The influence of age at onset and duration of illness on long-term outcome in patients with obsessive-compulsive disorder: a report from the International College of Obsessive Compulsive Spectrum Disorders (ICOCS).

PubMed

Dell'Osso, Bernardo; Benatti, Beatrice; Buoli, Massimiliano; Altamura, A Carlo; Marazziti, Donatella; Hollander, Eric; Fineberg, Naomi; Stein, Dan J; Pallanti, Stefano; Nicolini, Humberto; Van Ameringen, Michael; Lochner, Christine; Hranov, Georgi; Karamustafalioglu, Oguz; Hranov, Luchezar; Menchon, Jose M; Zohar, Joseph

2013-08-01

Several studies reported a negative effect of early onset and long duration of illness on long-term outcome in psychiatric disorders, including Obsessive-Compulsive Disorder (OCD). OCD is a prevalent, comorbid and disabling condition, associated with reduced quality of life and overall well-being for affected patients and related caregivers. The present multicenter naturalistic study sought to assess the influence of early onset and duration of illness on long-term outcome in a sample of 376 OCD out-patients worldwide, as part of the "International College of Obsessive-Compulsive Spectrum Disorders" (ICOCS) network. Binary logistic regressions were performed with age at the onset and duration of illness, as continuous independent variables, on a series of different outcome dependent variables, including lifetime number of hospitalizations and suicide attempts, poly-therapy and psychiatric comorbidity. Correlations in terms of disability (SDS) were analyzed as well. Results showed that a longer duration of illness (but not earlier age of onset) was associated with hospitalization (odds ratio=1.03, p=0.01), earlier age at onset with CBT (odds ratio=0.94, p<0.001) and both a later age at onset (odds ratio=1.05, p=0.02) and a shorter duration of illness (odds ratio=0.93, p=0.02) with panic disorder comorbidity. In addition, earlier age at onset inversely correlated with higher social disability (r=-0.12, p=0.048) and longer duration of illness directly correlated with higher disability in work, social and family life (r=0.14, p=0.017; r=0.13, p=0.035; r=0.14, p=0.02). The findings from the present large, multicenter study indicate early onset and long duration of illness as overall negative predictors of long-term outcome in OCD. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

The role of transanal endorectal pull-through in the treatment of Hirschsprung's disease - a multicenter experience.

PubMed

Höllwarth, M E; Rivosecchi, M; Schleef, J; Deluggi, S; Fasching, G; Ceriati, E; Ciprandi, G; DePeppo, F

2002-09-01

The transanal approach (TAA) is a new technique for surgery of Hirschsprung's disease (HD) that was introduced by de la Torre in 1998. The purpose of this multicenter study, including experience from three Austrian and one Italian departments of peadiatric surgery, was to evaluate the role of this approach in HD in 18 children aged 1-72 months. In 14 children the TAA only was performed; in 3 an additional laparoscopy was performed and in 1 conversion to a laparotomy was necessary. One complication (abscess) occurred after laparoscopic-assisted pull-through. The postoperative recovery was rapid, no severe long-term problems were observed. The transanal pull-through technique is generally possible in most classic cases of HD with extension of the disease to the sigmoid colon. If necessary, it can be combined with laparoscopy. Our preliminary results show that the technique is safe, less invasive, and gives excellent cosmetic results, and allows rapid recovery. Long-term results are still pending.

Effect of structured physical activity on prevention of serious fall injuries in adults aged 70-89: randomized clinical trial (LIFE Study)

USDA-ARS?s Scientific Manuscript database

OBJECTIVE: To test whether a long term, structured physical activity program compared with a health education program reduces the risk of serious fall injuries among sedentary older people with functional limitations. DESIGN: Multicenter, single blinded randomized trial (Lifestyle Interventions and ...

Safety and effectiveness of iguratimod in patients with rheumatoid arthritis: Final report of a 52-week, multicenter postmarketing surveillance study.

PubMed

Mimori, Tsuneyo; Harigai, Masayoshi; Atsumi, Tatsuya; Fujii, Takao; Kuwana, Masataka; Matsuno, Hiroaki; Momohara, Shigeki; Takei, Syuji; Tamura, Naoto; Takasaki, Yoshinari; Yamamoto, Kazuhiko; Ikeuchi, Satoshi; Kushimoto, Satoru; Koike, Takao

2018-04-27

We evaluated the long-term (52 weeks) safety and effectiveness of iguratimod (IGU) in patients with rheumatoid arthritis (RA). This multicenter, prospective, observational study included all evaluable RA patients who received IGU since its market launch in 2012. We evaluated adverse events (AEs); adverse drug reactions (ADRs); ADRs of special interest, including liver and renal dysfunctions, interstitial lung disease, gastrointestinal and blood disorders, and infection; and change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) at week 52. Safety and effectiveness were analyzed in 2666 and 1614 patients, respectively. The incidences of AEs, serious AEs, ADRs, and serious ADRs were 46.92, 7.35, 38.26, and 4.58%, respectively. The incidence of ADRs peaked at approximately 4 weeks of treatment. Subsequently, the ADR incidence did not increase over time. Improvement of RA activity was shown up to week 52. Long-term treatment with IGU in patients with RA resulted in a tolerable safety profile and an improvement in RA activity. IGU could be considered a useful treatment option for patients with RA.

No sex differences in use of dopaminergic medication in early Parkinson disease in the US and Canada - baseline findings of a multicenter trial.

PubMed

Umeh, Chizoba C; Pérez, Adriana; Augustine, Erika F; Dhall, Rohit; Dewey, Richard B; Mari, Zoltan; Simon, David K; Wills, Anne-Marie A; Christine, Chadwick W; Schneider, Jay S; Suchowersky, Oksana

2014-01-01

Sex differences in Parkinson disease clinical features have been reported, but few studies have examined sex influences on use of dopaminergic medication in early Parkinson disease. The objective of this study was to test if there are differences in the type of dopaminergic medication used and levodopa equivalent daily dose between men and women with early Parkinson disease enrolled in a large multicenter study of Creatine as a potential disease modifying therapy - the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease Long-Term Study-1. Baseline data of 1,741 participants from 45 participating sites were analyzed. Participants from the United States and Canada were enrolled within five years of Parkinson Disease diagnosis. Two outcome variables were studied: type of dopaminergic medication used and levodopa equivalent daily dose at baseline in the Long-Term Study-1. Chi-square statistic and linear regression models were used for statistical analysis. There were no statistically significant differences in the frequency of use of different types of dopaminergic medications at baseline between men and women with Parkinson Disease. A small but statistically significant difference was observed in the median unadjusted levodopa equivalent daily dose at baseline between women (300 mg) and men (325 mg), but this was not observed after controlling for disease duration (years since Parkinson disease diagnosis), disease severity (Unified Parkinson's Disease Rating Scale Motor and Activities of Daily Living Scores), and body weight. In this large multicenter study, we did not observe sex differences in the type and dose of dopaminergic medications used in early Parkinson Disease. Further research is needed to evaluate the influence of male or female sex on use of dopaminergic medication in mid- and late-stage Parkinson Disease.

Diagnosis, Treatment and Long-Term Follow Up of Patients with ADA Deficiency: a Single-Center Experience.

PubMed

Baffelli, Renata; Notarangelo, Lucia D; Imberti, Luisa; Hershfield, Michael S; Serana, Federico; Santisteban, Ines; Bolda, Federica; Porta, Fulvio; Lanfranchi, Arnalda

2015-10-01

We carried out a retrospective analysis of 27 patients with Adenosine Deaminase (ADA) deficiency diagnosed in a single center from 1997 to the 2013, for evaluating whether data regarding types of disease-inducing mutations, biochemical and immunological features as well as clinical outcomes of patients treated with enzyme replacement or transplantation, were comparable to those obtained in multicenter studies. The ADA deficiency diagnosis was performed with biochemical, immunological and molecular techniques. Ten patients treated with hematopoietic stem cell transplantation and three in treatment with enzyme replacement were followed up in our center. Twenty-four different mutations were identified and five were not previously reported. Identical mutations were found among patients from the same Romani ethnic group or from the same geographical region. A more rapid recovery was observed in enzyme replacement treated patients in comparison with those transplanted that, however, showed a continuous and long-lasting improvement both in terms of immune and metabolic recovery. The data obtained in our single center are comparable with those that have been reported in multicenter surveys.

BIOCHEMICAL CONTROL DURING LONG-TERM FOLLOW-UP OF 230 ADULT PATIENTS WITH CUSHING DISEASE: A MULTICENTER RETROSPECTIVE STUDY.

PubMed

Geer, Eliza B; Shafiq, Ismat; Gordon, Murray B; Bonert, Vivien; Ayala, Alejandro; Swerdloff, Ronald S; Katznelson, Laurence; Lalazar, Yelena; Manuylova, Ekaterina; Pulaski-Liebert, Karen J; Carmichael, John D; Hannoush, Zeina; Surampudi, Vijaya; Broder, Michael S; Cherepanov, Dasha; Eagan, Marianne; Lee, Jackie; Said, Qayyim; Neary, Maureen P; Biller, Beverly M K

2017-08-01

Cushing disease (CD) results from excessive exposure to glucocorticoids caused by an adrenocorticotropic hormone-secreting pituitary tumor. Inadequately treated CD is associated with significant morbidity and elevated mortality. Multicenter data on CD patients treated in routine clinical practice are needed to assess treatment outcomes in this rare disorder. The study purpose was to describe the burden of illness and treatment outcomes for CD patients. Eight pituitary centers in four U.S. regions participated in this multicenter retrospective chart review study. Subjects were CD patients diagnosed at ≥18 years of age within the past 20 years. Descriptive statistical analyses were conducted to examine presenting signs, symptoms, comorbidities, and treatment outcomes. Of 230 patients, 79% were female (median age at diagnosis, 39 years; range, 18 to 78 years). Length of follow-up was 0 to 27.5 years (median, 1.9 years). Pituitary adenomas were 0 to 51 mm. The most common presenting comorbidities included hypertension (67.3%), polycystic ovary syndrome (43.5%), and hyperlipidemia (41.5%). Biochemical control was achieved with initial pituitary surgery in 41.4% patients (91 of 220), not achieved in 50.0% of patients (110 of 220), and undetermined in 8.6% of patients (19 of 220). At the end of follow-up, control had been achieved with a variety of treatment methods in 49.1% of patients (110 of 224), not achieved in 29.9% of patients (67 of 224), and undetermined in 21.0% of patients (47 of 224). Despite multiple treatments, at the end of follow-up, biochemical control was still not achieved in up to 30% of patients. These multicenter data demonstrate that in routine clinical practice, initial and long-term control is not achieved in a substantial number of patients with CD. BLA = bilateral adrenalectomy CD = Cushing disease CS = Cushing syndrome eCRF = electronic case report form MRI = magnetic resonance imaging PCOS = polycystic ovary syndrome.

Large Extremity Peripheral Nerve Repair

DTIC Science & Technology

2014-10-01

Shahani B. Peripheral-nerve allotransplantation in rats immunosuppressed with transient or long-term FK-506. Journal of reconstructive microsurgery ...multicenter study of utilization and outcomes in sensory, mixed, and motor nerve reconstructions . Microsurgery . 2012 Jan;32(1):1-14. PubMed PMID: 22121093...PTB method can provide fixation strengths 6 approaching that of conventional microsurgery and that the PTB repair is unlikely to be disturbed in

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.

Open-label, randomized, multicenter, phase III study to evaluate the safety and efficacy of benzoyl peroxide gel in long-term use in patients with acne vulgaris: A secondary publication.

PubMed

Kawashima, Makoto; Nagare, Toshitaka; Katsuramaki, Tsuneo

2017-06-01

An open-label, randomized, multicenter study was conducted to evaluate the safety and efficacy of long-term use of 2.5% and 5% benzoyl peroxide (BPO) gels administrated once daily for 52 weeks to Japanese patients with acne vulgaris. The efficacy of the study drugs was evaluated by counting inflammatory lesions and non-inflammatory lesions. Safety was evaluated based on adverse events, local skin tolerability scores and laboratory test values. In total, 458 subjects were included in the efficacy and safety analyses. The total lesion count, the efficacy end-point, was similarly changed both in the 2.5% and 5% BPO groups over the course of the study. The median rates of reduction from baseline to week 12 were approximately 65%. Thereafter, the counts were maintained at a reduced level without increasing until week 52. The median rates at week 52 were approximately 80%. Similar trends were observed for inflammatory and non-inflammatory lesion counts. Bacteriological evaluation indicated similar distribution of the minimum inhibitory concentration of each of the antibacterial drugs against Propionibacterium acnes between the values at baseline and at week 52, suggesting that long-term use did not result in changes in the drug sensitivity. The incidence of adverse events was 84.0% in the 2.5% BPO group and 87.2% in the 5% BPO group. Many of the adverse events occurred within the first month and were mild or moderate in severity and transient. The results suggest that both 2.5% and 5% BPO gels are effective and safe for long-term treatment of patients with acne vulgaris. © 2017 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

The PANGAEA study design - a prospective, multicenter, non-interventional, long-term study on fingolimod for the treatment of multiple sclerosis in daily practice.

PubMed

Ziemssen, Tjalf; Kern, Raimar; Cornelissen, Christian

2015-06-18

Fingolimod (Gilenya) is an oral medication for patients with highly active relapsing-remitting Multiple Sclerosis (RRMS). Clinical trials and post-marketing experience on more than 114,000 patients have established a detailed safety profile. Total patient exposure now exceeds 195,000 patient-years as stated in the last financial report (Dec 2014) of the Novartis Pharma AG, Basel, Switzerland. However, less is known about the safety of long-term fingolimod use in daily practice. Here, we describe the study design of PANGAEA (Post-Authorization Non-interventional German sAfety of GilEnyA in RRMS patients), a prospective, multicenter, non-interventional, long-term study to collect safety, efficacy, and pharmacoeconomic data on RRMS patients treated with fingolimod (0.5 mg/daily) under real-world conditions in Germany. PANGAEA is striving to assess a real-world safety and efficacy profile of fingolimod, based on data from 4,000 RRMS patients, obtained during a 60-month observational phase. A pharmacoeconomic sub-study of 800 RRMS patients further collects patient-reported outcome measures of disability, quality of life, compliance, treatment satisfaction, and usage of resources during a 24-month observational phase. Descriptive statistical analyses of the safety set as well as of stratified subgroups such as patients with concomitant diabetes mellitus and pretreated patients (e.g., natalizumab) will be conducted. PANGAEA seeks to confirm the current safety profile of fingolimod obtained in phase I-III clinical trials. The study design presented here will additionally provide guidance on the therapeutic use of fingolimod in clinical practice and possibly assists physicians in making evidence-based decisions.

[Utilization of multimodal therapy concepts in stomach carcinoma in Germany].

PubMed

Bösing, N M; Heise, J W; Röher, H D

2000-01-01

In view of disappointing results after surgery alone multimodal therapeutic regimes are used to improve long-term prognosis in locally advanced gastric carcinomas. In presence of many reports about encouraging results ("down staging", improved R0-resection rates) but simultaneously missing evidence of efficiency of neoadjuvant therapies in respect to long-term survival (large randomized multicenter trials do not exist until today) and the herewith related uncertainties, we started an inquiry among many surgical units with the intention to evaluate the clinical practice of multimodal treatment for gastric cancer patients in Germany today. In a questionnaire (3/99) we asked among 97 surgical units (41 university hospitals, 56 big community hospitals) in Germany for the management of gastric cancer patients with special interest to practice and state of adjuvant and neoadjuvant therapeutic strategies. Further we analyzed all resected gastric cancer patients (1986-1995) without neoadjuvant treatment in advanced stage of disease (pT3/4NxMx; stage III/IV (UICC'92) in respect to R0-resection rate and long-term prognosis (Kaplan-Meier). Overall feedback amounted to 78% (76/97) and was higher in university hospitals (90%) than in big community hospitals (70%). Today, neoadjuvant therapies are of more interest than adjuvant therapeutic regimes. But also neoadjuvant therapy is only used in 32% as a rule (in 16% with, in 16% without study conditions). 25% of all surgical units do not employ any neoadjuvant therapy in locally advanced gastric cancer until today. In all other surgical units neoadjuvant treatment is performed more individually and sporadically (43%) only in some patients. Neoadjuvant therapies are practiced by haematooncologists in 50%, gastroenterologists in 32% and surgeons in 27%. The predominant neoadjuvant therapeutic strategy is chemotherapy alone (84%). Many surgical units in Germany are interested to participate in a multicenter trial with more interest in neoadjuvant than adjuvant therapy. 185 of 309 resected gastric cancer patients (60%) were classified as stage IIIa, stage IIIb or stage IV patients. R0-resection rate of these advanced gastric cancer patients amounted to 37%; only 24% of them survived 5 years or more. Considering the missing evidence that multimodal therapies are able to prolong long-term survival in advanced gastric cancer patients, its use without study conditions is questionable. Conclusions, taken from data of clinical trials regarding carcinomas of the esophagus and esophagealgastric junction, are inconsistent in respect to long-term prognosis and results are not transferable to gastric carcinomas. A prospective randomized multicenter trial in advanced gastric cancer patients is of great importance. Following our data, in Germany a high readiness to participate in the forthcoming EORTC-study is present.

Effects of Intranasal Oxytocin on Long-Term Memory in Healthy Humans: A Systematic Review.

PubMed

Brambilla, Michela; Manenti, Rosa; de Girolamo, Giovanni; Adenzato, Mauro; Bocchio-Chiavetto, Luisella; Cotelli, Maria

2016-12-01

Preclinical Research The neuropeptide oxytocin (Oxt) is implicated in complex emotional and social behaviors and appears to play an important role in learning and memory. Animal studies have shown that the effects of exogenous Oxt on memory vary according to the timing of administration, context, gender, and dose and may improve the memory of social, but not nonsocial stimuli. Oxt is intimately involved in a broad array of neuropsychiatric functions and may therefore be a pharmacological target for several psychiatric disorders. This review summarizes the potential effects of Oxt on long-term memory processes in healthy humans based on a PubMed search over the period 1980-2016. The effects of intranasal Oxt on human memory are controversial and the studies included in this review have applied a variety of learning paradigms, in turn producing variable outcomes. Specifically, data on the long-term memory of nonemotional stimuli found no effect or even worsening in memory, while studies using emotional stimuli showed an improvement of long-term memory performance. In conclusion, this review identified a link between long-term memory performance and exogenous intranasal Oxt in humans, although these results still warrant further confirmation in large, multicenter randomized controlled trials. Drug Dev Res 77 : 479-488, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Safety and effectiveness of long-term growth hormone therapy in Japanese patients with adult growth hormone deficiency: a postmarketing, multicenter, observational study.

PubMed

Shimatsu, Akira; Ishii, Hitoshi; Nishinaga, Hiromi; Murai, Osamu; Chihara, Kazuo

2017-07-28

We aimed to evaluate the long-term safety and effectiveness of growth hormone (GH) therapy in Japanese patients with adult growth hormone deficiency (AGHD). In this observational, multicenter study, Norditropin ® (Novo Nordisk A/S, Bagsvaerd, Denmark) was administered as injections of 0.021 mg/kg/week as a starting dose divided into 6-7 doses/week. The dose was increased according to clinical response. Patients' data were obtained from medical records. Measurements (lipids, glucose metabolism, and body composition) taken at baseline; 3, 6, and 12 months; and yearly until the end of the study were collected. Adverse drug reactions (ADRs), serious ADRs, and serious adverse events (SAEs) were evaluated. Of 387 registered patients, 334 were eligible for safety. After GH treatment initiation, a marked decrease in total cholesterol was observed earlier in the child-onset group than in the adult-onset group. LDL-cholesterol also decreased, but no significant differences in changes in LDL-cholesterol between adult-onset and child-onset groups were found. A significant increase in HDL-cholesterol starting 1 year after GH treatment initiation was found in the adult-onset group. There was no effect of GH treatment on glucose metabolism. Because of the small number of dual-energy X-ray absorptiometry data, the overall assessment of changes of body composition was difficult. Fifty-six (16.8%), 12 (3.6%), and 35 (10.5%) patients experienced ADRs, serious ADRs, and SAEs, respectively. This study demonstrated a favorable long-term safety and effectiveness profile of GH therapy in AGHD patients in the real-life Japanese clinical practice setting.

Long-Term Follow-Up of Testicular Microlithiasis in Children and Adolescents: Multicenter Prospective Cohort Study of the Italian Society of Pediatric Urology.

PubMed

Marte, Antonio; Pintozzi, Lucia; Cretì, Giuseppe; Chiesa, Pierluigi Lelli; Renzo, Dacia Di; Gasparella, Marco; Maggio, Giovanni Di; Bagnara, Vincenzo; Merlini, Emilio; Tadini, Barbara; Caldarulo, Eustachio; Sangiorgio, Luciano; Battaglino, Gianfranco; Nappo, Simona Gerocarni; Caione, Paolo

2017-04-01

Introduction  Testicular microlithiasis (TM), characterized by the presence of intratubular calcifications in a single or both the gonads, is an uncommon entity with unknown etiology and outcome in pediatric and adolescent age. In this study, the results of a multicenter long-term survey are presented. Materials and Methods  From 11 units of pediatric urology/surgery, patients with TM were identified and yearly, followed up in a 7-year period, adopting a specific database. The recorded items were: age at diagnosis, presenting symptoms/associated abnormalities, ultrasonographic finding, surgery and histology at biopsy, if performed. Results  Out of 85 patients, 81 were evaluated yearly (4 patients lost to follow-up). TM was bilateral in 66.6% of the patients. Associate genital abnormalities were present in 90%, more frequently undescended/retractile testis (23.4%) and varicocele (22.2%). TM remained unchanged at 4.7 years follow-up in 77 patients (93.8%) and was reduced in 4 patients after 1 to 5 years of inguinoscrotal surgery. Orchiectomy was performed in three patients (3.7%), one for severe testicular hypoplasia and two for seminoma (2.5%), respectively, concurrent and metachronous to diagnosis of TM. Tumorectomy with parenchymal sparing surgery was performed in a teratoma associated with TM. Conclusion  TM is a controversial entity, often associated with several inguinogenital features, which rarely can recover. Testicular malignancy, although present in TM, has not proven definitively associated to microliths. Proper counseling, yearly ultrasound, and self-examination are long-term recommended. Georg Thieme Verlag KG Stuttgart · New York.

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.

Long-term follow-up of patients with an isolated ovarian recurrence after conservative treatment of epithelial ovarian cancer: review of the results of an international multicenter study comprising 545 patients.

PubMed

Bentivegna, Enrica; Fruscio, Robert; Roussin, Stephanie; Ceppi, Lorenzo; Satoh, Toyomi; Kajiyama, Hiroaki; Uzan, Catherine; Colombo, Nicoletta; Gouy, Sebastien; Morice, Philippe

2015-11-01

To determine the long-term outcomes of patients with an isolated ovarian recurrence after fertility sparing surgery (FSS) for epithelial ovarian cancer (EOC) and to evaluate the recurrence rates (and location) according to the new 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system. Retrospective multicenter study. Teams having reported recurrence after FSS for EOC. Four series comprising 545 patients undergoing FSS and 63 (12%) recurrences. FSS (salpingo-oophorectomy for a majority of cases) for EOC. Recurrences rates and characteristics of recurrent disease. Among 63 recurrent patients, 24 (38%) recurrences were isolated on the spared ovary, and 39 (62%) arose at an extraovarian site. Among the patients with an isolated ovarian recurrence, three patients died after a median follow-up period of 186 months (range: 28-294 months). Among the patients with recurrent extraovarian disease, 24 died and 7 were alive with persistent disease after a median follow-up period of 34 months (range: 3-231 months). The overall rate of isolated ovarian and extrapelvic recurrences was higher for grade 3 tumors (compared with grades 1/2). The long-term survival of patients with an isolated ovarian recurrence after FSS for EOC remains favorable. The prognosis of patients with an extraovarian recurrence is poor compared with those who have an isolated recurrent ovarian tumor. Grade 3 tumors (compared to grades 1/2) give rise to a higher rate of extraovarian recurrences. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Long-term outcomes in primary spinal osteochondroma: a multicenter study of 27 patients

PubMed Central

Sciubba, Daniel M.; Macki, Mohamed; Bydon, Mohamad; Germscheid, Niccole M.; Wolinsky, Jean-Paul; Boriani, Stefano; Bettegowda, Chetan; Chou, Dean; Luzzati, Alessandro; Reynolds, Jeremy J.; Szövérfi, Zsolt; Zadnik, Patti; Rhines, Laurence D.; Gokaslan, Ziya L.; Fisher, Charles G.; Varga, Peter Paul

2016-01-01

OBJECT Clinical outcomes in patients with primary spinal osteochondromas are limited to small series and sporadic case reports. The authors present data on the first long-term investigation of spinal osteochondroma cases. METHODS An international, multicenter ambispective study on primary spinal osteochondroma was performed. Patients were included if they were diagnosed with an osteochondroma of the spine and received surgical treatment between October 1996 and June 2012 with at least 1 follow-up. Perioperative prognostic variables, including patient age, tumor size, spinal level, and resection, were analyzed in reference to long-term local recurrence and survival. Tumor resections were compared using Enneking appropriate (EA) or Enneking inappropriate surgical margins. RESULTS Osteochondromas were diagnosed in 27 patients at an average age of 37 years. Twenty-two lesions were found in the mobile spine (cervical, thoracic, or lumbar) and 5 in the fixed spine (sacrum). Twenty-three cases (88%) were benign tumors (Enneking tumor Stages 1–3), whereas 3 (12%) exhibited malignant changes (Enneking tumor Stages IA–IIB). Sixteen patients (62%) underwent en bloc treatment—that is, wide or marginal resection—and 10 (38%) underwent intralesional resection. Twenty-four operations (92%) followed EA margins. No one received adjuvant therapy. Two patients (8%) experienced recurrences: one in the fixed spine and one in the mobile spine. Both recurrences occurred in latent Stage 1 tumors following en bloc resection. No osteochondroma-related deaths were observed. CONCLUSIONS In the present study, most patients underwent en bloc resection and were treated as EA cases. Both recurrences occurred in the Stage 1 tumor cohort. Therefore, although benign in character, osteochondromas still require careful management and thorough follow-up. PMID:25793467

Clinical features and long-term progression of reticular pseudodrusen in age-related macular degeneration: findings from a multicenter cohort.

PubMed

Gil, J Q; Marques, J P; Hogg, R; Rosina, C; Cachulo, M L; Santos, A; Staurenghi, G; Chakravarthy, U; Silva, R

2017-03-01

PurposeTo determine whether reticular pseudodrusen (RPD) confer a long-term increased risk of progression to late age-related macular degeneration (AMD) in the fellow eye of patients with unilateral wet-AMD.Patients and methodsThis was a multicenter, combined prospective and retrospective, longitudinal, observational, study. Patients with wet-AMD in one eye were recruited from two centers and evaluated on the risk of progression to late-AMD in the second eye (study eye). A minimum follow-up of 5 years was required, unless progression occurred first. Baseline retinal profile of patients was evaluated using multimodal imaging. Baseline images were graded by two separate centers.ResultsWe recruited 88 patients (48 female) with a mean age of 75.6±7.1 years and mean follow-up of 65.7±20.9 months. Baseline prevalence of RPD was 58% (n=51). There was no statistically significant association of RPD with increased age (P=0.29) or sex distribution (P=0.39). The most sensitive image modality for RPD was IR (93%), followed by FAF (92%), OCT (74%, RF (33%) and CFP (29%). After 5 years, 54.50% (n=48) of the study eyes progressed to late-AMD. Of those, 81.25% (n=39) developed CNV and 18.75% (n=9) geographic atrophy. After correcting for age and sex, the presence of RPD was significantly associated with development of late-stage AMD (OR=2.55, P=0.03).ConclusionA multimodal approach is mandatory for RPD detection. RPD are highly prevalent in the fellow eyes of patients with unilateral neovascular AMD. Presence of RPD is associated with increased long-term risk of progression, highlighting the importance of comprehensive multimodal retinal imaging and careful monitoring of at-risk patients.

Long-term safety of crisaborole ointment 2% in children and adults with mild to moderate atopic dermatitis.

PubMed

Eichenfield, Lawrence F; Call, Robert S; Forsha, Douglass W; Fowler, Joseph; Hebert, Adelaide A; Spellman, Mary; Stein Gold, Linda F; Van Syoc, Merrie; Zane, Lee T; Tschen, Eduardo

2017-10-01

Long-term topical treatment is often required for atopic dermatitis (AD), a chronic inflammatory skin disease. To assess the long-term safety results from a multicenter, open-label, 48-week safety study (AD-303) of patients (N = 517) ≥2 years of age with mild to moderate AD who continued crisaborole treatment, a topical phosphodiesterase-4 inhibitor, after completing a 28-day phase 3 pivotal study (AD-301, AD-302). Global disease severity was assessed in patients every 4 weeks, and if assessed as mild or greater, a 28-day treatment period with crisaborole applied twice daily was initiated. Adverse events (AEs), including treatment-emergent AEs (TEAEs), and serious AEs were analyzed. During the pivotal studies and AD-303, 65% of patients reported ≥1 TEAE, most of which were mild (51.2%) or moderate (44.6%) and considered unrelated to treatment (93.1%). The frequency and severity of TEAEs were consistent. The most frequently reported treatment-related AEs (overall, 10.2%) were dermatitis atopic (3.1%), application-site pain (2.3%), and application-site infection (1.2%). Nine patients (1.7%) discontinued the long-term study because of TEAEs. Long-term efficacy was not analyzed. Crisaborole ointment had a low frequency of treatment-related AEs over 48 weeks of treatment of patients with AD. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Stenting of aortic coarctation: acute, intermediate, and long-term results of a prospective multi-institutional registry--Congenital Cardiovascular Interventional Study Consortium (CCISC).

PubMed

Holzer, Ralf; Qureshi, Shakeel; Ghasemi, Abdolrahim; Vincent, Julie; Sievert, Horst; Gruenstein, Daniel; Weber, Howard; Alday, Luis; Peirone, Alejandro; Zellers, Thomas; Cheatham, John; Slack, Michael; Rome, Jonathan

2010-10-01

Since the 1980s, stent implantation has evolved as an important therapeutic strategy for coarctation of the aorta. However, available data is frequently flawed by short follow-up, lack of adequate follow-up imaging, and retrospective nature of data collection. Data was prospectively collected using a multicenter registry congenital cardiovascular interventional study consortium (CCISC). Between 2000 and 2009, 302 patients from 34 centers with a median weight of 58 kg underwent stent implantation for coarctation. Eligible patients (44%) completed intermediate follow-up (3-18 months) with integrated imaging (cath, CT, MRI), whereas 21% completed long-term follow-up (>18-60 months). Procedural success was defined as UL/LL systolic gradient of less than 20 mm Hg, lack of significant recurrent obstruction, and freedom from unplanned repeat intervention. Acute procedural success was 96%. Cumulative intermediate success was 86%, and cumulative long-term success was 77%. Unplanned repeat interventions were required in 4%, and aortic wall complications were seen in 1% of patients (dissection n = 1 and aneurysm n = 3). Other adverse events (n = 15) occurred mainly acutely and included technical complications such as stent malposition (n = 9). At long-term follow-up, 23% of patients continued to have systolic blood pressure above the 95th centile, 9% had an upper-to-lower limb blood pressure gradient in excess of 20 mm Hg, and 32% were taking antihypertensive medication. This study documented acute, intermediate, and long-term outcome data comparable or superior with other surgical or interventional series. However, even with successful initial stent therapy, patients continue to require long-term follow-up and have associated long-term morbidity, relating to aortic wall complications, systemic hypertension, recurrent obstruction as well as need for repeat intervention. © 2010 Wiley-Liss, Inc.

Effect of long-term proton pump inhibitor administration on gastric mucosal atrophy: A meta-analysis

PubMed Central

Li, Zhong; Wu, Cong; Li, Ling; Wang, Zhaoming; Xie, Haibin; He, Xiaozhou; Feng, Jin

2017-01-01

Background/Aims: Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related gastrointestinal diseases. Recently, some studies have reported that PPIs can alter the gastric mucosal architecture; however, the relationship remains controversial. This meta-analysis study was designed to quantify the association between long-term PPI administration and gastric atrophy. Materials and Methods: A PubMed search was conducted to identify studies using the keywords proton pump inhibitors or PPI and gastric atrophy or atrophic gastritis; the timeframe of publication searched was up to May 2016. Heterogeneity among studies was tested with the Q test; odds ratios (OR) and 95% confidence intervals (CI) were calculated. P values were calculated by I2 tests and regarded as statistically significant when <0.05. Results: We identified 13 studies that included 1465 patients under long-term PPI therapy and 1603 controls, with a total gastric atrophy rate of 14.50%. There was a higher presence of gastric atrophy (15.84%; statistically significant) in PPI group compared to the control group (13.29%) (OR: 1.55, 95% CI: 1.00–2.41). Conclusions: The pooled data suggest that long-term PPI use is associated with increased rates of gastric atrophy. Large-scale multicenter studies should be conducted to further investigate the relationship between acid suppressants and precancerous diseases. PMID:28721975

Quality of life in women undergoing urinary diversion for bladder cancer: results of a multicenter study among long-term disease-free survivors.

PubMed

Gacci, Mauro; Saleh, Omar; Cai, Tommaso; Gore, John L; D'Elia, Carolina; Minervini, Andrea; Masieri, Lorenzo; Giannessi, Claudia; Lanciotti, Michele; Varca, Virginia; Simonato, Alchiede; Serni, Sergio; Carmignani, Giorgio; Carini, Marco

2013-03-12

Women undergoing radical cystectomy (RC) and urinary diversion for bladder cancer experience substantial limitations in health-related quality of life (HRQOL). However, the level of discomfort caused by different urinary diversion has been never evaluated in long term survivors. The aim of this multicenter study is to evaluate differences in HRQOL among recurrence-free women undergoing cutaneous ureterostomy (CUS), Bricker's ileal conduit (BK-IC) and Orthotopic neobladder VIP (ONB-VIP) in disease-free females treated with radical cystectomy (RC), with long-term follow up (mean 60.1 months; range 36-122 months). All consecutively treated female patients from two urological institutions who underwent RC and urinary diversion from January 2000 to December 2008, with no evidence of tumor recurrence at a minimum follow up of 36 months, were included. Patients received the European Organisation for Research and Treatment of Cancer (EORTC) generic (QLQ-C30) and bladder cancer-specific instruments (QLQ-BLM30) and the Functional Assessment of Cancer Therapy for Bladder Cancer (FACT-BL). Clinical data and questionnaire results were analyzed in order to evaluate the HRQOL differences among diversion groups. We identified 37 females (median age: 68, range 45-82 years), including 12 status-post CUS, 16 who underwent BK-IC, and 9 who underwent ONB-VIP. Most were healthy (24/37 with no comorbidities, 4/37 Charlson 1-2, 9/37 Charlson 3 or greater - we didn't considered bladder cancer in Charlson evaluation because bladder cancer was the main inclusion criteria). Women undergoing CUS endorsed worse FACT-BL scores compared with BK-IC and ONB-VIP patients, worse HRQOL regarding physical and emotional well-being (p=0.008 and p=0.02, respectively), and a trend toward worse EORTC QLQ-C30 scores for appetite loss and fatigue (p=0.05 for both). In our study long-term disease-free females treated with CUS endorsed worse HRQOL compared with women who underwent BK-IC or ONB-VIP, mostly due to worse physical and emotional perception of their body image.

First long-term evidence supporting endovascular repair of abdominal aortic aneurysms.

PubMed

Indes, Jeffrey E; Muhs, Bart E; Dardik, Alan

2013-04-01

The traditional method of treating abdominal aortic aneurysms with open surgical repair has been steadily replaced by endovascular repair, thought to be a more minimally invasive approach. It is not known, however, whether the endovascular approach is truly less invasive for operative physiology; in addition, this approach has a different spectrum of complications. As such, it is uncertain whether elective endovascular repair of nonruptured aortic aneurysms reduces long-term morbidity and mortality compared with traditional open approaches. In this article, the authors evaluate a recent publication investigating long-term outcomes of a prospective randomized multicenter trial evaluating patients with asymptomatic abdominal aortic aneurysms treated with either endovascular or open repair, and discuss the results in the context of current evidence.

Development of Novel Combinatorial Treatment to Prevent Chemotherapeutic Resistance and Enhance Efficacy of Riluzole in a Rodent Model of SCI

DTIC Science & Technology

2016-10-01

site as well as in the cervical and lumbar cords out to at least 10 months post-injury. While our rodent study was ongoing, a multi-center clinical...lead to a preservation of motor function and an attenuation in long-term pathologies like neuropathic pain in rats following an acute therapeutic...chemotherapeutic resistance, mass spectrometry, riluzole, licofelone, neuropathic pain , locomotor, bioavailability 11 University of Mississippi

Long-term evolution after in-hospital cardiac arrest in children: Prospective multicenter multinational study.

PubMed

Del Castillo, Jimena; López-Herce, Jesús; Matamoros, Martha; Cañadas, Sonia; Rodríguez-Calvo, Ana; Cecchetti, Corrado; Rodriguez-Núñez, Antonio; Álvarez, Angel Carrillo

2015-11-01

The main objective was to study survival and neurologic evolution of children who suffered in-hospital pediatric cardiac arrest (CA). The secondary objective was to analyze the influence of risk factors on the long term outcome after CA. prospective, international, observational, multicentric study in 48 hospitals of 12 countries. CA in children between 1 month and 18 years were analyzed using the Utstein template. Survival and neurological state measured by Pediatric Cerebral Performance Category (PCPC) scale one year after hospital discharge was evaluated. 502 patients with in-hospital CA were evaluated. 197 of them (39.2%) survived to hospital discharge. PCPC at hospital discharge was available in 156 of survivors (79.2%). 76.9% had good neurologic state (PCPC 1-2) and 23.1% poor PCPC values (3-6). One year after cardiac arrest we could obtain data from 144 patients (28.6%). PCPC was available in 116 patients. 88 (75.9%) had a good neurologic evaluation and 28 (24.1%) a poor one. A neurological deterioration evaluated by PCPC scale was observed in 40 patients (7.9%). One year after cardiac arrest PCPC scores compared to hospital discharge had worsen in 7 patients (6%), remained constant in 103 patients (88.8%) and had improved in 6 patients (5.2%). Survival one year after cardiac arrest in children after in-hospital cardiac arrest is high. Neurologic outcome of these children a year after cardiac arrest is mostly the same as after hospital discharge. The factors associated with a worst long-term neurological outcome are the etiology of arrest being a traumatic or neurologic illness, and the persistency of higher lactic acid values 24h after ROSC. A standardised basic protocol even practicable for lower developed countries would be a first step for the new multicenter studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Correlation between cognitive impairment during the acute phase of first cerebral infarction and development of long-term pseudobulbar affect

PubMed Central

Wang, Yuan; Wang, Yuliang; Ma, Wenbin; Lu, Shujun; Chen, Jinbo; Cao, Lili

2018-01-01

Purpose The relationship between cognitive impairment during the acute phase of first cerebral infarction and the development of long-term pseudobulbar affect (PBA) has not been elucidated. Therefore, in this study, we aimed to determine if cognitive impairment during the acute phase of cerebral infarction will increase the risk of long-term post-infarction PBA. Patients and methods This was a nested case–control study using a prospective approach. A consecutive multicenter matched 1:1 case–control study of cognitive impairment cases following acute cerebral infarction (N=26) with 26 sex-, education years-, and age-matched controls. Univariate and multivariate conditional logistic regression analyses were performed to study the clinical features and changes in cognitive domain as well as the risk factors for PBA. Results Long-term PBA was independently predicted by low Montreal cognitive assessment (MoCA) scores at baseline. Multivariable regression models showed that post-infarction low MoCA scores remained independent predictors of long-term PBA (odds ratio [OR]=0.72; 95% confidence interval [CI]=0.54–0.95; P=0.018). Among all cognitive disorders, digit span test (DST) scores (OR=0.39; 95% CI=0.16–0.91, P=0.030), StroopC time (OR=1.15; 95% CI=1.01–1.31; P=0.037), and clock-drawing task (CDT) scores (OR=0.62; 95% CI=0.42–0.90; P=0.013) were found to be the independent risk factors for PBA. Conclusion Cognitive impairment during the acute phase of cerebral infarction increased the risk of cerebral infarction-induced long-term PBA. Development of PBA was closely associated with executive function, attention, and visuospatial disorder. PMID:29636612

Correlation between cognitive impairment during the acute phase of first cerebral infarction and development of long-term pseudobulbar affect.

PubMed

Wang, Yuan; Wang, Yuliang; Ma, Wenbin; Lu, Shujun; Chen, Jinbo; Cao, Lili

2018-01-01

The relationship between cognitive impairment during the acute phase of first cerebral infarction and the development of long-term pseudobulbar affect (PBA) has not been elucidated. Therefore, in this study, we aimed to determine if cognitive impairment during the acute phase of cerebral infarction will increase the risk of long-term post-infarction PBA. This was a nested case-control study using a prospective approach. A consecutive multicenter matched 1:1 case-control study of cognitive impairment cases following acute cerebral infarction (N=26) with 26 sex-, education years-, and age-matched controls. Univariate and multivariate conditional logistic regression analyses were performed to study the clinical features and changes in cognitive domain as well as the risk factors for PBA. Long-term PBA was independently predicted by low Montreal cognitive assessment (MoCA) scores at baseline. Multivariable regression models showed that post-infarction low MoCA scores remained independent predictors of long-term PBA (odds ratio [OR]=0.72; 95% confidence interval [CI]=0.54-0.95; P =0.018). Among all cognitive disorders, digit span test (DST) scores (OR=0.39; 95% CI=0.16-0.91, P =0.030), StroopC time (OR=1.15; 95% CI=1.01-1.31; P =0.037), and clock-drawing task (CDT) scores (OR=0.62; 95% CI=0.42-0.90; P =0.013) were found to be the independent risk factors for PBA. Cognitive impairment during the acute phase of cerebral infarction increased the risk of cerebral infarction-induced long-term PBA. Development of PBA was closely associated with executive function, attention, and visuospatial disorder.

Symptomatic muscular sarcoidosis: Lessons from a nationwide multicenter study.

PubMed

Cohen Aubart, Fleur; Abbara, Salam; Maisonobe, Thierry; Cottin, Vincent; Papo, Thomas; Haroche, Julien; Mathian, Alexis; Pha, Micheline; Gilardin, Laurent; Hervier, Baptiste; Soussan, Michael; Morlat, Philippe; Nunes, Hilario; Benveniste, Olivier; Amoura, Zahir; Valeyre, Dominique

2018-05-01

To describe clinicopathologic features of muscular sarcoidosis and the associated sarcoidosis phenotype through a nationwide multicenter study. Patients were included if they had histologically proven sarcoidosis and symptomatic muscular involvement confirmed by biological, imaging, or histologic examinations. Forty-eight patients (20 males) were studied, with a median age at muscular symptoms onset of 45 years (range 18-71). Four patterns were identified: a nodular pattern (27%); smoldering phenotype (29%); acute, subacute, or progressive myopathic type (35%); and combined myopathic and neurogenic pattern (10%). In all patterns, sarcoidosis was multivisceral with a median of 3 extramuscular organs involved (mostly lungs, lymph nodes, eyes, and skin) and a prolonged course with long-term use of corticosteroids and immunosuppressive drugs. Muscular patterns differed according to clinical presentation (myalgia, nodules, or weakness), electromyographic findings, muscular MRI, and response to sarcoidosis treatment. The myopathic and neuromuscular patterns were more severe. This nationwide study of muscular sarcoidosis allowed the identification of 4 patterns of granulomatous myositis, which differed by phenotypes and the clinical course.

Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy: the 3-year, multicenter, comparative Aldose Reductase Inhibitor-Diabetes Complications Trial.

PubMed

Hotta, Nigishi; Akanuma, Yasuo; Kawamori, Ryuzo; Matsuoka, Kempei; Oka, Yoshitomo; Shichiri, Motoaki; Toyota, Takayoshi; Nakashima, Mitsuyoshi; Yoshimura, Isao; Sakamoto, Nobuo; Shigeta, Yukio

2006-07-01

We sought to evaluate the long-term efficacy and safety of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy. Subjects with diabetic neuropathy, median motor nerve conduction velocity (MNCV) >or=40 m/s, and HbA(1c)

Changing requirements and resulting needs for IT-infrastructure for longitudinal research in the neurosciences.

PubMed

Buckow, Karoline; Quade, Matthias; Rienhoff, Otto; Nussbeck, Sara Y

2016-01-01

The observation of growing "difficulties" in IT-infrastructures in neuroscience research during the last years led to a search for reasons and an analysis on how this phenomenon is reflected in the scientific literature. With a retrospective analysis of nine examples of multicenter research projects in the neurosciences and a literature review the observation was systematically analyzed. Results show that the rise in complexity mainly stems from two reasons: (1) more and more need for information on quality and context of research data (metadata) and (2) long-term requirements to handle the consent and identity/pseudonyms of study participants and biomaterials in relation to legal requirements. The combination of these two aspects together with very long study times and data evaluation periods are components of the subjectively perceived "difficulties". A direct consequence of this result is that big multicenter trials are becoming part of integrated research data environments and are not standing alone for themselves anymore. This drives up the resource needs regarding the IT-infrastructure in neuroscience research. In contrast to these findings, literature on this development is scarce and the problem probably underestimated. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Long-term dizziness handicap in patients with vestibular schwannoma: a multicenter cross-sectional study.

PubMed

Carlson, Matthew L; Tveiten, Øystein Vesterli; Driscoll, Colin L; Neff, Brian A; Shepard, Neil T; Eggers, Scott D; Staab, Jeffrey P; Tombers, Nicole M; Goplen, Frederik K; Lund-Johansen, Morten; Link, Michael J

2014-12-01

(1) To characterize long-term dizziness following observation, microsurgery, and stereotactic radiosurgery (SRS) for small to medium-sized vestibular schwannoma (VS) using a validated self-assessment inventory; and (2) to identify clinical variables associated with long-term dizziness handicap. Cross-sectional observational study. Two independent tertiary academic referral centers: one located in the United States and one in Norway. All patients with sporadic VS of less than 3 cm who underwent primary microsurgery, SRS, or observation between 1998 and 2008 were identified. Subjects were surveyed via a postal questionnaire using the Dizziness Handicap Inventory (DHI) and a VS symptom questionnaire. The overall survey response rate was 79%. A total of 538 respondents (mean age, 64 years; 56% female) were analyzed, and the mean time interval between treatment and survey was 7.7 years. Pretreatment variables associated with greater dizziness handicap included female sex, older age, larger tumor size, preexisting diagnosis of headache or migraine, and symptoms of dizziness predating treatment. Significant posttreatment features strongly associated with poor long-term DHI scores included frequency and severity of ongoing headache. On multivariable analysis, treatment modality did not influence long-term dizziness handicap. At a mean of approximately 8 years following treatment, over half of patients with VS reported ongoing dizziness. The authors have identified several baseline features that may help predict the risk of lasting dizziness. Treatment modality does not appear to influence long-term DHI score. We found a strong association between posttreatment headache and poor dizziness handicap. Future study is needed to further define this relationship. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

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.

Long-term outcomes and recurrence patterns of standard versus extended pancreatectomy for pancreatic head cancer: a multicenter prospective randomized controlled study.

PubMed

Jang, Jin-Young; Kang, Jae Seung; Han, Youngmin; Heo, Jin Seok; Choi, Seong Ho; Choi, Dong Wook; Park, Sang Jae; Han, Sung-Sik; Yoon, Dong Sup; Park, Joon Seong; Yu, Hee Chul; Kang, Koo Jeong; Kim, Sang Geol; Lee, Hongeun; Kwon, Wooil; Yoon, Yoo-Seok; Han, Ho-Seong; Kim, Sun-Whe

2017-07-01

Our previous randomized controlled trial revealed no difference in 2-year overall survival (OS) between extended and standard resection for pancreatic adenocarcinoma. The present study evaluated the 5-year OS and recurrence patterns according to the extent of pancreatectomy. Between 2006 and 2009, 169 consecutive patients were prospectively enrolled and randomized to standard (n = 83) or extended resection (n = 86) groups to compare 5-year OS rate, long-term recurrence patterns and factors associated with long-term survival. The surgical R0 rate was similar between the standard and extended groups (85.5 vs. 90.7%, P = 0.300). Five-year OS (18.4 vs. 14.4%, P = 0.388), 5-year disease-free survival (14.8 vs. 14.0%, P = 0.531), and overall recurrence rates (74.7 vs. 69.9%, P = 0.497) were not significantly different between the two groups, although the incidence of peritoneal seeding was higher in the extended group (25 vs. 8.1%, P = 0.014). Extended pancreatectomy does not have better short-term and long-term survival outcomes, and shows similar R0 rates and overall recurrence rates compared with standard pancreatectomy. Extended pancreatectomy does not have to be performed routinely for all cases of resectable pancreatic adenocarcinoma, especially considering its associated increased morbidity shown in our previous study. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Efficacy of long-term 4.0 g/day mesalazine (Pentasa) for maintenance therapy in ulcerative colitis.

PubMed

Takeshima, Fuminao; Matsumura, Masato; Makiyama, Kazuya; Ohba, Kazuo; Yamakawa, Masaki; Nishiyama, Hitoshi; Yamao, Takuji; Akazawa, Yuko; Yamaguchi, Naoyuki; Ohnita, Ken; Ichikawa, Tatsuki; Isomoto, Hajime; Nakao, Kazuhiko

2014-07-27

High-dose (4.0 g/day) mesalazine is typically used for induction therapy, but its efficacy as maintenance therapy remains to be determined. We conducted a multicenter retrospective study to investigate the efficacy of continuous treatment with 4.0 g/day of mesalazine. Japanese ulcerative colitis (UC) patients receiving acute induction therapy with 4.0 g/day mesalazine were enrolled and followed. Those who clinically improved or who achieved clinical remission were categorized into 2 sub-groups according to the median duration of treatment with 4.0 g/day of mesalazine. The clinical relapse frequency and the time to relapse were analyzed. We enrolled 180 patients with active UC, and then 115 patients who clinically improved or who achieved clinical remission after treatment with 4.0 g/day mesalazine were categorized into 2 sub-groups according to the median of treatment duration: a short-term treatment group (≤105 days, n=58) and a long-term treatment group (>105 days, n=57). Overall, 45 (39.1%) patients relapsed: 28 (48.3%) in the short-term treatment group and 17 (29.8%) in the long-term treatment group. This difference was statistically significant (p<0.05). The relapse-free rate in the long-term treatment group was significantly higher than that in the short-term treatment group (p<0.05). The mean time to relapse in the long-term treatment group was significantly longer than that in the short-term treatment group (425.6±243.8 days vs. 277.4±224.5 days; p<0.05). Long-term continuous treatment with high-dose mesalazine (4.0 g/day) may be more effective than short-term treatment for maintenance of remission in UC patients.

Antiretroviral therapeutic drug monitoring in HIV-infected pregnant women: maternal immunovirological outcome at delivery and during the 18 month follow-up period.

PubMed

Nicastri, Emanuele; Ivanovic, Jelena; Signore, Fabrizio; Tempestilli, Massimo; Bellagamba, Rita; Viscione, Magdalena; Pisani, Giuseppe; Vallone, Cristina; Tommasi, Chiara; Gallo, Anna L; De Nardo, Pasquale; Pucillo, Paolo L; Narciso, Pasquale

2012-10-01

No data are available on the long-term immunovirological outcome of HIV-positive pregnant women experiencing sub-therapeutic antiretroviral drug (ARV) concentrations during pregnancy. The objective of our study was to assess the long-term virological outcome in pregnant women treated with HAART. A prospective, multi-center study enrolled 60 HIV-infected pregnant women stratified into 3 groups according to the response to HAART. Group A, women successfully treated with HAART; Group B, women with confirmed virological failure during HAART; Group C, women successfully treated with HAART during pregnancy for prevention of vertical transmission only. Smoking, alcohol use, low adherence to therapy, and increased viral load at delivery were significantly associated to virological failure at univariate analysis. At multivariate regression analysis, only adherence to therapy was reported as an independent variable related to the virological response (p < 0.001). Virological failure during follow-up was reported in 2 (25.0%) of the 8 women with sub therapeutic Ctrough and in 4 of the 33 (12.1%) women with therapeutic Ctrough (p=0.33). In group C, the viro-immunological set points during follow-up did not differ from those observed before HAART initiation. No significantly increased rate of virological failure after delivery was reported in women with sub-therapeutic ARV concentrations during pregnancy and long-term follow-up. The long-term virological outcome was independently associated to reduced adherence to therapy. Evaluation of the clinical impact of the low plasma ARV concentrations during pregnancy on the long-term virological outcome deserves further larger studies.

Scleroderma in children: an update.

PubMed

Zulian, Francesco; Cuffaro, Giorgio; Sperotto, Francesca

2013-09-01

Scleroderma, in its localized and systemic presentation, represents the third most frequent rheumatic condition in childhood after juvenile idiopathic arthritis and systemic lupus erythematosus. Early diagnosis, appropriate assessment and effective treatment are crucial to improve the long-term outcome. Recent studies, concerning histopathology and clinical associations with other conditions, open new horizons on the etiopathogenesis of scleroderma. New developments have been also reached in the field of outcome measures. In juvenile localized scleroderma (JLS), new techniques such as Doppler and laser Doppler imaging have shown their usefulness for the daily monitoring of the patients. In juvenile systemic sclerosis (JSSc), a new severity score has been developed and needs to be validated in future trials. Finally, a randomized, double-blind controlled trial, a multicenter consensus statement and long-term follow-up studies have confirmed the important role of methotrexate (MTX) for the treatment of JLS. Studies over recent years highlighted the role of imaging as outcome measures for JLS and introduced a severity score for JSSc. New studies on MTX confirmed its important role for the treatment of JLS.

Comparison of the long-term clinical performance of a biodegradable and a titanium fixation system in maxillofacial surgery: A multicenter randomized controlled trial.

PubMed

Gareb, B; van Bakelen, N B; Buijs, G J; Jansma, J; de Visscher, J G A M; Hoppenreijs, Th J M; Bergsma, J E; van Minnen, B; Stegenga, B; Bos, R R M

2017-01-01

Biodegradable fixation systems could reduce or eliminate problems associated with titanium removal of implants in a second operation. The aim of this study was to compare the long-term (i.e. >5 years postoperatively) clinical performance of a titanium and a biodegradable system in oral and maxillofacial surgery. The present multicenter Randomized Controlled Trial (RCT) was performed in four hospitals in the Netherlands. Patients treated with a bilateral sagittal split osteotomy (BSSO) and/or a Le Fort-I osteotomy, and those treated for fractures of the mandible, maxilla, or zygoma were included from December 2006 to July 2009. The patients were randomly assigned to either a titanium (KLS Martin) or a biodegradable group (Inion CPS). After >5 years postoperatively, plate removal was performed in 22 of the 134 (16.4%) patients treated with titanium and in 23 of the 87 (26.4%) patients treated with the biodegradable system (P = 0.036, hazard ratio (HR) biodegradable (95% CI) = 2.0 (1.05-3.8), HR titanium = 1). Occlusion, VAS pain scores, and MFIQ showed good and (almost) pain free mandibular function in both groups. In conclusion, the performance of the Inion CPS biodegradable system was inferior compared to the KLS Martin titanium system regarding plate/screws removal in the abovementioned surgical procedures. http://controlled-trials.com ISRCTN44212338.

Temporal trends in patient characteristics and survival of intensive care admissions with sepsis: a multicenter analysis*.

PubMed

Dreiher, Jacob; Almog, Yaniv; Sprung, Charles L; Codish, Shlomi; Klein, Moti; Einav, Sharon; Bar-Lavie, Yaron; Singer, Pierre P; Nimrod, Adi; Sachs, Jeffrey; Talmor, Daniel; Friger, Michael; Greenberg, Dan; Olsfanger, David; Hersch, Moshe; Novack, Victor

2012-03-01

To estimate in-hospital, 1-yr, and long-term mortality and to assess time trends in incidence and outcomes of sepsis admissions in the intensive care unit. A population-based, multicenter, retrospective cohort study. Patients hospitalized with sepsis in the intensive care unit in seven general hospitals in Israel during 2002-2008. None. Survival data were collected and analyzed according to demographic and background clinical characteristics, as well as features of the sepsis episode, using Kaplan-Meier approach for long-term survival. A total of 5,155 patients were included in the cohort (median age: 70, 56.3% males; median Charlson comorbidity index: 4). The mean number of intensive care unit admissions per month increased over time, while no change in in-hospital mortality was observed. The proportion of patients surviving to hospital discharge was 43.9%. The 1-, 2-, 5-, and 8-yr survival rates were 33.0%, 29.8%, 23.3%, and 19.8%, respectively. Mortality was higher in older patients, patients with a higher Charlson comorbidity index, and those with multiorgan failure, and similar in males and females. One-year age-standardized mortality ratio was 21-fold higher than expected, based on the general population rates. Mortality following intensive care unit sepsis admission remains high and is correlated with underlying patients' characteristics, including age, comorbidities, and the number of failing organ systems.

Combined-modality therapy for primary central nervous system lymphoma: Long-term data from a Phase II multicenter study (Trans-Tasman Radiation Oncology Group)

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

O'Brien, Peter C.; Roos, Daniel E.; Pratt, Gary

2006-02-01

Purpose: To assess, in a multicenter setting, the long-term outcomes of a brief course of high-dose methotrexate followed by radiotherapy for patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Forty-six patients were entered in a Phase II protocol consisting of methotrexate (1 g/m{sup 2} on Days 1 and 8), followed by whole-brain irradiation (45-50.4 Gy). The median follow-up time was 7 years, with a minimum follow-up of 5 years. Results: The 5-year survival estimate was 37% ({+-}14%, 95% confidence interval [CI]), with progression-free survival being 36% ({+-}15%, 95% CI), and median survival 36 months. Of the originalmore » 46 patients, 10 were alive, all without evidence of disease recurrence. A total of 11 patients have developed neurotoxicity, with the actuarial risk being 30% ({+-}18%, 95% CI) at 5 years but continuing to increase. For patients aged >60 years the risk of neurotoxicity at 7 years was 58% ({+-}30%, 95% CI). Conclusion: Combined-modality therapy, based on high-dose methotrexate, results in improved survival outcomes in PCNSL. The risk of neurotoxicity for patients aged >60 years is unacceptable with this regimen, although survival outcomes for patients aged >60 years were higher than in many other series.« less

Changes in plasma ACTH levels and corticotroph tumor size in patients with Cushing's disease during long-term treatment with the glucocorticoid receptor antagonist mifepristone.

PubMed

Fleseriu, Maria; Findling, James W; Koch, Christian A; Schlaffer, Sven-Martin; Buchfelder, Michael; Gross, Coleman

2014-10-01

Pituitary effects of long-term therapy with mifepristone, a glucocorticoid receptor antagonist, in Cushing's disease (CD) patients are not well understood. Our objective was to report changes in ACTH and pituitary magnetic resonance imaging (MRI) findings during long-term use of mifepristone in CD patients. The Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing's Syndrome (SEISMIC) was a 24-week, open-label study of mifepristone, and its long-term extension (LTE) is a multicenter U.S. study. Forty-three CD patients (mean age 45.3 years) were enrolled in SEISMIC with 27 continuing into the LTE study. Mifepristone (300-1200 mg) was administered once daily. ACTH and pituitary MRI were assessed at baseline and at regular intervals during treatment. A ≥2-fold increase in ACTH was observed in 72% of patients treated for a median duration of 11.3 months. The mean peak increase in ACTH was 2.76 ± 1.65-fold during SEISMIC, and mean ACTH concentrations remained stable during the LTE. ACTH was directly correlated with mifepristone dose and declined to near baseline levels after mifepristone discontinuation. Tumor regressed in 2 patients and progressed in 3 patients with macroadenomas. An additional microadenoma was identified after 25 months of treatment after a baseline tumor-negative MRI. In the largest prospective study to date, long-term mifepristone treatment increased ACTH in approximately two-thirds of patients with CD. ACTH elevations were observed within the first few weeks of treatment, were dose-dependent, and generally remained stable over time. Corticotroph tumor progression and regression may occur over time, but patients may have significant increases in ACTH levels without evidence of tumor growth.

Clinical Presentation, Management and Outcome of Acute Coronary Syndrome in Yemen: Data from GULF RACE - 2 Registry

PubMed Central

Ahmed, Al-Motarreb; Abdulwahab, Al-Matry; Hesham, Al-Fakih; Nawar, Wather

2013-01-01

Background: Acute Coronary Syndrome (ACS) is increasing in Yemen in recent years and there are no data available on its short and long-term outcome. We evaluated the clinical pictures, management, in-hospital, and long-term outcomes of the ACS patients in Yemen. Design and Setting: A 9-month prospective, multi-center study conducted in 26 hospitals from 9 governorates. The study included 30-day and 1-year mortality follow-up. Patients and Methods: One thousand seven hundred and sixty one patients with ACS were collected prospectively during the 9-month period. Patients with ST-elevation myocardial infarction (STEMI) and non-ST-elevation acute coronary syndrome (NSTEACS), including non-ST-elevation myocardial infarction and unstable angina were included. Conclusions: ACS patients in Yemen present at a relatively young age with high prevalence of Smoking, khat chewing and hypertension. STEMI patients present late, and their acute management is poor. In-hospital evidence-based medication rates are high, but coronary revascularization procedures were very low. In-hospital mortality was high and long-term mortality rates increased two folds compared with the in-hospital mortality. PMID:24695681

Clinical experience with adalimumab in a multicenter Swiss cohort of patients with Crohn's disease.

PubMed

Nichita, Cristina; Stelle, Marc; Vavricka, Stephan; El-Wafa Ali, Abdou; Ballabeni, Pierluigi; de Saussure, Philippe; Straumann, Alex; Rogler, Gerhard; Michetti, Pierre

2010-01-01

Controlled clinical trials have demonstrated the efficacy and safety of adalimumab in patients with moderate-to-severe Crohn's disease (CD), but there is, however, only limited long-term experience with adalimumab in daily practice. To assess the long-term effectiveness and safety of adalimumab in a multicenter cohort of practice-based patients with moderate-to-severe CD. We retrospectively reviewed the charts of CD patients who received adalimumab over a 3-year period. Disease severity was scored using the Harvey-Bradshaw index (HBI). Remission was defined as an HBI of 3 points at evaluation compared to the baseline. Univariate logistic regression analysis was used to identify the predictive variables associated with response. The charts of 55 patients were reviewed; remission and response rates observed at weeks 4-6 were 52.7 and 83.6%, respectively. Remission was maintained at weeks 12, 24 and 52 in 89.6, 72.4 and 44.7% of patients, respectively. Remission and response rates were not influenced by smoking status, disease location or duration, the first month total dose, or previous infliximab therapy. The remission rate at weeks 4-6 was significantly higher in patients intolerant of infliximab as compared to those who lost response to this drug. Adalimumab was well tolerated overall. Adalimumab can be considered a suitable option in patients with moderate-to-severe CD, demonstrating sustained long-term effectiveness. Copyright (c) 2010 S. Karger AG, Basel.

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 effects of whole-vault cranioplasty versus strip craniectomy on long-term neuropsychological outcomes in sagittal craniosynostosis.

PubMed

Hashim, Peter W; Patel, Anup; Yang, Jenny F; Travieso, Roberto; Terner, Jordan; Losee, Joseph E; Pollack, Ian; Jane, John; Jane, John; Kanev, Paul; Mayes, Linda; Duncan, Charles; Bridgett, David J; Persing, John A

2014-09-01

The optimal type of surgical management for isolated sagittal synostosis remains a source of significant debate. There is a paucity of data regarding possible differences in long-term neuropsychological outcomes following treatment with whole-vault cranioplasty or endoscopic strip craniectomy. This study provides the first comparative analysis examining the effects of the two techniques related to long-term intellectual functioning. A total of 70 patients were enrolled in this multicenter study, 29 of whom had previously undergone endoscopic strip craniectomy and 41 of whom had previously undergone whole-vault cranioplasty. All patients completed a battery of neurodevelopmental tests (Beery-Buktenica Developmental Test of Visual-Motor Integration, Wechsler Abbreviated Scale of Intelligence, and Wechsler Fundamentals) to evaluate various domains of neuropsychological function. In a group comparison of those treated before 6 months of age, whole-vault patients obtained higher scores relative to endoscopic strip craniectomy patients on visuomotor integration, full-scale intelligence quotient, verbal intelligence quotient, word reading, and reading comprehension (p < 0.05 for all). When compared against strip craniectomy performed before 3 months of age, the whole-vault group still showed significantly higher scores in verbal intelligence quotient, reading comprehension, and word reading (p < 0.05 for all). The type of surgical intervention for isolated sagittal synostosis impacts long-term neuropsychological outcomes. Patients undergoing early whole-vault cranioplasty attained higher intelligence quotient and achievement scores relative to those undergoing strip craniectomy. Surgical management with whole-vault cranioplasty performed before 6 months of age provides the most favorable long-term intellectual outcomes in patients with isolated sagittal synostosis. Therapeutic, II.

Uterine artery embolization for treatment of leiomyomata: long-term outcomes from the FIBROID Registry.

PubMed

Goodwin, Scott C; Spies, James B; Worthington-Kirsch, Robert; Peterson, Eric; Pron, Gaylene; Li, Shuang; Myers, Evan R

2008-01-01

To assess long-term clinical outcomes of uterine artery embolization across a wide variety of practice settings in a large patient cohort. The Fibroid Registry for Outcomes Data (FIBROID) for Uterine Embolization was a 3-year, single-arm, prospective, multi-center longitudinal study of the short- and long-term outcomes of uterine artery embolization for leiomyomata. Two thousand one hundred twelve patients with symptomatic leiomyomata were eligible for long-term follow-up at 27 sites representing a geographically diverse set of practices, including academic centers, community hospitals, and closed-panel health maintenance organizations. At 36 months after treatment, 1,916 patients remained in the study, and of these, 1,278 patients completed the survey. The primary measures of outcome were the symptom and health-related quality-of-life scores from the Uterine Fibroid Symptom and Quality of Life questionnaire. Mean symptom scores improved 41.41 points (P<.001), and the quality of life scores improved 41.47 points (P<.001), both moving into the normal range for this questionnaire. The improvements were independent of practice setting. During the 3 years of the study, Kaplan-Meier estimates of hysterectomy, myomectomy, or repeat uterine artery embolization were 9.79%, 2.82%, and 1.83% of the patients, respectively. Uterine artery embolization results in a durable improvement in quality of life. These results are achievable when the procedure is performed in any experienced community or academic interventional radiology practice. III.

Prospective, Multicenter, Randomized, Crossover Clinical Trial Comparing the Safety and Effectiveness of Cooled Radiofrequency Ablation With Corticosteroid Injection in the Management of Knee Pain From Osteoarthritis.

PubMed

Davis, Tim; Loudermilk, Eric; DePalma, Michael; Hunter, Corey; Lindley, David; Patel, Nilesh; Choi, Daniel; Soloman, Marc; Gupta, Anita; Desai, Mehul; Buvanendran, Asokumar; Kapural, Leonardo

2018-01-01

Osteoarthritis (OA) of the knee affects the aging population and has an associated influence on the health care system. Rigorous studies evaluating radiofrequency ablation for OA-related knee pain are lacking. This study compared long-term clinical safety and effectiveness of cooled radiofrequency ablation (CRFA) with intra-articular steroid (IAS) injection in managing OA-related knee pain. This is a prospective, multicenter, randomized trial with 151 subjects with chronic (≥6 months) knee pain that was unresponsive to conservative modalities. Knee pain (Numeric Rating Scale [NRS]), Oxford Knee Score, overall treatment effect (Global Perceived Effect), analgesic drug use, and adverse events were compared between CRFA and IAS cohorts at 1, 3, and 6 months after intervention. There were no differences in demographics between study groups. At 6 months, the CRFA group had more favorable outcomes in NRS: pain reduction 50% or greater: 74.1% versus 16.2%, P < 0.0001 (25.9% and 83.8% of these study cohorts, respectively, were nonresponders). Mean NRS score reduction was 4.9 ± 2.4 versus 1.3 ± 2.2, P < 0.0001; mean Oxford Knee Score was 35.7 ± 8.8 vs 22.4 ± 8.5, P < 0.0001; mean improved Global Perceived Effect was 91.4% vs 23.9%, P < 0.0001; and mean change in nonopioid medication use was CRFA > IAS (P = 0.02). There were no procedure-related serious adverse events. This study demonstrates that CRFA is an effective long-term therapeutic option for managing pain and improving physical function and quality of life for patients with painful knee OA when compared with IAS injection. ClinicalTrials.gov (NCT02343003).

Prospective, Multicenter, Randomized, Crossover Clinical Trial Comparing the Safety and Effectiveness of Cooled Radiofrequency Ablation With Corticosteroid Injection in the Management of Knee Pain From Osteoarthritis

PubMed Central

Davis, Tim; Loudermilk, Eric; DePalma, Michael; Hunter, Corey; Lindley, David; Patel, Nilesh; Choi, Daniel; Soloman, Marc; Gupta, Anita; Desai, Mehul; Buvanendran, Asokumar; Kapural, Leonardo

2018-01-01

Background and Objectives Osteoarthritis (OA) of the knee affects the aging population and has an associated influence on the health care system. Rigorous studies evaluating radiofrequency ablation for OA-related knee pain are lacking. This study compared long-term clinical safety and effectiveness of cooled radiofrequency ablation (CRFA) with intra-articular steroid (IAS) injection in managing OA-related knee pain. Methods This is a prospective, multicenter, randomized trial with 151 subjects with chronic (≥6 months) knee pain that was unresponsive to conservative modalities. Knee pain (Numeric Rating Scale [NRS]), Oxford Knee Score, overall treatment effect (Global Perceived Effect), analgesic drug use, and adverse events were compared between CRFA and IAS cohorts at 1, 3, and 6 months after intervention. Results There were no differences in demographics between study groups. At 6 months, the CRFA group had more favorable outcomes in NRS: pain reduction 50% or greater: 74.1% versus 16.2%, P < 0.0001 (25.9% and 83.8% of these study cohorts, respectively, were nonresponders). Mean NRS score reduction was 4.9 ± 2.4 versus 1.3 ± 2.2, P < 0.0001; mean Oxford Knee Score was 35.7 ± 8.8 vs 22.4 ± 8.5, P < 0.0001; mean improved Global Perceived Effect was 91.4% vs 23.9%, P < 0.0001; and mean change in nonopioid medication use was CRFA > IAS (P = 0.02). There were no procedure-related serious adverse events. Conclusions This study demonstrates that CRFA is an effective long-term therapeutic option for managing pain and improving physical function and quality of life for patients with painful knee OA when compared with IAS injection. Clinical Trial Registration: ClinicalTrials.gov (NCT02343003). PMID:29095245

A 5-year multicenter prospective cohort study on the long-term visual prognosis and predictive factors for visual outcome in Japanese patients with age-related macular degeneration: the AMD2000 study.

PubMed

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

2018-03-01

In this study (AMD2000), we aimed to determine the visual prognosis of Japanese patients with age-related macular degeneration (AMD). This was a multicenter prospective observational cohort study. In total, 460 patients with AMD were recruited from April 2006 to March 2009 from 18 clinical trial sites in Japan. They were followed up for 5 years, as they continued to receive medical treatment. Of the 409 study eyes followed up for at least 1 year, 243 eyes (59.4%) were treated with photodynamic therapy (PDT) using verteporfin, and 58 eyes (14.2%) were treated with intravitreal injections of antivascular endothelial growth factor agents as the initial treatment. The mean best-corrected visual acuities (BCVA) for typical AMD (tAMD; 0.688 ± 0.498) and polypoidal choroidal vasculopathy (PCV; 0.451 ± 0.395) were significantly less at 2 years (tAMD, 0.779 ± 0.632, P < 0.05; PCV, 0.534 ± 0.618, P < 0.05) and at 5 years (AMD, 0.873 ± 0.718, P < 0.05; PCV, 0.635 ± 0.668, P < 0.05) than at baseline. In eyes with tAMD, absence of blocked fluorescence was associated with 5-year maintenance of the baseline BCVA. Regarding PCV, the presence of polypoidal lesions and cystoid macular edema as well as the lesion size was associated with 5-year maintenance of the baseline BCVA. In some patients, the diagnosis changed: of the 192 eyes initially diagnosed with typical AMD, 19 were newly diagnosed with PCV during follow-up. Maintaining the baseline BCVA over the long term is difficult in Japanese eyes with wet AMD.

Colorectal Cancer and Long-Term Exposure to Trihalomethanes in Drinking Water: A Multicenter Case-Control Study in Spain and Italy.

PubMed

Villanueva, Cristina M; Gracia-Lavedan, Esther; Bosetti, Cristina; Righi, Elena; Molina, Antonio José; Martín, Vicente; Boldo, Elena; Aragonés, Nuria; Perez-Gomez, Beatriz; Pollan, Marina; Acebo, Ines Gomez; Altzibar, Jone M; Zabala, Ana Jiménez; Ardanaz, Eva; Peiró, Rosana; Tardón, Adonina; Chirlaque, Maria Dolores; Tavani, Alessandra; Polesel, Jerry; Serraino, Diego; Pisa, Federica; Castaño-Vinyals, Gemma; Espinosa, Ana; Espejo-Herrera, Nadia; Palau, Margarita; Moreno, Victor; La Vecchia, Carlo; Aggazzotti, Gabriella; Nieuwenhuijsen, Mark J; Kogevinas, Manolis

2017-01-01

Evidence on the association between colorectal cancer and exposure to disinfection by-products in drinking water is inconsistent. We assessed long-term exposure to trihalomethanes (THMs), the most prevalent group of chlorination by-products, to evaluate the association with colorectal cancer. A multicenter case-control study was conducted in Spain and Italy in 2008-2013. Hospital-based incident cases and population-based (Spain) and hospital-based (Italy) controls were interviewed to ascertain residential histories, type of water consumed in each residence, frequency and duration of showering/bathing, and major recognized risk factors for colorectal cancer. We estimated adjusted odds ratios (OR) for colorectal cancer in association with quartiles of estimated average lifetime THM concentrations in each participant's residential tap water (micrograms/liter; from age 18 to 2 years before the interview) and estimated average lifetime THM ingestion from drinking residential tap water (micrograms/day). We analyzed 2,047 cases and 3,718 controls. Median values (ranges) for average lifetime residential tap water concentrations of total THMs, chloroform, and brominated THMs were 30 (0-174), 17 (0-63), and 9 (0-145) μg/L, respectively. Total THM concentration in residential tap water was not associated with colorectal cancer (OR = 0.92, 95% CI: 0.66, 1.28 for highest vs. lowest quartile), but chloroform concentrations were inversely associated (OR = 0.31, 95% CI: 0.24, 0.41 for highest vs. lowest quartile). Brominated THM concentrations showed a positive association among men in the highest versus the lowest quartile (OR = 1.43, 95% CI: 0.83, 2.46). Patterns of association were similar for estimated average THM ingestion through residential water consumption. We did not find clear evidence of an association between detailed estimates of lifetime total THM exposure and colorectal cancer in our large case-control study population. Negative associations with chloroform concentrations and ingestion suggest differences among specific THMs, but these findings should be confirmed in other study populations. Citation: Villanueva CM, Gracia-Lavedan E, Bosetti C, Righi E, Molina AJ, Martín V, Boldo E, Aragonés N, Perez-Gomez B, Pollan M, Gomez Acebo I, Altzibar JM, Jiménez Zabala A, Ardanaz E, Peiró R, Tardón A, Chirlaque MD, Tavani A, Polesel J, Serraino D, Pisa F, Castaño-Vinyals G, Espinosa A, Espejo-Herrera N, Palau M, Moreno V, La Vecchia C, Aggazzotti G, Nieuwenhuijsen MJ, Kogevinas M. 2017. Colorectal cancer and long-term exposure to trihalomethanes in drinking water: a multicenter case---control study in Spain and Italy. Environ Health Perspect 125:56-65; http://dx.doi.org/10.1289/EHP155.

Colorectal Cancer and Long-Term Exposure to Trihalomethanes in Drinking Water: A Multicenter Case–Control Study in Spain and Italy

PubMed Central

Villanueva, Cristina M.; Gracia-Lavedan, Esther; Bosetti, Cristina; Righi, Elena; Molina, Antonio José; Martín, Vicente; Boldo, Elena; Aragonés, Nuria; Perez-Gomez, Beatriz; Pollan, Marina; Acebo, Ines Gomez; Altzibar, Jone M.; Zabala, Ana Jiménez; Ardanaz, Eva; Peiró, Rosana; Tardón, Adonina; Chirlaque, Maria Dolores; Tavani, Alessandra; Polesel, Jerry; Serraino, Diego; Pisa, Federica; Castaño-Vinyals, Gemma; Espinosa, Ana; Espejo-Herrera, Nadia; Palau, Margarita; Moreno, Victor; La Vecchia, Carlo; Aggazzotti, Gabriella; Nieuwenhuijsen, Mark J; Kogevinas, Manolis

2016-01-01

Background: Evidence on the association between colorectal cancer and exposure to disinfection by-products in drinking water is inconsistent. Objectives: We assessed long-term exposure to trihalomethanes (THMs), the most prevalent group of chlorination by-products, to evaluate the association with colorectal cancer. Methods: A multicenter case–control study was conducted in Spain and Italy in 2008–2013. Hospital-based incident cases and population-based (Spain) and hospital-based (Italy) controls were interviewed to ascertain residential histories, type of water consumed in each residence, frequency and duration of showering/bathing, and major recognized risk factors for colorectal cancer. We estimated adjusted odds ratios (OR) for colorectal cancer in association with quartiles of estimated average lifetime THM concentrations in each participant’s residential tap water (micrograms/liter; from age 18 to 2 years before the interview) and estimated average lifetime THM ingestion from drinking residential tap water (micrograms/day). Results: We analyzed 2,047 cases and 3,718 controls. Median values (ranges) for average lifetime residential tap water concentrations of total THMs, chloroform, and brominated THMs were 30 (0–174), 17 (0–63), and 9 (0–145) μg/L, respectively. Total THM concentration in residential tap water was not associated with colorectal cancer (OR = 0.92, 95% CI: 0.66, 1.28 for highest vs. lowest quartile), but chloroform concentrations were inversely associated (OR = 0.31, 95% CI: 0.24, 0.41 for highest vs. lowest quartile). Brominated THM concentrations showed a positive association among men in the highest versus the lowest quartile (OR = 1.43, 95% CI: 0.83, 2.46). Patterns of association were similar for estimated average THM ingestion through residential water consumption. Conclusions: We did not find clear evidence of an association between detailed estimates of lifetime total THM exposure and colorectal cancer in our large case–control study population. Negative associations with chloroform concentrations and ingestion suggest differences among specific THMs, but these findings should be confirmed in other study populations. Citation: Villanueva CM, Gracia-Lavedan E, Bosetti C, Righi E, Molina AJ, Martín V, Boldo E, Aragonés N, Perez-Gomez B, Pollan M, Gomez Acebo I, Altzibar JM, Jiménez Zabala A, Ardanaz E, Peiró R, Tardón A, Chirlaque MD, Tavani A, Polesel J, Serraino D, Pisa F, Castaño-Vinyals G, Espinosa A, Espejo-Herrera N, Palau M, Moreno V, La Vecchia C, Aggazzotti G, Nieuwenhuijsen MJ, Kogevinas M. 2017. Colorectal cancer and long-term exposure to trihalomethanes in drinking water: a multicenter case–––control study in Spain and Italy. Environ Health Perspect 125:56–65; http://dx.doi.org/10.1289/EHP155 PMID:27383820

Prospective multi-center study of an automatic online seizure detection system for epilepsy monitoring units.

PubMed

Fürbass, F; Ossenblok, P; Hartmann, M; Perko, H; Skupch, A M; Lindinger, G; Elezi, L; Pataraia, E; Colon, A J; Baumgartner, C; Kluge, T

2015-06-01

A method for automatic detection of epileptic seizures in long-term scalp-EEG recordings called EpiScan will be presented. EpiScan is used as alarm device to notify medical staff of epilepsy monitoring units (EMUs) in case of a seizure. A prospective multi-center study was performed in three EMUs including 205 patients. A comparison between EpiScan and the Persyst seizure detector on the prospective data will be presented. In addition, the detection results of EpiScan on retrospective EEG data of 310 patients and the public available CHB-MIT dataset will be shown. A detection sensitivity of 81% was reached for unequivocal electrographic seizures with false alarm rate of only 7 per day. No statistical significant differences in the detection sensitivities could be found between the centers. The comparison to the Persyst seizure detector showed a lower false alarm rate of EpiScan but the difference was not of statistical significance. The automatic seizure detection method EpiScan showed high sensitivity and low false alarm rate in a prospective multi-center study on a large number of patients. The application as seizure alarm device in EMUs becomes feasible and will raise the efficiency of video-EEG monitoring and the safety levels of patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

MiDas: Automatic Extraction of a Common Domain of Discourse in Sleep Medicine for Multi-center Data Integration

PubMed Central

Sahoo, Satya S.; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S.; Zhang, Guo-Qiang

2011-01-01

Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI’s Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry. PMID:22195180

MiDas: automatic extraction of a common domain of discourse in sleep medicine for multi-center data integration.

PubMed

Sahoo, Satya S; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S; Zhang, Guo-Qiang

2011-01-01

Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI's Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry.

Meconium ileus in patients with cystic fibrosis is not a risk factor for clinical deterioration and survival: the Israeli Multicenter Study.

PubMed

Efrati, Ori; Nir, Judith; Fraser, Drora; Cohen-Cymberknoh, Malena; Shoseyov, David; Vilozni, Daphna; Modan-Moses, Dalit; Levy, Ran; Szeinberg, Amir; Kerem, Eitan; Rivlin, Joseph

2010-02-01

Patients with cystic fibrosis (CF) presenting with meconium ileus (MI) tend to have worse outcomes than those without MI. We evaluated the clinical characteristics and survival rates among Israeli patients with CF with and without MI after a prolonged follow-up (15-30 years). A multicenter retrospective study. Forty-nine patients with CF, representing 13.8% of all patients with CF in Israel, presented with MI (current age 17.4 +/- 7.9 years) between 1975 and 2006. They were compared with 38 patients with CF (current age 19.3 +/- 6.5 years) without MI matched by sex and CF transmembrane conductance regulator mutation. A total of 66.2% of patients with MI and 73.6% without MI were followed for a prolonged period (24.9 +/- 2.7 years). Of the patients with MI, 31 were managed operatively, whereas 18 were treated successfully with gastrograffin enema, with similar clinical outcomes. Five patients in the MI group and 3 in the control group died during the study period. Bacterial colonization, z score of body mass index, and pulmonary function tests were similar in patients with and without MI in the long term. In younger patients, many clinical parameters were more prevalent in patients with MI (P = 0.004). However, these differences disappeared after the long-term follow-up (up to 31-years). Patients with CF presenting with MI had similar pulmonary function and nutritional status, as well as survival rates as did the control patients without MI. The distinct genetic mutation found in our population may explain in part the favorable results compared with other studies. In addition, it seems that early diagnosis and treatment of MI in patients with CF may be beneficial, subsequently lowering morbidity, and increasing survival.

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.

Endovascular treatment of mycotic aortic aneurysms: a European multicenter study.

PubMed

Sörelius, Karl; Mani, Kevin; Björck, Martin; Sedivy, Petr; Wahlgren, Carl-Magnus; Taylor, Peter; Clough, Rachel E; Lyons, Oliver; Thompson, Matt; Brownrigg, Jack; Ivancev, Krassi; Davis, Meryl; Jenkins, Michael P; Jaffer, Usman; Bown, Matt; Rancic, Zoran; Mayer, Dieter; Brunkwall, Jan; Gawenda, Michael; Kölbel, Tilo; Jean-Baptiste, Elixène; Moll, Frans; Berger, Paul; Liapis, Christos D; Moulakakis, Konstantinos G; Langenskiöld, Marcus; Roos, Håkan; Larzon, Thomas; Pirouzram, Artai; Wanhainen, Anders

2014-12-09

Mycotic aortic aneurysm (MAA) is a rare and life-threatening disease. The aim of this European multicenter collaboration was to study the durability of endovascular aortic repair (EVAR) of MAA, by assessing late infection-related complications and long-term survival. All EVAR treated MAAs, between 1999 and 2013 at 16 European centers, were retrospectively reviewed. One hundred twenty-three patients with 130 MAAs were identified. Mean age was 69 years (range 39-86), 87 (71%) were men, 58 (47%) had immunodeficiency, and 47 (38%) presented with rupture. Anatomic locations were ascending/arch (n=4), descending (n=34), paravisceral (n=15), infrarenal aorta (n=63), and multiple (n=7). Treatments were thoracic EVAR (n=43), fenestrated/branched EVAR (n=9), and infrarenal EVAR (n=71). Antibiotic was administered for mean 30 weeks. Mean follow-up was 35 months (range 1 week to 149 months). Six patients (5%) were converted to open repair during follow-up. Survival was 91% (95% confidence interval, 86% to 96%), 75% (67% to 83%), 55% (44% to 66%), and 41% (28% to 54%) after 1, 12, 60, and 120 months, respectively. Infection-related death occurred in 23 patients (19%), 9 after discontinuation of antibiotic treatment. A Cox regression analysis demonstrated non-Salmonella-positive culture as predictors for late infection-related death. Endovascular treatment of MAA is feasible and for most patients a durable treatment option. Late infections do occur, are often lethal, and warrant long-term antibiotic treatment and follow-up. Patients with non-Salmonella-positive blood cultures were more likely to die from late infection. © 2014 American Heart Association, Inc.

A long-term, phase 2, multicenter, randomized, open-label, comparative safety study of pomaglumetad methionil (LY2140023 monohydrate) versus atypical antipsychotic standard of care in patients with schizophrenia

PubMed Central

2013-01-01

Background We compared the time to discontinuation due to lack of tolerability over 24 weeks in patients suffering from schizophrenia treated with pomaglumetad methionil (LY2140023 monohydrate, the prodrug of metabotropic glutamate 2/3 receptor agonist, LY404039) or standard of care (SOC: olanzapine, risperidone, or aripiprazole). Methods Study HBBR was a multicenter, randomized, open-label study comparing the long-term safety and tolerability of LY2140023 with SOC for schizophrenia. Patients had moderate symptomatology with prominent negative symptoms and evidence of functional impairment. Those who met entry criteria were randomized to open-label treatment with either LY2140023 (target dose: 40 mg twice daily [BID]; n = 130) or SOC (n = 131). Results There was no statistically significant difference between LY2140023 and SOC for time to discontinuation due to lack of tolerability (primary objective; P = .184). The Kaplan-Meier estimates revealed comparable time to event profiles. Only 27% of LY2140023 and 45% of SOC patients completed the 24-week open-label, active treatment phase. Twenty-seven patients (20.8%) in the LY2140023 group and 15 patients (11.5%) in the SOC group discontinued due to lack of efficacy (P = .044). Twenty-three patients (17.7%) in the LY2140023 group and 19 patients (14.5%) in the SOC group discontinued due to adverse events (physician and subject decision combined, P = .505). The incidence of serious adverse events was comparable between groups. LY2140023-treated patients reported significantly more treatment-emergent adverse events of vomiting, agitation, and dyspepsia, while SOC-treated patients reported significantly more akathisia and weight gain. The incidence of treatment-emergent parkinsonism (P = .011) and akathisia (P = .029) was significantly greater in SOC group. Improvement in PANSS total score over the initial 6 to 8 weeks of treatment was similar between groups, but improvement was significantly greater in the SOC group at 24-week endpoint (P = .004). LY2140023 and SOC groups had comparable negative symptom improvement at 24-week endpoint (P = .444). Conclusion These data provide further evidence that the potential antipsychotic LY2140023 monohydrate, with a glutamatergic mechanism of action, may have a unique tolerability profile characterized by a low association with some adverse events such as extrapyramidal symptoms and weight gain that may characterize currently available dopaminergic antipsychotics. Trials registration A Long-term, Phase 2, Multicenter, Randomized, Open-label, Comparative Safety Study of LY2140023 Versus Atypical Antipsychotic Standard of Care in Patients with DSM-IV-TR Schizophrenia ClinicalTrials.gov identifier: NCT00845026. PMID:23694720

Pomaglumetad Methionil (LY2140023 Monohydrate) and Aripiprazole in Patients with Schizophrenia: A Phase 3, Multicenter, Double-Blind Comparison.

PubMed

Adams, David H; Zhang, Lu; Millen, Brian A; Kinon, Bruce J; Gomez, Juan-Carlos

2014-01-01

We tested the hypothesis that long-term treatment with pomaglumetad methionil would demonstrate significantly less weight gain than aripiprazole in patients with schizophrenia. In this 24-week, multicenter, randomized, double-blind, Phase 3 study, 678 schizophrenia patients were randomized to either pomaglumetad methionil (n = 516) or aripiprazole (n = 162). Treatment groups were also compared on efficacy and various safety measures, including serious adverse events (SAEs), discontinuation due to adverse events (AEs), treatment-emergent adverse events (TEAEs), extrapyramidal symptoms (EPS), and suicide-related thoughts and behaviors. The pomaglumetad methionil group showed significantly greater weight loss at Week 24 (Visit 12) compared with the aripiprazole group (-2.8 ± 0.4 versus 0.4 ± 0.6; P < 0.001). However, change in Positive and Negative Syndrome Scale (PANSS) total scores for aripiprazole was significantly greater than for pomaglumetad methionil (-15.58 ± 1.58 versus -12.03 ± 0.99; P = 0.045). The incidences of SAEs (8.2% versus 3.1%; P = 0.032) and discontinuation due to AEs (16.2% versus 8.7%; P = 0.020) were significantly higher for pomaglumetad methionil compared with aripiprazole. No statistically significant differences in the incidence of TEAEs, EPS, or suicidal ideation or behavior were noted between treatment groups. In conclusion, long-term treatment with pomaglumetad methionil resulted in significantly less weight gain than aripiprazole. This trial is registered with ClinicalTrials.gov NCT01328093.

A Multicenter Study on Long-Term Outcomes After Lung Transplantation Comparing Donation After Circulatory Death and Donation After Brain Death.

PubMed

van Suylen, V; Luijk, B; Hoek, R A S; van de Graaf, E A; Verschuuren, E A; Van De Wauwer, C; Bekkers, J A; Meijer, R C A; van der Bij, W; Erasmus, M E

2017-10-01

The implementation of donation after circulatory death category 3 (DCD3) was one of the attempts to reduce the gap between supply and demand of donor lungs. In the Netherlands, the total number of potential lung donors was greatly increased by the availability of DCD3 lungs in addition to the initial standard use of donation after brain death (DBD) lungs. From the three lung transplant centers in the Netherlands, 130 DCD3 recipients were one-to-one nearest neighbor propensity score matched with 130 DBD recipients. The primary end points were primary graft dysfunction (PGD), posttransplant lung function, freedom from chronic lung allograft dysfunction (CLAD), and overall survival. PGD did not differ between the groups. Posttransplant lung function was comparable after bilateral lung transplantation, but seemed worse after DCD3 single lung transplantation. The incidence of CLAD (p = 0.17) nor the freedom from CLAD (p = 0.36) nor the overall survival (p = 0.40) were significantly different between both groups. The presented multicenter results are derived from a national context where one third of the lung transplantations are performed with DCD3 lungs. We conclude that the long-term outcome after lung transplantation with DCD3 donors is similar to that of DBD donors and that DCD3 donation can substantially enlarge the donor pool. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Comparison of the long-term clinical performance of a biodegradable and a titanium fixation system in maxillofacial surgery: A multicenter randomized controlled trial

PubMed Central

van Bakelen, N. B.; Buijs, G. J.; Jansma, J.; de Visscher, J. G. A. M.; Hoppenreijs, Th. J. M.; Bergsma, J. E.; van Minnen, B.; Stegenga, B.; Bos, R. R. M.

2017-01-01

Background Biodegradable fixation systems could reduce or eliminate problems associated with titanium removal of implants in a second operation. Aim The aim of this study was to compare the long-term (i.e. >5 years postoperatively) clinical performance of a titanium and a biodegradable system in oral and maxillofacial surgery. Materials and methods The present multicenter Randomized Controlled Trial (RCT) was performed in four hospitals in the Netherlands. Patients treated with a bilateral sagittal split osteotomy (BSSO) and/or a Le Fort-I osteotomy, and those treated for fractures of the mandible, maxilla, or zygoma were included from December 2006 to July 2009. The patients were randomly assigned to either a titanium (KLS Martin) or a biodegradable group (Inion CPS). Results After >5 years postoperatively, plate removal was performed in 22 of the 134 (16.4%) patients treated with titanium and in 23 of the 87 (26.4%) patients treated with the biodegradable system (P = 0.036, hazard ratio (HR) biodegradable (95% CI) = 2.0 (1.05–3.8), HR titanium = 1). Occlusion, VAS pain scores, and MFIQ showed good and (almost) pain free mandibular function in both groups. Conclusion In conclusion, the performance of the Inion CPS biodegradable system was inferior compared to the KLS Martin titanium system regarding plate/screws removal in the abovementioned surgical procedures. Trial registration http://controlled-trials.com ISRCTN44212338. PMID:28493922

The effect of a therapeutic regimen of Traditional Chinese Medicine rehabilitation for post-stroke cognitive impairment: study protocol for a randomized controlled trial.

