-CSF type, timing of administration, and number of doses. 512 eligible patients were enrolled (median age, 62). The most common tumor types were breast (36 %), lung (18 %), and colorectal (13 %). A total of 1,164 G-CSF cycles (daily G-CSF, 718; pegfilgrastim, 446) were observed. Daily G-CSF was administered later than 72 h after chemotherapy in 42 % of cycles, and the median [range] number of doses was four [1, 10]. Pegfilgrastim was administered later than 72 h in 8 % of cycles. G-CSF prophylaxis in Italy is frequently administered in a manner which is not supported by evidence-based guidelines. As this practice may lead to poor outcomes, educational initiatives are recommended.

Duration of Mechanical Ventilation in the Emergency Department.

PubMed

Angotti, Lauren B; Richards, Jeremy B; Fisher, Daniel F; Sankoff, Jeffrey D; Seigel, Todd A; Al Ashry, Haitham S; Wilcox, Susan R

2017-08-01

Due to hospital crowding, mechanically ventilated patients are increasingly spending hours boarding in emergency departments (ED) before intensive care unit (ICU) admission. This study aims to evaluate the association between time ventilated in the ED and in-hospital mortality, duration of mechanical ventilation, ICU and hospital length of stay (LOS). This was a multi-center, prospective, observational study of patients ventilated in the ED, conducted at three academic Level I Trauma Centers from July 2011 to March 2013. All consecutive adult patients on invasive mechanical ventilation were eligible for enrollment. We performed a Cox regression to assess for a mortality effect for mechanically ventilated patients with each hour of increasing LOS in the ED and multivariable regression analyses to assess for independently significant contributors to in-hospital mortality. Our primary outcome was in-hospital mortality, with secondary outcomes of ventilator days, ICU LOS and hospital LOS. We further commented on use of lung protective ventilation and frequency of ventilator changes made in this cohort. We enrolled 535 patients, of whom 525 met all inclusion criteria. Altered mental status without respiratory pathology was the most common reason for intubation, followed by trauma and respiratory failure. Using iterated Cox regression, a mortality effect occurred at ED time of mechanical ventilation > 7 hours, and the longer ED stay was also associated with a longer total duration of intubation. However, adjusted multivariable regression analysis demonstrated only older age and admission to the neurosciences ICU as independently associated with increased mortality. Of interest, only 23.8% of patients ventilated in the ED for over seven hours had changes made to their ventilator. In a prospective observational study of patients mechanically ventilated in the ED, there was a significant mortality benefit to expedited transfer of patients into an appropriate ICU setting.

[Adult patients treated for focal epilepsy with antiepileptic drugs (AEDs) in combination in France: description according to the 2009 ILAE definition of AED resistance (ESPERA study)].

PubMed

Vespignani, H; de Zélicourt, M; Laurendeau, C; Fagnani, F; Levy-Bachelot, L; Murat, C; Kahane, P; de Toffol, B

2014-02-01

To describe the adult population treated with antiepileptic drugs (AEDs) in combination for focal epilepsy according to the definition of AED resistance proposed by the International League Against Epilepsy (ILAE) in 2009 and to evaluate its implementation in current practice. ESPERA was a multicenter, observational, cross-sectional study with a clinical data collection covering the past 12 months conducted by neurologists. Classifications according to AED responsiveness established by investigators for each enrolled patient were revised by two experts. Seventy-one neurologists enrolled 405 patients. Their mean age was 42.7 years (sex-ratioM/F 0.98). According to the investigators, 60% of epilepsies were drug-resistant, 37% drug-responsive and 3% had an undefined drug-responsiveness. After revision of experts, 71% of epilepsies were classified as drug resistant, 22% as responsive and 7% as undefined. Among the participating neurologists, 76% have made at least one error in classifying their patients according to the 2009 ILAE definition of AED resistance. Because of epilepsy, 24% of patients (age≤65) were inactive and 42% could not drive (respectively 29 and 49% of patients with AED resistant epilepsy). Half of patients had at least one other chronic condition. Number of prescribed drugs in combination and health care resource utilisation were significantly higher in patients with drug-resistant epilepsies than in patients with drug responsive epilepsies. ESPERA study shows that the use of new definition of drug-resistance in everyday practice seems difficult without any additional training and that the social and professional disability is frequent in adults with focal epilepsies treated with polytherapy. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Incidence of Respiratory Disease During the First Two Years of Life in Children with Hemodynamically Significant Congenital Heart Disease in Italy: A Retrospective Study.