PubMed

Huang, Jia; Lin, Zhengkun; Wang, Qin; Liu, Feiwen; Liu, Jiao; Fang, Yunhua; Chen, Shanjia; Zhou, Xiaoxuan; Hong, Wenjun; Wu, Jinsong; Madrigal-Mora, Natalia; Zheng, Guohua; Yang, Shanli; Tao, Jing; Chen, Lidian

2015-06-16

Post-stroke cognitive impairment (PSCI) lessens quality of life, restricts the rehabilitation of stroke, and increases the social and economic burden stroke imposes on patients and their families. Therefore effective treatment is of paramount importance. However, the treatment of PSCI is very limited. The primary aim of this protocol is to propose a lower cost and more effective therapy, and to confirm the long-term effectiveness of a therapeutic regimen of Traditional Chinese Medicine (TCM) rehabilitation for PSCI. A prospective, multicenter, large sample, randomized controlled trial will be conducted. A total of 416 eligible patients will be recruited from seven inpatient and outpatient stroke rehabilitation units and randomly allocated into a therapeutic regimen of TCM rehabilitation group or cognitive training (CT) control group. The intervention period of both groups will last 12 weeks (30 minutes per day, five days per week). Primary and secondary outcomes will be measured at baseline, 12 weeks (at the end of the intervention), and 36 weeks (after the 24-week follow-up period). This protocol presents an objective design of a multicenter, large sample, randomized controlled trial that aims to put forward a lower cost and more effective therapy, and confirm the long-term effectiveness of a therapeutic regimen of TCM rehabilitation for PSCI through subjective and objective assessments, as well as highlight its economic advantages. This trial was registered with the Chinese Clinical Trial Registry (identifier: ChiCTR-TRC-14004872 ) on 23 June 2014.

Long-term follow-up of patients with retinitis pigmentosa (RP) receiving intraocular ciliary neurotrophic factor implants

PubMed Central

Birch, David G.; Bennett, Lea D.; Duncan, Jacque L.; Weleber, Richard G.; Pennesi, Mark E.

2016-01-01

Purpose To evaluate the long-term efficacy of ciliary neurotrophic factor delivered via an intraocular encapsulated cell implant for the treatment of retinitis pigmentosa (RP). Design Long-term follow up of a multicenter, sham-controlled study. Methods Thirty-six patients at three CNTF4 sites were randomly assigned to receive a high- or low- dose implant in one eye and sham surgery in the fellow eye. The primary endpoint (change in visual field sensitivity at 12 months) has been reported previously.1 Here we report long-term visual acuity, visual field and optical coherence tomography (OCT) outcomes in 24 patients either retaining or explanting the device at 24 months relative to sham-treated eyes. Results Eyes retaining the implant showed significantly greater visual field loss from baseline than either explanted eyes or sham eyes through 42 months. By 60 months and continuing through 96 months, visual field loss was comparable among sham-treated eyes, eyes retaining the implant and explanted eyes, as was visual acuity and OCT macular volume. Conclusions Over the short term, ciliary neurotrophic factor released continuously from an intra-vitreal implant lead to loss of total visual field sensitivity that was greater than the natural progression in the sham-treated eye. This additional loss of sensitivity related to the active implant was reversible when the implant was removed. Over the long term (60 – 96 months), there was no evidence of efficacy for visual acuity, visual field sensitivity or OCT measures of retinal structure. PMID:27457255

Determinants of 1-year survival in critically ill acute leukemia patients: a GRRR-OH study.

PubMed

Tavares, Márcio; Lemiale, Virginie; Mokart, Djamel; Pène, Frédéric; Lengliné, Etienne; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Lebert, Christine; Perez, Pierre; Meert, Anne-Pascale; Benoit, Dominique; Darmon, Michael; Azoulay, Elie

2018-06-01

Acute leukemia (AL) is the most common hematological malignancy requiring intensive care unit (ICU) management. Data on long-term survival are limited. This is a post hoc analysis of the prospective multicenter data from France and Belgium: A Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique [A Research Group on Acute Respiratory Failure in Onco-Hematological Patients (French)] Study, to identify determinants of 1-year survival in critically ill AL patients. A total of 278 patients were admitted in the 17 participating ICUs. Median age was 58 years and 70% had newly diagnosed leukemia. ICU mortality rate was 28.6 and 39.6% of the patients alive at 1 year. Admission for intensive monitoring was independently associated with better 1-year survival by multivariate analysis. Conversely, relapsed/refractory disease, secondary leukemia, mechanical ventilation and renal replacement therapy were independently associated with 1-year mortality. This study confirms the impact of organ dysfunction on long-term survival in ICU patients with AL. Follow-up studies to assess respiratory and renal recovery are warranted.

Inverse Relationship of Blood Pressure to Long-Term Outcomes and Benefit of Cardiac Resynchronization Therapy in Patients With Mild Heart Failure: A Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy Long-Term Follow-Up Substudy.

PubMed

Biton, Yitschak; Moss, Arthur J; Kutyifa, Valentina; Mathias, Andrew; Sherazi, Saadia; Zareba, Wojciech; McNitt, Scott; Polonsky, Bronislava; Barsheshet, Alon; Brown, Mary W; Goldenberg, Ilan

2015-09-01

Previous studies have shown that low blood pressure is associated with increased mortality and heart failure (HF) in patients with left ventricular dysfunction. Cardiac resynchronization therapy (CRT) was shown to increase systolic blood pressure (SBP). Therefore, we hypothesized that treatment with CRT would provide incremental benefit in patients with lower SBP values. The independent contribution of SBP to outcome was analyzed in 1267 patients with left bundle brunch block enrolled in Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT). SBP was assessed as continuous measures and further categorized into approximate quintiles. The risk of long-term HF or death and CRT with defibrillator versus implantable cardioverter defibrillator benefit was assessed in multivariate Cox proportional hazards regression models. Multivariate analysis showed that in the implantable cardioverter defibrillator arm, each 10-mm Hg decrement of SBP was independently associated with a significant 21% (P<0.001) increased risk for HF or death, and patients with lower quintile SBP (<110 mm Hg) experienced a corresponding >2-fold risk-increase. CRT with defibrillator provided the greatest HF or mortality risk reduction in patients with SBP<110 mm Hg hazard ratio of 0.34, P<0.001, when compared with hazard ratio of 0.52, P<0.001, in those with 110>SBP≥136 mm Hg and hazard ratio of 0.94, P=0.808, with SBP>136 mm Hg (P for trend=0.001). In patients with mild HF, prolonged QRS, and left bundle brunch block, low SBP is related to higher risk of mortality or HF with implantable cardioverter defibrillator therapy alone. Treatment with CRT is associated with incremental clinical benefits in patients with lower baseline SBP values. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271. © 2015 American Heart Association, Inc.

Long-term outcome and prognostic factors of juvenile dermatomyositis: a multinational, multicenter study of 490 patients.

PubMed

Ravelli, Angelo; Trail, Lucia; Ferrari, Cristina; Ruperto, Nicolino; Pistorio, Angela; Pilkington, Clarissa; Maillard, Susan; Oliveira, Sheila K; Sztajnbok, Flavio; Cuttica, Ruben; Beltramelli, Matilde; Corona, Fabrizia; Katsicas, Maria Martha; Russo, Ricardo; Ferriani, Virginia; Burgos-Vargas, Ruben; Magni-Manzoni, Silvia; Solis-Valleoj, Eunice; Bandeira, Marcia; Zulian, Francesco; Baca, Vicente; Cortis, Elisabetta; Falcini, Fernanda; Alessio, Maria; Alpigiani, Maria Giannina; Gerloni, Valeria; Saad-Magalhaes, Claudia; Podda, Rosanna; Silva, Clovis A; Lepore, Loredana; Felici, Enrico; Rossi, Federica; Sala, Elena; Martini, Alberto

2010-01-15

To investigate the long-term outcome and prognostic factors of juvenile dermatomyositis (DM) through a multinational, multicenter study. Patients consisted of inception cohorts seen between 1980 and 2004 in 27 centers in Europe and Latin America. Predictor variables were sex, continent, ethnicity, onset year, onset age, onset type, onset manifestations, course type, disease duration, and active disease duration. Outcomes were muscle strength/endurance, continued disease activity, cumulative damage, muscle damage, cutaneous damage, calcinosis, lipodystrophy, physical function, and health-related quality of life (HRQOL). A total of 490 patients with a mean disease duration of 7.7 years were included. At the cross-sectional visit, 41.2-52.8% of patients, depending on the instrument used, had reduced muscle strength/endurance, but less than 10% had severe impairment. Persistently active disease was recorded in 41.2-60.5% of the patients, depending on the activity measure used. Sixty-nine percent of the patients had cumulative damage. The frequency of calcinosis and lipodystrophy was 23.6% and 9.7%, respectively. A total of 40.7% of the patients had decreased functional ability, but only 6.5% had major impairment. Only a small fraction had decreased HRQOL. A chronic course, either polycyclic or continuous, consistently predicted a poorer outcome. Mortality rate was 3.1%. This study confirms the marked improvement in functional outcome of juvenile DM when compared with earlier literature. However, many patients had continued disease activity and cumulative damage at followup. A chronic course was the strongest predictor of poor prognosis. These findings highlight the need for treatment strategies that enable a better control of disease activity over time and the reduction of nonreversible damage.

Acute postoperative seizures and long-term seizure outcome after surgery for hippocampal sclerosis.

PubMed

Di Gennaro, Giancarlo; Casciato, Sara; Quarato, Pier Paolo; Mascia, Addolorata; D'Aniello, Alfredo; Grammaldo, Liliana G; De Risi, Marco; Meldolesi, Giulio N; Romigi, Andrea; Esposito, Vincenzo; Picardi, Angelo

2015-01-01

To assess the incidence and the prognostic value of acute postoperative seizures (APOS) in patients surgically treated for drug-resistant temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS). We studied 139 consecutive patients with TLE-HS who underwent epilepsy surgery and were followed up for at least 5 years (mean duration of follow-up 9.1 years, range 5-15). Medical charts were reviewed to identify APOS, defined as ictal events with the exception of auras occurring within the first 7 days after surgery. Seizure outcome was determined at annual intervals. Patients who were in Engel Class Ia at the last contact were classified as having a favorable outcome. Seizure outcome was favorable in 99 patients (71%). Six patients (4%) experienced APOS and in all cases their clinical manifestations were similar to the habitual preoperative seizures. All patients with APOS had unfavorable long-term outcome, as compared with 35 (26%) of 133 in whom APOS did not occur (p<0.001). Our study suggests that APOS, despite being relatively uncommon in patients undergoing resective surgery for TLE-HS, are associated with a worse long-term seizure outcome. Given some study limitations, our findings should be regarded as preliminary and need confirmation from future larger, prospective, multicenter studies. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Long-term efficacy and safety of sacral nerve stimulation for fecal incontinence.

PubMed

Mellgren, Anders; Wexner, Steven D; Coller, John A; Devroede, Ghislain; Lerew, Darin R; Madoff, Robert D; Hull, Tracy

2011-09-01

Sacral nerve stimulation is effective in the treatment of urinary incontinence and is currently under Food and Drug Administration review in the United States for fecal incontinence. Previous reports have focused primarily on short-term results of sacral nerve stimulation for fecal incontinence. The present study reports the long-term effectiveness and safety of sacral nerve stimulation for fecal incontinence in a large prospective multicenter study. Patients with fecal incontinent episodes more than twice per week were offered participation in this multicentered prospective trial. Patients showing ≥ 50% improvement during test stimulation were offered chronic implantation of the InterStim Therapy system (Medtronic; Minneapolis, MN). The aims of the current report were to provide 3-year follow-up data on patients from that study who underwent sacral nerve stimulation and were monitored under the rigors of an Food and Drug Administration-approved investigational protocol. One hundred thirty-three patients underwent test stimulation with a 90% success rate, of whom 120 (110 females) with a mean age of 60.5 years and a mean duration of fecal incontinence of 7 years received chronic implantation. Mean length of follow-up was 3.1 (range, 0.2-6.1) years, with 83 patients completing all or part of the 3-year follow-up assessment. At 3 years follow-up, 86% of patients (P < .0001) reported ≥ 50% reduction in the number of incontinent episodes per week compared with baseline and the number of incontinent episodes per week decreased from a mean of 9.4 at baseline to 1.7. Perfect continence was achieved in 40% of subjects. The therapy also improved the fecal incontinence severity index. Sacral nerve stimulation had a positive impact on the quality of life, as evidenced by significant improvements in all 4 scales of the Fecal Incontinence Quality of Life instrument at 12, 24, and 36 months of follow-up. The most common device- or therapy-related adverse events through the mean 36 months of follow-up included implant site pain (28%), paresthesia (15%), change in the sensation of stimulation (12%), and infection (10%). There were no reported unanticipated adverse device effects associated with sacral nerve stimulation therapy. Sacral nerve stimulation using InterStim Therapy is a safe and effective treatment for patients with fecal incontinence. These data support long-term safety and effectiveness to 36 months.

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.

Changes in Plasma ACTH Levels and Corticotroph Tumor Size in Patients With Cushing's Disease During Long-term Treatment With the Glucocorticoid Receptor Antagonist Mifepristone

PubMed Central

Findling, James W.; Koch, Christian A.; Schlaffer, Sven-Martin; Buchfelder, Michael; Gross, Coleman

2014-01-01

Context: Pituitary effects of long-term therapy with mifepristone, a glucocorticoid receptor antagonist, in Cushing's disease (CD) patients are not well understood. Objective: Our objective was to report changes in ACTH and pituitary magnetic resonance imaging (MRI) findings during long-term use of mifepristone in CD patients. Design and Setting: The Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing's Syndrome (SEISMIC) was a 24-week, open-label study of mifepristone, and its long-term extension (LTE) is a multicenter U.S. study. Patients: Forty-three CD patients (mean age 45.3 years) were enrolled in SEISMIC with 27 continuing into the LTE study. Interventions: Mifepristone (300–1200 mg) was administered once daily. Main Outcome Measures: ACTH and pituitary MRI were assessed at baseline and at regular intervals during treatment. Results: A ≥2-fold increase in ACTH was observed in 72% of patients treated for a median duration of 11.3 months. The mean peak increase in ACTH was 2.76 ± 1.65-fold during SEISMIC, and mean ACTH concentrations remained stable during the LTE. ACTH was directly correlated with mifepristone dose and declined to near baseline levels after mifepristone discontinuation. Tumor regressed in 2 patients and progressed in 3 patients with macroadenomas. An additional microadenoma was identified after 25 months of treatment after a baseline tumor-negative MRI. Conclusions: In the largest prospective study to date, long-term mifepristone treatment increased ACTH in approximately two-thirds of patients with CD. ACTH elevations were observed within the first few weeks of treatment, were dose-dependent, and generally remained stable over time. Corticotroph tumor progression and regression may occur over time, but patients may have significant increases in ACTH levels without evidence of tumor growth. PMID:25013998

A Multicenter, Open-Label Trial to Evaluate the Quality of Life in Adults with ADHD Treated with Long-Acting Methylphenidate (OROS MPH): Concerta Quality of Life (CONQoL) Study

ERIC Educational Resources Information Center

Mattos, Paulo; Rodrigues Louza, Mario; Fernandes Palmini, Andre Luis; de Oliveira, Irismar Reis; Lopes Rocha, Fabio

2013-01-01

The available literature provides few studies on the effectiveness of methylphenidate in improving quality of life in individuals with ADHD. Objective: To assess the effectiveness of Methyphenidate OROS formulation (OROS MPH) through QoL in adults with ADHD. Method: A 12-week, multicenter, open-label trial involving 60 patients was used. The…

The Effect of Three or Six Years of Denosumab Exposure in Women With Postmenopausal Osteoporosis: Results From the FREEDOM Extension

PubMed Central

Chapurlat, Roland; Brandi, Maria-Luisa; Brown, Jacques P.; Czerwiński, Edward; Krieg, Marc-Antoine; Mellström, Dan; Radominski, Sebastião C.; Reginster, Jean-Yves; Resch, Heinrich; Ivorra, Jose A. Román; Roux, Christian; Vittinghoff, Eric; Daizadeh, Nadia S.; Wang, Andrea; Bradley, Michelle N.; Franchimont, Nathalie; Geller, Michelle L.; Wagman, Rachel B.; Cummings, Steven R.; Papapoulos, Socrates

2013-01-01

Context: The Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) extension is evaluating the long-term efficacy and safety of denosumab for up to 10 years. Objective: The objective of the study was to report results from the first 3 years of the extension, representing up to 6 years of denosumab exposure. Design, Setting, and Participants: This was a multicenter, international, open-label study of 4550 women. Intervention: Women from the FREEDOM denosumab group received 3 more years of denosumab for a total of 6 years (long-term) and women from the FREEDOM placebo group received 3 years of denosumab (crossover). Main Outcome Measures: Bone turnover markers (BTMs), bone mineral density (BMD), fracture, and safety data are reported. Results: Reductions in BTMs were maintained (long-term) or achieved rapidly (crossover) after denosumab administration. In the long-term group, BMD further increased for cumulative 6-year gains of 15.2% (lumbar spine) and 7.5% (total hip). During the first 3 years of denosumab treatment, the crossover group had significant gains in lumbar spine (9.4%) and total hip (4.8%) BMD, similar to the long-term group during the 3-year FREEDOM trial. In the long-term group, fracture incidences remained low and below the rates projected for a virtual placebo cohort. In the crossover group, 3-year incidences of new vertebral and nonvertebral fractures were similar to those of the FREEDOM denosumab group. Incidence rates of adverse events did not increase over time. Six participants had events of osteonecrosis of the jaw confirmed by adjudication. One participant had a fracture adjudicated as consistent with atypical femoral fracture. Conclusion: Denosumab treatment for 6 years remained well tolerated, maintained reduced bone turnover, and continued to increase BMD. Fracture incidence remained low. PMID:23979955

Preeclampsia and Long-term Renal Function in Women Who Underwent Kidney Transplantation.

PubMed

Vannevel, Valerie; Claes, Kathleen; Baud, David; Vial, Yvan; Golshayan, Delaviz; Yoon, Eugene W; Hodges, Ryan; Le Nepveu, Anne; Kerr, Peter G; Kennedy, Claire; Higgins, Mary; Resch, Elisabeth; Klaritsch, Philipp; Van Mieghem, Tim

2018-01-01

Preeclampsia often complicates pregnancies after maternal kidney transplantation. We aimed to assess whether preeclampsia is associated with kidney function decline either during the pregnancy or in the long term. We performed an international multicenter retrospective cohort study. Renal function at conception, pregnancy outcomes, and short- and long-term graft outcomes were collected for women who were pregnant after renal transplantation and had transplant and obstetric care at the participating centers. In women who had multiple pregnancies during the study period, only the last pregnancy was included. Univariate and multivariable analyses were performed. We retrieved pregnancy outcomes and long-term renal outcomes for 52 women. Chronic hypertension was present at baseline in 27%. Mean estimated glomerular filtration rate (GFR) at start of pregnancy was 52.4±17.5 mL/min/1.73 m. Mean estimated GFR at delivery was 47.6±21.6 mL/min/1.73 m, which was significantly lower than at conception (P=.03). Twenty women (38%) developed preeclampsia. In multivariable analysis, women who developed preeclampsia had a 10.7-mL/min/1.73 m higher drop in estimated GFR between conception and delivery than women who did not develop preeclampsia (P=.02). Long-term estimated GFR follow-up was obtained at a median of 5.8 years (range 1.3-27.5 years). Mean estimated GFR at last follow-up was 38±23 mL/kg/1.73 m. Seventeen women (33%) experienced graft loss over the follow-up period. Incidence of graft loss was similar in women with and without preeclampsia in their last pregnancy (30% and 34%, respectively; P=.99). In multivariable analysis, the decrease in estimated GFR between conception and last follow-up was similar in women who experienced preeclampsia during pregnancy and those who did not (difference -2.69 mL/min/1.73 m, P=.65). Preeclampsia commonly complicates pregnancies after renal transplantation but is not associated with long-term renal dysfunction or graft loss.

The Association Between Nutritional Adequacy and Long-Term Outcomes in Critically Ill Patients Requiring Prolonged Mechanical Ventilation: A Multicenter Cohort Study.

PubMed

Wei, Xuejiao; Day, Andrew G; Ouellette-Kuntz, Hélène; Heyland, Daren K

2015-08-01

To examine the association between short-term nutritional adequacy received while in the ICU and long-term outcomes including 6-month survival and health-related quality of life in critically ill patients requiring prolonged mechanical ventilation. Retrospective analysis of data prospectively collected in the context of a multicenter randomized controlled trial. An international sample of ICUs. Adult patients who were mechanically ventilated for more than 8 days in the ICU. None. Nutritional adequacy was obtained from the average proportion of prescribed calories received over the amount prescribed during the first 8 days. Survival status and health-related quality of life as assessed using the Short-Form 36 v2 were obtained at 3- and 6 months post ICU admission. Of the 1,223 patients enrolled in the randomized controlled trial, 475 met the inclusion criteria for this study. At 6-month follow-up, 302 of the 475 patients (64%) were alive. Survival time in those who received low nutritional adequacy was significantly shorter than those who received high nutritional adequacy while adjusting for important covariates (adjusted hazard ratio, 1.7; 95% CI, 1.1-2.6). At 3-month follow-up, a 25% increase in nutritional adequacy was associated with improvements in Physical Functioning and Role Physical of 7.3 (p = 0.02) and 8.3 (p = 0.004) points, respectively. At 6-month follow-up, adjusted increases in Physical Functioning and Role Physical scores for every 25% increase in nutrition adequacy became smaller and were no longer statistically significant (adjusted estimate for Physical Functioning = 4.2, p = 0.14; for Role Physical = 3.2, p = 0.25). Greater amounts of nutritional intake received during the first week in the ICU were associated with longer survival time and faster physical recovery to 3 months but not 6 months post ICU discharge in critically ill patients requiring prolonged mechanical ventilation. Current recommendations to underfeed critically ill patients may cause harm in some long-stay patients.

[Gender-specific differences of the early postoperative and oncosurgical long-term outcome in rectal cancer-data obtained in a prospective multicenter observational study].

PubMed

Katzenstein, J; Steinert, R; Ptok, H; Otto, R; Gastinger, I; Lippert, H; Meyer, F

2018-04-11

Gender-specific aspects have been increasingly considered in clinical medicine, also in oncological surgery. To analyze gender-specific differences of early postoperative and oncological outcomes after rectal cancer resection based on data obtained in a prospective multicenter observational study. As part of the multicenter prospective observational study "Quality assurance in primary rectal cancer", data on tumor site, exogenic and endogenic risk factors, neoadjuvant treatment, surgical procedures, tumor stage, intraoperative and postoperative complications of patients with the histological diagnosis of rectal cancer were registered. Data from the years 2005-2006 and 2010-2011 were investigated with respect to gender-specific differences of postoperative morbidity, hospital mortality, local recurrency rate, disease-free and overall survival by univariable and multivariable analyses. Overall, data from 10,657 patients were evaluated: 60.9% of the patients were male, who were significantly younger (p < 0.001). Men had a significantly higher rate of alcohol (p < 0.001) and nicotine abuse (p < 0.001) as well as a trend to a higher body mass index (BMI) compared with women. Although, there was no significant difference in the distribution of various tumor stages comparing men and women, neoadjuvant radiochemotherapy was used significantly more often in male patients (p < 0.001). In addition, male patients underwent an abdominoperineal rectum exstirpation more often, whereas creation of an enterostoma and Hartmann's procedure were more frequently used in women (p < 0.001 each). Multivariate analysis revealed that male patients developed a higher overall morbidity (odds ratio, OR: 1.5; p < 0.001) during both study periods and from 2010-2011 a higher hospital mortality (OR: 1.8; p < 0.001). After a median follow-up period of 36 months, gender did not have a significant impact on overall survival, disease-free survival or on the local tumor recurrency. The 5‑year overall survival was 60.5%, disease-free survival 63.8% and local recurrency rate was 5%. Independent of other variables, gender differences were found with respect to early postoperative outcome but not to oncological long-term results after surgery of rectal cancer.

Long-term safety and tolerability of once-daily mesalamine granules in the maintenance of remission of ulcerative colitis.

PubMed

Lichtenstein, Gary R; Barrett, Andrew C; Bortey, Enoch; Paterson, Craig; Forbes, William P

2014-08-01

Ulcerative colitis (UC), a chronic, relapsing, and remitting inflammatory bowel disease, requires long-term treatment to maintain remission. In this study, the long-term safety and tolerability of mesalamine granules (MG) therapy was evaluated in the maintenance of UC remission. Previous prospective studies evaluating different oral mesalamine formulations have not exceeded a duration of 14 months. A phase 3, multicenter, 24-month, open-label extension study evaluating MG 1.5 g once daily in patients who achieved previous remission from mild to moderate UC was performed. Eligible patients had successfully participated in 1 of 2 previous 6-month double-blind, placebo-controlled trials or were new patients in remission. Safety assessments included monitoring of adverse events (AEs) and clinical laboratory tests. Risk of UC recurrence was assessed by the occurrence of UC-related AEs. Of the 393 patients enrolled (280 from the double-blind studies; 113 new patients), 388 were included in the safety population. The most common AEs included nasopharyngitis (13.9%), headache (11.6%), and diarrhea (10.8%), and the incidence of these events was generally lower in the MG group versus historical placebo group from the double-blind studies. Pancreatic, renal, and hepatic AEs occurred in 23 patients (5.9%). The risk of UC-related AEs was low and was maintained for 24 months during the open-label study. Once-daily MG has a favorable safety profile for the maintenance of remission for up to 2 years in patients with UC.

Long-Term Efficacy and Safety of Cyclosporine in a Cohort of Steroid-Refractory Acute Severe Ulcerative Colitis Patients from the ENEIDA Registry (1989-2013): A Nationwide Multicenter Study.

PubMed

Ordás, I; Domènech, E; Mañosa, M; García-Sánchez, V; Iglesias-Flores, E; Peñalva, M; Cañas-Ventura, A; Merino, O; Fernández-Bañares, F; Gomollón, F; Vera, M; Gutiérrez, A; Garcia-Planella, E; Chaparro, M; Aguas, M; Gento, E; Muñoz, F; Aguirresarobe, M; Muñoz, C; Fernández, L; Calvet, X; Jiménez, C E; Montoro, M A; Mir, A; De Castro, M L; García-Sepulcre, M F; Bermejo, F; Panés, J; Esteve, M

2017-11-01

To determine the efficacy and safety of cyclosporine (CyA) in a large national registry-based population of patients with steroid-refractory (SR) acute severe ulcerative colitis (ASUC) and to establish predictors of efficacy and adverse events. Multicenter study of SR-ASUC treated with CyA, based on data from the ENEIDA registry. SR-ASUC patients treated with infliximab (IFX) or sequential rescue therapy (CyA-IFX or IFX-CyA) were used as comparators. Of 740 SR-ASUC patients, 377 received CyA, 131 IFX and 63 sequential rescue therapy. The cumulative colectomy rate was higher in the CyA (24.1%) and sequential therapy (32.7%) than in the IFX group (14.5%; P=0.01) at 3 months and 5 years. There were no differences in early and late colectomy between CyA and IFX in patients treated after 2005. 62% of patients receiving CyA remained colectomy-free in the long term (median 71 months). There were no differences in mortality between CyA (2.4%), IFX (1.5%) and sequential therapy (0%; P=0.771). The proportion of patients with serious adverse events (SAEs) was lower in CyA (15.4%) than in IFX treated patients (26.5%) or sequential therapy (33.4%; P<0.001). This difference in favor of CyA was maintained when only patients treated after 2005 were analyzed. Treatment with CyA showed a lower rate of SAE and a similar efficacy to that of IFX thereby supporting the use of either CyA or IFX in SR-ASUC. In addition, the risk-benefit of sequential CyA-IFX for CyA non-responders is acceptable.

Processes to manage analyses and publications in a phase III multicenter randomized clinical trial

PubMed Central

2014-01-01

Background The timely publication of findings in peer-reviewed journals is a primary goal of clinical research. In clinical trials, the processes leading to publication can be complex from choice and prioritization of analytic topics through to journal submission and revisions. As little literature exists on the publication process for multicenter trials, we describe the development, implementation, and effectiveness of such a process in a multicenter trial. Methods The Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial included a data coordinating center (DCC) and clinical centers that recruited and followed more than 1,000 patients. Publication guidelines were approved by the steering committee, and the publications committee monitored the publication process from selection of topics to publication. Results A total of 73 manuscripts were published in 23 peer-reviewed journals. When manuscripts were closely tracked, the median time for analyses and drafting of manuscripts was 8 months. The median time for data analyses was 5 months and the median time for manuscript drafting was 3 months. The median time for publications committee review, submission, and journal acceptance was 7 months, and the median time from analytic start to journal acceptance was 18 months. Conclusions Effective publication guidelines must be comprehensive, implemented early in a trial, and require active management by study investigators. Successful collaboration, such as in the HALT-C trial, can serve as a model for others involved in multidisciplinary and multicenter research programs. Trial registration The HALT-C Trial was registered with clinicaltrials.gov (NCT00006164). PMID:24886378

Long-term effects of islet transplantation.

PubMed

Holmes-Walker, D Jane; Kay, Thomas W H

2016-10-01

Islet transplantation has made great progress in recent years. This is a remarkable technical feat but raises the question of what the long-term benefits and risks are for type I diabetes recipients. Graft survival continues to improve, and recent multicenter studies show that islet transplantation is particularly effective to prevent hypoglycemic events even in those who do not become insulin-independent and to achieve excellent glycemic control. Concerns include histocompatability leucocyte antigen (HLA) sensitization and other risks including from immunosuppression that islet transplantation shares with other forms of allotransplantation. Reversal of hypoglycemia unawareness and protection from severe hypoglycemia events are two of the main benefits of islet transplantation and they persist for the duration of graft function. Islet transplantation compares favorably with other therapies for those with hypoglycemia unawareness, although new technologies have not been tested head-to-head with transplantation. HLA sensitization increases with time after transplantation especially if immunosuppression is ceased and is a risk for those who may require future transplantation as well as being associated with loss of graft function.

The PER (Preoperative Esophagectomy Risk) Score: A Simple Risk Score to Predict Short-Term and Long-Term Outcome in Patients with Surgically Treated Esophageal Cancer.

PubMed

Reeh, Matthias; Metze, Johannes; Uzunoglu, Faik G; Nentwich, Michael; Ghadban, Tarik; Wellner, Ullrich; Bockhorn, Maximilian; Kluge, Stefan; Izbicki, Jakob R; Vashist, Yogesh K

2016-02-01

Esophageal resection in patients with esophageal cancer (EC) is still associated with high mortality and morbidity rates. We aimed to develop a simple preoperative risk score for the prediction of short-term and long-term outcomes for patients with EC treated by esophageal resection. In total, 498 patients suffering from esophageal carcinoma, who underwent esophageal resection, were included in this retrospective cohort study. Three preoperative esophagectomy risk (PER) groups were defined based on preoperative functional evaluation of different organ systems by validated tools (revised cardiac risk index, model for end-stage liver disease score, and pulmonary function test). Clinicopathological parameters, morbidity, and mortality as well as disease-free survival (DFS) and overall survival (OS) were correlated to the PER score. The PER score significantly predicted the short-term outcome of patients with EC who underwent esophageal resection. PER 2 and PER 3 patients had at least double the risk of morbidity and mortality compared to PER 1 patients. Furthermore, a higher PER score was associated with shorter DFS (P < 0.001) and OS (P < 0.001). The PER score was identified as an independent predictor of tumor recurrence (hazard ratio [HR] 2.1; P < 0.001) and OS (HR 2.2; P < 0.001). The PER score allows preoperative objective allocation of patients with EC into different risk categories for morbidity, mortality, and long-term outcomes. Thus, multicenter studies are needed for independent validation of the PER score.

Multicenter Analysis of Immune Biomarkers and Heart Transplant Outcomes: Results of the Clinical Trials in Organ Transplantation-05 Study.

PubMed

Starling, R C; Stehlik, J; Baran, D A; Armstrong, B; Stone, J R; Ikle, D; Morrison, Y; Bridges, N D; Putheti, P; Strom, T B; Bhasin, M; Guleria, I; Chandraker, A; Sayegh, M; Daly, K P; Briscoe, D M; Heeger, P S

2016-01-01

Identification of biomarkers that assess posttransplant risk is needed to improve long-term outcomes following heart transplantation. The Clinical Trials in Organ Transplantation (CTOT)-05 protocol was an observational, multicenter, cohort study of 200 heart transplant recipients followed for the first posttransplant year. The primary endpoint was a composite of death, graft loss/retransplantation, biopsy-proven acute rejection (BPAR), and cardiac allograft vasculopathy (CAV) as defined by intravascular ultrasound (IVUS). We serially measured anti-HLA- and auto-antibodies, angiogenic proteins, peripheral blood allo-reactivity, and peripheral blood gene expression patterns. We correlated assay results and clinical characteristics with the composite endpoint and its components. The composite endpoint was associated with older donor allografts (p < 0.03) and with recipient anti-HLA antibody (p < 0.04). Recipient CMV-negativity (regardless of donor status) was associated with BPAR (p < 0.001), and increases in plasma vascular endothelial growth factor-C (OR 20; 95%CI:1.9-218) combined with decreases in endothelin-1 (OR 0.14; 95%CI:0.02-0.97) associated with CAV. The remaining biomarkers showed no relationships with the study endpoints. While suboptimal endpoint definitions and lower than anticipated event rates were identified as potential study limitations, the results of this multicenter study do not yet support routine use of the selected assays as noninvasive approaches to detect BPAR and/or CAV following heart transplantation. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Effectiveness of Robot Paro in Intramural Psychogeriatric Care: A Multicenter Quasi-Experimental Study.

PubMed

Bemelmans, Roger; Gelderblom, Gert Jan; Jonker, Pieter; de Witte, Luc

2015-11-01

Together with care professionals, specific psychogeriatric care applications were developed for the seal robot Paro. This study aims to evaluate the outcomes of the developed Paro interventions, applying the robot in psychogeriatric care. A multicenter quasi-experimental time series ABAB study (n = 91) with within-subject comparison was conducted to assess both the short-term effects of the Paro interventions for therapeutic applications, and the facilitation of daily care activities by care providers. Small-scale care units (8-10 residents each), spread over 6 different locations, in 3 Dutch care institutions for intramural psychogeriatric care. A total of 91 patients with dementia, in all stages of dementia. Two user-centered intervention types were applied, one for therapeutic purposes and one for the facilitation of daily care activities. Effectiveness was measured with a goal attainment scale (IPPA) and a mood scale (Coop/Wonca), by means of a registration form. A total of 106 user-specific interventions were defined for 91 participants; 71 participants completed the study, 14 were men and 57 were women. All interventions combined show a significant effect (P < .001). Paro should be seen as a tool for care staff and not as a replacement of care. Successful implementation of Paro in daily intramural psychogeriatric care practice can increase the quality of care and the quality of life for the elderly. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Management of portal hypertension in children

PubMed Central

Gugig, Roberto; Rosenthal, Philip

2012-01-01

Portal hypertension can be caused by a wide variety of conditions. It frequently presents with bleeding from esophageal varices. The approach to acute variceal hemorrhage in children is a stepwise progression from least invasive to most invasive. Management of acute variceal bleeding is straightforward. But data on primary prophylaxis and long term management prevention of recurrent variceal bleeding in children is scarce, therefore prospective multicenter trials are needed to establish best practices. PMID:22468080

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.

Peripheral nerve field stimulation (PNFS) in chronic low back pain: a prospective multicenter study.

PubMed

Kloimstein, Herwig; Likar, Rudolf; Kern, Michael; Neuhold, Josef; Cada, Miroslav; Loinig, Nadja; Ilias, Wilfried; Freundl, Brigitta; Binder, Heinrich; Wolf, Andreas; Dorn, Christian; Mozes-Balla, Eva Maria; Stein, Rolf; Lappe, Ivo; Sator-Katzenschlager, Sabine

2014-02-01

The goal of this study was to evaluate the long-term efficacy and safety of peripheral nerve field stimulation (PNFS) for chronic low back pain (cLBP). In this prospective, multicenter observational study, 118 patients were admitted to 11 centers throughout Austria and Switzerland. After a screening visit, all patients underwent a trial stimulation period of at least seven days before implantation of the permanent system. Leads were placed in the subcutaneous tissues of the lower back directly in the region of greatest pain. One hundred five patients were implanted with a permanent stimulating system. Patients' evaluation of pain and functional levels were completed before implantation and one, three, and six months after implantation. Adverse events, medication usage, and coverage of the painful area and predictive value of transcutaneous electrical nerve stimulation (TENS) were monitored. All pain and quality-of-life measures showed statistically significant improvement during the treatment period. These included the average pain visual analog scale, the Oswestry Disability Questionnaire, the Becks Depression Inventory, and the Short Form-12 item Health survey. Additionally, medication usage with opioids, nonsteroidal anti-inflammatory drugs, and anti-convulsants showed a highly significant reduction. Complications requiring surgical intervention were reported in 9.6% of the patients. The degree of coverage of painful areas seems to be an important criterion for efficacy of PNFS, whereas TENS is presumably no predictor. This prospective, multicenter study confirms that PNFS is an effective therapy for the management of cLBP. Significant improvements in many aspects of the pain condition were measured, and complications were minimal. © 2013 International Neuromodulation Society.

Effects of heat and moisture exchangers on tracheal mucociliary clearance in laryngectomized patients: a multi-center case-control study.

PubMed

van den Boer, C; Muller, S H; van der Noort, V; Olmos, R A Valdés; Minni, A; Parrilla, C; Hilgers, F J M; van den Brekel, M W M; van der Baan, S

2015-11-01

After total laryngectomy, inspired air is no longer optimally conditioned by the upper airways. Impaired mucociliary clearance and histological changes of respiratory epithelium, such as loss of ciliated cells, have been described in laryngectomized patients. Heat and moisture exchangers (HMEs) are passive humidifiers that re-condition the inspired air. Aim of this study was to assess the effect of HMEs on tracheal epithelium and tracheal mucus transport velocity (TMV). Tracheal brush biopsies were collected in three groups of TLE patients: 21 long-term HME users, 10 non-HME users, and 16 non-HME users before and after 4-9 months HME use. Tracheal epithelium biopsies were assessed using a digital high-speed camera mounted onto a light microscope. TMV was determined by scintigraphy in the first two patient groups. Significantly more ciliated cells were found in HME users compared to non-HME users (p = 0.05). TMV was higher in HME users (median 2 mm/min; 0-7.9) compared to non-HME users (median 0.8 mm/min; 0-12.3), but this difference was not significant (p = 0.37). One-hour breathing without HME in long-term HME users did not measurably decrease TMV (p = 0.13). The long-term use of an HME restores/prevents the loss of tracheal ciliated cells. A significant improvement in TMV was not found. Short-term (one hour) detachment of an HME has no measurable effect on TMV.

Risk of Endophthalmitis and Other Long-Term Complications of Trabeculectomy in the Collaborative Initial Glaucoma Treatment Study (CIGTS)

PubMed Central

Zahid, Sarwar; Musch, David C.; Niziol, Leslie M.; Lichter, Paul R.

2012-01-01

Purpose To report the risk of endophthalmitis and other long-term complications in patients randomized to trabeculectomy in the Collaborative Initial Glaucoma Treatment Study (CIGTS). Design A longitudinal cohort study using data collected from a multicenter, randomized clinical trial. Methods Long-term post-operative complications in the 300 patients randomized to trabeculectomy in CIGTS were tabulated. Kaplan-Meier analyses were used to estimate the time-related probability of blebitis, hypotony, and endophthalmitis. Results 285 patients were included in the final trabeculectomy cohort after accounting for assignment refusal and other early events. Patients were followed for an average of 7.2 years. 163 patients (57%) received 5-fluorouracil (5-FU) intraoperatively. Of the 247 patients with at least 5 years of follow-up, 50 required further treatment for glaucoma. Cataract extraction was performed in 57 patients (20%). Forty patients (14%) required bleb revision at least once. Bleb-related complications included bleb leak (N = 15), blebitis (N = 8), and hypotony (N = 4). Three patients were noted to have endophthalmitis, although the diagnosis in two patients was presumptive. The occurrences of blebitis, hypotony, or endophthalmitis were not significantly associated with 5-FU use. The Kaplan-Meier calculated risks of blebitis and hypotony at 5 years were both 1.5%, while the risk of endophthalmitis was 1.1%. Conclusions The potential efficacy of trabeculectomy must be weighed against the long-term risk of complications, especially endophthalmitis, when selecting treatments for patients with open-angle glaucoma. We report a low 5-year risk of endophthalmitis (1.1%) and other bleb-related complications in the trabeculectomy cohort of the CIGTS. PMID:23246272

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.

Over- and undersupply in home care: a representative multicenter correlational study.

PubMed

Lahmann, Nils A; Suhr, Ralf; Kuntz, Simone; Kottner, Jan

2015-04-01

Quality assurance and funding of care become a major challenge against the background of demographic changes in western societies. The primary aim of the study was to identify possible misclassification, respectively over and undersupply of care by comparing the Barthel Index of clients of home care service with the level of care (Stage 0, I, II, III) according to the statutory German long-term care insurance. In 2012, a multi-center point prevalence study of 878 randomly selected clients of 100 randomly selected home care services across Germany was conducted. According to a standardized study protocol, demographics, the Barthel Index and the nurses' professional judgment-whether a client requires more nursing care-were assessed. Associations of the Barthel items and professional judgment were analyzed using univariate (Chi-square) and multivariate (logistic regression and classification-regression-tree-models) statistics. In each level of care, the Barthel Index showed large variability e.g. in level II ranging from 0 to 100 points. Multivariate logistic regression regarding possible under- and oversupply revealed occasionally fecal incontinence (2.1; 95 % CI 1.2-3.7), urinary incontinence (2.0; 95 % CI 1.1-3.6), feeding (1.7; 95 % CI 1.0-2.9), immobility (0.2; 95 % CI 0.1-0.6) and to be female (1.8; 95 % CI 1.2-2.6) to be statistically significantly associated. The variability in Barthel Index in each level of care found in this study indicated a large general misclassification of home care clients according to their actual need of care. Professional caregivers identified occasional incontinence, help with eating and drinking and mobility (especially in female clients) as areas of possible under- and oversupply of care. The statutory German long-term care insurance classification should be modified according to the above finding to increase the quality of care in home care clients.

Long-term effects of edaravone on survival of patients with amyotrophic lateral sclerosis.

PubMed

Okada, Masamitsu; Yamashita, Satoshi; Ueyama, Hidetsugu; Ishizaki, Masatoshi; Maeda, Yasushi; Ando, Yukio

2018-06-01

Oxidative stress has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Edaravone, a free radical scavenger, was approved as a therapeutic drug for ALS in 2015 in Japan. A phase 3 clinical trial demonstrated a smaller decline in ALS functional scale scores compared with placebo. However, the long-term effects of edaravone on ALS patients remain unclear. This study aimed to retrospectively investigate the long-term effects of edaravone on the survival of ALS patients. We retrospectively analyzed 27 consecutive patients with ALS who were treated with edaravone and 30 consecutive ALS patients who were not treated with edaravone between 2010 and 2016. The differences of ALSFRS-R scores from baseline to 6 months was significantly reduced in the edaravone group, compared to the control group. The changes in serum creatinine, as a possible marker of ALS severity, from baseline to 6 and 12 months were significantly improved in the edaravone group, compared to the control group. The survival rate was significantly improved in the edaravone group compared with control patients. Our retrospective single-center analysis suggests slower progression and better prognosis of ALS patients with edaravone treatment. Further investigation, including prospective multicenter analysis, is warranted to confirm the usefulness of edaravone for a better prognosis of ALS.

Current status in the treatment options for esophageal achalasia

PubMed Central

Chuah, Seng-Kee; Chiu, Chien-Hua; Tai, Wei-Chen; Lee, Jyong-Hong; Lu, Hung-I; Changchien, Chi-Sin; Tseng, Ping-Huei; Wu, Keng-Liang

2013-01-01

Recent advances in the treatment of achalasia include the use of high-resolution manometry to predict the outcome of patients and the introduction of peroral endoscopic myotomy (POEM). The first multicenter randomized, controlled, 2-year follow-up study conducted by the European Achalasia Trial group indicated that laparoscopic Heller myotomy (LHM) was not superior to pneumatic dilations (PD). Publications on the long-term success of laparoscopic surgery continue to emerge. In addition, laparoscopic single-site surgery is applicable to advanced laparoscopic operations such as LHM and anterior fundoplication. The optimal treatment option is an ongoing matter of debate. In this review, we provide an update of the current progress in the treatment of esophageal achalasia. Unless new conclusive data prove otherwise, LHM is considered the most durable treatment for achalasia at the expense of increased reflux-associated complications. However, PD is the first choice for non-surgical treatment and is more cost-effective. Repeated PD according to an “on-demand” strategy based on symptom recurrence can achieve long-term remission. Decision making should be based on clinical evidence that identifies a subcategory of patients who would benefit from specific treatment options. POEM has shown promise but its long-term efficacy and safety need to be assessed further. PMID:24023484

Current status in the treatment options for esophageal achalasia.

PubMed

Chuah, Seng-Kee; Chiu, Chien-Hua; Tai, Wei-Chen; Lee, Jyong-Hong; Lu, Hung-I; Changchien, Chi-Sin; Tseng, Ping-Huei; Wu, Keng-Liang

2013-09-07

Recent advances in the treatment of achalasia include the use of high-resolution manometry to predict the outcome of patients and the introduction of peroral endoscopic myotomy (POEM). The first multicenter randomized, controlled, 2-year follow-up study conducted by the European Achalasia Trial group indicated that laparoscopic Heller myotomy (LHM) was not superior to pneumatic dilations (PD). Publications on the long-term success of laparoscopic surgery continue to emerge. In addition, laparoscopic single-site surgery is applicable to advanced laparoscopic operations such as LHM and anterior fundoplication. The optimal treatment option is an ongoing matter of debate. In this review, we provide an update of the current progress in the treatment of esophageal achalasia. Unless new conclusive data prove otherwise, LHM is considered the most durable treatment for achalasia at the expense of increased reflux-associated complications. However, PD is the first choice for non-surgical treatment and is more cost-effective. Repeated PD according to an "on-demand" strategy based on symptom recurrence can achieve long-term remission. Decision making should be based on clinical evidence that identifies a subcategory of patients who would benefit from specific treatment options. POEM has shown promise but its long-term efficacy and safety need to be assessed further.

Dual Antiplatelet Therapy for 6 Versus 18 Months After Biodegradable Polymer Drug-Eluting Stent Implantation.

PubMed

Nakamura, Masato; Iijima, Raisuke; Ako, Junya; Shinke, Toshiro; Okada, Hisayuki; Ito, Yoshiaki; Ando, Kenji; Anzai, Hitoshi; Tanaka, Hiroyuki; Ueda, Yasunori; Takiuchi, Shin; Nishida, Yasunori; Ohira, Hiroshi; Kawaguchi, Katsuhiro; Kadotani, Makoto; Niinuma, Hiroyuki; Omiya, Kazuto; Morita, Takashi; Zen, Kan; Yasaka, Yoshinori; Inoue, Kenji; Ishiwata, Sugao; Ochiai, Masahiko; Hamasaki, Toshimitsu; Yokoi, Hiroyoshi

2017-06-26

The NIPPON (Nobori Dual Antiplatelet Therapy as Appropriate Duration) study was a multicenter randomized investigation of the noninferiority of short-term versus long-term dual antiplatelet therapy (DAPT) in patients with implantation of the Nobori drug-eluting stent (DES) (Terumo, Tokyo, Japan), which has a biodegradable abluminal coating. The optimum duration of DAPT for patients with a biodegradable polymer-coated DES is unclear. The subjects were 3,773 patients with stable or acute coronary syndromes undergoing Nobori stent implantation. They were randomized 1:1 to receive DAPT for 6 or 18 months. The primary endpoint was net adverse clinical and cerebrovascular events (NACCE) (all-cause mortality, myocardial infarction, stroke, and major bleeding) from 6 to 18 months after stenting. Intention-to-treat analysis was performed in 3,307 patients who were followed for at least 6 months. NACCE occurred in 34 patients (2.1%) receiving short-term DAPT and 24 patients (1.5%) receiving long-term DAPT (difference 0.6%, 95% confidence interval [CI]: 1.5 to 0.3). Because the lower limit of the 95% CI was inside the specified margin of -2%, noninferiority of short-term DAPT was confirmed. Mortality was 1.0% with short-term DAPT versus 0.4% with long-term DAPT, whereas myocardial infarction was 0.2% versus 0.1%, and major bleeding was 0.7% versus 0.7%, respectively. The estimated probability of NACCE was lower in the long-term DAPT group (hazard ratio: 1.44, 95% CI: 0.86 to 2.43). Six months of DAPT was not inferior to 18 months of DAPT following implantation of a DES with a biodegradable abluminal coating. However, this result needs to be interpreted with caution given the open-label design and wide noninferiority margin of the present study. (Nobori Dual Antiplatelet Therapy as Appropriate Duration [NIPPON]; NCT01514227). Copyright © 2017. Published by Elsevier Inc.

Spine device clinical trials: design and sponsorship.

PubMed

Cher, Daniel J; Capobianco, Robyn A

2015-05-01

Multicenter prospective randomized clinical trials represent the best evidence to support the safety and effectiveness of medical devices. Industry sponsorship of multicenter clinical trials is purported to lead to bias. To determine what proportion of spine device-related trials are industry-sponsored and the effect of industry sponsorship on trial design. Analysis of data from a publicly available clinical trials database. Clinical trials of spine devices registered on ClinicalTrials.gov, a publicly accessible trial database, were evaluated in terms of design, number and location of study centers, and sample size. The relationship between trial design characteristics and study sponsorship was evaluated using logistic regression and general linear models. One thousand six hundred thrity-eight studies were retrieved from ClinicalTrials.gov using the search term "spine." Of the 367 trials that focused on spine surgery, 200 (54.5%) specifically studied devices for spine surgery and 167 (45.5%) focused on other issues related to spine surgery. Compared with nondevice trials, device trials were far more likely to be sponsored by the industry (74% vs. 22.2%, odds ratio (OR) 9.9 [95% confidence interval 6.1-16.3]). Industry-sponsored device trials were more likely multicenter (80% vs. 29%, OR 9.8 [4.8-21.1]) and had approximately four times as many participating study centers (p<.0001) and larger sample sizes. There were very few US-based multicenter randomized trials of spine devices not sponsored by the industry. Most device-related spine research is industry-sponsored. Multicenter trials are more likely to be industry-sponsored. These findings suggest that previously published studies showing larger effect sizes in industry-sponsored vs. nonindustry-sponsored studies may be biased as a result of failure to take into account the marked differences in design and purpose. Copyright © 2015 Elsevier Inc. All rights reserved.

Multicenter review of diaphragm pacing in spinal cord injury: successful not only in weaning from ventilators but also in bridging to independent respiration.

PubMed

Posluszny, Joseph A; Onders, Raymond; Kerwin, Andrew J; Weinstein, Michael S; Stein, Deborah M; Knight, Jennifer; Lottenberg, Lawrence; Cheatham, Michael L; Khansarinia, Saeid; Dayal, Saraswati; Byers, Patricia M; Diebel, Lawrence

2014-02-01

Ventilator-dependent spinal cord-injured (SCI) patients require significant resources related to ventilator dependence. Diaphragm pacing (DP) has been shown to successfully replace mechanical ventilators for chronic ventilator-dependent tetraplegics. Early use of DP following SCI has not been described. Here, we report our multicenter review experience with the use of DP in the initial hospitalization after SCI. Under institutional review board approval for humanitarian use device, we retrospectively reviewed our multicenter nonrandomized interventional protocol of laparoscopic diaphragm motor point mapping with electrode implantation and subsequent diaphragm conditioning and ventilator weaning. Twenty-nine patients with an average age of 31 years (range, 17-65 years) with only two females were identified. Mechanism of injury included motor vehicle collision (7), diving (6), gunshot wounds (4), falls (4), athletic injuries (3), bicycle collision (2), heavy object falling on spine (2), and motorcycle collision (1). Elapsed time from injury to surgery was 40 days (range, 3-112 days). Seven (24%) of the 29 patients who were evaluated for the DP placement had nonstimulatable diaphragms from either phrenic nerve damage or infarction of the involved phrenic motor neurons and were not implanted. Of the stimulatable patients undergoing DP, 72% (16 of 22) were completely free of ventilator support in an average of 10.2 days. For the remaining six DP patients, two had delayed weans of 180 days, three had partial weans using DP at times during the day, and one patient successfully implanted went to a long-term acute care hospital and subsequently had life-prolonging measures withdrawn. Eight patients (36%) had complete recovery of respiration, and DP wires were removed. Early laparoscopic diaphragm mapping and DP implantation can successfully wean traumatic cervical SCI patients from ventilator support. Early laparoscopic mapping is also diagnostic in that a nonstimulatable diaphragm is a convincing evidence of an inability to wean from ventilator support, and long-term ventilator management can be immediately instituted. Therapeutic study, level V.

Maternal inflammatory bowel disease has short and long-term effects on the health of their offspring: a multicenter study in Israel.

PubMed

Dotan, Iris; Alper, Arik; Rachmilewitz, Daniel; Israeli, Eran; Odes, Shmuel; Chermesh, Irit; Naftali, Timna; Fraser, Gerald; Shitrit, Ariella Bar-Gil; Peles, Vardit; Reif, Shimon

2013-08-01

There are concerns about the effect of inflammatory bowel diseases (IBD) on fertility, pregnancy and pregnancy outcomes, but no long-term data on the health of offspring born to IBD mothers. The aims were to assess the short- and long-term effects of maternal IBD on the morbidity and development of their offspring. Female IBD patients and controls completed questionnaires on their pregnancy outcome, and their offspring's short- and long-term health and development. IBD and control mothers (159 and 175, respectively) were recruited. Medical data of 412 IBD and 417 control offspring were recorded. IBD mothers had significantly more singleton pregnancies, their offspring's birth weight was significantly lower, and they breastfed significantly less compared to controls (P=0.028, 0.007, and <0.0001, respectively). There were significantly more congenital anomalies (mainly limb deformities) among the IBD offspring (P<0.035). Offspring born post-maternal IBD diagnosis, compared to pre-diagnosis, tended to have more neurodevelopmental problems (e.g., gross motor delay, P=0.03). IBD was significantly more prevalent in the offspring of IBD mothers, while allergies and atopic dermatitis were more frequent in offspring of control mothers. More offspring of IBD mothers taking medications during pregnancy were born preterm and had lower birth weights compared to offspring of IBD mothers not taking medications during pregnancy. Children of mothers taking steroids had the lowest birth weights, compared to those of IBD mothers taking 5ASAs or immunomodulators. Maternal IBD affects pregnancy and the offspring's immediate and long-term morbidity, specifically, congenital anomalies and neurodevelopmental problems. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

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.

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.

Mechanical ventilation weaning and extubation after spinal cord injury: a Western Trauma Association multicenter study.

PubMed

Kornblith, Lucy Z; Kutcher, Matthew E; Callcut, Rachael A; Redick, Brittney J; Hu, Charles K; Cogbill, Thomas H; Baker, Christopher C; Shapiro, Mark L; Burlew, Clay C; Kaups, Krista L; DeMoya, Marc A; Haan, James M; Koontz, Christopher H; Zolin, Samuel J; Gordy, Stephanie D; Shatz, David V; Paul, Doug B; Cohen, Mitchell J

2013-12-01

Respiratory failure after acute spinal cord injury (SCI) is well recognized, but data defining which patients need long-term ventilator support and criteria for weaning and extubation are lacking. We hypothesized that many patients with SCI, even those with cervical SCI, can be successfully managed without long-term mechanical ventilation and its associated morbidity. Under the auspices of the Western Trauma Association Multi-Center Trials Group, a retrospective study of patients with SCI at 14 major trauma centers was conducted. Comprehensive injury, demographic, and outcome data on patients with acute SCI were compiled. The primary outcome variable was the need for mechanical ventilation at discharge. Secondary outcomes included the use of tracheostomy and development of acute lung injury and ventilator-associated pneumonia. A total of 360 patients had SCI requiring mechanical ventilation. Sixteen patients were excluded for death within the first 2 days of hospitalization. Of the 344 patients included, 222 (64.5%) had cervical SCI. Notably, 62.6% of the patients with cervical SCI were ventilator free by discharge. One hundred forty-nine patients (43.3%) underwent tracheostomy, and 53.7% of them were successfully weaned from the ventilator, compared with an 85.6% success rate among those with no tracheostomy (p < 0.05). Patients who underwent tracheostomy had significantly higher rates of ventilator-associated pneumonia (61.1% vs. 20.5%, p < 0.05) and acute lung injury (12.8% vs. 3.6%, p < 0.05) and fewer ventilator-free days (1 vs. 24 p < 0.05). When controlled for injury severity, thoracic injury, and respiratory comorbidities, tracheostomy after cervical SCI was an independent predictor of ventilator dependence with an associated 14-fold higher likelihood of prolonged mechanical ventilation (odds ratio, 14.1; 95% confidence interval, 2.78-71.67; p < 0.05). While many patients with SCI require short-term mechanical ventilation, the majority can be successfully weaned before discharge. In patients with SCI, tracheostomy is associated with major morbidity, and its use, especially among patients with cervical SCI, deserves further study. Prognostic study, level III.

Multicenter evaluation of the Bayer Immuno I CA 15-3 assay.

PubMed

Cheli, C D; Morris, D L; Kish, L; Goldblatt, J; Neaman, I; Allard, W J; Yeung, K K; Wu, A H; Moore, R; Chan, D W; Fritsche, H A; Schwartz, M K; Very, D L

1998-04-01

We conducted a multicenter evaluation of the analytical and clinical features of the automated Bayer Immuno 1 CA 15-3 assay and compared assay performance to two manual tests. Results of the 10-day imprecision study of the Bayer Immuno 1 assay pooled across four evaluation sites and three lots of reagent produced total CV < or = 4%. Lot-to-lot reproducibility for 26 different lots of reagents and calibrators manufactured over a 2-year period was demonstrated (CV, 1.1%). Results for the Bayer Immuno 1 assay correlated well with the Biomira TRUQUANT BR 27.29 and Centocor CA 15-3 RIAs (r > or = 0.94). The upper limit of the reference interval for the Bayer Immuno 1 assay was 35.9 kilounits/L (35.9 units/mL); values were similar for all methods. Longitudinal monitoring of healthy women yielded assay values with an average CV of 11% and 21% for the Bayer Immuno 1 and Biomira assays, respectively. The Bayer Immuno 1 assay demonstrated the analytical features, intermethod correlation, and long-term performance characteristics that are essential for longitudinal monitoring of breast cancer patients.

Long-term Outcomes of Laparoscopic Versus Open Surgery for Clinical Stage II/III Gastric Cancer: A Multicenter Cohort Study in Japan (LOC-A Study).

PubMed

Kinoshita, Takahiro; Uyama, Ichiro; Terashima, Masanori; Noshiro, Hirokazu; Nagai, Eishi; Obama, Kazutaka; Tamamori, Yutaka; Nabae, Toshinaga; Honda, Michitaka; Abe, Takayuki

2018-04-24

A large-scale multicenter historical cohort study was conducted to investigate the efficacy of laparoscopic gastrectomy (LG) in comparison to open gastrectomy (OG) for locally advanced gastric cancer. LG is now practiced widely, but its applicability for advanced gastric cancer is still controversial. As oncologic outcomes of randomized trials are still pending, there is an urgent need for information that would be relevant to current practice. Through a consensus meeting involving surgeons and biostatisticians, 30 preoperative variables possibly influencing the choice of surgical approach and associated with outcome were identified to enable rigorous estimation of propensity scores. A total of 1948 consecutive patients who underwent gastrectomy for clinical stage II/III gastric adenocarcinoma between 2008 and 2014 were identified, and their clinical data were collected from 8 participating hospitals. After propensity score matching, 610 cases (OG = 305, LG = 305) were finally selected for comparison of long-term outcomes. In the propensity-matched OG and LG populations, the mean observation period was 3.5 and 3.4 years, and the 5-year overall survival was 53.0% and 54.2%, respectively. The hazard ratio (LG/OG) for overall survival was 1.01 (95% confidence interval, 0.80-1.29), and noninferiority of LG was demonstrated statistically as the upper 95% confidence limit was less than the prespecified margin (1.33). The recurrence rate was 30.8% and 29.8% for OG and LG, respectively, and the hazard ratio for recurrence was 0.98 (95% confidence interval, 0.74-1.31). The patterns of recurrence in the 2 groups were similar. This observational study strictly adjusted for confounding factors has provided evidence to suggest that LG is oncologically comparable to OG for locally advanced gastric cancer. The validity of this result will be examined in ongoing randomized trials.

Design innovations and baseline findings in a long-term Parkinson's trial: the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson's Disease Long-Term Study-1.

PubMed

Elm, Jordan J

2012-10-01

Based on the preclinical data and the results of a phase II futility study, creatine was selected for an efficacy trial in Parkinson's disease (PD). We present the design rationale and a description of the study cohort at baseline. A randomized, multicenter, double-blind, parallel-group, placebo-controlled phase III study of creatine (10 g daily) in participants with early, treated PD, the Long-term Study-1 (LS-1), is being conducted by the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson's Disease network. The study utilizes a global statistical test (GST) encompassing five clinical rating scales to provide a multidimensional assessment of disease progression. A total of 1,741 PD participants from 45 sites in the United States and Canada were randomized 1:1 to either 10 g of creatine/day or matching placebo. Participants are being evaluated for a minimum of 5 years. The LS-1 baseline cohort includes participants treated with dopaminergic therapy and generally mild PD. LS-1 represents the largest cohort of patients with early treated PD ever enrolled in a clinical trial. The GST approach should provide high power to test the hypothesis that daily administration of creatine (10 g/day) is more effective than placebo in slowing clinical decline in PD between baseline and the 5-year follow-up visit against the background of dopaminergic therapy and best PD care. Copyright © 2012 Movement Disorder Society.

Rationale and Methodology of the SARAH Trial: Long-Term Cardiovascular Outcomes in Patients With Resistant Hypertension and Obstructive Sleep Apnea.

PubMed

Sapiña-Beltrán, Esther; Torres, Gerard; Martínez-Alonso, Montserrat; Sánchez-de-la-Torre, Manuel; Franch, Maria; Bravo, Carmen; Masa, Juan F; Felez, Miquel; Fortuna-Gutierrez, Ana Maria; Abad, Jorge; García-Río, Francisco; Drager, Luciano F; Lee Chi-Hang, Ronald; Martínez-García, Miguel Ángel; Barbé, Ferran; Dalmases, Mireia

2018-05-22

Patients with resistant hypertension (RH) have a high risk of developing cardiovascular events; therefore, new therapeutic approaches to better control blood pressure may be useful in improving cardiovascular outcomes. The prevalence of obstructive sleep apnea (OSA) is very high among patients with RH. Continuous positive airway pressure (CPAP) has been shown to be an effective treatment for reducing blood pressure in patients with RH. Nevertheless, the long-term effect of CPAP treatment on cardiovascular outcomes has not been explored. The main objective of the SARAH study is to assess the impact of OSA and its treatment on cardiovascular outcomes (morbidity and mortality) in patients with RH. This study is a multi-center, prospective, observational cohort study. A total of 1371 patients with RH will be enrolled in the study and followed once a year for five years. At inclusion, ambulatory blood pressure monitoring (ABPM) and a sleep study will be performed in all subjects. Socio-demographic, clinical and cardiovascular variables will be collected at baseline and follow-up. Subsequently, subjects with OSA will be managed according to local standard practice. Based on the OSA diagnosis and its treatment, three cohorts of subjects with RH will be defined: non-OSA, treated OSA and non-treated OSA. This study will contribute to elucidating the long-term impact of OSA treatments on blood pressure control and cardiovascular outcomes in patients with RH. These results will contribute to improve the cardiovascular prognosis of patients with RH. Copyright © 2018 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Long-term safety and effectiveness of lubiprostone, a chloride channel (ClC-2) activator, in patients with chronic idiopathic constipation.

PubMed

Lembo, Anthony J; Johanson, John F; Parkman, Henry P; Rao, Satish S; Miner, Philip B; Ueno, Ryuji

2011-09-01

Lubiprostone helps relieve constipation in short-term 4-week studies. There are limited data on long-term pharmacological treatment with lubiprostone for chronic idiopathic constipation. To examine the long-term safety and effectiveness of lubiprostone in patients with chronic idiopathic constipation. In this prospective, multicenter, open-labeled trial, 248 patients aged ≥18 years with chronic idiopathic constipation were directed to take lubiprostone 24 mcg BID as needed for 48 weeks. Patients were allowed to decrease the dose in response to the perceived severity of constipation and need for relief. Hematology and chemistry profiles and assessment of constipation symptoms and its severity were performed at all visits. Adverse events (AEs) were recorded. Of the 248 patients who entered the trial, 127 (51%) completed the trial. A dose reduction was observed in 17% of the patients, resulting in an average study medication exposure across the study of approximately 1.7 capsules (or approximately 40.8 mcg) per day. The most common treatment-related AEs were nausea (19.8%), diarrhea (9.7%), abdominal distension (6.9%), headache (6.9%), and abdominal pain (5.2%). No deaths were reported and of the 16 reported serious AEs, one was considered possibly treatment related. Average changes in serum electrolytes were not clinically relevant at any time point during the study. On average, lubiprostone significantly (p < 0.0001) reduced patient-reported constipation severity, abdominal bloating, and abdominal discomfort across 48 weeks when compared to baseline. During this 48-week open-label study, lubiprostone was well tolerated. Bowel symptoms consistently improved over 48 weeks in adult patients with chronic idiopathic constipation.

Conversion in laparoscopic colorectal cancer surgery: impact on short- and long-term outcome.

PubMed

Scheidbach, Hubert; Garlipp, Benjamin; Oberländer, Henrik; Adolf, Daniela; Köckerling, Ferdinand; Lippert, Hans

2011-12-01

Despite the well-documented safety and effectiveness of laparoscopic colorectal surgery in curative intention, the role of conversion and its impact on short- and long-term outcome after resection of a carcinoma are unclear and continue to give rise to controversial discussion. Within the framework of a prospective, multicenter observational study (Laparoscopic Colorectal Surgery Study Group), into which a total of 5,863 patients from 69 hospitals were recruited over a period of 10 years, a subgroup of all patients who had undergone curative resection was analyzed with regard to the effects of conversion. Of the 1409 patients who had undergone curative resection for colorectal carcinoma, conversion had to be performed in 80 (5.7%) cases for the most diverse reasons. The duration of surgery (median: 183 vs. 241 minutes; P<.001) was significantly longer in the conversion group. Perioperatively, significant disadvantages were noted in converted patients in terms of intraoperative blood loss (median: 243 vs. 573 mL, P<.001), need for perioperative blood transfusion (10.8% vs. 33.8%; P<.001), and resumption of bowel movement (median: after 3 vs. 4 days; P<.001). With regard to postoperative morbidity, significant disadvantages were observed in converted patients, in particular in terms of specific surgical complications, including a higher rate of anastomotic insufficiency (5.0% vs. 13.8%; P=.003) and a higher reoperation rate (4.9% vs. 15.0%; P=.001). In the long term, conversion was associated with lower overall survival, but not with poorer disease-free survival. Significantly higher postoperative morbidity was observed in patients after conversion, in particular in terms of specific surgical complications. In addition, conversion is associated with overall lower survival but not with poorer disease-free survival.

Very low dose naltrexone addition in opioid detoxification: a randomized, controlled trial.

PubMed

Mannelli, Paolo; Patkar, Ashwin A; Peindl, Kathi; Gorelick, David A; Wu, Li-Tzy; Gottheil, Edward

2009-04-01

Although current treatments for opioid detoxification are not always effective, medical detoxification remains a required step before long-term interventions. The use of opioid antagonist medications to improve detoxification has produced inconsistent results. Very low dose naltrexone (VLNTX) was recently found to reduce opioid tolerance and dependence in animal and clinical studies. We decided to evaluate safety and efficacy of VLNTX adjunct to methadone in reducing withdrawal during detoxification. In a multi-center, double-blind, randomized study at community treatment programs, where most detoxifications are performed, 174 opioid-dependent subjects received NTX 0.125 mg, 0.250 mg or placebo daily for 6 days, together with methadone in tapering doses. VLNTX-treated individuals reported attenuated withdrawal symptoms [F = 7.24 (2,170); P = 0.001] and reduced craving [F = 3.73 (2,107); P = 0.03]. Treatment effects were more pronounced at discharge and were not accompanied by a significantly higher retention rate. There were no group differences in use of adjuvant medications and no treatment-related adverse events. Further studies should explore the use of VLNTX, combined with full and partial opioid agonist medications, in detoxification and long-term treatment of opioid dependence.

A phase1 study of stereotactic gene delivery of AAV2-NGF for Alzheimer's disease.

PubMed

Rafii, Michael S; Baumann, Tiffany L; Bakay, Roy A E; Ostrove, Jeffrey M; Siffert, Joao; Fleisher, Adam S; Herzog, Christopher D; Barba, David; Pay, Mary; Salmon, David P; Chu, Yaping; Kordower, Jeffrey H; Bishop, Kathie; Keator, David; Potkin, Steven; Bartus, Raymond T

2014-09-01

Nerve growth factor (NGF) is an endogenous neurotrophic-factor protein with the potential to restore function and to protect degenerating cholinergic neurons in Alzheimer's disease (AD), but safe and effective delivery has proved unsuccessful. Gene transfer, combined with stereotactic surgery, offers a potential means to solve the long-standing delivery obstacles. An open-label clinical trial evaluated the safety and tolerability, and initial efficacy of three ascending doses of the genetically engineered gene-therapy vector adeno-associated virus serotype 2 delivering NGF (AAV2-NGF [CERE-110]). Ten subjects with AD received bilateral AAV2-NGF stereotactically into the nucleus basalis of Meynert. AAV2-NGF was safe and well-tolerated for 2 years. Positron emission tomographic imaging and neuropsychological testing showed no evidence of accelerated decline. Brain autopsy tissue confirmed long-term, targeted, gene-mediated NGF expression and bioactivity. This trial provides important evidence that bilateral stereotactic administration of AAV2-NGF to the nucleus basalis of Meynert is feasible, well-tolerated, and able to produce long-term, biologically active NGF expression, supporting the initiation of an ongoing multicenter, double-blind, sham-surgery-controlled trial. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

[Stinging nettle root extract (Bazoton-uno) in long term treatment of benign prostatic syndrome (BPS). Results of a randomized, double-blind, placebo controlled multicenter study after 12 months].

PubMed

Schneider, T; Rübben, H

2004-03-01

Phytotherapy of BPS has a long tradition in Germany; nevertheless, data referring to single phytotherapeutic agents are rare. We therefore performed a randomized, double-blind, placebo-controlled multicenter study for 1 year with Bazoton uno (459 mg dry extract of stinging nettle roots) with 246 patients. The IPSS decreased on average from 18.7+/-0.3 to 13.0+/-0.5 with a statistically significant difference compared to placebo (18.5+/-0.3 to 13.8+/-0.5; p=0.0233). The median Q(max) increased by 3.0+/-0.4 ml/s in comparison to 2.9+/-0.4 ml/s (placebo), thus not statistically significantly different, as well as the median volume of residual urine, which changed from 35.5+/-3.4 ml before therapy to 20.0+/-2.8 ml and from 40.0+/-4.0 ml to 21.0+/-2.9 ml under placebo application. The number of adverse events (29/38) as well as urinary infections etc. (3/10 events) was smaller under Bazoton uno therapy compared to placebo. Treatment with Bazoton uno can therefore be considered a safe therapeutic option for BPS, especially for reducing irritative symptoms and BPS-associated complications due to the postulated antiphlogistic and antiproliferative effects of the stinging nettle extract. A strong increase of Q(max) or reduction of residual urine are not to be expected.

The prognostic importance of worsening renal function during an acute myocardial infarction on long-term mortality.

PubMed

Amin, Amit P; Spertus, John A; Reid, Kimberly J; Lan, Xiao; Buchanan, Donna M; Decker, Carole; Masoudi, Frederick A

2010-12-01

Although an acute worsening in renal function (WRF) commonly occurs among patients hospitalized for acute myocardial infarction (AMI), its long-term prognostic significance is unknown. We examined predictors of WRF and its association with 4-year mortality. Acute myocardial infarction patients from the multicenter PREMIER study (N=2,098) who survived to hospital discharge were followed for at least 4 years. Worsening in renal function was defined as an increase in creatinine during hospitalization of ≥0.3 mg/dL above the admission value. Correlates of WRF were determined with multivariable logistic regression models and used, along with other important clinical covariates, in Cox proportional hazards models to define the independent association between WRF and mortality. Worsening in renal function was observed in 393 (18.7%) of AMI survivors. Diabetes, left ventricular systolic dysfunction, and a history of chronic kidney disease (documented history of renal failure with baseline creatinine>2.5 mg/dL) were independently associated with WRF. During 4-year follow-up, 386 (18.6%) patients died. Mortality was significantly higher in the WRF group (36.6% vs 14.4% in those without WRF, P<.001). After adjusting for other factors associated with WRF and long-term mortality, including baseline creatinine, WRF was independently associated with a higher risk of death (hazard ratio=1.64, 95% CI 1.23-2.19). Worsening in renal function occurs in approximately 1 of 6 AMI survivors and is independently associated with an adverse long-term prognosis. Further studies on interventions to minimize WRF or to more aggressively treat patients developing WRF should be tested. Copyright © 2010 Mosby, Inc. All rights reserved.

Urgent Chemotherapy for Life-Threatening Complications Related to Solid Neoplasms.

PubMed

Zerbib, Yoann; Rabbat, Antoine; Fartoukh, Muriel; Bigé, Naïke; Andréjak, Claire; Mayaux, Julien; De Prost, Nicolas; Misset, Benoît; Lemiale, Virginie; Bruneel, Fabrice; Maizel, Julien; Ricome, Sylvie; Jacobs, Frédéric; Bornstain, Caroline; Dupont, Hervé; Baudin, François; Azoulay, Elie; Pène, Frédéric

2017-07-01

Solid neoplasms can be directly responsible for organ failures at the time of diagnosis or relapse. The management of such specific complications relies on urgent chemotherapy and eventual instrumental or surgical procedures, combined with advanced life support. We conducted a multicenter study to address the prognosis of this condition. A multicenter retrospective (2001-2015) chart review. Medical and respiratory ICUs. Adult patients who received urgent chemotherapy in the ICU for organ failure related to solid neoplasms were included. The modalities of chemotherapy, requirements of adjuvant instrumental or surgical procedures, and organ supports were collected. Endpoints were short- and long-term survival rates. None. One hundred thirty-six patients were included. Lung cancer was the most common malignancy distributed into small cell lung cancer (n = 57) and non-small cell lung cancer (n = 33). The main reason for ICU admission was acute respiratory failure in 111 patients (81.6%), of whom 89 required invasive mechanical ventilation. Compression and tissue infiltration by tumor cells were the leading mechanisms resulting in organ involvement in 78 (57.4%) and 47 (34.6%) patients. The overall in-ICU, in-hospital, 6-month, and 1-year mortality rates were 37%, 58%, 74%, and 88%, respectively. Small cell lung cancer was identified as an independent predictor of hospital survival. However, this gain in survival was not sustained since the 1-year survival rates of small cell lung cancer, non-small cell lung cancer, and non-lung cancer patients all dropped below 20%. Urgent chemotherapy along with aggressive management of organ failures in the ICU can be lifesaving in very selected cancer patients, most especially with small cell lung cancer, although the long-term survival is hardly sustainable.

Long-Term Survival in Patients Receiving a Continuous-Flow Left Ventricular Assist Device.

PubMed

Gosev, Igor; Kiernan, Michael S; Eckman, Peter; Soleimani, Behzad; Kilic, Ahmet; Uriel, Nir; Rich, Jonathan D; Katz, Jason N; Cowger, Jennifer; Lima, Brian; McGurk, Siobhan; Brisco-Bacik, Meredith A; Lee, Sanjin; Joseph, Susan M; Patel, Chetan B

2018-03-01

Long-term survivors after implantation of left ventricular assist devices (LVADs) are increasing in prevalence. We describe the characteristics and outcomes in patients surviving longer than 4 years on LVAD support. We performed a multicenter, retrospective analysis of patients surviving at least 4 years on continuous-flow LVAD (CF-LVAD) support with a HeartMate II at centers participating in the Evolving Mechanical support Research Group. Between 2005 and 2010, 156 long-term survivors were identified with a mean survival of 7.1 years (95% confidence interval: 6.7 to 7.5 years). The mean age was 58.2 ± 15.2 years and 30.1% were women. Readmission rate was low at 1.1 events per patient per year with the most common reasons leading to readmission being infection (0.10 readmissions per patient per year) and gastrointestinal bleeding (0.07 readmissions per patient per year). Two years after implantation, 97% of patients were either New York Heart Association functional class I or II, with 92% at 4 years. Patients surviving 4 years on CF-LVAD support can anticipate ongoing long-term survival with sustained improvements in functionality and low rates of rehospitalization. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Systemic hydrocortisone to prevent bronchopulmonary dysplasia in preterm infants (the SToP-BPD study); a multicenter randomized placebo controlled trial

PubMed Central

2011-01-01

Background Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants. Methods/Design The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortality or BPD at 36 weeks postmenstrual age. Secondary outcomes are short term effects on the pulmonary condition, adverse effects during hospitalization, and long-term neurodevelopmental sequelae assessed at 2 years corrected gestational age. Analysis will be on an intention to treat basis. Discussion This trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants. Trial registration number Netherlands Trial Register (NTR): NTR2768 PMID:22070744

Treatment Strategy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma.

PubMed

Nakamura, Shotaro; Matsumoto, Takayuki

2015-09-01

Recent trends and current knowledge on the diagnosis and treatment strategy for gastric mucosa-associated lymphoid tissue (MALT) lymphoma are reviewed. Helicobacter pylori infection plays the causative role in the pathogenesis, and H pylori eradication is the first-line treatment of this disease, which leads to complete remission in 60% to 90% of cases. A Japanese multicenter study confirmed that the long-term outcome of gastric MALT lymphoma after H pylori eradication is excellent. Treatment strategies for patients not responding to H pylori eradication including "watch and wait" strategy, radiotherapy, chemotherapy, rituximab immunotherapy, and combination of these should be tailored in consideration of the disease extent in each patient. Copyright © 2015 Elsevier Inc. All rights reserved.

Prognosis after surgical treatment for pancreatic cancer in patients aged 80 years or older: a multicenter study.

PubMed

Sho, Masayuki; Murakami, Yoshiaki; Kawai, Manabu; Motoi, Fuyuhiko; Satoi, Sohei; Matsumoto, Ippei; Honda, Goro; Uemura, Kenichiro; Yanagimoto, Hiroaki; Kurata, Masanao; Akahori, Takahiro; Kinoshita, Shoichi; Nagai, Minako; Nishiwada, Satoshi; Fukumoto, Takumi; Unno, Michiaki; Yamaue, Hiroki; Nakajima, Yoshiyuki

2016-03-01

The optimal therapeutic strategy for very elderly pancreatic cancer patients remains to be determined. The aim of this study was to clarify the role of pancreatic resection in patients 80 years of age or older. A retrospective multicenter analysis of 1401 patients who had undergone pancreatic resection for pancreatic cancer was performed. The patients aged ≥ 80 years (n = 99) were compared with a control group <80 years of age (n = 1302). There were no significant differences in the postoperative complications and mortality between the two groups. However, the prognosis of octogenarians was poorer than that of younger patients for both resectable and borderline resectable tumors. Importantly, there were few long-term survivors in the elderly group, especially among those with borderline resectable pancreatic cancer. A multivariate analysis of the prognostic factors in the very elderly patients indicated that the completion of adjuvant chemotherapy was the only significant factor. In addition, preoperative albumin level was the only independent risk factor for a failure to complete adjuvant chemotherapy. This study demonstrates that the postoperative prognosis in octogenarian patients was not good as that in younger patients possibly due to less frequent completion of adjuvant chemotherapy. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Prospective Observational Post-Marketing Study of Tafluprost for Glaucoma and Ocular Hypertension: Effectiveness and Treatment Persistence.

PubMed

Kuwayama, Yasuaki; Hashimoto, Masako; Kakegawa, Reiko; Nomura, Akio; Shimada, Fumiki

2017-06-01

The aim of this study was to investigate the long-term intraocular pressure (IOP)-lowering effect and safety of tafluprost, a prostaglandin analogue, in actual clinical practice and to determine persistency of tafluprost as an indicator of its benefit-risk balance. This was a large-scale, post-marketing, multicenter, non-interventional, open-label, long-term study. Patients with glaucoma or ocular hypertension who initiated tafluprost treatment were registered and prospectively observed over a 2-year period in the real-world setting in Japan. Long-term IOP and safety data were collected. Of the 4502 patients registered from 553 medical institutions, 4265 patients were analyzed. The majority of patients had normal-tension glaucoma (44.4%) and primary open-angle glaucoma (37.8%), and patients with ocular hypertension constituted 7.0%. Treatment patterns with tafluprost during the study period were as follows: naïve monotherapy (48.1%), switching monotherapy (18.4%), and concomitant therapy (33.5%). In all patients analyzed, mean IOP was significantly reduced from 18.6 ± 5.9 mmHg (month 0) to 15 mmHg or below throughout the 2-year observation period after initiation of tafluprost. Significant IOP-lowering effects were shown in various treatment patterns and disease types. Adverse reactions were observed in 795 patients (18.64%). Major adverse reactions included eyelid pigmentation, ocular hyperemia, eyelash changes, eyelid hypertrichosis, and iris hyperpigmentation. Kaplan-Meier curves showed that 84.6% and 76.1% of patients were persistent on tafluprost for 1 and 2 years, respectively, when discontinuation due to insufficient efficacy or adverse events was defined as a treatment failure event. Furthermore, among treatment-naïve patients (n = 2304), the persistency rates on tafluprost monotherapy were 77.0% for 1 year and 67.0% for 2 years. Tafluprost showed significant long-term IOP-lowering effects regardless of treatment patterns or diagnosis, with minimum safety concerns in the actual clinical practice. The observed treatment persistence suggests that tafluprost can be used long term owing to its benefit-risk profile. Santen Pharmaceutical Co., Ltd., Osaka, Japan.

Prospective Study of Particulate Air Pollution Exposures, Subclinical Atherosclerosis, and Clinical Cardiovascular Disease

PubMed Central

Kaufman, Joel D.; Adar, Sara D.; Allen, Ryan W.; Barr, R. Graham; Budoff, Matthew J.; Burke, Gregory L.; Casillas, Adrian M.; Cohen, Martin A.; Curl, Cynthia L.; Daviglus, Martha L.; Roux, Ana V. Diez; Jacobs, David R.; Kronmal, Richard A.; Larson, Timothy V.; Liu, Sally Lee-Jane; Lumley, Thomas; Navas-Acien, Ana; O'Leary, Daniel H.; Rotter, Jerome I.; Sampson, Paul D.; Sheppard, Lianne; Siscovick, David S.; Stein, James H.; Szpiro, Adam A.; Tracy, Russell P.

2012-01-01

The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) was initiated in 2004 to investigate the relation between individual-level estimates of long-term air pollution exposure and the progression of subclinical atherosclerosis and the incidence of cardiovascular disease (CVD). MESA Air builds on a multicenter, community-based US study of CVD, supplementing that study with additional participants, outcome measurements, and state-of-the-art air pollution exposure assessments of fine particulate matter, oxides of nitrogen, and black carbon. More than 7,000 participants aged 45–84 years are being followed for over 10 years for the identification and characterization of CVD events, including acute myocardial infarction and other coronary artery disease, stroke, peripheral artery disease, and congestive heart failure; cardiac procedures; and mortality. Subcohorts undergo baseline and follow-up measurements of coronary artery calcium using computed tomography and carotid artery intima-medial wall thickness using ultrasonography. This cohort provides vast exposure heterogeneity in ranges currently experienced and permitted in most developed nations, and the air monitoring and modeling methods employed will provide individual estimates of exposure that incorporate residence-specific infiltration characteristics and participant-specific time-activity patterns. The overarching study aim is to understand and reduce uncertainty in health effect estimation regarding long-term exposure to air pollution and CVD. PMID:23043127

[Is there an age limit for cadaveric kidney donors currently?].

PubMed

Cofán Pujol, F; Oppenheimer Salinas, F; Talbot-Wright, R; Carretero González, P

1996-12-01

The insufficient number of kidney transplants has gradually raised the age limit to the cadaver kidney donor. The use of grafts harvested from older donors has been debated due to the existing structural and functional changes that might influence renal function and long-term graft survival. The foregoing aspects are discussed herein. The anatomical, histological and functional changes in the kidney associated with ageing are analyzed. The clinical experience with renal grafts from older donors before and after cyclosporine became available are reviewed. The ethical issues on whether grafts from very old donors should be used and who should receive these grafts are discussed. The use of grafts from donors over 60 years old had no significant short and medium term differences in comparison with younger donors in terms of graft survival, although a higher incidence of acute tubular necrosis and poor renal function have been observed. There are no conclusive studies on the long-term effects on graft survival when kidneys from donors aged over 65 are utilized. In our experience, the results achieved with grafts from donors over 70 has been unsatisfactory. The guidelines utilized in the selection of grafts derived from older donors are presented. Grafts from donors aged 60 to 70 may be utilized in renal transplantation following precise selection criteria. Graft survival has been satisfactory, although a higher incidence of acute tubular necrosis and higher creatinine levels have been observed. We do not advocate the use of grafts from donors over 70, except in very exceptional cases. Long-term multicenter studies on grafts from very old donors and trials using alternative immunosuppressor modalities that might permit optimal use of these grafts are warranted.

Fusiform dilatation of the internal carotid artery in childhood-onset craniopharyngioma: multicenter study on incidence and long-term outcome.

PubMed

Hoffmann, Anika; Warmuth-Metz, Monika; Lohle, Kristin; Reichel, Julia; Daubenbüchel, Anna M M; Sterkenburg, Anthe S; Müller, Hermann L

2016-08-01

Fusiform dilatations of the internal carotid artery (FDCA) represent a vascular complication following surgery for suprasellar tumors in children. Incidence rate and long-term prognosis of FDCA in terms of survival rates, vascular complications, and quality of survival are unknown for patients with childhood-onset craniopharyngioma. Magnetic resonance imaging (MRI) results of 583 patients with childhood-onset craniopharyngioma, recruited from 2001 to 2015 in the German Childhood Craniopharyngioma Registry, were reviewed for FDCA. Risk factors for FDCA and long-term outcome after FDCA were analyzed. Fourteen of 583 patients (2.4 %) developed FDCA based on reference assessment of MRI. FDCA occurred ipsilateral to the surgical approach and was not related to degree of resection, hypothalamic involvement, or irradiation. The median time interval between first detection of FDCA and initial surgery was 0.79 years (range 0.01-5.56 years). During a median follow-up of 6.47 years (range 1.2-21.9 years) after first detection of FDCA, no bleeding or cerebrovascular events were observed in any patient. Irradiation was not related to FDCA. Survival rates and functional capacity were similar in patients with and without FDCA. Clinically the FDCA was unapparent in all cases and not treated. FDCA is a rare complication related to surgical treatment of childhood-onset craniopharyngioma without major impact on prognosis and clinical course of the disease. KRANIOPHARYNGEOM 2000-NCT00258453; KRANIOPHARYNGEOM 2007-NCT01272622.

Long-term immunogenicity of two doses of 2009 A/H1N1v vaccine with and without AS03(A) adjuvant in HIV-1-infected adults.

PubMed

Durier, Christine; Desaint, Corinne; Lucht, Frédéric; Girard, Pierre-Marie; Lévy, Yves; May, Thierry; Michelet, Christian; Rami, Agathe; Roman, François; Delfraissy, Jean-François; Aboulker, Jean-Pierre; Launay, Odile

2013-01-02

In immunocompromised patients, alternative schedules more immunogenic than the standard influenza vaccine regimen are necessary to enhance and prolong vaccine efficacy. We previously reported that the AS03A-adjuvanted 2009 A/H1N1v vaccine yielded a higher short-term immune response than the nonadjuvanted one in HIV-1-infected adults. This study reports the long-term persistence of the immune response. In a prospective, multicenter, randomized, patient-blinded trial, two doses of AS03A-adjuvanted H1N1v vaccine containing 3.75 μg haemagglutinin (n = 155; group A) or nonadjuvanted H1N1v vaccine containing 15 μg haemagglutinin (n = 151; group B), were administered 21 days apart. Haemagglutination inhibition and neutralizing antibodies were assessed 6 and 12 months after vaccination. In group A and B, the seroprotection rates were 83.7 and 59.4% at month 6, and 70.4 and 49.3 at month 12, respectively. In a multivariate analysis, persistence of seroprotection 12 months after vaccination was negatively associated with current smoking (odds ratio = 0.6, P = 0.03) and positively related with the AS03A-adjuvanted H1N1v vaccine (odds ratio = 2.7, P = 0.0002). In HIV-1-infected adults, two doses of adjuvanted influenza vaccine induce long-term persistence of immune response up to 1 year after vaccination.

After initial treatment for primary breast cancer: information needs, health literacy, and the role of health care workers.

PubMed

Schmidt, Anna; Ernstmann, Nicole; Wesselmann, Simone; Pfaff, Holger; Wirtz, Markus; Kowalski, Christoph

2016-02-01

After a short hospital stay of just some days follows long-term outpatient care for breast cancer patients. The aim of the study is to describe the information needs of breast cancer outpatients and to get in touch with aspects of health literacy, as well as contact various health care workers. In a multicenter study, patients were asked about their information needs 10 weeks after surgery. The analysis on hand includes data about 1248 female patients. In addition to descriptive analyses identifying the most prevalent information needs, logistic regression analyses were calculated to identify factors associated with these. The results show that information needs of breast cancer outpatients are mainly in "follow-up after acute treatment", "coping with long-term side effects", and "heredity of breast cancer". In addition to sociodemographic patient characteristics, perceived helpful contacts with various health care workers as well as a satisfactory patient's level of health literacy reduced the probability of unmet information needs. Breast cancer outpatients have numerous information needs. In addition to provide information at the right time regarding a specific disease phase, it is important that health professionals' support affected breast cancer patients in coping with the new situation.

Aripiprazole once-monthly as maintenance treatment for bipolar I disorder: a 52-week, multicenter, open-label study.

PubMed

Calabrese, Joseph R; Jin, Na; Johnson, Brian; Such, Pedro; Baker, Ross A; Madera, Jessica; Hertel, Peter; Ottinger, Jocelyn; Amatniek, Joan; Kawasaki, Hiroaki

2018-06-10

The long-acting injectable antipsychotic aripiprazole once-monthly 400 mg (AOM 400) was recently approved for maintenance treatment of bipolar I disorder (BP-I). The purpose of this study was to evaluate the safety, tolerability, and efficacy of AOM 400 as long-term maintenance treatment for BP-I. This open-label multicenter study evaluated the effectiveness of AOM 400 as maintenance treatment for BP-I by assessing safety and tolerability (primary objective) and efficacy (secondary objective). The study enrolled AOM 400-naive ("de novo") patients as well as AOM 400-experienced ("rollover") patients with BP-I from a lead-in randomized, placebo-controlled clinical trial that demonstrated the efficacy of AOM 400 in the maintenance treatment of BP-I (Calabrese et al. in J Clin Psychiatry 78:324-331, 2017). Safety variables included frequency and severity of treatment-emergent adverse events (TEAEs) and TEAEs resulting in study discontinuation. Efficacy was assessed by the proportion of patients maintaining stability throughout the maintenance phase, as well as mean changes from baseline in Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale, and Clinical Global Impressions for Bipolar Disorder-Severity of Illness Scale (CGI-BP-S) total scores. Patient acceptability and tolerability of treatment was assessed using the Patient Satisfaction with Medication Questionnaire-Modified. Of 464 patients entering the maintenance phase, 379 (82%) were de novo and 85 (18%) were rollover. TEAEs were more common in de novo than rollover patients. The overall discontinuation rate due to TEAEs was 10.3% (48/464). Improvements in YMRS and CGI-BP-S total scores were maintained during the study, and the vast majority of both de novo (87.0%) and rollover (97.6%) patients maintained stability through their last visit. Overall, the need for rescue medication during the maintenance phase was minimal (< 10% of patients). Patient satisfaction levels were high, with both de novo and rollover patients rating the side effect burden of AOM 400 as greatly improved relative to previous medications. AOM 400 was safe, effective, and well tolerated by both de novo and AOM 400-experienced patients with BP-I for long-term maintenance treatment. Trial registration ClinicalTrials.gov, NCT01710709.