PubMed

Pongiglione, Giacomo; Possidoni, Alessandro; di Luzio Paparatti, Umberto; Costanzo, Anna Maria; Gualberti, Giuliana; Bonvicini, Marco; Rimini, Alessandro; Agnoletti, Gabriella; Calabrò, Maria Pia; Pozzi, Marco; Tumbarello, Roberto; Salice, Patrizia; Fiorini, Patrizio; Russo, Maria Giovanna; Milanesi, Ornella

2016-12-01

Children affected by hemodynamically significant congenital heart disease (HSCHD) experience severe respiratory complications that can increase the frequency of hospitalizations. The aim of the SINERGY study was to describe the incidence of respiratory diseases and to collect information on active and passive immunoprophylaxis in the first 2 years of life. In this retrospective, multicenter, and epidemiologic study, children with HSCHD were enrolled across 11 Italian sites. Children born between December 31, 2007, and December 31, 2012, were observed during their first 2 years of life. Data were collected through hospital database searches and parent interviews. Four hundred twenty children were enrolled: 51.7 % were female, 79.5 % were born full-term (≥37 weeks), and 77.6 % weighed >2500 g at birth. The most frequent heart defects were ventricular septal defect (23.1 %) and coarctation of the aorta (14.3 %). The incidence of respiratory diseases was 63.1 %. Frequent respiratory diseases not requiring hospitalization were upper respiratory tract infections (76.4 %), acute bronchitis (43.3 %), and influenza (22.1 %), while those requiring hospitalization were bronchitis and bronchiolitis (8.3 % each one). While active immunoprophylaxis was applied with wide compliance (diphtheria/pertussis/tetanus, 99.5 %; Haemophilus influenzae type b, 72.5 %; pneumococcus, 79.9 %; meningococcus, 77.4 %), only 54 % of children received respiratory syncytial virus (RSV) passive prophylaxis (palivizumab). Of the 35 hospitalizations due to bronchiolitis, 27 (77.1 %) did not receive prophylaxis against RSV, compared with 8 (22.9 %) who received prophylaxis (P < 0.0001). Children with HSCHD are at major risk of respiratory diseases. Passive immunoprophylaxis can help to prevent hospitalizations for bronchiolitis.

Patient and Disease Characteristics Associated With the Presence of Diabetes Mellitus in Adults With Chronic Pancreatitis in the United States.

PubMed

Bellin, Melena D; Whitcomb, David C; Abberbock, Judah; Sherman, Stuart; Sandhu, Bimaljit S; Gardner, Timothy B; Anderson, Michelle A; Lewis, Michele D; Alkaade, Samer; Singh, Vikesh K; Baillie, John; Banks, Peter A; Conwell, Darwin; Cote, Gregory A; Guda, Nalini M; Muniraj, Thiruvengadam; Tang, Gong; Brand, Randall E; Gelrud, Andres; Amann, Stephen T; Forsmark, Christopher E; Wilcox, C Mel; Slivka, Adam; Yadav, Dhiraj

2017-09-01

Diabetes mellitus (DM) is a common complication of chronic pancreatitis (CP). Past studies for DM risk factors in CP have been limited to single centers or highly focused on a single etiology such as alcoholic or hereditary disease. We studied risk factors for DM in a large population of patients with CP of all etiologies enrolled in the North American Pancreatitis 2 studies. Participants (1,171) with CP (n=383 with DM, n=788 without DM) were enrolled prospectively from 26 participating centers. Questionnaires were completed by patients and physicians in a cross-sectional assessment. Patient demographics and disease characteristics were compared for CP with DM vs. without DM. Logistic regression was performed to assess the variables associated with DM diagnosis in a multivariable model. Diabetics were more likely to be black (P=0.02), overweight, or obese (P<0.001), and with a family history of DM (P=0.0005). CP patients with DM were more likely to have pancreatic calcifications (63% vs. 54%, P=0.002), atrophy (44% vs. 32%, P<0.0001), and prior pancreas surgery (26.9% vs. 16.9%, P<0.0001). In multivariate logistic regression modeling, the strongest risk factors for DM were obesity (odds ratio (OR) 2.8, 95% confidence interval (CI) 1.9, 4.2) and exocrine insufficiency (OR 2.4, 95% CI 1.8, 3.2). In this large multicenter cohort of patients with CP, exocrine insufficiency, calcifications, and pancreas surgery conveyed higher odds of having DM. However, the traditional 'type 2 DM' risk factors of obesity and family history were similarly important in conveying risk for DM.

Impact of use of angiotensin II receptor blocker on all-cause mortality in hemodialysis patients: prospective cohort study using a propensity-score analysis.

PubMed

Tanaka, Marenao; Yamashita, Tomohisa; Koyama, Masayuki; Moniwa, Norihito; Ohno, Kohei; Mitsumata, Kaneto; Itoh, Takahito; Furuhashi, Masato; Ohnishi, Hirofumi; Yoshida, Hideaki; Tsuchihashi, Kazufumi; Miura, Tetsuji

2016-06-01

It is controversial whether treatment with an angiotensin II receptor blocker (ARB) or a calcium channel blocker (CCB) improves prognosis of hemodialysis (HD) patients. This study was designed as a multicenter prospective cohort study. HD patients (n = 1071) were enrolled from 22 institutes in January 2009 and followed up for 3 years. Patients with missing data, kidney transplantation or retraction of consent during the follow-up period (n = 204) were excluded, and 867 patients contributed to analysis of mortality. Propensity score (PS) for use of ARB and that for CCB was calculated using a multiple logistic regression model. ARB and CCB were prescribed in 45.6 and 54.7 % of patients at enrollment. During the 3-year follow-up period, all-cause mortality and cardiovascular mortality rates were 18.8 and 5.1 %, respectively. Kaplan-Meier curves showed that all-cause and cardiovascular mortality rates were lower in the ARB group than in the non-ARB group, though the mortality rates were similar in the CCB group and non-CCB group. In PS-stratified Cox regression analysis, ARB treatment was associated with 34 and 45 % reduction of all-cause death and cardiovascular death, respectively. In PS matching analysis, ARB treatment was associated with a significant reduction (46 % reduction) in the risk of all-cause death. A significant impact of CCB treatment on all-cause or cardiovascular mortality was not detected in PS analysis. The use of an ARB, but not a CCB, is associated with reduced all-cause and cardiovascular mortalities in patients on HD.

Management of post-LASIK dry eye: a multicenter randomized comparison of a new multi-ingredient artificial tear to carboxymethylcellulose

PubMed Central

Wallerstein, Avi; Jackson, W Bruce; Chambers, Jeffrey; Moezzi, Amir M; Lin, Hugh; Simmons, Peter A