Lumen-apposing covered self-expandable metal stents for short benign gastrointestinal strictures: a multicenter study.

PubMed

Yang, Dennis; Nieto, Jose M; Siddiqui, Ali; Riff, Brian P; DiMaio, Christopher J; Nagula, Satish; Ismail, Amr M; Ngamreungphong, Saowanee; Khashab, Mouen A; Wagh, Mihir S; Tzimas, Demetrios; Buscaglia, Jonathan M; Strand, Daniel S; Wang, Andrew Y; Chauhan, Shailendra S; Forsmark, Christopher E; Draganov, Peter V

2017-04-01

Background and study aim  Use of the fully covered self-expandable metal stent (SEMS) for benign luminal gastrointestinal (GI) stricture (BLGS) has been limited by the migration rate. The role of the lumen-apposing metal stent (LAMS) for BLGS is not well defined. We assessed the safety, feasibility, and efficacy of LAMS for the treatment of BLGS. Patients and methods  This was an observational, open-label, retrospective, single-arm, multicenter consecutive case series of patients undergoing LAMS placement for BLGS. Technical success was defined as successful placement of the LAMS. Short- and long-term clinical success rates were defined as symptom improvement/resolution with indwelling stent and after stent removal, respectively. All adverse events and additional interventions were recorded. Results  A total of 30 patients (mean age 51.6 years; 63.3 % women) underwent LAMS placement for GI strictures (83.9 % anastomotic). Median stricture diameter and length were 4.5 mm (range 2 - 10 mm) and 8 mm (range 5 - 10 mm), respectively. Technical success was achieved in 29 patients (96.7 %), with an adverse event rate of 13.3 %. The stent migration rate was 8.0 % (2/25) on follow-up endoscopy. Short-term clinical success was achieved in 90.0 % (27/30) at a median of 60 days (interquartile range [IQR] 40 - 90 days). Most patients (19/23; 82.6 %) experienced sustained symptom improvement/resolution without the need for additional interventions at a median follow-up of 100 days (IQR 60 - 139 days) after LAMS removal. Conclusion  This multicenter study demonstrated that LAMS placement represents a safe, feasible, and effective therapeutic option for patients with BLGS and is associated with a low stent migration rate. Our initial findings suggest that future prospective comparative studies are needed on the use of LAMS, endoscopic dilation, and conventional SEMS. . © Georg Thieme Verlag KG Stuttgart · New York.

Pediatric Cancer Survivorship Research: Experience of the Childhood Cancer Survivor Study

PubMed Central

Leisenring, Wendy M.; Mertens, Ann C.; Armstrong, Gregory T.; Stovall, Marilyn A.; Neglia, Joseph P.; Lanctot, Jennifer Q.; Boice, John D.; Whitton, John A.; Yasui, Yutaka

2009-01-01

The Childhood Cancer Survivor Study (CCSS) is a comprehensive multicenter study designed to quantify and better understand the effects of pediatric cancer and its treatment on later health, including behavioral and sociodemographic outcomes. The CCSS investigators have published more than 100 articles in the scientific literature related to the study. As with any large cohort study, high standards for methodologic approaches are imperative for valid and generalizable results. In this article we describe methodological issues of study design, exposure assessment, outcome validation, and statistical analysis. Methods for handling missing data, intrafamily correlation, and competing risks analysis are addressed; each with particular relevance to pediatric cancer survivorship research. Our goal in this article is to provide a resource and reference for other researchers working in the area of long-term cancer survivorship. PMID:19364957

Healthcare-associated infections in pediatric cancer patients: results of a prospective surveillance study from university hospitals in Germany and Switzerland.

PubMed

Simon, Arne; Ammann, Roland A; Bode, Udo; Fleischhack, Gudrun; Wenchel, Hans-Martin; Schwamborn, Dorothee; Gravou, Chara; Schlegel, Paul-Gerhardt; Rutkowski, Stefan; Dannenberg, Claudia; Körholz, Dieter; Laws, Hans Jürgen; Kramer, Michael H

2008-05-23

Pediatric cancer patients face an increased risk of healthcare-associated infection (HAI). To date, no prospective multicenter studies have been published on this topic. Prospective multicenter surveillance for HAI and nosocomial fever of unknown origin (nFUO) with specific case definitions and standardized surveillance methods. 7 pediatric oncology centers (university facilities) participated from April 01, 2001 to August 31, 2005. During 54,824 days of inpatient surveillance, 727 HAIs and nFUOs were registered in 411 patients. Of these, 263 (36%) were HAIs in 181 patients, for an incidence density (ID) (number of events per 1,000 inpatient days) of 4.8 (95% CI 4.2 to 5.4; range 2.4 to 11.7; P < 0.001), and 464 (64%) were nFUO in 230 patients. Neutropenia at diagnosis correlated significantly with clinical severity of HAI. Of the 263 HAIs, 153 (58%) were bloodstream infections (BSI). Of the 138 laboratory-confirmed BSIs, 123 (89%) were associated with use of a long-term central venous catheter (CVAD), resulting in an overall ID of 2.8 per 1,000 utilization days (95% CI 2.3 to 3.3). The ID was significantly lower in Port-type than in Hickman-type CVADs. The death of 8 children was related to HAI, including six cases of aspergillosis. The attributable mortality was 3.0% without a significant association to neutropenia at time of NI diagnosis. Our study confirmed that pediatric cancer patients are at an increased risk for specific HAIs. The prospective surveillance of HAI and comparison with cumulative multicenter results are indispensable for targeted prevention of these adverse events of anticancer treatment.

Long-term safety and efficacy of a novel once-weekly oral trelagliptin as monotherapy or in combination with an existing oral antidiabetic drug in patients with type 2 diabetes mellitus: A 52-week open-label, phase 3 study.

PubMed

Inagaki, Nobuya; Sano, Hiroki; Seki, Yoshifumi; Kuroda, Shingo; Kaku, Kohei

2016-09-01

Trelagliptin is a novel once-weekly oral dipeptidyl peptidase-4 inhibitor for type 2 diabetes mellitus that was first approved in Japan. We evaluated long-term safety and efficacy of trelagliptin in Japanese patients with type 2 diabetes mellitus. This was a phase 3, multicenter, open-label study to evaluate long-term safety and efficacy of trelagliptin. Patients with type 2 diabetes mellitus inadequately controlled despite diet/exercise or treatment with one of the existing oral antidiabetic drugs along with diet/exercise received trelagliptin 100 mg orally once weekly for 52 weeks as monotherapy or combination therapies. The primary end-points were the safety variables, and the secondary end-points were glycosylated hemoglobin and fasting plasma glucose. A total of 680 patients received the following antidiabetic therapies: trelagliptin monotherapy (n = 248), combination with a sulfonylurea (n = 158), a glinide (n = 67), an α-glucosidase inhibitor (n = 65), a biguanide (n = 70), or a thiazolidinedione (n = 72). During the study, 79.8% of the patients experienced at least one adverse event for monotherapy, 87.3% for combination with a sulfonylurea, 77.6% for a glinide, 81.5% for an α-glucosidase inhibitor, 64.3% for a biguanide, and 84.7% for a thiazolidinedione, respectively. Most of the adverse events were mild or moderate. The change in glycosylated hemoglobin from baseline at the end of the treatment period was -0.74 to -0.25% for each therapy. Once-weekly oral trelagliptin provides well-tolerated long-term safety and efficacy in both monotherapy and combination therapies in Japanese patients with type 2 diabetes mellitus. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Hemoglobin A1c and short-term outcomes in patients with acute myocardial infarction undergoing primary angioplasty: an observational multicenter study.

PubMed

Tian, Li; Zhu, Jun; Liu, Lisheng; Liang, Yan; Li, Jiandong; Yang, Yanmin

2013-01-01

Several studies to date have examined whether admission levels of hemoglobin A1c (HbA1c) correlate with short-term and long-term outcomes in patients with acute myocardial infarction treated with primary percutaneous coronary intervention (PCI). However, the results have been ambiguous. We speculated that admission levels of HbA1c correlate with short-term outcomes of patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI. In this observational multicenter study, 608 patients with STEMI who underwent primary PCI between June 2001 and July 2004 were enrolled. Blood samples were collected upon admission to hospital for HbA1c measurement. Follow-up was carried out at 7 and 30 days after hospital admission. According to the new American Diabetes Association criteria, patients were stratified into three groups: I, HbA1c 5.6% or less (n=262); II, HbA1c 5.7-6.4% (n=182); and III, HbA1c at least 6.5% (n=164). The primary outcomes were all-cause mortality and major adverse cardiac events at follow-up. The 7-day mortality was similar (P=0.179) between groups I (1.9%), II (2.2%), and III (0.0%); the 30-day mortality was also similar (P=0.241) between groups I (3.8%), II (2.2%), and III (1.2%). MACE at the 7- day and 30-day follow-up were not significantly different between the three groups either (P>0.05). Rates of target vessel revascularization and rehospitalization, and MACE-free survival curves, at the 30-day follow-up were also similar among the three groups. After adjusting the baseline characteristics, HbA1c was not an independent predictor of short-term outcomes (hazards ratio: 0.431; 95% confidence interval: 0.175-1.061, P=0.067). Admission levels of HbA1c are not an independent prognostic marker for short-term outcomes in STEMI patients treated with primary PCI.

The Long-Term Safety of S-Flurbiprofen Plaster for Osteoarthritis Patients: An Open-Label, 52-Week Study.

PubMed

Yataba, Ikuko; Otsuka, Noboru; Matsushita, Isao; Matsumoto, Hideo; Hoshino, Yuichi

2016-08-01

The newly developed S-flurbiprofen plaster (SFPP) is a tape-type patch that shows innovative percutaneous absorption. This study was designed to evaluate the safety of a long-term 52-week SFPP application to osteoarthritis (OA) patients. This was a multi-center, open-label, uncontrolled prospective study that included 201 OA patients. SFPP at 40 mg/day was applied to the site of pain in 101 patients and at 80 mg/day (2 patches) in 100 patients at a total of 301 sites for 52 weeks. The affected sites assessed included the knee (192), lumbar spine (66), cervical spine (26), and others (17). Drug safety was evaluated by medical examination, laboratory tests, and examination of vital signs. Efficacy was evaluated by the patient's and clinician's global assessments and clinical symptoms. Most patients (80.1 %) completed the 52-week SFPP application. The majority of drug-related adverse events (AEs) included mild dermatitis at the application sites and occurred in 46.8 % of the sites. No photosensitive dermatitis was observed. Systemic AEs occurred in 9.0 % of the patients; a serious AE (gastric ulcer hemorrhage) occurred in one patient. No clinically significant changes in the laboratory tests and vital signs were observed. The efficacy evaluation showed an improvement from 2 weeks after the SFPP application, which continued during the 52 weeks' treatment. No apparent safety concerns were observed, even during the long-term SFPP application. Therefore, SFPP could be an additional pharmacotherapy in OA treatment.

Short- and long-term performance of a tripolar down-sized single lead for implantable cardioverter defibrillator treatment: a randomized prospective European multicenter study. European Endotak DSP Investigator Group.

PubMed

Sandstedt, B; Kennergren, C; Schaumann, A; Herse, B; Neuzner, J

1998-11-01

A new, thinner (10 Fr) and more flexible, single-pass transvenous endocardial ICD lead, Endotak DSP, was compared with a conventional lead, Endotak C, as a control in a prospective randomized multicenter study in combination with a nonactive can ICD. A total of 123 patients were enrolled, 55 of whom received a down-sized DSP lead. Lead-alone configuration was successfully implanted in 95% of the DSP patients vs 88% in the control group. The mean defibrillation threshold (DFT) was determined by means of a step-down protocol, and was identical in the two groups, 10.5 +/- 4.8 J in the DSP group versus 10.5 +/- 4.8 J in the control group. At implantation, the DSP mean pacing threshold was lower, 0.51 +/- 0.18 V versus 0.62 +/- 0.35 V (p < 0.05) in the control group, and the mean pacing impedance higher, 594 +/- 110 omega vs 523 +/- 135 omega (p < 0.05). During the follow-up period, the statistically significant difference in thresholds disappeared, while the difference in impedance remained. Tachyarrhythmia treatment by shock or antitachycardia pacing (ATP) was delivered in 53% and 41%, respectively, of the patients with a 100% success rate. In the DSP group, all 28 episodes of polymorphic ventricular tachycardia or ventricular fibrillation were converted by the first shock as compared to 57 of 69 episodes (83%) in the control group (p < 0.05). Monomorphic ventricular tachycardias were terminated by ATP alone in 96% versus 94%. Lead related problems were minor and observed in 5% and 7%, respectively. In summary, both leads were safe and efficacious in the detection and treatment of ventricular tachyarrhythmias. There were no differences between the DSP and control groups regarding short- or long-term lead related complications.

In vivo and in vitro performance of a China-made hemodialysis machine: a multi-center prospective controlled study.

PubMed

Wang, Yong; Chen, Xiang-Mei; Cai, Guang-Yan; Li, Wen-Ge; Zhang, Ai-Hua; Hao, Li-Rong; Shi, Ming; Wang, Rong; Jiang, Hong-Li; Luo, Hui-Min; Zhang, Dong; Sun, Xue-Feng

2017-08-02

To evaluate the in vivo and in vitro performance of a China-made dialysis machine (SWS-4000). This was a multi-center prospective controlled study consisting of both long-term in vitro evaluations and cross-over in vivo tests in 132 patients. The China-made SWS-4000 dialysis machine was compared with a German-made dialysis machine (Fresenius 4008) with regard to Kt/V values, URR values, and dialysis-related adverse reactions in patients on maintenance hemodialysis, as well as the ultrafiltration rate, the concentration of electrolytes in the proportioned dialysate, the rate of heparin injection, the flow rate of the blood pump, and the rate of malfunction. The Kt/V and URR values at the 1st and 4th weeks of dialysis as well as the incidence of adverse effects did not differ between the two groups in cross-over in vivo tests (P > 0.05). There were no significant differences between the two groups in the error values of the ultrafiltration rate, the rate of heparin injection or the concentrations of electrolytes in the proportioned dialysate at different time points under different parameter settings. At weeks 2 and 24, with the flow rate of the blood pump set at 300 mL/min, the actual error of the SWS-4000 dialysis machine was significantly higher than that of the Fresenius 4008 dialysis machine (P < 0.05), but there was no significant difference at other time points or under other settings (P > 0.05). The malfunction rate was higher in the SWS-4000 group than in the Fresenius 4008 group (P < 0.05). The in vivo performance of the SWS-4000 dialysis machine is roughly comparable to that of the Fresenius 4008 dialysis machine; however, the malfunction rate of the former is higher than that of the latter in in vitro tests. The stability and long-term accuracy of the SWS-4000 dialysis machine remain to be improved.

A multicenter experience with the surgical treatment of infected abdominal aortic endografts.

PubMed

Davila, Victor J; Stone, William; Duncan, Audra A; Wood, Emily; Jordan, William D; Zea, Nicholas; Sternbergh, W Charles; Money, Samuel R

2015-10-01

Single-center experiences with the treatment of infected endografts after endovascular aortic repair (I-EVAR) have been reported. We performed a multicenter review of the surgical care of these patients to elucidate short-term and long-term outcomes. A retrospective analysis of all EVAR explants from 1997 to 2014 at four institutions was performed. Patients with I-EVAR undergoing surgical treatment were reviewed. Data were obtained detailing preoperative demographics, and postoperative morbidity and mortality. Thirty-six patients (30 male) were treated with endovascular graft excision and revascularization for I-EVAR with a median age of 69 years (range, 54-80 years). Average time from the initial EVAR to presentation was 589 days (range, 43-2466 days). Preoperative comorbidities included hypertension, 32 (89%); tobacco use, 31(86%); coronary artery disease, 26 (72%); hyperlipidemia, 25 (69%), peripheral artery disease, 13 (36%); cerebrovascular disease, 10 (28%); diabetes, 10 (28%); chronic obstructive pulmonary disease, 9 (25%); and chronic kidney disease, 9 (25%). The most common presenting patient characteristics were leukocytosis, 23 (63%); pain, 21 (58%); and fever, 20 (56%), which were present an average of 65 days (range, 0-514 days) before explantation. Nine different types of endograft were removed. Three patients (8%) underwent emergency explantation. Thirty-four patients (89%) underwent total graft excision, and two patients (6%) underwent partial excision. Methods of reconstruction were in situ in 27 (75%) and extra-anatomic in nine (28%). Conduits used were Dacron (DuPont, Wilmington, Del), with or without rifampin, polytetrafluoroethylene, cryopreserved allograft, and femoral vein. Forty-nine organisms grew from operative cultures. Gram-positive organisms were the most common, found in 24 (67%), including Staphylococcus in 13 (36%) and Streptococcus in six (17%). Anaerobes were cultured in 6 patients (17%), gram-negative organisms in 6 (17%), and fungus in 5 (14%). Thirty-one patients (86%) received long-term antibiotics. Early complications included acute renal failure requiring dialysis, 12 (33%); respiratory failure, 3 (8%); bleeding, 4 (11%); and sepsis, 2 (6%). Six patients required re-exploration due to hematoma, infected hematoma, lymphatic leak, bowel perforation, open abdomen at initial operation, and anastomotic bleeding. Perioperative mortality was 8% (3 of 36), and long-term mortality was 25% (9 of 36) at a mean follow-up of 569 days (range, 0-3079 days). Type of reconstruction (in situ vs extra-anatomic) or conduit type did not affect perioperative or overall mortality. I-EVAR is a rare but potentially devastating clinical problem. Although perioperative mortality is acceptable, long-term mortality is high. The most common postoperative complication was acute renal failure requiring dialysis. Although this is the largest series of I-EVAR, further studies are needed to understand the risk factors and preventive measures. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Effect of lyophilized lactobacilli and 0.03 mg estriol (Gynoflor®) on vaginitis and vaginosis with disrupted vaginal microflora: a multicenter, randomized, single-blind, active-controlled pilot study.

PubMed

Donders, G G G; Van Bulck, B; Van de Walle, P; Kaiser, R R; Pohlig, G; Gonser, S; Graf, F

2010-01-01

To evaluate the efficacy of lyophilized lactobacilli in combination with 0.03 mg estriol when compared to metronidazole in the treatment of bacterial vaginal infections. Multicenter, randomized, single-blind, active-controlled pilot study in 3 independent gynecological practices in Belgium. Forty-six, 18- to 50-year-old premenopausal women with a disrupted vaginal flora due to a bacterial vaginal infection (bacterial vaginosis, aerobic vaginitis) were included, provided that fresh phase-contrast microscopy of the vaginal fluid showed lactobacillary flora grade 2B or 3. Patients were given a blinded box with either 12 vaginal tablets of Gynoflor® (study medication) or 6 vaginal suppositories containing 500 mg metronidazole (control medication). Eight efficacy variables were studied to assess the status of the vaginal flora at entry, 3-7 days (control 1), 4-6 (control 2) weeks and 4 months after the end of therapy. At control 1, the combined variables equally improved in the lactobacilli group as in the metronidazole group. At control 2, the lactobacillus preparation showed slightly inferior results when compared to metronidazole. At 4 months, this analysis could not be performed due to low numbers, but analysis of recurrence rate and extra medication needed was not different between both groups. Lyophilized lactobacilli in combination with low-dose estriol are equivalent to metronidazole in the short-term treatment of bacterial vaginal infections, but have less effect after 1 month. Further studies are required to evaluate the long-term efficacy of lactobacilli when applied repeatedly. Copyright © 2010 S. Karger AG, Basel.

Comparison of Hepatic 2D Sandwich Cultures and 3D Spheroids for Long-term Toxicity Applications: A Multicenter Study

PubMed Central

Bell, Catherine C; Dankers, Anita C A; Sison-Young, Rowena; Jenkins, Roz; Rowe, Cliff; Goldring, Chris E; Park, Kevin; Regan, Sophie L; Walker, Tracy; Schofield, Chris; Baze, Audrey; Foster, Alison J; Williams, Dominic P; van de Ven, Amy W M; Jacobs, Frank; van Houdt, Jos; Lähteenmäki, Tuula; Snoeys, Jan; Juhila, Satu; Richert, Lysiane; Ingelman-Sundberg, Magnus

2018-01-01

Abstract Primary human hepatocytes (PHHs) are commonly used for in vitro studies of drug-induced liver injury. However, when cultured as 2D monolayers, PHH lose crucial hepatic functions within hours. This dedifferentiation can be ameliorated when PHHs are cultured in sandwich configuration (2Dsw), particularly when cultures are regularly re-overlaid with extracellular matrix, or as 3D spheroids. In this study, the 6 participating laboratories evaluated the robustness of these 2 model systems made from cryopreserved PHH from the same donors considering both inter-donor and inter-laboratory variability and compared their suitability for use in repeated-dose toxicity studies using 5 different hepatotoxins with different toxicity mechanisms. We found that expression levels of proteins involved in drug absorption, distribution, metabolism, and excretion, as well as catalytic activities of 5 different CYPs, were significantly higher in 3D spheroid cultures, potentially affecting the exposure of the cells to drugs and their metabolites. Furthermore, global proteomic analyses revealed that PHH in 3D spheroid configuration were temporally stable whereas proteomes from the same donors in 2Dsw cultures showed substantial alterations in protein expression patterns over the 14 days in culture. Overall, spheroid cultures were more sensitive to the hepatotoxic compounds investigated, particularly upon long-term exposures, across testing sites with little inter-laboratory or inter-donor variability. The data presented here suggest that repeated-dosing regimens improve the predictivity of in vitro toxicity assays, and that PHH spheroids provide a sensitive and robust system for long-term mechanistic studies of drug-induced hepatotoxicity, whereas the 2Dsw system has a more dedifferentiated phenotype and lower sensitivity to detect hepatotoxicity. PMID:29329425

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.

[Test set for the evaluation of hearing and speech development after cochlear implantation in children].

PubMed

Lamprecht-Dinnesen, A; Sick, U; Sandrieser, P; Illg, A; Lesinski-Schiedat, A; Döring, W H; Müller-Deile, J; Kiefer, J; Matthias, K; Wüst, A; Konradi, E; Riebandt, M; Matulat, P; Von Der Haar-Heise, S; Swart, J; Elixmann, K; Neumann, K; Hildmann, A; Coninx, F; Meyer, V; Gross, M; Kruse, E; Lenarz, T

2002-10-01

Since autumn 1998 the multicenter interdisciplinary study group "Test Materials for CI Children" has been compiling a uniform examination tool for evaluation of speech and hearing development after cochlear implantation in childhood. After studying the relevant literature, suitable materials were checked for practical applicability, modified and provided with criteria for execution and break-off. For data acquisition, observation forms for preparation of a PC-version were developed. The evaluation set contains forms for master data with supplements relating to postoperative processes. The hearing tests check supra-threshold hearing with loudness scaling for children, speech comprehension in silence (Mainz and Göttingen Test for Speech Comprehension in Childhood) and phonemic differentiation (Oldenburg Rhyme Test for Children), the central auditory processes of detection, discrimination, identification and recognition (modification of the "Frankfurt Functional Hearing Test for Children") and audiovisual speech perception (Open Paragraph Tracking, Kiel Speech Track Program). The materials for speech and language development comprise phonetics-phonology, lexicon and semantics (LOGO Pronunciation Test), syntax and morphology (analysis of spontaneous speech), language comprehension (Reynell Scales), communication and pragmatics (observation forms). The MAIS and MUSS modified questionnaires are integrated. The evaluation set serves quality assurance and permits factor analysis as well as controls for regularity through the multicenter comparison of long-term developmental trends after cochlear implantation.

Peripheral Applications of Drug-Coated Balloons: Past, Present and Future

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

Krokidis, Miltiadis, E-mail: mkrokidis@hotmail.com; Spiliopoulos, Stavros, E-mail: stavspiliop@upatras.gr; Katsanos, Konstantinos, E-mail: katsanos@med.upatras.gr

2013-04-15

Drug-coated balloon (DCB) technologies represent the latest and hottest development in the field of endovascular treatment of peripheral arterial disease. Initial experience with paclitaxel-coated balloon use in the femoral artery has demonstrated lower mid-term restenosis and superior mid-term clinical outcomes in terms of improved wound healing and reduced repeat angioplasty rates compared with standard balloon angioplasty. Many companies are presently developing and/or improving DCB catheters and therefore ongoing, technical improvements of the already existing platforms, new drugs, and innovative carriers are expected. The ongoing basic research studies and various multicenter randomized, controlled trials that are currently in progress will offermore » valuable scientific insights regarding the long-term effectiveness and other crucial issues, such as efficacy in various vascular beds, optimal balloon dosage, and post angioplasty antiplatelet therapy. Future applications of these devices also could include in-stent restenosis, anastomotic stenosis of surgical bypass, and benign stenoses of the central venous system. The authors envision that DCB angioplasty will evolve to a major paradigm shift in the endovascular treatment of occlusive vascular diseases.« less

BCAA-enriched snack improves nutritional state of cirrhosis.

PubMed

Nakaya, Yutaka; Okita, Kiwamu; Suzuki, Kazuyuki; Moriwaki, Hisataka; Kato, Akinobu; Miwa, Yoshiyuki; Shiraishi, Koichi; Okuda, Hiroaki; Onji, Morikazu; Kanazawa, Hidenori; Tsubouchi, Hirohito; Kato, Shinzo; Kaito, Masahiko; Watanabe, Akiharu; Habu, Daiki; Ito, Susumu; Ishikawa, Tomohisa; Kawamura, Naohiro; Arakawa, Yasuyuki

2007-02-01

A late evening snack improves the catabolic state in patients with advanced liver cirrhosis. We tested whether long-term (3 mo) late evening snacking that included a branched-chain amino acid (BCAA)-enriched nutrient mixture produces a better nutritional state and better quality of life than ordinary food in patients with hepatitis C virus-positive liver cirrhosis. In a multicenter, randomized study, 48 patients with liver cirrhosis received late-evening supplementation with the BCAA-enriched nutrient mixture or ordinary food, such as a rice ball or bread, for 3 mo. During the study period, each patient was instructed on energy and protein intake. Blood biochemical data, nitrogen balance, respiratory quotient, and health-related quality of life (Short Form 36 questionnaire) were evaluated at baseline and at the end of the study. Total and late-evening energy intakes were similar in the two groups at 3 mo. Serum albumin level, nitrogen balance, and respiratory quotient were significantly improved by the BCAA mixture but not by ordinary food. The parameters of the Short Form 36 did not statistically significantly improve over 3 mo in either group. Long-term oral supplementation with a BCAA mixture is better than ordinary food in a late evening snack at improving the serum albumin level and the energy metabolism in patients with cirrhosis.

Pharmacogenetic study of second-generation antipsychotic long-term treatment metabolic side effects (the SLiM Study): rationale, objectives, design and sample description.

PubMed

Pina-Camacho, Laura; Díaz-Caneja, Covadonga M; Saiz, Pilar A; Bobes, Julio; Corripio, Iluminada; Grasa, Eva; Rodriguez-Jimenez, Roberto; Fernández, Miryam; Sanjuán, Julio; García-López, Aurelio; Tapia-Casellas, Cecilia; Álvarez-Blázquez, María; Fraguas, David; Mitjans, Marina; Arias, Bárbara; Arango, Celso

2014-01-01

Weight gain is an important and common side effect of second generation antipsychotics (SGAs). Furthermore, these drugs can induce other side effects associated with higher cardiovascular morbidity and mortality, such as insulin resistance, diabetes or metabolic syndrome. Preliminary studies show that inter-individual genetic differences produce varying degrees of vulnerability to the different SGA-induced side effects. The Second-generation antipsychotic Long-term treatment Metabolic side effects (SLiM) study aims to identify clinical, environmental and genetic factors that explain inter-individual differences in weight gain and metabolic changes in drug-naïve patients after six months of treatment with SGAs. The SLIM study is a multicenter, observational, six-month pharmacogenetic study where a cohort of 307 drug-naïve paediatric and adult patients (age range 8.8-90.1 years) and a cohort of 150 age- and sex- matched healthy controls (7.8-73.2 years) were recruited. This paper describes the rationale, objectives and design of the study and provides a description of the sample at baseline. Results from the SLiM study will provide a better understanding of the clinical, environmental, and genetic factors involved in weight gain and metabolic disturbances associated with SGA treatment. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

FTA Cards for Preservation of Nucleic Acids for Molecular Assays: A Review on the Use of Cytologic/Tissue Samples.

PubMed

da Cunha Santos, Gilda

2018-03-01

- Traditional methods for storing histologic and cytologic specimens for future use in molecular assays have consisted of either snap-freezing with cryopreservation or formalin-fixing, paraffin-embedding the samples. Although snap-freezing with cryopreservation is recommended for better preservation of nucleic acids, the infrastructure and space required for archiving impose challenges for high-volume pathology laboratories. Cost-effective, long-term storage at room temperature; relatively easy shipment; and standardized handling can be achieved with formalin-fixed, paraffin-embedded samples, but formalin fixation induces fragmentation and chemical modification of nucleic acids. Advances in next-generation sequencing platforms, coupled with an increase in diagnostic, prognostic, and predictive molecular biomarkers have created a demand for high-quality nucleic acids. To address issues of the quality of nucleic acid and logistics in sample acquisition, alternatives for specimen preservation and long-term storage have been described and include novel universal tissue fixatives, stabilizers, and technologies. - To collect, retrieve, and review information from studies describing the use of nucleic acids recovered from cytologic/tissue specimens stored on Flinders Technology Associates (FTA, GE Whatman, Maidstone, Kent, United Kingdom) cards for downstream molecular applications. - An electronic literature search in the PubMed (National Center for Biotechnology Information, Bethesda, Maryland) database allowed the selection of manuscripts addressing the use of FTA cards for storage of cytologic samples for molecular analysis. Only articles published in English were retrieved. - The use of FTA cards is a versatile method for fostering multicenter, international collaborations and clinical trials that require centralized testing, long-distance shipment, and high-quality nucleic acids for molecular techniques. Studies with controlled temperature are required to test the quality of recovered RNA after long-term storage.

Neuropsychiatric symptoms in geriatric patients admitted to skilled nursing facilities in nursing homes for rehabilitation after stroke: a longitudinal multicenter study.

PubMed

Buijck, Bianca I; Zuidema, Sytse U; Spruit-van Eijk, Monica; Geurts, Alexander C H; Koopmans, Raymond T C M

2012-07-01

To investigate the prevalence and course of neuropsychiatric symptoms (NPS) in geriatric patients admitted to skilled nursing facilities (SNFs) for rehabilitation after stroke. This was a longitudinal multicenter study within 15 SNFs in the Netherlands. NPS were assessed in 145 patients with stroke through the Neuropsychiatric Inventory-Nursing Home version (NPI-NH) with measurements on admission and at discharge. The prevalence and course of NPS were described in terms of cumulative prevalence (symptoms either on admission or at discharge), conversion (only symptoms at discharge), remission (only symptoms on admission), and persistence (symptoms both on admission and at discharge) for patients who were discharged to an independent living situation within one year after admission and patients who had to stay in the SNF for long term care. Eighty percent had a first-ever stroke and 74% could be successfully discharged. Overall, the most common NPS were depression (33%), eating changes (18%), night-time disturbances (19%), anxiety (15%), irritability (12%), and disinhibition (12%). One year after admission, the patients who were still in the SNF showed significantly more hallucinations (p = 0.016), delusions (p = 0.016), agitation (p = 0.004), depression (p = 0.000), disinhibition (p = 0.004), irritability (p = 0.018), and night-time disturbances (p = 0.001) than those who had been discharged. The overall prevalence of NPS in this study was lower than reported by other studies in different settings. There was a high prevalence of NPS in patients that could not be successfully discharged. The findings suggest that NPS should be optimally treated to improve outcome of rehabilitation. Copyright © 2011 John Wiley & Sons, Ltd.

Relationship of Kidney Injury Biomarkers with Long-Term Cardiovascular Outcomes after Cardiac Surgery.

PubMed

Parikh, Chirag R; Puthumana, Jeremy; Shlipak, Michael G; Koyner, Jay L; Thiessen-Philbrook, Heather; McArthur, Eric; Kerr, Kathleen; Kavsak, Peter; Whitlock, Richard P; Garg, Amit X; Coca, Steven G

2017-12-01

Clinical AKI, measured by serum creatinine elevation, is associated with long-term risks of adverse cardiovascular (CV) events and mortality in patients after cardiac surgery. To evaluate the relative contributions of urine kidney injury biomarkers and plasma cardiac injury biomarkers in adverse events, we conducted a multicenter prospective cohort study of 968 adults undergoing cardiac surgery. On postoperative days 1-3, we measured five urine biomarkers of kidney injury (IL-18, NGAL, KIM-1, L-FABP, and albumin) and five plasma biomarkers of cardiac injury (NT-proBNP, H-FABP, hs-cTnT, cTnI, and CK-MB). The primary outcome was a composite of long-term CV events or death, which was assessed via national health care databases. During a median 3.8 years of follow-up, 219 (22.6%) patients experienced the primary outcome (136 CV events and 83 additional deaths). Compared with patients without postsurgical AKI, patients who experienced AKI Network stage 2 or 3 had an adjusted hazard ratio for the primary composite outcome of 3.52 (95% confidence interval, 2.17 to 5.71). However, none of the five urinary kidney injury biomarkers were significantly associated with the primary outcome. In contrast, four out of five postoperative cardiac injury biomarkers (NT-proBNP, H-FABP, hs-cTnT, and cTnI) strongly associated with the primary outcome. Mediation analyses demonstrated that cardiac biomarkers explained 49% (95% confidence interval, 1% to 97%) of the association between AKI and the primary outcome. These results suggest that clinical AKI at the time of cardiac surgery is indicative of concurrent CV stress rather than an independent renal pathway for long-term adverse CV outcomes. Copyright © 2017 by the American Society of Nephrology.

Ward mortality after ICU discharge: a multicenter validation of the Sabadell score.

PubMed

Fernandez, Rafael; Serrano, Jose Manuel; Umaran, Isabel; Abizanda, Ricard; Carrillo, Andres; Lopez-Pueyo, Maria Jesus; Rascado, Pedro; Balerdi, Begoña; Suberviola, Borja; Hernandez, Gonzalo

2010-07-01

Tools for predicting post-ICU patients' outcomes are scarce. A single-center study showed that the Sabadell score classified patients into four groups with clear-cut differences in ward mortality. To validate the Sabadell score using a prospective multicenter approach. Thirty-one ICUs in Spain. All patients admitted in the 3-month study period. We recorded variables at ICU admission (age, sex, severity of illness, and do-not-resuscitate orders), during the ICU stay (ICU-specific treatments, ICU-acquired infection, and acute renal failure), and at ICU discharge (Sabadell score). Statistical analyses included one-way ANOVA and multiple regression analysis with ward mortality as the dependent variable. We admitted 4,132 patients (mean age 61.5 +/- 16.7 years) with mean predicted mortality of 23.8 +/- 22.7%; 545 patients (13%) died in the ICU and 3,587 (87%) were discharged to the ward. Overall ward mortality was 6.7%; ward mortality was 1.5% (36/2,422) in patients with score 0 (good prognosis), 9% (64/725) in patients with score 1 (long-term poor prognosis), 23% (79/341) in patients with score 2 (short-term poor prognosis), and 64% (63/99) in patients with score 3 (expected hospital death). Variables associated with ward mortality in the multivariate analysis were predicted risk of death (OR 1.016), ICU readmission (OR 5.9), Sabadell score 1 (OR 4.7), Sabadell score 2 (OR 15.7), and Sabadell score 3 (OR 107.2). We confirm the ability of the Sabadell score at ICU discharge to define four groups of patients with very different likelihoods of hospital survival.

Severe acute hypophosphatemia during renal replacement therapy adversely affects outcome of critically ill patients with acute kidney injury.

PubMed

Schiffl, Helmut; Lang, Susanne M

2013-02-01

Hypophosphatemia during renal replacement therapy (RRT) is common in critically ill patients with acute kidney injury (AKI). The clinical consequences of RRT-induced phosphate depletion are not well defined in this patient population, and there is no evidence that intravenous sodium phosphate supplementation (PS) prevents the clinical sequelae of acute hypophosphatemia. The purpose of this retrospective analysis of the Acute Renal Support Registry of the University of Munich was to examine the association between severe hypophosphatemia and severity of and recovery from AKI. 289 ICU patients with AKI on intermittent hemodialysis (IHD) were included in the study. One hundred and forty-nine patients received PS during IHD. Outcomes were short-term (at discharge) and long-term (at 1 year) recovery of renal function and mortality. The two patient groups did not differ in demographics, clinical features, renal characteristics, and frequency of hypophosphatemia at initiation of IHD. Without PS, the frequency of hypophosphatemia increased from 20 to 35%. Severe hypophosphatemia was found in 50% of these patients. By comparison, PS was not associated with an increased frequency of hypophosphatemia. Compared with patients with acute phosphate depletion, patients receiving PS developed less oliguria during IHD, had shorter duration of AKI, higher incidence of complete renal recovery at discharge, and a lower risk of de novo chronic kidney disease. Hypophosphatemia was associated with higher all-cause in-hospital mortality and higher risk of long-term mortality. This multicenter study indicates for the first time that hypophosphatemia during IHD adversely affects short- and long-term outcome of critically-ill patients with AKI. The clinical consequences of the acute hypophosphatemic syndrome may be prevented by PS.

Effects of long-term androgen replacement therapy on the physical and mental statuses of aging males with late-onset hypogonadism: a multicenter, randomized controlled trial in Japan (EARTH Study)

PubMed Central

Konaka, Hiroyuki; Sugimoto, Kazuhiro; Orikasa, Hideki; Iwamoto, Teruaki; Takamura, Toshinari; Takeda, Yoshiyu; Shigehara, Kazuyoshi; Iijima, Masashi; Koh, Eitetsu; Namiki, Mikio

2016-01-01

Androgen replacement therapy (ART) efficacy on late-onset hypogonadism (LOH) has been widely investigated in Western countries; however, it remains controversial whether ART can improve health and prolong active lifestyles. We prospectively assessed long-term ART effects on the physical and mental statuses of aging men with LOH in Japan. The primary endpoint was health-related quality of life assessed by questionnaires. Secondary endpoints included glycemic control, lipid parameters, blood pressure, waist circumference, body composition, muscular strength, International Prostate Symptom Scores (IPSS), International Index of Erectile Function-5 (IIEF-5) scores, and serum prostate-specific antigen levels. Of the 1637 eligible volunteers, 334 patients > 40 years with LOH were randomly assigned to either the ART (n = 169) or control groups (n = 165). Fifty-two weeks after the initial treatment, ART significantly affected the role physical subdomain of the short form-36 health survey (SF-36) scale (P = 0.0318). ART was also associated with significant decreases in waist circumstance (P = 0.002) and serum triglyceride (TG) (P = 0.013) and with significant increases in whole-body and leg muscle mass volumes (P = 0.071 and 0.0108, respectively), serum hemoglobin (P < 0.001), IPSS voiding subscore (P = 0.0418), and the second question on IIEF-5 (P = 0.0049). There was no significant difference between the groups in terms of severe adverse events. In conclusion, in patients with LOH, long-term ART exerted beneficial effects on Role Physical subdomain of the SF-36 scale, serum TG, waist circumstance, muscle mass volume, voiding subscore of IPSS, and the second question of IIEF-5. We hope our study will contribute to the future development of this area. PMID:25761833

Multicenter Analysis of Long-Term Oncologic Impact of Anastomotic Leakage After Laparoscopic Total Mesorectal Excision

PubMed Central

Kang, Jeonghyun; Choi, Gyu-Seog; Oh, Jae Hwan; Kim, Nam Kyu; Park, Jun Seok; Kim, Min Jung; Lee, Kang Young; Baik, Seung Hyuk

2015-01-01

Abstract This study aims to validate the oncologic outcomes of anastomotic leakage (AL) after laparoscopic total mesorectal excision (TME) in a large multicenter cohort. The impact of AL after laparoscopic TME for rectal cancer surgery has not yet been clearly described. This was a multicenter retrospective study of 1083 patients who underwent laparoscopic TME for nonmetastatic rectal cancer (stage 0–III). AL was defined as an anastomotic complication within 30 days of surgery irrespective of requiring a reoperation or interventional radiology. Estimated local recurrence (LR), disease-free survival (DFS), and overall survival (OS) were compared between the leakage group and the no leakage group using the log-rank method. Multivariate Cox-regression analysis was used to adjust confounding for survival. The incidence of AL was 6.4%. Mortality within 30 days of surgery occurred in 1 patient (1.4%) in the leakage group and 2 patients (0.2%) in the no leakage group. The leakage group showed a higher LR rate (6.4% vs 1.8%, P = 0.011). Five-year DFS and OS were significantly lower in the leakage group than the no leakage group (DFS 71.7% vs 82.1%, P = 0.016, OS 81.8% vs 93.5%, P = 0.007). Multivariate analysis showed that AL was an independent poor prognostic factor for DFS and OS (hazard ratio [HR] = 1.6; 95% confidence intervals [CI]: 1.0–2.6; P = 0.042, HR = 2.1; 95% CI: 1.0–4.2; P = 0.028, respectively). AL after laparoscopic TME was significantly associated with an increased rate of LR, systemic recurrence and poor OS. PMID:26200636

Safety aspects of lipidapheresis using DALI and MONET - Multicenter observational study.

PubMed

Kozik-Jaromin, Justyna; Röseler, Eberhard; Heigl, Franz; Spitthöver, Ralf; Ringel, Jens; Schmitz, Gerd; Heinzler, Rainer; Abdul-Rahman, Nadim; Leistikow, Frank; Himmelsbach, Frido; Schettler, Volker; Uhlenbusch-Körwer, Ingrid; Ramlow, Wolfgang

2017-11-01

Lipidapheresis was introduced for intractable hyperlipidemia as a more selective therapy than plasma exchange aiming to enhance efficacy and limit side-effects. Although this therapy is regarded safe, multicenter data from routine application are limited. We investigated direct adsorption of lipoproteins (DALI) and lipofiltration (MONET) regarding the short and the long-term safety aspects. This multicenter observational study prospectively evaluated 2154 DALI and 1297 MONET sessions of 122 patients during a period of 2 years. Safety parameters included clinical side-effects (adverse device effects, ADEs), technical complications, blood pressure and pulse rate. Also routinely performed laboratory parameters were documented. Analysis of laboratory parameters was not corrected for blood dilution. Overall 0.4% DALI and 0.5% MONET treatments were affected by ADE. Technical complications occurred in 2.1% and in 0.8% DALI and MONET sessions, respectively. The most frequent ADE was hypotension, and the majority of technical problems were related to vascular access. Both types of treatments led to a drop of thrombocytes in the range of 7-8%. Hematocrit and erythrocytes decreased only during the DALI treatments by about 6%. Leucocytes decreased during the DALI therapy (∼15%), whereas they increased during the MONET application (∼11%). MONET treatment was associated with a higher reduction of proteins (fibrinogen: 58% vs. 23%, albumin: 12% vs. 7%, CRP: 33% vs. 19% for MONET and DALI, respectively). Apart from severe thrombocytopenia in two DALI patients, changes of other parameters were typically transient. Under routine use the frequency of side-effects was low. Still, monitoring of blood count and proteins in chronic apheresis patients is recommended. Copyright © 2017. Published by Elsevier B.V.

Cubital tunnel syndrome: comparative results of a multicenter study of 4 surgical techniques with a mean follow-up of 92 months.

PubMed

Bacle, G; Marteau, E; Freslon, M; Desmoineaux, P; Saint-Cast, Y; Lancigu, R; Kerjean, Y; Vernet, E; Fournier, J; Corcia, P; Le Nen, D; Rabarin, F; Laulan, J

2014-06-01

Cubital tunnel syndrome is the second most frequent entrapment syndrome. Physiopathology is mixed, and treatment options are multiple, none having yet proved superior efficacy. The present retrospective multicenter study compared results and rates of complications and recurrence between the 4 main cubital tunnel syndrome treatments, to identify trends and optimize outcome. Patients presenting with primary clinical cubital tunnel syndrome diagnosed on electroneuromyography were included and operated on using 1 of the following 4 techniques: open or endoscopic in situ decompression, or subcutaneous or submuscular anterior transposition. Four specialized upper-limb surgery centers participated, each systematically performing 1 of the above procedures. Subjective and objective results and rates of complications and recurrence were compared at end of follow-up. Five hundred and two patients were included and 375 followed up for a mean 92 months (range, 9-144 months); 103 were lost to follow-up and 24 died. Whichever the procedure, more than 90% of patients were cured or showed improvement. There was a single case of scar pain at end of follow-up, managed by endoscopic decompression; there were no other long-term complications. None of the 4 techniques aggravated symptoms. There were 6 recurrences by end of follow-up: 1 associated with open in situ decompression and 5 with submuscular transposition. Surgery was effective in treating cubital tunnel syndrome. Submuscular anterior transposition was associated with recurrence. In contrast to literature reports, subcutaneous anterior transposition, which is a reliable and valid technique, was not associated with a higher complication rate than in situ decompression. Level IV. Multicenter retrospective. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

A double-blind study evaluating the long-term safety of varenicline for smoking cessation.

PubMed

Williams, Kathryn E; Reeves, Karen R; Billing, Clare B; Pennington, Ann M; Gong, Jason

2007-04-01

We assessed the safety of long-term varenicline administration for smoking cessation. In this randomized, double-blind, multicenter trial, eligible adult smokers (18-75 years) who smoked an average of > or =10 cigarettes/day were randomized to either varenicline 1 mg twice daily (BID) or placebo for 52 weeks. Subjects made weekly clinic visits until week 8, and then every 4 weeks until week 52, with a follow-up visit at week 53. The target quit date was the morning of the week 1 clinic visit. Brief counseling was provided at each visit, and vital signs, adverse events (AEs), and smoking status were documented. Other laboratory measures were collected at specified visits. A total of 251 subjects were randomized to varenicline and 126 to placebo. Approximately half of the subjects in each arm completed the study (53.8% varenicline; 46.8% placebo). Treatment-emergent AEs were observed in 96.4% of varenicline- and 82.5% of placebo-treated subjects during the study. Common varenicline-associated AEs were nausea (40.2%), abnormal dreams (22.7%), and insomnia (19.1%). Most AEs were considered mild or moderate in intensity. AEs leading to discontinuation of varenicline treatment included nausea (7.6%), insomnia (3.2%), and abnormal dreams (2.4%). A single varenicline-related serious AE, bilateral subcapsular cataracts, was observed. At week 52, 7-day point prevalence abstinence rates were 36.7% (varenicline) and 7.9% (placebo). Varenicline 1 mg BID can be safely administered for up to 1 year. Varenicline was also a more effective smoking cessation aid than placebo throughout the study, supporting both its short- (12-week) and long-term (52-week) efficacy.

Long-Term Response and Remission with Pixantrone in Patients with Relapsed or Refractory Aggressive Non-Hodgkin Lymphoma: Post-Hoc Analysis of the Multicenter, Open-Label, Randomized PIX301 Trial.

PubMed

Pettengell, Ruth; Coiffier, Bertrand; Egorov, Anton; Singer, Jack; Sivcheva, Lilia

2018-06-01

Pixantrone is recommended in relapsed and refractory non-Hodgkin lymphoma (NHL) or heavily pretreated NHL patients. Its conditional approval in Europe was based on results from the open-label, randomized, phase 3 PIX301 study, comparing pixantrone monotherapy with physician's choice of treatment in 140 patients with relapsed or refractory aggressive NHL. This post-hoc analysis of the PIX301 study investigated possible correlations between patient characteristics and clinical response in 17 patients (24%) treated with pixantrone who achieved a complete response (CR) or an unconfirmed complete response (CRu) at study end. These patients (10 male and 7 female) had a median age of 61 (range 41-75) years, and the most common diagnoses were diffuse large B-cell lymphoma (n = 10) and transformed indolent lymphoma (n = 4). Most had received two prior lines of therapy (n = 12). There was wide variation in the time from diagnosis to study entry (219-4777 days). Among the 17 patients who achieved a CR/CRu with pixantrone, 6 had stable or progressive disease as a response to their last regimen, 7 had a partial response, and 4 had a CR/CRu. Four patients from the pixantrone group survived without progression for more than 400 days. Prior response to previous therapies did not appear to affect long-term response to pixantrone. These observations suggest that pixantrone monotherapy in patients with multiply relapsed or refractory aggressive NHL who had received at least two prior therapies can be associated with durable responses and long-term remission, and this may be unrelated to the clinical response to the last therapy.

Prophylaxis of Venous Thromboembolism in Geriatric Settings: A Cluster-Randomized Multicomponent Interventional Trial.

PubMed

Rwabihama, Jean Paul; Audureau, Etienne; Laurent, Marie; Rakotoarisoa, Lalaina; Jegou, Marc; Saddedine, Sofiane; Krypciak, Sébastien; Herbaud, Stéphane; Benzengli, Hind; Segaux, Lauriane; Guery, Esther; Ambime, Gabin; Rabus, Marie-Thérèse; Perilliat, Jean-Guy; David, Jean-Philippe; Paillaud, Elena

2018-06-01

To evaluate the efficacy of an intervention on the practice of venous thromboembolism prevention. A multicenter, prospective, controlled, cluster-randomized, multifaceted intervention trial consisting of educational lectures, posters, and pocket cards reminding physicians of the guidelines for thromboprophylaxis use. Twelve geriatric departments with 1861 beds total, of which 202, 803, and 856 in acute care, post-acute care, and long-term care wards, respectively. Patients hospitalized between January 1 and May 31, 2015, in participating departments. The primary endpoint was the overall adequacy of thromboprophylaxis prescription at the patient level, defined as a composite endpoint consisting of indication, regimen, and duration of treatment. Geriatric departments were divided into an intervention group (6 departments) and control group (6 departments). The preintervention period was 1 month to provide baseline practice levels, the intervention period 2 months, and the postintervention period 1 month in acute care and post-acute care wards or 2 months in long-term care wards. Multivariable regression was used to analyze factors associated with the composite outcome. We included 2962 patients (1426 preintervention and 1536 postintervention), with median age 85 [79;90] years. For the overall 18.9% rate of inadequate thromboprophylaxis, 11.1% was attributable to underuse and 7.9% overuse. Intervention effects were more apparent in post-acute and long-term care wards although not significantly [odds ratio 1.44 (95% confidence interval 0.78;2.66), P = .241; and 1.44 (0.68, 3.06), P = .345]. Adequacy rates significantly improved in the postintervention period for the intervention group overall (from 78.9% to 83.4%; P = .027) and in post-acute care (from 75.4% to 86.3%; P = .004) and long-term care (from 87.0% to 91.7%; P = .050) wards, with no significant trend observed in the control group. This study failed to demonstrate improvement in prophylaxis adequacy with our intervention. However, the intervention seemed to improve practices in post-acute and long-term care but not acute care wards. Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Financial Impact of Allogeneic Hematopoietic Cell Transplantation on Patients and Families over 2-years: Results from a Multicenter Pilot Study

PubMed Central

Denzen, Ellen M.; Thao, Viengneesee; Hahn, Theresa; Lee, Stephanie J.; McCarthy, Philip L.; Rizzo, J. Douglas; Ammi, Monique; Drexler, Rebecca; Flesch, Susan; James, Heather; Omondi, Nancy; Murphy, Elizabeth; Pederson, Kate; Majhail, Navneet S.

2016-01-01

Hematopoietic cell transplantation (HCT) is a procedure that can significantly influence the socioeconomic wellbeing of patients, caregivers and their families. Among 30 allogeneic HCT recipients and their caregivers enrolled on a pilot study evaluating the feasibility of studying financial impact of HCT, 16 agreed to participate in the long-term phase, completed a baseline questionnaire and received phone interviews at 6, 12, 18 and 24 months post-HCT. Analyses showed that by 2-years post-HCT, 54% of patients who previously contributed to household earnings had not returned to work and 80% of patients/caregivers reported transplant as having moderate to great impact on household income. However, patients’ level of confidence in their ability to meet household financial obligations increased from baseline to 2-years. A relatively large proportion of patients reported inability to pay for medical care through this time period. Case studies demonstrated patient individual perception of financial impact of HCT varies considerably, regardless of actual income. We demonstrate the feasibility of conducting a study to evaluate financial impact of allogeneic HCT through 2-years post-transplantation. Some patients/caregivers continue to experience significant long-term financial burden after this procedure. Our study lays the foundation for a larger evaluation of patient/caregiver financial burden associated with HCT. PMID:27088381

Financial impact of allogeneic hematopoietic cell transplantation on patients and families over 2 years: results from a multicenter pilot study.

PubMed

Denzen, E M; Thao, V; Hahn, T; Lee, S J; McCarthy, P L; Rizzo, J D; Ammi, M; Drexler, R; Flesch, S; James, H; Omondi, N; Murphy, E; Pederson, K; Majhail, N S

2016-09-01

Hematopoietic cell transplantation (HCT) is a procedure that can significantly influence the socioeconomic wellbeing of patients, caregivers and their families. Among 30 allogeneic HCT recipients and their caregivers enrolled on a pilot study evaluating the feasibility of studying financial impact of HCT, 16 agreed to participate in the long-term phase, completed a baseline questionnaire and received phone interviews at 6, 12, 18 and 24 months post HCT. Analyses showed that by 2 years post HCT, 54% of patients who previously contributed to household earnings had not returned to work and 80% of patients/caregivers reported transplant as having moderate to great impact on household income. However, patients' levels of confidence in their abilities to meet household financial obligations increased from baseline to 2 years. A relatively large proportion of patients reported inability to pay for medical care through this time period. Case studies demonstrated that patients' individual perceptions of the financial impact of HCT varies considerably, regardless of actual income. We demonstrate the feasibility of conducting a study to evaluate the financial impact of allogeneic HCT through 2 years post transplantation. Some patients/caregivers continue to experience a significant long-term financial burden after this procedure. Our study lays the foundation for a larger evaluation of patient/caregiver financial burden associated with HCT.

Prostate cancer-related anxiety in long-term survivors after radical prostatectomy.

PubMed

Meissner, Valentin H; Herkommer, Kathleen; Marten-Mittag, Birgitt; Gschwend, Jürgen E; Dinkel, Andreas

2017-12-01

Knowledge of the psychological distress of long- and very long-term (>10 years) prostate cancer (PC) survivors is limited. This study intended to examine the parameters influencing anxiety related to prostate-specific antigen (PSA) and PC in long-term survivors after radical prostatectomy. We surveyed 4719 PC survivors from the German multicenter prospective database "Familial Prostate Cancer." We evaluated the association of PC-related anxiety (MAX-PC) with sociodemographic characteristics, family history of PC, global health status/quality of life (EORTC QLQ-C30), depression and anxiety (PHQ-2; GAD-2), latest PSA level, time since radical prostatectomy, and current therapy. The survey participants' mean age was 75.2 years (SD = 6.5). Median follow-up was 11.5 years, and 19.5% of participants had survived more than 15 years since the initial treatment. The final regression analysis found that younger age, lower global health status/quality of life, higher depression and anxiety scores, higher latest PSA level, and shorter time since radical prostatectomy predicted increased PSA-related anxiety and PC anxiety. Familial PC was predictive only of PSA anxiety (all p < 0.05). The final model explained 12% of the variance for PSA anxiety and 24% for PC anxiety. PC-related anxiety remained relevant many years after prostatectomy and was influenced by younger age, psychological status, rising PSA level, and shorter time since initial treatment. Survivors with these characteristics are at increased risk of PC-related anxieties, which should be considered by the treating physician during follow-up.

Alternative right ventricular pacing sites.

PubMed

Łuciuk, Dariusz; Łuciuk, Marek; Gajek, Jacek

2015-01-01

The main adverse effect of chronic stimulation is stimulation-induced heart failure in case of ventricular contraction dyssynchrony. Because of this fact, new techniques of stimulation should be considered to optimize electrotherapy. One of these methods is pacing from alternative right ventricular sites. The purpose of this article is to review currently accumulated data about alternative sites of cardiac pacing. Medline and PubMed bases were used to search English and Polish reports published recently. Recent studies report a deleterious effect of long term apical pacing. It is suggested that permanent apical stimulation, by omitting physiological conduction pattern with His-Purkinie network, may lead to electrical and mechanical dyssynchrony of heart muscle contraction. In the long term this pathological situation can lead to severe heart failure and death. Because of this, scientists began to search for some alternative sites of cardiac pacing to reduce the deleterious effect of stimulation. Based on current accumulated data, it is suggested that the right ventricular outflow tract, right ventricular septum, direct His-bundle or biventricular pacing are better alternatives due to more physiological electrical impulse propagation within the heart and the reduction of the dyssynchrony effect. These methods should preserve a better left ventricular function and prevent the development of heart failure in permanent paced patients. As there is still not enough, long-term, randomized, prospective, cross-over and multicenter studies, further research is required to validate the benefits of using this kind of therapy. The article should pay attention to new sites of cardiac stimulation as a better and safer method of treatment.

AURORA: bariatric surgery registration in women of reproductive age - a multicenter prospective cohort study.

PubMed

Jans, Goele; Matthys, Christophe; Bel, Sarah; Ameye, Lieveke; Lannoo, Matthias; Van der Schueren, Bart; Dillemans, Bruno; Lemmens, Luc; Saey, Jean-Pierre; van Nieuwenhove, Yves; Grandjean, Pascale; De Becker, Ben; Logghe, Hilde; Coppens, Marc; Roelens, Kristien; Loccufier, Anne; Verhaeghe, Johan; Devlieger, Roland

2016-07-29

The expansion of the obesity epidemic is accompanied with an increase in bariatric procedures, in particular in women of reproductive age. The weight loss induced by the surgery is believed to reverse the negative impact of overweight and obesity on female reproduction, however, research is limited to in particular retrospective cohort studies and a growing number of small case-series and case-(control) studies. AURORA is a multicenter prospective cohort study. The main objective is to collect long-term data on reproductive outcomes before and after bariatric surgery and in a subsequent pregnancy. Women aged 18-45 years are invited to participate at 4 possible inclusion moments: 1) before surgery, 2) after surgery, 3) before 15 weeks of pregnancy and 4) in the immediate postpartum period (day 3-4). Depending on the time of inclusion, data are collected before surgery (T1), 3 weeks and 3, 6, 12 or x months after surgery (T2-T5) and during the first, second and third trimester of pregnancy (T6-T8), at delivery (T9) and 6 weeks and 6 months after delivery (T10-T11). Online questionnaires are send on the different measuring moments. Data are collected on contraception, menstrual cycle, sexuality, intention of becoming pregnant, diet, physical activity, lifestyle, psycho-social characteristics and dietary supplement intake. Fasting blood samples determine levels of vitamin A, D, E, K, B-1, B-12 and folate, albumin, total protein, coagulation parameters, magnesium, calcium, zinc and glucose. Participants are weighted every measuring moment. Fetal ultrasounds and pregnancy course and complications are reported every trimester of pregnancy. Breastfeeding is recorded and breast milk composition in the postpartum period is studied. AURORA is a multicenter prospective cohort study extensively monitoring women before undergoing bariatric surgery until a subsequent pregnancy and postpartum period. Retrospectively registered (July 2015 - NCT02515214 ).

Computer Assisted Multi-Center Creation of Medical Knowledge Bases

PubMed Central

Giuse, Nunzia Bettinsoli; Giuse, Dario A.; Miller, Randolph A.

1988-01-01

Computer programs which support different aspects of medical care have been developed in recent years. Their capabilities range from diagnosis to medical imaging, and include hospital management systems and therapy prescription. In spite of their diversity these systems have one commonality: their reliance on a large body of medical knowledge in computer-readable form. This knowledge enables such programs to draw inferences, validate hypotheses, and in general to perform their intended task. As has been clear to developers of such systems, however, the creation and maintenance of medical knowledge bases are very expensive. Practical and economical difficulties encountered during this long-term process have discouraged most attempts. This paper discusses knowledge base creation and maintenance, with special emphasis on medical applications. We first describe the methods currently used and their limitations. We then present our recent work on developing tools and methodologies which will assist in the process of creating a medical knowledge base. We focus, in particular, on the possibility of multi-center creation of the knowledge base.

Sociodemographic characteristics and attitudes towards motherhood among single women compared with cohabiting women treated with donor semen - a Danish multicenter study.

PubMed

Salomon, Maria; Sylvest, Randi; Hansson, Helena; Nyboe Andersen, Anders; Schmidt, Lone

2015-05-01

To examine sociodemographic characteristics, family backgrounds, reproductive histories, and attitudes towards motherhood in single vs. cohabiting women seeking treatment with donor semen. Baseline data collection in a multicenter cohort study. All nine public fertility clinics in Denmark. In total n = 311 childless women initiating assisted reproduction using donor semen. Self-reported questionnaire responses from n = 184 single women seeking treatment by using donor semen were compared with responses from n = 127 cohabiting women. Sociodemographic characteristics, family backgrounds, reproductive histories, attitudes towards motherhood. Single women were 3.5 years older on average when initiating treatment compared with cohabiting women. No significant differences were found regarding sociodemographic characteristics, previous long-term relationships, previous pregnancies, or attitudes towards motherhood between single women and cohabiting women. The vast majority of single women wanted to achieve parenthood with a partner, 85.8% wished to have a partner in the future, and approximately half of them preferred for a partner to take parental responsibilities. In this study single women seeking treatment with donor semen in the public health system did not differ from cohabiting women, except that they were older. To be a single mother by choice is not their preferred way of parenthood, but a solution they needed to accept. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Multilineage response in aplastic anemia patients following long-term administration of filgrastim (recombinant human granulocyte colony stimulating factor).

PubMed

Sonoda, Y; Ohno, Y; Fujii, H; Takahashi, T; Nakayama, S; Haruyama, H; Nasu, K; Shimazaki, C; Hara, H; Kanamaru, A

1993-11-01

The present multicenter study was undertaken to confirm whether filgrastim/recombinant human granulocyte colony stimulating factor (rhG-CSF) could mobilize residual multipotential stem cells by its G0-shortening effect in patients with aplastic anemia (AA) and induce a multilineage response. Twenty-seven patients with acquired severe or moderate AA received long-term administration (2 to 12+ months) of rhG-CSF in doses from 100 to 400 micrograms/body/day by s.c. injection or 250 to 1,500 micrograms/body/day by i.v. infusion. Twenty-six out of the 27 evaluable patients showed a substantial increase in neutrophils associated with a recovery of myeloid precursors in bone marrow within one month of therapy. Interestingly, 10 out of the 27 patients showed a dramatic improvement in severe anemia after two to ten months of therapy. Moreover, severe thrombocytopenia improved after two to four months of therapy in three out of these ten patients accompanied by a significant increase in megakaryocytes in bone marrow. Clonal cultures of bone marrow cells revealed a recovery in myeloid as well as erythroid precursors in most of these ten patients. In two patients who showed a trilineage response, mixed and megakaryocyte colony formations also recovered. These results suggest that long-term administration of rhG-CSF mobilizes myeloid, erythroid, megakaryocyte and multipotential progenitor cells and induces a multilineage response in some patients with AA.

Clinical study of repaglinide efficacy and safety in type 2 diabetes mellitus patients with blood glucose levels inadequately controlled by sitagliptin.

PubMed

Kawamori, Ryuzo; Kaku, Kohei; Hanafusa, Toshiaki; Ioriya, Katsuhisa; Kageyama, Shigeru; Hotta, Nigishi

2016-03-01

The aim of the present study was to evaluate the long-term efficacy and safety of adding repaglinide in patients with type 2 diabetes mellitus whose blood glucose levels were not sufficiently controlled by treatment with a dipeptidyl peptidase-4 inhibitor, sitagliptin, in addition to diet and exercise therapies. This was a multicenter, uncontrolled, dose-titration study with a treatment period of 52 weeks. The primary end-point was the change in glycated hemoglobin levels from baseline. The glycated hemoglobin level was 7.43 ± 0.57% (mean ± standard deviation) at baseline, and decreased to 6.93 ± 0.91% at the end of the study. The mean changes in glycated hemoglobin levels at 4 weeks and at the end of the study were -0.44 ± 0.28% and -0.50 ± 0.82%, respectively. The glycated hemoglobin-lowering effect was maintained for 52 weeks. The rate of adverse events was 86.0% (86/100), and there were 352 adverse events. The rate of adverse drug reactions was 21.0% (21/100). Hypoglycemia was reported in 5.0% (5/100) of patients, but there was no incidence of 'major hypoglycemia'. Combination therapy with repaglinide and sitagliptin was considered effective for a long term without clinical safety problems in patients with type 2 diabetes mellitus.

An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics.

PubMed

Johnson, Jeremy R; Lossignol, Dominique; Burnell-Nugent, Mary; Fallon, Marie T

2013-08-01

Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group. This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer. In total, 43 patients with cancer-related pain experiencing inadequate analgesia despite chronic opioid dosing, who had participated in a previous three-arm (THC/CBD spray, THC spray, or placebo), two-week parent randomized controlled trial, entered this open-label, multicenter, follow-up study. Patients self-titrated THC/CBD spray (n=39) or THC spray (n=4) to symptom relief or maximum dose and were regularly reviewed for safety, tolerability, and evidence of clinical benefit. The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for "pain severity" and "worst pain" domains showed a decrease (i.e., improvement) at each visit in the THC/CBD spray patients. Similarly, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 scores showed a decrease (i.e., improvement) from baseline in the domains of insomnia, pain, and fatigue. No new safety concerns associated with the extended use of THC/CBD spray arose from this study. This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Long-term effect of the insoluble thread-lifting technique.

PubMed

Fukaya, Mototsugu

2017-01-01

Although the thread-lifting technique for sagging faces has become more common and popular, medical literature evaluating its effects is scarce. Studies on its long-term prognosis are particularly uncommon. One hundred individuals who had previously undergone insoluble thread-lifting were retrospectively investigated. Photos in frontal and oblique views from the first and last visits were evaluated by six female individuals by guessing the patients' ages. The mean guessed age was defined as the apparent age, and the difference between the real and apparent ages was defined as the youth value. The difference between the youth values before and after the thread-lift was defined as the rejuvenation effect and analyzed in relation to the time since the operation, the number of threads used and the number of thread-lift operations performed. The rejuvenation effect decreased over the first year after the operation, but showed an increasing trend thereafter. The rejuvenation effect increased with the number of threads used and the number of thread-lift operations performed. The insoluble thread-lifting technique appears to be associated with both early and late effects. The rejuvenation effect appeared to decrease during the first year, but increased thereafter. A multicenter trial is necessary to confirm these findings.

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.

Long-term application of computer-based pleoptics in home therapy: selected results of a prospective multicenter study.

PubMed

Kämpf, Uwe; Shamshinova, Angelika; Kaschtschenko, Tamara; Mascolus, Wilfried; Pillunat, Lutz; Haase, Wolfgang

2008-01-01

The paper presents selected results of a prospective multicenter study. The reported study was aimed at the evaluation of a software-based stimulation method of computer training applied in addition to occlusion as a complementary treatment for therapy-resistant cases of amblyopia. The stimulus was a drifting sinusoidal grating of a spatial frequency of 0.3 cyc/deg and a temporal frequency of 1 cyc/sec, reciprocally coordinated with each other to a drift of 0.33 deg/sec. This pattern was implemented as a background stimulus into simple computer games to bind attention by sensory-motor coordination tasks. According to an earlier proposed hypothesis, the stimulation aims at the provocation of stimulus-induced phase-coupling in order to contribute to the refreshment of synchronization and coordination processes in the visual transmission channels. To assess the outcome of the therapy, we studied the development of the visual acuity during a period of 6 months. Our cooperating partners of this prospective multicenter study were strabologic departments in ophthalmic clinics and private practices as well. For the issue of therapy control, a partial sample of 55 patients from an overall sample of 198 patients was selected, according to the criterion of strong therapy resistance. The visual acuity was increased about two logarithmic steps by an occlusion combined with computer training in addition to the earlier obtained gain of the same amount by occlusion alone. Recalculated relatively to the duration of the therapy periods, the computer training combined with occlusion was found to be about twice as effective as the preceding occlusion alone. The results of combined computer training and occlusion show an additional increase of the same amount as the preceding occlusion alone, which yielded at its end no further advantage to the development of visual acuity in the selected sample of our 55 therapy-resistant patients. In a concluding theoretical note, a preliminary hypothesis about the neuronal mechanisms of the stimulus-induced treatment effect is discussed.

Endovascular Management of the Arteria Profunda Femoralis: Long-Term Angiographic and Clinical Outcomes

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

Karnabatidis, Dimitrios, E-mail: karnaby@med.upatras.gr; Spiliopoulos, Stavros; Pastromas, Georgios

2012-10-15

Purpose: This study was designed to investigate the long-term angiographic and clinical outcomes of percutaneous transluminal angioplasty (PTA) of the arteria profunda femoralis (PFA), in a series of patients suffering from critical limb ischemia (CLI) or severe intermittent claudication (IC). Methods: Our department's database was searched to identify patients who underwent PTA or bail-out stenting of the PFA. Among the study's inclusion criteria were Rutherford categories 3-6 and {>=}70% stenosis of the PFA. Only de novo stenotic lesions were assessed. Primary endpoints were technical success, angiographic lesion primary patency, angiographic binary in-lesion restenosis, and target lesion recanalization (TLR) rates. Secondarymore » endpoints included patient survival, limb salvage, and complication rates. Patient's baseline demographics, lesion, and procedural details were analyzed. Results: Between 2001 and 2011, 20 consecutive patients (17 males) with a mean age of 73 {+-} 9 (range 53-87) years underwent PTA or bail-out stenting in 23 PFA lesions. Critical limb ischemia was the indication in eight of 20 patients (40%). The mean lesion length was 31 {+-} 9.5 mm. The procedural technical success was 100% (23/23), whereas mean time angiographic and clinical follow-up was 26.8 {+-} 24.6 months. According to the Kaplan-Meier analysis, primary patency and binary restenosis rate were 95 and 86.1% respectively up to 8 years follow-up. No TLR procedures were performed. The 8-year patient survival and limb salvage rates were 87.5 and 84.7% respectively. Conclusions: PTA or stenting of focal, stenotic, PFA lesions, in patients suffering from CLI or IC, exhibit high long-term primary patency rates, as well as low binary restenosis and TLR rates. Large, multicenter studies are required to validate these results.« less

Long-Term Nightly Treatment with Indiplon in Adults with Primary Insomnia: Results of a Double-Blind, Placebo-Controlled, 3-Month Study

PubMed Central

Scharf, Martin B.; Black, Jed; Hull, Steven; Landin, Rick; Farber, Robert

2007-01-01

Objectives: To evaluate the efficacy and safety of indiplon in primary insomnia. Design: Randomized, double-blind, placebo-controlled, 3-month study. Setting: Multi-center outpatient setting. Patients: N=702 (61% female; mean age 46 years) who met DSM-IV criteria for primary insomnia of at least 3 months' duration. Interventions: Indiplon 10 mg (n=236), indiplon 20 mg (n=233), or placebo (n=233). Measurements: Subjective assessment of each of the following: latency to sleep onset (sLSO), total sleep time (sTST), number of awakenings after sleep onset (sNAASO), wake time after sleep onset (sWASO), sleep quality, Insomnia Severity Index (ISI), and global improvement. Results: Treatment with indiplon resulted in significant improvement relative to placebo at all time points for the primary endpoint, sLSO. Mean sLSO at Month 1 for each treatment group was: 10 mg (34.0 ± 1.3 mins), 20 mg (33.0 ± 1.3 mins), and placebo (48.7 ± 1.9 mins; P <0.0001 for both comparisons); efficacy was sustained through Month 3. Both doses of indiplon resulted in significant improvement in sleep maintenance and duration endpoints, sTST and sWASO, as well as sleep quality, ISI, and global improvement at all assessment time points. Conclusions: In patients with chronic insomnia, long-term nightly treatment with 10 mg and 20 mg doses of indiplon resulted in significant and sustained efficacy in sleep onset, maintenance, and duration, and significant associated improvement in both daytime functioning and quality of life. Citation: Scharf MB; Black J; Hull S et al. Long-term nightly treatment with indiplon in adults with primary insomnia: Results of a double-blind, placebo-controlled, 3-month study. SLEEP 2007;30(6):743-752. PMID:17580596

Health status and health resource use among long-term survivors of breast, colorectal and prostate cancer.

PubMed

Ferro, Tàrsila; Aliste, Luisa; Valverde, Montserrat; Fernández, M Paz; Ballano, Concepción; Borràs, Josep M

2014-01-01

The growing number of long-term cancer survivors poses a new challenge to health care systems. In Spain, follow-up is usually carried out in oncology services, but knowledge of cancer survivors' health care needs in this context is limited. The purpose of this study was to ascertain the health status of long-term survivors of breast, prostate, and colorectal cancer and to characterize their use of health care services. Retrospective multicenter cohort study. We collected data from patients' clinical histories and through telephone interviews, using a specially designed questionnaire that included the SF-36v2 Quality of Life and Nottingham Health Profile scales. The questionnaire was completed by 51.2% (n= 583) of the potential sample. No significant differences were observed between 5-year and 10-year survivors. Overall, more than 80% of respondents were undergoing drug treatment for morbidity related to advanced age. Quality of life was good in most patients, and cancer-related morbidity was low and of little complexity. For the most part, participants reported using primary care services for care of chronic diseases and opportunistic treatment of sequelae related to the cancer treatment. Oncological follow-up was centralized at the hospital. Survivors of breast, prostate and colorectal cancer with tumoral detection at an early stage and without recurrences or second neoplasms experienced little morbidity and enjoyed good quality of life. This study proposes exploration of a follow-up model in the Spanish health system in which primary care plays a more important role than is customary in cancer survivors in Spain. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

Ablating Atrial Fibrillation: Customizing Lesion Sets Guided by Rotor Mapping

PubMed Central

Zaman, Junaid A. B.; Narayan, Sanjiv M.

2015-01-01

Ablation occupies an increasing role in the contemporary management of atrial fibrillation (AF), but results are suboptimal, particularly for persistent AF. While an anatomic approach to ablation is a highly efficacious and safe method to isolate pulmonary vein (PV) triggers, recurrence of AF is not always associated with PV reconnection, and there is compelling evidence that non-PV sites sustain AF after it is triggered. Recent developments in wide-area mapping and signal processing now identify rotors in the vast majority of AF patients that sustain AF and whose elimination improves long-term freedom from AF in multicenter studies. Investigators have now demonstrated rotor and focal sources for AF that show many analogous properties between approaches: they lie in spatially reproducible regions temporally over hours to days, and they are amenable to targeted ablation. This review outlines the rationale and technical developments supporting this mechanistic paradigm for human AF, and discusses how rotor mapping may be implemented for individual patient customization of lesion sets. Mechanistic studies are required to explain why rotor elimination (or other ablation approaches) producing long-term elimination of AF may not always terminate AF acutely, how AF correlates with structural changes on magnetic resonance imaging, and how these findings can be integrated clinically with current ablation strategies to improve patient outcomes. PMID:26306123

Ablating Atrial Fibrillation: Customizing Lesion Sets Guided by Rotor Mapping.

PubMed

Zaman, Junaid A B; Narayan, Sanjiv M

2015-01-01

Ablation occupies an increasing role in the contemporary management of atrial fibrillation (AF), but results are suboptimal, particularly for persistent AF. While an anatomic approach to ablation is a highly efficacious and safe method to isolate pulmonary vein (PV) triggers, recurrence of AF is not always associated with PV reconnection, and there is compelling evidence that non-PV sites sustain AF after it is triggered. Recent developments in wide-area mapping and signal processing now identify rotors in the vast majority of AF patients that sustain AF and whose elimination improves long-term freedom from AF in multicenter studies. Investigators have now demonstrated rotor and focal sources for AF that show many analogous properties between approaches: they lie in spatially reproducible regions temporally over hours to days, and they are amenable to targeted ablation. This review outlines the rationale and technical developments supporting this mechanistic paradigm for human AF, and discusses how rotor mapping may be implemented for individual patient customization of lesion sets. Mechanistic studies are required to explain why rotor elimination (or other ablation approaches) producing long-term elimination of AF may not always terminate AF acutely, how AF correlates with structural changes on magnetic resonance imaging, and how these findings can be integrated clinically with current ablation strategies to improve patient outcomes.

Spontaneous Remission of Nephrotic Syndrome in Idiopathic Membranous Nephropathy

PubMed Central

Polanco, Natalia; Gutiérrez, Elena; Covarsí, Adelardo; Ariza, Francisco; Carreño, Agustín; Vigil, Ana; Baltar, José; Fernández-Fresnedo, Gema; Martín, Carmen; Pons, Salvador; Lorenzo, Dolores; Bernis, Carmen; Arrizabalaga, Pilar; Fernández-Juárez, Gema; Barrio, Vicente; Sierra, Milagros; Castellanos, Ines; Espinosa, Mario; Rivera, Francisco; Oliet, Aniana; Fernández-Vega, Francisco

2010-01-01

Spontaneous remission is a well known characteristic of idiopathic membranous nephropathy, but contemporary studies describing predictors of remission and long-term outcomes are lacking. We conducted a retrospective, multicenter cohort study of 328 patients with nephrotic syndrome resulting from idiopathic membranous nephropathy that initially received conservative therapy. Spontaneous remission occurred in 104 (32%) patients: proteinuria progressively declined after diagnosis until remission of disease at 14.7 ± 11.4 months. Although spontaneous remission was more frequent with lower levels of baseline proteinuria, it also frequently occurred in patients with massive proteinuria: 26% among those with baseline proteinuria 8 to 12 g/24 h and 22% among those with proteinuria >12 g/24 h. Baseline serum creatinine and proteinuria, treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, and a >50% decline of proteinuria from baseline during the first year of follow-up were significant independent predictors for spontaneous remission. Only six patients (5.7%) experienced a relapse of nephrotic syndrome. The incidence of death and ESRD were significantly lower among patients with spontaneous remission. In conclusion, spontaneous remission is common among patients with nephrotic syndrome resulting from membranous nephropathy and carries a favorable long-term outcome with a low incidence of relapse. A decrease in proteinuria >50% from baseline during the first year predicts spontaneous remission. PMID:20110379

How I use hydroxyurea to treat young patients with sickle cell anemia

PubMed Central

2010-01-01

Hydroxyurea has many characteristics of an ideal drug for sickle cell anemia (SCA) and provides therapeutic benefit through multiple mechanisms of action. Over the past 25 years, substantial experience has accumulated regarding its safety and efficacy for patients with SCA. Early proof-of-principle studies were followed by prospective phase 1/2 trials demonstrating efficacy in affected adults, then adolescents and children, and more recently infants and toddlers. The phase 3 National Heart, Lung and Blood Institute–sponsored Multicenter Study of Hydroxyurea trial proved clinical efficacy for preventing acute vaso-occlusive events in severely affected adults. Based on this cumulative experience, hydroxyurea has emerged as an important therapeutic option for children and adolescents with recurrent vaso-occlusive events; recent evidence documents sustained long-term benefits with prevention or reversal of chronic organ damage. Despite abundant evidence for its efficacy, however, hydroxyurea has not yet translated into effective therapy for SCA. Because many healthcare providers have inadequate knowledge about hydroxyurea, patients and families are not offered treatment or decline because of unrealistic fears. Limited support for hydroxyurea by lay organizations and inconsistent medical delivery systems also contribute to underuse. Although questions remain regarding its long-term risks and benefits, current evidence suggests that many young patients with SCA should receive hydroxyurea treatment. PMID:20223921

Anemia and Long-Term Renal Prognosis in Patients with Post-Renal Acute Kidney Injury of Nonmalignant Cause.

PubMed

Sasaki, Sho; Kawarazaki, Hiroo; Hasegawa, Takeshi; Shima, Hideaki; Naganuma, Toshihide; Shibagaki, Yugo

2017-01-01

The renal prognosis of post-renal acute kidney injury (PoR-AKI) has not been verified so far. The objective of this study was to assess the association of baseline anemia with long-term renal prognosis in patients with PoR-AKI. We performed a multicenter retrospective cohort study. Consecutive adult patients from December 2006 to February 2010, who met the requirements as mentioned in the definition of PoR-AKI, were included. Patients without data on baseline renal function and at 6 months after PoR-AKI were excluded. We set baseline hemoglobin (Hb) level (g/dl) as the main exposure to be tested. The main outcome measure was long-term renal prognosis as determined by the difference between proximate estimated glomerular filtration rate (eGFR) at 6 months after diagnosis of PoR-AKI and baseline eGFR prior to the occurrence of the present PoR-AKI (ΔeGFR after 6 months) using the general linear model. We included 136 patients with PoR-AKI. The most frequent cause of PoR-AKI was malignancy, accounting for 39.0% (n = 53) of cases. Multivariate analysis adjusted for possible confounders showed that ΔeGFR after 6 months significantly changed by -4.28 ml/min/1.73 m2 for every 1 g/dl lower Hb at diagnosis (95% CI 1.86-6.69, p < 0.01). An additional multivariate analysis that was stratified by the presence or absence of malignancy as the cause of PoR-AKI yielded the same significant result only in the stratum of the nonmalignant cause of PoR-AKI. Patients with a nonmalignant cause of PoR-AKI who have baseline anemia may have poor long-term renal prognosis. In these cases, close observation of renal function after renal recovery may be required. © 2016 S. Karger AG, Basel.

Health status, resource consumption, and costs of dysthymia. A multi-center two-year longitudinal study.

PubMed

Barbui, Corrado; Motterlini, Nicola; Garattini, Livio

2006-02-01

In this study we estimated the health status, resource consumption and costs of a large cohort of patients with early and late-onset dysthymia. The DYSCO (DYSthymia COsts) project is a multi-center observational study which prospectively followed for two years a randomly chosen sample of patients with dysthymia in the Italian primary health care system. A total of 501 patients were followed for two years; 81% had early-onset dysthymic disorder. During the study, improvement was seen in most domains of the 36-Item Short Form Health Survey (SF-36) questionnaire. Comparison of the SF-36 scores for the two groups showed that only the physical health index significantly differed during the two years. The use of outpatient consultations, laboratory tests and diagnostic procedures was similar in the two groups, but patients with early-onset dysthymia were admitted significantly more than late-onset cases. Hospital admissions were almost entirely responsible for the higher total cost per patient per year of early-onset dysthymia. A first limitation of this study is that general practitioners were selected on the basis of their willingness to participate, not at random; secondly, no information was collected on concomitant psychiatric comorbidities. The present study provides the first prospective, long-term data on service use and costs in patients with dysthymia. Differently from patients with early-onset dysthymia, patients with late-onset dysthymia were admitted less and cost less.

MIOTIC study: a prospective, multicenter, randomized study to evaluate the long-term efficacy of mobile phone-based Internet of Things in the management of patients with stable COPD.

PubMed

Zhang, Jing; Song, Yuan-Lin; Bai, Chun-Xue

2013-01-01

Chronic obstructive pulmonary disease (COPD) is a common disease that leads to huge economic and social burden. Efficient and effective management of stable COPD is essential to improve quality of life and reduce medical expenditure. The Internet of Things (IoT), a recent breakthrough in communication technology, seems promising in improving health care delivery, but its potential strengths in COPD management remain poorly understood. We have developed a mobile phone-based IoT (mIoT) platform and initiated a randomized, multicenter, controlled trial entitled the 'MIOTIC study' to investigate the influence of mIoT among stable COPD patients. In the MIOTIC study, at least 600 patients with stable GOLD group C or D COPD and with a history of at least two moderate-to-severe exacerbations within the previous year will be randomly allocated to the control group, which receives routine follow-up, or the intervention group, which receives mIoT management. Endpoints of the study include (1) frequency and severity of acute exacerbation; (2) symptomatic evaluation; (3) pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) measurement; (4) exercise capacity; and (5) direct medical cost per year. Results from this study should provide direct evidence for the suitability of mIoT in stable COPD patient management.

Clinical Outcomes of Golimumab as First, Second or Third Anti-TNF Agent in Patients with Moderate-to-Severe Ulcerative Colitis.

PubMed

Taxonera, Carlos; Rodríguez, Cristina; Bertoletti, Federico; Menchén, Luís; Arribas, Julia; Sierra, Mónica; Arias, Lara; Martínez-Montiel, Pilar; Juan, Alba; Iglesias, Eva; Algaba, Alicia; Manceñido, Noemí; Rivero, Montserrat; Barreiro-de Acosta, Manuel; López-Serrano, Pilar; Argüelles-Arias, Federico; Gutierrez, Ana; Busquets, David; Gisbert, Javier P; Olivares, David; Calvo, Marta; Alba, Cristina

2017-08-01

Golimumab efficacy data in ulcerative colitis (UC) are limited to anti-tumor necrosis factor α (TNF)-naive patients. The aim of this study was to assess the short-term and long-term efficacy of golimumab used as first, second, or third anti-TNF in UC in a real-life clinical setting. This retrospective multicenter cohort study included patients with moderate-to-severe UC treated with golimumab. The primary efficacy endpoints were short-term partial Mayo score response, long-term golimumab failure-free survival, and colectomy-free survival. In 142 patients with UC, golimumab was administered as first (40%), second (23%), or third anti-TNF (37%). Ninety-two patients (65%, 95% confidence interval 56.6-73) achieved short-term clinical response. Forty-five patients (32%, 95% confidence interval 23.7-39.7) achieved clinical remission. Response rates for golimumab were 75% as first anti-TNF, 70% as second anti-TNF (ns versus first anti-TNF), and 50% as third anti-TNF (P = 0.007 versus first anti-TNF). After 12 months median follow-up (interquartile range 6-18), 60 patients (42%, 95% confidence interval 34-51) had golimumab failure, and 15 patients (11%) needed colectomy. Thirty-one patients (22%) needed golimumab dose escalation, and 71% of these regained response after escalation. Starting maintenance with 100 mg golimumab doses and short-term nonresponse were independent predictors of golimumab failure. In this real-life cohort of patients with UC, golimumab therapy was effective for inducing and maintaining clinical response. Although anti-TNF-naive patients had better outcomes, golimumab was also effective in anti-TNF-experienced patients. Only the patients given golimumab after previous failure of 2 anti-TNF agents had significantly worse outcomes. Golimumab dose escalation was beneficial and safe.

MIOTIC study: a prospective, multicenter, randomized study to evaluate the long-term efficacy of mobile phone-based Internet of Things in the management of patients with stable COPD

PubMed Central

Zhang, Jing; Song, Yuan-lin; Bai, Chun-xue

2013-01-01

Chronic obstructive pulmonary disease (COPD) is a common disease that leads to huge economic and social burden. Efficient and effective management of stable COPD is essential to improve quality of life and reduce medical expenditure. The Internet of Things (IoT), a recent breakthrough in communication technology, seems promising in improving health care delivery, but its potential strengths in COPD management remain poorly understood. We have developed a mobile phone-based IoT (mIoT) platform and initiated a randomized, multicenter, controlled trial entitled the ‘MIOTIC study’ to investigate the influence of mIoT among stable COPD patients. In the MIOTIC study, at least 600 patients with stable GOLD group C or D COPD and with a history of at least two moderate-to-severe exacerbations within the previous year will be randomly allocated to the control group, which receives routine follow-up, or the intervention group, which receives mIoT management. Endpoints of the study include (1) frequency and severity of acute exacerbation; (2) symptomatic evaluation; (3) pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) measurement; (4) exercise capacity; and (5) direct medical cost per year. Results from this study should provide direct evidence for the suitability of mIoT in stable COPD patient management. PMID:24082784

Effectiveness of Cranberry Capsules to Prevent Urinary Tract Infections in Vulnerable Older Persons: A Double-Blind Randomized Placebo-Controlled Trial in Long-Term Care Facilities

PubMed Central

Caljouw, Monique A A; van den Hout, Wilbert B; Putter, Hein; Achterberg, Wilco P; Cools, Herman J M; Gussekloo, Jacobijn

2014-01-01

Objectives To determine whether cranberry capsules prevent urinary tract infection (UTI) in long-term care facility (LTCF) residents. Design Double-blind randomized placebo-controlled multicenter trial. Setting Long-term care facilities (LTCFs). Participants LTCF residents (N = 928; 703 women, median age 84). Measurements Cranberry and placebo capsules were taken twice daily for 12 months. Participants were stratified according to UTI risk (risk factors included long-term catheterization, diabetes mellitus, ≥1 UTI in preceding year). Main outcomes were incidence of UTI according to a clinical definition and a strict definition. Results In participants with high UTI risk at baseline (n = 516), the incidence of clinically defined UTI was lower with cranberry capsules than with placebo (62.8 vs 84.8 per 100 person-years at risk, P = .04); the treatment effect was 0.74 (95% confidence interval (CI) = 0.57–0.97). For the strict definition, the treatment effect was 1.02 (95% CI = 0.68–1.55). No difference in UTI incidence between cranberry and placebo was found in participants with low UTI risk (n = 412). Conclusion In LTCF residents with high UTI risk at baseline, taking cranberry capsules twice daily reduces the incidence of clinically defined UTI, although it does not reduce the incidence of strictly defined UTI. No difference in incidence of UTI was found in residents with low UTI risk. PMID:25180378

Sleep, performance, and plasma levels in chronic insomniacs during 14-day use of flurazepam and midazolam: an introduction.

PubMed

Johnson, L C; Chernik, D A; Sateia, M J

1990-08-01

A review of the published literature reveals many unanswered questions regarding the effects of sedative-hypnotics on sleep, performance, and mood. The relationship between plasma half-life and hypnotic efficacy is also not clear. A randomized, double-blind, parallel-groups, multicenter study was designed to examine sleep, performance, and mood in patients with insomnia. A large, heterogeneous sample of patients with a history of benzodiazepine use for chronic insomnia was chosen to reflect the adult population for which sedative-hypnotics are often prescribed and to ensure statistical reliability. Although the major focus of the current study was on the effects of two benzodiazepine hypnotics on performance, this study also provided information on the following important issues: (1) effect of dose level; (2) short-versus long-term administration; and (3) significance of plasma half-life as it relates to hypnotic efficacy.

Zoster vaccine live for the prevention of shingles in the elderly patient

PubMed Central

Zussman, Jamie; Young, Lorraine

2008-01-01

Shingles, also known as herpes zoster, is a common disease in the elderly population that is caused by reactivation of latent varicella zoster virus. Its manifestations and complications can lead to significant short- and long-term morbidity. In 2006, the United States Food and Drug Administration approved Zoster Vaccine Live (Zostavax®) for the prevention of herpes zoster in immunocompetent adults age 60 and over. The approval was based on the results of a large, multi-center clinical trial, the Shingles Prevention Study. This study showed that vaccination significantly decreased shingles incidence, burden of illness due to disease, and the development of, and severity of postherpetic neuralgia. This review offers an overview of varicella zoster virus infection and complications, a summary of the Shingles Prevention Study, and a critical analysis designed to aid the practicing physician who has questions about vaccine administration. PMID:18686747

Risk-adapted, long-term management in childhood-onset craniopharyngioma.

PubMed

Müller, Hermann L

2017-04-01

This report is a review of findings on the diagnosis, treatment, clinical course, follow-up, and prognosis of craniopharyngioma patients with special regard to clinical trials and long-term management. Literature search on Pubmed for paper published after 1994. Craniopharyngiomas are rare, embryonic malformations of the sellar/parasellar region with low histological grade. Clinical manifestations are related to increased intracranial pressure, visual impairment, and hypothalamic/pituitary deficiencies. If the tumor is favorably localized, therapy of choice is complete resection, with care taken to preserve hypothalamic and optic functions. In patients with unfavorable tumor location (i.e. involvement of hypothalamic areas), recommended therapy is limited hypothalamus-sparing surgical strategy followed by irradiation. Irradiation has proven effective in treatment of recurrences and progression. Surgical lesions and/or anatomical involvement of posterior hypothalamic areas can result in serious sequelae, mainly hypothalamic syndrome. It is crucial that craniopharyngioma be managed as a frequently chronic disease, providing ongoing care of pediatric and adult patients' by experienced multidisciplinary teams in the context of multicenter trials.

High-dose N-acetylcysteine in the prevention of COPD exacerbations: rationale and design of the PANTHEON Study.

PubMed

Zheng, Jin-Ping; Wen, Fu-Qiang; Bai, Chun-Xue; Wan, Huan-Ying; Kang, Jian; Chen, Ping; Yao, Wan-Zhen; Ma, Li-Jun; Xia, Qi-Kui; Gao, Yi; Zhong, Nan-Shan

2013-04-01

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation; from a pathophysiological point of view it involves many components, including mucus hypersecretion, oxidative stress and inflammation. N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. Long-term efficacy of NAC 600mg/d in COPD is controversial; a dose-effect relationship has been demonstrated, but at present it is not known whether a higher dose provides clinical benefits. The PANTHEON Study is a prospective, ICS stratified, randomized, double-blind, placebo-controlled, parallel-group, multi-center trial designed to assess the efficacy and safety of high-dose (1200 mg/daily) NAC treatment for one year in moderate-to-severe COPD patients. The primary endpoint is the annual exacerbation rate. Secondary endpoints include recurrent exacerbations hazard ratio, time to first exacerbation, as well as quality of life and pulmonary function. The hypothesis, design and methodology are described and baseline characteristics of recruited patients are presented. 1006 COPD patients (444 treated with maintenance ICS, 562 ICS naive, aged 66.27±8.76 yrs, average post-bronchodilator FEV1 48.95±11.80 of predicted) have been randomized at 34 hospitals in China. Final results of this study will provide objective data on the effects of high-dose (1200 mg/daily) long-term NAC treatment in the prevention of COPD exacerbations and other outcome variables.