2018-01-01

Purpose To compare the efficacy and safety of a preservative-free, multi-ingredient formulation of carboxymethylcellulose 0.5%, hyaluronic acid 0.1%, and organic osmolytes (CMC-HA), to preservative-free carboxymethylcellulose 0.5% (CMC) in the management of postoperative signs and symptoms of dry eye following laser-assisted in situ keratomileusis (LASIK). Methods This was a double-masked, randomized, parallel-group study conducted in 14 clinical centers in Canada and Australia. Subjects with no more than mild dry eye instilled CMC-HA or CMC for 90 days post-LASIK. Ocular Surface Disease Index© (OSDI; primary efficacy measure), corneal staining, tear break-up time (TBUT), Schirmer’s test, acceptability/tolerability surveys, and visual acuity were assessed at screening and days 2, 10, 30, 60, and 90 post-surgery. Safety analyses included all enrolled. Results A total of 148 subjects (CMC-HA, n=75; CMC, n=73) were enrolled and assigned to receive treatment, and 126 subjects completed the study without any protocol violations. Post-LASIK, dry eye signs/symptoms peaked at 10 days. OSDI scores for both groups returned to normal with no differences between treatment groups at day 90 (P=0.775). Corneal staining, Schirmer’s test, TBUT, and survey results were comparable. Higher mean improvements in uncorrected visual acuity were observed in the CMC-HA group at all study visits, reaching statistical significance at day 30 (P=0.013). Both treatments were well tolerated. Conclusion CMC-HA-containing artificial tears relieved post-LASIK ocular dryness as well as CMC alone, and demonstrated incremental benefit in uncorrected vision, with a favorable safety profile. Results support use of CMC-HA eye drops to reduce signs and symptoms of ocular dryness post-LASIK. PMID:29765198

Determinants of adherence to delayed-release doxylamine and pyridoxine in patients with nausea and vomiting of pregnancy.

PubMed

Costantine, Maged M; Matok, Ilan; Chiossi, Guisseppe; Clark, Shannon; Miodovnik, Menachem; Umans, Jason G; Caritis, Steve; Hankins, Gary D V; Koren, Gideon

2012-10-01

Women often hesitate to take medications in pregnancy due to fears of perceived potential fetal damage. The authors' objective is to identify the determinants of adherence to delayed-release doxylamine-pyridoxine (Diclectin) in patients with nausea and vomiting of pregnancy (NVP). The authors performed a prespecified secondary analysis of a multicenter double-blind randomized controlled trial of Diclectin versus placebo for the treatment of NVP. Data on adherence to study medication were collected in all patients. The primary outcome of this analysis was adherence to study medication, which was determined by pill counting and patient diaries. The treatment regimen in the original trial was not fixed and depended on patient's symptoms. There was no difference in the adherence rates between subjects in the Diclectin or placebo arms of the study, so the 2 arms were analyzed as one cohort. The degree of adherence was analyzed in the various subgroups. Subsequently, a multiple linear regression model was constructed to identify predictors to adherence. Two hundred fifty-eight women were included in this analysis. There were no differences in adherence rates according to ethnicity, race, or the presence of adverse events. Gravidity, average number of prescribed tablets per day, site of enrollment, and change in NVP severity measured by the pregnancy unique-quantification of emesis score were associated with adherence. In multivariable analysis, average number of tablets per day, change in pregnancy unique-quantification of emesis, number of treatment days, site of enrollment were significantly predictive of adherence, with the former being negatively correlated. Adherence to antinauseants for NVP is affected by number of tablets prescribed per day, and treatment duration and effectiveness.

Determinants of Adherence to Delayed-Release Doxylamine and Pyridoxine in Patients with Nausea and Vomiting of Pregnancy

PubMed Central

Costantine, Maged M.; Matok, Ilan; Chiossi, Guisseppe; Clark, Shannon; Miodovnik, Menachem; Umans, Jason G.; Caritis, Steve; Hankins, Gary D.V.; Koren, Gideon

2012-01-01

Objective Women often hesitate to take medications in pregnancy due to fears of perceived potential fetal damage. The authors’ objective is to identify the determinants of adherence to delayed release doxylamine-pyridoxine (Diclectin®) in patients with nausea and vomiting of pregnancy (NVP). Methods The authors performed a pre-specified secondary analysis of a multicenter double blind randomized controlled trial of Diclectin® vs. placebo for the treatment of NVP. Data on adherence to study medication were collected in all patients. The primary outcome of this analysis was adherence with study medication, which was determined by pill counting and patient diaries. The treatment regimen in the original trial was not fixed and depended on patient’s symptoms. There was no difference in the adherence rates between subjects in the Diclectin® or placebo arms of the study, so the 2 arms were analyzed as one cohort. The degree of adherence was analyzed in the various subgroups. Subsequently, a multiple linear regression model was constructed to identify predictors to adherence. Results 258 women were included in this analysis. There was no difference in adherence rates according to ethnicity, race or the presence of adverse events. Gravidity, average number of prescribed tablets per day, site of enrollment, and change in NVP severity measured by the pregnancy unique-quantification of emesis (PUQE) score were associated with adherence. In multivariable analysis, average number of tablets per day, change in PUQE, number of treatment days, site of enrollment were significantly predictive of adherence, with the former being negatively correlated. Conclusion adherence to antinauseants for NVP is affected by number of tablets prescribed per day, and treatment duration and effectiveness. PMID:22972538

The Efficacy and Safety of Icotinib in Patients with Advanced Non-Small Cell Lung Cancer Previously Treated with Chemotherapy: A Single-Arm, Multi-Center, Prospective Study.

PubMed

Hu, Xingsheng; Zhang, Li; Shi, Yuankai; Zhou, Caicun; Liu, Xiaoqing; Wang, Dong; Song, Yong; Li, Qiang; Feng, Jifeng; Qin, Shukui; Xv, Nong; Zhou, Jianying; Zhang, Li; Hu, Chunhong; Zhang, Shucai; Luo, Rongcheng; Wang, Jie; Tan, Fenlai; Wang, Yinxiang; Ding, Lieming; Sun, Yan

2015-01-01

Icotinib is a small molecule targeting epidermal growth factor receptor tyrosine kinase, which shows non-inferior efficacy and better safety comparing to gefitinib in previous phase III trial. The present study was designed to further evaluate the efficacy and safety of icotinib in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy. Patients with NSCLC progressing after one or two lines of chemotherapy were enrolled to receive oral icotinib (125 mg tablet, three times per day). The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, time to progression, quality of life and safety. From March 16, 2010 to October 9, 2011, 128 patients from 15 centers nationwide were enrolled, in which 124 patients were available for efficacy evaluation and 127 patients were evaluable for safety. The median progression-free survival and time to progression were 5.0 months (95%CI 2.9-6.6 m) and 5.4 months (95%CI 3.1-7.9 m), respectively. The objective response rate and disease control rate were 25.8% and 67.7% respectively. Median overall survival exceeded 17.6 months (95%CI 14.2 m-NA) according to censored data. Further follow-up of overall survival is ongoing. The most frequent treatment-related adverse events were rash (26%, 33/127), diarrhea (12.6%, 16/127) and elevation of transaminase (15.7%, 20/127). In general, this study showed similar efficacy and numerically better safety when compared with that in ICOGEN trial, further confirming the efficacy and safety of icotinib in treating patients with advanced NSCLC previously treated with chemotherapy. ClinicalTrials.gov NCT02486354.

Characterization of Medication Use in a Multicenter Sample of Pediatric Inpatients with Autism Spectrum Disorder.

PubMed

Wink, Logan K; Pedapati, Ernest V; Adams, Ryan; Erickson, Craig A; Pedersen, Kahsi A; Morrow, Eric M; Kaplan, Desmond; Siegel, Matthew

2017-05-17

Nearly 11% of youth with Autism Spectrum Disorder (ASD) undergo psychiatric hospitalization, and 65% are treated with psychotropic medication. Here we characterize psychotropic medication usage in subjects enrolled in the Autism Inpatient Collection. Participant psychotropic medication usage rates topped 90% at admission and discharge, though there was a decline at 2-month follow-up. Antipsychotics, ADHD medications, and sleep aids were the most commonly reported classes of medications. The impact of age, gender, and non-verbal IQ on medication usage rates was minimal, though age and IQ may play a role in prescribing practices. Future work is indicated to explore medication usage trends, the impact of clinical factors on medication use rates, and the safety of psychotropic medications in youth with ASD.