Approaches for quantifying energy intake and %calorie restriction during calorie restriction interventions in humans: the multicenter CALERIE study.

PubMed

Racette, Susan B; Das, Sai Krupa; Bhapkar, Manjushri; Hadley, Evan C; Roberts, Susan B; Ravussin, Eric; Pieper, Carl; DeLany, James P; Kraus, William E; Rochon, James; Redman, Leanne M

2012-02-15

Calorie restriction (CR) is a component of most weight loss interventions and a potential strategy to slow aging. Accurate determination of energy intake and %CR is critical when interpreting the results of CR interventions; this is most accurately achieved using the doubly labeled water method to quantify total energy expenditure (TEE). However, the costs and analytical requirements of this method preclude its repeated use in many clinical trials. Our aims were to determine 1) the optimal TEE assessment time points for quantifying average energy intake and %CR during long-term CR interventions and 2) the optimal approach for quantifying short-term changes in body energy stores to determine energy intake and %CR during 2-wk DLW periods. Adults randomized to a CR intervention in the multicenter CALERIE study underwent measurements of TEE by doubly labeled water and body composition at baseline and months 1, 3, and 6. Average %CR achieved during the intervention was 24.9 ± 8.7%, which was computed using an approach that included four TEE assessment time points (i.e., TEE(baseline, months 1, 3, and 6)) plus the 6-mo change in body composition. Approaches that included fewer TEE assessments yielded %CR values of 23.4 ± 9.0 (TEE(baseline,) months 3 and 6), 25.0 ± 8.7 (TEE(baseline,) months 1 and 6), and 20.9 ± 7.1% (TEE(baseline, month 6)); the latter approach differed significantly from approach 1 (P < 0.001). TEE declined 9.6 ± 9.9% within 2-4 wk of CR beginning and then stabilized. Regression of daily home weights provided the most reliable estimate of short-term change in energy stores. In summary, optimal quantification of energy intake and %CR during weight loss necessitates a TEE measurement within the first month of CR to capture the rapid reduction in TEE.

Approaches for quantifying energy intake and %calorie restriction during calorie restriction interventions in humans: the multicenter CALERIE study

PubMed Central

Das, Sai Krupa; Bhapkar, Manjushri; Hadley, Evan C.; Roberts, Susan B.; Ravussin, Eric; Pieper, Carl; DeLany, James P.; Kraus, William E.; Rochon, James; Redman, Leanne M.

2012-01-01

Calorie restriction (CR) is a component of most weight loss interventions and a potential strategy to slow aging. Accurate determination of energy intake and %CR is critical when interpreting the results of CR interventions; this is most accurately achieved using the doubly labeled water method to quantify total energy expenditure (TEE). However, the costs and analytical requirements of this method preclude its repeated use in many clinical trials. Our aims were to determine 1) the optimal TEE assessment time points for quantifying average energy intake and %CR during long-term CR interventions and 2) the optimal approach for quantifying short-term changes in body energy stores to determine energy intake and %CR during 2-wk DLW periods. Adults randomized to a CR intervention in the multicenter CALERIE study underwent measurements of TEE by doubly labeled water and body composition at baseline and months 1, 3, and 6. Average %CR achieved during the intervention was 24.9 ± 8.7%, which was computed using an approach that included four TEE assessment time points (i.e., TEEbaseline, months 1, 3, and 6) plus the 6-mo change in body composition. Approaches that included fewer TEE assessments yielded %CR values of 23.4 ± 9.0 (TEEbaseline, months 3 and 6), 25.0 ± 8.7 (TEEbaseline, months 1 and 6), and 20.9 ± 7.1% (TEEbaseline, month 6); the latter approach differed significantly from approach 1 (P < 0.001). TEE declined 9.6 ± 9.9% within 2–4 wk of CR beginning and then stabilized. Regression of daily home weights provided the most reliable estimate of short-term change in energy stores. In summary, optimal quantification of energy intake and %CR during weight loss necessitates a TEE measurement within the first month of CR to capture the rapid reduction in TEE. PMID:22127229

Evaluation of the influence of pharmacists and GPs on patient perceptions of long-term topical corticosteroid use.

PubMed

Farrugia, Lisa L; Lee, Andrew; Fischer, Gayle; Blaszczynski, Alex; Carter, Stephen R; Smith, Saxon D

2017-03-01

To assess pharmacist and general practitioner (GP) advice and behaviors, as related to and reported by patients and parents of patients using topical corticosteroids (TCS) on a long-term basis. Multicenter cross-sectional survey of patients (aged 18+) and parents of pediatric patients (aged <18) with a history of long-term (≥1 month) TCS use, assessing: TCS treatment adherence and reasons for non-adherence; beliefs regarding TCS use and safety; messages regarding TCS received from community pharmacists, GPs, family/friends and the Internet; and experiences of GP and pharmacist counseling regarding TCS use. A total of 123 patients and 78 parents completed the survey (n = 201). 76.6% of respondents reported consistently ("Often" or "Always") receiving one or more message(s) regarding TCS "risk" from a GP and/or pharmacist (n = 192). Respondents reported being told to "try natural or complementary and alternative therapies before resorting to the use of TCS" significantly more often by pharmacists than by GPs (p = 0.039). High rates of consistently delivered messages about TCS "risk" from GPs and pharmacists affect patient/parent understanding about TCS safety and may lead to treatment non-adherence. This indicates a need for reeducation of these groups on the safety of TCS use.

Tolerance in liver transplantation: Biomarkers and clinical relevance

PubMed Central

Baroja-Mazo, Alberto; Revilla-Nuin, Beatriz; Parrilla, Pascual; Martínez-Alarcón, Laura; Ramírez, Pablo; Pons, José Antonio

2016-01-01

Transplantation is the optimal treatment for end-stage organ failure, and modern immunosuppression has allowed important progress in short-term outcomes. However, immunosuppression poorly influences chronic rejection and elicits chronic toxicity in current clinical practice. Thus, a major goal in transplantation is to understand and induce tolerance. It is well established that human regulatory T cells expressing the transcription factor FoxP3 play important roles in the maintenance of immunological self-tolerance and immune homeostasis. The major regulatory T cell subsets and mechanisms of expansion that are critical for induction and long-term maintenance of graft tolerance and survival are being actively investigated. Likewise, other immune cells, such as dendritic cells, monocyte/macrophages or natural killer cells, have been described as part of the process known as “operational tolerance”. However, translation of these results towards clinical practice needs solid tools to identify accurately and reliably patients who are going to be tolerant. In this way, a plethora of genetic and cellular biomarkers is raising and being validated worldwide in large multi-center clinical trials. Few of the studies performed so far have provided a detailed analysis of the impact of immunosuppression withdrawal on pre-existing complications derived from the long-term administration of immunosuppressive drugs and the side effects associated with them. The future of liver transplantation is aimed to develop new therapies which increase the actual low tolerant vs non-tolerant recipients ratio. PMID:27678350

One-year safety and efficacy study of bilastine treatment in Japanese patients with chronic spontaneous urticaria or pruritus associated with skin diseases.

PubMed

Yagami, Akiko; Furue, Masutaka; Togawa, Michinori; Saito, Akihiro; Hide, Michihiro

2017-04-01

A number of second-generation non-sedating antihistamines are used in clinical practices over the world. However, long-term safety and efficacy have not been proved high level evidence based medicine. We have performed an open-label, multicenter, phase III study to evaluate the long-term safety and efficacy of bilastine, a novel non-sedating H 1 -antihistamine for patients with chronic spontaneous urticaria (CSU) or pruritus associated with skin diseases (trial registration no. JapicCTI-142528). Patients aged 18-74 years were treated with bilastine 20 mg once daily for up to 52 weeks. Safety and tolerability were assessed on the basis of adverse events (AE), bilastine-related AE, laboratory tests and vital signs. Efficacy was assessed based on rash score, itch score, overall improvement and quality of life. One hundred and ninety-eight patients enrolled, 122 of whom (61.6%) completed the 52-week treatment period. AE were reported in 64.5% and bilastine-related AE in 2.5% of patients throughout the 52-week treatment period. All AE were mild to moderate in severity. AE associated with the nervous system occurred in 10 patients (5.1%) including seven patients (3.6%) with headache. Somnolence reported in two of these patients (1.0%) was related to bilastine. All efficacy variables improved during treatment with bilastine. In conclusion, long-term treatment with bilastine 20 mg once daily for 52 weeks is safe and well tolerated in Japanese patients with CSU or pruritus associated with skin diseases. Bilastine improved disease symptoms of both conditions early in treatment, and the efficacy was maintained throughout the treatment. © 2016 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

Defining Long-term Outcomes with Living Donor Liver Transplantation in North America

PubMed Central

Olthoff, Kim M.; Smith, Abigail R.; Abecassis, Michael; Baker, Talia; Emond, Jean C.; Berg, Carl L.; Beil, Charlotte A.; Burton, James R.; Fisher, Robert A.; Freise, Christopher E.; Gillespie, Brenda W.; Grant, David R.; Humar, Abhi; Kam, Igal; Merion, Robert M.; Pomfret, Elizabeth A.; Samstein, Benjamin; Shaked, Abraham

2015-01-01

Objective To compare long-term survival of living donor liver transplant (LDLT) at experienced transplant centers to outcomes of deceased donor liver transplant (DDLT) and identify key variables impacting patient and graft survival. Summary Background Data The Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) is a prospective multicenter NIH study comparing outcomes of LDLT and DDLT and associated risks. Methods Mortality and graft failure for 1427 liver recipients (963 LDLT) enrolled in A2ALL transplanted between 1/1/1998 and 1/31/2014 at 12 North American centers with median follow-up 6.7 years were analyzed using Kaplan-Meier and multivariable Cox models. Results Survival probability at 10 years was 70% for LDLT and 64% for DDLT. Unadjusted survival was higher with LDLT (HR=0.76, p=0.02) but attenuated after adjustment (HR=0.98, p=0.90) as LDLT recipients had lower mean MELD (15.5 vs 20.4) and fewer were transplanted from ICU, inpatient, on dialysis, ventilated, or with ascites. Post-transplant ICU days were less for LDLT. For all recipients female gender and primary sclerosing cholangitis were associated with improved survival, while dialysis and older recipient/donor age were associated with worse survival. Higher MELD score was associated with increased graft failure. Era of transplantation and type of donated lobe did not impact survival in LDLT. Conclusions LDLT provides significant long-term transplant benefit resulting in transplantation at a lower MELD score, decreased death on waitlist, and excellent post-transplant outcomes. Recipient diagnosis, disease severity, renal failure, and ages of recipient and donor should be considered in decision-making regarding timing of transplant and donor options. Clinical Trials ID NCT00096733. PMID:26258315

Amino Acid-based Formula in Cow's Milk Allergy: Long-term Effects on Body Growth and Protein Metabolism.

PubMed

Canani, Roberto Berni; Nocerino, Rita; Frediani, Tullio; Lucarelli, Sandra; Di Scala, Carmen; Varin, Elena; Leone, Ludovica; Muraro, Antonella; Agostoni, Carlo

2017-04-01

The long-term effects of amino acid-based formula (AAF) in the treatment of cow's milk allergy (CMA) are largely unexplored. The present study comparatively evaluates body growth and protein metabolism in CMA children treated with AAF or with extensively hydrolyzed whey formula (eHWF), and healthy controls. A 12-month multicenter randomized control trial was conducted in outpatients with CMA (age 5-12 m) randomized in 2 groups, treated with AAF (group 1) and eHWF (group 2), and compared with healthy controls (group 3) fed with follow-on (if age <12 months) or growing-up formula (if age >12 months). At enrolment (T0), after 3 (T3), 6 (T6), and 12 months (T12) a clinical evaluation was performed. At T0 and T3, in subjects with CMA serum levels of albumin, urea, total protein, retinol-binding protein, and insulin-like growth factor 1 were measured. Twenty-one subjects in group 1 (61.9% boys, age 6.5 ± 1.5 months), 19 in group 2 (57.9% boys, age 7 ± 1.7 months) and 25 subjects in group 3 (48% boys, age 5.5 ± 0.5 months) completed the study. At T0, the weight z score was similar in group 1 (-0.74) and 2 (-0.76), with differences compared to group 3 (-0.17, P < 0.05). At T12, the weight z score value was similar between the 3 groups without significant differences. There were no significant changes in protein metabolism in children in groups 1 and 2. Long-term treatment with AAF is safe and allows adequate body growth in children with CMA.

Cleaning at Home and at Work in Relation to Lung Function Decline and Airway Obstruction.

PubMed

Svanes, Øistein; Bertelsen, Randi J; Lygre, Stein H L; Carsin, Anne E; Antó, Josep M; Forsberg, Bertil; García-García, José M; Gullón, José A; Heinrich, Joachim; Holm, Mathias; Kogevinas, Manolis; Urrutia, Isabel; Leynaert, Bénédicte; Moratalla, Jesús M; Le Moual, Nicole; Lytras, Theodore; Norbäck, Dan; Nowak, Dennis; Olivieri, Mario; Pin, Isabelle; Probst-Hensch, Nicole; Schlünssen, Vivi; Sigsgaard, Torben; Skorge, Trude D; Villani, Simona; Jarvis, Debbie; Zock, Jan P; Svanes, Cecilie

2018-05-01

Cleaning tasks may imply exposure to chemical agents with potential harmful effects to the respiratory system, and increased risk of asthma and respiratory symptoms among professional cleaners and in persons cleaning at home has been reported. Long-term consequences of cleaning agents on respiratory health are, however, not well described. This study aimed to investigate long-term effects of occupational cleaning and cleaning at home on lung function decline and airway obstruction. The European Community Respiratory Health Survey (ECRHS) investigated a multicenter population-based cohort at three time points over 20 years. A total of 6,235 participants with at least one lung function measurement from 22 study centers, who in ECRHS II responded to questionnaire modules concerning cleaning activities between ECRHS I and ECRHS II, were included. The data were analyzed with mixed linear models adjusting for potential confounders. As compared with women not engaged in cleaning (ΔFEV 1  = -18.5 ml/yr), FEV 1 declined more rapidly in women responsible for cleaning at home (-22.1; P = 0.01) and occupational cleaners (-22.4; P = 0.03). The same was found for decline in FVC (ΔFVC = -8.8 ml/yr; -13.1, P = 0.02; and -15.9, P = 0.002; respectively). Both cleaning sprays and other cleaning agents were associated with accelerated FEV 1 decline (-22.0, P = 0.04; and -22.9, P = 0.004; respectively). Cleaning was not significantly associated with lung function decline in men or with FEV 1 /FVC decline or airway obstruction. Women cleaning at home or working as occupational cleaners had accelerated decline in lung function, suggesting that exposures related to cleaning activities may constitute a risk to long-term respiratory health.

Predictors of Clinical Response and Remission at One year among a Multicenter Cohort of Patients with Inflammatory Bowel Disease Treated with Vedolizumab

PubMed Central

Allegretti, Jessica R.; Barnes, Edward L.; Stevens, Betsey; Storm, Margaret; Ananthakrishnan, Ashwin; Yajnik, Vijay; Korzenik, Joshua

2017-01-01

Background Vedolizumab (VDZ) has demonstrated long term efficacy in Crohn’s disease (CD) and ulcerative colitis (UC) in phase III trials. Aims Our aim was to evaluate the efficacy of VDZ at week 54 in inflammatory bowel disease (IBD) in a multicenter cohort of patients. Methods Adult patients completing induction therapy with VDZ were eligible for this study. Clinical response and remission was assessed using the Harvey Bradshaw index (HBI) for CD, the simple clinical colitis activity index (SCCAI) for UC and physician assessment. Results Among 136 total patients (96 CD and 40 UC), 76 (56%) demonstrated clinical response or remission at week 54. In univariate analysis, for patients with CD concomitant initiation of immunomodulator therapy (2.71, 95% CI 1.11 – 6.57), the addition of an immunomodulator (OR 11.49, 3.16 – 41.75) and CRP <3 (4.92, 95% CI 1.99 – 12.15) were associated with increased odds of clinical response or remission at week 54. For UC patients hospitalization after VDZ induction was associated with decreased odds of response or remission at week 54 ( OR 0.22, 95%CI 0.05–0.88). On multivariate analysis in CD, addition of an immunomodulator (OR 8.33, 95% CI 2.15–32.26) remained significant predictors of clinical response or remission at week 54. Conclusions Among a multicenter cohort of patients with IBD demonstrating primary response to VDZ, the addition of combination therapy with an immunomodulator is a significant predictor of clinical response or remission at week 54 in patients with CD. PMID:28357697

A multicenter, randomized study to test immunosuppressive therapy with oral prednisone for the prevention of restenosis after percutaneous coronary interventions: cortisone plus BMS or DES versus BMS alone to eliminate restenosis (CEREA-DES) - study design and rationale.

PubMed

Ribichini, Flavio; Tomai, Fabrizio; De Luca, Giuseppe; Boccuzzi, Giacomo; Presbitero, Patrizia; Pesarini, Gabriele; Ferrero, Valeria; Ghini, Anna S; Pastori, Francesca; De Luca, Leonardo; Zavalloni, Denis; Soregaroli, Daniela; Garbo, Roberto; Franchi, Elena; Marino, Paolo; Minelli, Massimo; Vassanelli, Corrado

2009-02-01

Several randomized trials and registries have shown a reduction of restenosis after coronary angioplasty with drug-eluting stents (DESs) compared with bare metal stents (BMSs). However, cost-efficacy analysis and long-term outcome of DESs compared to BMSs deserve further assessment. Moreover, concern has been raised regarding adverse clinical events occurring late after DES implantation, in particular, late stent thrombosis related to the suspension of dual antiplatelet therapy. The use of a short-cycle oral treatment with prednisone at immunosuppressive dose after BMS implantation has shown remarkable efficacy in reducing restenosis in nondiabetic patients, with very low additional cost and without the need for long-term dual antiplatelet therapy. Such results are however limited by small sample size. Cortisone plus BMS or DES versus BMS alone to Eliminate Restenosis is an independent, prospective, multicenter, randomized study. It will randomize 375 nondiabetic patients with coronary artery disease in three different arms to BMS (control group), DES (DES group) or BMS followed by a 40-day prednisone treatment (prednisone group). The DES and the prednisone groups will be compared to the control group to investigate the expected clinical advantage. The primary endpoint of the study is the event-free survival of cardiovascular death, myocardial infarction and recurrence of ischemia-needing repeated target vessel revascularization at 1 year. Secondary endpoints are the event-free survival analysis at 2 and 3 years, the restenosis rate at 9 months, and cost-effectiveness at 1, 2 and 3 years. The expected primary endpoint rates are 90% for DESs and for prednisone-treated patients and 77% for BMSs. The study was designed as a superiority trial, to compare DES, and BMS and prednisone, with BMS alone. A sample size of 118 patients per group provides an 80% power, assuming a complete 12-month follow-up information available for each patient. To obviate for cases of drop out, the sample size was increased to 375 patients to be enrolled in five Italian hospitals. This study will provide a magnitude of the net clinical and economic benefits of DES and of the safety and efficacy of BMS and cortisone compared to the standard use of BMS alone in nondiabetic patients with coronary artery disease.

Long-Term Safety and Efficacy of Belimumab in Patients With Systemic Lupus Erythematosus: A Continuation of a Seventy-Six-Week Phase III Parent Study in the United States.

PubMed

Furie, Richard A; Wallace, Daniel J; Aranow, Cynthia; Fettiplace, James; Wilson, Barbara; Mistry, Prafull; Roth, David A; Gordon, David

2018-06-01

We undertook this US multicenter continuation study (GlaxoSmithKline study BEL112233; ClinicalTrials.gov identifier: NCT00724867) to assess long-term safety and efficacy of belimumab in patients with systemic lupus erythematosus (SLE) who completed the Study of Belimumab in Subjects with SLE 76-week trial (ClinicalTrials.gov identifier: NCT00410384). Patients continued to receive the same belimumab dose plus standard therapy; patients previously receiving placebo received 10 mg/kg belimumab. The primary outcome measure was long-term safety of belimumab (frequency of adverse events [AEs] and damage assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI], evaluated every 48 weeks [1 study year]). Other assessments included the SLE Responder Index (SRI), flare rates (using the modified SLE Flare Index [SFI]), prednisone use, and B cell levels. Of 268 patients, 140 completed the study and 128 withdrew. The mean ± SD score on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA-SLEDAI) at baseline was 7.8 ± 3.86. The mean ± SD SDI score increased by 0.4 ± 0.68 from its value at baseline (1.2 ± 1.51). The overall incidence of treatment-related and serious AEs remained stable or declined through study year 7. An SRI response was achieved by 41.9% and 75.6% of patients at the study year 1 and study year 7 midpoints, respectively. At the study year 7 midpoint, relative to baseline, 78.2% had achieved a ≥4-point reduction in the SELENA-SLEDAI score, 98.4% had no new British Isles Lupus Assessment Group (BILAG) A organ domain score and no more than 1 new BILAG B organ domain score, 93.7% had no worsening in the physician's global assessment of disease activity, 20.6% had experienced ≥1 severe SFI flare, the mean decrease in prednisone dose was 31.4%, and the median change in CD20+ B cell numbers was -83.2%. These long-term exposure results confirm the previously observed safety and efficacy profiles of belimumab in patients with SLE. © 2018 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial.

PubMed

Dreger, Peter; Döhner, Hartmut; Ritgen, Matthias; Böttcher, Sebastian; Busch, Raymonde; Dietrich, Sascha; Bunjes, Donald; Cohen, Sandra; Schubert, Jörg; Hegenbart, Ute; Beelen, Dietrich; Zeis, Matthias; Stadler, Michael; Hasenkamp, Justin; Uharek, Lutz; Scheid, Christof; Humpe, Andreas; Zenz, Thorsten; Winkler, Dirk; Hallek, Michael; Kneba, Michael; Schmitz, Norbert; Stilgenbauer, Stephan

2010-10-07

The purpose of this prospective multicenter phase 2 trial was to investigate the long-term outcome of reduced-intensity conditioning allogeneic stem cell transplantation (alloSCT) in patients with poor-risk chronic lymphocytic leukemia. Conditioning was fludarabine/ cyclophosphamide-based. Longitudinal quantitative monitoring of minimal residual disease (MRD) was performed centrally by MRD-flow or real-time quantitative polymerase chain reaction. One hundred eligible patients were enrolled, and 90 patients proceeded to alloSCT. With a median follow-up of 46 months (7-102 months), 4-year nonrelapse mortality, event-free survival (EFS) and overall survival (OS) were 23%, 42%, and 65%, respectively. Of 52 patients with MRD monitoring available, 27 (52%) were alive and MRD negative at 12 months after transplant. Four-year EFS of this subset was 89% with all event-free patients except for 2 being MRD negative at the most recent assessment. EFS was similar for all genetic subsets, including 17p deletion (17p-). In multivariate analyses, uncontrolled disease at alloSCT and in vivo T-cell depletion with alemtuzumab, but not 17p-, previous purine analogue refractoriness, or donor source (human leukocyte antigen-identical siblings or unrelated donors) had an adverse impact on EFS and OS. In conclusion, alloSCT for poor-risk chronic lymphocytic leukemia can result in long-term MRD-negative survival in up to one-half of the patients independent of the underlying genomic risk profile. This trial is registered at http://clinicaltrials.gov as NCT00281983.

Pathogenesis of Thromboembolism and Endovascular Management

PubMed Central

Behravesh, Sasan; Hoang, Peter; Nanda, Alisha; Wallace, Alex; Sheth, Rahul A.; Deipolyi, Amy R.; Memic, Adnan; Naidu, Sailendra

2017-01-01

Venous thromboembolism (VTE), a disease that includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is associated with high mortality, morbidity, and costs. It can result in long-term complications that include postthrombotic syndrome (PTS) adding to its morbidity. VTE affects 1/1000 patients, costs $13.5 billion annually to treat, and claims 100,000 lives annually in the US. The current standard of care for VTE is anticoagulation, though thrombolysis may be performed in patients with PE and threatened limb. This review discusses pathogenesis and medical treatment of VTE and then focuses on endovascular treatment modalities. Mechanical- and catheter-directed thrombolysis (CDT) is discussed, as well as patient selection criteria, and complications. The first prospective study (CaVenT) comparing CDT with anticoagulation alone in acute DVT, despite study shortcomings, corroborates the existing literature indicating improved outcomes with CDT. The potential of the ongoing prospective, multicenter, randomized ATTRACT trial is also highlighted. PMID:28154761

Progress in the understanding and utilization of biologic response modifiers in the treatment of uveitis.

PubMed

Maleki, Arash; Meese, Halea; Sahawneh, Haitham; Foster, C Stephen

2016-07-01

Uveitis is the third most common cause of blindness in developed countries. Considering the systemic and local complications of long-term corticosteroid therapy and the intolerance due to side effects and ineffectiveness of conventional chemotherapy, use of biologic response modifiers is a reasonable alternative in the treatment of non-infectious uveitis and persistent uveitic macular edema. The majority of the evidence presented here comes from open uncontrolled analyses. Based on these studies, tumor necrosis factor alpha inhibitors, especially infliximab and adalimumab, have been shown to be effective in the treatment of non-infectious uveitis in numerous studies. More research is necessary, particularly multi-center randomized clinical trials, to address the choice of biologic response modifier agent and the length of treatment as we employ biologic response modifiers in different types of uveitis and persistent uveitic macular edema.

Recovery, relapse, or else? Treatment outcomes in gambling disorder from a multicenter follow-up study.

PubMed

Müller, K W; Wölfling, K; Dickenhorst, U; Beutel, M E; Medenwaldt, J; Koch, A

2017-06-01

Gambling disorder is associated with various adverse effects. While data on the immediate effectiveness of treatment programs are available, follow-up studies examining long-term effects are scarce and factors contributing to a stable therapy outcome versus relapse are under-researched. Patients (n=270) finishing inpatient treatment for gambling disorder regularly participated in a prospective multicenter follow-up study (pre-treatment, post-treatment, 12-month follow-up). Criteria for gambling disorder, psychopathology, functional impairment were defined as endpoints. Changes in personality were defined as an additional parameter. At follow-up, three groups were identified: subjects maintaining full abstinence (41.6%), patients still meeting criteria for gambling disorder (29.2%), and subjects still participating in gambling without meeting the diagnostic criteria for gambling disorder (29.2%). Every group had improvements in functional impairment, abstinent subjects showed the lowest psychopathology. Significant decreases in neuroticism and increases in both extraversion and conscientiousness were found among abstinent subjects but not in patients still meeting criteria for gambling disorder. One year after treatment, a considerable percentage of patients kept on gambling but not all of them were classified with gambling disorder leading to the question if abstinence is a necessary goal for every patient. The changes of personality in abstinent patients indicate that after surmounting gambling disorder a subsequent maturing of personality might be a protective factor against relapse. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A multicenter study of preventable contact burns from glass fronted gas fireplaces.

PubMed

Wibbenmeyer, Lucy; Gittelman, Michael A; Kluesner, Karen; Liao, Junlin; Xing, Yunfan; Faraklas, Iris; Anyan, Walter; Gamero, Chelsea; Moulton, Steven; Nederveld, Cindy; Banks, Ashley; Ryan, Colleen M; Conway, Jennifer A; Reilly, Debra A; Fish, Joel; Kelly, Charis; Peltier, George; Schwantke, Emily; Conrad, Peggie F; Caruso, Daniel M; Richey, Karen J; McCrory, Kristine; Elfar, Mohamed S A; Pittinger, Timothy; Sadie, Christine; Greenhalgh, David; Palmieri, Tina; Grossman, Peter H; Richards, Kurt M; Joyce, Teresa; Pozez, Andrea L; Savetamal, Alisa; Harrington, David T; Duncan, Kimberley; Pomerantz, Wendy J; Dillard, B Daniel

2015-01-01

Glass fronted gas fireplaces (GFGFs) have exterior surfaces that can reach extremely high temperatures. Burn injuries from contact with the glass front can be severe with long-term sequelae. The Consumer Product Safety Commission reported that these injuries are uncommon, whereas single-center studies indicate a much higher frequency. The purpose of this multi-institutional study was to determine the magnitude and severity of GFGF injuries in North America. Seventeen burn centers elected to participate in this retrospective chart review. Chart review identified 402 children ≤10 years of age who sustained contact burns from contact with GFGF, who were seen or admitted to the study hospitals from January 2006 to December 2010. Demographic, burn, treatment, and financial data were collected. The mean age of the study group was 16.8 ± 13.3 months. The majority suffered burns to their hands (396, 98.5%), with burns to the face being the second, much less common site (14, 3.5%). Two hundred and sixty-nine required rehabilitation therapy (66.9%). The number of GFGF injuries reported was 20 times greater than the approximately 30 injuries estimated by the Consumer Product Safety Commission's 10-year review. For the affected children, these injuries are painful, often costly and occasionally can lead to long-term sequelae. Given that less than a quarter of burn centers contributed data, the injury numbers reported herein support a need for broader safety guidelines for gas fireplaces in order to have a significant impact on future injuries.

Design innovations and baseline findings in a long-term Parkinson’s trial: NET-PD LS-1

PubMed Central

2012-01-01

Background Based on the pre-clinical and the results of a phase 2 futility study, creatine was selected for an efficacy trial in Parkinson’s disease (PD). We present the design rationale and a description of the study cohort at baseline. Methods A randomized, multicenter, double-blind, parallel group, placebo controlled Phase 3 study of creatine (10 gm daily) in participants with early, treated PD, the Long-term Study – 1 (LS-1) is being conducted by the NINDS Exploratory Trials in Parkinson’s Disease (NET-PD) network. The study utilizes a global statistical test (GST) encompassing multiple clinical rating scales to provide a multidimensional assessment of disease progression. Results A total of 1,741 PD participants from 45 sites in the U.S. and Canada were randomized 1:1 to either 10-gm creatine/day or matching placebo. Participants are being evaluated for a minimum of 5 years. The LS-1 baseline cohort includes participants treated with dopaminergic therapy and generally mild PD. Conclusions LS-1 represents the largest cohort of patients with early treated PD ever enrolled in a clinical trial. The GST approach should provide high power to test the hypothesis that daily administration of creatine (10gm/day) is more effective than placebo in slowing clinical decline in PD between baseline and the 5 year follow-up visit against the background of dopaminergic therapy and best PD care. PMID:23079770

Perioperative Nutritional Management in Congenital Perineal and Vestibular Fistulas: A Systematic Review.

PubMed

Hofmeester, Marrigje Josien; Draaisma, Jos M T H; Versteegh, Hendt P; Huibregtse, Elizabeth C P; van Rooij, Iris A L M; de Blaauw, Ivo

2015-10-01

Surgical advancements have led to improved outcomes for children with congenital anorectal malformations with vestibular and perineal fistulas. However, the effect of perioperative nutritional management is debated and guidelines have not yet been established. The study aims to give an overview of available published evidence, regarding the impact of different perioperative nutritional management protocols on surgical outcome. A systematic literature review was conducted using PubMed, Embase, Cochrane Library, and CINAHL databases. All original articles concerning perioperative nutrition in children with vestibular and perineal fistulas were included. Methodological quality was assessed with the Rangel score. Included studies were subdivided into two groups: early enteral nutrition and prolonged fasting with or without parenteral nutrition. The database search resulted in 768 publications. Nine studies were eligible for inclusion. Wound complications were present in 56 of the 1,557 patients (4%) in whom this was assessed, and were more frequently seen in the prolonged fasting group (2 vs. 10%, p < 0.0001). Regarding the long-term outcome, constipation (grade II-III) was seen in 4% of the early feeding group, compared with 13% in the prolonged fasting group (p < 0.0001). This systematic review presents an overview of studies reporting on perioperative nutritional management in children with perineal and vestibular fistulas. Although study quality is low and study heterogeneity may also influence our results, early enteral feeding seems to be the preferable postoperative feeding strategy. Both early wound complications as well as long-term complications, in terms of clinically relevant constipation, seem to be lower in the early enteral feeding group. However, a prospective randomized, multicentered trial should be initiated to draw definitive conclusions regarding this matter. Georg Thieme Verlag KG Stuttgart · New York.

Improvement of long-term outcomes in pancreatic cancer and its associated factors within the gemcitabine era: a collaborative retrospective multicenter clinical review of 1,082 patients.

PubMed

Kuroda, Taira; Kumagi, Teru; Yokota, Tomoyuki; Seike, Hirotaka; Nishiyama, Mari; Imai, Yusuke; Inada, Nobu; Shibata, Naozumi; Imamine, Satoshi; Okada, Shin-ichi; Koizumi, Mitsuhito; Yamanishi, Hirofumi; Azemoto, Nobuaki; Miyaike, Jiro; Tanaka, Yoshinori; Tatsukawa, Haruka; Utsunomiya, Hiroki; Ohno, Yoshinori; Miyake, Teruki; Hirooka, Masashi; Furukawa, Shinya; Abe, Masanori; Ikeda, Yoshiou; Matsuura, Bunzo; Hiasa, Yoichi; Onji, Morikazu

2013-08-31

Although the outcomes of pancreatic cancer have been improved by gemcitabine, the changes in its characteristics and long-term outcomes within the gemcitabine era remain unclear. This study was conducted to identify clinical characteristics of pancreatic cancer patients within the gemcitabine era. A retrospective chart review was performed at 10 centers for 1,248 consecutive patients who were ever considered to have a diagnosis of pancreatic cancer between 2001 and 2010. Data collected included demographics, diagnosis date, clinical stage, treatment, and outcome 1,082 patients met the inclusion criteria and were analyzed further. The chi-square test, Student's t-test, and Mann-Whitney U-test were used for statistical analysis. Outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards regression. Differences in survival analyses were determined using the log-rank test. The distribution of clinical stages was: I, 2.2% II, 3.4% III, 13% IVa, 27% and IVb, 55%. Chemotherapy alone was administered to 42% of patients and 17% underwent resection. The 1-, 3-, and 5-year survival rates were 39%, 13%, and 6.9%, respectively. The median survival time was 257 days, but differed considerably among treatments and clinical stages. Demographics, distribution of clinical stage, and cause of death did not differ between groups A (2001-2005, n=406) and B (2006-2010, n=676). However, group B included more patients who underwent chemotherapy (P<0.0001) and fewer treated with best supportive care (P=0.0004), mirroring improvements in this group's long-term outcomes (P=0.0063). Finally, factors associated with long-term outcomes derived from multivariate analysis were clinical stage (P<0.0001), location of the tumor (P=0.0294) and treatments (surgery, chemotherapy) (<0.0001). Long-term outcomes in pancreatic cancer has improved even within the gemcitabine era, suggesting the importance of offering chemotherapy to patients previously only considered for best supportive care. Most patients are still diagnosed at an advanced stage, making clinical strategy development for diagnosing pancreatic cancer at earlier stages essential.

Long-term safety and efficacy of TAK-085 in Japanese subjects with hypertriglyceridemia undergoing lifestyle modification: the omega-3 fatty acids randomized long-term (ORL) study.

PubMed

Tatsuno, Ichiro; Saito, Yasushi; Kudou, Kentarou; Ootake, Jun

2013-01-01

TAK-085 is an omega-3 preparation that contains eicosapentaenoic acid ethyl-ester (EPA-E) and docosahexaenoic acid-ethyl ester used in the management of hypertriglyceridemia. The aim of the study was to evaluate the long-term safety (adverse events [AEs], laboratory parameters, vital signs, weight, and electrocardiograms) and effects on lipid profiles, especially triglyceride levels, of TAK-085 in Japanese patients with hypertriglyceridemia (triglyceride levels ≥150 mg/dL and <750 mg/dL). In this multicenter, open-label, randomized study, adults with hypertriglyceridemia undergoing lifestyle modification received TAK-085 2 g (2 g once daily; n = 165) or 4 g (2 g twice daily; n = 171), or EPA-E 1.8 g (0.6 g three times daily; n = 167) for 52 weeks. Patients were stratified for co-administration of a statin. TAK-085 was well tolerated throughout the 52-week study. Overall, no substantial differences were found in the tolerability of TAK-085 2 g, TAK-085 4 g, and EPA-E 1.8 g with incidence rates for AEs of 83.6%, 86.0%, and 89.2%, respectively. Most AEs were mild or moderate in severity. Triglyceride levels decreased from baseline in all groups by week 4, and the decreases were maintained throughout the study. At week 52 the reduction in triglycerides with TAK-085 2 g (-13.9%) was similar to that with EPA-E 1.8 g (-12.1%), whereas the reduction seen with TAK-085 4 g (-25.5%) was greater than that with EPA-E 1.8 g, as assessed by point estimates and 95% confidence intervals. TAK-085 was safe and well tolerated for up to 52 weeks of treatment in Japanese patients with hypertriglyceridemia undergoing lifestyle modification. Reductions in triglyceride levels achieved after 4 weeks were maintained at 52 weeks. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.

CLINICAL OUTCOMES AND SELF-REPORTED SYMPTOMS IN PATIENTS WITH ACROMEGALY: AN 8-YEAR FOLLOW-UP OF A LANREOTIDE STUDY.

PubMed

Khairi, Shafaq; Sagvand, Babak Torabi; Pulaski-Liebert, Karen J; Tritos, Nicholas A; Klibanski, Anne; Nachtigall, Lisa B

2017-01-01

The aim of this study was to evaluate the proportion of patients with acromegaly who remained on long-term lanreotide depot after completion of an open-label multicenter phase III clinical trial (SALSA: A Multi Center Open Label Study to Assess the Ability of Subjects With Acromegaly or Their Partners to Administer Somatuline Autogel), compare baseline and long-term follow-up symptoms scores, and correlate scores with individual longitudinal clinical outcomes. Records of all subjects previously enrolled at the Massachusetts General Hospital site of SALSA were reviewed. Those who remained on lanreotide were interviewed and asked to complete a questionnaire that they had filled out in SALSA in 2007 regarding their current symptomatology and injection side effects, as well as to complete the Acromegaly Quality of Life Questionnaire. Furthermore, clinical, biochemical, and radiographic data related to acromegaly and its comorbidities were tracked throughout follow-up. Six out of 7 patients chose to remain on lanreotide, and 5 of them continued lanreotide depot through last follow-up, for up to 8 years or in 1 case until death. In all cases, lanreotide remained well tolerated, and insulin-like growth factor-1 levels and pituitary imaging remained well controlled on stable doses. While comorbidities persisted or developed, the self-reported symptom score after up to 8 years of therapy showed a significant decrease in frequency or resolution in symptoms that were reported at baseline. This study shows a significant decrease in frequency or resolution in self-reported symptoms in well-controlled patients receiving long-term lanreotide therapy. AcroQoL = Acromegaly Quality of Life Questionnaire GH = growth hormone GI = gastrointestinal IGF-1 = insulin-like growth factor-1 SALSA = A Multi Center Open Label Study to Assess the Ability of Subjects With Acromegaly or Their Partners to Administer Somatuline Autogel.

Long-term Effects of Renin-Angiotensin System–Blocking Therapy and a Low Blood Pressure Goal on Progression of Hypertensive Chronic Kidney Disease in African Americans

PubMed Central

Appel, Lawrence J.; Wright, Jackson T.; Greene, Tom; Kusek, John W.; Lewis, Julia B.; Wang, Xuelei; Lipkowitz, Michael S.; Norris, Keith C.; Bakris, George L.; Rahman, Mahboob; Contreras, Gabriel; Rostand, Stephen G.; Kopple, Joel D.; Gabbai, Francis B.; Schulman, Gerald I.; Gassman, Jennifer J.; Charleston, Jeanne; Agodoa, Lawrence Y.

2013-01-01

Background Antihypertensive drugs that block the renin-angiotensin system (angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers) are recommended for patients with chronic kidney disease (CKD). A low blood pressure (BP) goal (BP, <130/80 mm Hg) is also recommended. The objective of this study was to determine the long-term effects of currently recommended BP therapy in 1094 African Americans with hypertensive CKD. Methods Multicenter cohort study following a randomized trial. Participants were 1094 African Americans with hypertensive renal disease (glomerular filtration rate, 20–65 mL/min/1.73 m2). Following a 3×2-factorial trial (1995–2001) that tested 3 drugs used as initial antihypertensive therapy (ACEIs, calcium channel blockers, and β-blockers) and 2 levels of BP control (usual and low), we conducted a cohort study (2002–2007) in which participants were treated with ACEIs to a BP lower than 130/80 mm Hg. The outcome measures were a composite of doubling of the serum creatinine level, end-stage renal disease, or death. Results During each year of the cohort study, the annual use of an ACEI or an angiotensin receptor blocker ranged from 83.7% to 89.0% (vs 38.5% to 49.8% during the trial). The mean BP in the cohort study was 133/78 mm Hg (vs 136/82 mm Hg in the trial). Overall, 567 participants experienced the primary outcome; the 10-year cumulative incidence rate was 53.9%. Of 576 participants with at least 7 years of follow-up, 33.5% experienced a slow decline in kidney function (mean annual decline in the estimated glomerular filtration rate, <1 mL/min/1.73 m2). Conclusion Despite the benefits of renin-angiotensin system–blocking therapy on CKD progression, most African Americans with hypertensive CKD who are treated with currently recommended BP therapy continue to progress during the long term. PMID:18443258

Norwegican Cartilage Project - a study protocol for a double-blinded randomized controlled trial comparing arthroscopic microfracture with arthroscopic debridement in focal cartilage defects in the knee.

PubMed

Aae, Tommy Frøseth; Randsborg, Per-Henrik; Breen, Anne Berg; Visnes, Håvard; Vindfeld, Søren; Sivertsen, Einar Andreas; Løken, Sverre; Brinchmann, Jan; Hanvold, Heidi Andreassen; Årøen, Asbjørn

2016-07-16

Focal lesions to the articular cartilage in the knee might have demolishing consequences to the knee. There exists a wide range of possible surgical procedures targeting these injuries, however no significant differences have been found between these procedures. This may support that the improvement is a result of rehabilitation, and not the surgery itself. Arthroscopic microfracture (MF) treatment has gained popularity, and has become the treatment of choice in patients with knee cartilage defects globally. In this study we want to increase knowledge, both clinical and economic, about arthroscopic microfracture (AF) compared to arthroscopic debridement (AD) and physical rehabilitation both in the short run, and in the long run. To compare arthroscopic microfracture with arthroscopic debridement and physiotherapy for the treatment of focal cartilage lesions in the knee, a long-term, double-blinded, randomized controlled multicenter trial will be conducted. A total of 114 men and non-pregnant women with a symptomatic focal full thickness cartilage lesion in the knee less than 2 cm2 will be included in the study. The two treatment allocations will receive identical rehabilitation, which is made up of 3 phases: accommodation, rehabilitation and return to activity. Follow up is 24 months, where all will be invited to participate in late follow ups after 5 and 10 years. The Knee Injury and Osteoarthritis Outcome Score (KOOS) knee-related quality of life (QoL) subscore is the primary endpoint. Clinical parameters, questionnaires and radiologic modalities (Magnetic Resonance Imaging (MRI) and x-ray) will be used as secondary endpoints. This is an ongoing multicenter study with a high level of evidence to compare arthroscopic microfracture with arthroscopic debridement and physiotherapy for the treatment of isolated symptomatic full thickness cartilage lesions in the knee joint. ClinicalTrials.gov ID: NCT02637505 (December 15, 2015).

Age of Red Cells for Transfusion and Outcomes in Critically Ill Adults.

PubMed

Cooper, D James; McQuilten, Zoe K; Nichol, Alistair; Ady, Bridget; Aubron, Cécile; Bailey, Michael; Bellomo, Rinaldo; Gantner, Dashiell; Irving, David O; Kaukonen, Kirsi-Maija; McArthur, Colin; Murray, Lynne; Pettilä, Ville; French, Craig

2017-11-09

It is uncertain whether the duration of red-cell storage affects mortality after transfusion among critically ill adults. In an international, multicenter, randomized, double-blind trial, we assigned critically ill adults to receive either the freshest available, compatible, allogeneic red cells (short-term storage group) or standard-issue (oldest available), compatible, allogeneic red cells (long-term storage group). The primary outcome was 90-day mortality. From November 2012 through December 2016, at 59 centers in five countries, 4994 patients underwent randomization and 4919 (98.5%) were included in the primary analysis. Among the 2457 patients in the short-term storage group, the mean storage duration was 11.8 days. Among the 2462 patients in the long-term storage group, the mean storage duration was 22.4 days. At 90 days, there were 610 deaths (24.8%) in the short-term storage group and 594 (24.1%) in the long-term storage group (absolute risk difference, 0.7 percentage points; 95% confidence interval [CI], -1.7 to 3.1; P=0.57). At 180 days, the absolute risk difference was 0.4 percentage points (95% CI, -2.1 to 3.0; P=0.75). Most of the prespecified secondary measures showed no significant between-group differences in outcome. The age of transfused red cells did not affect 90-day mortality among critically ill adults. (Funded by the Australian National Health and Medical Research Council and others; TRANSFUSE Australian and New Zealand Clinical Trials Registry number, ACTRN12612000453886 ; ClinicalTrials.gov number, NCT01638416 .).

Study protocol: The Improving Care of Acute Lung Injury Patients (ICAP) study

PubMed Central

Needham, Dale M; Dennison, Cheryl R; Dowdy, David W; Mendez-Tellez, Pedro A; Ciesla, Nancy; Desai, Sanjay V; Sevransky, Jonathan; Shanholtz, Carl; Scharfstein, Daniel; Herridge, Margaret S; Pronovost, Peter J

2006-01-01

Introduction The short-term mortality benefit of lower tidal volume ventilation (LTVV) for patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) has been demonstrated in a large, multi-center randomized trial. However, the impact of LTVV and other critical care therapies on the longer-term outcomes of ALI/ARDS survivors remains uncertain. The Improving Care of ALI Patients (ICAP) study is a multi-site, prospective cohort study that aims to evaluate the longer-term outcomes of ALI/ARDS survivors with a particular focus on the effect of LTVV and other critical care therapies. Methods Consecutive mechanically ventilated ALI/ARDS patients from 11 intensive care units (ICUs) at four hospitals in the city of Baltimore, MD, USA, will be enrolled in a prospective cohort study. Exposures (patient-based, clinical management, and ICU organizational) will be comprehensively collected both at baseline and throughout patients' ICU stay. Outcomes, including mortality, organ impairment, functional status, and quality of life, will be assessed with the use of standardized surveys and testing at 3, 6, 12, and 24 months after ALI/ARDS diagnosis. A multi-faceted retention strategy will be used to minimize participant loss to follow-up. Results On the basis of the historical incidence of ALI/ARDS at the study sites, we expect to enroll 520 patients over two years. This projected sample size is more than double that of any published study of long-term outcomes in ALI/ARDS survivors, providing 86% power to detect a relative mortality hazard of 0.70 in patients receiving higher versus lower exposure to LTVV. The projected sample size also provides sufficient power to evaluate the association between a variety of other exposure and outcome variables, including quality of life. Conclusion The ICAP study is a novel, prospective cohort study that will build on previous critical care research to improve our understanding of the longer-term impact of ALI/ARDS, LTVV and other aspects of critical care management. Given the paucity of information about the impact of interventions on long-term outcomes for survivors of critical illness, this study can provide important information to inform clinical practice. PMID:16420652

Long-term stability of cognitive behavioral therapy effects for panic disorder with agoraphobia: a two-year follow-up study.

PubMed

Gloster, Andrew T; Hauke, Christina; Höfler, Michael; Einsle, Franziska; Fydrich, Thomas; Hamm, Alfons; Sthröhle, Andreas; Wittchen, Hans-Ulrich

2013-12-01

Cognitive-behavioral therapy (CBT) aims to help patients establish new behaviors that will be maintained and adapted to the demands of new situations. The long-term outcomes are therefore crucial in testing the durability of CBT. A two-year follow-up assessment was undertaken on a subsample of n = 146 PD/AG patients from a multicenter randomized controlled trial. Treatment consisted of two variations of CBT: exposure in situ in the presence of the therapist (T+) or on their own following therapist preparation (T-). Both variations of CBT had high response rates and, overall, maintained the level of symptomatology observed at post-treatment with high levels of clinical significance. Effect sizes 24 months following treatment were somewhat lower than at the 6-month follow up. Once patients reached responder status, they generally tended to remain responders at subsequent assessments. Differences were observed for patients that obtained additional treatment during the follow-up period. Expert opinion and subjective appraisal of treatment outcome differed. No robust baseline predictors of 2-year outcome were observed. Most patients maintain clinically meaningful changes two years following treatment across multiple outcome measures. Approximately 1/3 of patients continued to experience meaningful residual problems. Copyright © 2013 Elsevier Ltd. All rights reserved.

Predictors and Long-Term Clinical Impact of Acute Stent Malapposition: An Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) Intravascular Ultrasound Substudy.

PubMed

Wang, Bin; Mintz, Gary S; Witzenbichler, Bernhard; Souza, Cristiano F; Metzger, D Christopher; Rinaldi, Michael J; Duffy, Peter L; Weisz, Giora; Stuckey, Thomas D; Brodie, Bruce R; Matsumura, Mitsuaki; Yamamoto, Myong-Hwa; Parvataneni, Rupa; Kirtane, Ajay J; Stone, Gregg W; Maehara, Akiko

2016-12-22

The impact of acute stent malapposition (ASM) on long-term clinical outcomes in patients undergoing percutaneous coronary intervention is still controversial. We sought to evaluate predictors and long-term clinical outcomes of ASM. ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective multicenter study of 8663 patients undergoing percutaneous coronary intervention using drug-eluting stents. In a prespecified intravascular ultrasound-guided substudy, 2072 patients with 2446 culprit lesions had post-percutaneous coronary intervention intravascular ultrasound and were classified according to the presence or absence of ASM. After intravascular ultrasound-guided percutaneous coronary intervention, the overall prevalence of ASM after successful drug-eluting stents implantation was 14.4% per patient and 12.6% per lesion. Compared to lesions without ASM, lesions with ASM had larger in-stent lumen areas, larger stent areas, and larger in-stent vessel areas. A larger mean plaque area along with more attenuated plaque was observed in lesions with ASM versus lesions without ASM. Lesions with ASM had greater proximal and distal reference lumen areas and more distal, but not proximal, reference calcium compared to lesions without ASM. At 2-year follow-up, there was no significant difference in the incidence of cardiac death; myocardial infarction; early, late, or very late stent thrombosis; or clinically driven target lesion revascularization in patients with ASM versus those without ASM. Furthermore, ASM was not an independent predictor of 2-year major adverse cardiac events or target lesion revascularization even when forced into the multivariate model. In patients treated with intravascular ultrasound-guided drug-eluting stents implantation, ASM was not associated with adverse clinical events during long-term follow-up including, but not limited to, stent thrombosis. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00638794. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Retrospective data collection of psoriasis treatment with fumaric acid esters in children and adolescents in Germany (KIDS FUTURE study).

PubMed

Reich, Kristian; Hartl, Christoph; Gambichler, Thilo; Zschocke, Ina

2016-01-01

Given that there is no standard systemic treatment for children and adolescents with plaque psoriasis, this non-interventional, multicenter, retrospective study collected data on the efficacy and safety of long-term treatment with fumaric acid esters (FAEs) in this particular patient group. In patients younger than 18 years of age at the start of FAE treatment, data on efficacy and safety was retrospectively collected for at least 36 months. Data from 127 patients (aged 6-17 years) was collected for treatment durations of up to 60 months. Physician's Global Assessment, Psoriasis Area and Severity Index, and Body Surface Area showed marked improvement in the first six months. After 36 months, these parameters had, on average, improved by up to two-thirds of baseline values. Thirty-seven patients experienced at least one adverse event (AE), which was FAE-related in 36 individuals. Three AEs (proteinuria (one case), flushing (two cases)) persisted during the observation period while on treatment. Fifteen AEs led to the discontinuation of therapy; nearly all of these cases were related to gastrointestinal disorders. The KIDS FUTURE study - for the first time - included a larger population of children and adolescents with psoriasis who were treated with FAEs. The data obtained suggests that long-term FAE therapy in this patient group may be effective and safe. The results are currently being verified in an ongoing clinical study. © 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Chemotherapy-induced amenorrhea in patients with breast cancer with a BRCA1 or BRCA2 mutation.

PubMed

Valentini, Adriana; Finch, Amy; Lubinski, Jan; Byrski, Tomasz; Ghadirian, Parviz; Kim-Sing, Charmaine; Lynch, Henry T; Ainsworth, Peter J; Neuhausen, Susan L; Greenblatt, Ellen; Singer, Christian; Sun, Ping; Narod, Steven A

2013-11-01

To determine the likelihood of long-term amenorrhea after treatment with chemotherapy in women with breast cancer who carry a BRCA1 or BRCA2 mutation. We conducted a multicenter survey of 1,954 young women with a BRCA1 or BRCA2 mutation who were treated for breast cancer. We included premenopausal women who were diagnosed with invasive breast cancer between 26 and 47 years of age. We determined the age of onset of amenorrhea after breast cancer for women who were and were not treated with chemotherapy, alone or with tamoxifen. We considered chemotherapy-induced amenorrhea to have occurred when the patient experienced ≥ 2 years of amenorrhea, commencing within 2 years of initiating chemotherapy, with no resumption of menses. Of the 1,426 women who received chemotherapy, 35% experienced long-term amenorrhea. Of the 528 women who did not receive chemotherapy, 5.3% developed long-term amenorrhea. The probabilities of chemotherapy-induced amenorrhea were 7.2% for women diagnosed before age 30 years, 33% for women age 31 to 44 years, and 79% for women diagnosed after age 45 years (P trend < .001). The probability of induced amenorrhea was higher for women who received tamoxifen than for those who did not (52% v 29%; P < .001). Age at treatment and use of tamoxifen are important predictors of chemotherapy-induced amenorrhea in women who carry a BRCA1 or BRCA2 mutation. The risk of induced long-term amenorrhea does not seem to be greater among mutation carriers than among women who do not carry a mutation.

[Patient education in rheumatology: a way to better disease management using patients' empowerment].

PubMed

Lind-Albrecht, Gudrun

2006-11-01

Patients' empowerment has become a main issue in modern treatment of chronic rheumatic diseases. Within this concept patient education is an important instrument. Specific standardized programs, developed by multicenter groups under the leadership of the DGRh (German Society for Rheumatology) have become widely used all over Germany. The DGRh takes care of the program quality and of the trainers and heads of courses. Based on modern educational theories for adults and using a modular concept, which must be adapted to the individual situation of the patients, the curricula are put into practice by trainees of the different professions concerned. Controlled studies have not only shown the progress of patients' knowledge, compliance and coping, but also showed striking socioeconomic advantages in long-term follow-up. Patient education leads to a better and cost-effective management of rheumatic diseases.

Rationale and Study Design for a Single-Arm Phase IIa Study Investigating Feasibility of Preventing Ischemic Cerebrovascular Events in High-Risk Patients with Acute Non-disabling Ischemic Cerebrovascular Events Using Remote Ischemic Conditioning

PubMed Central

Liu, Shi-Meng; Zhao, Wen-Le; Song, Hai-Qing; Meng, Ran; Li, Si-Jie; Ren, Chang-Hong; Ovbiagele, Bruce; Ji, Xun-Ming; Feng, Wu-Wei

2018-01-01

Background: Acute minor ischemic stroke (AMIS) or transient ischemic attack (TIA) is a common cerebrovascular event with a considerable high recurrence. Prior research demonstrated the effectiveness of regular long-term remote ischemic conditioning (RIC) in secondary stroke prevention in patients with intracranial stenosis. We hypothesized that RIC can serve as an effective adjunctive therapy to pharmacotherapy in preventing ischemic events in patients with AMIS/TIA. This study aimed to investigate the feasibility, safety, and preliminary efficacy of daily RIC in inhibiting cerebrovascular/cardiovascular events after AMIS/TIA. Methods: This is a single-arm, open-label, multicenter Phase IIa futility study with a sample size of 165. Patients with AMIS/TIA receive RIC as an additional therapy to secondary stroke prevention regimen. RIC consists of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs on bilateral upper limbs twice a day for 90 days. The antiplatelet strategy is based on individual physician's best practice: aspirin alone, clopidogrel alone, or combination of aspirin and clopidogrel. We will assess the recurrence rate of ischemic stroke/TIA within 3 months as the primary outcomes. Conclusions: The data gathered from the study will be used to determine whether a further large-scale, multicenter randomized controlled Phase II trial is warranted in patients with AMIS/TIA. Trial Registration: ClinicalTrials.gov, NCT03004820; https://www.clinicaltrials.gov/ct2/show/NCT03004820. PMID:29363651

Retrograde Intrarenal Surgery for Symptomatic Renal Sinus Cysts: Long-Term Results and Literature Review.

PubMed

Mancini, Vito; Cormio, Luigi; d'Altilia, Nicola; Benedetto, Giuseppe; Ferrarese, Paolo; Balzarro, Matteo; Defidio, Lorenzo; Carrieri, Giuseppe

2018-05-02

To report the long-term multicenter experience with retrograde intrarenal holmium-laser incision (RIR-HoLI) in the management of symptomatic renal sinus cysts (RSCs). In the literature, RIR-HoLI has been shown to be a safe and effective treatment, but there are only a few reports regarding long-term results and reproducibility of this procedure. From June 2010 to June 2015, 14 patients with symptomatic RSCs underwent RIR-HoLI. The mean age was 52.1 ± 11.28 years (range 28-77) and the mean cyst size was 53.2 ± 14.23 mm (range 35-90). In all cases, contrast-enhanced computer tomography (CT) showed compression of the renal pelvis by the cyst (no malignancy). Surgical outcome was assessed in terms of symptoms improvement (measured by Visual Analogue Scale [VAS] for pain) and renal ultrasound findings at 3-6-12 months postoperatively and then yearly. CT scan was carried out at 12 months follow-up. RIR-HoLI was successful in all patients. The mean operative time was 47.8 ± 13.54 min (range 30-80) and mean hospital stay was 3.5 days (range 2-5). There were 2 Clavien grade II complications (flank pain and urgency delaying discharge). After surgery, all patients -became asymptomatic (VAS score change, p = 0.0001). One patient had persistence of a small cyst (10 mm). Mean follow-up is 44 ± 17.24 months (range 24-84); all patients remained asymptomatic, with no signs of recurrence. RIR-HoLI proved to be a safe and effective treatment for symptomatic RSCs. In our experience, it provided excellent long-term results and was reproducible at 4 different -institutions. © 2018 S. Karger AG, Basel.

Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome.

PubMed

de Lind van Wijngaarden, Roderick F A; Siemensma, Elbrich P C; Festen, Dederieke A M; Otten, Barto J; van Mil, Edgar G A H; Rotteveel, Joost; Odink, Roelof J H; Bindels-de Heus, G C B Karen; van Leeuwen, Mariëtte; Haring, Danny A J P; Bocca, Gianni; Houdijk, E C A Mieke; Hoorweg-Nijman, J J Gera; Vreuls, René C F M; Jira, Petr E; van Trotsenburg, A S Paul; Bakker, Boudewijn; Schroor, Eelco J; Pilon, Jan Willem; Wit, Jan M; Drop, Stenvert L S; Hokken-Koelega, Anita C S

2009-11-01

Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Short-term GH treatment has beneficial effects. The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters. We conducted a multicenter prospective trial. Fifty-five children with a mean +/- sd age of 5.9 +/- 3.2 yr were followed during 4 yr of continuous GH treatment (1 mg/m(2) . d). Data were annually obtained in one center: fat percentage (fat%) and lean body mass (LBM) by dual-energy x-ray absorptiometry, height, weight, head circumference, bone age, blood pressure, and fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, and low-density lipoprotein. sd scores (SDS) were calculated according to Dutch and PWS reference values (SDS and SDS(PWS)). Fat%SDS was significantly lower after 4 yr of GH treatment (P < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but returned to baseline values the second year and remained unchanged thereafter. Mean +/- sd height normalized from -2.27 +/- 1.2 SDS to -0.24 +/- 1.2 SDS (P < 0.0001). Head circumference SDS increased from -0.79 +/- 1.0 at start to 0.07 +/- 1.1 SDS after 4 yr. BMISDS(PWS) significantly decreased. Mean +/- sd IGF-I and the IGF-I/IGF binding protein-3 ratio significantly increased to 2.08 +/- 1.1 and 2.32 +/- 0.9 SDS, respectively. GH treatment had no adverse effects on bone maturation, blood pressure, glucose homeostasis, and serum lipids. Our study in children with PWS shows that 4 yr of continuous GH treatment (1 mg/m(2) . d) improves body composition by decreasing fat%SDS and stabilizing LBMSDS and head circumference SDS and normalizes heightSDS without adverse effects. Thus, long-term continuous GH treatment is an effective and safe therapy for children with PWS.

Follow-up of the original cohort with the Ahmed glaucoma valve implant.

PubMed

Topouzis, F; Coleman, A L; Choplin, N; Bethlem, M M; Hill, R; Yu, F; Panek, W C; Wilson, M R

1999-08-01

To study the long-term results of the Ahmed glaucoma valve implant in patients with complicated glaucoma in whom short-term results have been reported. In this multicenter study, we analyzed the long-term outcome of a cohort of 60 eyes from 60 patients in whom the Ahmed glaucoma valve was implanted. Failure was characterized by at least one of the following: intraocular pressure greater than 21 mm Hg at both of the last two visits less than 6 mm Hg at both of the last two visits, loss of light perception, additional glaucoma surgery, devastating complications, and removal or replacement of the Ahmed glaucoma valve implant. Devastating complications included chronic hypotony, retinal detachment, malignant glaucoma, endophthalmitis, and phthisis bulbi; we also report results that add corneal complications (corneal decompensation or edema, corneal graft failure) as defining a devastating complication. The mean follow-up time for the 60 eyes was 30.5 months (range, 2.1 to 63.5). When corneal complications were included in the definition of failure, 26 eyes (43%) were considered failures. Cumulative probabilities of success at 1, 2, 3, and 4 years were 76%, 68%, 54%, and 45%, respectively. When corneal complications were excluded from the definition of failure, 13 eyes (21.5%) were considered failures. Cumulative probabilities of success at 1, 2, 3, and 4 years were 87%, 82%, 76%, and 76%, respectively. Most of the failures after 12 months of postoperative follow-up were because of corneal complications. The long-term performance of the Ahmed glaucoma valve implant is comparable to other drainage devices. More than 12 months after the implantation of the Ahmed glaucoma valve implant, the most frequent adverse outcome was corneal decompensation or corneal graft failure. These corneal problems may be secondary to the type of eyes that have drainage devices or to the drainage device itself. Further investigation is needed to identify the reasons that corneal problems follow drainage device implantation.

Long-Term Effects of Highly Active Antiretroviral Therapy on CD4+ Cell Evolution among Children and Adolescents Infected with HIV: 5 Years and Counting

PubMed Central

Patel, Kunjal; Hernán, Miguel A.; Williams, Paige L.; Seeger, John D.; McIntosh, Kenneth; Van Dyke, Russell B.; Seage, George R.

2011-01-01

Background Lower percentages of CD4+ T lymphocytes are associated with adverse clinical outcomes among children and adolescents infected with human immunodeficiency virus (HIV). CD4+ lymphocyte percentage generally increases with receipt of highly active antiretroviral therapy (HAART), but long-term follow-up is required to assess whether these increases in CD4+ cell percentage are maintained and whether they lead to normal CD4+ cell percentages in children with severe immunosuppression. Methods The study population included 1236 children and adolescents perinatally infected with HIV who were enrolled in a US-based multicenter prospective cohort study (Pediatric AIDS Clinical Trials Group 219/219C) and who were not receiving HAART at study initiation. We estimated the effects of HAART, HAART with protease inhibitors, and HAART with nonnucleoside reverse-transcriptase inhibitors on CD4+ cell percentage, using marginal structural models to account for confounding by severity. Results Initiation of any type of HAART increased CD4+ cell percentage by 2.34% (95% confidence interval, 1.35%–3.33%) in the first year, relative to noninitiation of HAART. The substantial increases in CD4+ cell percentage observed after the first year of experience with these combination therapies were followed by relatively smaller increases that continued for 5 years after initiation. Although larger increases in CD4+ cell percentage were observed among children with a greater degree of immunosuppression at baseline, the mean CD4+ cell percentage after 5 years of HAART did not reach normal levels. Conclusions Our study supports the initiation of HAART in children before severe immunosuppression occurs for long-term maintenance of normal CD4+ cell percentages. This beneficial result must be weighed against the evidence of potential adverse events associated with the prolonged use of such therapy. PMID:18426371

One-year clinical outcome of biodegradable polymer sirolimus-eluting stent in all-comers population. Insight from the ULISSE registry (ULtimaster Italian multicenter all comerS Stent rEgistry).

PubMed

Godino, Cosmo; Beneduce, Alessandro; Ferrante, Giuseppe; Ielasi, Alfonso; Pivato, Andrea Carlo; Chiarito, Mauro; Cappelletti, Alberto; Perfetti, Giulia; Magni, Valeria; Prati, Eugenio; Falcone, Stefania; Pierri, Adele; De Martini, Stefano; Montorfano, Matteo; Parisi, Rosario; Rutigliano, David; Locuratolo, Nicola; Anzuini, Angelo; Tespilli, Maurizio; Margonato, Alberto; Benassi, Alberto; Briguori, Carlo; Fabbiocchi, Franco; Reimers, Bernhard; Bartorelli, Antonio; Colombo, Antonio

2018-06-01

This study was designed to confirm in a large population of unselected patients the promising results of Ultimaster® biodegradable polymer sirolimus-eluting stent (BP-SES) already shown in previous trial. ULISSE is an observational, multicenter, national registry evaluating all patients undergoing PCI with the Ultimaster® BP-SES. Incidence of 1-year TLF (cardiac death or target vessel MI or clinically indicated TLR) was the primary endpoint. Pre-specified subgroup analysis was performed for diabetic patients and for those with lesion longer than 25 mm, bifurcation and CTO lesions. 1660 patients were enrolled in 9 Italian cardiology centers, 82% were males, mean age of 68 ± 10 years, and 29% were diabetics. Overall 2422 lesions were treated, 65% type B2/C lesions, 7% CTOs, 17% bifurcations and 38% long lesions. The incidence of 1-year TLF was 5%, with 3.2% of clinically indicated TLR. TLF occurred in 8% of the patients with diabetes mellitus, and 7% in bifurcation, 6.7% in CTO and 6.2% in long lesions. Definite overall ST was 0.9%, and 1.2% in patients treated for type B2/C lesions. Multivariate logistic regression analysis identified stenting on unprotected LMT (OR = 4.80), stenting on ISR lesion (OR = 3.19) and need for rotational atherectomy (OR = 6.24) as the strongest independent predictors of TLF. The results of this national all-comers registry show that the Ultimaster® BP-SES real-world performance was comparable with that observed in the clinical trial, with low rate of primary endpoint and TLR. Long term follow-up will be necessary to prove the theoretical advantage of the BP-SES over time. Copyright © 2017. Published by Elsevier B.V.

Determinants of intensive insulin therapeutic regimens in patients with type 1 diabetes: data from a nationwide multicenter survey in Brazil

PubMed Central

2014-01-01

Background To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D). Methods This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups. Results We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). The majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001). Conclusions Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits. PMID:24920963

Design and methodology of the NorthStar Study: NT-proBNP stratified follow-up in outpatient heart failure clinics -- a randomized Danish multicenter study.

PubMed

Schou, Morten; Gustafsson, Finn; Videbaek, Lars; Markenvard, John; Ulriksen, Hans; Ryde, Henrik; Jensen, Jens C H; Nielsen, Tonny; Knudsen, Anne S; Tuxen, Christian D; Handberg, Jens; Sørensen, Per J; Espersen, Geert; Lind-Rasmussen, Søren; Keller, Niels; Egstrup, Kenneth; Nielsen, Olav W; Abdulla, Jawdat; Nyvad, Ole; Toft, Jens; Hildebrandt, Per R

2008-10-01

Randomized clinical trials have shown that newly discharged and symptomatic patients with chronic heart failure (CHF) benefit from follow-up in a specialized heart failure clinic (HFC). Clinical stable and educated patients are usually discharged from the HFC when on optimal therapy. It is unknown if risk stratification using natriuretic peptides could identify patients who would benefit from longer-term follow-up. Furthermore, data on the use of natriuretic peptides for monitoring of stable patients with CHF are sparse. The aims of this study are to test the hypothesis that clinical stable, educated, and medical optimized patients with CHF with N-terminal pro-brain natriuretic peptide (NT-proBNP) levels > or = 1,000 pg/mL benefit from long-term follow-up in an HFC and to assess the efficacy of NT-proBNP monitoring. A total of 1,250 clinically stable, medically optimized, and educated patients with CHF will be enrolled from 18 HFCs in Denmark. The patients will be randomized to treatment in general practice, to a standard follow-up program in the HFC, or to NT-proBNP monitoring in the HFC. The patients will be followed for 30 months (median). Data will be collected from 2006 to 2009. At present (March 2008), 720 patients are randomized. Results expect to be presented in the second half of 2010. This article outlines the design of the NorthStar study. If our hypotheses are confirmed, the results will help cardiologists and nurses in HFCs to identify patients who may benefit from long-term follow-up. Our results may also indicate whether patients with CHF will benefit from adding serial NT-proBNP measurements to usual clinical monitoring.

Effect of Transcutaneous Electrical Nerve Stimulation on Pain, Function, and Quality of Life in Fibromyalgia: A Double-Blind Randomized Clinical Trial

PubMed Central

Noehren, Brian; Dailey, Dana L.; Rakel, Barbara A.; Vance, Carol G.T.; Zimmerman, Miriam B.; Crofford, Leslie J.

2015-01-01

Background Fibromyalgia is a common chronic pain condition that has a significant impact on quality of life and often leads to disability. To date, there have been few well-controlled trials assessing the utility of nonpharmacological treatment modalities such as transcutaneous electrical nerve stimulation (TENS) in the management of pain and improvement in function in individuals with fibromyalgia. Objectives The purpose of this study will be to complete a long-term, multicenter study to assess the effects of TENS in women with fibromyalgia. Design This will be a phase II randomized, double-blind, placebo-controlled, multicenter clinical trial. Participants Three hundred forty-three participants with fibromyalgia will be recruited for this study. Intervention Participants will be randomly assigned to 1 of 3 groups: the intervention (TENS), placebo, or no treatment. After completing the randomized period, all participants will receive the intervention for 1 month. The participants will be asked to use TENS at the highest tolerable level for at least 2 hours daily during physical activity. Measurements The primary outcome will be pain with movement, with secondary outcomes assessing functional abilities, patient-reported outcomes, and quantitative sensory testing. Limitations Because having participants refrain from their typical medications is not practical, their usage and any change in medication use will be recorded. Conclusions The results of this study will provide some of the first evidence from a large-scale, double-blind, placebo-controlled trial on the effectiveness of TENS on pain control and quality-of-life changes in patients with fibromyalgia. PMID:25212518

Effect of transcutaneous electrical nerve stimulation on pain, function, and quality of life in fibromyalgia: a double-blind randomized clinical trial.

PubMed

Noehren, Brian; Dailey, Dana L; Rakel, Barbara A; Vance, Carol G T; Zimmerman, Miriam B; Crofford, Leslie J; Sluka, Kathleen A

2015-01-01

Fibromyalgia is a common chronic pain condition that has a significant impact on quality of life and often leads to disability. To date, there have been few well-controlled trials assessing the utility of nonpharmacological treatment modalities such as transcutaneous electrical nerve stimulation (TENS) in the management of pain and improvement in function in individuals with fibromyalgia. The purpose of this study will be to complete a long-term, multicenter study to assess the effects of TENS in women with fibromyalgia. This will be a phase II randomized, double-blind, placebo-controlled, multicenter clinical trial. Three hundred forty-three participants with fibromyalgia will be recruited for this study. Participants will be randomly assigned to 1 of 3 groups: the intervention (TENS), placebo, or no treatment. After completing the randomized period, all participants will receive the intervention for 1 month. The participants will be asked to use TENS at the highest tolerable level for at least 2 hours daily during physical activity. The primary outcome will be pain with movement, with secondary outcomes assessing functional abilities, patient-reported outcomes, and quantitative sensory testing. Because having participants refrain from their typical medications is not practical, their usage and any change in medication use will be recorded. The results of this study will provide some of the first evidence from a large-scale, double-blind, placebo-controlled trial on the effectiveness of TENS on pain control and quality-of-life changes in patients with fibromyalgia. © 2015 American Physical Therapy Association.

Multicenter retrospective analysis of cardiovascular risk factors affecting long-term outcome of de novo cardiac transplant recipients.

PubMed

Kobashigawa, Jon A; Starling, Randall C; Mehra, Mandeep R; Kormos, Robert L; Bhat, Geetha; Barr, Mark L; Sigouin, Chris S; Kolesar, June; Fitzsimmons, William

2006-09-01

Previous risk factor studies in cardiac transplant patients have analyzed pre-transplant risk factors as they relate to outcomes. This study is the first in-depth multicenter assessment of ongoing post-transplant risk factors in heart transplant patients and their impact on 5-year outcomes. We reviewed 280 heart transplant patients who survived > 1 year for the impact of post-transplant risk factors (hyperlipidemia, hypertension, diabetes, body mass index [BMI] and renal dysfunction: 8 to 18 possible measurements over 5 years) on outcomes, including death, cardiac allograft vasculopathy (CAV) and non-fatal major adverse cardiac events (NF-MACE). Upon multivariate Cox regression analysis, significant findings were high total-cholesterol for NF-MACE (relative risk [RR] = 4.34, confidence interval [CI] 1.35 to 13.98, p = 0.01), presence of diabetes for NF-MACE (RR = 3.96, CI 1.24 to 12.65, p = 0.02) and high serum creatinine for graft death (RR = 1.59, CI 1.35 to 1.87, p < 0.001). No covariates were found to be significant for CAV. Other significant risk factors by univariate Cox regression models with time-dependent covariates included BMI > or = 33 for graft death. Post-transplant risk factors of hypercholesterolemia and diabetes are associated with NF-MACE, whereas high serum creatinine and BMI > or = 33 are associated with graft death. Risk factor modification, including direct therapy to minimize risk factors, should be considered.

Who donates their body to science? An international, multicenter, prospective study.

PubMed

Cornwall, Jon; Perry, Gary F; Louw, Graham; Stringer, Mark D

2012-01-01

The altruistic act of body donation provides a precious resource for both teaching and researching human anatomy. However, relatively little is known about individuals who donate their bodies to science (donors), and in particular whether donors in different geographical locations share similar characteristics. A multicenter prospective survey of donors registering during 2010 in three different geographical locations, New Zealand, Ireland, and the Republic of South Africa, was conducted to identify donor characteristics. The 28-question survey included sections on body donation program awareness, reasons for donating, giving tendency, education, ethnicity, relationship status, occupation, religion, and political preference. Two hundred surveys (81%) were returned [New Zealand 123 (85% response rate), Republic of South Africa 41 (67%), and Ireland 36 (92%)]. Results indicate that donors share certain characteristics including reason for donating (80% cited a desire to aid medical science as the main reason for wishing to donate their body); family structure (most donors are or have been in long-term partnerships and ≥ 85% have siblings); and a higher proportion with no religious affiliation compared to their reference population. Some variations between locations were noted including donor age, the mode of program awareness, occupation, relationship status, political preference, organ donor status and with whom donors had discussed their decision to donate. This information could be important for assisting the identification of potential body donors in new and established bequest programs. Copyright © 2012 American Association of Anatomists.

Long-Term Follow-Up of the Edmonton Protocol of Islet Transplantation in the United States.

PubMed

Brennan, D C; Kopetskie, H A; Sayre, P H; Alejandro, R; Cagliero, E; Shapiro, A M J; Goldstein, J S; DesMarais, M R; Booher, S; Bianchine, P J

2016-02-01

We report the long-term follow-up of the efficacy and safety of islet transplantation in seven type 1 diabetic subjects from the United States enrolled in the multicenter international Edmonton Protocol who had persistent islet function after completion of the Edmonton Protocol. Subjects were followed up to 12 years with serial testing for sustained islet allograft function as measured by C-peptide. All seven subjects demonstrated continued islet function longer than a decade from the time of first islet transplantation. One subject remained insulin independent without the need for diabetic medications or supplemental transplants. One subject who was insulin-independent for over 8 years experienced graft failure 10.9 years after the first islet transplant. The remaining six subjects demonstrated continued islet function upon trial completion, although three had received a supplemental islet transplant each. At trial completion, five subjects were receiving insulin and two remained insulin independent, although one was treated with liraglutide. The median hemoglobin A1c was 6.3% (45 mmol/mol). All subjects experienced progressive decline in the C-peptide/glucose ratio. No patients experienced severe hypoglycemia, opportunistic infection, or lymphoma. Thus, although the rate and duration of insulin independence was low, the Edmonton Protocol was safe in the long term. Alternative approaches to islet transplantation are under investigation. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Evaluation of the influence of family and friends, and the Internet on patient perceptions of long-term topical corticosteroid use.

PubMed

Smith, Saxon D; Farrugia, Lisa L; Harris, Victoria; Lee, Andrew; Carter, Stephen R; Blaszczynski, Alex; Fischer, Gayle

2017-11-01

Topical corticosteroids (TCS) are key to managing chronic inflammatory dermatoses (CID). Parents/patients cite TCS phobia as an impediment to treatment adherence. Family/friends and the Internet are a source of misinformation on TCS which can negatively impact perceptions of TCS safety. To assess information from family/friends and the Internet, as related to and reported by patients/parents using long-term TCS. A multicenter cross-sectional survey of patients (aged >18 years) and parents of patients (aged <18 years) with a history of CID requiring long-term (≥1 month) TCS use assessing messages about TCS received from family/friends and the Internet. A total of 123 patients and 78 parents completed the survey (n = 201). Parents/patients were more likely to be informed by the Internet "[having] my [child's] skin condition means that [I/he/she] will need to use topical corticosteroids" (p < .001) and that "inflamed skin conditions will improve with the topical corticosteroids" (p = .007). Family/friends were more likely to recommend parents/patients "try non-prescription creams/ointments before resorting to the use of prescription topical corticosteroids" (p = .014). High rates of messages about TCS "risk" from family/friends and the Internet may affect patient/parent understanding about TCS safety. This may contribute to treatment non-adherence.

Total laparoscopic gastropexy using 1 simple continuous barbed suture line in 63 dogs.

PubMed

Takacs, Joel D; Singh, Ameet; Case, J Brad; Mayhew, Philipp D; Giuffrida, Michelle A; Caceres, Ana V; Fox-Alvarez, W Alexander; Runge, Jeffrey J

2017-02-01

To describe the use and outcome of a single, simple continuous, barbed suture line for prophylactic, total laparoscopic gastropexy in dogs. Multi-center, retrospective case series. Sixty-three client-owned dogs. Medical records of dogs undergoing total laparoscopic gastropexy using a barbed suture at 4 academic veterinary hospitals from 2011-2015 were reviewed. Data collected included signalment, procedure time, procedure-associated complications, short-term complications, and long-term outcome. All procedures were performed under general anesthesia in dorsal to dorsal-left oblique recumbency. Laparoscopic ports were placed on ventral midline in 1 of 3 port configurations, and 5 mm laparoscopic needle drivers were used for intracorporeal sutured gastropexy with unidirectional barbed suture. The gastropexy was positioned just caudal to the 13th rib, 2-4 cm lateral to the rectus abdominis muscle. Sixty-three dogs underwent total laparoscopic gastropexy with a single, simple continuous, barbed suture line. Median gastropexy surgery time was 70 minutes (interquartile range [IQR] 60-90 minutes). One dog sustained splenic laceration from Veress needle penetration during initial abdominal insufflation. Short term (>24 hours to 6 months postoperative) complications included incisional seroma formation (n = 2) and suture reaction (n = 1). Long term (>6 months postoperative) complications included intermittent regurgitation and chronic diarrhea in 1 dog. Fifteen dogs had postoperative ultrasound and all had intact gastropexy sites. Total laparoscopic barbed gastropexy using a single, simple continuous, barbed suture line in dogs is safe and results in an intact gastropexy long term. © 2016 The American College of Veterinary Surgeons.

[Telemedicine in the ICU - the possibilities and limitations of an innovation].

PubMed

Deisz, R; Marx, G

2016-11-01

Intensive care medicine is challenged by demographic changes and an increasing number of patient combined with existing shortage of doctors. Telemedicine is a promising approach to ensure patient care in the coming years. Due to a shortage of intensive care physicians in the USA, comprehensive telemedicine coverage has already been established. To date, 11 % of all hospitals are supported by a telemedicine center. The beneficial impact in terms of quality of care, patient safety and economic factors has been confirmed in numerous multicenter studies. In the largest multicenter study by Lilly et al., including 107,432 critically ill patients in the intervention group, telemedicine interventions led to a reduced ICU and hospital mortality. In addition, tele-consulting significantly reduced the ICU- and hospital length of stay. These findings were further supported by following studies and metaanalysis, which confirmed these results. The incidence of ventilator-associated pneumonia and catheter-associated infections was significantly reduced, when compared to the preintervention group. Furthermore, patient safety and treatment outcomes were improved by increased guideline adherence. Last, the telemedicine intervention significantly decreased the overall treatment costs. These positive results were reproducible even in larger and academic hospitals. At the same time it should be pointed out that a transfer to other health care systems should be considered cautiously in the context of different local infrastructure and culture. Finally, it has to be investigated to what extent the results can be transferred to the health-care situation in Germany. Previous data demonstrated that telemedical support can improve the outcome in critically ill patients, both during hospitalization as well as in the long-term result until the discharge home. Telemedicine is neither a magic bullet nor a replacement for a physician. Instead it is a new type of medical cooperation to further improve the outcomes of critically ill patients.

Management of Charcot–Marie–Tooth disease: improving long-term care with a multidisciplinary approach

PubMed Central

McCorquodale, Donald; Pucillo, Evan M; Johnson, Nicholas E

2016-01-01

Charcot–Marie–Tooth (CMT) disease is the most common inherited neuropathy and one of the most common inherited diseases in humans. The diagnosis of CMT is traditionally made by the neurologic specialist, yet the optimal management of CMT patients includes genetic counselors, physical and occupational therapists, physiatrists, orthotists, mental health providers, and community resources. Rapidly developing genetic discoveries and novel gene discovery techniques continue to add a growing number of genetic subtypes of CMT. The first large clinical natural history and therapeutic trials have added to our knowledge of each CMT subtype and revealed how CMT impacts patient quality of life. In this review, we discuss several important trends in CMT research factors that will require a collaborative multidisciplinary approach. These include the development of large multicenter patient registries, standardized clinical instruments to assess disease progression and disability, and increasing recognition and use of patient-reported outcome measures. These developments will continue to guide strategies in long-term multidisciplinary efforts to maintain quality of life and preserve functionality in CMT patients. PMID:26855581

Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study

PubMed Central

Nilsson, Anna G; Bergthorsdottir, Ragnhildur; Burman, Pia; Dahlqvist, Per; Ekman, Bertil; Engström, Britt Edén; Ragnarsson, Oskar; Skrtic, Stanko; Wahlberg, Jeanette; Achenbach, Heinrich; Uddin, Sharif; Marelli, Claudio

2017-01-01

Objective To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI). Design Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden. Methods Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires. Results Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n = 2), gastritis (n = 1) and syncope (n = 1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6–5.4 episodes per patient per year), fasting plasma glucose (0.7 mmol/L; P < 0.0001) and HDL cholesterol (0.2 mmol/L; P < 0.0001) increased and patient-/investigator-assessed tolerability improved. QoL total scores were unchanged but worsening physical functioning was recorded (P = 0.008). Conclusions In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment. PMID:28292927

Long-term outcome of macroprolactinomas.

PubMed

Képénékian, Lori; Cebula, Hélène; Castinetti, Frédéric; Graillon, Thomas; Brue, Thierry; Goichot, Bernard

2016-12-01

Management of macroprolactinomas has dramatically changed in recent decades, from surgical to medical treatment as first-line therapy, with the development of dopamine agonists (DA). But few data exist on the long-term outcome of these patients. Retrospective descriptive multicenter study of patients with macroprolactinoma followed for at least 5 years between 1973 and 2008 at the University Hospitals of Strasbourg and Marseille. Forty-eight patients were included with 27 men, hypopituitarism in 33.3% of all patients and mean serum prolactin (PRL) level at diagnosis 2218.2±4154.7μg/L. Among the patients, 58.3% received medical treatment, 25% had additional surgery and 12.5% surgery and radiotherapy. The mean follow-up duration was 196±100 months. At the end of follow-up, 10 patients (20.8%) were cured (i.e. normal PRL level and normal imaging, no symptoms and withdrawal of DA≥1 year), 33 (68.8%) were controlled (i.e. normal PRL level, normal or abnormal imaging, no symptoms, DA in progress) and 5 (10.4%) were uncontrolled. Uncontrolled patients had significant higher baseline PRL level (P=0.0412) and cabergoline cumulative dose (P=0.0065) compared to the controlled group. There was no increase in frequency of hypopituitarism. Clinically significant valvular heart disease was found in 2 patients but screening was not systematic. Macroprolactinoma is currently most often a chronic disease controlled with DA. However, uncertainty about the adverse effects associated with high cumulative doses and the lack of data on the prognosis at very long-term should incite to revisit current strategies, including the role of surgery combined to medical treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Wound-healing outcomes using standardized assessment and care in clinical practice.

PubMed

Bolton, Laura; McNees, Patrick; van Rijswijk, Lia; de Leon, Jean; Lyder, Courtney; Kobza, Laura; Edman, Kelly; Scheurich, Anne; Shannon, Ron; Toth, Michelle

2004-01-01

Wound-healing outcomes applying standardized protocols have typically been measured within controlled clinical trials, not natural settings. Standardized protocols of wound care have been validated for clinical use, creating an opportunity to measure the resulting outcomes. Wound-healing outcomes were explored during clinical use of standardized validated protocols of care based on patient and wound assessments. This was a prospective multicenter study of wound-healing outcomes management in real-world clinical practice. Healing outcomes from March 26 to October 31, 2001, were recorded on patients in 3 long-term care facilities, 1 long-term acute care hospital, and 12 home care agencies for wounds selected by staff to receive care based on computer-generated validated wound care algorithms. After diagnosis, wound dimensions and status were assessed using a tool adapted from the Pressure Sore Status Toolfor use on all wounds. Wound, ostomy, and continence nursing professionals accessed consistent protocols of care, via telemedicine in home care or paper forms in long-term care. A physician entered assessments into a desktop computer in the wound clinic. Based on evidence that healing proceeds faster with fewer infections in environments without gauze, the protocols generally avoided gauze dressings. Most of the 767 wounds selected to receive the standardized-protocols of care were stage III-IV pressure ulcers (n = 373; mean healing time 62 days) or full-thickness venous ulcers (n = 124; mean healing time 57 days). Partial-thickness wounds healed faster than same-etiology full-thickness wounds. These results provide benchmarks for natural-setting healing outcomes and help to define and address wound care challenges. Outcomes primarily using nongauze protocols of care matched or surpassed best previously published results on similar wounds using gauze-based protocols of care, including protocols applying gauze impregnated with growth factors or other agents.

Five-year multicenter study of magnetic attachments used for natural overdenture abutments.

PubMed

Gonda, T; Yang, T C; Maeda, Y

2013-04-01

The purpose of this study was to examine a longitudinal clinical performance of magnetic attachments used for natural overdenture abutments. The study included 131 patients who had used removable prostheses (complete overdentures 31%, partial dentures 69%) more than 5 years (40-90 years old) with 211 magnetic attachments on natural abutments (Magfit 400 or 600; Aichi Steel co., Aichi, Japan) treated in 15 clinics using a standardized protocol. Analyses were performed on the degree of patient satisfaction regarding retention, complications of magnets (corrosion, detachment from denture base), abutments (pain during mastication, periodontal pocket formation, inflammation, mobility), and dentures (fracture etc.). Ninety-seven percent of patients were satisfied with the retention and stability of their dentures. No corrosion of magnet was observed, and 19 magnets were detached. Most frequent complication of abutments was periodontal pocket formation (52%), followed by the inflammation (29%), increase in mobility (27%) and pain (4%). Magnetic attachment on natural tooth abutments provided a viable and long-term treatment option. © 2013 Blackwell Publishing Ltd.

Dacrystic seizures: demographic, semiologic, and etiologic insights from a multicenter study in long-term video-EEG monitoring units.

PubMed

Blumberg, Julie; Fernández, Iván Sánchez; Vendrame, Martina; Oehl, Bernhard; Tatum, William O; Schuele, Stephan; Alexopoulos, Andreas V; Poduri, Annapurna; Kellinghaus, Christoph; Schulze-Bonhage, Andreas; Loddenkemper, Tobias

2012-10-01

To provide an estimate of the frequency of dacrystic seizures in video-electroencephalography (EEG) long-term monitoring units of tertiary referral epilepsy centers and to describe the clinical presentation of dacrystic seizures in relationship to the underlying etiology. We screened clinical records and video-EEG reports for the diagnosis of dacrystic seizures of all patients admitted for video-EEG long-term monitoring at five epilepsy referral centers in the United States and Germany. Patients with a potential diagnosis of dacrystic seizures were identified, and their clinical charts and video-EEG recordings were reviewed. We included only patients with: (1) stereotyped lacrimation, sobbing, grimacing, yelling, or sad facial expression; (2) long-term video-EEG recordings (at least 12 h); and (3) at least one brain magnetic resonance imaging (MRI) study. Nine patients (four female) with dacrystic seizures were identified. Dacrystic seizures were identified in 0.06-0.53% of the patients admitted for long-term video-EEG monitoring depending on the specific center. Considering our study population as a whole, the frequency was 0.13%. The presence of dacrystic seizures without other accompanying clinical features was found in only one patient. Gelastic seizures accompanied dacrystic seizures in five cases, and a hypothalamic hamartoma was found in all of these five patients. The underlying etiology in the four patients with dacrystic seizures without gelastic seizures was left mesial temporal sclerosis (three patients) and a frontal glioblastoma (one patient). All patients had a difficult-to-control epilepsy as demonstrated by the following: (1) at least three different antiepileptic drugs were tried in each patient, (2) epilepsy was well controlled with antiepileptic drugs in only two patients, (3) six patients were considered for epilepsy surgery and three of them underwent a surgical/radiosurgical or radioablative procedure. Regarding outcome, antiepileptic drugs alone achieved seizure freedom in two patients and did not change seizure frequency in another patient. Radiosurgery led to moderately good seizure control in one patient and did not improve seizure control in another patient. Three patients were or are being considered for epilepsy surgery on last follow-up. One patient remains seizure free 3 years after epilepsy surgery. Dacrystic seizures are a rare but clinically relevant finding during video-EEG monitoring. Our data show that when the patient has dacrystic and gelastic seizures, the cause is a hypothalamic hamartoma. In contrast, when dacrystic seizures are not accompanied by gelastic seizures the underlying lesion is most commonly located in the temporal cortex. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Patient Engagement and Study Design of PROP UP: A multi-site patient-centered prospective observational study of patients undergoing hepatitis C treatment

PubMed Central

Evon, Donna M.; Golin, Carol E.; Stewart, Paul; Fried, Michael W.; Alston, Shani; Reeve, Bryce; Lok, Anna S.; Sterling, Richard K.; Lim, Joseph K.; Reau, Nancy; Sarkar, Souvik; Nelson, David R.; Reddy, K. Rajender; Di Bisceglie, Adrian M.

2017-01-01

Background New highly efficacious direct-acting antiviral (DAA) therapies are available to treat chronic hepatitis C viral (HCV) infection. Real-world, patient-centered data on harms and benefits associated with these therapies are needed. Methods PROP UP is a multi-center prospective observational study that plans to enroll 1,600 patients starting treatment with recently-approved DAA regimens. Informed by extensive input from a HCV patient engagement group who prioritized outcomes most important to them, patient-reported outcomes will be characterized using surveys at five time points: Baseline (T1), treatment week 4 (T2), end of treatment (T3), 12 weeks post-treatment (T4), 12 months post-treatment (T5). Outcomes (1) Changes in side effects, functioning, pre-existing conditions, and out-of-pocket costs during therapy (T1 vs T2/T3); (2) Medication adherence in relation to a history of mental health/substance abuse, treatment regimens, pill burden, reasons for missed doses, and cure rates; (3) Short term impact of cure on functioning and amelioration of symptoms (T1 vs T4); (4) Long-term treatment harms or benefits of cure on symptoms, side effects, pre-existing conditions, and functioning (T1 vs T5). Similarities between regimens will be examined where comparisons are appropriate and meaningful. Conclusion PROP UP complements previous clinical trials by focusing on patient-reported outcomes in a representative sample of patients treated in clinical practice, by collaborating with a patient engagement group, by characterizing the experiences of vulnerable subgroups, and by investigating long-term harms and benefits of treatments. PROP UP is designed to provide novel and detailed information to support informed decision-making for patients and providers contemplating HCV treatment (PCORI CER-1408-20660; NCT02601820). PMID:28342989

Examining Time Use of Dutch Nursing Staff in Long-Term Institutional Care: A Time-Motion Study.

PubMed

Tuinman, Astrid; de Greef, Mathieu H G; Krijnen, Wim P; Nieweg, Roos M B; Roodbol, Petrie F

2016-02-01

Increasing residents' acuity levels and available resources in long-term institutional care requires insight into the care provided by nursing staff so as to guide task allocation and optimal use of resources, and enhance quality of care. The purpose of this study was to examine the relationship between time use and type of nursing staff, residents' acuity levels, and unit type by using a standardized nursing intervention classification. A multicenter cross-sectional observational study was performed using time-motion technique. Five Dutch long-term institutional care facilities participated. In total, 4 residential care units, 3 somatic units, and 6 psycho-geriatric units were included. Data were collected from 136 nursing staff members: 19 registered nurses, 89 nursing assistants, 9 primary caregivers, and 19 health care assistants. A structured observation list was used based on the Nursing Interventions Classification (NIC). Residents' acuity levels, representing residents' needs, were based on the Dutch Care Severity Index. Medians and interquartile ranges were calculated for time spent on interventions per type of nursing staff and units. Linear mixed models were used to examine the relationship between time spent on nursing interventions and the type of nursing staff, residents' acuity levels, and unit type. Observations resulted in 52,628 registered minutes for 102 nursing interventions categorized into 6 NIC domains for 335 residents. Nursing staff spent the most time on direct care interventions, particularly in the domain of basic physiological care. Variances in time spent on interventions between types of nursing staff were minimal. Unit type was more significantly (P < .05) associated with time spent on interventions in domains than the type of nursing staff. Residents' acuity levels did not affect time spent by nursing staff (P > .05). The current study found limited evidence for task allocation between the types of nursing staff, which may suggest a blurring of role differentiation. Also, findings suggest that residents received similar care regardless of their needs, implying that care is predominantly task-oriented instead of person-centered. Managers may reconsider whether the needs of residents are adequately met by qualified nursing staff, considering the differences in education and taking into account increasing acuity levels of residents and available resources. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Randomized controlled trial of laparoscopic transabdominal preperitoneal hernioplasty vs Shouldice repair.

PubMed

Tschudi, J F; Wagner, M; Klaiber, C; Brugger, J J; Frei, E; Krähenbühl, L; Inderbitzi, R; Boinski, J; Hsu Schmitz, S F; Hüsler, J

2001-11-01

There is a scarcity of data on long-term results after laparoscopic hernia repair. Herein we report on the outcome of a group of patients who were followed up for 5 years in a multicenter study on hernia repair. A total of 100 patients with 127 hernias were randomized to undergo either transabdominal preperitoneal (TAPP) or Shouldice hernia repair. Follow-up was by clinical examination and standardized questionnaire. Of the 100 patients who underwent surgery, 84 were available for follow-up at 5 years. The TAPP procedure was less painful than the Shouldice repair, with fewer patients receiving narcotic analgesics. The median time to return to 100% activity was shorter in the laparoscopic group (21 days) than in the Shouldice group (40 days). Up to 60 months after the operation, the complication rate was lower in laparoscopically repaired hernias (19/66) than in the open group (25/61). There were two recurrences (3.9%) in the TAPP group and five in the Shouldice group (10.2%). The TAPP hernia repair yields comparable or better results than Shouldice herniorrhaphy in terms of postoperative pain, recovery, and recurrence rate.

A clustering approach to identify severe bronchiolitis profiles in children

PubMed Central

Dumas, Orianne; Mansbach, Jonathan M; Jartti, Tuomas; Hasegawa, Kohei; Sullivan, Ashley F; Piedra, Pedro A; Camargo, Carlos A

2016-01-01

Objective Although bronchiolitis is generally considered a single disease, recent studies suggest heterogeneity. We aimed to identify severe bronchiolitis profiles using a clustering approach. Methods We analyzed data from two prospective, multi-center cohorts of children younger than 2 years hospitalized with bronchiolitis, one in the U.S. (2007–2010 winter seasons, n=2,207) and one in Finland (2008–2010 winter seasons, n=408). Severe bronchiolitis profiles were determined by latent class analysis, classifying children based on clinical factors and viral etiology. Results In the U.S. study, four profiles were identified. Profile A (12%) was characterized by history of wheezing and eczema, wheezing at the ED presentation and rhinovirus infection. Profile B (36%) included children with wheezing at the ED presentation, but, in contrast to profile A, most did not have history of wheezing or eczema; this profile had the largest probability of RSV-infection. Profile C (34%) was the most severely ill group, with longer hospital stay and moderate-to-severe retractions. Profile D (17%) had the least severe illness, including non-wheezing children with shorter length-of-stay. Two of these profiles (A and D) were replicated in the Finnish cohort; a third group (“BC”) included Finnish children with characteristics of profiles B and/or C in the U.S. population. Conclusion Several distinct clinical profiles (phenotypes) were identified by a clustering approach in two multicenter studies of children hospitalized for bronchiolitis. The observed heterogeneity has important implications for future research on the etiology, management and long-term outcomes of bronchiolitis, such as future risk of childhood asthma. PMID:27339060

Distraction arthrodesis of the sacroiliac joint: 2-year results of a descriptive prospective multi-center cohort study in 171 patients.

PubMed

Fuchs, Volker; Ruhl, Benjamin

2018-01-01

The aim of the given study was to evaluate the long-term outcomes of patients undergoing sacroiliac joint (SIJ) distraction arthrodesis to treat SIJ-related pain. Descriptive prospective multi-center cohort study involving 20 hospitals in Germany. Between January 2011 and June 2012, 171 patients with chronic SIJ pain underwent indirect arthrodesis of the SIJ using a distraction implant. The patients were questioned prior to surgery, 6-weeks, and 3-, 6-, 12- and 24-months postoperatively. Overall patient satisfaction was surveyed along with pain medication intake, the Million Visual Analogue Scale (MVAS), Oswestry Disability Index (ODI), Short-form McGill Pain Questionnaire (SF-MPQ), 12-Item Short-Form Health Survey (SF-12), Visual Analogue Scale (VAS) and a pain drawing. Bony fusion of the SIJ was evaluated using X-ray and computed tomography (CT). A majority of patients (73%) reported to feel better or much better 24 months post-surgery, 49% of the patients reduced their pain medication intake. The MVAS dropped from 63 to 36%, the ODI improved from 51 to 33%, the SF-MPQ decreased from 50 to 31%, the SF-12 physical component summary rose from 22 to 41%, the mental component summary increased from 40 to 55%, and pain as measured by the VAS decreased from 74 to 37 points (all comparisons p < 0.001). In the follow-up CT scans 31% of the patients showed SIJ fusion. SIJ distraction arthrodesis has shown satisfactory outcomes in patients with SIJ-related pain for all scores reported in the surveys, accompanied by increased functionality.

Automatic adaptive system dialysis for hemodialysis-associated hypotension and intolerance: a noncontrolled multicenter trial.

PubMed

Colì, Luigi; La Manna, Gaetano; Comai, Giorgia; Ursino, Mauro; Ricci, Davide; Piccari, Matteo; Locatelli, Francesco; Di Filippo, Salvatore; Cristinelli, Luciano; Bacchi, Massimo; Balducci, Alessandro; Aucella, Filippo; Panichi, Vincenzo; Ferrandello, Francesco Paolo; Tarchini, Renzo; Lambertini, Domenica; Mura, Carlo; Marinangeli, Giancarlo; Di Loreto, Ermanno; Quarello, Francesco; Forneris, Giacomo; Tancredi, Maurizio; Morosetti, Massimo; Palombo, Giuditta; Di Luca, Marina; Martello, Mauro; Emiliani, Giuseppe; Bellazzi, Roberto; Stefoni, Sergio

2011-07-01

Hemodialysis is complicated by a high incidence of intradialytic hypotension and disequilibrium symptoms caused by hypovolemia and a decrease in extracellular osmolarity. Automatic adaptive system dialysis (AASD) is a proprietary dialysis system that provides automated elaboration of dialysate and ultrafiltration profiles based on the prescribed decrease in body weight and sodium content. A noncontrolled (single arm), multicenter, prospective, clinical trial. 55 patients with intradialytic hypotension or disequilibrium syndrome in 15 dialysis units were studied over a 1-month interval using standard treatment (642 sessions) followed by 6 months using AASD (2,376 sessions). AASD (bicarbonate dialysis with dialysate sodium concentration and ultrafiltration rate profiles determined by the automated procedure). Primary and major secondary outcomes were the frequency of intradialytic hypotension and symptoms (hypotensive events, headache, nausea, vomiting, and cramps), respectively. More stable intradialytic systolic and diastolic blood pressures with lower heart rate were found using AASD compared with standard treatment. Sessions complicated by hypotension decreased from 58.7% ± 7.3% to 0.9% ± 0.6% (P < 0.001). The incidence of other disequilibrium syndrome symptoms was lower in patients receiving AASD. There were no differences in end-session body weight, interdialytic weight gain, or presession natremia between the standard and AASD treatment periods. A noncontrolled (single arm) study, no crossover from AASD to standard treatment. This study shows the long-term clinical efficacy of AASD for intradialytic hypotension and disequilibrium symptoms in a large number of patients and dialysis sessions. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Prognostic Score of Long-Term Survival After Surgery for Malignant Pleural Mesothelioma: A Multicenter Analysis.

PubMed

Leuzzi, Giovanni; Rea, Federico; Spaggiari, Lorenzo; Marulli, Giuseppe; Sperduti, Isabella; Alessandrini, Gabriele; Casiraghi, Monica; Bovolato, Pietro; Pariscenti, Gianluca; Alloisio, Marco; Infante, Maurizio; Pagan, Vittore; Fontana, Paolo; Oliaro, Alberto; Ruffini, Enrico; Ratto, Giovanni Battista; Leoncini, Giacomo; Sacco, Rocco; Mucilli, Felice; Facciolo, Francesco

2015-09-01

Despite ongoing efforts to improve therapy in malignant pleural mesothelioma, few patients undergoing extrapleural pneumonectomy experience long-term survival (LTS). This study aims to explore predictors of LTS after extrapleural pneumonectomy and to define a prognostic score. From January 2000 to December 2010, we retrospectively reviewed clinicopathologic and oncological factors in a multicenter cohort of 468 malignant pleural mesothelioma patients undergoing extrapleural pneumonectomy. LTS was defined as survival longer than 3 years. Associations were evaluated using χ(2), Student's t, and Mann-Whitney U tests. Logistic regression, Cox regression hazard model, and bootstrap analysis were applied to identify outcome predictors. Survival curves were calculated by the Kaplan-Meier method. Receiver operating characteristic analyses were used to estimate optimal cutoff and area under the curve for accuracy of the model. Overall, 107 patients (22.9%) survived at least 3 years. Median overall, cancer-specific, and disease-free survival times were 60 (95% confidence interval [CI], 51 to 69), 63 (95% CI, 54 to 72), and 49 months (95% CI, 39 to 58), respectively. At multivariate analysis, age (odds ratio, 0.51; 95% CI, 0.31 to 0.82), epithelioid histology (odds ratio, 7.07; 95% CI, 1.56 to 31.93), no history of asbestos exposure (odds ratio, 3.13; 95% CI, 1.13 to 8.66), and the ratio between metastatic and resected lymph nodes less than 22% (odds ratio, 4.12; 95% CI, 1.68 to 10.12) were independent predictors of LTS. According to these factors, we created a scoring system for LTS that allowed us to correctly predict overall, cancer-specific, and disease-free survival in the total sample, obtaining two different groups with favorable or poor prognosis (area under the curve, 0.74; standard error, 0.04; p < 0.0001). Our prognostic model facilitates the prediction of LTS after surgery for malignant pleural mesothelioma and can help to stratify the outcome and, eventually, tailor postoperative treatment. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Chemotherapy-Induced Amenorrhea in Patients With Breast Cancer With a BRCA1 or BRCA2 Mutation

PubMed Central

Valentini, Adriana; Finch, Amy; Lubiński, Jan; Byrski, Tomasz; Ghadirian, Parviz; Kim-Sing, Charmaine; Lynch, Henry T.; Ainsworth, Peter J.; Neuhausen, Susan L.; Greenblatt, Ellen; Singer, Christian; Sun, Ping; Narod, Steven A.

2013-01-01

Purpose To determine the likelihood of long-term amenorrhea after treatment with chemotherapy in women with breast cancer who carry a BRCA1 or BRCA2 mutation. Patients and Methods We conducted a multicenter survey of 1,954 young women with a BRCA1 or BRCA2 mutation who were treated for breast cancer. We included premenopausal women who were diagnosed with invasive breast cancer between 26 and 47 years of age. We determined the age of onset of amenorrhea after breast cancer for women who were and were not treated with chemotherapy, alone or with tamoxifen. We considered chemotherapy-induced amenorrhea to have occurred when the patient experienced ≥ 2 years of amenorrhea, commencing within 2 years of initiating chemotherapy, with no resumption of menses. Results Of the 1,426 women who received chemotherapy, 35% experienced long-term amenorrhea. Of the 528 women who did not receive chemotherapy, 5.3% developed long-term amenorrhea. The probabilities of chemotherapy-induced amenorrhea were 7.2% for women diagnosed before age 30 years, 33% for women age 31 to 44 years, and 79% for women diagnosed after age 45 years (P trend < .001). The probability of induced amenorrhea was higher for women who received tamoxifen than for those who did not (52% v 29%; P < .001). Conclusion Age at treatment and use of tamoxifen are important predictors of chemotherapy-induced amenorrhea in women who carry a BRCA1 or BRCA2 mutation. The risk of induced long-term amenorrhea does not seem to be greater among mutation carriers than among women who do not carry a mutation. PMID:23980083

Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation.

PubMed

Tarte, Karin; Gaillard, Julien; Lataillade, Jean-Jacques; Fouillard, Loic; Becker, Martine; Mossafa, Hossein; Tchirkov, Andrei; Rouard, Hélène; Henry, Catherine; Splingard, Marie; Dulong, Joelle; Monnier, Delphine; Gourmelon, Patrick; Gorin, Norbert-Claude; Sensebé, Luc

2010-02-25

Clinical-grade human mesenchymal stromal cells (MSCs) have been expanded in vitro for tissue engineering or immunoregulatory purposes without standardized culture conditions or release criteria. Although human MSCs show poor susceptibility for oncogenic transformation, 2 recent studies described their capacity to accumulate chromosomal instability and to give rise to carcinoma in immunocompromised mice after long-term culture. We thus investigated the immunologic and genetic features of MSCs expanded with fetal calf serum and fibroblast growth factor or with platelet lysate in 4 cell-therapy facilities during 2 multicenter clinical trials. Cultured MSCs showed a moderate expression of human leukocyte antigen-DR without alteration of their low immunogenicity or their immunomodulatory capacity. Moreover, some transient and donor-dependent recurring aneuploidy was detected in vitro, independently of the culture process. However, MSCs with or without chromosomal alterations showed progressive growth arrest and entered senescence without evidence of transformation either in vitro or in vivo.

Validation of transcutaneous bilirubin nomogram for identifying neonatal hyperbilirubinemia in healthy Chinese term and late-preterm infants: a multicenter study.

PubMed

Yu, Zhangbin; Han, Shuping; Wu, Jinxia; Li, Mingxia; Wang, Huaiyan; Wang, Jimei; Liu, Jiebo; Pan, Xinnian; Yang, Jie; Chen, Chao

2014-01-01

to prospectively validate a previously constructed transcutaneous bilirubin (TcB) nomogram for identifying severe hyperbilirubinemia in healthy Chinese term and late-preterm infants. this was a multicenter study that included 9,174 healthy term and late-preterm infants in eight hospitals of China. TcB measurements were performed using a JM-103 bilirubinometer. TcB values were plotted on a previously developed TcB nomogram, to identify the predictive ability for subsequent significant hyperbilirubinemia. in the present study, 972 neonates (10.6%) developed significant hyperbilirubinemia. The 40(th) percentile of the nomogram could identify all neonates who were at risk of significant hyperbilirubinemia, but with a low positive predictive value (PPV) (18.9%). Of the 453 neonates above the 95(th) percentile, 275 subsequently developed significant hyperbilirubinemia, with a high PPV (60.7%), but with low sensitivity (28.3%). The 75(th) percentile was highly specific (81.9%) and moderately sensitive (79.8%). The area under the curve (AUC) for the TcB nomogram was 0.875. this study validated the previously developed TcB nomogram, which could be used to predict subsequent significant hyperbilirubinemia in healthy Chinese term and late-preterm infants. However, combining TcB nomogram and clinical risk factors could improve the predictive accuracy for severe hyperbilirubinemia, which was not assessed in the study. Further studies are necessary to confirm this combination. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Improving the Accuracy of Diagnosing Placenta Previa on Transvaginal Ultrasound by Distinguishing between the Uterine Isthmus and Cervix: A Prospective Multicenter Observational Study.

PubMed

Hasegawa, Junichi; Kawabata, Ikuno; Takeda, Yoshiharu; Aoki, Hiroaki; Fukami, Takehiko; Tajima, Atsushi; Miyakoshi, Kei; Otsuki, Katsufumi; Shinozuka, Norio; Matsuda, Yoshio; Iwashita, Mitsutoshi; Okai, Takashi; Nakai, Akihito

2017-01-01

To clarify whether distinguishing between the uterine isthmus and cervix can improve the accuracy of diagnosing placenta previa at term. A multicenter prospective observational study was conducted among pregnant women with suspected placenta previa at 20-24 weeks' gestation. Subjects were divided into the open isthmus group and closed isthmus group. The accuracy of diagnosing placenta previa at term was compared between the 2 groups. We screened 9,341 patients, and 53 (0.6%) met the inclusion criteria. Nineteen cases with an open isthmus and 34 with a closed isthmus were followed. The accuracy for diagnosing placenta previa or a low-lying placenta at term was 94.7% in the open isthmus group and 26.5% in the closed isthmus group (p < 0.001). Elective or emergency Cesarean section was required in 100% of cases in the open isthmus group and 20.6% in the closed isthmus group (p < 0.001). A high prediction rate of placenta previa was obtained by using transvaginal ultrasound at 20-24 weeks' gestation after the isthmus opened by carefully distinguishing between the cervix and isthmus. © 2016 S. Karger AG, Basel.

Clinical outcomes of EUS-guided drainage of debris-containing pancreatic pseudocysts: a large multicenter study.

PubMed

Yang, Dennis; Amin, Sunil; Gonzalez, Susana; Mullady, Daniel; Edmundowicz, Steven A; DeWitt, John M; Khashab, Mouen A; Wang, Andrew Y; Nagula, Satish; Buscaglia, Jonathan M; Bucobo, Juan Carlos; Wagh, Mihir S; Draganov, Peter V; Stevens, Tyler; Vargo, John J; Khara, Harshit S; Diehl, David L; Keswani, Rajesh N; Komanduri, Srinadh; Yachimski, Patrick S; Prabhu, Anoop; Kwon, Richard S; Watson, Rabindra R; Goodman, Adam J; Benias, Petros; Carr-Locke, David L; DiMaio, Christopher J

2017-02-01

Background and study aims  Data on clinical outcomes of endoscopic drainage of debris-free pseudocysts (PDF) versus pseudocysts containing solid debris (PSD) are very limited. The aims of this study were to compare treatment outcomes between patients with PDF vs. PSD undergoing endoscopic ultrasound (EUS)-guided drainage via transmural stents. Patients and methods  Retrospective review of 142 consecutive patients with pseudocysts who underwent EUS-guided transmural drainage (TM) from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TM technical success, treatment outcomes (symptomatic and radiologic resolution), need for endoscopic re-intervention at follow-up, and adverse events (AEs). Results  TM was performed in 90 patients with PDF and 52 with PSD. Technical success: PDF 87 (96.7 %) vs. PSD 51 (98.1 %). There was no difference in the rates for endoscopic re-intervention (5.5 % in PDF vs. 11.5 % in PSD; P =  0.33) or AEs (12.2 % in PDF vs. 19.2 % in PSD; P  = 0.33). Median long-term follow-up after stent removal was 297 days (interquartile range [IQR]: 59 - 424 days) for PDF and 326 days (IQR: 180 - 448 days) for PSD ( P  = 0.88). There was a higher rate of short-term radiologic resolution of PDF (45; 66.2 %) vs. PSD (21; 51.2 %) (OR = 0.30; 95 % CI: 0.13 - 0.72; P  = 0.009). There was no difference in long-term symptomatic resolution (PDF: 70.4 % vs. PSD: 66.7 %; P  = 0.72) or radiologic resolution (PDF: 68.9 % vs. PSD: 78.6 %; P  = 0.72) Conclusions  There was no difference in need for endoscopic re-intervention, AEs or long-term treatment outcomes in patients with PDF vs. PSD undergoing EUS-guided drainage with transmural stents. Based on these results, the presence of solid debris in pancreatic fluid collections does not appear to be associated with a poorer outcome.

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.

Wing-shaped plastic stents vs. self-expandable metal stents for palliative drainage of malignant distal biliary obstruction: a randomized multicenter study.

PubMed

Schmidt, Arthur; Riecken, Bettina; Rische, Susanne; Klinger, Christoph; Jakobs, Ralf; Bechtler, Matthias; Kähler, Georg; Dormann, Arno; Caca, Karel

2015-05-01

Previous studies have shown superior patency rates for self-expandable metal stents (SEMS) compared with plastic stents in patients with malignant biliary obstruction. The aim of this study was to compare stent patency, patient survival, and complication rates between a newly designed, wing-shaped, plastic stent and SEMSs in patients with unresectable, malignant, distal, biliary obstruction. A randomized, multicenter trial was conducted at four tertiary care centers in Germany. A total of 37 patients underwent randomization between March 2010 and January 2013. Patients underwent endoscopic retrograde cholangiography with insertion of either a wing-shaped, plastic stent without lumen or an SEMS.  Stent failure occurred in 10/16 patients (62.5 %) in the winged-stent group vs. 4/18 patients (22.2 %) in the SEMS group (P = 0.034). The median time to stent failure was 51 days (range 2 - 92 days) for the winged stent and 80 days (range 28 - 266 days) for the SEMS (P = 0.002). Early stent failure (< 8 weeks after placement) occurred in 8 patients (50 %) vs. 2 patients (11.1 %), respectively (P = 0.022). After obtaining the results from this interim analysis, the study was discontinued because of safety concerns. The frequency of stent failure was significantly higher in the winged-stent group compared with the SEMS group. A high incidence of early stent failure within 8 weeks was observed in the winged-stent group. Thus, the winged, plastic stent without central lumen may not be appropriate for mid or long term drainage of malignant biliary obstruction. Study registration ClinicalTrials.gov (NCT01063634). © Georg Thieme Verlag KG Stuttgart · New York.

Improving cost efficiency in large programs

NASA Technical Reports Server (NTRS)

Hodge, John D.

1994-01-01

This paper examines the question of cost, from the birth of a program to its conclusion, particularly from the point of view of large multi-center programs, and suggests how to avoid some of the traps and pitfalls. Emphasis is given to cost in the systems engineering process, but there is an inevitable overlap with program management. (The terms systems engineering and program management have never been clearly defined.) In these days of vast Federal budget deficits and increasing overseas competition, it is imperative that we get more for each research and development dollar. This is the only way we will retain our leadership in high technology and, in the long run, our way of life.

The importance of cost considerations in the systems engineering process

NASA Technical Reports Server (NTRS)

Hodge, John D.

1993-01-01

This paper examines the question of cost, from the birth of a program to its conclusion, particularly from the point of view of large multi-center programs, and suggests how to avoid some of the traps and pitfalls. Emphasis is given to cost in the systems engineering process, but there is an inevitable overlap with program management. (These terms, systems engineering and program management, have never been clearly defined.) In these days of vast Federal budget deficits and increasing overseas competition, it is imperative that we get more for each research and development dollar. This is the only way we will retain our leadership in high technology and, in the long run, our way of life.

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

PubMed Central

2013-01-01

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

Low-Intensity Wheelchair Training in Inactive People with Long-Term Spinal Cord Injury: A Randomized Controlled Trial on Propulsion Technique.

PubMed

van der Scheer, Jan W; de Groot, Sonja; Vegter, Riemer J K; Hartog, Johanneke; Tepper, Marga; Slootman, Hans; Veeger, DirkJan H E J; van der Woude, Lucas H V

2015-11-01

The objective of this study was to investigate the effects of a low-intensity wheelchair training on propulsion technique in inactive people with long-term spinal cord injury. Participants in this multicenter nonblinded randomized controlled trial were inactive manual wheelchair users with spinal cord injury for at least 10 yrs (N = 29), allocated to exercise (n = 14) or no exercise. The 16-wk training consisted of wheelchair treadmill propulsion at 30%-40% heart rate reserve or equivalent in rate of perceived exertion, twice a week, 30 mins per session. Propulsion technique was assessed at baseline as well as after 8, 16, and 42 wks during two submaximal treadmill-exercise blocks using a measurement wheel attached to a participant's own wheelchair. Changes over time between the groups were analyzed using Mann-Whitney U tests on difference scores (P < 0.05/3). Data of 16 participants could be analyzed (exercise: n = 8). Significant differences between the exercise and control groups were only found in peak force after 8 wks (respective medians, -20 N vs. 1 N; P = 0.01; r(u) = 0.78). Significant training effects on propulsion technique were not found in this group. Perhaps, substantial effects require a higher intensity or frequency. Investigating whether more effective and feasible interventions exist might help reduce the population's risk of upper-body joint damage during daily wheelchair propulsion.

Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia

PubMed Central

2013-01-01

Introduction The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. Methods This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) < 40 kg/m2, and had a score ≥ 50 on a 100-mm pain visual analog scale (VAS) at baseline. All patients began treatment in the extension study with SXB 4.5 g/night (administered in 2 equally divided doses) for at least 1 week, followed by possible serial 1.5 g/night dose increases to 9 g/night (maximum) or reductions to 4.5 g/night (minimum). Results Of the 560 FM patients enrolled in this extension study, 319 (57.0%) completed the study. The main reason for early discontinuation was adverse events (AEs; 23.0% of patients). Patients were primarily middle-aged (mean 46.9 ± 10.8 years), female (91.1%), white (91.4%), with a mean duration of FM symptoms of 9.9 ± 8.7 years. Serious AEs were experienced by 3.6% of patients. The most frequently reported AEs (incidence ≥ 5% at any dose or overall) were nausea, headache, dizziness, nasopharyngitis, vomiting, sinusitis, diarrhea, anxiety, insomnia, influenza, somnolence, upper respiratory tract infection, muscle spasms, urinary tract infection, and gastroenteritis viral. Maintenance of SXB therapeutic response was demonstrated with continued improvement from controlled-study baseline in pain VAS, Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. Conclusions The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. Trial registration ClinicalTrials.gov NCT00423605. PMID:24286114

Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia.

PubMed

Spaeth, Michael; Alegre, Cayetano; Perrot, Serge; Wang, Youyu; Guinta, Diane R; Alvarez-Horine, Sarah; Russell, Irwin

2013-11-11

The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) < 40 kg/m2, and had a score ≥ 50 on a 100-mm pain visual analog scale (VAS) at baseline. All patients began treatment in the extension study with SXB 4.5 g/night (administered in 2 equally divided doses) for at least 1 week, followed by possible serial 1.5 g/night dose increases to 9 g/night (maximum) or reductions to 4.5 g/night (minimum). Of the 560 FM patients enrolled in this extension study, 319 (57.0%) completed the study. The main reason for early discontinuation was adverse events (AEs; 23.0% of patients). Patients were primarily middle-aged (mean 46.9 ± 10.8 years), female (91.1%), white (91.4%), with a mean duration of FM symptoms of 9.9 ± 8.7 years. Serious AEs were experienced by 3.6% of patients. The most frequently reported AEs (incidence ≥ 5% at any dose or overall) were nausea, headache, dizziness, nasopharyngitis, vomiting, sinusitis, diarrhea, anxiety, insomnia, influenza, somnolence, upper respiratory tract infection, muscle spasms, urinary tract infection, and gastroenteritis viral. Maintenance of SXB therapeutic response was demonstrated with continued improvement from controlled-study baseline in pain VAS, Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. ClinicalTrials.gov NCT00423605.

Predictors of short- and long-term adherence with a Mediterranean-type diet intervention: the PREDIMED randomized trial.

PubMed

Downer, Mary Kathryn; Gea, Alfredo; Stampfer, Meir; Sánchez-Tainta, Ana; Corella, Dolores; Salas-Salvadó, Jordi; Ros, Emilio; Estruch, Ramón; Fitó, Montserrat; Gómez-Gracia, Enrique; Arós, Fernando; Fiol, Miquel; De-la-Corte, Francisco Jose Garcia; Serra-Majem, Lluís; Pinto, Xavier; Basora, Josep; Sorlí, José V; Vinyoles, Ernest; Zazpe, Itziar; Martínez-González, Miguel-Ángel

2016-06-14

Dietary intervention success requires strong participant adherence, but very few studies have examined factors related to both short-term and long-term adherence. A better understanding of predictors of adherence is necessary to improve the design and execution of dietary intervention trials. This study was designed to identify participant characteristics at baseline and study features that predict short-term and long-term adherence with interventions promoting the Mediterranean-type diet (MedDiet) in the PREvención con DIeta MEDiterránea (PREDIMED) randomized trial. Analyses included men and women living in Spain aged 55-80 at high risk for cardiovascular disease. Participants were randomized to the MedDiet supplemented with either complementary extra-virgin olive oil (EVOO) or tree nuts. The control group and participants with insufficient information on adherence were excluded. PREDIMED began in 2003 and ended in 2010. Investigators assessed covariates at baseline and dietary information was updated yearly throughout follow-up. Adherence was measured with a validated 14-point Mediterranean-type diet adherence score. Logistic regression was used to examine associations between baseline characteristics and adherence at one and four years of follow-up. Participants were randomized to the MedDiet supplemented with EVOO (n = 2,543; 1,962 after exclusions) or tree nuts (n = 2,454; 2,236 after exclusions). A higher number of cardiovascular risk factors, larger waist circumference, lower physical activity levels, lower total energy intake, poorer baseline adherence to the 14-point adherence score, and allocation to MedDiet + EVOO each independently predicted poorer adherence. Participants from PREDIMED recruiting centers with a higher total workload (measured as total number of persons-years of follow-up) achieved better adherence. No adverse events or side effects were reported. To maximize dietary adherence in dietary interventions, additional efforts to promote adherence should be used for participants with lower baseline adherence to the intended diet and poorer health status. The design of multicenter nutrition trials should prioritize few large centers with more participants in each, rather than many small centers. This study was registered at controlled-trials.com (http://www.controlled-trials. com/ISRCTN35739639). International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005. parallel randomized trial.

Emerging indications of endoscopic radiofrequency ablation

PubMed Central

Becq, Aymeric; Camus, Marine; Rahmi, Gabriel; de Parades, Vincent; Marteau, Philippe

2015-01-01

Introduction Radiofrequency ablation (RFA) is a well-validated treatment of dysplastic Barrett's esophagus. Other indications of endoscopic RFA are under evaluation. Results Four prospective studies (total 69 patients) have shown that RFA achieved complete remission of early esophageal squamous intra-epithelial neoplasia at a rate of 80%, but with a substantial risk of stricture. In the setting of gastric antral vascular ectasia, two prospective monocenter studies, and a retrospective multicenter study, (total 51 patients), suggest that RFA is efficacious in terms of reducing transfusion dependency. In the setting of chronic hemorrhagic radiation proctopathy, a prospective monocenter study and a retrospective multicenter study (total 56 patients) suggest that RFA is an efficient treatment. A retrospective comparative study (64 patients) suggests that RFA improves stents patency in malignant biliary strictures. Conclusions Endoscopic RFA is an upcoming treatment modality in early esophageal squamous intra-epithelial neoplasia, as well as in gastric, rectal, and biliary diseases. PMID:26279839

The intracavitary ECG method for positioning the tip of central venous access devices in pediatric patients: results of an Italian multicenter study.

PubMed

Rossetti, Francesca; Pittiruti, Mauro; Lamperti, Massimo; Graziano, Ugo; Celentano, Davide; Capozzoli, Giuseppe

2015-01-01

The Italian Group for Venous Access Devices (GAVeCeLT) has carried out a multicenter study investigating the safety and accuracy of intracavitary electrocardiography (IC-ECG) in pediatric patients. We enrolled 309 patients (age 1 month-18 years) candidate to different central venous access devices (VAD) - 56 peripherally inserted central catheters (PICC), 178 short term centrally inserted central catheters (CICC), 65 long term VADs, 10 VADs for dialysis - in five Italian Hospitals. Three age groups were considered: A (<4 years, n = 157), B (4-11 years, n = 119), and C (12-18 years, n = 31). IC-ECG was applicable in 307 cases. The increase of the P wave on IC-ECG was detected in all cases but two. The tip of the catheter was positioned at the cavo-atrial junction (CAJ) (i.e., at the maximal height of the P wave on IC-ECG) and the position was checked during the procedure by fluoroscopy or chest x-ray, considering the CAJ at 1-2 cm (group A), 1.5-3 cm (group B), or 2-4 cm (group C) below the carina. There were no complications related to IC-ECG. The overall match between IC-ECG and x-ray was 95.8% (96.2% in group A, 95% in group B, and 96.8% in group C). In 95 cases, the IC-ECG was performed with a dedicated ECG monitor, specifically designed for IC-ECG (Nautilus, Romedex): in this group, the match between IC-ECG and x-ray was 98.8%. We conclude that the IC-ECG method is safe and accurate in the pediatric patients. The applicability of the method is 99.4% and its feasibility is 99.4%. The accuracy is 95.8% and even higher (98.8%) when using a dedicated ECG monitor.

Spontaneous and induced tolerance for liver transplant recipients.

PubMed

Feng, Sandy

2016-02-01

Transformative medical and surgical advances have remarkably improved short-term survival after liver transplantation. There is, however, pervasive concern that the cumulative toxicities of modern immunosuppression regimens severely compromise both quality and quantity of life for liver transplant recipients. The inherently tolerogenic nature of the liver offers the tantalizing opportunity to change the current paradigm of nonspecific and lifelong immunosuppression. Safe minimization or discontinuation of immunosuppression without damage to the liver allograft is an attractive strategy to improve long-term survival after liver transplantation. Recent prospective, multicenter clinical trials have demonstrated that immunosuppression can be safely withdrawn from selected liver transplant recipients with preservation of allograft histology. These successes have spurred multiple avenues of investigation to identify peripheral blood and/or tissue biomarkers and delineate mechanisms of tolerance. Concomitant advances in the ability to expand regulatory T cells in the laboratory have spawned clinical trials to facilitate immunosuppression minimization and/or discontinuation. This review will delineate the unique liver immunobiology that has driven the recent clinical trials to unmask spontaneous tolerance or induce tolerance for liver transplant recipients. The emerging results of these trials over the next 5 years hold promise to reduce the burden of lifelong immunosuppression and thereby optimize the long-term health of liver transplant recipients.

Soluble ST2 in ambulatory patients with heart failure: Association with functional capacity and long-term outcomes.

PubMed

Felker, G Michael; Fiuzat, Mona; Thompson, Vivian; Shaw, Linda K; Neely, Megan L; Adams, Kirkwood F; Whellan, David J; Donahue, Mark P; Ahmad, Tariq; Kitzman, Dalane W; Piña, Ileana L; Zannad, Faiez; Kraus, William E; O'Connor, Christopher M

2013-11-01

ST2 is involved in cardioprotective signaling in the myocardium and has been identified as a potentially promising biomarker in heart failure (HF). We evaluated ST2 levels and their association with functional capacity and long-term clinical outcomes in a cohort of ambulatory patients with HF enrolled in the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) study-a multicenter, randomized study of exercise training in HF. HF-ACTION randomized 2331 patients with left ventricular ejection fraction <0.35 and New York Heart Association class II to IV HF to either exercise training or usual care. ST2 was analyzed in a subset of 910 patients with evaluable plasma samples. Correlations and Cox models were used to assess the relationship among ST2, functional capacity, and long-term outcomes. The median baseline ST2 level was 23.7 ng/mL (interquartile range, 18.6-31.8). ST2 was modestly associated with measures of functional capacity. In univariable analysis, ST2 was significantly associated with death or hospitalization (hazard ratio, 1.48; P<0.0001), cardiovascular death or HF hospitalization (hazard ratio, 2.14; P<0.0001), and all-cause mortality (hazard ratio, 2.33; P<0.0001; all hazard ratios for log2 ng/mL). In multivariable models, ST2 remained independently associated with outcomes after adjustment for clinical variables and amino-terminal pro-B-type natriuretic peptide. However, ST2 did not add significantly to reclassification of risk as assessed by changes in the C statistic, net reclassification improvement, and integrated discrimination improvement. ST2 was modestly associated with functional capacity and was significantly associated with outcomes in a well-treated cohort of ambulatory patients with HF although it did not significantly affect reclassification of risk. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437.

Long-term treatment with oral sildenafil is safe and improves functional capacity and hemodynamics in patients with pulmonary arterial hypertension.

PubMed

Michelakis, Evangelos D; Tymchak, Wayne; Noga, Michelle; Webster, Linda; Wu, Xi-Chen; Lien, Dale; Wang, Shao-Hua; Modry, Dennis; Archer, Stephen L

2003-10-28

The prognosis and functional capacity of patients with pulmonary arterial hypertension (PAH) is poor, and there is a need for safe, effective, inexpensive oral treatments. A single dose of sildenafil, an oral phosphodiesterase type-5 (PD-5) inhibitor, is an effective and selective pulmonary vasodilator in PAH. However, the long-term effects of PD-5 inhibition and its mechanism of action in human pulmonary arteries (PAs) are unknown. We hypothesized that 3 months of sildenafil (50 mg orally every 8 hours) added to standard treatment would be safe and improve functional capacity and hemodynamics in PAH patients. We studied 5 consecutive patients (4 with primary pulmonary hypertension, 1 with Eisenmenger's syndrome; New York Heart Association class II to III). Functional class improved by > or =1 class in all patients. Pretreatment versus posttreatment values (mean+/-SEM) were as follows: 6-minute walk, 376+/-30 versus 504+/-27 m, P<0.0001; mean PA pressure, 70+/-3 versus 52+/-3 mm Hg, P<0.007; pulmonary vascular resistance index 1702+/-151 versus 996+/-92 dyne x s x cm(-5) x m(-2), P<0.006. The systemic arterial pressure was unchanged, and no adverse effects occurred. Sildenafil also reduced right ventricular mass measured by MRI. In 7 human PAs (6 cardiac transplant donors and 1 patient with PAH on autopsy), we showed that PD-5 is present in PA smooth muscle cells and that sildenafil causes relaxation by activating large-conductance, calcium-activated potassium channels. This small pilot study suggests that long-term sildenafil therapy might be a safe and effective treatment for PAH. At a monthly cost of 492 dollars Canadian, sildenafil is more affordable than most approved PAH therapies. A large multicenter trial is indicated to directly compare sildenafil with existing PAH treatments.

Long-term nitrite inhalant exposure and cancer risk in MSM

PubMed Central

Dutta, Anupriya; Uno, Hajime; Holman, Alex; Lorenz, David R.; Wolinsky, Steven M.; Gabuzda, Dana

2017-01-01

Objectives: Nitrite inhalants (poppers) are commonly used recreational drugs among MSM and were previously associated with elevated rates of high-risk sexual behavior, HIV and human herpesvirus type 8 (HHV-8) seroconversion, and transient immunosuppressive effects in experimental models. Whether long-term popper use is associated with cancer risk among MSM in the HAART era is unclear. Design: Prospective cohort study of cancer risk in 3223 HIV-infected and uninfected MSM in the Multicenter AIDS Cohort Study from 1996–2010. Methods: Poisson regression models were used to examine the association between heavy popper use (defined as daily or weekly use for at least 1 year) and risk of individual cancers or composite category of virus-associated cancers. Results: Among all participants, heavy popper use was not associated with increased risk of any individual cancers. Among HIV-uninfected men aged 50–70, heavy popper use was associated with increased risk of virus-associated cancer with causes linked to human papillomavirus, HHV-8, and Epstein–Barr virus in models adjusted for demographics, number of sexual partners, immunological parameters (CD4+ cell counts or CD4+/CD8+ ratios), and hepatitis B and C viruses [incidence rate ratio (IRR), 95% confidence interval (CI) 3.24, 1.05–9.96], or sexually transmitted infections (IRR 3.03, 95% CI, 1.01–9.09), as was cumulative use over a 5-year period (IRR 1.012, 95% CI 1.003–1.021; P = 0.007). There was no significant association between heavy popper use and virus-associated cancer in HIV-infected men. Conclusions: Long-term heavy popper use is associated with elevated risk of some virus-associated cancers with causes related to human papillomavirus, HHV-8, and Epstein–Barr virus infections in older HIV-uninfected MSM independent of sexual behavior and immunological parameters. PMID:28441176

Long-term safety and efficacy of the novel β3 -adrenoreceptor agonist vibegron in Japanese patients with overactive bladder: A phase III prospective study.

PubMed

Yoshida, Masaki; Kakizaki, Hidehiro; Takahashi, Satoru; Nagai, Shinji; Kurose, Takafumi

2018-05-11

To evaluate the long-term safety and efficacy of vibegron 50 mg and 100 mg, a novel β 3 -adrenoreceptor agonist, in Japanese patients with overactive bladder. This was a 1-year, multicenter, open-label, non-controlled study. After a 1-week observation phase, patients were treated with vibegron for 52 weeks. When the efficacy was insufficient after an 8-week treatment with 50 mg, the dose was increased to 100 mg and maintained for an additional 44 weeks. Among a total of 169 patients receiving one or more doses of vibegron, 118 (69.8%) received vibegron 50 mg for 52 weeks, and the dose was increased to 100 mg in 51 (30.2%) patients. The incidence of drug-related adverse events was 18.1% (21/116) in the vibegron 50 mg group and 11.8% (6/51) in the vibegron 100 mg group. Most frequent drug-related adverse events were dry mouth (3.0%), residual urine volume increased (3.0%), constipation (2.4%) and cystitis (1.8%). Statistically significant changes in overactive bladder symptom variables (daily means of micturitions, urgency episodes, urgency incontinence episodes, incontinence episodes and night-time frequency) from baseline were observed at week 4 and maintained until week 52. The condition of patients who did not respond well to vibegron 50 mg was much improved by increasing the dose to 100 mg. Vibegron improved the quality of life, and the proportion of patients' satisfaction after the treatment with vibegron was high. Long-term (52-week) treatment with vibegron is safe, well-tolerated and effective in patients with overactive bladder. © 2018 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.

Creative music therapy to promote brain structure, function, and neurobehavioral outcomes in preterm infants: a randomized controlled pilot trial protocol.

PubMed

Haslbeck, Friederike Barbara; Bucher, Hans-Ulrich; Bassler, Dirk; Hagmann, Cornelia

2017-01-01

Preterm birth is associated with increased risk of neurological impairment and deficits in cognition, motor function, and behavioral problems. Limited studies indicate that multi-sensory experiences support brain development in preterm infants. Music appears to promote neurobiological processes and neuronal learning in the human brain. Creative music therapy (CMT) is an individualized, interactive therapeutic approach based on the theory and methods of Nordoff and Robbins. CMT may promote brain development in preterm infants via concurrent interaction and meaningful auditory stimulation. We hypothesize that preterm infants who receive creative music therapy during neonatal intensive care admission will have developmental benefits short- and long-term brain function. A prospective, randomized controlled single-center pilot trial involving 60 clinically stable preterm infants under 32 weeks of gestational age is conducted in preparation for a multi-center trial. Thirty infants each are randomized to either standard neonatal intensive care or standard care with CMT. Music therapy intervention is approximately 20 min in duration three times per week. A trained music therapist sings for the infants in lullaby style, individually entrained and adjusted to the infant's rhythm and affect. Primary objectives of this study are feasibility of protocol implementation and investigating the potential mechanism of efficacy for this new intervention. To examine the effect of this new intervention, non-invasive, quantitative magnetic resonance imaging (MRI) methods at corrected age and standardized neurodevelopmental assessments using the Bayley Scales of Infant and Toddler Development third edition at a corrected age of 24 months and Kaufman Assessment Battery for Children at 5 years will be performed. All assessments will be performed and analyzed by blinded experts. To our knowledge, this is the first randomized controlled clinical trial to systematically examine possible effects of creative music therapy on short- and long-term brain development in preterm infants. This project lies at the interface of music therapy, neuroscience, and medical imaging. New insights into the potential role and impact of music on brain function and development may be elucidated. If such a low-cost, low-risk intervention is demonstrated in a future multi-center trial to be effective in supporting brain development in preterm neonates, findings could have broad clinical implications for this vulnerable patient population. ClinicalTrials.gov, NCT02434224.

Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach.

PubMed

Ferrario, Manuela; Cambiaghi, Alice; Brunelli, Laura; Giordano, Silvia; Caironi, Pietro; Guatteri, Luca; Raimondi, Ferdinando; Gattinoni, Luciano; Latini, Roberto; Masson, Serge; Ristagno, Giuseppe; Pastorelli, Roberta

2016-02-05

Septic shock remains a major problem in Intensive Care Unit, with high lethality and high-risk second lines treatments. In this preliminary retrospective investigation we examined plasma metabolome and clinical features in a subset of 20 patients with severe septic shock (SOFA score >8), enrolled in the multicenter Albumin Italian Outcome Sepsis study (ALBIOS, NCT00707122). Our purpose was to evaluate the changes of circulating metabolites in relation to mortality as a pilot study to be extended in a larger cohort. Patients were analyzed according to their 28-days and 90-days mortality. Metabolites were measured using a targeted mass spectrometry-based quantitative metabolomic approach that included acylcarnitines, aminoacids, biogenic amines, glycerophospholipids, sphingolipids, and sugars. Data-mining techniques were applied to evaluate the association of metabolites with mortality. Low unsaturated long-chain phosphatidylcholines and lysophosphatidylcholines species were associated with long-term survival (90-days) together with circulating kynurenine. Moreover, a decrease of these glycerophospholipids was associated to the event at 28-days and 90-days in combination with clinical variables such as cardiovascular SOFA score (28-day mortality model) or renal replacement therapy (90-day mortality model). Early changes in the plasma levels of both lipid species and kynurenine associated with mortality have potential implications for early intervention and discovering new target therapy.

Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach

PubMed Central

Ferrario, Manuela; Cambiaghi, Alice; Brunelli, Laura; Giordano, Silvia; Caironi, Pietro; Guatteri, Luca; Raimondi, Ferdinando; Gattinoni, Luciano; Latini, Roberto; Masson, Serge; Ristagno, Giuseppe; Pastorelli, Roberta

2016-01-01

Septic shock remains a major problem in Intensive Care Unit, with high lethality and high-risk second lines treatments. In this preliminary retrospective investigation we examined plasma metabolome and clinical features in a subset of 20 patients with severe septic shock (SOFA score >8), enrolled in the multicenter Albumin Italian Outcome Sepsis study (ALBIOS, NCT00707122). Our purpose was to evaluate the changes of circulating metabolites in relation to mortality as a pilot study to be extended in a larger cohort. Patients were analyzed according to their 28-days and 90-days mortality. Metabolites were measured using a targeted mass spectrometry-based quantitative metabolomic approach that included acylcarnitines, aminoacids, biogenic amines, glycerophospholipids, sphingolipids, and sugars. Data-mining techniques were applied to evaluate the association of metabolites with mortality. Low unsaturated long-chain phosphatidylcholines and lysophosphatidylcholines species were associated with long-term survival (90-days) together with circulating kynurenine. Moreover, a decrease of these glycerophospholipids was associated to the event at 28-days and 90-days in combination with clinical variables such as cardiovascular SOFA score (28-day mortality model) or renal replacement therapy (90-day mortality model). Early changes in the plasma levels of both lipid species and kynurenine associated with mortality have potential implications for early intervention and discovering new target therapy. PMID:26847922

The impact of the lung allocation score on short-term transplantation outcomes: a multicenter study.

PubMed

Kozower, Benjamin D; Meyers, Bryan F; Smith, Michael A; De Oliveira, Nilto C; Cassivi, Stephen D; Guthrie, Tracey J; Wang, Honkung; Ryan, Beverly J; Shen, K Robert; Daniel, Thomas M; Jones, David R

2008-01-01

The lung allocation score restructured the distribution of scarce donor lungs for transplantation. The algorithm ranks waiting list patients according to medical urgency and expected benefit after transplantation. The purpose of this study was to evaluate the impact of the lung allocation score on short-term outcomes after lung transplantation. A multicenter retrospective cohort study was performed with data from 5 academic medical centers. Results of patients undergoing transplantation on the basis of the lung allocation score (May 4, 2005 to May 3, 2006) were compared with those of patients receiving transplants the preceding year before the lung allocation score was implemented (May 4, 2004, to May 3, 2005). The study reports on 341 patients (170 before the lung allocation score and 171 after). Waiting time decreased from 680.9 +/- 528.3 days to 445.6 +/- 516.9 days (P < .001). Recipient diagnoses changed with an increase in idiopathic pulmonary fibrosis and a decrease in emphysema and cystic fibrosis (P = .002). Postoperatively, primary graft dysfunction increased from 14.1% (24/170) to 22.9% (39/171) (P = .04) and intensive care unit length of stay increased from 5.7 +/- 6.7 days to 7.8 +/- 9.6 days (P = .04). Hospital mortality and 1-year survival were the same between groups (5.3% vs 5.3% and 90% vs 89%, respectively; P > .6) This multicenter retrospective review of short-term outcomes supports the fact that the lung allocation score is achieving its objectives. The lung allocation score reduced waiting time and altered the distribution of lung diseases for which transplantation was done on the basis of medical necessity. After transplantation, recipients have significantly higher rates of primary graft dysfunction and intensive care unit lengths of stay. However, hospital mortality and 1-year survival have not been adversely affected.

Efficacy of a ketogenic diet in resistant myoclono-astatic epilepsy: A French multicenter retrospective study.

PubMed

Stenger, Elodie; Schaeffer, Mickael; Cances, Claude; Motte, Jacques; Auvin, Stéphane; Ville, Dorothée; Maurey, Hélène; Nabbout, Rima; de Saint-Martin, Anne

2017-03-01

Recent studies have suggested that the early introduction of a ketogenic diet (KD) could improve seizure control in myoclono-astatic epilepsy (MAE). This multicenter study sought to identify the benefits of KD use on seizure control and epilepsy and on developmental outcomes in children with resistant MAE. Fifty children who were diagnosed with severe MAE in the French network of Reference Centers for Rare Epilepsies and who were treated with KD between 2000 and 2013 were included in this study. The seizure frequency and EEG recordings were assessed two weeks before KD introduction, 2 and 6 months after, and during the last follow-up, which also included an assessment of developmental outcome. Patients had a median follow up of 52 months (range 13-136) and received 4.3 antiepileptic drugs [2-9] before KD introduction. Fifty-four percent (54%) of our patients were seizure-free after 6 months of KD or more, and 86% experienced more than a 70% seizure reduction after 2 months of KD. Forty-four percent (44%) of them had a clear benefit of early KD treatment (after four AEDs failed). Early KD treatment did not result in a greater seizure reduction (p=0.055), but significantly resulted in remission (p<0.028). Fifty percent of patients with resistant MAE had normal development outcomes. Earlier KD treatment, after three AEDs failed, was correlated with a better cognitive outcome (p<0.01). Early introduction of KD treatment in resistant MAE has a strong, persistent anticonvulsant effect with long-term remission and better cognitive outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Continuous glucose monitoring in hemodialyzed patients with type 2 diabetes: a multicenter pilot study.

PubMed

Képénékian, Lori; Smagala, Agnieszka; Meyer, Laurent; Imhoff, Olivier; Alenabi, Farideh; Serb, Liviu; Fleury, Dominique; Dorey, François; Krummel, Thierry; Le Floch, Jean-Pierre; Chantrel, François; Kessler, Laurence

2014-10-01

Hemodialyzed patients with diabetes face an increased cardiovascular risk. Optimal glycemic control can reduce morbidity and mortality, but it is difficult to achieve because of the alternation between dialysis and non-dialysis periods. This study evaluated the contribution of continuous glucose monitoring (CGM) to the management of insulin regimen. In this pilot prospective multicenter study, we performed CGM (Navigator®, Abbott, Rungis, France) for a total of 54 hours at baseline and for a 3-month follow-up period in a group of 28 hemodialyzed patients with type 2 diabetes treated by a basal-bolus detemir plus aspart insulin regimen. Insulin therapy was adapted to the CGM values. HbA1c and CGM parameters collected over the 3-month treatment period were compared using MANOVA for repeated measures. After 3 months, HbA1c significantly decreased from 8.4 ± 1.0% (65 ± 1 mmol/mol) to 7.6 ± 1.0% (60 ± 11 mmol/mol; p < 0.01). Similarly, mean CGM glucose values significantly decreased from 9.9 ± 1.9 to 8.9 ± 2.1 mmol/L (p = 0.05). The frequency of glucose values > 10 mmol/L significantly decreased from 41.3 ± 21.9% to 30.1 ± 22.4% (p < 0.05), without a significant increase in the frequency of glucose values < 3.3 mmol/L. Insulin requirements significantly increased from 70 ± 51 IU/d to 82 ± 77 IU/d (p < 0.001), without significant changes in body weight. CGM-adapted insulin regimen improves glycemic control without increasing hypoglycemic events in hemodialyzed diabetic patients. CGM could be a useful tool for the management of insulin therapy in these patients. These results need to be confirmed by long-term studies with larger sample sizes.

Music therapy in Huntington's disease: a protocol for a multi-center randomized controlled trial.

PubMed

van Bruggen-Rufi, Monique; Vink, Annemieke; Achterberg, Wilco; Roos, Raymund

2016-07-26

Huntington's disease is a progressive, neurodegenerative disease with autosomal dominant inheritance, characterized by motor disturbances, cognitive decline and behavioral and psychological symptoms. Since there is no cure, all treatment is aimed at improving quality of life. Music therapy is a non-pharmacological intervention, aiming to improve the quality of life, but its use and efficacy in patients with Huntington's disease has hardly been studied. In this article, a protocol is described to study the effects of music therapy in comparison with a control intervention to improve quality of life through stimulating expressive and communicative skills. By targeting these skills we assume that the social-cognitive functioning will improve, leading to a reduction in behavioral problems, resulting in an overall improvement of the quality of life in patients with Huntington's disease. The study is designed as a multi-center single-blind randomised controlled intervention trial. Sixty patients will be randomised using centre-stratified block-permuted randomisation. Patients will be recruited from four long-term care facilities specialized in Huntington's disease-care in The Netherlands. The outcome measure to assess changes in expressive and communication skills is the Behaviour Observation Scale Huntington and changes in behavior will be assessed by the Problem Behaviour Assesment-short version and by the BOSH. Measurements take place at baseline, then 8, 16 (end of intervention) and 12 weeks after the last intervention (follow-up). This randomized controlled study will provide greater insight into the effectiveness of music therapy on activities of daily living, social-cognitive functioning and behavior problems by improving expressive and communication skills, thus leading to a better quality of life for patients with Huntington's disease. Netherlands Trial Register: NTR4904 , registration date Nov. 15, 2014.

Low prevalence of hypopituitarism after traumatic brain injury: a multicenter study.

PubMed

Kokshoorn, N E; Smit, J W A; Nieuwlaat, W A; Tiemensma, J; Bisschop, P H; Groote Veldman, R; Roelfsema, F; Franken, A A M; Wassenaar, M J E; Biermasz, N R; Romijn, J A; Pereira, A M

2011-08-01

Hypopituitarism after traumatic brain injury (TBI) is considered to be a prevalent condition. However, prevalence rates differ considerably among reported studies, due to differences in definitions, endocrine assessments of hypopituitarism, and confounding factors, such as timing of evaluation and the severity of the trauma. Aim To evaluate the prevalence of hypopituitarism in a large cohort of TBI patients after long-term follow-up using a standardized endocrine evaluation. Study design Cross-sectional study. We included 112 patients with TBI, hospitalized for at least 3 days and duration of follow-up >1 year after TBI from five (neurosurgical) referral centers. Evaluation of pituitary function included fasting morning hormone measurements and insulin tolerance test (n=90) or, when contraindicated, ACTH stimulation and/or CRH stimulation tests and a GH releasing hormone-arginine test (n=22). Clinical evaluation included quality of life questionnaires. We studied 112 patients (75 males), with median age 48 years and mean body mass index (BMI) 26.7±4.8 kg/m(2). Mean duration of hospitalization was 11 (3-105), and 33% of the patients had a severe trauma (Glasgow Coma Scale <9) after TBI. The mean duration of follow-up was 4 (1-12) years. Hypopituitarism was diagnosed in 5.4% (6/112) of patients: severe GH deficiency (n=3), hypogonadism (n=1), adrenal insufficiency (n=2). Patients diagnosed with pituitary insufficiency had significantly higher BMI (P=0.002). In this study, the prevalence of hypopituitarism during long-term follow-up after TBI was low. Prospective studies are urgently needed to find reliable predictive tools for the identification of patients with a significant pre-test likelihood for hypopituitarism after TBI.

Biodegradable Stents for Caustic Esophageal Strictures: Do They Work?

PubMed

Kochhar, Rakesh; Samanta, Jayanta; Basha, Jahangeer; Verma, Abhai; Choudhuri, Gourdas; Lakhtakia, Sundeep; Reddy, D Nageshwar

2017-08-01

Biodegradable (BD) stents have been used for the management of various esophageal strictures (ES) but the experience of its use in caustic strictures is limited. The present study, aimed at evaluating efficacy of BD stents for the treatment of refractory caustic-induced ES, was a retrospective multi-center study conducted at three tertiary care centers in India wherein adult patients with refractory caustic induced strictures underwent placement of a BD stent. Patients were followed up for immediate complications and long term outcome. All 13 patients (39.3 ± 15.1 years) underwent successful BD stent placement. Retrosternal chest pain occurred in 2 patients and stent migration in 1 (7.6%) patient. At 3 months, restenosis with recurrence of dysphagia was seen in nine (69.2%) patients, at 6 months, 10 (77%) patients had dysphagia of whom three underwent surgery and the remaining seven patients required dilatations. At 1 year, one patient remained asymptomatic while nine had dysphagia. The requirement for dilatation was once in 3 months in seven patients & once in a month in two patients. At 2 years, the requirement of dilatations was further reduced to once in 4-6 months in all patients. Over a 3 year follow up three (23%) patients had undergone surgery, one was free of symptoms while nine patients continued to be on periodic dilatation although the requirement had reduced to once in 4-6 months. Efficacy of BD stents in patients with caustic-induced ES is limited and the short term radial force applied by the currently available BD stents is inadequate to provide long term relief in such patients.

Health-related quality of life in premature acute coronary syndrome: does patient sex or gender really matter?

PubMed

Leung Yinko, Sylvie S L; Pelletier, Roxanne; Behlouli, Hassan; Norris, Colleen M; Humphries, Karin H; Pilote, Louise

2014-07-28

Limited data exist as to the relative contribution of sex and gender on health-related quality of life (HRQL) among patients with acute coronary syndrome (ACS). This study aims to evaluate the effect of sex and gender-related variables on long-term HRQL among young adults with ACS. GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond-Premature Acute Coronary SYndrome) is a multicenter, prospective cohort study (January 2009 to August 2013) of adults aged 18 to 55 years, hospitalized with ACS. HRQL was measured at baseline, 1, 6, and 12 months using the Short Form-12 and Seattle Angina Questionnaire (SAQ) among 1213 patients. Median age was 49 years. Women reported worse HRQL than men over time post-ACS, both in terms of physical and mental functioning. Gender-related factors were more likely to be predictors of HRQL than sex. Femininity score, social support, and housework responsibility were the most common gender-related predictors of HRQL at 12 months. We observed an interaction between female sex and social support (β=0.44 [95% confidence interval, 0.01, 0.88]; P=0.047) for the physical limitation subscale of the SAQ. Young women with ACS report significantly poorer HRQL than young men. Gender appears to be more important than sex in predicting long-term HRQL post-ACS. Specific gender-related factors, such as social support, may be amenable to interventions and could improve the HRQL of patients with premature ACS. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

The clinical relevance of treating chronic wounds with an enhanced near-physiological concentration of platelet-rich plasma gel.

PubMed

de Leon, Jean M; Driver, Vickie R; Fylling, Carelyn P; Carter, Marissa J; Anderson, Carol; Wilson, Janice; Dougherty, Rita Michelle; Fuston, Denise; Trigilia, Donna; Valenski, Vicky; Rappl, Laurie M

2011-08-01

This study investigated clinical outcomes in chronic nonhealing wounds following the short-term use of an enhanced, near-physiological concentration of platelet-rich plasma (PRP) gel (AutoloGel System, Cytomedix, Inc, Gaithersburg, Maryland). Study design was a large, observational case series using a multicenter registry database (all wounds included), which compared different populations within the database. Thirty-nine centers contributed to the registry, including long-term acute-care centers, outpatient clinics, a durable medical equipment company, a home health agency, and a long-term-care center. The target population included 285 chronic wounds (patient n = 200). Wound etiologies included diabetic, pressure, or venous ulcer; dehisced, surgical, or traumatic wound; and wounds of other etiologies. Therapeutic, PRP gel is produced from patient blood utilizing autologous platelets and plasma that contribute growth factors, cytokines, and chemokines, in a fibrin matrix. Area and volume of the wound and the linear total of undermining and sinus tracts/tunneling were calculated. Clinical relevance was determined by analyzing outcomes in wounds that responded to treatment. A positive response occurred in 96.5% of wounds within 2.2 weeks with 2.8 treatments. In 86.3% of wounds, 47.5% area reduction occurred, and 90.5% of wounds had a 63.6% volume reduction. In 89.4% undermined and 85.7% of sinus tracts/tunneling wounds, 71.9% and 49.3% reductions in linear total were observed, respectively. In chronic wounds recalcitrant to other treatments, utilization of PRP gel can restart the healing process. Rapid treatment response was observed in 275 of 285 wounds, and the magnitude of response was consistently high, with statistically significant outcomes reported for various subgroups.

Long-term Outcome of Lupus Nephritis Class II in Argentine Patients

PubMed Central

Collado, Maria Victoria; Dorado, Enrique; Rausch, Silvia; Gomez, Graciela; Khoury, Marina; Zazzetti, Federico; Gargiulo, María; Suarez, Lorena; Chaparro, Rafael; Paira, Sergio; Galvan, Laura; Juarez, Vicente; Pisoni, Cecilia; Garcia, Mercedes; Martinez, Liliana; Alvarez, Analia; Alvarez, Clarisa; Barreira, Juan; Sarano, Judith

2016-01-01

Background There is controversy in medical literature over the outcome of patients with lupus nephritis (LN) class II. The aim of this study was to explore the risk of histological transformation (HT) and possible factors related to negative response to treatment in patients with mesangial LN class II. Methods A retrospective and multicenter study was carried out that includes patients who had received a diagnosis of LN class II on their first renal biopsy. Creatinine, urine sediment, and proteinuria were recorded at the time of the first biopsy, 6 months, and 1, 2, and 5 years after the first biopsy. Response to treatment, HT, and long-term outcome were evaluated. Results Forty-one patients were included. The manifestation at first biopsy was proteinuria greater than 0.5 g/d in 28 patients (68.29%; 8 [28.57%] of 28 patients had nephrotic syndrome), hematuria in 18 patients (43.90%), and deterioration of renal function in 3 patients (7.31%). During the follow-up (median, 8 years; range, 1–35 years), a new biopsy was performed in 18 patients (43.90%), and in 17 patients (17/18 [94.44%]), there was HT. Median time at rebiopsy was 32 months (range, 11–305 months). Of the 18 patients who had a second biopsy, 10 (55.55%) were on hydroxychloroquine versus 100% (19/19) of patients who did not undergo the procedure (P = 0.001). A year after the first renal biopsy, there are data available from 34 patients; of them, 24 patients (70.58%) had achieved response, and 10 patients (29.41%) had no response (NR) (missing data in 7). A higher 24-hour urinary protein at 6 months was predictor of worse outcome at 1 year, with statistical significance difference for the nonresponder group (median proteinuria, 2.3 g/d [range, 0–4.7 g/d]) compared with responders (median proteinuria, 0.28 g/d [range, 0–1.7 g/d]) (P = 0.0133). In the long-term follow-up (5 years), HT was the main cause of unfavorable outcome and was measured in 78.57% of patients (11/14 patients). Conclusions This series shows a high rate of HT in long-term follow-up. Proteinuria at 6 months made it possible to set aside patients who will have an unfavorable outcome in the long term and who will thus benefit from a more aggressive treatment. The results suggest that hydroxychloroquine had a nephroprotective effect. PMID:27152693

A randomized, controlled, multicenter contraceptive efficacy clinical trial of the intravas device, a nonocclusive surgical male sterilization.

PubMed

Lu, Wen-Hong; Liang, Xiao-Wei; Gu, Yi-Qun; Wu, Wei-Xiong; Bo, Li-Wei; Zheng, Tian-Gui; Chen, Zhen-Wen

2014-01-01

Because of unavoidable complications of vasectomy, this study was undertaken to assess the efficacy and safety of male sterilization with a nonobstructive intravas device (IVD) implanted into the vas lumen by a mini-surgical method compared with no-scalpel vasectomy (NSV). IVDs were categorized into two types: IVD-B has a tail used for fixing to the vas deferens (fixed wing) whereas IVD-A does not. A multicenter prospective randomized controlled clinical trial was conducted in China. The study was comprised of 1459 male volunteers seeking vasectomy who were randomly assigned to the IVD-A (n = 487), IVD-B (n = 485) or NSV (n = 487) groups and underwent operation. Follow-up included visits at the 3 rd -6 th and 12 th postoperative months. The assessments of the subjects involved regular physical examinations (including general and andrological examinations) and semen analysis. The subjects' partners also underwent monitoring for pregnancy by monthly interviews regarding menstruation and if necessary, urine tests. There were no significant differences in pregnancy rates (0.65% for IVD-A, 0 for IVD-B and 0.21% for NSV) among the three groups (P > 0.05). The cumulative rates of complications at the 12 th postoperative month were zero, 0.9% and 1.7% in the three groups, respectively. In conclusion, IVD male sterilization exhibits a low risk of long-term adverse events and was found to be effective as a male sterilization method, similar to the NSV technique. IVD male sterilization is expected to be a novel contraceptive method.

A fully covered self-expandable metal stent with antimigration features for benign biliary strictures: a prospective, multicenter cohort study.

PubMed

Walter, Daisy; Laleman, Wim; Jansen, Jeroen M; van Milligen de Wit, A W M; Weusten, Bas L; van Boeckel, Petra G; Hirdes, Meike M; Vleggaar, Frank P; Siersema, Peter D

2015-05-01

Self-expandable metal stents (SEMSs) are increasingly used for the treatment of benign biliary strictures (BBSs). A new fully covered SEMS (FCSEMS) with flared ends and high conformability was designed to prevent migration of the stent. To evaluate the efficacy of a novel FCSEMS with antimigration features. Prospective cohort study. Five hospitals in the Netherlands and Belgium. Consecutive patients with BBS. FCSEMS placement for 3 months. Initial and long term clinical success, stent migration rate and safety. Thirty-eight patients (24 men; mean age, 53 ± 16 years) were included. Stent placement was technically successful in 37 patients (97%). Two patients died of an unrelated cause before stent removal, and no data on these patients were available on stricture resolution. Initial clinical success was achieved in 28 of 35 patients (80%). During follow-up after stent removal, a symptomatic recurrent stricture developed in 6 of 28 patients (21%). Overall, the long-term clinical success rate was 63% (22 of 35 patients). Stent migration occurred in 11 of 35 patients (31%), including 5 symptomatic (14%) and 6 asymptomatic (17%) migrations. In total, 11 serious adverse events occurred in 10 patients (29%), with cholangitis (n = 5) being most common. Nonrandomized study design. Good initial clinical success was achieved after placement of this novel FCSEMS, but stricture recurrence was in the upper range compared with other FCSEMSs. The antimigration design could not prevent migration in a significant number of patients with a persisting stricture. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Long-term multiple risk factor interventions in Japanese elderly diabetic patients: the Japanese Elderly Diabetes Intervention Trial--study design, baseline characteristics and effects of intervention.

PubMed

Araki, Atsushi; Iimuro, Satoshi; Sakurai, Takashi; Umegaki, Hiroyuki; Iijima, Katsuya; Nakano, Hiroshi; Oba, Kenzo; Yokono, Koichi; Sone, Hirohito; Yamada, Nobuhiro; Ako, Junya; Kozaki, Koichi; Miura, Hisayuki; Kashiwagi, Atsunori; Kikkawa, Ryuichi; Yoshimura, Yukio; Nakano, Tadasumi; Ohashi, Yasuo; Ito, Hideki

2012-04-01

To evaluate long-term, multiple risk factor intervention on physical, psychological and mental prognosis, and development of complications and cardiovascular disease in elderly type 2 diabetes patients. Our randomized, controlled, multicenter, prospective intervention trial included 1173 elderly type 2 diabetes patients who were enrolled from 39 Japanese institutions and randomized to an intensive or conservative treatment group. Glycemic control, dyslipidemia, hypertension, obesity, diabetic complications and atherosclerotic disease were measured annually. Instrumental activity of daily living, cognitive impairment, depressive symptoms and diabetes burden were assessed at baseline and 3 years. There was no significant difference in clinical or cognitive parameters at baseline between the two groups. The prevalence of low activities of daily living, depressive symptoms and cognitive impairment was 13%, 28% and 4%, respectively, and was similar in the two groups. A small, but significant difference in HbA1c between the two groups was observed at 1 year after the start of intervention (7.9% vs 8.1%, P < 0.05), although this significant difference was not observed after the second year. With the exception of coronary revascularization, there was no significant difference in fatal or non-fatal events between the two groups. Composite events were also similar in the two groups. This study showed no significant differences in fatal or non-fatal events between intensive and conventional treatment. The present study might clarify whether treatment of risk factors influences function and quality of life in elderly diabetic patients. © 2012 Japan Geriatrics Society.

A minimal-contact intervention for cardiac inpatients: long-term effects on smoking cessation.

PubMed

Bolman, Catherine; de Vries, Hein; van Breukelen, Gerard

2002-08-01

This study examined the 1-year effects of a minimal-contact smoking cessation intervention for cardiac inpatients. The multicenter study included cardiac inpatients who had smoked prior to hospitalization. A pretest-posttest quasi-experimental design was used. Patients' experimental condition depended on the hospital they were assigned to. The design was partially randomized: 4 of the 11 hospitals selected the experimental condition themselves (2 experimental, 2 control), while the remaining 7 hospitals were randomly assigned. The experimental group consisted of patients of 5 hospitals (N = 388). Patients of 6 other hospitals served as the control group (N = 401). The intervention included stop-smoking advice by the cardiologist, brief counseling by the nurse, the provision of self-help materials, and aftercare by the cardiologist. Logistic regression analyses controlling for baseline differences and covariates did not show significant intervention effects on point prevalence and continuous abstinence. The study also showed that the outcomes were not significantly related to the way hospitals were assigned to the experimental condition. While short-term effects were found, the minimal-contact intervention did not result in significant effects after 12 months, at least if patients lost to follow-up were treated as posttest smokers. Efforts should be made to improve the intervention, especially the aftercare.

A novel rapid and selective enzymatic debridement agent for burn wound management: a multi-center RCT.

PubMed

Rosenberg, Lior; Krieger, Yuval; Bogdanov-Berezovski, Alex; Silberstein, Eldad; Shoham, Yaron; Singer, Adam J

2014-05-01

Excisional debridement followed by autografting is the standard of care (SOC) for deep burns, but is associated with serious potential complications. Conservative, non-surgical and current enzymatic debridement methods are inefficiently slow. We determined whether a non-surgical option of rapid enzymatic debridement with the debriding enzyme NexoBrid™ (NXB) would reduce need for surgery while achieving similar esthetic and functional outcomes as SOC. We conducted a multi-center, open-label, randomized, controlled clinical trial including patients aged 4-55 years with deep partial and full thickness burns covering 5-30% of their total body surface area (TBSA). Patients were randomly assigned to burn debridement with NXB (applied for 4h) or SOC, which included surgical excisional or non-surgical debridement. NXB significantly reduced the time from injury to complete débridement (2.2 vs. 8.7 days, P<0.0001), need for surgery (24.5% vs. 70.0%, P<0.0001), the area of burns excised (13.1% vs. 56.7%, P<0.0001) and the need for autografting (17.9% vs. 34.1%, P=0.01). Scar quality and quality of life scores were similar in both study groups as were the rates of adverse events. Enzymatic débridement with NXB resulted in reduced need for and extent of surgery compared with SOC while achieving comparable long-term results in patients with deep burns. Clinical Trials.gov NCT00324311. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

Gaps and opportunities in refractory status epilepticus research in children: a multi-center approach by the Pediatric Status Epilepticus Research Group (pSERG).

PubMed

Sánchez Fernández, Iván; Abend, Nicholas S; Agadi, Satish; An, Sookee; Arya, Ravindra; Carpenter, Jessica L; Chapman, Kevin E; Gaillard, William D; Glauser, Tracy A; Goldstein, David B; Goldstein, Joshua L; Goodkin, Howard P; Hahn, Cecil D; Heinzen, Erin L; Mikati, Mohamad A; Peariso, Katrina; Pestian, John P; Ream, Margie; Riviello, James J; Tasker, Robert C; Williams, Korwyn; Loddenkemper, Tobias

2014-02-01

Status epilepticus (SE) is a life-threatening condition that can be refractory to initial treatment. Randomized controlled studies to guide treatment choices, especially beyond first-line drugs, are not available. This report summarizes the evidence that guides the management of refractory convulsive SE (RCSE) in children, defines gaps in our clinical knowledge and describes the development and works of the 'pediatric Status Epilepticus Research Group' (pSERG). A literature review was performed to evaluate current gaps in the pediatric SE and RCSE literature. In person and online meetings helped to develop and expand the pSERG network. The care of pediatric RCSE is largely based on extrapolations of limited evidence derived from adult literature and supplemented with case reports and case series in children. No comparative effectiveness trials have been performed in the pediatric population. Gaps in knowledge include risk factors for SE, biomarkers of SE and RCSE, second- and third-line treatment options, and long-term outcome. The care of children with RCSE is based on limited evidence. In order to address these knowledge gaps, the multicenter pSERG was established to facilitate prospective collection, analysis, and sharing of de-identified data and biological specimens from children with RCSE. These data will allow identification of treatment strategies associated with better outcomes and delineate evidence-based interventions to improve the care of children with SE. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Impact of Adjuvant Chemotherapy on Long-Term Employment of Early-Stage Breast Cancer Survivors

PubMed Central

Jagsi, Reshma; Hawley, Sarah T.; Abrahamse, Paul; Li, Yun; Janz, Nancy K.; Griggs, Jennifer J.; Bradley, Cathy; Graff, John J.; Hamilton, Ann S.; Katz, Steven J.

2014-01-01

Background Many women with early-stage breast cancer are working at the time of diagnosis and survive without recurrence. The short-term impact of chemotherapy receipt on employment has been demonstrated, but the long-term impact merits further research. Methods We conducted a longitudinal multicenter cohort study of women diagnosed with non-metastatic breast cancer in 2005–2007, as reported to the population-based Los Angeles and Detroit SEER registries. Of 3133 individuals sent surveys, 2290 (73%) completed a baseline survey soon after diagnosis and 1536 (68%) completed a four-year follow-up questionnaire. Results Of the 1026 patients aged <65 at diagnosis whose breast cancer did not recur and who responded to both surveys, 746 (76%) worked for pay before diagnosis. Of these, 236 (30%) were no longer working at follow-up. Women who received chemotherapy as part of initial treatment were less likely to work at follow-up (38% vs. 27%, p=0.003). Chemotherapy receipt at the time of diagnosis (OR 1.4, p=0.04) was independently associated with unemployment during survivorship in a multivariable model. Many women who were not employed in the survivorship period wanted to work: 50% reported that it was important for them to work and 31% were actively seeking work. Conclusions Unemployment among breast cancer survivors four years after diagnosis is often undesired and appears related to the receipt of chemotherapy during initial treatment. These findings should be considered when patients decide whether to receive adjuvant chemotherapy, particularly when expected benefit is low. PMID:24777606

Long-term forecasting and comparison of mortality in the Evaluation of the Xience Everolimus Eluting Stent vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial: prospective validation of the SYNTAX Score II.

PubMed

Campos, Carlos M; van Klaveren, David; Farooq, Vasim; Simonton, Charles A; Kappetein, Arie-Pieter; Sabik, Joseph F; Steyerberg, Ewout W; Stone, Gregg W; Serruys, Patrick W

2015-05-21

To prospectively validate the SYNTAX Score II and forecast the outcomes of the randomized Evaluation of the Xience Everolimus-Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) Trial. Evaluation of the Xience Everolimus Eluting Stent vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization is a prospective, randomized multicenter trial designed to establish the efficacy and safety of percutaneous coronary intervention (PCI) with the everolimus-eluting stent compared with coronary artery bypass graft (CABG) surgery in subjects with unprotected left-main coronary artery (ULMCA) disease and low-intermediate anatomical SYNTAX scores (<33). After completion of patient recruitment in EXCEL, the SYNTAX Score II was prospectively applied to predict 4-year mortality in the CABG and PCI arms. The 95% prediction intervals (PIs) for mortality were computed using simulation with bootstrap resampling (10 000 times). For the entire study cohort, the 4-year predicted mortalities were 8.5 and 10.5% in the PCI and CABG arms, respectively [odds ratios (OR) 0.79; 95% PI 0.43-1.50). In subjects with low (≤22) anatomical SYNTAX scores, the predicted OR was 0.69 (95% PI 0.34-1.45); in intermediate anatomical SYNTAX scores (23-32), the predicted OR was 0.93 (95% PI 0.53-1.62). Based on 4-year mortality predictions in EXCEL, clinical characteristics shifted long-term mortality predictions either in favour of PCI (older age, male gender and COPD) or CABG (younger age, lower creatinine clearance, female gender, reduced left ventricular ejection fraction). The SYNTAX Score II indicates at least an equipoise for long-term mortality between CABG and PCI in subjects with ULMCA disease up to an intermediate anatomical complexity. Both anatomical and clinical characteristics had a clear impact on long-term mortality predictions and decision making between CABG and PCI. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Calculation of multicenter electric field gradient integrals over Slater-type orbitals using unsymmetrical one-range addition theorems.

PubMed

Guseinov, Israfil I; Görgün, Nurşen Seçkin

2011-06-01

The electric field induced within a molecule by its electrons determines a whole series of important physical properties of the molecule. In particular, the values of the gradient of this field at the nuclei determine the interaction of their quadrupole moments with the electrons. Using unsymmetrical one-range addition theorems introduced by one of the authors, the sets of series expansion relations for multicenter electric field gradient integrals over Slater-type orbitals in terms of multicenter charge density expansion coefficients and two-center basic integrals are presented. The convergence of the series is tested by calculating concrete cases for different values of quantum numbers, parameters and locations of orbitals.

[Development and short-term effects of a standardized patient education program for in-patient cardiologic rehabilitation].

PubMed

Seekatz, B; Haug, G; Mosler, G; Schwaab, B; Altstidl, R; Worringen, U; Faller, H; Meng, K

2013-10-01

Patient education is an essential part in the treatment of coronary heart disease in medical rehabilitation. In the German-speaking area, no standardized and evaluated patient education program for coronary heart disease is available so far. In this paper, we demonstrate the development of a quality assured patient education program based on a health-education program of the German statutory pension insurance scheme. In a multi-level approach, an existing program was modified concerning treatment evidence, practical guidelines, theories of health and illness behavior and quality criteria for patient education as well as clinical experience and thereafter manualized. In a formative evaluation, feasibility and patient acceptance of this modified program were assessed using evaluation questionnaires of patients and trainers. Afterwards, effects of the patient education program as compared to a traditional education program were assessed on a short-term (at discharge), medium-term (6-month follow-up) and long-term (12-month follow-up) basis in a multicenter quasi-experimental control group study of patients with coronary heart disease (n=434). Results of the formative evaluation demonstrate an overall good acceptance and a good feasibility of the manualized program. Short-term results show a significant small treatment effect in the primary outcome variable patients' knowledge (p=0.001, η2 =0.028). Furthermore, small effects were also observed among some secondary outcomes, such as attitude towards medication, planning of physical activity, psychological quality of life and satisfaction with the education program. A standardized education program for patients with coronary heart disease has been developed in a systematic process based on established quality standards. Depending on the outstanding medium and long-term effects, the program may be recommended for general use in medical rehabilitation. The manual provides the prerequisites allowing for a successful transfer into clinical practice. © Georg Thieme Verlag KG Stuttgart · New York.

Impact of a Tutored Theoretical-Practical Training to Develop Undergraduate Students’ Skills for the Detection of Caries Lesions: Study Protocol for a Multicenter Controlled Randomized Study

PubMed Central

Ferreira, Fernanda Rosche; Mendes, Fausto Medeiros; Raggio, Daniela Prócida; Imparato, José Carlos; Bonecker, Marcelo; Magalhães, Ana Carolina; Wang, Linda; Rios, Daniela; Pessan, Juliano Pelim; Duque, Cristiane; Rebelo, Maria Augusta Bessa; Alves Filho, Ary Oliveira; Lima, Marina De Deus Moura; Moura, Marcoeli Silva; De Carli, Alessandro Diogo; Sanabe, Mariane Emi; Cenci, Maximiliano Sergio; Oliveira, Elenara Ferreira; Correa, Marcos Britto; Rocha, Rachel Oliveira; Zenkner, Julio Eduardo; Murisí, Pedroza Uribe; Martignon, Stefania; Lara, Juan Sebastian; Aquino, Fatima Gabriela; Carrillo, Alfredo; Chu, Chun Hung; Deery, Chris; Ricketts, David; Melo, Paulo; Antunes, José Leopoldo Ferreira; Ekstrand, Kim Rud

2017-01-01

Background Tutored laboratorial activities could be a manner of improving the competency development of students. However, its impact over conventional theoretical classes has not yet been tested. Additionally, different university contexts could influence this issue and should be explored. Objective To assess the impact of a tutored theoretical-practical training for teaching undergraduate students to detect caries lesions as compared with theoretical teaching activities. The impact of these teaching/learning activities will be assessed in terms of efficacy, cost/benefit, retention of knowledge/acquired competences, and student acceptability. Methods Sixteen centers (7 centers from Brazil and 9 centers from other countries throughout the world) are involved in the inclusion of subjects for this protocol. A randomized controlled study with parallel groups will be conducted. One group (control) will be exposed to a 60- to 90-minute conventional theoretical class and the other group (test) will be exposed to the same theoretical class and also a 90-minute laboratory class, including exercises and discussions based on the evaluation of a pool of images and extracted teeth. The mentioned outcomes will be evaluated immediately after the teaching activities and also in medium- and long-term analyses. To compare the long-term outcomes, students who enrolled in the university before the participating students will be interviewed for data collection and these data will be used as a control and compared with the trained group. This stage will be a nonrandomized phase of this study, nested in the main study. Appropriate statistical analysis will be performed according to the aims of this study. Variables related to the centers will also be analyzed and used to model adjustment as possible sources of variability among results. Results This ongoing study is funded by a Brazilian national funding agency (CNPq- 400736/2014-4). We expect that the tutored theoretical-practical training will improve the undergraduate students’ performance in the detection of caries lesions and subsequent treatment decisions, mainly in terms of long-term retention of knowledge. Our hypothesis is that tutored theoretical-practical training is a more cost-effective option for teaching undergraduate students to detect caries lesions. Conclusions If our hypothesis is confirmed, the use of laboratory training in conjunction with theoretical classes could be used as an educational strategy in Cariology to improve the development of undergraduate students’ skills in the detection of caries lesions and clinical decision-making. PMID:28814381

A phase 2, open-label, multicenter study of the long-term safety of siltuximab (an anti-interleukin-6 monoclonal antibody) in patients with multicentric Castleman disease.

PubMed

van Rhee, Frits; Casper, Corey; Voorhees, Peter M; Fayad, Luis E; van de Velde, Helgi; Vermeulen, Jessica; Qin, Xiang; Qi, Ming; Tromp, Brenda; Kurzrock, Razelle

2015-10-06

Multicentric Castleman disease (MCD) is a rare, systemic lymphoproliferative disorder driven by interleukin (IL)-6 overproduction. Siltuximab, an anti-IL-6 monoclonal antibody, has demonstrated durable tumor and symptomatic responses in a multinational, randomized, placebo-controlled study of MCD. This preplanned safety analysis was conducted to evaluate the long-term safety of siltuximab treatment among 19 patients with MCD who had stable disease or better and were enrolled in a phase-1 study and subsequent ongoing, open-label, phase-2 extension study. Dosing was 11 mg/kg administered intravenously every 3 weeks, per protocol, or every 6 weeks at the investigator's discretion. Safety monitoring focused on potential risks associated with the anti-IL-6 mechanism of action. Investigator-assessed disease control status was also documented. Median treatment duration for the 19 patients was 5.1 (range 3.4, 7.2) years, with 14 (74%) patients treated for >4 years. Grade-≥ 3 adverse events (AEs) reported in >1 patient included hypertension (n = 3) and nausea, cellulitis, and fatigue (n = 2 each). Grade-≥ 3 AEs at least possibly attributed to siltuximab were leukopenia, lymphopenia, and a serious AE of polycythemia (n = 1 each). Hypertriglyceridemia and hypercholesterolemia (total cholesterol) were reported in 8 and 9 patients, respectively. No disease relapses were observed, and 8 of 19 patients were able to switch to an every-6-week dosing schedule. All MCD patients in this extension study have received siltuximab for a prolonged duration (up to 7 years) without evidence of cumulative toxicity or treatment discontinuations and with few serious infections. All patients are alive, demonstrate sustained disease control, and continue to receive siltuximab.

GH treatment to final height produces similar height gains in patients with SHOX deficiency and Turner syndrome: results of a multicenter trial.

PubMed

Blum, Werner F; Ross, Judith L; Zimmermann, Alan G; Quigley, Charmian A; Child, Christopher J; Kalifa, Gabriel; Deal, Cheri; Drop, Stenvert L S; Rappold, Gudrun; Cutler, Gordon B

2013-08-01

Growth impairment in short stature homeobox-containing gene (SHOX) deficiency and Turner syndrome share a similar etiology. Because of the established effect of GH treatment on height in patients with Turner syndrome, we hypothesized that GH therapy would also stimulate growth in patients with SHOX deficiency. Our objectives were to evaluate long-term efficacy of GH treatment in short patients with SHOX deficiency and to compare the effect on final (adult) height (FH) in patients with SHOX deficiency and Turner syndrome. A prospective, multinational, open-label, randomized 3-arm study consisting of a 2-year control period and a subsequent extension period to FH. The treatment groups were 1) SHOX-D-C/GH (untreated during the control period, GH-treated during the extension), 2) SHOX-D-GH/GH, and 3) Turner-GH/GH (GH-treated during both study periods). Short-statured prepubertal patients with genetically confirmed SHOX deficiency (n = 49) or Turner syndrome (n = 24) who participated in the extension. Depending on the study arm, patients received a daily sc injection of 0.05 mg/kg recombinant human GH from start of the study or start of the extension until attainment of FH or study closure. Height SD score gain from start of GH treatment to FH was similar between the combined SHOX-deficient groups (n = 28, 1.34 ± 0.18 [least-squares mean ± SE]) and the Turner group (n = 19, 1.32 ± 0.22). In this FH population, 57% of the patients with SHOX deficiency and 32% of the patients with Turner syndrome achieved a FH greater than -2 SD score. GH treatment in short children with SHOX deficiency showed similar long-term efficacy as seen in girls with Turner syndrome.

Single-use autoinjector for once-weekly intramuscular injection of IFNβ-1a.

PubMed

Limmroth, Volker; Gerbershagen, Kathrin

2014-12-01

IFNβ products and glatiramer acetate are established treatment first-line options in long-term disease-modifying therapy of multiple sclerosis (MS). These self-injectable medications are used once weekly to once daily. Injection-related issues are common patient-cited reasons for nonadherence. Autoinjectors have been shown to support long-term adherence to injectable medications. The ability to self-inject in MS patients has been associated with a reduced risk of missed injections and drug discontinuation, and a beneficial effect on patient independence. The recently introduced easy-to-use prefilled once-weekly pen is a safe and effective device for intramuscular (IM) IFNβ-1a application and provides a convenient method for self-injection. We reviewed the available published evidence on the characteristics of this device. The once-weekly pen facilitates self-injection and was preferred over prefilled syringes by patients in a prospective open-label, multicenter Phase IIIb trial in MS patients who had been using IM IFNβ-1a in prefilled syringes. The simple and safe handling, shielded short needle, single-use disposable design and virtually painless injection by the device may contribute to adherence, quality of life and independence in patients using IM IFNβ-1a.

Feasibility of implementation of a "simplified, No-X-Ray, no-lead apron, two-catheter approach" for ablation of supraventricular arrhythmias in children and adults.

PubMed

Stec, Sebastian; Śledź, Janusz; Mazij, Mariusz; Raś, Małgorzata; Ludwik, Bartosz; Chrabąszcz, Michał; Śledź, Arkadiusz; Banasik, Małgorzata; Bzymek, Magdalena; Młynarczyk, Krzysztof; Deutsch, Karol; Labus, Michał; Śpikowski, Jerzy; Szydłowski, Lesław

2014-08-01

Although the "near-zero-X-Ray" or "No-X-Ray" catheter ablation (CA) approach has been reported for treatment of various arrhythmias, few prospective studies have strictly used "No-X-Ray," simplified 2-catheter approaches for CA in patients with supraventricular tachycardia (SVT). We assessed the feasibility of a minimally invasive, nonfluoroscopic (MINI) CA approach in such patients. Data were obtained from a prospective multicenter CA registry of patients with regular SVTs. After femoral access, 2 catheters were used to create simple, 3D electroanatomic maps and to perform electrophysiologic studies. Medical staff did not use lead aprons after the first 10 MINI CA cases. A total of 188 patients (age, 45 ± 21 years; 17% <19 years; 55% women) referred for the No-X-Ray approach were included. They were compared to 714 consecutive patients referred for a simplified approach using X-rays (age, 52 ± 18 years; 7% <19 years; 55% women). There were 9 protocol exceptions that necessitated the use of X-rays. Ultimately, 179/188 patients underwent the procedure without fluoroscopy, with an acute success rate of 98%. The procedure times (63 ± 26 vs. 63 ± 29 minutes, P > 0.05), major complications (0% vs. 0%, P > 0.05) and acute (98% vs. 98%, P > 0.05) and long-term (93% vs. 94%, P > 0.05) success rates were similar in the "No-X-Ray" and control groups. Implementation of a strict "No-X-Ray, simplified 2-catheter" CA approach is safe and effective in majority of the patients with SVT. This modified approach for SVTs should be prospectively validated in a multicenter study. © 2014 Wiley Periodicals, Inc.

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.

Ultrasonographic Changes at 12 Weeks of Anti-TNF Drugs Predict 1-year Sonographic Response and Clinical Outcome in Crohn's Disease: A Multicenter Study.

PubMed

Ripollés, Tomás; Paredes, José M; Martínez-Pérez, María J; Rimola, Jordi; Jauregui-Amezaga, Arantza; Bouzas, Rosa; Martin, Gregorio; Moreno-Osset, Eduardo

2016-10-01

The objective was to assess the long-term effect of biological treatment on transmural lesions of Crohn's disease evaluated with ultrasound, including contrast-enhanced ultrasound. Fifty-one patients with active Crohn's disease were included in a prospective multicenter longitudinal study. All patients underwent a clinical assessment and sonographic examination at baseline, 12 weeks after treatment initiation, and after 1-year of treatment. Patients were clinically followed at least 2 years from inclusion until the end of the study. Ultrasonographic evaluation included bowel wall thickness, color Doppler grade, parietal enhancement, and presence of transmural complications or stenosis. Sonographic changes after treatment were classified as normalization, improvement, or lack of response. Improvement at 52 weeks was more frequent in patients with improvement at final of induction (12 weeks) compared with patients who did not improve (85% versus 28%; P < 0.0001). One-year sonographic evolution correlated with clinical response; 28 of the 29 (96.5%) patients with sonographic improvement at 52 weeks showed clinical remission or response. Patients without sonographic improvement at 52 weeks of treatment were more likely to have a change or intensification in medication or surgery (13/20, 65%) during the next year of follow-up than patients with improvement on the sonography (3/28, 11%). Stricturing behavior was the only sonographic feature associated to a negative predictive value of response (P = 0.0001). Sonographic response after 12 weeks of therapy is more pronounced and predicts 1-year sonographic response. Sonographic response at 1-year examination correlates with 1-year clinical response and is a predictor of further treatment's efficacy, 1-year or longer period of follow-up.