Triiodothyronine Supplementation in Infants and Children Undergoing Cardiopulmonary Bypass (TRICC) A Multicenter Placebo-Controlled Randomized Trial: Age Analysis

PubMed Central

Portman, Michael A.; Slee, April; Olson, Aaron K.; Cohen, Gordon; Karl, Tom; Tong, Elizabeth; Hastings, Laura; Patel, Hitendra; Reinhartz, Olaf; Mott, Antonio R.; Mainwaring, Richard; Linam, Justin; Danzi, Sara

2011-01-01

Background Triiodothyronine levels decrease in infants and children after cardiopulmonary bypass. We tested the primary hypothesis that triiodothyronine (T3) repletion is safe in this population and produces improvements in postoperative clinical outcome. Methods and Results The TRICC study was a prospective, multicenter, double-blind, randomized, placebo-controlled trial in children younger than 2 years old undergoing heart surgery with cardiopulmonary bypass. Enrollment was stratified by surgical diagnosis. Time to extubation (TTE) was the primary outcome. Patients received intravenous T3 as Triostat (n=98) or placebo (n=95), and data were analyzed using Cox proportional hazards. Overall, TTE was similar between groups. There were no differences in adverse event rates, including arrhythmia. Prespecified analyses showed a significant interaction between age and treatment (P=0.0012). For patients younger than 5 months, the hazard ratio (chance of extubation) for Triostat was 1.72. (P=0.0216). Placebo median TTE was 98 hours with 95% confidence interval (CI) of 71 to 142 compared to Triostat TTE at 55 hours with CI of 44 to 92. TTE shortening corresponded to a reduction in inotropic agent use and improvement in cardiac function. For children 5 months of age, or older, Triostat produced a significant delay in median TTE: 16 hours (CI, 7–22) for placebo and 20 hours (CI, 16–45) for Triostat and (hazard ratio, 0.60; P=0.0220). Conclusions T3 supplementation is safe. Analyses using age stratification indicate that T3 supplementation provides clinical advantages in patients younger than 5 months and no benefit for those older than 5 months. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00027417. PMID:20837917

Patient-directed Internet-based Medical Image Exchange: Experience from an Initial Multicenter Implementation

PubMed Central

Greco, Giampaolo; Patel, Anand S.; Lewis, Sara C.; Shi, Wei; Rasul, Rehana; Torosyan, Mary; Erickson, Bradley J.; Hiremath, Atheeth; Moskowitz, Alan J.; Tellis, Wyatt M.; Siegel, Eliot L.; Arenson, Ronald L.; Mendelson, David S.

2015-01-01

Rationale and Objectives Inefficient transfer of personal health records among providers negatively impacts quality of health care and increases cost. This multicenter study evaluates the implementation of the first Internet-based image-sharing system that gives patients ownership and control of their imaging exams, including assessment of patient satisfaction. Materials and Methods Patients receiving any medical imaging exams in four academic centers were eligible to have images uploaded into an online, Internet-based personal health record. Satisfaction surveys were provided during recruitment with questions on ease of use, privacy and security, and timeliness of access to images. Responses were rated on a five-point scale and compared using logistic regression and McNemar's test. Results A total of 2562 patients enrolled from July 2012 to August 2013. The median number of imaging exams uploaded per patient was 5. Most commonly, exams were plain X-rays (34.7%), computed tomography (25.7%), and magnetic resonance imaging (16.1%). Of 502 (19.6%) patient surveys returned, 448 indicated the method of image sharing (Internet, compact discs [CDs], both, other). Nearly all patients (96.5%) responded favorably to having direct access to images, and 78% reported viewing their medical images independently. There was no difference between Internet and CD users in satisfaction with privacy and security and timeliness of access to medical images. A greater percentage of Internet users compared to CD users reported access without difficulty (88.3% vs. 77.5%, P < 0.0001). Conclusion A patient-directed, interoperable, Internet-based image-sharing system is feasible and surpasses the use of CDs with respect to accessibility of imaging exams while generating similar satisfaction with respect to privacy. PMID:26625706