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 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.

Long-Term Safety and Efficacy of Enzyme Replacement Therapyfor Fabry Disease

PubMed Central

Wilcox, William R.; Banikazemi, Maryam; Guffon, Nathalie; Waldek, Stephen; Lee, Philip; Linthorst, Gabor E.; Desnick, Robert J.; Germain, Dominique P.

2004-01-01

Elsewhere, we reported the safety and efficacy results of a multicenter phase 3 trial of recombinant human α-galactosidase A (rh-αGalA) replacement in patients with Fabry disease. All 58 patients who were enrolled in the 20-wk phase 3 double-blind, randomized, and placebo-controlled study received subsequently 1 mg/kg of rh-αGalA (agalsidase beta, Fabrazyme, Genzyme Corporation) biweekly in an ongoing open-label extension study. Evidence of long-term efficacy, even in patients who developed IgG antibodies against rh-αGalA, included the continuously normal mean plasma globotriaosylceramide (GL-3) levels during 30 mo of the extension study and the sustained capillary endothelial GL-3 clearance in 98% (39/40) of patients who had a skin biopsy taken after treatment for 30 mo (original placebo group) or 36 mo (original enzyme-treated group). The mean serum creatinine level and estimated glomerular filtration rate also remained stable after 30–36 mo of treatment. Infusion-associated reactions decreased over time, as did anti-rh-αGalA IgG antibody titers. Among seroconverted patients, after 30–36 mo of treatment, seven patients tolerized (no detectable IgG antibody), and 59% had ⩾4-fold reductions in antibody titers. As of 30 mo into the extension trial, three patients were withdrawn from the study because of positive serum IgE or skin tests; however, all have been rechallenged successfully at the time of this report. Thus, enzyme replacement therapy for 30–36 mo with agalsidase beta resulted in continuously decreased plasma GL-3 levels, sustained endothelial GL-3 clearance, stable kidney function, and a favorable safety profile. PMID:15154115

Long-term safety and efficacy of enzyme replacement therapy for Fabry disease.

PubMed

Wilcox, William R; Banikazemi, Maryam; Guffon, Nathalie; Waldek, Stephen; Lee, Philip; Linthorst, Gabor E; Desnick, Robert J; Germain, Dominique P

2004-07-01

Elsewhere, we reported the safety and efficacy results of a multicenter phase 3 trial of recombinant human alpha -galactosidase A (rh-alpha GalA) replacement in patients with Fabry disease. All 58 patients who were enrolled in the 20-wk phase 3 double-blind, randomized, and placebo-controlled study received subsequently 1 mg/kg of rh-alpha GalA (agalsidase beta, Fabrazyme, Genzyme Corporation) biweekly in an ongoing open-label extension study. Evidence of long-term efficacy, even in patients who developed IgG antibodies against rh- alpha GalA, included the continuously normal mean plasma globotriaosylceramide (GL-3) levels during 30 mo of the extension study and the sustained capillary endothelial GL-3 clearance in 98% (39/40) of patients who had a skin biopsy taken after treatment for 30 mo (original placebo group) or 36 mo (original enzyme-treated group). The mean serum creatinine level and estimated glomerular filtration rate also remained stable after 30-36 mo of treatment. Infusion-associated reactions decreased over time, as did anti-rh- alpha GalA IgG antibody titers. Among seroconverted patients, after 30-36 mo of treatment, seven patients tolerized (no detectable IgG antibody), and 59% had > or =4-fold reductions in antibody titers. As of 30 mo into the extension trial, three patients were withdrawn from the study because of positive serum IgE or skin tests; however, all have been rechallenged successfully at the time of this report. Thus, enzyme replacement therapy for 30-36 mo with agalsidase beta resulted in continuously decreased plasma GL-3 levels, sustained endothelial GL-3 clearance, stable kidney function, and a favorable safety profile.

Proton Pump Inhibitor Usage and the Risk of Mortality in Hemodialysis Patients.

PubMed

de Francisco, Angel L M; Varas, Javier; Ramos, Rosa; Merello, Jose Ignacio; Canaud, Bernard; Stuard, Stefano; Pascual, Julio; Aljama, Pedro

2018-03-01

Long-term inappropriate proton pump inhibitors use (PPIs) is a matter of concern because of the risks associated with their long-term use in older patients with chronic conditions. The risk of PPI treatment in hemodialysis patients remains unexplored. We assessed the relationship between the use of PPIs and the risk of death in hemodialysis patients throughout a retrospective multicenter propensity score-matched study. Information about demographic, hemodialysis treatment, laboratory data, and concomitant medication was obtained from the EuCliD database (Fresenius Medical Care). We studied 1776 hemodialysis patients on PPI therapy compared to 466 patients not receiving PPIs. The resulting population comprising 2 groups of 410 matched patients was studied. PPI use was associated with hypomagnesemia (Mg <1.8 mg/dl (0.75 mmol/l); odds ratio [OR] = 2.70, 95% confidence interval [CI] = 1.38-5.27, P  < 0.01). The exposure to PPIs in the full patient cohort was identified as an independent predictor for all-cause mortality in both univariate (HR = 3.16, 95% CI = 1.69-5.90, P  < 0.01) and multivariate (HR = 2.70, 95% CI = 1.38-5.27, P  < 0.01) Cox regression models. Moreover PPI use was identified as a predictor of CV mortality (HR = 1.51, 95% CI = 1.05-2.20, P  = 0.03) Of the 820 patients matched throughout the propensity score analysis, the hazard ratios for all-cause mortality (HR = 1.412, 95% CI = 1.04-1.93, P  = 0.03) and CV mortality (HR = 1.67, 95% CI = 1.03-2.71, P  = 0.04) were higher among patients on PPIs versus those not on PPIs. The study data suggest that the PPI treatment should be regularly monitored and prescribed only when indicated.

Long-term effect of epoetin alfa on clinical and biochemical markers in friedreich ataxia.

PubMed

Saccà, Francesco; Puorro, Giorgia; Marsili, Angela; Antenora, Antonella; Pane, Chiara; Casali, Carlo; Marcotulli, Christian; Defazio, Giovanni; Liuzzi, Daniele; Tatillo, Chiara; Cambriglia, Donata Maria; Schiano di Cola, Giuseppe; Giuliani, Luigi; Guardasole, Vincenzo; Salzano, Andrea; Ruvolo, Antonio; De Rosa, Anna; Cittadini, Antonio; De Michele, Giuseppe; Filla, Alessandro

2016-05-01

Friedreich ataxia is an autosomal recessive disease with no available therapy. Clinical trials with erythropoietin in Friedreich ataxia patients have yielded conflicting results, and the long-term effect of the drug remains unknown. We designed a double-blind, placebo-controlled, multicenter trial to test the efficacy of epoetin alfa on 56 patients with Friedreich ataxia. The primary endpoint of the study was the effect of epoetin alfa on peak oxygen uptake (VO2 max) at the cardiopulmonary exercise test. Secondary endpoints were frataxin levels in peripheral blood mononuclear cells, improvement in echocardiography findings, vascular reactivity, neurological progression, upper limb dexterity, safety, and quality of life. Epoetin alfa or placebo (1:1 ratio) was administered subcutaneously at a dose of 1200 IU/Kg of body weight every 12 weeks for 48 weeks. A total of 56 patients were randomized; 27 completed the study in the active treatment group, and 26 completed the study in the placebo group[KG1]. VO2 max was not modified after treatment (0.01 [-0.04 to 0.05]; P = .749), as well as most of the secondary endpoint measures, including frataxin. The 9-hole peg test showed a significant amelioration in the treatment group (-17.24 sec. [-31.5 to -3.0]; P = .018). The treatment was safe and well tolerated. Although results are not in favor of an effect of epoetin alfa in Friedreich ataxia, this is the largest trial testing its effect. It is still possible that epoetin alfa may show some symptomatic effect on upper-limb performance. This study provides class I evidence that erythropoietin does not ameliorate VO2 max in patients with Friedreich ataxia. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Lurasidone for the Treatment of Irritability Associated with Autistic Disorder

ERIC Educational Resources Information Center

Loebel, Antony; Brams, Matthew; Goldman, Robert S.; Silva, Robert; Hernandez, David; Deng, Ling; Mankoski, Raymond; Findling, Robert L.

2016-01-01

The aim of this study was to evaluate the short-term efficacy and safety of lurasidone in treating irritability associated with autistic disorder. In this multicenter trial, outpatients age 6-17 years who met DSM-IV-TR criteria for autistic disorder, and who demonstrated irritability, agitation, and/or self-injurious behaviors were randomized to…

Platelet-Derived Growth Factor Promotes Periodontal Regeneration in Localized Osseous Defects: 36-Month Extension Results From a Randomized, Controlled, Double-Masked Clinical Trial

PubMed Central

Nevins, Myron; Kao, Richard T.; McGuire, Michael K.; McClain, Pamela K.; Hinrichs, James E.; McAllister, Bradley S.; Reddy, Michael S.; Nevins, Marc L.; Genco, Robert J.; Lynch, Samuel E.; Giannobile, William V.

2017-01-01

Background Recombinant human platelet-derived growth factor (rhPDGF) is safe and effective for the treatment of periodontal defects in short-term studies up to 6 months in duration. We now provide results from a 36-month extension study of a multicenter, randomized, controlled clinical trial evaluating the effect and long-term stability of PDGF-BB treatment in patients with localized severe periodontal osseous defects. Methods A total of 135 participants were enrolled fromsix clinical centers for an extension trial. Eighty-three individuals completed the study at 36 months and were included in the analysis. The study investigated the local application of β-tricalcium phosphate scaffold matrix with or without two different dose levels of PDGF (0.3 or 1.0 mg/mL PDGF-BB) in patients possessing one localized periodontal osseous defect. Composite analysis for clinical and radiographic evidence of treatment success was defined as percentage of cases with clinical attachment level (CAL) ≥2.7mmand linear bone growth (LBG) ≥1.1 mm. Results The participants exceeding this composite outcome benchmark in the 0.3 mg/mL rhPDGF-BB group went from 62.2% at 12 months, 75.9% at 24 months, to 87.0% at 36 months compared with 39.5%, 48.3%, and 53.8%, respectively, in the scaffold control group at these same time points (P <0.05). Although there were no significant increases in CAL and LBG at 36 months among all groups, there were continued increases in CAL gain, LBG, and percentage bone fill over time, suggesting overall stability of the regenerative response. Conclusion PDGF-BB in a synthetic scaffold matrix promotes long-term stable clinical and radiographic improvements as measured by composite outcomes for CAL gain and LBG for patients possessing localized periodontal defects (ClinicalTrials.gov no. CT01530126). PMID:22612364

Incidence of Extrusion Following Type I Polypropylene Mesh “Kit” Repairs in the Correction of Pelvic Organ Prolapse

PubMed Central

Lukban, James C.; Beyer, Roger D.; Moore, Robert D.

2012-01-01

Introduction and Hypothesis. We sought to determine the mesh extrusion (vaginal exposure) rates and subject outcomes following IntePro (Type I polypropylene) mesh “kit” repairs for vaginal prolapse. Methods. Data were pooled from two prospective multicenter studies evaluating the safety and efficacy of the Perigee and Apogee (American Medical Systems, Minnetonka, Minn, USA) to treat anterior and posterior/apical prolapses, respectively. Extrusions involving the anterior compartment (AC) or posterior compartment/apex (PC/A) were recorded. Results. Two hundred sixty women underwent mesh placement, with a total of 368 mesh units inserted (173 in the AC and 195 in the PC/A). Extrusions were noted in 13 (7.5%) of AC implants and 27 (13.8%) of PC/A implants through 12 months. No difference was seen between those with and without extrusion in regard to anatomic cure, postoperative painor quality of life at 1 year. Conclusions. Extrusion had no apparent effect on short-term outcomes. Given the unknown long-term sequellae of vaginal mesh exposure, a thorough assessment of risks and benefits of transvaginal mesh placement should be considered at the time of preoperative planning. PMID:22190952

Target Selection Recommendations Based on Impact of Deep Brain Stimulation Surgeries on Nonmotor Symptoms of Parkinson's Disease

PubMed Central

Wang, Xiao-Hong; Zhang, Lin; Sperry, Laura; Olichney, John; Farias, Sarah Tomaszewski; Shahlaie, Kiarash; Chang, Norika Malhado; Liu, Ying; Wang, Su-Ping; Wang, Cui

2015-01-01

Objective: This review examines the evidence that deep brain stimulation (DBS) has extensive impact on nonmotor symptoms (NMSs) of patients with Parkinson's disease (PD). Data Sources: We retrieved information from the PubMed database up to September, 2015, using various search terms and their combinations including PD, NMSs, DBS, globus pallidus internus (GPi), subthalamic nucleus (STN), and ventral intermediate thalamic nucleus. Study Selection: We included data from peer-reviewed journals on impacts of DBS on neuropsychological profiles, sensory function, autonomic symptoms, weight changes, and sleep disturbances. For psychological symptoms and cognitive impairment, we tried to use more reliable proofs: Random, control, multicenter, large sample sizes, and long period follow-up clinical studies. We categorized the NMSs into four groups: those that would improve definitively following DBS; those that are not significantly affected by DBS; those that remain controversial on their surgical benefit; and those that can be worsened by DBS. Results: In general, it seems to be an overall beneficial effect of DBS on NMSs, such as sensory, sleep, gastrointestinal, sweating, cardiovascular, odor, urological symptoms, and sexual dysfunction, GPi-DBS may produce similar results; Both STN and Gpi-DBS are safe with regard to cognition and psychology over long-term follow-up, though verbal fluency decline is related to DBS; The impact of DBS on behavioral addictions and dysphagia is still uncertain. Conclusions: As the motor effects of STN-DBS and GPi-DBS are similar, NMSs may determine the target choice in surgery of future patients. PMID:26668154

Neuroendocrine Disturbances One to Five or More Years after Traumatic Brain Injury and Aneurysmal Subarachnoid Hemorrhage: Data from the German Database on Hypopituitarism.

PubMed

Krewer, Carmen; Schneider, Manfred; Schneider, Harald Jörn; Kreitschmann-Andermahr, Ilonka; Buchfelder, Michael; Faust, Michael; Berg, Christian; Wallaschofski, Henri; Renner, Caroline; Uhl, Eberhard; Koenig, Eberhard; Jordan, Martina; Stalla, Günter Karl; Kopczak, Anna

2016-08-15

Neuroendocrine disturbances are common after traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH), but only a few data exist on long-term anterior pituitary deficiencies after brain injury. We present data from the Structured Data Assessment of Hypopituitarism after TBI and SAH, a multi-center study including 1242 patients. We studied a subgroup of 351 patients, who had sustained a TBI (245) or SAH (106) at least 1 year before endocrine assessment (range 1-55 years) in a separate analysis. The highest prevalence of neuroendocrine disorders was observed 1-2 years post-injury, and it decreased over time only to show another maximum in the long-term phase in patients with brain injury occurring ≥5 years prior to assessment. Gonadotropic and somatotropic insufficiencies were most common. In the subgroup from 1 to 2 years after brain injury (n = 126), gonadotropic insufficiency was the most common hormonal disturbance (19%, 12/63 men) followed by somatotropic insufficiency (11.5%, 7/61), corticotropic insufficiency (9.2%, 11/119), and thyrotropic insufficiency (3.3%, 4/122). In patients observed ≥ 5 years after brain injury, the prevalence of somatotropic insufficiency increased over time to 24.1%, whereas corticotropic and thyrotrophic insufficiency became less frequent (2.5% and 0%, respectively). The prevalence differed regarding the diagnostic criteria (laboratory values vs. physician`s diagnosis vs. stimulation tests). Our data showed that neuroendocrine disturbances are frequent even years after TBI or SAH, in a cohort of patients who are still on medical treatment.

Influence of educational attainments on long term glucose control and morbid events in patients with type 2 diabetes receiving integrated care from 15 China urban communities: The Beijing Community Diabetes Study 11.

PubMed

Yang, Guang-Ran; Yuan, Shen-Yuan; Fu, Han-Jing; Wan, Gang; Zhu, Liang-Xiang; Yuan, Ming-Xia; Lv, Yu-Jie; Zhang, Jian-Dong; Du, Xue-Ping; Li, Yu-Ling; Ji, Yu; Zhou, Li; Li, Yue

2015-12-01

To investigate the effects of educational attainment on glucose control and morbid events in patients with type 2 diabetes in Beijing communities. In this prospective multi-center study, 2866 type 2 diabetes patients receiving integrated care from 15 Beijing urban communities were investigated. Educational attainment was categorized into three levels: low, medium, and high. After a 42-month management, glucose control parameters and morbid events were analyzed. At baseline, the percentages of patients with good glucose control (HbA1c ≤ 7.0%) in the low, medium and high educational groups were 49.09%, 54.82% and 62.59%, respectively (P<0.001). After the 42-month management, fasting plasma glucose and HbA1c values were the highest in the low educational group (7.51 ± 2.05 mmol/l and 7.20 ± 1.27%, respectively). Percentages of patients with good glucose control in the three groups were 49.6%, 55.83% and 67.23%, respectively, and the incidences of combined morbid events were 4.5%, 2.4% and 1.5%, respectively. Cox regression analysis showed that educational level was related to the incidence of combined morbid events (medium level, HR=0.572; high level, HR=0.351; P<0.05). Educational level was associated with long-term glucose control, and seemed to be related to the incidence of combined morbid events in people with type 2 diabetes. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Multicenter evaluation of quality of life and patient satisfaction after breast reconstruction, a long-term retrospective study.

PubMed

Ménez, T; Michot, A; Tamburino, S; Weigert, R; Pinsolle, V

2018-04-01

Breast reconstruction techniques are multiple and they should be chosen in order to improve women's satisfaction and well-being, thus obtaining a personalized treatment. This report's major purpose was to study, through the Breast-Q questionnaire, how the functional and aesthetic outcomes, as well as the complications, of the main autologous breast reconstruction techniques, can affect patients quality of life and well-being at long-term. The secondary purpose was to analyse, thus to identify, the independent factors characterizing the different reconstructive techniques, which may affect patients' satisfaction. Women who underwent autologous breast reconstruction through deep inferior epigastric artery perforator or Latissimus dorsi muscle flap from May 2006 to May 2013 were included. The assessment was based on the Breast-Q reconstruction questionnaire. All times of post-mastectomy reconstruction were concerned: immediate, delayed, after previous procedure failure or conversion to another reconstructive technique due to the patient's dissatisfaction. A total of 98 patients were included. Concerning patients satisfaction, the breast-Q score is highest in patients who underwent immediate breast reconstruction, while scores after delayed breast reconstruction, previous surgery failure or conversion to another technique are generally equivalent. Higher scores have been observed in patients who underwent reconstruction through autologous Latissimus dorsi compared to Latissimus dorsi with prosthetic implant reconstruction. The authors identified factors of higher patients' satisfaction, like absence of major complication and advanced patient's age, in order to personalize the surgical planning according to the patient's priorities. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The cost-effectiveness of a new percutaneous ventricular assist device for high-risk PCI patients: mid-stage evaluation from the European perspective.

PubMed

Roos, Johanna B; Doshi, Sagar N; Konorza, Thomas; Palacios, Igor; Schreiber, Ted; Borisenko, Oleg V; Henriques, Jose P S

2013-01-01

A new and smaller percutaneous ventricular assist device (pVAD, Impella, Abiomed, Danvers, MA) has been developed to provide circulatory support in hemodynamically unstable patients and to prevent hemodynamic collapse during high-risk percutaneous coronary interventions (PCI). The objective of the study was to assess the cost-effectiveness of this specific device compared to the intra-aortic balloon pump (IABP) from the European perspective. Additional analysis on extracorporeal membrane oxygenation was conducted for observational purposes only, given its use in some European countries. A combination of a decision tree and Markov model was developed to assess the cost-effectiveness of the small, pVAD. The short-term (30-day) effectiveness and safety (early survival, risk of bleeding, and stroke) were modeled, as well as long-term risk of major adverse cardiovascular events (recurrent myocardial infarction, stroke, and heart failure). The short-term effectiveness and safety data for the device were obtained from two registries (the Europella and USpella), both of which are large multi-center studies in high-risk patient groups. Probabilities of long-term major adverse cardiovascular events were obtained from various published clinical studies. The economic analysis was conducted from a German statutory health insurance perspective and only direct medical costs were included. Cost-effectiveness was estimated over a 10-year time horizon. Compared with IABP, the pVAD generated an incremental quality-adjusted life-year (QALY) of 0.22 (with Euro-registry data) and 0.27 (with US-registry data). The incremental cost-effectiveness ratio (ICER) of the device varied between €38,069 (with Euro-registry data) and €31,727 (with US-registry data) per QALY compared with IABP. Unadjusted, indirect comparisons of short-term effectiveness and safety between the interventions were used in the model. Cost and utility data were retrieved from various sources. Therefore, differences in patient populations may bias the estimated cost-effectiveness. Compared with IABP, the pVAD is a cost-effective intervention for high-risk PCI patients, with ICERs well-below the conventional cost-effectiveness threshold.

Congenital H-type tracheoesophageal fistula: A multicenter review of outcomes in a rare disease.

PubMed

Fallon, Sara C; Langer, Jacob C; St Peter, Shawn D; Tsao, KuoJen; Kellagher, Caroline M; Lal, Dave R; Whitehouse, Jill S; Diesen, Diana L; Rollins, Michael D; Pontarelli, Elizabeth; Malek, Marcus M; Iqbal, Corey W; Upperman, Jeffrey S; Leys, Charles M; Wulkan, Mark L; Hill, Sarah J; Blakely, Martin L; Kane, Timothy D; Wesson, David E

2017-11-01

To perform a multicenter review of outcomes in patients with H-type tracheoesophageal fistula (TEF) in order to better understand the incidence and causes of post-operative complications. H-type TEF without esophageal atresia (EA) is a rare anomaly with a fundamentally different management algorithm than the more common types of EA/TEF. Outcomes after surgical treatment of H-type TEF are largely unknown, but many authoritative textbooks describe a high incidence of respiratory complications. A multicenter retrospective review of all H-type TEF patients treated at 14 tertiary children's hospital from 2002-2012 was performed. Data were systematically collected concerning associated anomalies, operative techniques, hospital course, and short and long-term outcomes. Descriptive analyses were performed. We identified 102 patients (median 9.5 per center, range 1-16) with H-type TEF. The overall survival was 97%. Most patients were repaired via the cervical approach (96%). The in-hospital complication rate, excluding vocal cord issues, was 16%; this included an 8% post-operative leak rate. Twenty-two percent failed initial extubation after repair. A total of 22% of the entire group had vocal cord abnormalities (paralysis or paresis) on laryngoscopy that were likely because of recurrent laryngeal nerve injury. Nine percent required a tracheostomy. Only 3% had a recurrent fistula, all of which were treated with reoperation. There is a high rate of recurrent laryngeal nerve injury after H-type TEF repair. This underscores the need for meticulous surgical technique at the initial repair and suggests that early vocal cord evaluation should be performed for any post-operative respiratory difficulty. Routine evaluation of vocal cord function after H-type TEF repair should be considered. Level IV. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy of a Computer-Assisted Cognitive Rehabilitation Intervention in Relapsing-Remitting Multiple Sclerosis Patients: A Multicenter Randomized Controlled Trial

PubMed Central

Kosmidis, Mary H.; Zampakis, Petros; Malefaki, Sonia; Ntoskou, Katerina; Nousia, Anastasia; Bakirtzis, Christos; Papathanasopoulos, Panagiotis

2017-01-01

Cognitive impairment is frequently encountered in multiple sclerosis (MS) affecting between 40–65% of individuals, irrespective of disease duration and severity of physical disability. In the present multicenter randomized controlled trial, fifty-eight clinically stable RRMS patients with mild to moderate cognitive impairment and relatively low disability status were randomized to receive either computer-assisted (RehaCom) functional cognitive training with an emphasis on episodic memory, information processing speed/attention, and executive functions for 10 weeks (IG; n = 32) or standard clinical care (CG; n = 26). Outcome measures included a flexible comprehensive neuropsychological battery of tests sensitive to MS patient deficits and feedback regarding personal benefit gained from the intervention on four verbal questions. Only the IG group showed significant improvements in verbal and visuospatial episodic memory, processing speed/attention, and executive functioning from pre - to postassessment. Moreover, the improvement obtained on attention was retained over 6 months providing evidence on the long-term benefits of this intervention. Group by time interactions revealed significant improvements in composite cognitive domain scores in the IG relative to the demographically and clinically matched CG for verbal episodic memory, processing speed, verbal fluency, and attention. Treated patients rated the intervention positively and were more confident about their cognitive abilities following treatment. PMID:29463950

Long-Term Outcomes of Stenting the Proximal Left Anterior Descending Artery in the PROTECT Trial.

PubMed

Roguin, Ariel; Camenzind, Edoardo; Kerner, Arthur; Beyar, Rafael; Boersma, Eric; Mauri, Laura; Steg, Ph Gabriel; Wijns, William

2017-03-27

This study sought to compare the outcomes of patients undergoing drug-eluting stent implantation according to lesion location within or outside the proximal left anterior descending (LAD) artery. Proximal LAD artery involvement is considered uniquely in revascularization guidelines. The impact of LAD lesion location on long-term outcomes after revascularization is poorly understood in context of current percutaneous coronary intervention and medical therapy. Among 8,709 patients enrolled in PROTECT (Patient Related Outcomes with Endeavor Versus Cypher Stenting Trial), a multicenter percutaneous coronary intervention trial, we compared the outcomes of 2,534 patients (29.1%) (3,871 lesions [31.5%]) with stents implanted in the proximal LAD to 6,172 patients (70.9%) (8,419 lesions [68.5%]) with stents implanted outside the proximal LAD. At the 4-year follow-up, death rates were the same (5.8% vs. 5.8%; p > 0.999), but more myocardial infarctions occurred in the proximal LAD group (6.2% vs. 4.9%; p = 0.015). The rate of clinically driven target vessel failure (TVF) (14.8% vs. 13.5%; p = 0.109), major adverse cardiac event(s) (MACE) (15.0% vs. 13.7%; hazard ratio: 1.1; 95% confidence interval: 0.97 to 1.31; p = 0.139), and stent thrombosis (2.1% vs. 2.0%; p = 0.800) were similar. Drug-eluting stent type had no interaction with MACE or TVF. In multivariate analysis, the proximal LAD was a predictor of myocardial infarction (p = 0.038) but not of TVF (p = 0.149) or MACE (p = 0.069). In this study of contemporary percutaneous coronary intervention, proximal LAD location was associated with higher rates of myocardial infarction during the long-term follow-up, but there were no differences in stent thrombosis, death, TVF, or overall MACE. This finding may suggest that, in the drug-eluting stent era, proximal LAD no longer confers a different prognosis than other lesion sites. (Randomized Study Comparing Endeavor With Cypher Stents [PROTECT]; NCT00476957). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Target Selection Recommendations Based on Impact of Deep Brain Stimulation Surgeries on Nonmotor Symptoms of Parkinson's Disease.

PubMed

Wang, Xiao-Hong; Zhang, Lin; Sperry, Laura; Olichney, John; Farias, Sarah Tomaszewski; Shahlaie, Kiarash; Chang, Norika Malhado; Liu, Ying; Wang, Su-Ping; Wang, Cui

2015-12-20

This review examines the evidence that deep brain stimulation (DBS) has extensive impact on nonmotor symptoms (NMSs) of patients with Parkinson's disease (PD). We retrieved information from the PubMed database up to September, 2015, using various search terms and their combinations including PD, NMSs, DBS, globus pallidus internus (GPi), subthalamic nucleus (STN), and ventral intermediate thalamic nucleus. We included data from peer-reviewed journals on impacts of DBS on neuropsychological profiles, sensory function, autonomic symptoms, weight changes, and sleep disturbances. For psychological symptoms and cognitive impairment, we tried to use more reliable proofs: Random, control, multicenter, large sample sizes, and long period follow-up clinical studies. We categorized the NMSs into four groups: those that would improve definitively following DBS; those that are not significantly affected by DBS; those that remain controversial on their surgical benefit; and those that can be worsened by DBS. In general, it seems to be an overall beneficial effect of DBS on NMSs, such as sensory, sleep, gastrointestinal, sweating, cardiovascular, odor, urological symptoms, and sexual dysfunction, GPi-DBS may produce similar results; Both STN and Gpi-DBS are safe with regard to cognition and psychology over long-term follow-up, though verbal fluency decline is related to DBS; The impact of DBS on behavioral addictions and dysphagia is still uncertain. As the motor effects of STN-DBS and GPi-DBS are similar, NMSs may determine the target choice in surgery of future patients.

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

Neonatal posthemorrhagic hydrocephalus from prematurity: pathophysiology and current treatment concepts

PubMed Central

Robinson, Shenandoah

2013-01-01

Object Preterm infants are at risk for perinatal complications, including germinal matrix–intraventricular hemorrhage (IVH) and subsequent posthemorrhagic hydrocephalus (PHH). This review summarizes the current understanding of the epidemiology, pathophysiology, management, and outcomes of IVH and PHH in preterm infants. Methods The MEDLINE database was systematically searched using terms related to IVH, PHH, and relevant neurosurgical procedures to identify publications in the English medical literature. To complement information from the systematic search, pertinent articles were selected from the references of articles identifed in the initial search. Results This review summarizes the current knowledge regarding the epidemiology and pathophysiology of IVH and PHH, primarily using evidence-based studies. Advances in obstetrics and neonatology over the past few decades have contributed to a marked improvement in the survival of preterm infants, and neurological morbidity is also starting to decrease. The incidence of IVH is declining, and the incidence of PHH will likely follow. Currently, approximately 15% of preterm infants who suffer severe IVH will require permanent CSF diversion. The clinical presentation and surgical management of symptomatic PHH with temporary ventricular reservoirs (ventricular access devices) and ventriculosubgaleal shunts and permanent ventriculoperitoneal shunts are discussed. Preterm infants who develop PHH that requires surgical treatment remain at high risk for other related neurological problems, including cerebral palsy, epilepsy, and cognitive and behavioral delay. This review highlights numerous opportunities for further study to improve the care of these children. Conclusions A better grasp of the pathophysiology of IVH is beginning to impact the incidence of IVH and PHH. Neonatologists conduct rigorous Class I and II studies to advance the outcomes of preterm infants. The need for well-designed multicenter trials is essential because of the declining incidence of IVH and PHH, variations in referral patterns, and neonatal ICU and neurosurgical management. Well-designed multicenter trials will eventually produce evidence to enable neurosurgeons to provide their smallest, most vulnerable patients with the best practices to minimize perioperative complications and permanent shunt dependence, and most importantly, optimize long-term neurodevelopmental outcomes. (http://thejns.org/doi/abs/10.3171/2011.12.PEDS11136) PMID:22380952

Urinary biomarkers may provide prognostic information for subclinical acute kidney injury after cardiac surgery.

PubMed

Albert, Christian; Albert, Annemarie; Kube, Johanna; Bellomo, Rinaldo; Wettersten, Nicholas; Kuppe, Hermann; Westphal, Sabine; Haase, Michael; Haase-Fielitz, Anja

2018-06-01

This study aimed to determine the biomarker-specific outcome patterns and short-and long-term prognosis of cardiac surgery-asoociated acute kidney injury (AKI) identified by standard criteria and/or urinary kidney biomarkers. Patients enrolled (N = 200), originated a German multicenter study (NCT00672334). Standard risk injury, failure, loss, and end-stage renal disease classification (RIFLE) criteria (including serum creatinine and urine output) and urinary kidney biomarker test result (neutrophil gelatinase-associated lipocalin, midkine, interleukin 6, and proteinuria) were used for diagnosis of postoperative AKI. Primary end point was acute renal replacement therapy or in-hospital mortality. Long-term end points among others included 5-year mortality. Patients with single-biomarker-positive subclinical AKI (RIFLE negative) were identified. We controlled for systemic inflammation using C-reactive protein test. Urinary biomarkers (neutrophil gelatinase-associated lipocalin, midkine, and interleukin 6) were identified as independent predictors of the primary end point. Neutrophil gelatinase-associated lipocalin, midkine, or interleukin 6 positivity or de novo/worsening proteinuria identified 21.1%, 16.9%, 30.5%, and 48.0% more cases, respectively, with likely subclinical AKI (biomarker positive/RIFLE negative) additionally to cases with RIFLE positivity alone. Patients with likely subclinical AKI (neutrophil gelatinase-associated lipocalin or interleukin 6 positive) had increased risk of primary end point (adjusted hazard ratio, 7.18; 95% confidence interval, 1.52-33.93 [P = .013] and hazard ratio, 6.27; 95% confidence interval, 1.12-35.21 [P = .037]), respectively. Compared with biomarker-negative/RIFLE-positive patients, neutrophil gelatinase-associated lipocalin positive/RIFLE-positive or midkine-positive/RIFLE-positive patients had increased risk of primary end point (odds ratio, 9.6; 95% confidence interval, 1.4-67.3 [P = .033] and odds ratio, 14.7; 95% confidence interval, 2.0-109.2 [P = .011], respectively). Three percent to 11% of patients appear to be influenced by single-biomarker-positive subclinical AKI. During follow-up, kidney biomarker-defined short-term outcomes appeared to translate into long-term outcomes. Urinary kidney biomarkers identified RIFLE-negative patients with high-risk subclinical AKI as well as a higher risk subgroup of patients among RIFLE-AKI-positive patients. These findings support the concept that urinary biomarkers define subclinical AKI and higher risk subpopulations with worse long-term prognosis among standard patients with AKI. Copyright © 2017 The American Association for Thoracic Surgery. All rights reserved.

Long-term outcomes of fertility-sparing treatment of atypical polypoid adenomyoma with medroxyprogesterone acetate.

PubMed

Nomura, Hidetaka; Sugiyama, Yuko; Tanigawa, Terumi; Matoda, Maki; Kanao, Hiroyuki; Kondo, Eiji; Takeshima, Nobuhiro

2016-01-01

Our objective was to analyze the long-term oncologic outcomes of fertility-preserving hormonal treatment with medroxyprogesterone acetate (MPA) in patients with APA. In a retrospective chart review, we identified patients with APA who were treated with MPA for fertility preservation at our hospital between 2001 and 2011. Eighteen patients with histologically diagnosed APA were identified. Clinical data including treatment, obstetrical, and oncologic outcomes were recorded. The mean observation period was 77.6 months (median 73.5, range 22-142), and the mean age was 33.6 years. Four patients also developed well-differentiated endometrial carcinoma. After the treatment, 14 patients (77.8 %) achieved either a complete response or partial response. Eight patients experienced recurrence, while four experienced persistent disease. Ten patients (55.6 %) eventually underwent hysterectomy. The median time to hysterectomy was 40.3 months (range 24-68). Nine patients progressed to endometrial cancer, and one experienced persistent APA. Among younger patients (<35 years of age), four out of five patients who were married could have children. Seven patients (38.9 %) showed no evidence of the disease during the observation period (median 60 months, range 22-117 months). No one died because of the disease during the observation period. MPA yields a high response rate in APA, and if only younger patients are considered, a favorable pregnancy rate can be obtained. However, because recurrence rate is high, long-term follow-up under supervision of a trained gynecologic oncologist is required. To confirm MPA's utility, multi-center collaboration would be warranted.

Caregiver Ratings of Long-term Executive Dysfunction and Attention Problems After Early Childhood Traumatic Brain Injury: Family Functioning Is Important

PubMed Central

Kurowski, Brad G.; Taylor, H. Gerry; Yeates, Keith Owen; Walz, Nicolay C.; Stancin, Terry; Wade, Shari L.

2013-01-01

Objective To evaluate the relationship of family and parenting factors to long-term executive dysfunction and attention problems after early childhood traumatic brain injury (TBI). We hypothesized that the magnitude of executive dysfunction and attention problems would be moderated by family and parenting factors. Design A multicenter, prospective cohort study that included an orthopedic injury (OI) reference group. Setting Three tertiary academic children’s hospital medical centers and one general medical center. Participants Children, ages 3–7 years, hospitalized for OI, moderate TBI, or severe TBI. Methods and Outcome Measurements Parental ratings of family functioning and parenting styles were obtained 18 months after the injury occurred. The main outcome measurements, which were parental ratings of children’s executive function and attention, were performed at least 24 months after the injury occurred (mean, 39 months; range, 25–63 months). Analysis Group comparisons were conducted with use of t-tests, χ2 analysis, analysis of variance, and Pearson and Spearman correlations. Regression analysis was used to examine associations of the outcomes with family functioning and parenting styles and to test moderating effects of these factors on group differences. Results Participants with severe TBI demonstrated increased executive dysfunction and attention problems compared with those who sustained moderate TBI or OI. Lower levels of family dysfunction were associated with better executive function and attention across groups but did not moderate group differences. However, attention deficits after severe TBI were exacerbated under conditions of more permissive parenting relative to attention deficits after OIs. Conclusions Executive function and attention problems persisted on a long-term basis (>24 months) after early childhood TBI, and positive global family functioning and nonpermissive parenting were associated with better outcomes. Better characterization of the optimal family environment for recovery from early childhood TBI could help target future interventions. PMID:21944301

Effect of Bone Marrow-Derived Mononuclear Cell Treatment, Early or Late After Acute Myocardial Infarction: Twelve Months CMR and Long-Term Clinical Results.

PubMed

Sürder, Daniel; Manka, Robert; Moccetti, Tiziano; Lo Cicero, Viviana; Emmert, Maximilian Y; Klersy, Catherine; Soncin, Sabrina; Turchetto, Lucia; Radrizzani, Marina; Zuber, Michel; Windecker, Stephan; Moschovitis, Aris; Bühler, Ines; Kozerke, Sebastian; Erne, Paul; Lüscher, Thomas F; Corti, Roberto

2016-07-22

Intracoronary delivery of autologous bone marrow-derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction (AMI). To demonstrate long-term efficacy of BM-MNC treatment after AMI. In a multicenter study, we randomized 200 patients with large AMI in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were either administered 5 to 7 days (early) or 3 to 4 weeks (late) after AMI. Cardiac magnetic resonance imaging was performed at baseline and after 12 months. The current analysis investigates the change from baseline to 12 months in global LV ejection fraction, LV volumes, scar size, and N-terminal pro-brain natriuretic peptide values comparing the 2 treatment groups with control in a linear regression model. Besides the complete case analysis, multiple imputation analysis was performed to address for missing data. Furthermore, the long-term clinical event rate was computed. The absolute change in LV ejection fraction from baseline to 12 months was -1.9±9.8% for control (mean±SD), -0.9±10.5% for the early treatment group, and -0.7±10.1% for the late treatment group. The difference between the groups was not significant, both for complete case analysis and multiple imputation analysis. A combined clinical end point occurred equally in all the groups. Overall, 1-year mortality was low (2.25%). Among patients with AMI and LV dysfunction, treatment with BM-MNC either 5 to 7 days or 3 to 4 weeks after AMI did not improve LV function at 12 months, compared with control. The results are limited by an important drop out rate. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186. © 2016 American Heart Association, Inc.

Long-term durability of sacral nerve stimulation therapy for chronic fecal incontinence.

PubMed

Hull, Tracy; Giese, Chad; Wexner, Steven D; Mellgren, Anders; Devroede, Ghislain; Madoff, Robert D; Stromberg, Katherine; Coller, John A

2013-02-01

Limited data have been published regarding the long-term results of sacral nerve stimulation, or sacral neuromodulation, for severe fecal incontinence. The aim was to assess the outcome of sacral nerve stimulation with the use of precise tools and data collection, focusing on the long-term durability of the therapy. Five-year data were analyzed. Patients entered in a multicenter, prospective study for fecal incontinence were followed at 3, 6, and 12 months and annually after device implantation. Patients with chronic fecal incontinence in whom conservative treatments had failed or who were not candidates for more conservative treatments were selected. Patients with ≥ 50% improvement over baseline in fecal incontinence episodes per week during a 14-day test stimulation period received sacral nerve stimulation therapy. Patients were assessed with a 14-day bowel diary and Fecal Incontinence Quality of Life and Fecal Incontinence Severity Index questionnaires. Therapeutic success was defined as ≥ 50% improvement over baseline in fecal incontinence episodes per week. All adverse events were collected. A total of 120 patients (110 women; mean age, 60.5 years) underwent implantation. Seventy-six of these patients (63%) were followed a minimum of 5 years (maximum, longer than 8 years) and are the basis for this report. Fecal incontinence episodes per week decreased from a mean of 9.1 at baseline to 1.7 at 5 years, with 89% (n = 64/72) having ≥ 50% improvement (p < 0.0001) and 36% (n = 26/72) having complete continence. Fecal Incontinence Quality of Life scores also significantly improved for all 4 scales between baseline and 5 years (n = 70; p < 0.0001). Twenty-seven of the 76 (35.5%) patients required a device revision, replacement, or explant. The therapeutic effect and improved quality of life for fecal incontinence is maintained 5 years after sacral nerve stimulation implantation and beyond. Device revision, replacement, or explant rate was acceptable, but future efforts should be aimed at improvement.

Caregiver ratings of long-term executive dysfunction and attention problems after early childhood traumatic brain injury: family functioning is important.

PubMed

Kurowski, Brad G; Taylor, H Gerry; Yeates, Keith Owen; Walz, Nicolay C; Stancin, Terry; Wade, Shari L

2011-09-01

To evaluate the relationship of family and parenting factors to long-term executive dysfunction and attention problems after early childhood traumatic brain injury (TBI). We hypothesized that the magnitude of executive dysfunction and attention problems would be moderated by family and parenting factors. A multicenter, prospective cohort study that included an orthopedic injury (OI) reference group. Three tertiary academic children's hospital medical centers and one general medical center. Children, ages 3-7 years, hospitalized for OI, moderate TBI, or severe TBI. METHODS AND OUTCOME MEASUREMENTS: Parental ratings of family functioning and parenting styles were obtained 18 months after the injury occurred. The main outcome measurements, which were parental ratings of children's executive function and attention, were performed at least 24 months after the injury occurred (mean, 39 months; range, 25-63 months). Group comparisons were conducted with use of t-tests, χ(2) analysis, analysis of variance, and Pearson and Spearman correlations. Regression analysis was used to examine associations of the outcomes with family functioning and parenting styles and to test moderating effects of these factors on group differences. Participants with severe TBI demonstrated increased executive dysfunction and attention problems compared with those who sustained moderate TBI or OI. Lower levels of family dysfunction were associated with better executive function and attention across groups but did not moderate group differences. However, attention deficits after severe TBI were exacerbated under conditions of more permissive parenting relative to attention deficits after OIs. Executive function and attention problems persisted on a long-term basis (>24 months) after early childhood TBI, and positive global family functioning and nonpermissive parenting were associated with better outcomes. Better characterization of the optimal family environment for recovery from early childhood TBI could help target future interventions. Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Long-term quality of life improvement for chronic intractable back and leg pain patients using spinal cord stimulation: 12-month results from the SENZA-RCT.

PubMed

Amirdelfan, Kasra; Yu, Cong; Doust, Matthew W; Gliner, Bradford E; Morgan, Donna M; Kapural, Leonardo; Vallejo, Ricardo; Sitzman, B Todd; Yearwood, Thomas L; Bundschu, Richard; Yang, Thomas; Benyamin, Ramsin; Burgher, Abram H; Brooks, Elizabeth S; Powell, Ashley A; Subbaroyan, Jeyakumar

2018-06-01

Chronic axial low-back pain is a debilitating disorder that impacts all aspects of an afflicted individual's life. Effective, durable treatments have historically been elusive. Interventional therapies, such as spinal cord stimulation (SCS), have shown limited efficacy at best. Recently, a novel treatment, 10 kHz SCS, has demonstrated superior pain relief compared with traditional SCS in a randomized controlled trial (RCT). In this manuscript, we report on the long-term improvements in quality of life (QoL) outcomes for subjects enrolled in this study. A prospective, multicenter, randomized controlled trial (SENZA-RCT) was conducted. Patients with both chronic back and leg pain were enrolled and randomized (1:1) into 10 kHz SCS or traditional SCS treatment groups. A total of 171 subjects received a permanent SCS device implant. QoL and functionality measures were collected up to 12 months. The device remote control utilization, which is an indication of patient interaction with the device for adjustments, was collected at 24-month post-implantation. At 12 months, a higher proportion of 10 kHz SCS subjects had marked improvement of their disability (Oswestry Disability Index) to a "moderate" or "minimal" impact on their daily function versus the control group. The subjects also reported better improvement in the Global Assessment of Functioning, Clinician Global Impression of Change, Pittsburgh Sleep Quality Index, and short-form McGill Pain Questionnaire, compared to traditional SCS subjects. The 10 kHz SCS subjects also reported far higher rates of both driving and sleeping with their device turned on, as well as reduced reliance on their programmers to adjust therapy settings. In addition to superior pain relief, 10 kHz SCS provides long-term improvements in quality of life and functionality for subjects with chronic low-back and leg pain. ClinicalTrials.gov (NCT01609972).

Eating behavior, weight problems and eating disorders in 101 long-term survivors of childhood-onset craniopharyngioma.

PubMed

Hoffmann, Anika; Postma, Frank P; Sterkenburg, Anthe S; Gebhardt, Ursel; Müller, Hermann L

2015-01-01

As a result of hypothalamic involvement and/or treatment-related hypothalamic damage, up to 75% of childhood craniopharyngioma patients develop hypothalamic obesity. Eating behavior was analyzed in 101 survivors of childhood craniopharyngioma, recruited from 1980 to 2001 in the HIT-Endo multicenter study, and in 85 body mass index (BMI)-matched healthy controls using the Inventory for Eating Behavior and Weight Problems (IEG) and the Inventory for Eating Disorders (ESI). Severely obese patients (BMI>8 SD; n=9) presented with pathological eating behavior, more weight problems, and eating disorders, as compared to obese (BMI 3-8 SD; n=44) and normal or overweight patients (BMI<3 SD; n=48). Craniopharyngioma patients with different degrees of obesity showed similar or even less pathological findings as compared to BMI-matched normal controls. Severe obesity is associated with pathological eating behavior/disorders in craniopharyngioma patients. As these disorders are not disease-specific, risk factors for hypothalamic obesity should be the focus of further craniopharyngioma research.

Rational polytherapy with lacosamide in clinical practice: results of a Spanish cohort analysis RELACOVA.

PubMed

Villanueva, Vicente; López-Gomáriz, Elena; López-Trigo, Javier; Palau, Juan; García, Manuel; Villarroya, Teresa; Bonet, Macarena; Santafé, Consuelo

2012-03-01

There has been little long-term success with polytherapy for patients with refractory partial-onset epilepsy. The rational combination of antiepileptic drugs based on their mechanism of action may help improve treatment efficacy and tolerability. Lacosamide, a novel sodium channel blocker (SCB), was investigated in 158 patients with partial-onset epilepsy in the prospective, multicenter, observational, RELACOVA cohort study conducted in Spain. After 12 months' treatment with lacosamide, 47% of patients were responders (≥50% reduction in seizure frequency) and 24% were seizure free. Lacosamide was well tolerated; dizziness was the most frequent adverse event. Efficacy was better (responder rate, 65% vs 38%; seizure free rate, 35% vs 17%) and there was a lower adverse event rate (33% vs 58%) in patients receiving non-SCBs (n=49) versus those receiving SCBs (n=104) as concomitant therapy at baseline. Further investigation of lacosamide combination therapy is warranted. Copyright © 2012 Elsevier Inc. All rights reserved.

Impact of the ALMS and MAINTAIN trials on the management of lupus nephritis.

PubMed

Morris, Heather K; Canetta, Pietro A; Appel, Gerald B

2013-06-01

Current treatment of lupus nephritis consists of both induction and maintenance therapy, with the latter being designed to consolidate remissions and prevent relapses. Long-term maintenance treatment with intravenous cyclophosphamide was effective but associated with considerable toxicity. A small but well-designed controlled trial found that for post-induction maintenance therapy, both oral mycophenolate mofetil (MMF) and oral azathioprine were superior in efficacy and had reduced toxicity than a regimen of continued every third month intravenous cyclophosphamide. Although these oral agents were rapidly accepted and utilized as maintenance medications, their usage was based on scant evidence and there were no comparisons between the two. Recently, two relatively large, randomized, well-controlled, multicenter trials dealing with maintenance therapy for severe lupus nephritis have been completed. The Aspreva Lupus Management Study (ALMS) maintenance and MAINTAIN nephritis trials provide important information regarding the comparative efficacy and safety of MMF and azathioprine as maintenance therapies, as well as information on the effect of dosage and duration of treatment with these agents.

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.

Similar outcomes of allogeneic hematopoietic cell transplantation from unrelated donor and umbilical cord blood vs. sibling donor for pediatric acute myeloid leukemia: Multicenter experience in China.

PubMed

Tang, Xiangfeng; Chen, Jing; Fang, Jianpei; Sun, Xin; Qin, Mao Quan; Li, Junhui; Zhu, Yiping; Luan, Zuo

2015-06-01

In a multicenter study, we have conducted a retrospective study on 73 pediatric AML patients who were primary refractory or in greater than CR1 and investigated MSD (or MMSD) (n = 20), URD (n = 23), and UCB (n = 30) HCT between January 1998 and October 2009. The median day to neutrophil engraftment was similar in all groups. The median day to platelet engraftment was longer in the UCB group. The number of HLA mismatch was higher in the UCB group (p = 0.034); however, the cumulative incidence of grade III-IV aGVHD was not different among all groups (p = 0.125); furthermore, cGVHD was lower in the UCB group (p = 0.078). The risk of relapse did not differ among all groups (RR = 1.28, p = 0.125), but the patients of MSD (or MMSD) grafts had a trend of higher risk recurrence. Sixty-two patients survived with a median follow-up of 58.2 months. Five-yr LFS was 73.1%, 59.8%, and 59.6% for URD, UCB, and MSD (or MMDS), respectively (p = 0.426). Five-yr LFS in CR1 was 68.9%, with a significantly better result compared to 41.7% in CR2 (p = 0.025). Our comparisons suggest that pediatric AML patients receiving UCB had a higher early TRM, a lower cGVHD rate, and a similar long-term survival. The outcome of URD and UCB is comparable to that of a suitable sibling for pediatric AML. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Salvage Surgery After Chemoradiotherapy in the Management of Esophageal Cancer: Is It a Viable Therapeutic Option?

PubMed

Markar, Sheraz; Gronnier, Caroline; Duhamel, Alain; Pasquer, Arnaud; Théreaux, Jérémie; du Rieu, Mael Chalret; Lefevre, Jérémie H; Turner, Kathleen; Luc, Guillaume; Mariette, Christophe

2015-11-20

The aim of this large multicenter study was to assess the impact of salvage esophagectomy after definitive chemoradiotherapy (SALV) on clinical outcome. Data from consecutive adult patients undergoing resection for esophageal cancer in 30 European centers from 2000 to 2010 were collected. First, groups undergoing SALV (n = 308) and neoadjuvant chemoradiotherapy followed by planned esophagectomy (NCRS; n = 540) were compared. Second, patients who benefited from SALV for persistent (n = 234) versus recurrent disease (n = 74) were compared. Propensity score matching and multivariable analyses were used to compensate for differences in some baseline characteristics. SALV versus NCRS groups: In-hospital mortality was similar in both groups (8.4% v 9.3%). The only significant differences in complications were seen for anastomotic leak (17.2% v 10.7%; P = .007) and surgical site infection, which were both more frequent in the SALV group. At 3 years, groups had similar overall (43.3% v 40.1%; P = .542) and disease-free survival (39.2% v 32.8%; P = .232) after matching, along with a similar recurrence pattern. Persistent versus recurrent disease groups: There were no significant differences between groups in incidence of in-hospital mortality or major complications. At 3 years, overall (40.9% v 56.2%; P = .046) and disease-free survival (36.6% v 51.6%; P = .095) were lower in the persistent disease group. The results of this large multicenter study from the modern era suggest that SALV can offer acceptable short- and long-term outcomes in selected patients at experienced centers. Persistent cancer after definitive chemoradiotherapy seems to be more biologically aggressive, with poorer survival compared with recurrent cancer. © 2015 by American Society of Clinical Oncology.

Presence of bone marrow micro-metastases in stage I-III colon cancer patients is associated with worse disease-free and overall survival.

PubMed

Viehl, Carsten T; Weixler, Benjamin; Guller, Ulrich; Dell-Kuster, Salome; Rosenthal, Rachel; Ramser, Michaela; Banz, Vanessa; Langer, Igor; Terracciano, Luigi; Sauter, Guido; Oertli, Daniel; Zuber, Markus

2017-05-01

The prognostic significance of bone marrow micro-metastases (BMM) in colon cancer patients remains unclear. We conducted a prospective cohort study with long-term follow-up to evaluate the relevance of BMM as a prognostic factor for disease free (DFS) and overall survival (OS) in stage I-III colon cancer patients. In this prospective multicenter cohort study 144 stage I-III colon cancer patients underwent bone marrow aspiration from both iliac crests prior to open oncologic resection. The bone marrow aspirates were stained with the pancytokeratin antibody A45-B/B3 and analyzed for the presence of epithelial tumor cells. DFS and OS were analyzed using a Cox proportional hazard model and robust standard errors to account for clustering in the multicenter setting. Median overall follow-up was 6.2 years with no losses to follow-up, and 7.3 years in patients who survived. BMM were found in 55 (38%) patients. In total, 30 (21%) patients had disease recurrence and 56 (39%) patients died. After adjusting for known prognostic factors, BMM positive patients had a significantly worse DFS (hazard ratio [HR] 1.33; 95% confidence interval [95% CI]: 1.02-1.73; P = 0.037) and OS (HR 1.30; 95% CI: 1.09-1.55; P = 0.003) compared to BMM negative patients. Bone marrow micro-metastases occur in over one third of stage I-III colon cancer patients and are a significant, independent negative prognostic factor for DFS and OS. Future trials should evaluate whether node-negative colon cancer patients with BMM benefit from adjuvant chemotherapy. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

rhBMP-2 for posterolateral instrumented lumbar fusion: a multicenter prospective randomized controlled trial.

PubMed

Hurlbert, R John; Alexander, David; Bailey, Stewart; Mahood, James; Abraham, Ed; McBroom, Robert; Jodoin, Alain; Fisher, Charles

2013-12-01

Multicenter randomized controlled trial. To evaluate the effect of recombinant human bone morphogenetic protein (rhBMP-2) on radiographical fusion rate and clinical outcome for surgical lumbar arthrodesis compared with iliac crest autograft. In many types of spinal surgery, radiographical fusion is a primary outcome equally important to clinical improvement, ensuring long-term stability and axial support. Biologic induction of bone growth has become a commonly used adjunct in obtaining this objective. We undertook this study to objectify the efficacy of rhBMP-2 compared with traditional iliac crest autograft in instrumented posterolateral lumbar fusion. Patients undergoing 1- or 2-level instrumented posterolateral lumbar fusion were randomized to receive either autograft or rhBMP-2 for their fusion construct. Clinical and radiographical outcome measures were followed for 2 to 4 years postoperatively. One hundred ninety seven patients were successfully randomized among the 8 participating institutions. Adverse events attributable to the study drug were not significantly different compared with controls. However, the control group experienced significantly more graft-site complications as might be expected. 36-Item Short Form Health Survey, Oswestry Disability Index, and leg/back pain scores were comparable between the 2 groups. After 4 years of follow-up, radiographical fusion rates remained significantly higher in patients treated with rhBMP-2 (94%) than those who received autograft (69%) (P = 0.007). The use of rhBMP-2 for instrumented posterolateral lumbar surgery significantly improves the chances of radiographical fusion compared with the use of autograft. However, there is no associated improvement in clinical outcome within a 4-year follow-up period. These results suggest that use of rhBMP-2 should be considered in cases where lumbar arthrodesis is of primary concern.

A MULTI-CENTER CLUSTER-RANDOMIZED TRIAL OF A MULTI-FACTORIAL INTERVENTION TO IMPROVE ANTIHYPERTENSIVE MEDICATION ADHERENCE AND BLOOD PRESSURE CONTROL AMONG PATIENTS AT HIGH CARDIOVASCULAR RISK (The COM99 study)*

PubMed Central

Pladevall, Manel; Brotons, Carlos; Gabriel, Rafael; Arnau, Anna; Suarez, Carmen; de la Figuera, Mariano; Marquez, Emilio; Coca, Antonio; Sobrino, Javier; Divine, George; Heisler, Michele; Williams, L Keoki

2010-01-01

Background Medication non-adherence is common and results in preventable disease complications. This study assesses the effectiveness of a multifactorial intervention to improve both medication adherence and blood pressure control and to reduce cardiovascular events. Methods and Results In this multi-center, cluster-randomized trial, physicians from hospital-based hypertension clinics and primary care centers across Spain were randomized to receive and provide the intervention to their high-risk patients. Eligible patients were ≥50 years of age, had uncontrolled hypertension, and had an estimated 10-year cardiovascular risk greater than 30%. Physicians randomized to the intervention group counted patients’ pills, designated a family member to support adherence behavior, and provided educational information to patients. The primary outcome was blood pressure control at 6 months. Secondary outcomes included both medication adherence and a composite end-point of all cause mortality and cardiovascular-related hospitalizations. Seventy-nine physicians and 877 patients participated in the trial. The mean duration of follow-up was 39 months. Intervention patients were less likely to have an uncontrolled systolic blood pressure (odds ratio 0.62; 95% confidence interval [CI] 0.50–0.78) and were more likely to be adherent (OR 1.91; 95% CI 1.19–3.05) when compared with control group patients at 6 months. After five years 16% of the patients in the intervention group and 19% in the control group met the composite end-point (hazard ratio 0.97; 95% CI 0.67–1.39). Conclusions A multifactorial intervention to improve adherence to antihypertensive medication was effective in improving both adherence and blood pressure control, but it did not appear to improve long-term cardiovascular events. PMID:20823391

French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: Results at 2 years (FNCLCC-GORTEC)

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

Bensadoun, Rene-Jean; Benezery, Karen; Dassonville, Olivier

Background: Unresectable carcinomas of the oropharynx and hypopharynx still have a poor long-term prognosis. Following a previous phase II study, this phase III multicenter trial was conducted between November 1997 and March 2002. Methods: Nontreated, strictly unresectable cases were eligible. Twice-daily radiation: two fractions of 1.2 Gy/day, 5 days per week, with no split (D1{sup {yields}}D46). Total tumor doses: 80.4 Gy/46 day (oropharynx), 75.6 Gy/44 day (hypopharynx). Chemotherapy (arm B): Cisplatin 100 mg/m{sup 2} (D1, D22, D43); 5FU, continuous infusion (D1{sup {yields}}D5), 750 mg/m{sup 2}/day cycle 1; 430 mg/m{sup 2}/day cycles 2 and 3. Results: A total of 163 evaluablemore » patients. Grade 3-4 acute mucositis 82.6% arm B/69.5% arm A (NS); Grade 3-4 neutropenia 33.3% arm B/2.4% arm A (p < 0.05). Enteral nutrition through gastrostomy tube was more frequent in arm B before treatment and at 6 months (p < 0.01). At 24 months, overall survival (OS), disease-free survival (DFS), and specific survival (SS) were significantly better in arm B. OS: 37.8% arm B vs. 20.1% arm A (p = 0.038); DFS: 48.2% vs. 25.2% (p = 0.002); SS: 44.5% vs. 30.2% (p 0.021). No significant difference between the two arms in the amount of side effects at 1 and 2 years. Conclusion: For these unresectable cases, chemoradiation provides better outcome than radiation alone, even with an 'aggressive' dose-intensity radiotherapy schedule.« less

Crossing the perspectives of patients, families, and physicians on cancer treatment: A qualitative study.

PubMed

Orri, Massimiliano; Sibeoni, Jordan; Bousquet, Guilhem; Labey, Mathilde; Gueguen, Juliette; Laporte, Cyril; Winterman, Sabine; Picard, Camille; Nascimbeni, Clara; Verneuil, Laurence; Revah-Levy, Anne

2017-03-28

Patients, family members, and physicians participate in cancer care, but their perspectives about what is helpful during cancer treatment have rarely been compared. The aim of this study was to compare these three perspectives. Multicenter qualitative study (with previously published protocol) based on 90 semi-structured interviews. Participants (purposively selected until data saturation) came from three different subsamples: (i) patients with cancer (n=30), (ii) their relatives (n=30), and (iii) their referring physicians (n=10, interviewed more than once). Our analysis found 3 main axes (perceived positive effects of cancer treatment, perceived negative effects of cancer treatment, doctor-physician relationship), each composed of 2 main themes. The findings showed that patients, families, and physicians shared the long-term objective of increasing survival (while reducing side effects). However, patients and relatives also pointed out the importance of living with cancer each day and thus of factors helping them to live as well as possible in daily life. The physicians' difficulty in coping with patients' suffering may limit their access to elements that can improve patients' capacity to live as well as possible. During cancer treatment (and not only at the end of life), attention should be given to enhancing the capacity of patients to live as well as possible (not only as long as possible) to meet the goals of patient-centered care and satisfy this important need of patients and families.

Air pollution and nonmalignant respiratory mortality in 16 cohorts within the ESCAPE project.

PubMed

Dimakopoulou, Konstantina; Samoli, Evangelia; Beelen, Rob; Stafoggia, Massimo; Andersen, Zorana Jovanovic; Hoffmann, Barbara; Fischer, Paul; Nieuwenhuijsen, Mark; Vineis, Paolo; Xun, Wei; Hoek, Gerard; Raaschou-Nielsen, Ole; Oudin, Anna; Forsberg, Bertil; Modig, Lars; Jousilahti, Pekka; Lanki, Timo; Turunen, Anu; Oftedal, Bente; Nafstad, Per; Schwarze, Per E; Penell, Johanna; Fratiglioni, Laura; Andersson, Niklas; Pedersen, Nancy; Korek, Michal; De Faire, Ulf; Eriksen, Kirsten Thorup; Tjønneland, Anne; Becker, Thomas; Wang, Meng; Bueno-de-Mesquita, Bas; Tsai, Ming-Yi; Eeftens, Marloes; Peeters, Petra H; Meliefste, Kees; Marcon, Alessandro; Krämer, Ursula; Kuhlbusch, Thomas A J; Vossoughi, Mohammad; Key, Timothy; de Hoogh, Kees; Hampel, Regina; Peters, Annette; Heinrich, Joachim; Weinmayr, Gudrun; Concin, Hans; Nagel, Gabriele; Ineichen, Alex; Jacquemin, Bénédicte; Stempfelet, Morgane; Vilier, Alice; Ricceri, Fulvio; Sacerdote, Carlotta; Pedeli, Xanthi; Katsoulis, Michalis; Trichopoulou, Antonia; Brunekreef, Bert; Katsouyanni, Klea

2014-03-15

Prospective cohort studies have shown that chronic exposure to particulate matter and traffic-related air pollution is associated with reduced survival. However, the effects on nonmalignant respiratory mortality are less studied, and the data reported are less consistent. We have investigated the relationship of long-term exposure to air pollution and nonmalignant respiratory mortality in 16 cohorts with individual level data within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE). Data from 16 ongoing cohort studies from Europe were used. The total number of subjects was 307,553. There were 1,559 respiratory deaths during follow-up. Air pollution exposure was estimated by land use regression models at the baseline residential addresses of study participants and traffic-proximity variables were derived from geographical databases following a standardized procedure within the ESCAPE study. Cohort-specific hazard ratios obtained by Cox proportional hazard models from standardized individual cohort analyses were combined using metaanalyses. We found no significant associations between air pollution exposure and nonmalignant respiratory mortality. Most hazard ratios were slightly below unity, with the exception of the traffic-proximity indicators. In this study of 16 cohorts, there was no association between air pollution exposure and nonmalignant respiratory mortality.

Entyvio lengthen dose-interval study: lengthening vedolizumab dose interval and the risk of clinical relapse in inflammatory bowel disease.

PubMed

Chan, Webber; Lynch, Nicole; Bampton, Peter; Chang, Jeff; Chung, Alvin; Florin, Timothy; Hetzel, David J; Jakobovits, Simon; Moore, Gregory; Pavli, Paul; Radford-Smith, Graham; Thin, Lena; Baraty, Brandon; Haifer, Craig; Yau, Yunki; Leong, Rupert W L

2018-07-01

Vedolizumab (VDZ), an α4β7 anti-integrin antibody, is efficacious in the induction and maintenance of remission in ulcerative colitis (UC) and Crohn's disease (CD). In the GEMINI long-term safety study, enrolled patients received 4-weekly VDZ. Upon completion, patients were switched to 8-weekly VDZ in Australia. The clinical success rate of treatment de-escalation for patients in remission on VDZ has not been described previously. To determine the proportion of patients who relapsed after switching from 4 to 8-weekly VDZ, the mean time to relapse, and the recapture rate when switching back to 8-weekly dosing. This was a retrospective, observational, multicenter study of patients previously recruited into GEMINI long-term safety in Australia. Data on the demographics and biochemical findings were collected. There were 34 patients [23 men, mean age 49.1 (±13.1) years] and their mean disease duration was 17.6 (±8.5) years. The mean 4-weekly VDZ infusion duration was 286.5 (±48.8) weeks. A total of five (15%) patients relapsed on dose-interval increase (4/17 UC, 1/17 CD) at a median duration from dose interval lengthening to flare of 14 weeks (interquartile range=6-25). Eighty percent (4/5) of patients re-entered remission following dose-interval decrease back to 4-weekly. No clinical predictors of relapse could be determined because of the small cohort size. The risk of patients relapsing when switching from 4 to 8-weekly VDZ ∼15% and is similar between CD and UC. Dose-interval decrease recaptures 80% of patients who relapsed. Therapeutic drug monitoring of VDZ may be of clinical relevance.

Surgical Management of Patients with Synchronous Colorectal Liver Metastasis: A Multicenter International Analysis

PubMed Central

Mayo, Skye C; Pulitano, Carlo; Marques, Hugo; Lamelas, Jorge; Wolfgang, Christopher L; de Saussure, Wassila; Choti, Michael A; Gindrat, Isabelle; Aldrighetti, Luca; Barrosso, Eduardo; Mentha, Gilles; Pawlik, Timothy M

2014-01-01

BACKGROUND The goal of this study was to investigate the surgical management and outcomes of patients with primary colorectal cancer (CRC) and synchronous liver metastasis (sCRLM). STUDY DESIGN Using a multi-institutional database, we identified 1,004 patients treated for sCRLM between 1982 and 2011. Clinicopathologic and outcomes data were evaluated with uni- and multivariable analyses. RESULTS A simultaneous CRC and liver operation was performed in 329 (33%) patients; 675 (67%) underwent a staged approach (“classic” staged approach, n = 647; liver-first strategy, n = 28). Patients managed with the liver-first approach had more hepatic lesions and were more likely to have bilateral disease than those in the other 2 groups (p < 0.05). The use of staged operative strategies increased over the time of the study from 58% to 75% (p < 0.001). Liver-directed therapy included hepatectomy (90%) or combined resection + ablation (10%). A major resection (>3 segments) was more common with a staged approach (39% vs 24%; p < 0.001). Overall, 509 patients (50%) received chemotherapy in either the preoperative (22%) or adjuvant (28%) settings, with 11% of patients having both. There were 197 patients (20%) who had a complication in the postoperative period, with no difference in morbidity between staged and simultaneous groups or major vs minor hepatectomies (p > 0.05). Ninety-day postoperative mortality was 3.0%, with no difference between simultaneous and staged approaches (p = 0.94). The overall median and 5-year survivals were 50.9 months and 44%, respectively; long-term survival was the same regardless of the operative approach (p > 0.05). CONCLUSIONS Simultaneous and staged resections for sCRLM can be performed with comparable morbidity, mortality, and long-term oncologic outcomes. PMID:23433970

Lamivudine switch therapy in chronic hepatitis B patients achieving undetectable hepatitis B virus DNA after 3 years of entecavir therapy: A prospective, open-label, multicenter study.

PubMed

Yeh, Ming-Lun; Huang, Ching-I; Hsieh, Ming-Yen; Huang, Chung-Feng; Hsieh, Meng-Hsuan; Huang, Jee-Fu; Dai, Chia-Yen; Lin, Zu-Yau; Chen, Shinn-Chern; Yu, Ming-Lung; Chuang, Wan-Long

2016-11-01

The subsequent maintenance therapy in chronic hepatitis B (CHB) patients after long-term viral replication suppression is still uncertain. We aim to evaluate the efficacy of lamivudine (LAM) maintenance therapy in CHB patients achieving undetectable hepatitis B virus (HBV) DNA after 3 years of entecavir (ETV) therapy. Consecutive CHB patients who received at least 3 years of ETV and achieved HBV DNA negativity were allocated either LAM switch therapy or stopped ETV therapy in a prospective, open-label study. Another group of sex- and age-matched patients with continuous ETV therapy for at least 4 years served as historical control group. The primary outcome measurement of the study was relapse of HBV DNA (defined as serum HBV DNA level ≥ 2000 IU/mL). A total of 74 patients, including 42 of LAM switch and 32 of the nonswitch group, were enrolled. There were no significant differences in demographics, except a higher proportion of patients with positive hepatitis B envelope antigen in the nonswitch group at the initiation of ETV therapy. The LAM switch group had significantly lower 1-year relapse rate of HBV within 1 year compared to the nonswitch group (14.3% vs. 75%, p<0.001). However, none of the 48 historical control patients developed relapse of HBV, which was significantly lower than the rate in LAM switch group (p < 0.001). LAM switch was the only factor associated with HBV DNA relapse. In conclusion, continuous long-term potent nucleot(s)ide analogue therapy is mandatory for prevention of viral relapse in CHB patients. Copyright © 2016 Kaohsiung Medical University. Published by Elsevier Taiwan.. All rights reserved.

Effects of cyclosporine A pretreatment of deceased organ donors on kidney graft function (Cis-A-rein): study protocol for a randomized controlled trial.

PubMed

Orban, Jean-Christophe; Fontaine, Eric; Cassuto, Elisabeth; Baumstarck, Karine; Leone, Marc; Constantin, Jean-Michel; Ichai, Carole

2018-04-17

Renal transplantation represents the treatment of choice of end-stage kidney disease. Delayed graft function (DGF) remains the most frequent complication after this procedure, reaching more than 30%. Its prevention is essential as it impedes early- and long-term prognosis of transplantation. Numerous pharmacological interventions aiming to prevent ischemia-reperfusion injuries failed to reduce the rate of DGF. We hypothesize that cyclosporine as an early preconditioning procedure in donors would be associated with decreased DGF. The Cis-A-rein study is an investigator-initiated, prospective, multicenter, double-blind, randomized, controlled study performed to assess the effects of a donor preconditioning with cyclosporine A on kidney grafts function in transplanted patients. After randomization, a brain dead donor will receive 2.5 mg kg -1 of cyclosporine A or the same volume of 5% glucose solution. The primary objective is to compare the rate of DGF, defined as the need for at least one dialysis session within the 7 days following transplantation, between both groups. The secondary objectives include rate of slow graft function, mild and severe DGF, urine output and serum creatinine during the first week after transplantation, rate of primary graft dysfunction, renal function and mortality at 1 year. The sample size (n = 648) was determined to obtain 80% power to detect a 10% difference for rate of DGF at day 7 between the two groups (30% of the patients in the placebo group and 20% of the patients in the intervention group). Delayed graft function is a major issue after renal transplantation, impeding long-term prognosis. Cyclosporine A pretreatment in deceased donors could improve the outcome of patients after renal transplantation. ClinicalTrials.gov, ID: NCT02907554 Registered on 20 September 2016.

Right unilateral electroconvulsive therapy does not cause more cognitive impairment than pharmacologic treatment in treatment-resistant bipolar depression: A 6-month randomized controlled trial follow-up study.

PubMed

Bjoerke-Bertheussen, Jeanette; Schoeyen, Helle; Andreassen, Ole A; Malt, Ulrik F; Oedegaard, Ketil J; Morken, Gunnar; Sundet, Kjetil; Vaaler, Arne E; Auestad, Bjoern; Kessler, Ute

2017-12-21

Electroconvulsive therapy is an effective treatment for bipolar depression, but there are concerns about whether it causes long-term neurocognitive impairment. In this multicenter randomized controlled trial, in-patients with treatment-resistant bipolar depression were randomized to either algorithm-based pharmacologic treatment or right unilateral electroconvulsive therapy. After the 6-week treatment period, all of the patients received maintenance pharmacotherapy as recommended by their clinician guided by a relevant treatment algorithm. Patients were assessed at baseline and at 6 months. Neurocognitive functions were assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, and autobiographical memory consistency was assessed using the Autobiographical Memory Interview-Short Form. Seventy-three patients entered the trial, of whom 51 and 26 completed neurocognitive assessments at baseline and 6 months, respectively. The MATRICS Consensus Cognitive Battery composite score improved by 4.1 points in both groups (P = .042) from baseline to 6 months (from 40.8 to 44.9 and from 41.9 to 46.0 in the algorithm-based pharmacologic treatment and electroconvulsive therapy groups, respectively). The Autobiographical Memory Interview-Short Form consistency scores were reduced in both groups (72.3% vs 64.3% in the algorithm-based pharmacologic treatment and electroconvulsive therapy groups, respectively; P = .085). This study did not find that right unilateral electroconvulsive therapy caused long-term impairment in neurocognitive functions compared to algorithm-based pharmacologic treatment in bipolar depression as measured using standard neuropsychological tests, but due to the low number of patients in the study the results should be interpreted with caution. ClinicalTrials.gov: NCT00664976. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tolerability and safety of Souvenaid in patients with mild Alzheimer's disease: results of multi-center, 24-week, open-label extension study.

PubMed

Olde Rikkert, Marcel G M; Verhey, Frans R; Blesa, Rafael; von Arnim, Christine A F; Bongers, Anke; Harrison, John; Sijben, John; Scarpini, Elio; Vandewoude, Maurits F J; Vellas, Bruno; Witkamp, Renger; Kamphuis, Patrick J G H; Scheltens, Philip

2015-01-01

The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to improve synapse formation and function in patients with Alzheimer's disease (AD). Two double-blind randomized controlled trials (RCT) with Souvenaid of 12 and 24 week duration (Souvenir I and Souvenir II) showed that memory performance was improved in drug-naïve mild AD patients, whereas no effects on cognition were observed in a 24-week RCT (S-Connect) in mild to moderate AD patients using AD medication. Souvenaid was well-tolerated in all RCTs. In this 24-week open-label extension (OLE) study to the 24-week Souvenir II RCT, long-term safety and intake adherence of the medical food Souvenaid was evaluated. Patients with mild AD (n = 201) received Souvenaid once-daily during the OLE. Main outcome parameters were safety and product intake adherence. The memory domain z-score from a revised neuropsychological test battery was continued as exploratory parameter. Compared to the RCT, a similar (low) incidence and type of adverse events was observed, being mainly (68.3%) of mild intensity. Pooled data (RCT and OLE) showed that 48-week use of Souvenaid was well tolerated with high intake adherence (96.1%). Furthermore, a significant increase in the exploratory memory outcome was observed in both the active-active and control-active groups during Souvenaid intervention. Souvenaid use for up to 48-weeks was well tolerated with a favorable safety profile and high intake adherence. The findings in this OLE study warrant further investigation toward the long-term safety and efficacy of Souvenaid in a well-controlled, double-blind RCT.

Durability of treatment effects of the Sleep Position Trainer versus oral appliance therapy in positional OSA: 12-month follow-up of a randomized controlled trial.

PubMed

de Ruiter, Maurits H T; Benoist, Linda B L; de Vries, Nico; de Lange, Jan

2018-05-01

The Sleep Position Trainer (SPT) is a new option for treating patients with positional obstructive sleep apnea (POSA). This study investigated long-term efficacy, adherence, and quality of life during use of the SPT device compared with oral appliance therapy (OAT) in patients with POSA. This prospective, multicenter trial randomized patients with mild to moderate POSA (apnea-hypopnea index [AHI] 5-30/h) to SPT or OAT. Polysomnography was performed at baseline and after 3 and 12 months' follow-up. The primary endpoint was OSA severity; adherence, quality of life, and adverse events were also assessed. Ninety-nine patients were randomized and 58 completed the study (29 in each group). Median AHI in the SPT group decreased from 13.2/h at baseline to 7.1/h after 12 months (P < 0.001); corresponding values in the OAT group were 13.4/h and 5.0/h (P < 0.001), with no significant between-group difference (P = 1.000). Improvements throughout the study were maintained at 12 months. Long-term median adherence was also similar in the two treatment groups; the proportion of patients who used their device for ≥ 4 h for 5 days in a week was 100% in the SPT group and 97.0% in the OAT group (P = 0.598). The efficacy of SPT therapy was maintained over 12 months and was comparable to that of OAT in patients with mild to moderate POSA. Adherence was relatively high, and similar in the two groups. www.clinicaltrials.gov (NCT02045576).

A multicenter study of sleep-wake rhythm disorders: therapeutic effects of vitamin B12, bright light therapy, chronotherapy and hypnotics.

PubMed

Yamadera, H; Takahashi, K; Okawa, M

1996-08-01

One hundred and six subjects with primary sleep-wake rhythm disorders [13 non-24 hour sleep-wake syndrome (non-24), 76 delayed sleep phase syndrome (DSPS), 11 irregular sleep-wake pattern (irregular) and six long sleepers] were treated with vitamin B12, bright light, chronotherapy and/or hypnotics. These therapies caused moderate or remarkable improvement in 32% of the non-24, 42% of DSPS, 45% of irregular and 67% of long sleepers. A lack of adequate sleep, unpleasant feelings at waking and daytime drowsiness were also improved in DSPS.

Vitamins (A, C and E) and oxidative status of hemodialysis patients treated with HFR and HFR-Supra.

PubMed

Palleschi, Simonetta; Ghezzi, Paolo M; Palladino, Giuseppe; Rossi, Barbara; Ganadu, Marino; Casu, Domenica; Cossu, Maria; Mattana, Giovanni; Pinna, Antonio Maria; Contu, Bruno; Ghisu, Tonina; Monni, Alessandro; Gazzanelli, Luana; Mereu, Maria Cristina; Logias, Franco; Passaghe, Mario; Amore, Alessandro; Bolasco, Piergiorgio

2016-08-26

Hemodiafiltration with on-line endogenous reinfusion (HFR) is an extracorporeal dialytic method that combines diffusion, convection and adsorption. HFR-Supra (HFR-S) is a second-generation system with increased convective permeability and adsorption capability. Previous studies suggested that HFR reduces oxidative stress compared to standard haemodialysis. The principal aim of the present study was to compare antioxidant vitamins behavior and oxidative status of hemodialysis patients treated with HFR and HFR-S. The study was designed as a multicenter, randomized, crossover trial. Forty-one patients were recruited from 19 dialysis centers and after a 4-month washout stabilization period in on-line hemodiafiltration (ol-HDF), each patient was randomized to a sequence of treatments (HFR-S followed by HFR or viceversa) with each treatment applied over 6 months. Plasma levels of Advanced Oxidation Protein Products, Total Antioxidant Status, vitamins C, A and E and their ligands (Retinol Binding Protein and total lipids) were measured at baseline and at the end of each treatment period. Results show that the higher convective permeability of HFR-S with respect to HFR did not produce additional beneficial effects on the patients' oxidative status, a slight decrease of both Vitamin A and Retinol Binding Protein being the only difference registered in the long-term. However, as compared to ol-HDF, both the re-infusive techniques allowed to reduce the intradialytic loss of Vitamin C and, in the long-term, improve the patients' oxidative status and increase Retinol Binding Protein plasma values. No significant differences were found between the Vitamin C concentration of pre- and post cartridge UF neither in HFR-S nor in HFR showing that the sorbent resin does not adsorb Vitamin C. HFR-S and HFR are almost equivalent in term of impact on antioxidant vitamins and oxidative status of hemodialysis patients. Nonetheless, as compared to ol-HDF, both treatments produced a sensible sparing of Vitamin C and may represent a new approach for reducing oxidative stress and related complications in dialysis patients. Long-term effects of re-infusive treatments on patients' cardiovascular morbidity and mortality need to be evaluated. ClinicalTrials.gov Identifier NCT01492491 , retrospectively registered in 10 December 2011.

Patient engagement and study design of PROP UP: A multi-site patient-centered prospective observational study of patients undergoing hepatitis C treatment.

PubMed

Evon, Donna M; Golin, Carol E; Stewart, Paul; Fried, Michael W; Alston, Shani; Reeve, Bryce; Lok, Anna S; Sterling, Richard K; Lim, Joseph K; Reau, Nancy; Sarkar, Souvik; Nelson, David R; Reddy, K R; Di Bisceglie, Adrian M

2017-06-01

New highly efficacious direct-acting antiviral (DAA) therapies are available to treat chronic hepatitis C viral (HCV) infection. Real-world, patient-centered data on harms and benefits associated with these therapies are needed. PROP UP is a multi-center prospective observational study that plans to enroll 1600 patients starting treatment with recently-approved DAA regimens. Informed by extensive input from a HCV patient engagement group who prioritized outcomes most important to them, patient-reported outcomes will be characterized using surveys at five time points: Baseline (T1), treatment week 4 (T2), end of treatment (T3), 12weeks post-treatment (T4), 12months post-treatment (T5). (1) Changes in side effects, functioning, pre-existing conditions, and out-of-pocket costs during therapy (T1 vs T2/T3); (2) Medication adherence in relation to a history of mental health/substance abuse, treatment regimens, pill burden, reasons for missed doses, and cure rates; (3) Short term impact of cure on functioning and amelioration of symptoms (T1 vs T4); (4) Long-term treatment harms or benefits of cure on symptoms, side effects, pre-existing conditions, and functioning (T1 vs T5). Similarities between regimens will be examined where comparisons are appropriate and meaningful. PROP UP complements previous clinical trials by focusing on patient-reported outcomes in a representative sample of patients treated in clinical practice, by collaborating with a patient engagement group, by characterizing the experiences of vulnerable subgroups, and by investigating long-term harms and benefits of treatments. PROP UP is designed to provide novel and detailed information to support informed decision-making for patients and providers contemplating HCV treatment (PCORI CER-1408-20,660; NCT02601820). Copyright © 2017 Elsevier Inc. All rights reserved.

A bio-psycho-social exercise program (RÜCKGEWINN) for chronic low back pain in rehabilitation aftercare--study protocol for a randomised controlled trial.

PubMed

Hentschke, Christian; Hofmann, Jana; Pfeifer, Klaus

2010-11-17

There is strong, internationally confirmed evidence for the short-term effectiveness of multimodal interdisciplinary specific treatment programs for chronic back pain. However, the verification of long-term sustainability of achieved effects is missing so far. For long-term improvement of pain and functional ability high intervention intensity or high volume seems to be necessary (> 100 therapy hours). Especially in chronic back pain rehabilitation, purposefully refined aftercare treatments offer the possibility to intensify positive effects or to increase their sustainability. However, quality assured goal-conscious specific aftercare programs for the rehabilitation of chronic back pain are absent. This study aims to examine the efficacy of a specially developed bio-psycho-social chronic back pain specific aftercare intervention (RÜCKGEWINN) in comparison to the current usual aftercare (IRENA) and a control group that is given an educational booklet addressing pain-conditioned functional ability and back pain episodes. Overall rehabilitation effects as well as predictors for compliance to the aftercare programs are analysed. Therefore, a multicenter prospective 3-armed randomised controlled trial is conducted. 456 participants will be consecutively enrolled in inpatient and outpatient rehabilitation and assigned to either one of the three study arms. Outcomes are measured before and after rehabilitation. Aftercare programs are assessed at ten month follow up after dismissal form rehabilitation. Special methodological and logistic challenges are to be mastered in this trial, which accrue from the interconnection of aftercare interventions to their residential district and the fact that the proportion of patients who take part in aftercare programs is low. The usability of the aftercare program is based on the transference into the routine care and is also reinforced by developed manuals with structured contents, media and material for organisation assistance as well as training manuals for therapists in the aftercare.

A Multicenter Analysis of Factors Associated With Apixaban-Related Bleeding in Hospitalized Patients With End-Stage Renal Disease on Hemodialysis.

PubMed

Steuber, Taylor D; Shiltz, Dane L; Cairns, Alex C; Ding, Qian; Binger, Katie J; Courtney, Julia R

2017-11-01

In 2014, the United States Food and Drug Administration approved a labeling change for apixaban to include recommendations for patients with severe renal impairment and patients with end-stage renal disease (ESRD) on hemodialysis (HD), though these recommendations are largely based on pharmacokinetic and pharmacodynamic data. Identify variables associated with bleeding events in hospitalized patients with ESRD on HD receiving apixaban. This retrospective, multicenter cohort study evaluated hospitalized patients with ESRD on HD receiving apixaban from January 1, 2013, through March 31, 2016. Correlational analysis and logistic regression were completed to identify factors associated with bleeding. A total of 114 adults were included in the analysis. The median length of stay (LOS) was 6.2 (interquartile range = 3.8-11.9) days and bleeding events occurred in a total of 17 patients (15%). A weak correlation was identified for higher cumulative apixaban exposure, increased number of HD sessions while receiving apixaban, and increased hospital LOS ( P < 0.05; correlation coefficient < 0.40). When controlling for confounders, logistic regression revealed that composite bleeding events were independently increased by continuation of outpatient apixaban (odds ratio = 13.07; 95% CI = 1.54-110.54; P = 0.018), increased total daily dose of apixaban (odds ratio = 1.72; 95% CI = 1.20 to 2.48; P = 0.003), and total HD sessions while receiving apixaban (odds ratio = 2.04; 95% CI = 1.06-3.92; P = 0.033). The association between these factors and increased bleeding should prompt concern for long-term anticoagulation with apixaban in patients with ESRD receiving chronic HD.

Stability validation of paraformaldehyde-fixed samples for the assessment of the platelet PECAM-1, P-selectin, and PAR-1 thrombin receptor by flow cytometry.

PubMed

Atar, Oliver D; Eisert, Christian; Pokov, Ilya; Serebruany, Victor L

2010-07-01

Sample fixation for storage and/or transportation represents an unsolved challenge for multicenter clinical trials assessing serial changes in platelet activity, or monitoring various antiplatelet regimens. Whole blood flow cytometry represents a major advance in defining platelet function, although special training and expensive equipment is required. We sought to determine how fixation with 2% paraformaldehyde (PFA), and storage of blood samples over 1 week affects the flow cytometry readings for both intact and thrombin-activating four major surface platelet receptors. Whole blood platelet expression of PECAM-1, P-selectin, PAR-1 inactive receptor (SPAN-12), and cleaved (WEDE-15) epitope was assessed immediately after blood draw, after staining with 2% PFA, and at day 1, 3, 5, and 7. The study was performed in 6 volunteers with multiple risk factors for vascular disease, not receiving any antiplatelet agents. Staining with PFA resulted in a slight decrease of fluorescence intensity, especially for PECAM-1, while antigen expression at day 1, 3 and 5 remains consistent, and highly reproducible. At day 7 there was a small but inconsistent trend towards diminished fluorescence intensity. The platelet data were consistent while validated with the isotype-matched irrelevant antibody. These data suggest that there is a 5 day window to perform final flow cytometry readings of whole blood PFA-fixed inactivated platelet samples. In contrast, thrombin activation cause gradual loss of flow cytometry signal, and cannot be recommended for long-term storage. This is critical logistic information for conducting multicenter platelet substudies within the framework of major clinical trials.

Multicenter case-control study of risk factors associated with development of vaccine-associated sarcomas in cats.

PubMed

Kass, Philip H; Spangler, William L; Hendrick, Mattie J; McGill, Lawrence D; Esplin, D Glen; Lester, Sally; Slater, Margaret; Meyer, E Kathryn; Boucher, Faith; Peters, Erika M; Gobar, Glenna G; Htoo, Thurein; Decile, Kendra

2003-11-01

To determine whether particular vaccine brands, other injectable medications, customary vaccination practices, or various host factors were associated with the formation of vaccine-associated sarcomas in cats. Prospective multicenter case-control study. Cats in the United States and Canada with soft tissue sarcomas or basal cell tumors. Veterinarians submitting biopsy specimens from cats with a confirmed diagnosis of soft tissue sarcoma or basal cell tumor were contacted for patient medical history. Time window statistical analyses were used in conjunction with various assumptions about case definitions. No single vaccine brand or manufacturer within antigen class was found to be associated with sarcoma formation. Factors related to vaccine administration were also not associated with sarcoma development, with the possible exception of vaccine temperature prior to injection. Two injectable medications (long-acting penicillin and methyl prednisolone acetate) were administered to case cats more frequently than to control cats. Findings do not support the hypotheses that specific brands or types of vaccine within antigen class, vaccine practices such as reuse of syringes, concomitant viral infection, history of trauma, or residence either increase or decrease the risk of vaccine-associated sarcoma formation in cats. There was evidence to suggest that certain long-acting injectable medications may also be associated with sarcoma formation.

A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer.

PubMed

Troyer, Dean A; Jamaspishvili, Tamara; Wei, Wei; Feng, Ziding; Good, Jennifer; Hawley, Sarah; Fazli, Ladan; McKenney, Jesse K; Simko, Jeff; Hurtado-Coll, Antonio; Carroll, Peter R; Gleave, Martin; Lance, Raymond; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; Brooks, James D; Squire, Jeremy A

2015-08-01

Loss of the phosphatase and tensin homolog (PTEN) tumor suppressor gene is a promising marker of aggressive prostate cancer. Active surveillance and watchful waiting are increasingly recommended to patients with small tumors felt to be low risk, highlighting the difficulties of Gleason scoring in this setting. There is an urgent need for predictive biomarkers that can be rapidly deployed to aid in clinical decision-making. Our objectives were to assess the incidence and ability of PTEN alterations to predict aggressive disease in a multicenter study. We used recently developed probes optimized for sensitivity and specificity in a four-color FISH deletion assay to study the Canary Retrospective multicenter Prostate Cancer Tissue Microarray (TMA). This TMA was constructed specifically for biomarker validation from radical prostatectomy specimens, and is accompanied by detailed clinical information with long-term follow-up. In 612 prostate cancers, the overall rate of PTEN deletion was 112 (18.3%). Hemizygous PTEN losses were present in 55/612 (9.0%) of cancers, whereas homozygous PTEN deletion was observed in 57/612 (9.3%) of tumors. Significant associations were found between PTEN status and pathologic stage (P < 0.0001), seminal vesicle invasion (P = 0.0008), extracapsular extension (P < 0.0001), and Gleason score (P = 0.0002). In logistic regression analysis of clinical and pathological variables, PTEN deletion was significantly associated with extracapsular extension, seminal vesicle involvement, and higher Gleason score. In the 406 patients in which clinical information was available, PTEN homozygous (P = 0.009) deletion was associated with worse post-operative recurrence-free survival (number of events = 189), pre-operative prostate specific antigen (PSA) (P < 0.001), and pathologic stage (P = 0.03). PTEN status assessed by FISH is an independent predictor for recurrence-free survival in multivariate models, as were seminal vesicle invasion, extracapsular extension, and Gleason score, and preoperative PSA. Furthermore, these data demonstrate that the assay can be readily introduced at first diagnosis in a cost effective manner analogous to the use of FISH for analysis of HER2/neu status in breast cancer. Combined with published research beginning 17 years ago, both the data and tools now exist to implement a PTEN assay in the clinic. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.

Candidacy for bilateral hearing aids: a retrospective multicenter study.

PubMed

Boymans, Monique; Goverts, S Theo; Kramer, Sophia E; Festen, Joost M; Dreschler, Wouter A

2009-02-01

The goal of this study was to find factors for refining candidacy criteria for bilateral hearing aid fittings. Clinical files of 1,000 consecutive hearing aid fittings were analyzed. Case history, audiometric, and rehabilitation data were collected from clinical files, and an extensive questionnaire on long-term outcome measures was conducted. After at least 2 years of hearing aid use, 505 questionnaires were returned. In order to compare differences in benefits between unilateral and bilateral fittings, two subgroups were composed in which most relevant variables (age, degree of hearing loss, and audiometric asymmetry) were matched for unilateral fittings (n=212) and bilateral fittings (n=477). The bilateral group had significantly higher benefit scores than the unilateral group for detection, speech intelligibility in reverberation, and localization, but poorer scores for comfort of loud sounds. The benefit of bilateral hearing aids was not significantly related to the level of technology of the hearing aids. The analysis of the relation between objective parameters and the subjective outcome measures showed that candidacy for a successful bilateral fitting could not be predicted from age, maximum speech intelligibility, employment, exposure to background noise, or social activities.

Treatment of juvenile idiopathic arthritis-associated uveitis: challenges and update.

PubMed

Rabinovich, C Egla

2011-09-01

To update the current understanding of the risk factors for poor outcomes in juvenile idiopathic arthritis-related uveitis. In addition, current therapies, both traditional and biological, are reviewed. Male sex, independent of age or antinuclear antibody status, is associated with increased ocular morbidity. Having anterior chamber inflammation on first exam increases the risk of developing vision-threatening eye complications. Presence of one complication increases the risk of developing another. Risk of cataract development associated with topical glucocorticoid use is better defined. Longer duration of remission on therapy has been found to decrease the risk of disease flare after discontinuation of methotrexate. Recent studies of both nonbiological and biological therapies for arthritis-related uveitis are discussed. With a better understanding of risk factors associated with the ocular morbidity of uveitis associated with juvenile idiopathic arthritis, aggressive therapies can be targeted for improved visual outcomes. Alternative treatments to avoid long-term corticosteroid use include the use of antimetabolites and biological therapies. More prospective comparator studies and/or use of multicenter databases are needed to better understand best treatments.

Early comprehensive care of preterm infants-effects on quality of life, childhood development, and healthcare utilization: study protocol for a cohort study linking administrative healthcare data with patient reported primary data.

PubMed

Schmitt, Jochen; Arnold, Katrin; Druschke, Diana; Swart, Enno; Grählert, Xina; Maywald, Ulf; Fuchs, Andreas; Werblow, Andreas; Schemken, Maryan; Reichert, Jörg; Rüdiger, Mario

2016-07-22

About 9 % of all children in Germany are born preterm. Despite significant improvements of medical care, preterm infants are at a greater risk to develop short and long term health complications. Negative consequences of preterm birth include neurodevelopmental disabilities, behavioral problems or learning disorders. Most data on effects of prematurity are derived from single or multi-center studies and not population-based. Since some of the long term problems of preterm delivery are associated with a disturbed parent-child interaction originating in the neonatal period, several intervention programs became available aiming to strengthen the early parent-child relationship. However, there is insufficient knowledge regarding the psychosocial and socioeconomic impact of these interventions. Prior to introducing them into routine care, those effects have to be rigorously evaluated. The population-based cohort study EcoCare-PIn (Early comprehensive Care of Preterm Infants-effects on quality of life, childhood development, and healthcare utilization) will investigate the following primary research questions: 1) What are the short- and long-term consequences of preterm birth with regard to parental stress, parent-child relationship, childhood development, quality of life and healthcare utilization including costs? 2) Does early family-centered psychosocial care prevent the hypothesized negative consequences of preterm birth on the above mentioned outcomes? EcoCare-PIn examines the research questions by means of a linkage of a) pseudonymized administrative individual-level claims data from the German statutory health insurance AOK PLUS on approximately 140,000 children born between 2007 and 2013 in Saxony, and b) primary data collected from the parents/caregivers of all very low birth weight (<1,500 g; n = 1,000) and low birth weight infants (1,500 to 2,500 g; n = 5,500) and a matched sample of infants above 2,500 g birth weight (n = 10,000). In Saxony, approximately 50 % of all individuals are insured at the AOK PLUS. The linkage of patient-level administrative and primary data is a novel approach in neonatal research and probably the only way to overcome shortcomings of studies solely relying on one data source. The study results are based on an observation period of up to 8 years and will directly inform perinatal healthcare provision in Saxony and Germany as a whole.

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.

Long-Term Results of a Phase II Trial of Ultrasound-Guided Radioactive Implantation of the Prostate for Definitive Management of Localized Adenocarcinoma of the Prostate (RTOG 98-05)

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

Lawton, Colleen A., E-mail: clawton@mcw.edu; Hunt, Daniel; Lee, W. Robert

2011-09-01

Purpose: To evaluate the long-term effectiveness of transrectal ultrasound-guided permanent radioactive I{sup 125} implantation of the prostate for organ confined adenocarcinoma of the prostate compared with historical data of prostatectomy and external beam radiotherapy within a cooperative group setting. Methods and Materials: Patients accrued to this study had histologically confirmed, locally confined adenocarcinoma of the prostate clinical stage T1b, T1c, or T2a; no nodal or metastatic disease; prostate-specific antigen level of {<=}10 ng/ml; and a Gleason score of {<=}6. All patients underwent transrectal ultrasound-guided radioactive I{sup 125} seed implantation into the prostate. The prescribed dose was 145 Gy to themore » prostate planning target volume. Results: A total of 101 patients from 27 institutions were accrued to this protocol; by design, no single institution accrued more than 8 patients. There were 94 eligible patients. The median follow up was 8.1 years (range, 0.1-9.2 years). After 8 years, 8 patients had protocol-defined biochemical (prostate-specific antigen) failure (cumulative incidence, 8.0%); 5 patients had local failure (cumulative incidence, 5.5%); and 1 patient had distant failure (cumulative incidence, 1.1%; this patient also had biochemical failure and died of causes not related to prostate cancer). The 8-year overall survival rate was 88%. At last follow-up, no patient had died of prostate cancer or related toxicities. Three patients had maximum late toxicities of Grade 3, all of which were genitourinary. No Grade 4 or 5 toxicities were observed. Conclusions: The long-term results of this clinical trial have demonstrated that this kind of trial can be successfully completed through the RTOG and that results in terms of biochemical failure and toxicity compare very favorably with other brachytherapy published series as well as surgical and external beam radiotherapy series. In addition, the prospective, multicenter design highlights the probable generalizability of the outcomes.« less

Kidney Outcomes 5 Years After Pediatric Cardiac Surgery

PubMed Central

Greenberg, Jason H.; Zappitelli, Michael; Devarajan, Prasad; Thiessen-Philbrook, Heather R.; Krawczeski, Catherine; Li, Simon; Garg, Amit X.; Coca, Steve; Parikh, Chirag R.

2017-01-01

IMPORTANCE Acute kidney injury (AKI) after pediatric cardiac surgery is associated with high short-term morbidity and mortality; however, the long-term kidney outcomes are unclear. OBJECTIVE To assess long-term kidney outcomes after pediatric cardiac surgery and to determine if perioperative AKI is associated with worse long-term kidney outcomes. DESIGN, SETTING, AND PARTICIPANTS This prospective multicenter cohort study recruited children between ages 1 month to 18 years who underwent cardiopulmonary bypass for cardiac surgery and survived hospitalization from 3 North American pediatric centers between July 2007 and December 2009. Children were followed up with telephone calls and an in-person visit at 5 years after their surgery. EXPOSURES Acute kidney injury defined as a postoperative serum creatinine rise from preoperative baseline by 50% or 0.3 mg/dL or more during hospitalization for cardiac surgery. MAIN OUTCOMES AND MEASURES Hypertension (blood pressure ≥95th percentile for height, age, sex, or self-reported hypertension), microalbuminuria (urine albumin to creatinine ratio >30 mg/g), and chronic kidney disease (serum creatinine estimated glomerular filtration rate [eGFR] <90 mL/min/1.73 m2 or microalbuminuria). RESULTS Overall, 131 children (median [interquartile range] age, 7.7 [5.9–9.9] years) participated in the 5-year in-person follow-up visit; 68 children (52%) were male. Fifty-seven of 131 children (44%) had postoperative AKI. At follow-up, 22 children (17%) had hypertension (10 times higher than the published general pediatric population prevalence), while 9 (8%), 13 (13%), and 1 (1%) had microalbuminuria, an eGFR less than 90 mL/min/1.73 m2, and an eGFR less than 60 mL/min/1.73 m2, respectively. Twenty-one children (18%) had chronic kidney disease. Only 5 children (4%) had been seen by a nephrologist during follow-up. There was no significant difference in renal outcomes between children with and without postoperative AKI. CONCLUSIONS AND RELEVANCE Chronic kidney disease and hypertension are common 5 years after pediatric cardiac surgery. Perioperative AKI is not associated with these complications. Longer follow-up is needed to ascertain resolution or worsening of chronic kidney disease and hypertension. PMID:27618162

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.

Laparoscopic bridging vs. anatomic open reconstruction for midline abdominal hernia mesh repair [LABOR]: single-blinded, multicenter, randomized, controlled trial on long-term functional results.

PubMed

Stabilini, Cesare; Bracale, Umberto; Pignata, Giusto; Frascio, Marco; Casaccia, Marco; Pelosi, Paolo; Signori, Alessio; Testa, Tommaso; Rosa, Gian Marco; Morelli, Nicola; Fornaro, Rosario; Palombo, Denise; Perotti, Serena; Bruno, Maria Santina; Imperatore, Mikaela; Righetti, Carolina; Pezzato, Stefano; Lazzara, Fabrizio; Gianetta, Ezio

2013-10-28

Re-approximation of the rectal muscles along the midline is recommended by some groups as a rule for incisional and ventral hernia repairs. The introduction of laparoscopic repair has generated a debate because it is not aimed at restoring abdominal wall integrity but instead aims just to bridge the defect. Whether restoration of the abdominal integrity has a real impact on patient mobility is questionable, and the available literature provides no definitive answer. The present study aims to compare the functional results of laparoscopic bridging with those of re-approximation of the rectal muscle in the midline as a mesh repair for ventral and incisional abdominal defect through an "open" access. We hypothesized that, for the type of defect suitable for a laparoscopic bridging, the effect of an anatomical reconstruction is near negligible, thus not a fixed rule. The LABOR trial is a multicenter, prospective, two-arm, single-blinded, randomized trial. Patients of more than 60 years of age with a defect of less than 10 cm at its greatest diameter will be randomly submitted to open Rives or laparoscopic defect repair. All the participating patients will have a preoperative evaluation of their abdominal wall strength and mobility along with volumetry, respiratory function test, intraabdominal pressure and quality of life assessment.The primary outcome will be the difference in abdominal wall strength as measured by a double leg-lowering test performed at 12 months postoperatively. The secondary outcomes will be the rate of recurrence and changes in baseline abdominal mobility, respiratory function tests, intraabdominal pressure, CT volumetry and quality of life at 6 and 12 months postoperatively. The study will help to define the most suitable treatment for small-medium incisional and primary hernias in patients older than 60 years. Given a similar mid-term recurrence rate in both groups, if the trial shows no differences among treatments (acceptance of the null-hypothesis), then the choice of whether to submit a patient to one intervention will be made on the basis of cost and the surgeon's experience. Current Controlled Trials ISRCTN93729016.

Testing the methodology for dosimetry audit of heterogeneity corrections and small MLC-shaped fields: Results of IAEA multi-center studies

PubMed Central

Izewska, Joanna; Wesolowska, Paulina; Azangwe, Godfrey; Followill, David S.; Thwaites, David I.; Arib, Mehenna; Stefanic, Amalia; Viegas, Claudio; Suming, Luo; Ekendahl, Daniela; Bulski, Wojciech; Georg, Dietmar

2016-01-01

Abstract The International Atomic Energy Agency (IAEA) has a long tradition of supporting development of methodologies for national networks providing quality audits in radiotherapy. A series of co-ordinated research projects (CRPs) has been conducted by the IAEA since 1995 assisting national external audit groups developing national audit programs. The CRP ‘Development of Quality Audits for Radiotherapy Dosimetry for Complex Treatment Techniques’ was conducted in 2009–2012 as an extension of previously developed audit programs. Material and methods. The CRP work described in this paper focused on developing and testing two steps of dosimetry audit: verification of heterogeneity corrections, and treatment planning system (TPS) modeling of small MLC fields, which are important for the initial stages of complex radiation treatments, such as IMRT. The project involved development of a new solid slab phantom with heterogeneities containing special measurement inserts for thermoluminescent dosimeters (TLD) and radiochromic films. The phantom and the audit methodology has been developed at the IAEA and tested in multi-center studies involving the CRP participants. Results. The results of multi-center testing of methodology for two steps of dosimetry audit show that the design of audit procedures is adequate and the methodology is feasible for meeting the audit objectives. A total of 97% TLD results in heterogeneity situations obtained in the study were within 3% and all results within 5% agreement with the TPS predicted doses. In contrast, only 64% small beam profiles were within 3 mm agreement between the TPS calculated and film measured doses. Film dosimetry results have highlighted some limitations in TPS modeling of small beam profiles in the direction of MLC leave movements. Discussion. Through multi-center testing, any challenges or difficulties in the proposed audit methodology were identified, and the methodology improved. Using the experience of these studies, the participants could incorporate the auditing procedures in their national programs. PMID:26934916

Testing the methodology for dosimetry audit of heterogeneity corrections and small MLC-shaped fields: Results of IAEA multi-center studies.

PubMed

Izewska, Joanna; Wesolowska, Paulina; Azangwe, Godfrey; Followill, David S; Thwaites, David I; Arib, Mehenna; Stefanic, Amalia; Viegas, Claudio; Suming, Luo; Ekendahl, Daniela; Bulski, Wojciech; Georg, Dietmar

2016-07-01

The International Atomic Energy Agency (IAEA) has a long tradition of supporting development of methodologies for national networks providing quality audits in radiotherapy. A series of co-ordinated research projects (CRPs) has been conducted by the IAEA since 1995 assisting national external audit groups developing national audit programs. The CRP 'Development of Quality Audits for Radiotherapy Dosimetry for Complex Treatment Techniques' was conducted in 2009-2012 as an extension of previously developed audit programs. The CRP work described in this paper focused on developing and testing two steps of dosimetry audit: verification of heterogeneity corrections, and treatment planning system (TPS) modeling of small MLC fields, which are important for the initial stages of complex radiation treatments, such as IMRT. The project involved development of a new solid slab phantom with heterogeneities containing special measurement inserts for thermoluminescent dosimeters (TLD) and radiochromic films. The phantom and the audit methodology has been developed at the IAEA and tested in multi-center studies involving the CRP participants. The results of multi-center testing of methodology for two steps of dosimetry audit show that the design of audit procedures is adequate and the methodology is feasible for meeting the audit objectives. A total of 97% TLD results in heterogeneity situations obtained in the study were within 3% and all results within 5% agreement with the TPS predicted doses. In contrast, only 64% small beam profiles were within 3 mm agreement between the TPS calculated and film measured doses. Film dosimetry results have highlighted some limitations in TPS modeling of small beam profiles in the direction of MLC leave movements. Through multi-center testing, any challenges or difficulties in the proposed audit methodology were identified, and the methodology improved. Using the experience of these studies, the participants could incorporate the auditing procedures in their national programs.

Multicenter retrospective analysis regarding the clinical manifestations and treatment results in patients with hairy cell leukemia: twenty-four year Turkish experience in cladribine therapy.

PubMed

Hacioglu, Sibel; Bilen, Yusuf; Eser, Ali; Sivgin, Serdar; Gurkan, Emel; Yildirim, Rahsan; Aydogdu, Ismet; Dogu, Mehmet Hilmi; Yilmaz, Mehmet; Kayikci, Omur; Tombak, Anil; Kuku, Irfan; Celebi, Harika; Akay, Meltem Olga; Esen, Ramazan; Korkmaz, Serdal; Keskin, Ali

2015-12-01

In this multicenter retrospective analysis, we aimed to present clinical, laboratory and treatment results of 94 patients with Hairy cell leukemia diagnosed in 13 centers between 1990 and 2014. Sixty-six of the patients were males and 28 were females, with a median age of 55. Splenomegaly was present in 93.5% of cases at diagnosis. The laboratory findings that came into prominence were pancytopenia with grade 3 bone marrow fibrosis. Most of the patients with an indication for treatment were treated with cladribine as first-line treatment. Total and complete response of cladribine was 97.3% and 80.7%. The relapse rate after cladribine was 16.6%, and treatment related mortality was 2.5%. Most preferred therapy (95%) was again cladribine at second-line, and third line with CR rate of 68.4% and 66.6%, respectively. The 28-month median OS was 91.7% in all patients and 25-month median OS 96% for patients who were given cladribine as first-line therapy. In conclusion, the first multicenter retrospective Turkish study where patients with HCL were followed up for a long period has revealed demographic characteristics of patients with HCL, and confirmed that cladribine treatment might be safe and effective in a relatively large series of the Turkish study population. Copyright © 2014 John Wiley & Sons, Ltd.

The NLstart2run study: health effects of a running promotion program in novice runners, design of a prospective cohort study

PubMed Central

2013-01-01

Background Running is associated with desirable lifestyle changes. Therefore several initiatives have been undertaken to promote running. Exact data on the health effects as a result of participating in a short-term running promotion program, however, is scarce. One important reason for dropout from a running program is a running-related injury (RRI). The incidence of RRIs is high, especially in novice runners. Several studies examined potential risk factors for RRIs, however, due to the often underpowered studies it is not possible to reveal the complex mechanism leading to an RRI yet. The primary objectives are to determine short- and long-term health effects of a nationwide “Start to Run” program and to identify determinants for RRIs in novice runners. Secondary objectives include examining reasons and determinants for dropout, medical consumption and economical consequences of RRIs as a result of a running promotion program. Methods/design The NLstart2run study is a multi-center prospective cohort study with a follow-up at 6, 12, 24 and 52 weeks. All participants that sign up for the Start to Run program in 2013, which is offered by the Dutch Athletics Federation, will be asked to participate in the study. During the running program a digital running log will be completed by the participants every week to administer exposure and running related pain. After the running program the log will be completed every second week. An RRI is defined as any musculoskeletal ailment of the lower extremity or back that the participant attributed to running and hampers running ability for at least one week. Discussion The NLstart2run study will provide insight into the short- and long-term health effects as a result of a short-term running promotion program. Reasons and determinants for dropout from a running promotion program will be examined as well. The study will result in several leads for future RRI prevention and as a result minimize dropout due to injury. This information may increase the effectiveness of future running promotion programs and will thereby contribute positively to public health. Trial registration The Netherlands National Trial Register NTR3676. The NTR is part of the WHO Primary Registries. PMID:23890182

The NLstart2run study: health effects of a running promotion program in novice runners, design of a prospective cohort study.

PubMed

Kluitenberg, Bas; van Middelkoop, Marienke; Diercks, Ron L; Hartgens, Fred; Verhagen, Evert; Smits, Dirk-Wouter; Buist, Ida; van der Worp, Henk

2013-07-26

Running is associated with desirable lifestyle changes. Therefore several initiatives have been undertaken to promote running. Exact data on the health effects as a result of participating in a short-term running promotion program, however, is scarce. One important reason for dropout from a running program is a running-related injury (RRI). The incidence of RRIs is high, especially in novice runners. Several studies examined potential risk factors for RRIs, however, due to the often underpowered studies it is not possible to reveal the complex mechanism leading to an RRI yet.The primary objectives are to determine short- and long-term health effects of a nationwide "Start to Run" program and to identify determinants for RRIs in novice runners. Secondary objectives include examining reasons and determinants for dropout, medical consumption and economical consequences of RRIs as a result of a running promotion program. The NLstart2run study is a multi-center prospective cohort study with a follow-up at 6, 12, 24 and 52 weeks. All participants that sign up for the Start to Run program in 2013, which is offered by the Dutch Athletics Federation, will be asked to participate in the study.During the running program a digital running log will be completed by the participants every week to administer exposure and running related pain. After the running program the log will be completed every second week. An RRI is defined as any musculoskeletal ailment of the lower extremity or back that the participant attributed to running and hampers running ability for at least one week. The NLstart2run study will provide insight into the short- and long-term health effects as a result of a short-term running promotion program. Reasons and determinants for dropout from a running promotion program will be examined as well. The study will result in several leads for future RRI prevention and as a result minimize dropout due to injury. This information may increase the effectiveness of future running promotion programs and will thereby contribute positively to public health. The Netherlands National Trial Register NTR3676. The NTR is part of the WHO Primary Registries.

[Motivation and significance of IARC classification for mobile phone].

PubMed

L'Abbate, N

2011-01-01

In May 2011, the IARC Working Group discussed the possibility that exposure to RF-EMF (radiofrequency electromagnetic fields) have to produce an increased risk for brain tumors and evaluated the available literature on different categories of subjects exposed, including, among others, a Danish cohort study, five case-control studies and the largest multi-center case-control study (INTERPHONE) on the use of mobile phone and brain tumors, including glioma, meningioma and acoustic neuroma. The Working Group also examined a number of studies with objectives related to various mechanisms ofcarcerogenesis. The findings have been reviewed critically and generally assessed as "limited" among users of wireless phones for glioma and acoustic neuroma and "inappropriate" to draw conclusions for other types of tumors. The evidence from occupational and environmental exposures were considered "insufficient" in the same way. Given the limited evidence in humans and in experimental animals, the Working Group has classified a large majority the RF-EMF fields as "possibly carcinogenic to humans" (Group 2B). The Director of IARC has recommended, however,further research in the long-term use of mobile phones and adoption of pragmatic steps to reduce exposure, such as hands-free devices or sms.

A manual-based phenomenological art therapy for individuals diagnosed with moderate to severe depression (PATd): A randomized controlled study.

PubMed

Blomdahl, Christina; Guregård, Suzanne; Rusner, Marie; Wijk, Helle

2018-05-14

This study investigated the effects of manual-based Phenomenological Art Therapy for individuals living with depression in addition to treatment as usual (PATd/TAU) compared with only treatment as usual (TAU) for individuals diagnosed with moderate to severe depression. 79 adults (men = 29.1%) were included in this randomized-controlled-trial (RCT), multicenter study in Sweden with an intention-to-treat design. Participants were randomized into either the PATd/TAU-group (n = 43) or TAU-group (n = 36). Data were collected at baseline and at end of treatment. The main outcomes were depression levels and self-esteem. Secondary outcomes were suicide ideation and sickness absence. The PATd/TAU-group showed a significant decrease of depression levels. The PATd/TAU-group returned to work to a higher degree than the TAU-group. Self-esteem significantly improved in both groups. Suicide ideation was unaffected. Manual-based PATd works as expected, being an effective treatment, and contributes to recovery for individuals with moderate to severe depression. This outcome needs to be confirmed and its long-term effects examined in further studies. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

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...

Sampling versus systematic full lymphatic dissection in surgical treatment of non-small cell lung cancer.

PubMed

Koulaxouzidis, Georgios; Karagkiouzis, Grigorios; Konstantinou, Marios; Gkiozos, Ioannis; Syrigos, Konstantinos

2013-04-22

The extent of mediastinal lymph node assessment during surgery for non-small cell cancer remains controversial. Different techniques are used, ranging from simple visual inspection of the unopened mediastinum to an extended bilateral lymph node dissection. Furthermore, different terms are used to define these techniques. Sampling is the removal of one or more lymph nodes under the guidance of pre-operative findings. Systematic (full) nodal dissection is the removal of all mediastinal tissue containing the lymph nodes systematically within anatomical landmarks. A Medline search was conducted to identify articles in the English language that addressed the role of mediastinal lymph node resection in the treatment of non-small cell lung cancer. Opinions as to the reasons for favoring full lymphatic dissection include complete resection, improved nodal staging and better local control due to resection of undetected micrometastasis. Arguments against routine full lymphatic dissection are increased morbidity, increase in operative time, and lack of evidence of improved survival. For complete resection of non-small cell lung cancer, many authors recommend a systematic nodal dissection as the standard approach during surgery, and suggest that this provides both adequate nodal staging and guarantees complete resection. Whether extending the lymph node dissection influences survival or recurrence rate is still not known. There are valid arguments in favor in terms not only of an improved local control but also of an improved long-term survival. However, the impact of lymph node dissection on long-term survival should be further assessed by large-scale multicenter randomized trials.

Surgical management of patients with synchronous colorectal liver metastasis: a multicenter international analysis.

PubMed

Mayo, Skye C; Pulitano, Carlo; Marques, Hugo; Lamelas, Jorge; Wolfgang, Christopher L; de Saussure, Wassila; Choti, Michael A; Gindrat, Isabelle; Aldrighetti, Luca; Barrosso, Eduardo; Mentha, Gilles; Pawlik, Timothy M

2013-04-01

The goal of this study was to investigate the surgical management and outcomes of patients with primary colorectal cancer (CRC) and synchronous liver metastasis (sCRLM). Using a multi-institutional database, we identified 1,004 patients treated for sCRLM between 1982 and 2011. Clinicopathologic and outcomes data were evaluated with uni- and multivariable analyses. A simultaneous CRC and liver operation was performed in 329 (33%) patients; 675 (67%) underwent a staged approach ("classic" staged approach, n = 647; liver-first strategy, n = 28). Patients managed with the liver-first approach had more hepatic lesions and were more likely to have bilateral disease than those in the other 2 groups (p < 0.05). The use of staged operative strategies increased over the time of the study from 58% to 75% (p < 0.001). Liver-directed therapy included hepatectomy (90%) or combined resection + ablation (10%). A major resection (>3 segments) was more common with a staged approach (39% vs 24%; p < 0.001). Overall, 509 patients (50%) received chemotherapy in either the preoperative (22%) or adjuvant (28%) settings, with 11% of patients having both. There were 197 patients (20%) who had a complication in the postoperative period, with no difference in morbidity between staged and simultaneous groups or major vs minor hepatectomies (p > 0.05). Ninety-day postoperative mortality was 3.0%, with no difference between simultaneous and staged approaches (p = 0.94). The overall median and 5-year survivals were 50.9 months and 44%, respectively; long-term survival was the same regardless of the operative approach (p > 0.05). Simultaneous and staged resections for sCRLM can be performed with comparable morbidity, mortality, and long-term oncologic outcomes. Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Multicenter study of the efficacy and safety of disopyramide in obstructive hypertrophic cardiomyopathy.

PubMed

Sherrid, Mark V; Barac, Ivan; McKenna, William J; Elliott, Perry M; Dickie, Shaughan; Chojnowska, Lidia; Casey, Susan; Maron, Barry J

2005-04-19

In this study we assessed the long-term efficacy and safety of disopyramide for patients with obstructive hypertrophic cardiomyopathy (HCM). It has been reported that disopyramide may reduce left ventricular outflow gradient and improve symptoms in patients with HCM. However, long-term efficacy and safety of disopyramide has not been shown in a large cohort. Clinical and echocardiographic data were evaluated in 118 obstructive HCM patients treated with disopyramide at 4 HCM treatment centers. Mortality in the disopyramide-treated patients was compared with 373 obstructive HCM patients not treated with disopyramide. Patients were followed with disopyramide for 3.1 +/- 2.6 years; dose 432 +/- 181 mg/day (97% also received beta-blockers). Seventy-eight patients (66%) were maintained with disopyramide without the necessity for major non-pharmacologic intervention with surgical myectomy, alcohol ablation, or pacing; outflow gradient at rest decreased from 75 +/- 33 to 40 +/- 32 mm Hg (p < 0.0001) and mean New York Heart Association functional class from 2.3 +/- 0.7 to 1.7 +/- 0.6 (p < 0.0001). Forty other patients (34%) could not be satisfactorily managed with disopyramide and required major invasive interventions because of inadequate symptom and gradient control or vagolytic side effects. All-cause annual cardiac death rate between disopyramide and non-disopyramide-treated patients did not differ significantly, 1.4% versus 2.6%/year (p = 0.07). There was also no difference in sudden death rate, 1.0%/year versus 1.8%/year (p = 0.08). Two-thirds of obstructed HCM patients treated with disopyramide could be managed medically with amelioration of symptoms and about 50% reduction in subaortic gradient over >/=3 years. Disopyramide therapy does not appear to be proarrhythmic in HCM and should be considered before proceeding to surgical myectomy or alternate strategies.

Long Term Natural History Data in Ambulant Boys with Duchenne Muscular Dystrophy: 36-Month Changes

PubMed Central

Sormani, Maria Pia; Messina, Sonia; D′Amico, Adele; Carlesi, Adelina; Vita, Gianluca; Fanelli, Lavinia; Berardinelli, Angela; Torrente, Yvan; Lanzillotta, Valentina; Viggiano, Emanuela; D′Ambrosio, Paola; Cavallaro, Filippo; Frosini, Silvia; Barp, Andrea; Bonfiglio, Serena; Scalise, Roberta; De Sanctis, Roberto; Rolle, Enrica; Graziano, Alessandra; Magri, Francesca; Palermo, Concetta; Rossi, Francesca; Donati, Maria Alice; Sacchini, Michele; Arnoldi, Maria Teresa; Baranello, Giovanni; Mongini, Tiziana; Pini, Antonella; Battini, Roberta; Pegoraro, Elena; Previtali, Stefano; Bruno, Claudio; Politano, Luisa; Comi, Giacomo P.; Bertini, Enrico; Mercuri, Eugenio

2014-01-01

The 6 minute walk test has been recently chosen as the primary outcome measure in international multicenter clinical trials in Duchenne muscular dystrophy ambulant patients. The aim of the study was to assess the spectrum of changes at 3 years in the individual measures, their correlation with steroid treatment, age and 6 minute walk test values at baseline. Ninety-six patients from 11 centers were assessed at baseline and 12, 24 and 36 months after baseline using the 6 minute walk test and the North Star Ambulatory Assessment. Three boys (3%) lost the ability to perform the 6 minute walk test within 12 months, another 13 between 12 and 24 months (14%) and 11 between 24 and 36 months (12%). The 6 minute walk test showed an average overall decline of −15.8 (SD 77.3) m at 12 months, of −58.9 (SD 125.7) m at 24 months and −104.22 (SD 146.2) m at 36 months. The changes were significantly different in the two baseline age groups and according to the baseline 6 minute walk test values (below and above 350 m) (p<0.001). The changes were also significantly different according to steroid treatment (p = 0.01). Similar findings were found for the North Star Ambulatory Assessment. These are the first 36 month longitudinal data using the 6 minute walk test and North Star Ambulatory Assessment in Duchenne muscular dystrophy. Our findings will help not only to have a better idea of the progression of the disorder but also provide reference data that can be used to compare with the results of the long term extension studies that are becoming available. PMID:25271887

Long term natural history data in ambulant boys with Duchenne muscular dystrophy: 36-month changes.

PubMed

Pane, Marika; Mazzone, Elena Stacy; Sivo, Serena; Sormani, Maria Pia; Messina, Sonia; D'Amico, Adele; Carlesi, Adelina; Vita, Gianluca; Fanelli, Lavinia; Berardinelli, Angela; Torrente, Yvan; Lanzillotta, Valentina; Viggiano, Emanuela; D Ambrosio, Paola; Cavallaro, Filippo; Frosini, Silvia; Barp, Andrea; Bonfiglio, Serena; Scalise, Roberta; De Sanctis, Roberto; Rolle, Enrica; Graziano, Alessandra; Magri, Francesca; Palermo, Concetta; Rossi, Francesca; Donati, Maria Alice; Sacchini, Michele; Arnoldi, Maria Teresa; Baranello, Giovanni; Mongini, Tiziana; Pini, Antonella; Battini, Roberta; Pegoraro, Elena; Previtali, Stefano; Bruno, Claudio; Politano, Luisa; Comi, Giacomo P; Bertini, Enrico; Mercuri, Eugenio

2014-01-01

The 6 minute walk test has been recently chosen as the primary outcome measure in international multicenter clinical trials in Duchenne muscular dystrophy ambulant patients. The aim of the study was to assess the spectrum of changes at 3 years in the individual measures, their correlation with steroid treatment, age and 6 minute walk test values at baseline. Ninety-six patients from 11 centers were assessed at baseline and 12, 24 and 36 months after baseline using the 6 minute walk test and the North Star Ambulatory Assessment. Three boys (3%) lost the ability to perform the 6 minute walk test within 12 months, another 13 between 12 and 24 months (14%) and 11 between 24 and 36 months (12%). The 6 minute walk test showed an average overall decline of -15.8 (SD 77.3) m at 12 months, of -58.9 (SD 125.7) m at 24 months and -104.22 (SD 146.2) m at 36 months. The changes were significantly different in the two baseline age groups and according to the baseline 6 minute walk test values (below and above 350 m) (p<0.001). The changes were also significantly different according to steroid treatment (p = 0.01). Similar findings were found for the North Star Ambulatory Assessment. These are the first 36 month longitudinal data using the 6 minute walk test and North Star Ambulatory Assessment in Duchenne muscular dystrophy. Our findings will help not only to have a better idea of the progression of the disorder but also provide reference data that can be used to compare with the results of the long term extension studies that are becoming available.

Long-term prognostic impact of CT-Leaman score in patients with non-obstructive CAD: Results from the COronary CT Angiography EvaluatioN For Clinical Outcomes InteRnational Multicenter (CONFIRM) study.

PubMed

Andreini, Daniele; Pontone, Gianluca; Mushtaq, Saima; Gransar, Heidi; Conte, Edoardo; Bartorelli, Antonio L; Pepi, Mauro; Opolski, Maksymilian P; Ó Hartaigh, Bríain; Berman, Daniel S; Budoff, Matthew J; Achenbach, Stephan; Al-Mallah, Mouaz; Cademartiri, Filippo; Callister, Tracy Q; Chang, Hyuk-Jae; Chinnaiyan, Kavitha; Chow, Benjamin J W; Cury, Ricardo; Delago, Augustin; Hadamitzky, Martin; Hausleiter, Joerg; Feuchtner, Gudrun; Kim, Yong-Jin; Kaufmann, Philipp A; Leipsic, Jonathon; Lin, Fay Y; Maffei, Erica; Raff, Gilbert; Shaw, Leslee J; Villines, Todd C; Dunning, Allison; Marques, Hugo; Rubinshtein, Ronen; Hindoyan, Niree; Gomez, Millie; Min, James K

2017-03-15

Non-obstructive coronary artery disease (CAD) identified by coronary computed tomography angiography (CCTA) demonstrated prognostic value. CT-adapted Leaman score (CT-LeSc) showed to improve the prognostic stratification. Aim of the study was to evaluate the capability of CT-LeSc to assess long-term prognosis of patients with non-obstructive (CAD). From 17 centers, we enrolled 2402 patients without prior CAD history who underwent CCTA that showed non-obstructive CAD and provided complete information on plaque composition. Patients were divided into a group without CAD and a group with non-obstructive CAD (<50% stenosis). Segment-involvement score (SIS) and CT-LeSc were calculated. Outcomes were non-fatal myocardial infarction (MI) and the combined end-point of MI and all-cause mortality. Patient mean age was 56±12years. At follow-up (mean 59.8±13.9months), 183 events occurred (53 MI, 99 all-cause deaths and 31 late revascularizations). CT-LeSc was the only multivariate predictor of MI (HRs 2.84 and 2.98 in two models with Framingham and risk factors, respectively) and of MI plus all-cause mortality (HR 2.48 and 1.94 in two models with Framingham and risk factors, respectively). This was confirmed by a net reclassification analysis confirming that the CT-LeSc was able to correctly reclassify a significant proportion of patients (cNRI 0.28 and 0.23 for MI and MI plus all-cause mortality, respectively) vs. baseline model, whereas SIS did not. CT-LeSc is an independent predictor of major acute cardiac events, improving prognostic stratification of patients with non-obstructive CAD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Central nervous system involvement in eosinophilic granulomatosis with polyangiitis (Churg-Strauss): Report of 26 patients and review of the literature.

PubMed

André, Raphaël; Cottin, Vincent; Saraux, Jean-Luc; Blaison, Gilles; Bienvenu, Boris; Cathebras, Pascal; Dhote, Robin; Foucher, Aurélie; Gil, Helder; Lapoirie, Joëlle; Launay, David; Loustau, Valentine; Maurier, François; Pertuiset, Edouard; Zénone, Thierry; Seebach, Jörg; Costedoat-Chalumeau, Nathalie; Puéchal, Xavier; Mouthon, Luc; Guillevin, Loïc; Terrier, Benjamin

2017-09-01

Although peripheral nervous system involvement is common in eosinophilic granulomatosis with polyangiitis (EGPA), central nervous system (CNS) manifestations are poorly described. This study aimed to describe CNS involvement in EGPA. This retrospective, observational, multicenter study included patients with EGPA and CNS involvement affecting cranial nerves, brain and/or spinal cord. We also undertook a systematic literature review. We analyzed 26 personal cases and 62 previously reported cases. At EGPA diagnosis, asthma was noted in 97%, eosinophilia in 98%, peripheral neuropathy in 55% and cardiac involvement in 41%. 38/71 (54%) were ANCA-positive, with a perinuclear-labeling pattern and/or anti-MPO specificity. CNS was involved in 86% at EGPA diagnosis, preceded EGPA in 2%, and occurred during follow-up in 12% after a median of 24months. Main neurological manifestations were ischemic cerebrovascular lesions in 46 (52%), intracerebral hemorrhage and/or subarachnoid hemorrhage in 21 (24%), loss of visual acuity in 28 (33%) (15 with optic neuritis, 9 with central retinal artery occlusion, 4 with cortical blindness), and cranial nerves palsies in 18 (21%), with 25 patients having ≥1 of these clinical CNS manifestations. Among the 81 patients with assessable neurological responses, 43% had complete responses without sequelae, 43% had partial responses with long-term sequelae and 14% refractory disease. After a mean follow-up of 36months, 11 patients died including 5 from intracerebral hemorrhages. EGPA-related CNS manifestations form 4 distinct neurological pictures: ischemic lesions, intracerebral hemorrhages, cranial nerve palsies and loss of visual acuity. Such manifestation should prompt practitioners to consider EGPA in such conditions. Long-term neurological sequelae were common, and intracerebral hemorrhages had the worst prognostic impact. Copyright © 2017 Elsevier B.V. All rights reserved.

Long-term clinical and quality of life outcomes after stenting of femoropopliteal artery stenosis: 3-year results from the STROLL study.

PubMed

Bunte, Matthew C; Cohen, David J; Jaff, Michael R; Gray, William A; Magnuson, Elizabeth A; Li, Haiyan; Feiring, Andrew; Cioppi, Marco; Hibbard, Robert; Gray, Bruce; Khatib, Yazan; Jessup, David; Patarca, Roberto; Du, Jing; Stoll, Hans-Peter; Massaro, Joe; Safley, David M

2018-03-09

To evaluate the clinical and health status outcomes of patients undergoing superficial femoral artery (SFA) revascularization using the Shape Memory Alloy Recoverable Technology (S.M.A.R.T.®) nitinol self-expanding stent through 3 years of follow-up. Limited long-term data are available describing the durability of benefits after femoropopliteal revascularization. In a multicenter, prospective, core-lab adjudicated study, 250 subjects with de novo or restenotic femoropopliteal arterial lesions were treated with the S.M.A.R.T.® stent. The primary endpoint of target vessel patency, a composite of ultrasound-assessed patency and freedom from clinically driven target lesion revascularization (TLR), was evaluated through 3 years. Secondary endpoints included stent fracture and health status. Health status was measured using generic and disease-specific instruments, including the Peripheral Artery Questionnaire (PAQ). At 3-year follow-up, Kaplan-Meier estimated target vessel patency was 72.7%, freedom from clinically driven TLR was 78.5%, and the incidence of stent fracture was 3.6%. The PAQ summary score was markedly impaired at baseline (mean 37.3 ± 19.6 points) and improved substantially at 1 month (mean change from baseline of 31.4 points, 95% CI: 28.5-34.3; P < 0.001). Disease-specific health status benefits assessed by the PAQ were largely preserved through 3 years of follow-up (mean change from baseline, 28.0 points, 95% CI: 24.3-31.7; P < 0.0001). In patients undergoing revascularization for moderately complex SFA disease, use of the self-expanding S.M.A.R.T® stent was associated with a high rate of target vessel patency through 3 years and led to substantial and sustained health status benefits. © 2018 Wiley Periodicals, Inc.

Long-term safety and efficacy of taliglucerase alfa in pediatric Gaucher disease patients who were treatment-naïve or previously treated with imiglucerase.

PubMed

Zimran, Ari; Gonzalez-Rodriguez, Derlis Emilio; Abrahamov, Aya; Cooper, Peter A; Varughese, Sheeba; Giraldo, Pilar; Petakov, Milan; Tan, Ee Shien; Chertkoff, Raul

2018-02-01

Taliglucerase alfa is an enzyme replacement therapy approved for treatment of Gaucher disease (GD) in children and adults in several countries. This multicenter extension study assessed the efficacy and safety of taliglucerase alfa in pediatric patients with GD who were treatment-naïve (n=10) or switched from imiglucerase (n=5). Patients received taliglucerase alfa 30 or 60U/kg (treatment-naïve) or the same dose as previously treated with imiglucerase every other week. In treatment-naïve patients, taliglucerase alfa 30 and 60U/kg, respectively, reduced mean spleen volume (-18.6 multiples of normal [MN] and -26.0MN), liver volume (-0.8MN and -0.9MN), and chitotriosidase activity (-72.7% and -84.4%), and increased mean Hb concentration (+2.0g/dL and +2.3g/dL) and mean platelet count (+38,200/mm 3 and +138,250/mm 3 ) from baseline through 36 total months of treatment. In patients previously treated with imiglucerase, these disease parameters remained stable through 33 total months of treatment with taliglucerase alfa. Most adverse events were mild/moderate; treatment was well tolerated. These findings extend the taliglucerase alfa safety and efficacy profile and demonstrate long-term clinical improvement in treatment-naïve children receiving taliglucerase alfa and maintenance of disease stability in children switched to taliglucerase alfa. Treatment was well-tolerated, with no new safety signals. This study is registered at www.clinicaltrials.gov as NCT01411228. Copyright © 2016 Shire Human Genetic Therapies, Inc. Published by Elsevier Inc. All rights reserved.

Ten-Year Results From the Natrelle 410 Anatomical Form-Stable Silicone Breast Implant Core Study

PubMed Central

Maxwell, G. Patrick; Van Natta, Bruce W.; Bengtson, Bradley P.; Murphy, Diane K.

2015-01-01

Background Silicone breast implants have long been used for breast augmentation and reconstruction. During this time, these medical devices have gone through a number of modifications to improve their safety, quality, and clinical outcome performance. Objectives The authors conducted a 10-year study to determine the safety and effectiveness of Natrelle 410 silicone breast implants. Methods This prospective, multicenter study enrolled 941 subjects who were undergoing either augmentation, augmentation revision, reconstruction, or reconstruction revision. Data on complications, reoperations, explantations, and subject satisfaction were collected at annual clinic visits, and one-third of subjects underwent biennial magnetic resonance imaging (MRI) to screen for implant rupture. The authors used the Kaplan-Meier estimator to calculate risk rates for local complications, reoperations, and explantations. Results Capsular contracture rates increased approximately 1% per year from the previously reported 6-year rates. The rates were significantly lower than those from the Natrelle round gel core study. The overall rate of confirmed ruptured implants in subjects who underwent MRI was 5.7%. Eleven late seromas were reported. The most common reason for explantation was a subject requesting a size or style change. Satisfaction rates remained high through 10 years, with most subjects saying they were somewhat or definitely satisfied with their implants. Conclusions This 10-year prospective trial demonstrated the long-term safety and effectiveness of Natrelle 410 anatomical form-stable implants. The complication rates were low and the satisfaction rates were high. Level of Evidence: 1 Therapeutic PMID:25717116

Efficacy and safety of long-term losartan therapy demonstrated by a prospective observational study in Japanese patients with hypertension: The Japan Hypertension Evaluation with Angiotensin II Antagonist Losartan Therapy (J-HEALTH) study.

PubMed

Naritomi, Hiroaki; Fujita, Toshiro; Ito, Sadayoshi; Ogihara, Toshio; Shimada, Kazuyuki; Shimamoto, Kazuaki; Tanaka, Heizo; Yoshiike, Nobuo

2008-02-01

The Japan Hypertension Evaluation with Angiotensin II Antagonist Losartan Therapy (J-HEALTH) study is a nationwide, prospective, multicentered, observational study that was designed to enroll 30,000 hypertensive Japanese patients from more than 3,000 private practitioners. It is the first large-scale observational study to assess the efficacy and safety of losartan, an angiotensin II receptor antagonist, in Japan. Patients were enrolled between June 2000 and May 2002, and followed up to June 2005. The data from 29,850 patients were used for the analysis of safety and efficacy. These patients were treated with losartan mostly at a daily dose of 25-50 mg. The mean follow-up period was 2.9 years. The patients were aged 62.4+/-12.1 years (mean+/-SD) and their mean systolic/diastolic blood pressure was 165.3+/-17.2/94.3+/-11.7 mmHg (mean+/-SD). Mean blood pressure in patients who were evaluated for efficacy decreased from 165.8/94.8 mmHg (n=26,512) at baseline to 145.5/84.4 mmHg after 3 months (n=21,269) and 138.6/80.0 mmHg after 36 months of treatment (n=13,879). Blood pressure was well controlled during the study period by losartan alone or losartan-based combination therapy. In nearly half of the patients, blood pressure was reduced to less than 140/90 mmHg during the study period. In addition to its antihypertensive effect, losartan reduced the uric acid level in patients whose baseline uric acid level was > or =7 mg/dL. Losartan also prevented acceleration of proteinuria. Adverse drug reactions occurred in 1,081 of the 29,850 patients. Long-term losartan therapy was effective and well tolerated in Japanese clinical practice.

Multicenter trial evaluating the use of covered self-expanding metal stents in benign biliary strictures: time to revisit our therapeutic options?

PubMed

Kahaleh, Michel; Brijbassie, Alan; Sethi, Amrita; Degaetani, Marisa; Poneros, John M; Loren, David E; Kowalski, Thomas E; Sejpal, Divyesh V; Patel, Sandeep; Rosenkranz, Laura; McNamara, Kevin N; Raijman, Isaac; Talreja, Jayant P; Gaidhane, Monica; Sauer, Bryan G; Stevens, Peter D

2013-09-01

Covered self-expanding metal stents are being used more frequently in benign biliary strictures (BBS). We report the results of a multicenter study with fully covered self-expanding metal stent (FCSEMS) placement for the management of BBS. : To prospectively evaluate the efficacy and safety of FCSEMS in the management of BBS. Patients with BBS from 6 tertiary care centers who received FCSEMS with flared ends between April 2009 and October 2010 were included in this retrospective study.Efficacy was measured after removal of FCSEMS by evaluating stricture resolution on the basis of symptom resolution, imaging, laboratory studies, and/or choledochoscopy at removal. Safety profile was evaluated by assessing postprocedural complications. A total of 133 patients (78, 58.6% males) with a mean age of 59.2±14.8 years with BBS received stents. Of the 133 stents placed, 97 (72.9%) were removed after a mean stent duration of 95.5±48.7 days. Stricture resolution after FCSEMS removal was as follows: postsurgical, 11/12 (91.6%); gallstone-related disease, 16/19 (84.2%); chronic pancreatitis, 26/31 (80.7%); other etiology, 4/5 (80.0%); and anastomotic strictures, 19/31(61.2%). Ninety-four patients were included in the logistic regression analyses. Patients who had indwelling stents for >90 days were 4.3 times more likely to have resolved strictures [odds ratio, 4.3 (95% confidence interval, 1.24-15.09)] and patients with nonmigrated stents were 5.4 times more likely to have resolved strictures [odds ratio, 5.4 (95% confidence interval, 1.001-29.29)]. FCSEMS for BBS had an acceptable rate of stricture resolution for postsurgical strictures, gallstone-related strictures, and those due to chronic pancreatitis. Predictors for stricture resolution include longer indwell time and absence of migration. Further study is warranted to assess long-term efficacy in a prospective manner with longer than 3-month time of stent indwelling time.

Randomized multicenter study of multiple plastic stents vs. covered self-expandable metallic stent in the treatment of biliary stricture in chronic pancreatitis.

PubMed

Haapamäki, Carola; Kylänpää, Leena; Udd, Marianne; Lindström, Outi; Grönroos, Juha; Saarela, Arto; Mustonen, Harri; Halttunen, Jorma

2015-07-01

The use of covered self-expandable metallic stents (cSEMS) in benign biliary indications is evolving. The aim of the study was to assess the safety and feasibility of cSEMS compared with multiple plastic stents in the treatment of benign biliary stricture (BBS) caused by chronic pancreatitis. This was a prospective, multicenter, randomized study of 60 patients with BBS caused by chronic pancreatitis. All patients received an initial plastic stent before randomization. At randomization, the stent was replaced either with a single cSEMS or three plastic stents. After 3 months, the position of the cSEMS was checked or another three plastic stents were added. At 6 months after randomization, all stents were removed. Clinical follow-up including abdominal ultrasound and laboratory tests were performed at 6 months and 2 years after stent removal. Two patients dropped out of the cSEMS group before stent removal. In April 2014, the median follow-up was 40 months (range 1 - 66 months). The 2-year, stricture-free success rate was 90 % (95 % confidence interval [CI] 72 % - 97 %) in the plastic stent group and 92 % (95 %CI 70 % - 98 %) in the cSEMS group (P = 0.405). There was one late recurrence in the plastic stent group 50 months after stent removal. Stent migration occurred three times (10 %) in the plastic stent group and twice in the cSEMS group (7 %; P = 1.000). A 6-month treatment with either six 10-Fr plastic stents or with one 10-mm cSEMS produced good long-term relief of biliary stricture caused by chronic pancreatitis.Study registered at ClinicalTrials.gov (NCT01085747). © Georg Thieme Verlag KG Stuttgart · New York.

CONKO-005: Adjuvant Chemotherapy With Gemcitabine Plus Erlotinib Versus Gemcitabine Alone in Patients After R0 Resection of Pancreatic Cancer: A Multicenter Randomized Phase III Trial.

PubMed

Sinn, Marianne; Bahra, Marcus; Liersch, Torsten; Gellert, Klaus; Messmann, Helmut; Bechstein, Wolf; Waldschmidt, Dirk; Jacobasch, Lutz; Wilhelm, Martin; Rau, Bettina M; Grützmann, Robert; Weinmann, Arndt; Maschmeyer, Georg; Pelzer, Uwe; Stieler, Jens M; Striefler, Jana K; Ghadimi, Michael; Bischoff, Sven; Dörken, Bernd; Oettle, Helmut; Riess, Hanno

2017-10-10

Purpose Gemcitabine is standard of care in the adjuvant treatment of resectable pancreatic ductal adenocarcinoma (PDAC). The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with gemcitabine has shown efficacy in the treatment of advanced PDAC and was considered to improve survival in patients with primarily resectable PDAC after R0 resection. Patients and Methods In an open-label, multicenter trial, patients were randomly assigned to one of two study arms: gemcitabine 1,000 mg/m 2 days 1, 8, 15, every 4 weeks plus erlotinib 100 mg once per day (GemErlo) or gemcitabine (Gem) alone for six cycles. The primary end point of the study was to improve disease-free survival (DFS) from 14 to 18 months by adding erlotinib to gemcitabine. Results In all, 436 patients were randomly assigned at 57 study centers between April 2008 and July 2013. A total of 361 instances (83%) of disease recurrence were observed after a median follow-up of 54 months. Median treatment duration was 22 weeks in both arms. There was no difference in median DFS (GemErlo 11.4 months; Gem 11.4 months) or median overall survival (GemErlo 24.5 months; Gem 26.5 months). There was a trend toward long-term survival in favor of GemErlo (estimated survival after 1, 2, and 5 years for GemErlo was 77%, 53%, and 25% v 79%, 54%, and 20% for Gem, respectively). The occurrence or the grade of rash was not associated with a better survival in the GemErlo arm. Conclusion To the best of our knowledge, CONKO-005 is the first study to investigate the combination of chemotherapy and a targeted therapy in the adjuvant treatment of PDAC. GemErlo for 24 weeks did not improve DFS or overall survival over Gem.

The NEtherlands Cervical Kinematics (NECK) trial. Cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in the treatment of cervical disc herniation; a double-blind randomised multicenter study.

PubMed

Arts, Mark P; Brand, Ronald; van den Akker, Elske; Koes, Bart W; Peul, Wilco C

2010-06-16

Patients with cervical radicular syndrome due to disc herniation refractory to conservative treatment are offered surgical treatment. Anterior cervical discectomy is the standard procedure, often in combination with interbody fusion. Accelerated adjacent disc degeneration is a known entity on the long term. Recently, cervical disc prostheses are developed to maintain motion and possibly reduce the incidence of adjacent disc degeneration. A comparative cost-effectiveness study focused on adjacent segment degeneration and functional outcome has not been performed yet. We present the design of the NECK trial, a randomised study on cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in patients with cervical disc herniation. Patients (age 18-65 years) presenting with radicular signs due to single level cervical disc herniation lasting more than 8 weeks are included. Patients will be randomised into 3 groups: anterior discectomy only, anterior discectomy with interbody fusion, and anterior discectomy with disc prosthesis. The primary outcome measure is symptomatic adjacent disc degeneration at 2 and 5 years after surgery. Other outcome parameters will be the Neck Disability Index, perceived recovery, arm and neck pain, complications, re-operations, quality of life, job satisfaction, anxiety and depression assessment, medical consumption, absenteeism, and costs. The study is a randomised prospective multicenter trial, in which 3 surgical techniques are compared in a parallel group design. Patients and research nurses will be kept blinded of the allocated treatment for 2 years. The follow-up period is 5 years. Currently, anterior cervical discectomy with fusion is the golden standard in the surgical treatment of cervical disc herniation. Whether additional interbody fusion or disc prosthesis is necessary and cost-effective will be determined by this trial. Netherlands Trial Register NTR1289.

A multicenter study on Leigh syndrome: disease course and predictors of survival

PubMed Central

2014-01-01

Background Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite the fact that Leigh syndrome is the most common phenotype of mitochondrial disorders in children, longitudinal natural history data is missing. This study was undertaken to assess the phenotypic and genotypic spectrum of patients with Leigh syndrome, characterise the clinical course and identify predictors of survival in a large cohort of patients. Methods This is a retrospective study of patients with Leigh syndrome that have been followed at eight centers specialising in mitochondrial diseases in Europe; Gothenburg, Rotterdam, Helsinki, Copenhagen, Stockholm, Brussels, Bergen and Oulu. Results A total of 130 patients were included (78 males; 52 females), of whom 77 patients had identified pathogenic mutations. The median age of disease onset was 7 months, with 80.8% of patients presenting by the age of 2 years. The most common clinical features were abnormal motor findings, followed by abnormal ocular findings. Epileptic seizures were reported in 40% of patients. Approximately 44% of patients experienced acute exacerbations requiring hospitalisation during the previous year, mainly due to infections. The presence of pathological signs at birth and a history of epileptic seizures were associated with higher occurrence of acute exacerbations and/or relapses. Increased lactate in the cerebrospinal fluid was significantly correlated to a more severe disease course, characterised by early onset before 6 months of age, acute exacerbations and/or relapses, as well as brainstem involvement. 39% of patients had died by the age of 21 years, at a median age of 2.4 years. Disease onset before 6 months of age, failure to thrive, brainstem lesions on neuroimaging and intensive care treatment were significantly associated with poorer survival. Conclusions This is a multicenter study performed in a large cohort of patients with Leigh syndrome. Our data help define the natural history of Leigh syndrome and identify novel predictors of disease severity and long-term prognosis. PMID:24731534

A multicenter study on Leigh syndrome: disease course and predictors of survival.

PubMed

Sofou, Kalliopi; De Coo, Irenaeus F M; Isohanni, Pirjo; Ostergaard, Elsebet; Naess, Karin; De Meirleir, Linda; Tzoulis, Charalampos; Uusimaa, Johanna; De Angst, Isabell B; Lönnqvist, Tuula; Pihko, Helena; Mankinen, Katariina; Bindoff, Laurence A; Tulinius, Már; Darin, Niklas

2014-04-15

Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite the fact that Leigh syndrome is the most common phenotype of mitochondrial disorders in children, longitudinal natural history data is missing. This study was undertaken to assess the phenotypic and genotypic spectrum of patients with Leigh syndrome, characterise the clinical course and identify predictors of survival in a large cohort of patients. This is a retrospective study of patients with Leigh syndrome that have been followed at eight centers specialising in mitochondrial diseases in Europe; Gothenburg, Rotterdam, Helsinki, Copenhagen, Stockholm, Brussels, Bergen and Oulu. A total of 130 patients were included (78 males; 52 females), of whom 77 patients had identified pathogenic mutations. The median age of disease onset was 7 months, with 80.8% of patients presenting by the age of 2 years. The most common clinical features were abnormal motor findings, followed by abnormal ocular findings. Epileptic seizures were reported in 40% of patients. Approximately 44% of patients experienced acute exacerbations requiring hospitalisation during the previous year, mainly due to infections. The presence of pathological signs at birth and a history of epileptic seizures were associated with higher occurrence of acute exacerbations and/or relapses. Increased lactate in the cerebrospinal fluid was significantly correlated to a more severe disease course, characterised by early onset before 6 months of age, acute exacerbations and/or relapses, as well as brainstem involvement. 39% of patients had died by the age of 21 years, at a median age of 2.4 years. Disease onset before 6 months of age, failure to thrive, brainstem lesions on neuroimaging and intensive care treatment were significantly associated with poorer survival. This is a multicenter study performed in a large cohort of patients with Leigh syndrome. Our data help define the natural history of Leigh syndrome and identify novel predictors of disease severity and long-term prognosis.

The NEtherlands Cervical Kinematics (NECK) Trial. Cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in the treatment of cervical disc herniation; a double-blind randomised multicenter study

PubMed Central

2010-01-01

Background Patients with cervical radicular syndrome due to disc herniation refractory to conservative treatment are offered surgical treatment. Anterior cervical discectomy is the standard procedure, often in combination with interbody fusion. Accelerated adjacent disc degeneration is a known entity on the long term. Recently, cervical disc prostheses are developed to maintain motion and possibly reduce the incidence of adjacent disc degeneration. A comparative cost-effectiveness study focused on adjacent segment degeneration and functional outcome has not been performed yet. We present the design of the NECK trial, a randomised study on cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in patients with cervical disc herniation. Methods/Design Patients (age 18-65 years) presenting with radicular signs due to single level cervical disc herniation lasting more than 8 weeks are included. Patients will be randomised into 3 groups: anterior discectomy only, anterior discectomy with interbody fusion, and anterior discectomy with disc prosthesis. The primary outcome measure is symptomatic adjacent disc degeneration at 2 and 5 years after surgery. Other outcome parameters will be the Neck Disability Index, perceived recovery, arm and neck pain, complications, re-operations, quality of life, job satisfaction, anxiety and depression assessment, medical consumption, absenteeism, and costs. The study is a randomised prospective multicenter trial, in which 3 surgical techniques are compared in a parallel group design. Patients and research nurses will be kept blinded of the allocated treatment for 2 years. The follow-up period is 5 years. Discussion Currently, anterior cervical discectomy with fusion is the golden standard in the surgical treatment of cervical disc herniation. Whether additional interbody fusion or disc prothesis is necessary and cost-effective will be determined by this trial. Trial Registration Netherlands Trial Register NTR1289 PMID:20553591

Costs and outcomes of treating chronic hepatitis C patients in routine care - results from a nationwide multicenter trial.

PubMed

Stahmeyer, J T; Krauth, C; Bert, F; Pfeiffer-Vornkahl, H; Alshuth, U; Hüppe, D; Mauss, S; Rossol, S

2016-02-01

Viral hepatitis is a major public health problem affecting millions of people worldwide. Long-term consequences are the development of liver cirrhosis and hepatocellular carcinoma. The aim of the study was to assess outcomes and costs of treating patients with chronic hepatitis C in clinical practice in Germany. We carried out a prospective noninterventional study. Information on treatment outcomes, resource utilization and quality of life was provided by 281 physicians throughout Germany. Data of 3708 monoinfected HCV-patients treated between 2008 and 2011 were analysed. Therapy consisted of peginterferon/ribavirin. Mean age of patients was 43.7 years, 60.3% were male and estimated duration of infection was 13.6 years. Predominantly genotype 1 (61.3%) or 3 (28.5%) infections were observed. Sustained viral response (SVR)-rates in most frequently observed genotypes were 49.2% in GT-1 and 61.9% in GT-3 treatment-naive patients (Relapser: GT-1: 35.3% and GT-3: 57.3%; Nonresponder: GT-1: 25.0% and GT-3: 33.3%). Average treatment costs were lowest in treatment-naive patients (€18 965) and higher in patients who failed previous treatments (relapsers: €24 753; nonresponders: €19 511). Differences according to genotype were observed. Average costs per SVR in treatment-naive patients were €44 744 for GT-1 and €22 218 for GT-3. Treatment was associated with a decrease in quality of life; post-treatment quality of life was higher in patients achieving SVR. Our insight on real-life treatment outcomes and costs can serve as a reference for a comparison with other treatments. There is high need for short-term and long-term cost-effectiveness analysis in real-life settings as newly introduced treatment strategies with direct acting antivirals result in high SVR-rates but are more costly. © 2015 John Wiley & Sons Ltd.

The laparoscopic mini-gastric bypass: the Italian experience: outcomes from 974 consecutive cases in a multicenter review.

PubMed

Musella, M; Susa, A; Greco, F; De Luca, M; Manno, E; Di Stefano, C; Milone, M; Bonfanti, R; Segato, G; Antonino, A; Piazza, L

2014-01-01

Due to the failure of the "old Mason loop," the mini-gastric bypass (MGB) has been viewed with skepticism. During the past 12 years, a growing number of authors from around the world have continued to report excellent short- and long-term results with MGB. One university center, three regional hospitals, and two private hospitals participated in this study. From July 2006 to December 2012, 475 men (48.8 %) and 499 women (51.2 %) underwent 974 laparoscopic MGBs. The mean age of these patients was 39.4, and their preoperative body mass index was 48 ± 4.58 kg/m(2). Type 2 diabetes mellitus (T2DM) affected 224 (22.9 %) of the 974 patients, whereas 291 of the 974 patients (29.8 %) presented with hypertension. The preoperative gastrointestinal status was explored in all the patients through esophagogastroduodenoscopia. The major end points of the study were definitions of both MGB safety and efficacy in the long term as well as the endoscopic changes in symptomatic patients eventually produced by surgery. The rate of conversion to open surgery was 1.2 % (12/974), and the mortality rate was 0.2 % (2/974). The perioperative morbidity rate was 5.5 % (54/974), with 20 (2 %) of the 974 patients requiring an early surgical revision. The mean hospital length of stay was 4.0 ± 1.7 days. At this writing, 818 patients are being followed up. Late complications have affected 74 (9 %) of the 818 patients. The majority of these complications (66/74, 89.1 %) have occurred within 1 year after surgery. Bile reflux gastritis was symptomatic, with endoscopic findings reported for 8 (0.9 %) and acid peptic ulcers for 14 (1.7 %) of the 818 patients. A late revision surgery was required for 7 (0.8 %) of the 818 patients. No patient required revision surgery due to biliary gastritis. At 60 months, the percentage of excess weight loss was 77 ± 5.1 %, the T2DM remission was 84.4 %, and the resolution of hypertension was 87.5 %. Despite initial skepticism, this study, together with many other large-scale, long-term similar studies from around the world (e.g., Taiwan, United States, France, Spain, India, Lebanon) demonstrated the MGB to be a short, simple, low-risk, effective, and durable bariatric procedure.

Long-term exposure and safety of lacosamide monotherapy for the treatment of partial-onset (focal) seizures: Results from a multicenter, open-label trial.

PubMed

Vossler, David G; Wechsler, Robert T; Williams, Paulette; Byrnes, William; Therriault, Sheila

2016-10-01

To assess long-term use and safety of lacosamide (LCM) ≤800 mg/day monotherapy in patients with partial-onset seizures (POS) enrolled previously in a historical-controlled, conversion-to-monotherapy study (SP902; NCT00520741). Patients completing or exiting SP902 with LCM as monotherapy or as adjunctive therapy were eligible to enter this 2-year open-label extension (OLE) trial (SP904; NCT00530855) at a starting dose ±100 mg/day of their final SP902 dose. Investigators could adjust the LCM dose to 100-800 mg/day and add up to two antiepileptic drugs to optimize tolerability and seizure reduction. Three hundred twenty-two patients received LCM: 210 patients (65.2%) completed and 112 (34.8%) discontinued, most commonly owing to withdrawal of consent (9.3%). Two hundred fifty-eight patients (80.1%) had ≥1 year of and 216 (67.1%) had ≥2 years of LCM exposure, of whom 179/258 (69.4%) achieved LCM monotherapy lasting for any 12-month period, and 126/216 (58.3%) patients exposed for ≥24 months achieved LCM monotherapy for any 24-month period. Total exposure = 525.5 patient-years. The median modal dose was 500 mg/day. Two hundred ninety-two patients (90.7%) achieved LCM monotherapy at some point during the study. Sixty-five of 87 patients who exited and 193/235 who completed SP902 were exposed for ≥12 months, and 43.1% and 78.2%, respectively, achieved LCM monotherapy for ≥12 months. Median LCM monotherapy duration was 587.0 days (2-791 days); 91.0% of patients reported treatment-emergent adverse events, of which the most common were dizziness (27.3%), headache (17.1%), and nausea (14.3%). Compared with the SP902 study baseline, 74.2% of patients had a ≥50% seizure reduction and 5.6% were seizure-free at 24 months. The majority of patients were receiving LCM monotherapy at 0, 12, and 24 months in this OLE. Lacosamide monotherapy (median dose of 500 mg/day) had a safety profile similar to that of adjunctive therapy studies. These results support the use of lacosamide as long-term monotherapy treatment for adults with POS. © 2016 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Temporary Inferior Vena Cava Filters: How Do We Move Forward?

PubMed

Arous, Edward J; Messina, Louis M

2016-05-01

Despite their widespread use, the indications for the selective use of temporary inferior vena cava (IVC) filters remains uncertain with few trials supporting their use. Additionally, the risks of long-term temporary IVC filter insertion are being increasingly discussed amongst the mainstream media and through multiple class action lawsuits. Retrievable IVC filters were specifically designed to have a less secure implantation in order to facilitate retrieval. However, multiple reports have demonstrated significant filter-related complications, most commonly related to duration of implantation. Furthermore, the risk is not isolated to one manufacturer alone. The incidence of filter-related complications is linearly related to its duration of time on the market. Currently, the FDA recommends that IVC filters be removed within 25-54 days of their implantation. Unfortunately, little evidence exists to show that this recommendation is followed routinely. Recently, the PRESERVE Trial (NCT02381509) was initiated as a multicenter non-randomized open label study to determine the safety and effectiveness of commercially available IVC filters (both temporary and permanent) in individuals who require mechanical prophylaxis against pulmonary embolism. Until such evidence is developed, temporary IVC filters should be implanted based on best available evidence and routinely removed within the guidelines of the FDA of 25-54 days. A fair question at this point is whether the design features themselves that are required to manufacture a low profile removable IVC filter can achieve effective prophylaxis against pulmonary embolism at a low rate of short and long-term complications. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Drug-coated balloons for de novo lesions in small coronary arteries: rationale and design of BASKET-SMALL 2.

PubMed

Gilgen, Nicole; Farah, Ahmed; Scheller, Bruno; Ohlow, Marc-Alexander; Mangner, Norman; Weilenmann, Daniel; Wöhrle, Jochen; Jamshidi, Peiman; Leibundgut, Gregor; Möbius-Winkler, Sven; Zweiker, Robert; Krackhardt, Florian; Butter, Christian; Bruch, Leonhard; Kaiser, Christoph; Hoffmann, Andreas; Rickenbacher, Peter; Mueller, Christian; Stephan, Frank-Peter; Coslovsky, Michael; Jeger, Raban

2018-05-01

The treatment of coronary small vessel disease (SVD) remains an unresolved issue. Drug-eluting stents (DES) have limited efficacy due to increased rates of instent-restenosis, mainly caused by late lumen loss. Drug-coated balloons (DCB) are a promising technique because native vessels remain structurally unchanged. Basel Stent Kosten-Effektivitäts Trial: Drug-Coated Balloons vs. Drug-Eluting Stents in Small Vessel Interventions (BASKET-SMALL 2) is a multicenter, randomized, controlled, noninferiority trial of DCB vs DES in native SVD for clinical endpoints. Seven hundred fifty-eight patients with de novo lesions in vessels <3 mm in diameter and an indication for percutaneous coronary intervention such as stable angina pectoris, silent ischemia, or acute coronary syndromes are randomized 1:1 to angioplasty with DCB vs implantation of a DES after successful initial balloon angioplasty. The primary endpoint is the combination of cardiac death, nonfatal myocardial infarction, and target-vessel revascularization up to 1 year. Secondary endpoints include stent thrombosis, Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding, and long-term outcome up to 3 years. Based on clinical endpoints after 1 year, we plan to assess the noninferiority of DCB compared to DES in patients undergoing primary percutaneous coronary intervention for SVD. Results will be available in the second half of 2018. This study will compare DCB and DES regarding long-term safety and efficacy for the treatment of SVD in a large all-comer population. © 2018 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.

Endoscopic balloon dilatation of Crohn's disease strictures: results from a large United kingdom series.

PubMed

Bhalme, Mahesh; Sarkar, Sanchoy; Lal, Simon; Bodger, Keith; Baker, Rose; Willert, Robert P

2014-02-01

Stricturing is a common complication of Crohn's disease. Endoscopic balloon dilatation (EBD) offers a valuable alternative to surgical intervention, but there are limited data on factors influencing its safety and efficacy. A multicenter retrospective audit across 4 U.K. teaching hospitals was performed on the use of EBD for Crohn's strictures between 1998 and 2011. Demographics, smoking status, medications, C-reactive protein, endoscopic findings, and subsequent surgery at follow-up were recorded. Success of EBD was defined as symptomatic improvement without the need for surgery at follow-up. Seventy-nine patients (47 women; median age, 48 yr) were identified for this study. Forty-eight (61%) patients had ileocolonic anastomotic strictures, whereas the rest had de novo strictures. In total, 191 EBDs (range, 1-11; median 2) were carried out on 93 strictures (range, 1-5; median 1) over a median duration of 12 months (range, 1-84). There were no serious adverse events. Success at index EBD was 34%, with a further 43% achieving long-term benefit from additional EBDs. Eighteen (23%) patients required surgery. Time to surgery after the first EDB was 2.6 to 71.1 months (median, 12.8 mo). Longer Crohn's disease duration (P = 0.03) and high C-reactive protein (P = 0.008) were associated with an increased need for subsequent surgery. EBD was safe and effective in achieving long-term symptom improvement and avoidance of surgery in most patients. Prospective controlled trials are needed to evaluate the effect of other factors, including Crohn's disease phenotype, and the role of concomitant medication to identify those best suited to EBD.

Peroral endoscopic myotomy as salvation technique post-Heller: International experience.

PubMed

Tyberg, Amy; Sharaiha, Reem Z; Familiari, Pietro; Costamagna, Guido; Casas, Fernando; Kumta, Nikhil A; Barret, Maximilien; Desai, Amit P; Schnoll-Sussman, Felice; Saxena, Payal; Martínez, Guadalupe; Zamarripa, Felipe; Gaidhane, Monica; Bertani, Helga; Draganov, Peter V; Balassone, Valerio; Sharata, Ahmed; Reavis, Kevin; Swanstrom, Lee; Invernizzi, Martina; Seewald, Stefan; Minami, Hitomi; Inoue, Haruhiro; Kahaleh, Michel

2018-01-01

Treatment for achalasia has traditionally been Heller myotomy (HM). Despite its excellent efficacy rate, a number of patients remain symptomatic post-procedure. Limited data exist as to the best management for recurrence of symptoms post-HM. We present an international, multicenter experience evaluating the efficacy and safety of post-HM peroral endoscopic myotomy (POEM). Patients who underwent POEM post-HM from 13 centers from January 2012 to January 2017 were included as part of a prospective registry. Technical success was defined as successful completion of the myotomy. Clinical success was defined as an Eckardt score of ≤3 on 12-month follow up. Adverse events (AE) including anesthesia-related, operative, and postoperative complications were recorded. Fifty-one patients were included in the study (mean age 54.2, 47% male). Technical success was achieved in 100% of patients. Clinical success on long-term follow up was achieved in 48 patients (94%), with a mean change in Eckardt score of 6.25. Seven patients (13%) had AE: six experienced periprocedural mucosal defect treated endoscopically and two patients developed mediastinitis treated conservatively. For patients with persistent symptoms after HM, POEM is a safe salvation technique with good short-term efficacy. As a result of the challenge associated with repeat HM, POEM might become the preferred technique in this patient population. Further studies with longer follow up are needed. © 2017 Japan Gastroenterological Endoscopy Society.

Psoriasis and Cardiovascular Risk: Strength in Numbers Part II

PubMed Central

Gelfand, Joel M.; Mehta, Nehal N.; Langan, Sinéad M.

2012-01-01

Summary The Psoralen plus Ultraviolet-A (PUVA) cohort study has been a tremendous success in determining how a novel treatment (i.e. PUVA) impacts the long-term risk of keratinocyte carcinoma. The ability to follow patients from the initial multi-center clinical trial for over three decades has been a remarkable achievement in dermatoepidemiology. In this issue, Stern and Huibregste report results from the PUVA follow-up study and conclude that only patients with exceptionally severe psoriasis have an increased overall mortality risk and that there is no significant risk of cardiovascular mortality associated with psoriasis. The results are in contrast to a large and growing body of literature that suggests patients with more severe psoriasis have a clinically significant increased risk of mortality in general, and cardiovascular disease in particular. In addition, the authors found no association between severe psoriasis and obesity or between obesity and cardiovascular mortality, despite extensive literature establishing these associations. Basic principles of epidemiological study design may explain these discrepancies. Ultimately, however, , randomized clinical trials will be necessary to determine whether severe psoriasis is in fact a “visible killer”, as four decades ago (after many years of controversy), hypertension was recognized to be a “silent killer”. PMID:21494241

Similar Occurrence of Febrile Episodes Reported in Non-Atopic Children at Three to Five Years of Age after Prebiotics Supplemented Infant Formula

PubMed Central

van Stuijvenberg, Margriet; Stam, José; Grüber, Christoph; Mosca, Fabio; Arslanoglu, Sertac; Chirico, Gaetano; Braegger, Christian P.; Riedler, Josef; Boehm, Günther; Sauer, Pieter J. J.

2015-01-01

This is a follow up study of a multicenter randomised placebo-controlled trial in seven centres in five West European countries. The RCT assessed the effect of infant formula supplemented with a mixture of prebiotics (with neutral short-chain and long-chain oligosaccharides and pectin-derived acidic oligosaccharides) during infancy in term-born children (n=1130). In the follow-up study 672 children (60% of the study population) participated: 232 (56%) from the prebiotics group (PG), 243 (58%) from the control group (CG), and 197 (66%) from the non-randomised breast-fed group (BG). The primary outcome was the occurrence of febrile episodes at three to five years of age prospectively documented by the parents: in the PG 1.17 (interquartile range 0.50-2.08) episodes per year versus 1.20 (0.52-2.57) in the CG; and 1.48 (0.65-2.60) in the BG. This specific prebiotics mixture given during infancy in healthy non-atopic subjects does not decrease febrile episodes and therefore seems not to prevent infection between their third and fifth birthday. PMID:26076141

Multicenter study of pars plana vitrectomy for optic disc pit maculopathy: MACPIT study.

PubMed

Avci, R; Kapran, Z; Ozdek, Ş; Teke, M Y; Oz, O; Guven, D; Yilmaz, S; Kaderli, B; Durukan, A H; Sobaci, G; Unver, Y B; Akduman, L; Kaynak, S; Dogan, I; Inan, U U

2017-09-01

PurposeTo evaluate surgical intervention with pars plana vitrectomy (PPV) for correction of optic disc pit maculopathy (ODP-M).Patients and methodsRetrospective chart review from 13 centres of 51 eyes of 50 patients with ODP-M who underwent PPV between 2002-2014. Anatomic and final best-corrected visual acuity (BCVA) outcomes were evaluated for all cases with different adjuvant techniques.ResultsThere were 23 males and 27 females with median age 25.5 (6-68) years. Preoperative median foveal thickness was 694.5 (331-1384) μm and improved to 252.5 (153-1405) μm. Median BCVA improved from 20/200 (20/20000 to 20/40) to 20/40 (20/2000 to 20/20) with 20/40 or better in 31 eyes. Complete retinal reattachment was achieved in 44 eyes (86.3%) at 7.1 (5.9) months. The good surgical outcomes were achieved in different adjuvant groups. Median follow-up was 24 (6 to 120) months.ConclusionsThese results confirm the long-term effectiveness of PPV for ODP-M. Prospective studies are needed to determine the effectiveness of any adjuvant technique in improving the success of PPV for ODP-M.

Similar Occurrence of Febrile Episodes Reported in Non-Atopic Children at Three to Five Years of Age after Prebiotics Supplemented Infant Formula.

PubMed

van Stuijvenberg, Margriet; Stam, José; Grüber, Christoph; Mosca, Fabio; Arslanoglu, Sertac; Chirico, Gaetano; Braegger, Christian P; Riedler, Josef; Boehm, Günther; Sauer, Pieter J J

2015-01-01

This is a follow up study of a multicenter randomised placebo-controlled trial in seven centres in five West European countries. The RCT assessed the effect of infant formula supplemented with a mixture of prebiotics (with neutral short-chain and long-chain oligosaccharides and pectin-derived acidic oligosaccharides) during infancy in term-born children (n=1130). In the follow-up study 672 children (60% of the study population) participated: 232 (56%) from the prebiotics group (PG), 243 (58%) from the control group (CG), and 197 (66%) from the non-randomised breast-fed group (BG). The primary outcome was the occurrence of febrile episodes at three to five years of age prospectively documented by the parents: in the PG 1.17 (interquartile range 0.50-2.08) episodes per year versus 1.20 (0.52-2.57) in the CG; and 1.48 (0.65-2.60) in the BG. This specific prebiotics mixture given during infancy in healthy non-atopic subjects does not decrease febrile episodes and therefore seems not to prevent infection between their third and fifth birthday.

Doxapram Treatment for Apnea of Prematurity: A Systematic Review.

PubMed

Vliegenthart, Roseanne J S; Ten Hove, Christine H; Onland, Wes; van Kaam, Anton H L C

2017-01-01

Apnea of prematurity (AOP) is a common complication of preterm birth, for which caffeine is the first treatment of choice. In case of persistent AOP, doxapram has been advocated as an additional therapy. To identify and appraise all existing evidence regarding efficacy and safety of doxapram use for AOP in infants born before 34 weeks of gestational age. All studies reporting on doxapram use for AOP were identified by searching electronic databases, references from relevant studies, and abstracts from the Societies for Pediatric Research. Two reviewers independently assessed study eligibility and quality, and extracted data on study design, patient characteristics, efficacy and safety outcomes. The randomized controlled trials showed less apnea during doxapram treatment when compared to placebo, but no difference in treatment effect when compared to theophylline. No serious adverse effects were reported. We identified 28 observational studies consisting mainly of cohort studies and case series (n = 1,994). There was considerable heterogeneity in study design and quality. Most studies reported a positive effect of doxapram on apnea rate. A few studies reported on long-term outcomes with conflicting results. A range of possible doxapram-related short-term adverse effects were reported, sometimes associated with the use of higher doses. Based on the limited number of studies and level of evidence, no firm conclusions on the efficacy and safety of doxapram in preterm infants can be drawn. For this reason, routine use cannot be recommended. A large multicenter randomized controlled trial is urgently needed to provide more conclusive evidence. © 2016 The Author(s) Published by S. Karger AG, Basel.

Short- and long-term outcomes following laparoscopic vs open surgery for pathological T4 colorectal cancer: 10 years of experience in a single center.

PubMed

Yang, Zi-Feng; Wu, De-Qing; Wang, Jun-Jiang; Lv, Ze-Jian; Li, Yong

2018-01-07

To evaluate the short-term and long-term outcomes following laparoscopic vs open surgery for pathological T4 (pT4) colorectal cancer. We retrospectively analyzed the short- and long-term outcomes of proven pT4 colorectal cancer patients who underwent complete resection by laparoscopic or open surgery from 2006 to 2015 at Guangdong General Hospital. A total of 211 pT4 colorectal cancer patients were included in this analysis, including 101 cases in the laparoscopy (LAP) group and 110 cases in the open surgery (OPEN) group [including 15 (12.9%) cases of conversion to open surgery]. Clinical information (age, gender, body mass index, comorbidities, American Society of Anesthesiologists score, etc .) did not differ between the two groups. In terms of blood loss, postoperative complications and rate of recovery, the LAP group performed significantly more favorably ( P < 0.05). With regard to pT4a/b and combined organ resection, there were significantly more cases in the OPEN group ( P < 0.05). The 3- and 5-year overall survival rates were 74.9% and 60.5%, respectively, for the LAP group and 62.4% and 46.5%, respectively, for the OPEN group ( P = 0.060). The 3- and 5-year disease-free survival rates were 68.0% and 57.3%, respectively, for the LAP group and 55.8% and 39.8%, respectively, for the OPEN group ( P = 0.053). Multivariate analysis showed that IIIB/IIIC stage, lymph node status, and CA19-9 were significant predictors of overall survival. PT4a/b, IIIC stage, histological subtypes, CA19-9, and adjuvant chemotherapy were independent factors affecting disease-free survival. Laparoscopy is safely used in the treatment of pT4 colorectal cancer while offering advantages of minimal invasiveness and faster recovery. Laparoscopy is able to achieve good oncologic outcomes similar to those of open surgery. We recommend that laparoscopy be carried out in experienced centers. It is still required to screen the appropriate cases for laparoscopic surgery, optimize the preoperative diagnosis process, and reduce the conversion rate. Multi-center, prospective, and large-sample studies are required to assess these issues.

Outcome of the Respiratory Syncytial Virus related acute lower respiratory tract infection among hospitalized newborns: a prospective multicenter study.

PubMed

Alan, Serdar; Erdeve, Omer; Cakir, Ufuk; Akduman, Hasan; Zenciroglu, Aysegul; Akcakus, Mustafa; Tunc, Turan; Gokmen, Zeynel; Ates, Can; Atasay, Begum; Arsan, Saadet

2016-01-01

To determine the incidence and outcomes of respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (ALRI) including morbidity, nosocomial infection and mortality among newborn infants who were admitted to the neonatal intensive care units (NICUs). A multicenter, prospective study was conducted in newborns who were hospitalized with community acquired or nosocomial RSV infection in 44 NICUs throughout Turkey. Newborns with ALRI were screened for RSV infection by Respi-Strip®-test. Main outcome measures were the incidence of RSV-associated admissions in the NICUs and morbidity, mortality and epidemics results related to these admissions. The incidence of RSV infection was 1.24% (n: 250) and RSV infection constituted 19.6% of all ALRI hospitalizations, 226 newborns (90.4%) had community-acquired whereas 24 (9.6%) patients had nosocomial RSV infection in the NICUs. Of the 250 newborns, 171 (68.4%) were full-term infants, 183 (73.2%) had a BW >2500 g. RSV-related mortality rate was 1.2%. Four NICUs reported seven outbreaks on different months, which could be eliminated by palivizumab prophylaxis in one NICU. RSV-associated ALRI both in preterm and term infants accounts an important percent of hospitalizations in the season, and may threat other high-risk patients in the NICU.

A multicenter randomized controlled trial of two group education programs for fatigue in multiple sclerosis: Long-term (12-month) follow-up at one site.

PubMed

Hugos, Cinda L; Cameron, Michelle H; Chen, Zunqiu; Chen, Yiyi; Bourdette, Dennis

2018-05-01

A four-site RCT of Fatigue: Take Control (FTC), a multicomponent group program, found no significant differences from a control program, MS: Take Control (MSTC), in fatigue on the Modified Fatigue Impact Scale (MFIS) through 6 months. Assess FTC for a delayed effect on fatigue. Of 78 subjects at one site, 74 randomized to FTC or MSTC completed the MFIS at 12 months. Compared to baseline, FTC produced greater improvements in MFIS scores than MSTC (FTC -8.9 (confidence interval (CI): 32.2, 45), MSTC -2.5 (CI 39.6, 47.7), p = 0.03) at 12 months. The delayed effect of FTC on fatigue suggests the need for longer follow-up when assessing interventions for fatigue.

Multi-Center Traffic Management Advisor Operational Field Test Results

NASA Technical Reports Server (NTRS)

Farley, Todd; Landry, Steven J.; Hoang, Ty; Nickelson, Monicarol; Levin, Kerry M.; Rowe, Dennis W.

2005-01-01

The Multi-Center Traffic Management Advisor (McTMA) is a research prototype system which seeks to bring time-based metering into the mainstream of air traffic control (ATC) operations. Time-based metering is an efficient alternative to traditional air traffic management techniques such as distance-based spacing (miles-in-trail spacing) and managed arrival reservoirs (airborne holding). While time-based metering has demonstrated significant benefit in terms of arrival throughput and arrival delay, its use to date has been limited to arrival operations at just nine airports nationally. Wide-scale adoption of time-based metering has been hampered, in part, by the limited scalability of metering automation. In order to realize the full spectrum of efficiency benefits possible with time-based metering, a much more modular, scalable time-based metering capability is required. With its distributed metering architecture, multi-center TMA offers such a capability.

Crossing the perspectives of patients, families, and physicians on cancer treatment: A qualitative study

PubMed Central

Bousquet, Guilhem; Labey, Mathilde; Gueguen, Juliette; Laporte, Cyril; Winterman, Sabine; Picard, Camille; Nascimbeni, Clara; Verneuil, Laurence; Revah-Levy, Anne

2017-01-01

Purpose Patients, family members, and physicians participate in cancer care, but their perspectives about what is helpful during cancer treatment have rarely been compared. The aim of this study was to compare these three perspectives. Methods Multicenter qualitative study (with previously published protocol) based on 90 semi-structured interviews. Participants (purposively selected until data saturation) came from three different subsamples: (i) patients with cancer (n=30), (ii) their relatives (n=30), and (iii) their referring physicians (n=10, interviewed more than once). Results Our analysis found 3 main axes (perceived positive effects of cancer treatment, perceived negative effects of cancer treatment, doctor-physician relationship), each composed of 2 main themes. The findings showed that patients, families, and physicians shared the long-term objective of increasing survival (while reducing side effects). However, patients and relatives also pointed out the importance of living with cancer each day and thus of factors helping them to live as well as possible in daily life. The physicians difficulty in coping with patients suffering may limit their access to elements that can improve patients capacity to live as well as possible. Conclusions During cancer treatment (and not only at the end of life), attention should be given to enhancing the capacity of patients to live as well as possible (not only as long as possible) to meet the goals of patient-centered care and satisfy this important need of patients and families. PMID:27769072

Multicenter AIDS Cohort Study Quantitative Coronary Plaque Progression Study: rationale and design.

PubMed

Nakanishi, Rine; Post, Wendy S; Osawa, Kazuhiro; Jayawardena, Eranthi; Kim, Michael; Sheidaee, Nasim; Nezarat, Negin; Rahmani, Sina; Kim, Nicholas; Hathiramani, Nicolai; Susarla, Shriraj; Palella, Frank; Witt, Mallory; Blaha, Michael J; Brown, Todd T; Kingsley, Lawrence; Haberlen, Sabina A; Dailing, Christopher; Budoff, Matthew J

2018-01-01

The association of HIV with coronary atherosclerosis has been established; however, the progression of coronary atherosclerosis over time among participants with HIV is not well known. The Multicenter AIDS Cohort Study Quantitative Coronary Plaque Progression Study is a large prospective multicenter study quantifying progression of coronary plaque assessed by serial coronary computed tomography angiography (CTA). HIV-infected and uninfected men who were enrolled in the Multicenter AIDS Cohort Study Cardiovascular Substudy were eligible to complete a follow-up contrast coronary CTA 3-6 years after baseline. We measured coronary plaque volume and characteristics (calcified and noncalcified plaque including fibrous, fibrous-fatty, and low attenuation) and vulnerable plaque among HIV-infected and uninfected men using semiautomated plaque software to investigate the progression of coronary atherosclerosis over time. We describe a novel, large prospective multicenter study investigating incidence, transition of characteristics, and progression in coronary atherosclerosis quantitatively assessed by serial coronary CTAs among HIV-infected and uninfected men.

Quality of life in cancer patients undergoing anticoagulant treatment with LMWH for venous thromboembolism: the QUAVITEC study on behalf of the Groupe Francophone Thrombose et Cancer (GFTC).

PubMed

Farge, Dominique; Cajfinger, Francis; Falvo, Nicolas; Berremili, Toufek; Couturaud, Francis; Bensaoula, Okba; Védrine, Lionel; Bensalha, Hocine; Bonnet, Isabelle; Péré-Vergé, Denis; Coudurier, Marie; Li, Veronique; Rafii, Hanadi; Benzidia, Ilham; Connors, Jean M; Resche-Rigon, Matthieu

2018-06-05

Clinical guidelines recommend at least 3-months low molecular weight heparin (LMWH) treatment for established venous thromboembolism (VTE) in cancer patients. However, no study has analyzed the impact of 3-6 months of LMWH therapy on quality-of-life (QoL) in cancer patients. Among 400 cancer patients included at M0, 88.8% received long-term LMWH. Using a random-effects linear regression model with time as covariate, QoL scores in the MOS SF-36 (Global HRQoL, 1.3-fold per month [95% confidence interval (CI) 0.81-1.79], p < 0.0001) and EORTC QLQ-C30 (global health status/qol, 2.25-fold per month [95% CI 1.63-2.88]; p < 0.0001) questionnaires significantly improved over the 6-month study period in patients treated with LMWH, while VEINES-QOL scores did not change. In the MOS SF-36 and EORTC QLQ-C30, the following factors were associated with change in QoL: symptomatic VTE, cancer dissemination and histological type. Factors pertaining to reduced mobility were also identified as significant predictors of QoL outcomes, including being bedridden in the MOS SF-36 and ECOG score ≥ 2 in the EORTC QLQ-C30. Presence of acute infection and not undergoing anti-angiogenic therapy were additional factors associated with QoL improvement in the EORTC QLQ-C30. QUAVITEC, a prospective, longitudinal, multicenter study, recruited all consecutive eligible adult cancer patients with objectively confirmed VTE between February 2011 and 2012. Patients were asked to answer three QoL questionnaires at anticoagulant treatment initiation (M0) and at 3 (M3) and 6 (M6)-month follow-ups. QUAVITEC is the first study to show that QoL was improved in cancer patients receiving long-term LMWH treatment for established VTE.

Stereotactic Radiosurgery for Cushing Disease: Results of an International, Multicenter Study.

PubMed

Mehta, Gautam U; Ding, Dale; Patibandla, Mohana Rao; Kano, Hideyuki; Sisterson, Nathaniel; Su, Yan-Hua; Krsek, Michal; Nabeel, Ahmed M; El-Shehaby, Amr; Kareem, Khaled A; Martinez-Moreno, Nuria; Mathieu, David; McShane, Brendan; Blas, Kevin; Kondziolka, Douglas; Grills, Inga; Lee, John Y; Martinez-Alvarez, Roberto; Reda, Wael A; Liscak, Roman; Lee, Cheng-Chia; Lunsford, L Dade; Vance, Mary Lee; Sheehan, Jason P

2017-11-01

Cushing disease (CD) due to adrenocorticotropic hormone-secreting pituitary tumors can be a management challenge. To better understand the outcomes of stereotactic radiosurgery (SRS) for CD and define its role in management. International, multicenter, retrospective cohort analysis. Ten medical centers participating in the International Gamma Knife Research Foundation. Patients with CD with >6 months endocrine follow-up. SRS using Gamma Knife radiosurgery. The primary outcome was control of hypercortisolism (defined as normalization of free urinary cortisol). Radiologic response and adverse radiation effects (AREs) were recorded. In total, 278 patients met inclusion criteria, with a mean follow-up of 5.6 years (0.5 to 20.5 years). Twenty-two patients received SRS as a primary treatment of CD. Mean margin dose was 23.7 Gy. Cumulative initial control of hypercortisolism was 80% at 10 years. Mean time to cortisol normalization was 14.5 months. Recurrences occurred in 18% with initial cortisol normalization. Overall, the rate of durable control of hypercortisolism was 64% at 10 years and 68% among patients who received SRS as a primary treatment. AREs included hypopituitarism (25%) and cranial neuropathy (3%). Visual deficits were related to treatment of tumor within the suprasellar cistern (P = 0.01), whereas both visual (P < 0.0001) and nonvisual cranial neuropathy (P = 0.02) were related to prior pituitary irradiation. SRS for CD is well tolerated and frequently results in control of hypercortisolism. However, recurrences can occur. SRS should be considered for patients with persistent hypercortisolism after pituitary surgery and as a primary treatment in those unfit for surgery. Long-term endocrine follow-up is essential after SRS. Copyright © 2017 Endocrine Society

Costs and resource use following defunctioning stoma in low anterior resection for cancer - A long-term analysis of a randomized multicenter trial.

PubMed

Floodeen, H; Hallböök, O; Hagberg, L A; Matthiessen, P

2017-02-01

Defunctioning stoma in low anterior resection (LAR) for rectal cancer can prevent major complications, but overall cost-effectiveness for the healthcare provider is unknown. This study compared inpatient healthcare resources and costs within 5 years of LAR between two randomized groups of patients undergoing LAR with and without defunctioning stoma. Five-year follow-up of a randomized, multicenter trial on LAR (NCT 00636948) with (stoma; n = 116) or without (no stoma; n = 118) defunctioning stoma comparing inpatient healthcare resources and costs. Unplanned stoma formation, days with stoma, length of hospital stay, reoperations, and total associated inpatient costs were analyzed. Average costs were € 21.663 per patient with defunctioning stoma and € 15.922 per patient without defunctioning stoma within 5 years of LAR, resulting in an average cost-saving of € 5.741. There was no difference between groups regarding the total number of days with any stoma (stoma = 33 398 vs. no stoma = 34 068). The total number of unplanned reoperations were 70 (no stoma) and 32 (stoma); p < 0.001. In the group randomized to no stoma at LAR, 30.5% (36/118) required an unplanned stoma later. Randomization to defunctioning stoma in LAR was more expensive than no stoma, despite the cost-savings associated with a reduced frequency of anastomotic leakage. Both groups required the same total number of days with a stoma within five years of LAR. Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

The South Asian cataract management study: complications, vision outcomes, and corneal endothelial cell loss in a randomized multicenter clinical trial comparing intracapsular cataract extraction with and without anterior chamber intraocular lens implantation.

PubMed

Snellingen, T; Shrestha, J K; Huq, F; Husain, R; Koirala, S; Rao, G N; Pokhrel, R P; Kolstad, A; Upadhyay, M P; Apple, D J; Arnesen, E; Cheng, H; Olsen, E G; Vogel, M

2000-02-01

To determine clinical outcomes of primary intracapsular cataract surgery with and without implantation of anterior chamber lenses. A multicenter randomized clinical trial. One thousand two hundred twenty-nine male and female patients 40-75 years of age with senile cataract. Study patients were recruited from screening eye camps and outpatient clinics. Randomization to the two treatment groups was performed after screening for predetermined inclusion and exclusion criteria. Demographics, visual acuity, intraocular pressures, and corneal endothelial cell data were recorded before surgery and at 6 weeks, 12 months, and 24 months after surgery. Monitoring of the study was secured by a standardized image documentation procedure on all patients using the IMAGEnet digital imaging system. Analysis of corneal endothelial cell images was performed with the Cell Soft software (Topcon Corporation, Japan). Visual acuity and central corneal endothelial cell loss. The patients were randomized to intraocular lens (IOL; n = 616) and no IOL (n = 613) implantation. Surgical complications were reported in 177 (14.4%) patients (IOL = 14.8%; no IOL = 14.0%). The most frequent complication observed was vitreous loss which occurred in 10.3% of eyes (IOL = 11.2%; no IOL = 9.5%). At the final examination (2 years after surgery), 88% of the operated eyes had a best corrected vision of 6/18 or better (IOL = 88.8%; no IOL = 86.6%). Analysis of corneal endothelial cell data showed a small but significantly greater cell loss 6 weeks after surgery in eyes with IOL compared with those without IOL, but no overall difference was found between the treatment groups in the long term follow-up. The findings indicate that there is a rationale for the use of anterior chamber intraocular lenses in primary intracapsular cataract surgery.

Risk Factors for De Novo Malignancies in Women After Kidney Transplantation: A Multicenter Transversal Study.

PubMed

Helmy, Samir; Marschalek, Julian; Bader, Yvonne; Koch, Marianne; Schmidt, Alice; Kanzler, Marina; Gyoeri, Georg; Polterauer, Stephan; Reinthaller, Alexander; Grimm, Christoph

2016-06-01

Transplantation results in a 5-time elevated risk for a variety of malignancies (Kaposi sarcoma, skin, liver, lung, gastrointestinal cancer). A patient's risk for malignancies could be of particular interest for the follow-up programs of patients and risk adaption after kidney transplantation. The aim of this study was to identify independent risk factors for de novo malignancies in women after renal transplantation. This is a multicenter transversal study, conducted at the Medical University of Vienna and Hospital Rudolfstiftung, Vienna, Austria. We included female kidney graft recipients who were transplanted between 1980 and 2012 and followed-up at our institutions (N = 280). Clinical data of patients were extracted from hospital charts and electronic patient files. Patients were interviewed using a standardized questionnaire regarding their medical history, history of transplantation, and malignant diseases. Detailed information about present and past immunosuppressive regimens, rejection episodes and therapies, renal graft function, and information about primary disease was obtained. Diagnostic work-up and/or surgical exploration was performed if any presence of malignancy was suspected during routine follow-up. Histological specimens were obtained from all patients. the presence of de novo malignancy after kidney transplantation. Two hundred sixty-two women were included for statistical analysis. Median (interquartile range) follow-up period after transplantation was 101.1 (27.3-190.7) months. Thirty-two patients (12.2%) developed a malignancy: dermatologic malignancies (5.7%), breast cancer (3.4%), cervical cancer (0.8%), lung cancer (0.4%), gastrointestinal malignancies (1.5%), vulvar cancer (0.4%), and unclassified malignancies (1.9%). Median (interquartile range) time to malignancy after transplantation was 185.9 (92.0-257.6) months. Cumulative cancer rates were 4.9% (1 year), 14.4% (3 years), 16.4% (5 years), and 21.8% (10 years). Second transplantations were identified as independent risk factor for development of malignancy after transplantation. Long-term risk of developing a malignancy after kidney transplantation is high, which might justify a follow-up of more than 10 years.

Head and neck adenoid cystic carcinoma: A prospective multicenter REFCOR study of 95 cases.

PubMed

Meyers, M; Granger, B; Herman, P; Janot, F; Garrel, R; Fakhry, N; Poissonnet, G; Baujat, B

2016-02-01

To describe the clinical, histological and therapeutic characteristics of a prospective multicenter series of 95 head and neck adenoid cystic carcinoma patients, and to determine any prognostic factors for disease-free survival. Ninety-five patients with adenoid cystic carcinoma were included in the Réseau d'Expertise Français Des Cancers ORL Rares (REFCOR, French Rare Head and Neck Cancer Expert Network) database between 2009 and 2012. The primary site was the salivary glands in 39 cases, sinus cavities (including hard palate) in 36 cases, pharynx-larynx-trachea in 14 cases, and lips and oral cavity in 4 cases. The tumor was stage I in 15% of cases, stage II in 23%, stage III in 26% and stage IV in 36%. Nine patients had cervical lymph node involvement and 5 had metastases at diagnosis. Fifty-six percent of patients were managed by surgery with postoperative radiation therapy. During follow-up, 3 patients died, 9 developed metastases and 12 showed recurrence or local progression. Mean follow-up was 18 months. On univariate analysis, disease-free survival correlated with T stage (P=0.05), N stage (P=0.003), resection margins (P=0.04), lymph node involvement on histology (P=0.01), and absence of chemotherapy (P=0.03). On multivariate analysis, disease-free survival correlated with T stage (P=0.01), N stage (P=0.09) and surgery (P=0.005). The essential issue in adenoid cystic carcinoma is long-term control. The present results confirm that the reference attitude is radical surgical resection for optimal local control. Adjuvant radiation therapy did not emerge as a prognostic factor. This study also provides a starting-point for translational studies in pathology and genetics. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Conducting multicenter research in healthcare simulation: Lessons learned from the INSPIRE network.

PubMed

Cheng, Adam; Kessler, David; Mackinnon, Ralph; Chang, Todd P; Nadkarni, Vinay M; Hunt, Elizabeth A; Duval-Arnould, Jordan; Lin, Yiqun; Pusic, Martin; Auerbach, Marc

2017-01-01

Simulation-based research has grown substantially over the past two decades; however, relatively few published simulation studies are multicenter in nature. Multicenter research confers many distinct advantages over single-center studies, including larger sample sizes for more generalizable findings, sharing resources amongst collaborative sites, and promoting networking. Well-executed multicenter studies are more likely to improve provider performance and/or have a positive impact on patient outcomes. In this manuscript, we offer a step-by-step guide to conducting multicenter, simulation-based research based upon our collective experience with the International Network for Simulation-based Pediatric Innovation, Research and Education (INSPIRE). Like multicenter clinical research, simulation-based multicenter research can be divided into four distinct phases. Each phase has specific differences when applied to simulation research: (1) Planning phase , to define the research question, systematically review the literature, identify outcome measures, and conduct pilot studies to ensure feasibility and estimate power; (2) Project Development phase , when the primary investigator identifies collaborators, develops the protocol and research operations manual, prepares grant applications, obtains ethical approval and executes subsite contracts, registers the study in a clinical trial registry, forms a manuscript oversight committee, and conducts feasibility testing and data validation at each site; (3) Study Execution phase , involving recruitment and enrollment of subjects, clear communication and decision-making, quality assurance measures and data abstraction, validation, and analysis; and (4) Dissemination phase , where the research team shares results via conference presentations, publications, traditional media, social media, and implements strategies for translating results to practice. With this manuscript, we provide a guide to conducting quantitative multicenter research with a focus on simulation-specific issues.

Well-differentiated neuroendocrine tumor of the stomach

PubMed Central

Gumuscu, Burak; Norwood, Kevin; Parker, George A.; Bridges, C. Lee; Rountree, Carl B.

2016-01-01

Abstract Introduction: A 13-year-old African–American female presented to her primary care physician's office with fatigue, syncope, and hematemesis. After initial evaluation, the patient was referred to pediatric gastroenterology clinic for further evaluation. Main concerns, important findings: An upper gastrointestinal endoscopy was performed to evaluate the source of her bleeding. Endoscopy revealed a 3-cm mass in the lesser curvature of the stomach, and a biopsy of the mass revealed a concern for carcinoid (neuroendocrine) features. Diagnosis: She underwent an open gastrectomy. Post-surgical pathology reports confirmed a well-differentiated neuroendocrine tumor of the stomach. Conclusion: Neuroendocrine tumors of the stomach in children are rare and we presently do not have pediatric-specific diagnostic and treatment guidelines. Although adult-based The North American Neuroendocrine Tumor Society (NANETS) guidelines are helpful, they are clearly not geared toward pediatric patients. To establish pediatric guidelines and to assess effectiveness of treatments, multicenter data collection is essential. In the long run, accumulation of clinically useful treatment information and long-term follow-up guidelines should enable clinicians to improve standard of care given to children with neuroendocrine tumors. PMID:27442656

Efficacy of infliximab rescue therapy in patients with chronic refractory pouchitis: a multicenter study.

PubMed

Barreiro-de Acosta, M; García-Bosch, O; Souto, R; Mañosa, M; Miranda, J; García-Sanchez, V; Gordillo, J; Chacon, S; Loras, C; Carpio, D; Maroto, N; Menchén, L; Rojas-Feria, M; Sierra, M; Villoria, A; Marin-Jimenez, I

2012-05-01

Despite medical therapy, 30% of patients with ulcerative colitis (UC) need to undergo surgery. Around 50% of patients with proctocolectomy with ileal pouch-anal anastomosis (IPAA) develop complications of the pouch. Clinical evidence for the use of infliximab (IFX) in refractory pouchitis is limited. The aim of this study was to report efficacy of IFX in these patients. A retrospective, multicenter study was designed. Patients older than 18 years with chronic refractory pouchitis treated with IFX (5 mg/kg) were included. Short-term IFX efficacy was evaluated at week 8 and mid-term efficacy at weeks 26 and 52. Complete response was defined as cessation of diarrhea and urgency and partial response as marked clinical improvement but persisting symptoms. The modified Pouchitis Disease Activity Index (mPDAI) without endoscopy was calculated when available. Thirty-three consecutive UC patients with chronic refractory pouchitis were included (18 male, mean age 45 years, range 21-67). At week 8, 21% patients achieved complete response and 63% showed partial clinical response. At weeks 26 and 52, 33% and 27% achieved complete response and 33% and 18% showed partial clinical response, respectively. Thirteen patients (39%) withdrew treatment (four for lack of efficacy, four for loss of response and five for adverse events). None of the potential factors analyzed had an influence on response to IFX. IFX was effective in the short- and mid-term in patients with chronic refractory pouchitis. However, medication had to be discontinued in a high number of patients. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

Air Pollution and Nonmalignant Respiratory Mortality in 16 Cohorts within the ESCAPE Project

PubMed Central

Dimakopoulou, Konstantina; Samoli, Evangelia; Beelen, Rob; Stafoggia, Massimo; Andersen, Zorana Jovanovic; Hoffmann, Barbara; Fischer, Paul; Nieuwenhuijsen, Mark; Vineis, Paolo; Xun, Wei; Hoek, Gerard; Raaschou-Nielsen, Ole; Oudin, Anna; Forsberg, Bertil; Modig, Lars; Jousilahti, Pekka; Lanki, Timo; Turunen, Anu; Oftedal, Bente; Nafstad, Per; Schwarze, Per E.; Penell, Johanna; Fratiglioni, Laura; Andersson, Niklas; Pedersen, Nancy; Korek, Michal; De Faire, Ulf; Eriksen, Kirsten Thorup; Tjønneland, Anne; Becker, Thomas; Wang, Meng; Bueno-de-Mesquita, Bas; Tsai, Ming-Yi; Eeftens, Marloes; Peeters, Petra H.; Meliefste, Kees; Marcon, Alessandro; Krämer, Ursula; Kuhlbusch, Thomas A.J.; Vossoughi, Mohammad; Key, Timothy; de Hoogh, Kees; Hampel, Regina; Peters, Annette; Heinrich, Joachim; Weinmayr, Gudrun; Concin, Hans; Nagel, Gabriele; Ineichen, Alex; Jacquemin, Bénédicte; Stempfelet, Morgane; Vilier, Alice; Ricceri, Fulvio; Sacerdote, Carlotta; Pedeli, Xanthi; Katsoulis, Michalis; Trichopoulou, Antonia; Brunekreef, Bert

2014-01-01

Rationale: Prospective cohort studies have shown that chronic exposure to particulate matter and traffic-related air pollution is associated with reduced survival. However, the effects on nonmalignant respiratory mortality are less studied, and the data reported are less consistent. Objectives: We have investigated the relationship of long-term exposure to air pollution and nonmalignant respiratory mortality in 16 cohorts with individual level data within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE). Methods: Data from 16 ongoing cohort studies from Europe were used. The total number of subjects was 307,553. There were 1,559 respiratory deaths during follow-up. Measurements and Main Results: Air pollution exposure was estimated by land use regression models at the baseline residential addresses of study participants and traffic-proximity variables were derived from geographical databases following a standardized procedure within the ESCAPE study. Cohort-specific hazard ratios obtained by Cox proportional hazard models from standardized individual cohort analyses were combined using metaanalyses. We found no significant associations between air pollution exposure and nonmalignant respiratory mortality. Most hazard ratios were slightly below unity, with the exception of the traffic-proximity indicators. Conclusions: In this study of 16 cohorts, there was no association between air pollution exposure and nonmalignant respiratory mortality. PMID:24521254

A Comparison of Psychoanalytic Therapy and Cognitive Behavioral Therapy for Anxiety (Panic/Agoraphobia) and Personality Disorders (APD Study): Presentation of the RCT Study Design.

PubMed

Benecke, Cord; Huber, Dorothea; Staats, Hermann; Zimmermann, Johannes; Henkel, Miriam; Deserno, Heinrich; Wiegand-Grefe, Silke; Schauenburg, Henning

2016-09-01

Anxiety disorders, most notably panic disorders and agoraphobia, are common mental disorders, and there is a high comorbidity with personality disorders. Randomized controlled trails addressing this highly relevant group of patients are missing. The multicenter Anxiety and Personality Disorders (APD) study investigates 200 patients with panic disorder and/or agoraphobia with comorbid personality disorder in a randomized control-group comparison of psychoanalytic therapy (PT) and cognitive behavioral therapy (CBT), including 100 patients in each group. Each patient will be examined over a period of six years, regardless of the duration of the individual treatment. The main issues that are addressed in this study are the comparison of the efficacy of PT and CBT in this special patient population, the comparison of the sustainability of the effects of PT and CBT, the comparison of the long-term cost-benefit-ratios of PT and CBT as well as the investigation of prescriptive patient characteristics for individualized treatment recommendations (differential indication). The APD study compares efficacy, sustainability, and cost-benefit-ratios of CBT and PT for anxiety plus personality disorders in a randomized controlled trail. The study design meets the requirements for an efficacy study for PT, which were recently defined. Current Controlled Trials ISRCTN12449681.

An observational study of rotigotine transdermal patch and other currently prescribed therapies in patients with Parkinson's disease.

PubMed

Müller, Thomas; Tolosa, Eduardo; Badea, Letitia; Asgharnejad, Mahnaz; Grieger, Frank; Markowitz, Michael; Nondonfaz, Xavier; Bauer, Lars; Timmermann, Lars

2018-06-01

Real-world data from large cohorts of patients with Parkinson's disease on the long-term effectiveness of different dopamine-substituting drug therapies are rare. The objective of this study was to obtain information on real-world management of PD with dopamine-substituting drugs. SP0854 (NCT00599339) was a prospective, multicenter, non-interventional, multiple-cohort, post-authorization safety study of rotigotine versus other dopaminergic therapies. The study was also part of a European Medicines Agency risk-management plan for the non-ergoline dopamine agonist rotigotine, focussing on cardiovalvular fibrosis. Eligible patients requiring monotherapy with a dopamine agonist, or levodopa in combination with a dopamine agonist were followed for ≤ 33 months; 1531 of 2195 patients completed the study. Mean motor scores improved for all dopamine-substituting treatments. Patients with more severe motor-symptoms/increased disability were more likely to receive levodopa alone or in combination with a DA at study onset. More patients who started on combination therapy with levodopa remained on this treatment versus those starting on dopaminergic monotherapy. This real-world study showed that the dopamine-substituting therapies were efficacious, with a safety profile consistent with that expected of dopaminergic treatments. Cardiovalvular pathology was rare and not found to be causally-related to rotigotine.

Quantifying Risk Factors for Long-Term Sleep Problems After Burn Injury in Young Adults.

PubMed

Lee, Austin F; Ryan, Colleen M; Schneider, Jeffrey C; Kazis, Lewis E; Li, Nien Chen; Rose, Mary; Liang, Matthew H; Wang, Chao; Palmieri, Tina; Meyer, Walter J; Pidcock, Frank S; Reilly, Debra; Sheridan, Robert L; Tompkins, Ronald G

Restorative sleep is an important component of quality of life. Disturbances in sleep after burn injury were reported but all based on uncontrolled or nonstandardized data. The occurrence and the effect of long-term sleep problems in young adult burn survivors have not been well defined. This 5-year (2003-2008) prospective multicenter longitudinal study included adults with burn injuries ages 19 to 30 years who completed the Young Adult Burn Outcome Questionnaire (YABOQ) up to 36 months after injury. The items measured 15 patient-reported outcomes including physical, psychological, and social statuses and symptoms such as itch and pain. Scores of these 15 YABOQ outcome domains were standardized to a mean of 50 and a SD of 10 based on an age-matched nonburned reference group of young adults. Sleep quality was assessed using the item 'How satisfied are you now with your sleep,' rated by a 5-point Likert scale. Patients responding with very and somewhat dissatisfied were classified as having sleep dissatisfaction and the remaining as less or not dissatisfied. The associations between sleep dissatisfaction (yes/no) and YABOQ outcome domains were analyzed longitudinally using mixed-effect generalized linear models, adjusted for %TBSA burned, age, gender, and race. Generalized estimating equations were used to take into account correlated error resulting from repeated surveys on each patient over time. One hundred and fifty-two burn survivors participated in the YABOQ survey at baseline and during the follow-up who had at least one survey with a response to the sleep item. Among them, sleep dissatisfaction was twice as prevalent (76/152, 50%) when compared with the nonburned reference group (29/112, 26%). The likelihood of a burn survivor being dissatisfied with sleep was reduced over time after the burn injury. Sleep dissatisfaction following burns was significantly associated, in a dose-dependent manner, with increasing burn size (P = .001). Better sleep was associated with better outcomes in all domains (P < .05) except Fine Motor Function, and this association was significantly more apparent in the longer term compared with the shorter term with the same domains (P < .05). Dissatisfaction with sleep is highly prevalent following burn injuries in young adults. Lower satisfaction with sleep is associated with poorer scores in nearly all quality of life measures. Satisfaction with sleep should be addressed during the long-term clinical follow-up of young adults with burn injuries. Further research should be undertaken to understand the components of sleep quality that are important to burn survivors and which ones might be modified and tested in future intervention studies.

Expanding the Use of Time-Based Metering: Multi-Center Traffic Management Advisor

NASA Technical Reports Server (NTRS)

Landry, Steven J.; Farley, Todd; Hoang, Ty

2005-01-01

Time-based metering is an efficient air traffic management alternative to the more common practice of distance-based metering (or "miles-in-trail spacing"). Despite having demonstrated significant operational benefit to airspace users and service providers, time-based metering is used in the United States for arrivals to just nine airports and is not used at all for non-arrival traffic flows. The Multi-Center Traffic Management Advisor promises to bring time-based metering into the mainstream of air traffic management techniques. Not constrained to operate solely on arrival traffic, Multi-Center Traffic Management Advisor is flexible enough to work in highly congested or heavily partitioned airspace for any and all traffic flows in a region. This broader and more general application of time-based metering is expected to bring the operational benefits of time-based metering to a much wider pool of beneficiaries than is possible with existing technology. It also promises to facilitate more collaborative traffic management on a regional basis. This paper focuses on the operational concept of the Multi-Center Traffic Management Advisor, touching also on its system architecture, field test results, and prospects for near-term deployment to the United States National Airspace System.

Effect of ezetimibe add-on therapy over 52 weeks extension analysis of prospective randomized trial (RESEARCH study) in type 2 diabetes subjects.

PubMed

Sakamoto, Kentaro; Kawamura, Mitsunobu; Watanabe, Takayuki; Ashidate, Keiko; Kohro, Takahide; Tanaka, Akira; Mori, Yasumichi; Tagami, Motoki; Hirano, Tsutomu; Yamazaki, Tsutomu; Shiba, Teruo

2017-06-24

Lowering cholesterol levels decreases the risk of atherosclerotic diseases. Effective ways to stably reduce LDL-C level are warranted in type 2 diabetic patients, a high-risk population for CVD, with various anti-diabetic therapeutic background. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles. We evaluated long-term ezetimibe add-on therapy in T2DM patients with hypercholesterolemia. In a randomized, multicenter, open-label, prospective study, a total of 109 T2DM patients not attaining LDL-C target value despite first-line dose statin (10 mg of atorvastatin or 1 mg of pitavastatin) therapy in Japan were recruited. We investigated the difference in cholesterol lowering effect between ezetimibe (10 mg) add-on statin (EAT) group and double-dose statin (DST) group. Changes of parameters related to atherosclerotic event risks were assessed. The reduction of LDL-C was larger in the EAT group (28.3%) than in the DST group (9.2%) at 52 weeks as well as the primary endpoint of 12 weeks. EAT achieved significant lower levels of TC and apo B, respectively. Both treatments attained significant reduction in sd-LDL-C or hsCRP on this long-term basis. Notably, sd-LDL-C in EAT reduced as low as 36.1 ± 14.9 mg/dl to reach near the threshold (35.0 mg/dl) for atherosclerosis with significantly higher achievement rate (55.6%) than DST treatment. Simultaneously, hsCRP reduction by EAT attained as low value as 0.52 ± 0.43 mg/l. In the present 52-week long-term period, ezetimibe add-on therapy showed a robust advantage in lowering LDL-C and in attaining target LDL-C values compared with the doubling of statin dose. Moreover, it's meaningful that sd-LDL, powerfully atherogenic lipoprotein, exhibited prominent decrease consistently prominently by ezetimibe add-on therapy. DM patients with hypercholesterolemia are at high risk for CAD, and adding ezetimibe onto usual-dose statin treatment in Japan has been suggested as the first-line therapy for those DM patients who failed to attain the target LDL-C value (UMIN000002593).

Single-course specific immunotherapy with mixed pollen allergoids: results of a multi-centre study.

PubMed

Drachenberg, K J; Pröll, S; Urban, E; Woroniecki, S R

2003-01-01

A short-term immunotherapy vaccine for the treatment of pollen allergy has been developed utilising L-tyrosine adsorbed allergoids. The reduced number of injections could provide advantages over long-term therapy schedules. This would improve compliance and support application of specific immunotherapy (SIT) to a greater extent. We report a multicenter study to evaluate the efficacy and safety of this treatment in a clinical practice setting. Patients (n = 1808) with a diagnosis of sensitivities to various pollens and symptoms of allergic asthma and/or allergic rhinitis and/or allergic conjunctivitis were selected. The vaccine formulation was made up according to individual sensitivities and contained L-tyrosine adsorbed allergoids. The patients were treated with a 3-injection initial course followed by a 3-injection maintenance course. Efficacy was measured by consumption of symptomatic anti-allergic medication compared with that in the previous season and by physician assessment using a 5-point scale. All adverse events were recorded. Efficacy was demonstrated by a considerable decrease in regular and frequent use of medication compared with that in the previous season (p < 0.001). In addition, in 80 % of the patients, the physician's assessment was either "good" or "very good". These outcomes were unaffected by the closeness of the treatment course to the onset of the pollen season. Tolerability was good and most local and systemic reactions were mild. The treatment of pollen-allergic patients with a short-term SIT using a 6-injection pollen allergoid/L-tyrosine vaccine in a clinical practice setting provided a high level of efficacy with a low incidence of mainly mild adverse events.

Pulmonary vein reconnection following catheter ablation of atrial fibrillation using the second-generation cryoballoon versus open-irrigated radiofrequency: results of a multicenter analysis.

PubMed

Aryana, Arash; Singh, Sheldon M; Mugnai, Giacomo; de Asmundis, Carlo; Kowalski, Marcin; Pujara, Deep K; Cohen, Andrew I; Singh, Steve K; Fuenzalida, Charles E; Prager, Nelson; Bowers, Mark R; O'Neill, Padraig Gearoid; Brugada, Pedro; d'Avila, André; Chierchia, Gian-Battista

2016-12-01

Catheter ablation of atrial fibrillation (CAAF) using the cryoballoon has emerged as an alternate strategy to point-by-point radiofrequency. However, there is little comparative data on long-term durability of pulmonary vein (PV) isolation comparing these two modalities. In this multicenter, retrospective analysis, the incidences/patterns of late PV reconnection following an index CAAF using the second-generation cryoballoon versus open-irrigated, non-force-sensing radiofrequency were examined. Of the 2002 patients who underwent a first-time CAAF, 186/1126 patients (16.5 %) ablated using cryoballoon and 174/876 patients (19.9 %) with non-contact force-guided radiofrequency required a repeat procedure at 11 ± 5 months. During follow-up, the incidence of atrial flutters/tachycardias was lower (19.9 vs. 32.8 %; p = 0.005) and fewer patients exhibited PV reconnection (47.3 vs. 60.9 %; p = 0.007) with cryoballoon versus radiofrequency. Additionally, fewer PVs had reconnected with cryoballoon versus radiofrequency (18.8 vs. 34.6 %; p < 0.001). With cryoballoon, the right inferior (p < 0.001) and left common (p = 0.039) PVs were more likely to exhibit late reconnection, versus the left superior PV with radiofrequency (p = 0.012). However, when comparing the two strategies, the left common PV was more likely to exhibit reconnection with cryoballoon, whereas all other PVs with the exception of the right inferior PV demonstrated a lower reconnection rate with cryoballoon versus radiofrequency. Lastly, in a logistic regression multivariate analysis, cryoballoon ablation and PV ablation time emerged as significant predictors of durable PV isolation at repeat procedure. In this large multicenter, retrospective analysis, CAAF using the second-generation cryoballoon was associated with improved durability of PV isolation compared to open-irrigated, non-force-sensing radiofrequency.

Short-term complications in intra- and extra-articular anterior cruciate ligament reconstruction. Comparison with the literature on isolated intra-articular reconstruction. A multicenter study by the French Arthroscopy Society.

PubMed

Panisset, J C; Pailhé, R; Schlatterer, B; Sigwalt, L; Sonnery-Cottet, B; Lutz, C; Lustig, S; Batailler, C; Bertiaux, S; Ehkirch, F P; Colombet, P; Steltzlen, C; Louis, M L; D'ingrado, P; Dalmay, F; Imbert, P; Saragaglia, D

2017-12-01

Lateral tenodesis (LT) is performed to limit the risk of iterative tear following anterior cruciate ligament (ACL) reconstruction in at-risk patients. By adding an extra procedure to isolated ACL graft, LT reconstruction increases operating time and may complicate postoperative course. The objective of the present study was to evaluate the rate of early complications. The study hypothesis was that associating ALL reconstruction to ACL reconstruction does not increase the complications rate found with isolated ACL reconstruction. A prospective multicenter study included 392 patients: 70% male; mean age, 29.9 years; treated by associated ACL and LT reconstruction. All adverse events were inventoried. Mean hospital stay was 2 days, with 46% day-surgery. Walking was resumed at a mean 27 days, with an advantage for patients treated by the hamstring technique. The early postoperative complications rate was 12%, with 1.7% specifically implicating LT reconstruction: pain, hematoma, stiffness in flexion and extension, and infection. There was a 5% rate of surgical revision during the first year, predominantly comprising arthrolysis for extension deficit. The 1-year recurrence rate was 2.8%. The complications rate for combined intra- and extra-articular reconstruction was no higher than for isolated intra-articular ACL reconstruction, with no increase in infection or stiffness rates. The rate of complications specific to ALL reconstruction was low, at 1.7%, and mainly involved fixation error causing lateral soft-tissue impingement. IV, prospective multicenter study. Copyright © 2017. Published by Elsevier Masson SAS.

Employers' and employees' views on responsibilities for career management in nursing: a cross-sectional survey.

PubMed

Philippou, Julia

2015-01-01

To examine nurse employees' and employers' views about responsibilities for managing nurses' careers. Career management policies are associated with cost savings, in terms of workforce recruitment and retention and an increase in job and career satisfaction. In nursing, responsibility for career management remains relatively unexplored. A multicenter, cross-sectional questionnaire survey. Data were collected from 871 nurse employees and employers in the British National Health Service. The study was conducted in 2008, a period when policy reforms aimed at modernizing the healthcare workforce in England. In the current discussions in Europe and the USA about the future of nursing, these data reveal insights not previously reported. Exploratory analyses were undertaken using descriptive and inferential statistics. The analysis indicated a temporal dimension to career management responsibilities. Short-term responsibilities for securing funding and time for development lay more with employers. Medium-term responsibilities for assessing nurses' strengths and weakness, determining job-related knowledge and skills and identifying education and training needs appeared to be shared. Long-term responsibilities for developing individual careers and future development plans lay primarily with employees. New ways of managing nurses' career development that lead to greater independence for employees and greater flexibility for employers, while retaining a high-calibre and competent workforce, are needed. Ultimately, career management responsibilities should not tilt to either side but rather be shared to benefit both parties. Clarifying employers' and employees' responsibilities for career management may help both parties to develop a common understanding of each other's role and to meet their obligations in a constructive dialogue. © 2014 John Wiley & Sons Ltd.

[A self-report study of sexual victimization in Spanish community adolescents and at-risk groups].

PubMed

Pereda, Noemí; Abad, Judit; Guilera, Georgina; Arch, Mila

2015-01-01

To determine the extent of sexual victimization in four groups of Spanish adolescents based on their own reports. An observational, cross-sectional, multicenter study was conducted. Sexual victimization was assessed by seven questions included in the Juvenile Victimization Questionnaire. The samples were composed of 1,105 adolescents (mean age [M]=14.52, standard deviation [SD]=1.76) from seven secondary schools; 149 adolescents (M=14.28; SD=1.45) from 14 child and adolescent mental health centers; 129 adolescents (M=14.59, SD=1.62) institutionalized in 18 long-term (78.3%) and short-term (21.7%) residential centers belonging to the child protection system; and 101 adolescents (M=16.08, SD=0.99) recruited from three detention centers (77.2%) and five open regime teams or follow-up services for court orders for minors not requiring loss of freedom (22.8%). The extent of lifetime sexual victimization ranged from 14.7% of the adolescents in the community sample to 23.5% of youths attended in mental health services, 35.6% of youths involved in the juvenile justice system, and 36.4% of children protected by the child welfare system. Most of the victims were female, the only exception being the group of male victims from the juvenile justice system. Sexual victimization of children is widespread in Spain and its distribution differs depending on the group of children under study. Copyright © 2015 SESPAS. Published by Elsevier Espana. All rights reserved.

Stem cells therapy for ALS.

PubMed

Mazzini, Letizia; Vescovi, Angelo; Cantello, Roberto; Gelati, Maurizio; Vercelli, Alessandro

2016-01-01

Despite knowledge on the molecular basis of amyotrophic lateral sclerosis (ALS) having quickly progressed over the last few years, such discoveries have not yet translated into new therapeutics. With the advancement of stem cell technologies there is hope for stem cell therapeutics as novel treatments for ALS. We discuss in detail the therapeutic potential of different types of stem cells in preclinical and clinical works. Moreover, we address many open questions in clinical translation. SC therapy is a potentially promising new treatment for ALS and the need to better understand how to develop cell-based experimental treatments, and how to implement them in clinical trials, becomes more pressing. Mesenchymal stem cells and neural fetal stem cells have emerged as safe and potentially effective cell types, but there is a need to carry out appropriately designed experimental studies to verify their long-term safety and possibly efficacy. Moreover, the cost-benefit analysis of the results must take into account the quality of life of the patients as a major end point. It is our opinion that a multicenter international clinical program aime d at fine-tuning and coordinating transplantation procedures and protocols is mandatory.

Quantitative aspects of the clinical performance of transverse tripolar spinal cord stimulation.

PubMed

Wesselink, W A; Holsheimer, J; King, G W; Torgerson, N A; Boom, H B

1999-01-01

A multicenter study was initiated to evaluate the performance of the transverse tripolar system for spinal cord stimulation. Computer modeling had predicted steering of paresthesia with a dual channel stimulator to be the main benefit of the system. The quantitative analysis presented here includes the results of 484 tests in 30 patients. For each test, paresthesia coverage as a function of voltage levels was stored in a computerized database, including a body map which enabled calculation of the degree of paresthesia coverage of separate body areas, as well as the overlap with the painful areas. The results show that with the transverse tripolar system steering of the paresthesia is possible, although optimal steering requires proper placement of the electrode with respect to the spinal cord. Therefore, with this steering ability as well as a larger therapeutic stimulation window as compared to conventional systems, we expect an increase of the long-term efficacy of spinal cord stimulation. Moreover, in view of the stimulation-induced paresthesia patterns, the system allows selective stimulation of the medial dorsal columns.

Laboratory surveillance of antimicrobial resistance and multidrug resistance among Streptococcus pneumoniae isolated in the Kinki region of Japan, 2001-2015.

PubMed

Toda, Hirofumi; Satoh, Kaori; Komatsu, Masaru; Fukuda, Saori; Nakamura, Tatsuya; Jikimoto, Takumi; Nishio, Hisaaki; Yamasaki, Katsutoshi; Maede, Takuya; Orita, Tamaki; Sueyoshi, Noriyuki; Kita, Machiko; Toyokawa, Masahiro; Nishi, Isao; Akagi, Masahiro; Higuchi, Takefumi; Kofuku, Tomomi; Nakai, Isako; Ono, Tamotsu; Shimakawa, Koichi; Hikita, Yoshie; Moro, Kunihiko; Kida, Kaneyuki; Oohama, Masanobu; Wada, Yasunao; Tobe, Toru; Kamisako, Toshinori; Tanaka, Yuji

2018-03-01

The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced among children in Japan in 2010. There are no long-term multicenter surveillance studies of antimicrobial resistance in S. pneumoniae before and after the introduction of PCV7. Therefore, we examined chronological trends in antimicrobial resistance among 4534 strains of S. pneumoniae isolated from both children and adults in the Kinki region of Japan during 2001-2015. High-level penicillin and third-generation cephalosporin resistance in S. pneumoniae increased among both children and adults during the period before the introduction of PCV7 (2001-2010). Besides penicillin and cephalosporin, pneumococcal carbapenem and macrolide resistance increased among children. The rate of resistance to these antibiotics was higher among children than among adults. The introduction of PCV7 decreased the rate of non-susceptibility to β-lactam antibiotics and the rate of multidrug resistant S. pneumoniae among children, but not among adults. Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Oxytocin for Male Subjects with Autism Spectrum Disorder and Comorbid Intellectual Disabilities: A Randomized Pilot Study

PubMed Central

Munesue, Toshio; Nakamura, Hiroyuki; Kikuchi, Mitsuru; Miura, Yui; Takeuchi, Noriyuki; Anme, Tokie; Nanba, Eiji; Adachi, Kaori; Tsubouchi, Kiyotaka; Sai, Yoshimichi; Miyamoto, Ken-ichi; Horike, Shin-ichi; Yokoyama, Shigeru; Nakatani, Hideo; Niida, Yo; Kosaka, Hirotaka; Minabe, Yoshio; Higashida, Haruhiro

2016-01-01

Approximately half of autism spectrum disorder (ASD) individuals suffer from comorbid intellectual disabilities (IDs). Oxytocin (OXT) receptors are highly expressed in temporal lobe structures and are likely to play a modulatory role in excitatory/inhibitory balance, at least based on animal model findings. Thus, it is feasible that in the highly representative group of Kanner-type ASD subjects, OXT could have a beneficial effect on social communication and social interaction. The aim of this pilot study is to investigate the feasibility and adverse events, such as epilepsy, of the long-term administration of intranasal OXT for adolescent and adult ASD subjects with ID because such patients frequently have seizures. We also addressed the question on how to scale the OXT effects to the core symptoms of social deficits because of the relative difficulty in obtaining objective measurements. Twenty-nine males (aged 15–40 years old) participated in a randomized, double-blind, and placebo-controlled crossover study (each for 8 weeks) with OXT (16 IU/day). Except for seizures experienced by one participant, other serious adverse events did not occur. The primary and secondary outcomes measured using the Childhood Autism Rating Scale and several standard scales, respectively, revealed no difference between the OXT and placebo groups. Instead, in an exploratory analysis, the social interactions observed in the play sessions or in daily life were significantly more frequent in the initial half period in the OXT-first arm of the crossover trial. There were also significant correlations between the plasma OXT concentration and subscale scores for irritability on the Aberrant Behavior Checklist. In conclusion, this pilot study demonstrates that long-term administration of intranasal OXT is tolerable in a representative cohort of ASD individuals with ID and suggests that future multicenter trials of OXT are warranted and should include measurements of reciprocal social interactions based on daily life under closer surveillance for epilepsy. Trial registration: UMIN000007250. PMID:26834651

Long-Term Survival With Implantable Cardioverter-Defibrillator in Different Symptomatic Functional Classes of Heart Failure.

PubMed

Biton, Yitschak; Rosero, Spencer; Moss, Arthur; Zareba, Wojciech; Kutyifa, Valentina; Baman, Jayson; Barsheshet, Alon; McNitt, Scott; Polonsky, Bronislava; Goldenberg, Ilan

2018-03-01

The ACC/AHA/HRS (American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society) guidelines recommend implantable cardioverter-defibrillator (ICD) therapy primary prevention in all patients with severely reduced left ventricular ejection fraction (≤30%) regardless of New York Heart Association (NYHA) functional class, whereas recent European guidelines limit the indication to those with symptomatic heart failure (NYHA ≥ II). We therefore aimed to evaluate the long-term survival benefit of primary ICD therapy among postmyocardial infarction patients with and without heart failure (HF) symptoms who were enrolled in MADIT-II (Multicenter Automatic Defibrillator Implantation Trial II). We classified 1,164 MADIT-II patient groups according to the baseline NYHA class (NYHA I [n = 442], NYHA II [n = 425], and NYHA III [n = 297]); patients with NYHA IV were excluded. Multivariate Cox proportional hazards regression modeling was performed to compare the mortality reduction with ICD versus non-ICD therapy during 8 years of follow-up between the 3 NYHA groups. The median (interquartile range) follow-up time was 7.6 (3.5 to 9) years. At 8 years of follow-up, the cumulative probability of mortality in the non-ICD treatment arm was 57% for NYHA I, 57% for NYHA II, and 76% for NYHA III (p <0.001). Multivariate models demonstrated similar long-term mortality risk reduction with ICD compared with the non-ICD treatment arm regardless of HF symptoms: NYHA I (HR = 0.63, 0.46 to 0.85, p = 0.003), NYHA II (HR = 0.68, 0.50 to 0.93, p = 0.017), and NYHA III (HR = 0.68, 0.50 to 0.94, p = 0.018); p for NYHA class by treatment arm interaction >0.10. In conclusion, primary ICD therapy provides consistent long-term survival benefit among patients with previous myocardial infarction and severe left ventricular dysfunction, regardless of HF symptoms. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-term outcomes of internet-based self-management support in adults with asthma: randomized controlled trial.

PubMed

van Gaalen, Johanna L; Beerthuizen, Thijs; van der Meer, Victor; van Reisen, Patricia; Redelijkheid, Geertje W; Snoeck-Stroband, Jiska B; Sont, Jacob K

2013-09-12

Long-term asthma management falls short of the goals set by international guidelines. The Internet is proposed as an attractive medium to support guided self-management in asthma. Recently, in a multicenter, pragmatic randomized controlled parallel trial with a follow-up period of 1 year, patients were allocated Internet-based self-management (IBSM) support (Internet group [IG]) or usual care (UC) alone. IBSM support was automatically terminated after 12 months of follow-up. In this study, IBSM support has been demonstrated to improve asthma-related quality of life, asthma control, lung function, and the number of symptom-free days as compared to UC. IBSM support was based on known key components for effective self-management and included weekly asthma control monitoring and treatment advice, online and group education, and communication (both online and offline) with a respiratory nurse. The objective of the study was to assess the long-term effects of providing patients 1 year of IBSM support as compared to UC alone. Two hundred adults with physician-diagnosed asthma (3 or more months of inhaled corticosteroids prescribed in the past year) from 37 general practices and 1 academic outpatient department who previously participated were invited by letter for additional follow-up at 1.5 years after finishing the study. The Asthma Control Questionnaire (ACQ) and the Asthma Quality of Life Questionnaire (AQLQ) were completed by 107 participants (60 UC participants and 47 IG participants). A minimal clinical important difference in both questionnaires is 0.5 on a 7-point scale. At 30 months after baseline, a sustained and significant difference in terms of asthma-related quality of life of 0.29 (95% CI 0.01-0.57) and asthma control of -0.33 (95% CI -0.61 to -0.05) was found in favor of the IBSM group. No such differences were found for inhaled corticosteroid dosage or for lung function, measured as forced expiratory volume in 1 second. Improvements in asthma-related quality of life and asthma control were sustained in patients who received IBSM support for 1 year, even up to 1.5 years after terminating support. Future research should be focused on implementation of IBSM on a wider scale within routine asthma care. International Standard Randomized Controlled Trial Number (ISRCTN): 79864465; http://www.controlled-trials.com/ISRCTN79864465 (Archived by WebCite at http://www.webcitation.org/6J4VHhPk4).

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

PubMed

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

2015-01-16

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

A multicenter, open-label trial to evaluate the quality of life in adults with ADHD treated with long-acting methylphenidate (OROS MPH): Concerta Quality of Life (CONQoL) study.

PubMed

Mattos, Paulo; Louzã, Mário Rodrigues; Palmini, André Luís Fernandes; de Oliveira, Irismar Reis; Rocha, Fábio Lopes

2013-07-01

The available literature provides few studies on the effectiveness of methylphenidate in improving quality of life in individuals with ADHD. To assess the effectiveness of methylphenidate OROS formulation (OROS MPH) through QoL in adults with ADHD. A 12-week, multicenter, open-label trial involving 60 patients was used. The measures used were Adult Self-Rating Scale, Adult ADHD Quality of Life Scale (AAQoL), State and Trait Anxiety Inventory (STAI), Hamilton Depression Rating Scale (HAM-D), Clinical Global Impression (CGI), and safety measures. A significance statistic level of 5% was adopted. Analyses included 60 patients (66.7% male; M age = 31.1 years) for safety and 58 patients for effectiveness. All AAQoL subscales improved from baseline to Week 12 (p < .0001), as well as the Total AAQoL (p < .0001). A significant reduction on Clinical Global Impression-Improvement (CGI-I), HAM-D, STAI, and ASRS scores was observed (p < .0001). No serious adverse event was reported. Treatment of adult ADHD patients with OROS MPH improves QoL.

Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group.

PubMed

Guerriero, S; Condous, G; van den Bosch, T; Valentin, L; Leone, F P G; Van Schoubroeck, D; Exacoustos, C; Installé, A J F; Martins, W P; Abrao, M S; Hudelist, G; Bazot, M; Alcazar, J L; Gonçalves, M O; Pascual, M A; Ajossa, S; Savelli, L; Dunham, R; Reid, S; Menakaya, U; Bourne, T; Ferrero, S; Leon, M; Bignardi, T; Holland, T; Jurkovic, D; Benacerraf, B; Osuga, Y; Somigliana, E; Timmerman, D

2016-09-01

The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes of endometriosis. Currently, it is difficult to compare results between published studies because authors use different terms when describing the same structures and anatomical locations. We hope that the terms and definitions suggested herein will be adopted in centers around the world. This would result in consistent use of nomenclature when describing the ultrasound location and extent of endometriosis. We believe that the standardization of terminology will allow meaningful comparisons between future studies in women with an ultrasound diagnosis of endometriosis and should facilitate multicenter research. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Long-term lamivudine treatment for chronic hepatitis B in Japanese patients: A project of Kyushu University Liver Disease Study

PubMed Central

Furusyo, Norihiro; Takeoka, Hiroaki; Toyoda, Kazuhiro; Murata, Masayuki; Tanabe, Yuichi; Kajiwara, Eiji; Shimono, Junya; Masumoto, Akihide; Maruyama, Toshihiro; Nomura, Hideyuki; Nakamuta, Makoto; Takahashi, Kazuhiro; Shimoda, Shinji; Azuma, Koichi; Sakai, Hironori; Hayashi, Jun; Group, the Kyushu University Liver Disease Study

2006-01-01

AIM: To determine the efficacy of long-term lamivudine treatment of a large number of Japanese patients with chronic hepatitis B. METHODS: In this retrospective, multi-center trial, 318 Japanese patients with chronic hepatitis B received 100 mg of lamivudine daily for up to 36 (median 21) mo. Virological response was a decline to a serum HBV DNA level less than 3.7  log copies/mL. Virological breakthrough was defined as the reappearance of a serum HBV DNA level to more than 10-fold the minimum during treatment. RESULTS: Lamivudine produced virological response in 86.8% of the 318 patients at 6 mo, in 80.2% of 252 patients at 12 mo, in 69.2% of 133 patients at 24 mo, and in 53.6% of 28 patients at 36 mo. Forward stepwise logistic regression analysis showed an HBV DNA level less than 6.8  log copies/mL (P < 0.0001), HBeAg negativity (P < 0.0001), a platelet count of 100 × 109/L or more (P = 0.0162) at baseline, and a decline of the HBV DNA level of more than 3.2  log copies/mL as compared with the baseline level at 3 mo after the start of treatment (P = 0.0003) to be significantly associated with virological response. Among patients with a virological response, virological breakthrough was seen in 5.3% of 19 patients who responded virologically at 1 mo, in 20.7% of 203 patients at 3 mo, in 27.5% of 51 patients at 6 mo, in 33.3% of 12 patients at 9 mo, and in 100% of 3 patients at ≥15 mo. A virological breakthrough was found significantly more often in patients with delayed virological response. CONCLUSION: Lamivudine treatment could suppress serum HBV DNA in most of the tested Japanese patients. Long-term efficacy might be seen in patients without HBeAg at baseline, in the absence of cirrhosis, and in patients with a decline in HBV DNA level soon after the start of treatment. PMID:16489669

A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer

PubMed Central

Troyer, Dean A; Jamaspishvili, Tamara; Wei, Wei; Feng, Ziding; Good, Jennifer; Hawley, Sarah; Fazli, Ladan; McKenney, Jesse K; Simko, Jeff; Hurtado-Coll, Antonio; Carroll, Peter R; Gleave, Martin; Lance, Raymond; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; Brooks, James D; Squire, Jeremy A

2015-01-01

BACKGROUND Loss of the phosphatase and tensin homolog (PTEN) tumor suppressor gene is a promising marker of aggressive prostate cancer. Active surveillance and watchful waiting are increasingly recommended to patients with small tumors felt to be low risk, highlighting the difficulties of Gleason scoring in this setting. There is an urgent need for predictive biomarkers that can be rapidly deployed to aid in clinical decision-making. Our objectives were to assess the incidence and ability of PTEN alterations to predict aggressive disease in a multicenter study. METHODS We used recently developed probes optimized for sensitivity and specificity in a four-color FISH deletion assay to study the Canary Retrospective multicenter Prostate Cancer Tissue Microarray (TMA). This TMA was constructed specifically for biomarker validation from radical prostatectomy specimens, and is accompanied by detailed clinical information with long-term follow-up. RESULTS In 612 prostate cancers, the overall rate of PTEN deletion was 112 (18.3%). Hemizygous PTEN losses were present in 55/612 (9.0%) of cancers, whereas homozygous PTEN deletion was observed in 57/612 (9.3%) of tumors. Significant associations were found between PTEN status and pathologic stage (P < 0.0001), seminal vesicle invasion (P = 0.0008), extracapsular extension (P < 0.0001), and Gleason score (P = 0.0002). In logistic regression analysis of clinical and pathological variables, PTEN deletion was significantly associated with extracapsular extension, seminal vesicle involvement, and higher Gleason score. In the 406 patients in which clinical information was available, PTEN homozygous (P = 0.009) deletion was associated with worse post-operative recurrence-free survival (number of events = 189), pre-operative prostate specific antigen (PSA) (P < 0.001), and pathologic stage (P = 0.03). CONCLUSION PTEN status assessed by FISH is an independent predictor for recurrence-free survival in multivariate models, as were seminal vesicle invasion, extracapsular extension, and Gleason score, and preoperative PSA. Furthermore, these data demonstrate that the assay can be readily introduced at first diagnosis in a cost effective manner analogous to the use of FISH for analysis of HER2/neu status in breast cancer. Combined with published research beginning 17 years ago, both the data and tools now exist to implement a PTEN assay in the clinic. Prostate 75: 1206–1215, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc. PMID:25939393

Inter-vender and test-retest reliabilities of resting-state functional magnetic resonance imaging: Implications for multi-center imaging studies.

PubMed

An, Hyeong Su; Moon, Won-Jin; Ryu, Jae-Kyun; Park, Ju Yeon; Yun, Won Sung; Choi, Jin Woo; Jahng, Geon-Ho; Park, Jang-Yeon

2017-12-01

This prospective multi-center study aimed to evaluate the inter-vendor and test-retest reliabilities of resting-state functional magnetic resonance imaging (RS-fMRI) by assessing the temporal signal-to-noise ratio (tSNR) and functional connectivity. Study included 10 healthy subjects and each subject was scanned using three 3T MR scanners (GE Signa HDxt, Siemens Skyra, and Philips Achieva) in two sessions. The tSNR was calculated from the time course data. Inter-vendor and test-retest reliabilities were assessed with intra-class correlation coefficients (ICCs) derived from variant component analysis. Independent component analysis was performed to identify the connectivity of the default-mode network (DMN). In result, the tSNR for the DMN was not significantly different among the GE, Philips, and Siemens scanners (P=0.638). In terms of vendor differences, the inter-vendor reliability was good (ICC=0.774). Regarding the test-retest reliability, the GE scanner showed excellent correlation (ICC=0.961), while the Philips (ICC=0.671) and Siemens (ICC=0.726) scanners showed relatively good correlation. The DMN pattern of the subjects between the two sessions for each scanner and between three scanners showed the identical patterns of functional connectivity. The inter-vendor and test-retest reliabilities of RS-fMRI using different 3T MR scanners are good. Thus, we suggest that RS-fMRI could be used in multicenter imaging studies as a reliable imaging marker. Copyright © 2017 Elsevier Inc. All rights reserved.

Cardiovascular RiskprofilE - IMaging and gender-specific disOrders (CREw-IMAGO): rationale and design of a multicenter cohort study.

PubMed

Zoet, Gerbrand A; Meun, Cindy; Benschop, Laura; Boersma, Eric; Budde, Ricardo P J; Fauser, Bart C J M; de Groot, Christianne J M; van der Lugt, Aad; Maas, Angela H E M; Moons, Karl G M; Roeters van Lennep, Jeanine E; Roos-Hesselink, Jolien W; Steegers, Eric A P; van Rijn, Bas B; Laven, Joop S E; Franx, Arie; Velthuis, Birgitta K

2017-08-07

Reproductive disorders, such as polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI) and hypertensive pregnancy disorders (HPD) like pre-eclampsia (PE), are associated with an increased risk of cardiovascular disease (CVD). Detection of early signs of cardiovascular disease (CVD), as well as identification of risk factors among women of reproductive age which improve cardiovascular risk prediction, is a challenge and current models might underestimate long-term health risks. The aim of this study is to assess cardiovascular disease in patients with a history of a reproductive disorder by low-dose computed tomography (CT). Women of 45 - 55 years, who experienced a reproductive disorder (PCOS, POI, HPD), are invited to participate in this multicenter, prospective, cohort study. Women will be recruited after regular cardiovascular screening, including assessment of classical cardiovascular risk factors. CT of the coronary arteries (both coronary artery calcium scoring (CACS), and contrast-enhanced coronary CT angiography (CCTA)) and carotid siphon calcium scoring (CSC) is planned in 300 women with HPD and 300 women with PCOS or POI. In addition, arterial stiffness (non-invasive pulse wave velocity (PWV)) measurement and cell-based biomarkers (inflammatory circulating cells) will be obtained. Initial inclusion is focused on women of 45 - 55 years. However, the age range (40 - 45 years and/or ≥ 55 years) and group composition may be adjusted based on the findings of the interim analysis. Participants can potentially benefit from information obtained in this study concerning their current cardiovascular health and expected future risk of cardiovascular events. The results of this study will provide insights in the development of CVD in women with a history of reproductive disorders. Ultimately, this study may lead to improved cardiovascular prediction models and will provide an opportunity for timely adjustment of preventive strategies. Limitations of this study include the possibility of overdiagnosis and the average radiation dose of 3.5 mSv during coronary and carotid siphon CT, although the increased lifetime malignancy risk is negligible. Netherlands Trial Register, NTR5531 . Date registered: October 21st, 2015.

Remission of acromegaly after treatment withdrawal in patients controlled by cabergoline alone or in combination with octreotide: results from a multicenter study.

PubMed

Casagrande, A; Bronstein, M D; Jallad, R S; Mota, J I; Tabet, A; Abucham, J

2017-05-01

Remission of acromegaly has been reported after somatostatin analogs withdrawal, but not after withdrawal of combination therapy with cabergoline, and only in case reports of patients controlled by cabergoline alone. To establish the remission rates (normal IGF-1 for age/sex: IGF-1 ≤ 1.00 xULN) after withdrawal of combined treatment with octreotide LAR and cabergoline and of cabergoline alone, we prospectively studied 16 patients with acromegaly controlled by those treatments in the preceding 2 years as part of a larger study on remission of acromegaly after withdrawal of different medical treatments. Among 97 patients with controlled acromegaly included in the entire study, only 16 patients had been on combination therapy (n = 12) or cabergoline alone (n = 4). At 8 weeks after treatment withdrawal, three patients (19%) were in remission (short-term remission). At 60 weeks (long-term remission), IGF-1 levels were still in the normal range in two patients (12.5%) and remained normal up to 108 weeks after treatment withdrawal (last visit). One patient had been treated with cabergoline alone and another one with combination of octreotide and cabergoline before treatment withdrawal. Remission of acromegaly after treatment withdrawal seems to be uncommon in patients controlled by cabergoline, either as monotherapy or in combination with octreotide. In the future, larger studies and/or meta-analysis will be necessary to accurately establish the remission rates of acromegaly after withdrawal of cabergoline with or without somatostatin analogs.

Cognitive consequences of early versus late antiepileptic drug withdrawal after pediatric epilepsy surgery, the TimeToStop (TTS) trial: study protocol for a randomized controlled trial.

PubMed

Boshuisen, Kim; Lamberink, Herm J; van Schooneveld, Monique Mj; Cross, J Helen; Arzimanoglou, Alexis; van der Tweel, Ingeborg; Geleijns, Karin; Uiterwaal, Cuno Spm; Braun, Kees Pj

2015-10-26

The goals of intentional curative pediatric epilepsy surgery are to achieve seizure-freedom and antiepileptic drug (AED) freedom. Retrospective cohort studies have indicated that early postoperative AED withdrawal unmasks incomplete surgical success and AED dependency sooner, but not at the cost of long-term seizure outcome. Moreover, AED withdrawal seemed to improve cognitive outcome. A randomized trial is needed to confirm these findings. We hypothesized that early AED withdrawal in children is not only safe, but also beneficial with respect to cognitive functioning. This is a multi-center pragmatic randomized clinical trial to investigate whether early AED withdrawal improves cognitive function, in terms of attention, executive function and intelligence, quality of life and behavior, and to confirm safety in terms of eventual seizure freedom, seizure recurrences and "seizure and AED freedom." Patients will be randomly allocated in parallel groups (1:1) to either early or late AED withdrawal. Randomization will be concealed and stratified for preoperative IQ and medical center. In the early withdrawal arm reduction of AEDs will start 4 months after surgery, while in the late withdrawal arm reduction starts 12 months after surgery, with intended complete cessation of drugs after 12 and 20 months respectively. Cognitive outcome measurements will be performed preoperatively, and at 1 and 2 years following surgery, and consist of assessment of attention and executive functioning using the EpiTrack Junior test and intelligence expressed as IQ (Wechsler Intelligence Scales). Seizure outcomes will be assessed at 24 months after surgery, and at 20 months following start of AED reduction. We aim to randomize 180 patients who underwent anticipated curative epilepsy surgery below 16 years of age, were able to perform the EpiTrack Junior test preoperatively, and have no predictors of poor postoperative seizure prognosis (multifocal magnetic resonance imaging (MRI) abnormalities, incomplete resection of the lesion, epileptic postoperative electroencephalogram (EEG) abnormalities, or more than three AEDs at the time of surgery). Growing experience with epilepsy surgery has changed the view towards postoperative medication policy. In a European collaboration, we designed a multi-center pragmatic randomized clinical trial comparing early with late AED withdrawal to investigate benefits and safety of early AED withdrawal. The TTS trial is supported by the Dutch Epilepsy Fund (NL 08-10) ISRCTN88423240/ 08/05/2013.

Serum periostin: a novel biomarker for asthma management.

PubMed

Matsumoto, Hisako

2014-06-01

Chronic airway inflammation and remodeling are fundamental features of asthma. Even with adequate inhaled corticosteroid (ICS) treatment, there are still patients who exhibit Th2/eosinophilic inflammation and develop airflow limitation, a functional consequence of airway remodeling. There are few biomarkers that are applicable in the clinical setting that reflect refractory Th2/eosinophilic inflammation and remodeling of the asthmatic airways. Therefore, establishing such biomarkers is essential for managing patients who suffer from these conditions. This review addresses the importance of serum periostin measurements by describing observations made in a KiHAC multicenter cohort with periostin used as a marker of pulmonary function decline and refractory Th2/eosinophilic inflammation in patients with asthma receiving long-term ICS treatment. Furthermore, serum periostin could be a companion diagnostic for targeted therapy against refractory Th2/eosinophilic inflammation. Finally, the distinct characteristics of serum periostin as compared to conventional biomarkers are addressed.

Deferasirox for the treatment of chronic iron overload in transfusional hemosiderosis.

PubMed

Shashaty, George; Frankewich, Raymond; Chakraborti, Tamal; Choudary, Jasti; Al-Fayoumi, Suliman; Kacuba, Alice; Castillo, Sonia; Robie-Suh, Kathy; Rieves, Dwaine; Weiss, Karen; Pazdur, Richard

2006-12-01

This report describes the Food and Drug Administration's review of data and analyses leading to the approval of the oral iron chelator, deferasirox for the treatment of chronic iron overload due to transfusional hemosiderosis. The FDA reviewed findings of a controlled, open-label, randomized multicenter phase III study of deferasirox vs. deferoxamine in 586 patients with beta-thalessemia and transfusional hemosiderosis. The study results as well as the results of the FDA review of chemistry, preclinical pharmacology, and supportive studies are described. Following 48 weeks of treatment in the phase III study, patients' liver iron concentrations (a key endpoint variable) had decreased an average of 2.4 mg of iron (Fe)/g dry weight (dw) and 2.9 mg Fe/g dw in the deferasirox and deferoxamine groups, respectively, despite continued blood transfusions in both cohorts. Deferasirox was associated with serum creatinine increases in approximately a third of patients. Common adverse events included gastrointestinal symptoms and skin rash. Other data provided supportive evidence of deferasirox safety and efficacy. The FDA granted deferasirox accelerated approval on November 2, 2005, for use in treating chronic iron overload due to transfusional hemosiderosis in patients > or =2 years of age. The sponsor must obtain clinical data demonstrating the drug's long-term safety and effectiveness.

Outcomes of Pediatric Low-grade Gliomas Treated With Radiation Therapy: A Single-institution Study

PubMed Central

Raikar, Sunil S.; Halloran, Donna R.; Elliot, Michael; McHugh, Michele; Patel, Shaun; Gauvain, Karen M.

2014-01-01

Summary Radiation therapy is often considered the treatment of choice for low-grade gliomas. However, given the long-term effects of radiation on the developing brain, the appropriate use of radiation therapy in pediatric patients remains controversial. The purpose of this study was to evaluate progression-free survival (PFS) of pediatric low-grade glioma patients treated with radiation therapy. Data were obtained through a retrospective chart review of patients treated between 1991 and 2008 from a single tertiary care center in the midwest. The study population consisted of 17 patients, of whom 8 (47%) had tumor recurrence after radiation therapy. The median follow-up time was 8.2 years, with a range of 2.3 to 17.2 years. The median age at diagnosis was 5.4 years, and the median age at radiation therapy was 9.4 years. The 3- and the 10-year PFS were 69% ± 11.7% and 46% ± 13.3%, respectively. A significant difference in PFS was seen when comparing brainstem tumors with hypothalamic/optic pathway tumors (P = 0.019). Differences in PFS based on the age at diagnosis, the extent of initial surgery, and indication for radiation therapy were not significant. A larger multicenter study is needed to better assess PFS in these patients. PMID:24714505

Tendinopathy in Sport

PubMed Central

Ackermann, Paul W.; Renström, Per

2012-01-01

Context: Tendinopathy is increasing in prevalence and accounts for a substantial part of all sports injuries and occupational disorders. Despite the magnitude of the disorder, high-quality scientific data on etiology and available treatments have been limited. Evidence Acquisition: The authors conducted a MEDLINE search on tendinopathy, or “tendonitis” or “tendinosis” or “epicondylitis” or “jumpers knee” from 1980 to 2011. The emphasis was placed on updates on epidemiology, etiology, and recent patient-oriented Level 1 literature. Results: Repetitive exposure in combination with recently discovered intrinsic factors, such as genetic variants of matrix proteins, and metabolic disorders is a risk factor for the development of tendinopathy. Recent findings demonstrate that tendinosis is characterized by a fibrotic, failed healing response associated with pathological vessel and sensory nerve ingrowth. This aberrant sensory nerve sprouting may partly explain increased pain signaling and partly, by release of neuronal mediators, contribute to the fibrotic alterations observed in tendinopathy. The initial nonoperative treatment should involve eccentric exercise, which should be the cornerstone (basis) of treatment of tendinopathy. Eccentric training combined with extracorporeal shockwave treatment has in some reports shown higher success rates compared to any therapies alone. Injection therapies (cortisone, sclerosing agents, blood products including platelet-rich plasma) may have short-term effects but have no proven long-term treatment effects or meta-analyses to support them. For epicondylitis, cortisone injections have demonstrated poorer long-time results than conservative physiotherapy. Today surgery is less indicated because of successful conservative therapies. New minioperative procedures that, via the endoscope, remove pathologic tissue or abnormal neoinnervation demonstrate promising results but need confirmation by Level 1 studies. Conclusions: Novel targeted therapies are emerging, but multicenter trials are needed to confirm the results of exercise and mini-invasive treatments. PMID:23016086

Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results.

PubMed

Wang, Michael L; Blum, Kristie A; Martin, Peter; Goy, Andre; Auer, Rebecca; Kahl, Brad S; Jurczak, Wojciech; Advani, Ranjana H; Romaguera, Jorge E; Williams, Michael E; Barrientos, Jacqueline C; Chmielowska, Ewa; Radford, John; Stilgenbauer, Stephan; Dreyling, Martin; Jedrzejczak, Wieslaw Wiktor; Johnson, Peter; Spurgeon, Stephen E; Zhang, Liang; Baher, Linda; Cheng, Mei; Lee, Dana; Beaupre, Darrin M; Rule, Simon

2015-08-06

Ibrutinib, an oral inhibitor of Bruton tyrosine kinase, is approved for patients with mantle cell lymphoma (MCL) who have received one prior therapy. We report the updated safety and efficacy results from the multicenter, open-label phase 2 registration trial of ibrutinib (median 26.7-month follow-up). Patients (N = 111) received oral ibrutinib 560 mg once daily, and those with stable disease or better could enter a long-term extension study. The primary end point was overall response rate (ORR). The median patient age was 68 years (range, 40-84), with a median of 3 prior therapies (range, 1-5). The median treatment duration was 8.3 months; 46% of patients were treated for >12 months, and 22% were treated for ≥2 years. The ORR was 67% (23% complete response), with a median duration of response of 17.5 months. The 24-month progression-free survival and overall survival rates were 31% (95% confidence interval [CI], 22.3-40.4) and 47% (95% CI, 37.1-56.9), respectively. The most common adverse events (AEs) in >30% of patients included diarrhea (54%), fatigue (50%), nausea (33%), and dyspnea (32%). The most frequent grade ≥3 infections included pneumonia (8%), urinary tract infection (4%), and cellulitis (3%). Grade ≥3 bleeding events in ≥2% of patients were hematuria (2%) and subdural hematoma (2%). Common all-grade hematologic AEs were thrombocytopenia (22%), neutropenia (19%), and anemia (18%). The prevalence of infection, diarrhea, and bleeding was highest for the first 6 months of therapy and less thereafter. With longer follow-up, ibrutinib continues to demonstrate durable responses and favorable safety in relapsed/refractory MCL. The trial is registered to www.ClinicalTrials.gov as #NCT01236391. © 2015 by The American Society of Hematology.

Essure Permanent Birth Control, Effectiveness and Safety: An Italian 11-Year Survey.

PubMed

Franchini, Mario; Zizolfi, Brunella; Coppola, Carmela; Bergamini, Valentino; Bonin, Cecilia; Borsellino, Giovanni; Busato, Enrico; Calabrese, Stefania; Calzolari, Stefano; Fantin, Gian Piero; Giarrè, Giovanna; Litta, Piero; Luerti, Massimo; Mangino, Francesco Paolo; Marchino, Gian Luigi; Molinari, Maria Antonietta; Scatena, Elisa; Scrimin, Federica; Telloli, Paolo; Di Spiezio Sardo, Attilio

To describe safety, tolerability, and effectiveness results through a minimum 2-year follow-up of patients who underwent permanent sterilization with the Essure insert. A retrospective multicenter study (Canadian Task Force classification II2). Seven general hospitals and 4 clinical teaching centers in Italy. A total of 1968 women, mean age 39.5 years (range, 23-48 years) who underwent office hysteroscopic sterilization using the Essure insert between April 1, 2003, and December 30, 2014. The women underwent office hysteroscopic bilateral Essure insert placement, with satisfactory device location and tube occlusion based on hysterosalpingography or hysterosalpingo-contrast sonography (HyCoSy). Placement rate, successful bilateral tubal occlusion, perioperative adverse events, early postoperative (during the first 3 months of follow-up), and late complications were evaluated. Satisfactory insertion was accomplished in 97.2% of women and, in 4, perforation and 1 expulsion were detected during hysterosalpingography. Three unintended pregnancies occurred before the 3-month confirmation test. Two pregnancies were reported among women relying on the Essure inserts. Postprocedure pain was minimal and brief; in 9 women, pelvic pain became intractable, necessitating removal of the devices via laparoscopy. On telephone interviews, overall satisfaction was rated as "very satisfied" by the majority of women (97.6%), and no long-term adverse events were reported. The findings from this extended Italian survey further support the effectiveness, tolerability, and satisfaction of Essure hysteroscopic sterilization when motivated women are selected and well informed of the potential risks of the device. Moreover, the results do not demonstrate an increased incidence of complications and pregnancies associated with long-term Essure use. Patients with a known hypersensitivity to nickel may be less suitable candidates for the Essure insert. Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.

Rationale and design of a trial on the role of bosentan in Fontan patients: improvement of exercise capacity?

PubMed

Schuuring, Mark J; Vis, Jeroen C; Bouma, Berto J; van Dijk, Arie P J; van Melle, Joost P; Pieper, Petronella G; Vliegen, Hubert W; Sieswerda, Gertjan Tj; Mulder, Barbara J M

2011-07-01

The Fontan circulation is a palliative procedure performed in patients with complex congenital heart disease (CHD), making transpulmonary blood flow dependent on the systemic venous pressure. In a Fontan circulation a low pulmonary vascular resistance (PVR) is crucial, as is epitomized by the observation that a high PVR is a strong predictor of mortality. Long-term follow-up has shown that PVR may rise many years after the Fontan procedure has been performed, possibly due to micro-emboli from a dilated right atrium or from the venous system. Other mechanisms of increased PVR might be aging, obstructed airways caused by lymphatic dysfunction, lack of pulsatile pulmonary flow causing a release of endothelium-derived vasoactive molecules, and prolonged overexpression of vasoconstrictors such as endothelin-1. Mean plasma level of endothelin-1 has been shown to be significantly higher in Fontan patients compared to healthy controls. In patients with pulmonary arterial hypertension (PAH), therapy with bosentan, an endothelin-1 receptor antagonist, has demonstrated to improve exercise capacity and to reduce the elevated PVR. In addition, reduction of PVR is shown early and late after the Fontan procedure on treatment with exogenous NO, another advanced PAH therapy. However, the long term effect of reducing the PVR by bosentan treatment on exercise capacity in Fontan patients is still unknown. We designed a prospective, multicenter, randomized open label trial to study the effect of bosentan in Fontan patients. The primary endpoint will be the change in maximum exercise capacity (peak V'O2). We hypothesize that treatment with bosentan, an endothelin-1 receptor antagonist, improves maximum exercise capacity and functional capacity in adult Fontan patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Three-Gene Immunohistochemical Panel Adds to Clinical Staging Algorithms to Predict Prognosis for Patients With Esophageal Adenocarcinoma

PubMed Central

Ong, Chin-Ann J.; Shapiro, Joel; Nason, Katie S.; Davison, Jon M.; Liu, Xinxue; Ross-Innes, Caryn; O'Donovan, Maria; Dinjens, Winand N.M.; Biermann, Katharina; Shannon, Nicholas; Worster, Susannah; Schulz, Laura K.E.; Luketich, James D.; Wijnhoven, Bas P.L.; Hardwick, Richard H.; Fitzgerald, Rebecca C.

2013-01-01

Purpose Esophageal adenocarcinoma (EAC) is a highly aggressive disease with poor long-term survival. Despite growing knowledge of its biology, no molecular biomarkers are currently used in routine clinical practice to determine prognosis or aid clinical decision making. Hence, this study set out to identify and validate a small, clinically applicable immunohistochemistry (IHC) panel for prognostication in patients with EAC. Patients and Methods We recently identified eight molecular prognostic biomarkers using two different genomic platforms. IHC scores of these biomarkers from a UK multicenter cohort (N = 374) were used in univariate Cox regression analysis to determine the smallest biomarker panel with the greatest prognostic power with potential therapeutic relevance. This new panel was validated in two independent cohorts of patients with EAC who had undergone curative esophagectomy from the United States and Europe (N = 666). Results Three of the eight previously identified prognostic molecular biomarkers (epidermal growth factor receptor [EGFR], tripartite motif-containing 44 [TRIM44], and sirtuin 2 [SIRT2]) had the strongest correlation with long-term survival in patients with EAC. Applying these three biomarkers as an IHC panel to the validation cohort segregated patients into two different prognostic groups (P < .01). Adjusting for known survival covariates, including clinical staging criteria, the IHC panel remained an independent predictor, with incremental adverse overall survival (OS) for each positive biomarker (hazard ratio, 1.20; 95% CI, 1.03 to 1.40 per biomarker; P = .02). Conclusion We identified and validated a clinically applicable IHC biomarker panel, consisting of EGFR, TRIM44, and SIRT2, that is independently associated with OS and provides additional prognostic information to current survival predictors such as stage. PMID:23509313

Protocol for the effect evaluation of Individual Placement and Support (IPS): a randomized controlled multicenter trial of IPS versus treatment as usual for patients with moderate to severe mental illness in Norway.

PubMed

Sveinsdottir, Vigdis; Løvvik, Camilla; Fyhn, Tonje; Monstad, Karin; Ludvigsen, Kari; Øverland, Simon; Reme, Silje Endresen

2014-11-18

Roughly one third of disability pensions in Norway are issued for mental and behavioral disorders, and vocational rehabilitation offered to this group has traditionally been dominated by train-and-place approaches with assisted or sheltered employment. Based on a more innovative place-and-train approach, Individual Placement and Support (IPS) involves supported employment in real-life competitive work settings, and has shown great promise for patients with severe mental illness. The study is a multicenter Randomized Controlled Trial (RCT) of IPS in a Norwegian context, involving an effect evaluation, a process evaluation, and a cost/benefit analysis. IPS will be compared to high quality treatment as usual (TAU), with labor market participation and educational activity at 12 months post inclusion as the primary outcome. The primary outcome will be measured using register data, and the project will also include complete follow-up up to 4 years after inclusion for long-term outcome data. Secondary outcomes include mental health status, disability and quality of life, collected through survey questionnaires at baseline, and after 6 and 12 months. Participants will include patients undergoing treatment for moderate to severe mental illness who are either unemployed or on sickness or social benefits. The estimated total sample size of 400-500 will be randomly assigned to the interventions. To be eligible, participants must have an expressed desire to work, and sufficient Norwegian reading and writing skills to fill out the questionnaires. The Effect Evaluation of Individual Placement and Support (IPS) will be one of the largest randomized controlled trials to date investigating the effectiveness of IPS on competitive employment, and the first study to evaluate the effectiveness of IPS for patients with moderate to severe mental illness within a Norwegian context. Clinicaltrials.gov: NCT01964092 . Registered October 16th, 2013.

A prospective, multicenter study of a double stent system for palliative treatment of malignant extrahepatic biliary obstructions.

PubMed

Kim, Jong Woo; Gwon, Dong Il; Han, Young-Min; Won, Je Hwan; Hong, Hyun Pyo; Ko, Gi-Young; Yoon, Hyun-Ki; Sung, Kyu-Bo

2015-10-01

A double stent system (covered stent in uncovered stent) was designed to provide long-term patency without tumor ingrowth or stent-related complications, such as stent migration, cholecystitis, or pancreatitis. To investigate the safety and efficacy of double stents in patients with malignant extrahepatic biliary obstructions. This prospective, nonrandomized, multicenter study enrolled 160 consecutive patients (102 men; mean age, 64 years; range, 33-91 years) with malignant extrahepatic biliary obstructions treated with a double stent system from January 2010 to March 2012. The technical success rate of the double stent placement was 100%. No stent migration was observed. Procedure-related minor (self-limiting hemobilia [n = 6] and cholangitis [n = 2]) and major (pancreatitis [n = 16], cholecystitis [n = 3], and hepatic abscess [n = 2]) complications occurred in a total of 29 patients. The mean serum bilirubin level, which was 8.9 ± 5.6 mg/dL before drainage, decreased to 2.2 ± 4.6 mg/dL 1 month after stent placement (P < 0.001). Successful internal drainage was achieved in 148 patients (92.5%). During the mean follow-up period of 205 days, acute cholecystitis (n = 3) and hepatic abscess (n = 2) occurred in five patients. The median patient survival and stent patency time were 135 days (95% confidence interval [CI], 96-160 days) and 114 days (95% CI, 83-131 days), respectively. Of 153 patients, 22 (14.4%) presented with stent dysfunction due to sludge incrustation (n = 17), tumor overgrowth (n = 4), or blood clot (n = 1), and required repeat intervention. Tumor ingrowth was not observed in any of these patients. Percutaneous treatment of malignant extrahepatic biliary obstruction using a double stent safely and effectively achieves internal biliary drainage. © The Foundation Acta Radiologica 2014.

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.

Udenafil for the treatment of erectile dysfunction

PubMed Central

Cho, Min Chul; Paick, Jae-Seung

2014-01-01

Erectile dysfunction (ED) is often perceived by both patients and sexual partners as a serious problem that can jeopardize quality of life, psychosocial or emotional well-being, and the partnership in the long term. Since their introduction, oral phosphodiesterase type 5 inhibitors (PDE5Is) have been found to be highly effective and well tolerated, and are available as the first-line therapy for the treatment of ED. Udenafil is one of the selective PDE5Is made available in recent years for the treatment of ED. Udenafil has clinical properties of both relatively rapid onset and long duration of action due to its pharmacokinetic profile, thereby providing an additional treatment option for ED men to better suit individual needs. There is positive evidence that udenafil is effective and well tolerated in the treatment of ED of a broad spectrum of etiologies or severity. Udenafil is as effective in the treatment of diabetes mellitus-associated ED as other PDE5Is. Due to the clinical property of relatively long duration of action, udenafil may be another option in daily dosing treatment for ED, as suggested by its favorable efficacy and safety profile. Most adverse effects reported from clinical trials are mild or moderate in severity, without any serious adverse event, with headache and flushing being the most common. Also, the concomitant use of anti-hypertensive drugs or alpha-1-blockers does not significantly affect the efficacy and safety profile of udenafil. However, additional studies with larger cohorts including prospective, multicenter, comparative studies with patients of different ethnicities are needed to further validate the favorable findings of udenafil in the treatment of ED. PMID:24868160

Effects of Continuous Positive Airway Pressure on Neurocognitive Function in Obstructive Sleep Apnea Patients: The Apnea Positive Pressure Long-term Efficacy Study (APPLES)

PubMed Central

Kushida, Clete A.; Nichols, Deborah A.; Holmes, Tyson H.; Quan, Stuart F.; Walsh, James K.; Gottlieb, Daniel J.; Simon, Richard D.; Guilleminault, Christian; White, David P.; Goodwin, James L.; Schweitzer, Paula K.; Leary, Eileen B.; Hyde, Pamela R.; Hirshkowitz, Max; Green, Sylvan; McEvoy, Linda K.; Chan, Cynthia; Gevins, Alan; Kay, Gary G.; Bloch, Daniel A.; Crabtree, Tami; Dement, William C.

2012-01-01

Study Objective: To determine the neurocognitive effects of continuous positive airway pressure (CPAP) therapy on patients with obstructive sleep apnea (OSA). Design, Setting, and Participants: The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, randomized, double-blind, 2-arm, sham-controlled, multicenter trial conducted at 5 U.S. university, hospital, or private practices. Of 1,516 participants enrolled, 1,105 were randomized, and 1,098 participants diagnosed with OSA contributed to the analysis of the primary outcome measures. Intervention: Active or sham CPAP Measurements: Three neurocognitive variables, each representing a neurocognitive domain: Pathfinder Number Test-Total Time (attention and psychomotor function [A/P]), Buschke Selective Reminding Test-Sum Recall (learning and memory [L/M]), and Sustained Working Memory Test-Overall Mid-Day Score (executive and frontal-lobe function [E/F]) Results: The primary neurocognitive analyses showed a difference between groups for only the E/F variable at the 2 month CPAP visit, but no difference at the 6 month CPAP visit or for the A/P or L/M variables at either the 2 or 6 month visits. When stratified by measures of OSA severity (AHI or oxygen saturation parameters), the primary E/F variable and one secondary E/F neurocognitive variable revealed transient differences between study arms for those with the most severe OSA. Participants in the active CPAP group had a significantly greater ability to remain awake whether measured subjectively by the Epworth Sleepiness Scale or objectively by the maintenance of wakefulness test. Conclusions: CPAP treatment improved both subjectively and objectively measured sleepiness, especially in individuals with severe OSA (AHI > 30). CPAP use resulted in mild, transient improvement in the most sensitive measures of executive and frontal-lobe function for those with severe disease, which suggests the existence of a complex OSA-neurocognitive relationship. Clinical Trial Information: Registered at clinicaltrials.gov. Identifier: NCT00051363. Citation: Kushida CA; Nichols DA; Holmes TH; Quan SF; Walsh JK; Gottlieb DJ; Simon RD; Guilleminault C; White DP; Goodwin JL; Schweitzer PK; Leary EB; Hyde PR; Hirshkowitz M; Green S; McEvoy LK; Chan C; Gevins A; Kay GG; Bloch DA; Crabtree T; Demen WC. Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: the Apnea Positive Pressure Long-term Efficacy Study (APPLES). SLEEP 2012;35(12):1593-1602. PMID:23204602

Impact of pre-transplant pulmonary hypertension on survival after heart transplantation: a UNOS registry analysis.

PubMed

Vakil, Kairav; Duval, Sue; Sharma, Alok; Adabag, Selcuk; Abidi, Kashan Syed; Taimeh, Ziad; Colvin-Adams, Monica

2014-10-20

Severe pre-transplant pulmonary hypertension (PH) has been associated with adverse short-term clinical outcomes after heart transplantation in relatively small single-center studies. The impact of pre-transplant PH on long-term survival after heart transplantation has not been examined in a large, multi-center cohort. Adults (≥18 years) who underwent first time heart transplantation in the United States between 1987 and 2012 were retrospectively identified from the United Network for Organ Sharing registry. Pre-transplant PH was classified as mild, moderate, or severe based on pulmonary vascular resistance (PVR), trans-pulmonary gradient (TPG), and pulmonary artery (PA) mean pressure. Primary outcome was all-cause mortality. Data from 26,649 heart transplant recipients (mean age 52±12 years; 76% male; 76% Caucasian) were analyzed. During a mean follow-up of 5.7±4.8 years, there were 10,334 (39%) deaths. Pre-transplant PH (PVR≥2.5 WU) was a significant predictor of mortality (hazard ratio 1.10, 95% confidence interval 1.05-1.14, p<0.0001) in multivariable analysis. However, the severity of pre-transplant PH (mild/moderate vs. severe) did not affect short or long-term survival. Similarly, even in patients who were supported with either a left ventricular assist device or a total artificial heart prior to transplant, severe pre-transplant PH was not associated with worse survival when compared to patients with mild/moderate pre-transplant PH. Pre-transplant PH (PVR≥2.5 WU) is associated with a modest increase in mortality when compared to patients without pre-transplant PH. However, the severity of pre-transplant PH, assessed by PVR, TPG, or mean PA pressure, is not a discriminating factor for poor survival in patients listed for heart transplantation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Computer and internet use by persons after traumatic spinal cord injury.

PubMed

Goodman, Naomi; Jette, Alan M; Houlihan, Bethlyn; Williams, Steve

2008-08-01

To determine whether computer and internet use by persons post spinal cord injury (SCI) is sufficiently prevalent and broad-based to consider using this technology as a long-term treatment modality for patients who have sustained SCI. A multicenter cohort study. Twenty-six past and current U.S. regional Model Spinal Cord Injury Systems. Patients with traumatic SCI (N=2926) with follow-up interviews between 2004 and 2006, conducted at 1 or 5 years postinjury. Not applicable. Results revealed that 69.2% of participants with SCI used a computer; 94.2% of computer users accessed the internet. Among computer users, 19.1% used assistive devices for computer access. Of the internet users, 68.6% went online 5 to 7 days a week. The most frequent use for internet was e-mail (90.5%) and shopping sites (65.8%), followed by health sites (61.1%). We found no statistically significant difference in computer use by sex or level of neurologic injury, and no difference in internet use by level of neurologic injury. Computer and internet access differed significantly by age, with use decreasing as age group increased. The highest computer and internet access rates were seen among participants injured before the age of 18. Computer and internet use varied by race: 76% of white compared with 46% of black subjects were computer users (P<.001), and 95.3% of white respondents who used computers used the internet, compared with 87.6% of black respondents (P<.001). Internet use increased with education level (P<.001): eighty-six percent of participants who did not graduate from high school or receive a degree used the internet, while over 97% of those with a college or associate's degree did. While the internet holds considerable potential as a long-term treatment modality after SCI, limited access to the internet by those who are black, those injured after age 18, and those with less education does reduce its usefulness in the short term for these subgroups.

Long-term immunogenicity of an initial booster dose of an inactivated, Vero cell culture-derived Japanese encephalitis vaccine (JE-VC) and the safety and immunogenicity of a second JE-VC booster dose in children previously vaccinated with an inactivated, mouse brain-derived Japanese encephalitis vaccine.

PubMed

Yun, Ki Wook; Lee, Hoan Jong; Park, Ji Young; Cho, Hye-Kyung; Kim, Yae-Jean; Kim, Kyung-Hyo; Kim, Nam Hee; Hong, Young Jin; Kim, Dong Ho; Kim, Hwang Min; Cha, Sung-Ho

2018-03-07

This study was performed with the aim of determining the long-term immunogenicity of an inactivated, Vero cell culture-derived Japanese encephalitis (JE) vaccine (JE-VC) and an inactivated, mouse brain-derived JE vaccine (JE-MB) after the 1st booster dose at 2 years of age, as well as the safety and immunogenicity of the 2nd booster dose of JE-VC at 6 years of age, in children primed and given a 1st booster dose of either JE-VC or JE-MB. In this multicenter, open-label clinical trial, the study population consisted of healthy Korean children (aged 6 years) who participated in the previous JE vaccine trial. All subjects were subcutaneously vaccinated once for the booster immunization with Boryung Cell Culture Japanese Encephalitis Vaccine® (JE-VC). Approximately 4 years after the 1st booster dose of JE-VC, the seroprotection rate (SPR) and geometric mean titer (GMT) of the neutralizing antibody were 100% and 1113.8, respectively. In children primed and given a 1st booster dose of JE-MB, the SPR and GMT were 88.5% and 56.3, respectively. After the 2nd booster dose of JE-VC, all participants primed and given a 1st booster dose of either JE-MB or JE-VC were seroprotective against JE virus. The GMT of the neutralizing antibody was higher in children primed and given a 1st booster dose of JE-VC (8144.1) than in those primed and given a 1st booster dose of JE-MB (942.5) after the vaccination (p < 0.001). In addition, the 2nd booster dose of JE-VC showed a good safety profile with no serious vaccine-related adverse events. The 1st booster dose of JE-VC and JE-MB showed long-term immunogenicity of at least 4 years, and the 2nd booster dose of JE-VC showed a good safety and immunogenicity profile in children primed and given a 1st booster dose of either JE-VC or JE-MB. ClinicalTtrials.gov Identifier: NCT02532569. Copyright © 2018 Elsevier Ltd. All rights reserved.

Influence of marital status and employment status on long-term adherence with continuous positive airway pressure in sleep apnea patients.

PubMed

Gagnadoux, Frédéric; Le Vaillant, Marc; Goupil, François; Pigeanne, Thierry; Chollet, Sylvaine; Masson, Philippe; Humeau, Marie-Pierre; Bizieux-Thaminy, Acya; Meslier, Nicole

2011-01-01

Long-term adherence is a major issue in patients receiving home continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea-hypopnea syndrome (OSAHS). In a multicenter prospective cohort (the Institut de Recherche en Santé Respiratoire des Pays de la Loire [IRSR] sleep cohort) of consecutive OSAHS patients in whom CPAP had been prescribed for at least 90 days, we studied the impact on long-term treatment adherence of socioeconomic factors, patients and disease characteristics prior to CPAP initiation. Among 1,141 patients in whom CPAP had been prescribed for an average of 504±251 days (range: 91 to 1035), 674 (59%) were adherent with a mean daily use of CPAP≥4 h (mean: 6.42±1.35 h). Stepwise regression analysis identified 4 independent factors of CPAP adherence including apnea-hypopnea index (AHI) (OR: 1.549, 95%CI 1.163 to 2.062 for AHI≥30 vs. AHI<30; p = 0.003), body mass index (BMI) (OR: 1.786, 95%CI 1.131 to 2.822 for BMI≥25 and <30 kg/m(2), p = 0.01; OR: 1.768, 95%CI 1.145-2.731 for BMI≥30 kg/m(2), p = 0.01 vs. BMI<25 kg/m(2)), employment status (OR: 1.414, 95%CI 1.097-1.821 for retired vs. employed; p = 0.007) and marital status (OR: 1.482, 95%CI 1.088-2.019 for married or living as a couple vs. living alone; p = 0.01). Age, gender, Epworth sleepiness scale, depressive syndrome, associated cardiovascular morbidities, educational attainment and occupation category did not influence CPAP adherence. Marital status and employment status are independent factors of CPAP adherence in addition to BMI and disease severity. Patients living alone and/or working patients are at greater risk of non-adherence, whereas adherence is higher in married and retired patients. These findings suggest that the social context of daily life should be taken into account in risk screening for CPAP non-adherence. Future interventional studies targeting at-risk patients should be designed to address social motivating factors and work-related barriers to CPAP adherence.

A multi-centre, open label, long-term follow-up study to evaluate the benefits of a new viscoelastic hydrogel (Hymovis®) in the treatment of knee osteoarthritis.

PubMed

Benazzo, F; Perticarini, L; Padolino, A; Castelli, A; Gifuni, P; Lovato, M; Manzini, C; Giordan, N

2016-03-01

To evaluate the long-term efficacy and safety of Hymovis® in the symptomatic treatment of knee osteoarthritis (OA). This is a prospective, multi-center, open label, phase III clinical study. Two intra-articular injections (3 mL) of Hymovis® (8 mg/mL HYADD® 4) were administered 1 week apart at the beginning of the study on day 0 and day 7 and after 6 months from baseline, on day 182 and 189. Follow-up assessment were conducted for 52 weeks. 50 subjects, > 40 years old, with knee OA, with clinical and radiological confirm, complain pain in the target knee were enrolled. The variables considered were: WOMAC questionnaire, Joint Space Width (JSW), OMERACT OARSI responder criteria, EQ-5D questionnaire, rescue medication consumption. After the injections of Hymovis®, pain perceived by the patient when walking on a flat surface (WOMAC A1 score) significantly improves at the end of the study respect to the baseline. WOMAC stiffness, physical function and total score significantly improve during the study since 3 months after treatment, and it is maintained up to the end of the study (p < 0.001). By the x-ray analysis of knee, a radiological progression of OA was observed in the 26% of patients at the end of the study, while 88% of patients result to be responder to the therapy classified as per OMERACT-OARSI criteria. The EQ-5D weighted index increased significantly, against baseline, at each study time point (p < 0.001). Investigator's and patient's global assessment of the disease measured by the VAS both show a marked improvement in patient's health conditions. Results from this study confirm that Hymovis® alleviate the knee pain since the first treatment cycle. The patients treated with two cycles of intra-articular injections of Hymovis® have a progressive pain reduction that is maintained up to one year after the treatment start with improve of all the scores considered in this study. Hymovis® is effective and safe in symptomatic treatment of painful knee OA.

Salivary Telomere Length and Lung Function in Adolescents Born Very Preterm: A Prospective Multicenter Study.

PubMed

Hadchouel, Alice; Marchand-Martin, Laetitia; Franco-Montoya, Marie-Laure; Peaudecerf, Laetitia; Ancel, Pierre-Yves; Delacourt, Christophe

2015-01-01

Preterm birth is associated with abnormal respiratory functions throughout life. The mechanisms underlying these long-term consequences are still unclear. Shortening of telomeres was associated with many conditions, such as chronic obstructive pulmonary disease. We aimed to search for an association between telomere length and lung function in adolescents born preterm. Lung function and telomere length were measured in 236 adolescents born preterm and 38 born full-term from the longitudinal EPIPAGE cohort. Associations between telomere length and spirometric indices were tested in univariate and multivariate models accounting for confounding factors in the study population. Airflows were significantly lower in adolescents born preterm than controls; forced expiratory volume in one second was 12% lower in the extremely preterm born group than controls (p<0.001). Lower birth weight, bronchopulmonary dysplasia and postnatal sepsis were significantly associated with lower airflow values. Gender was the only factor that was significantly associated with telomere length. Telomere length correlated with forced expiratory flow 25-75 in the extremely preterm adolescent group in univariate and multivariate analyses (p = 0.01 and p = 0.02, respectively). We evidenced an association between telomere length and abnormal airflow in a population of adolescents born extremely preterm. There was no evident association with perinatal events. This suggests other involved factors, such as a continuing airway oxidative stress leading to persistent inflammation and altered lung function, ultimately increasing susceptibility to chronic obstructive pulmonary disease.

Predictors of survival in octogenarians after mitral valve surgery for degenerative disease: The Mitral Surgery in Octogenarians study.

PubMed

Chivasso, Pierpaolo; Bruno, Vito D; Farid, Shakil; Malvindi, Pietro Giorgio; Modi, Amit; Benedetto, Umberto; Ciulli, Franco; Abu-Omar, Yasir; Caputo, Massimo; Angelini, Gianni D; Livesey, Steve; Vohra, Hunaid A

2018-04-01

An increasing number of octogenarians are referred to undergo mitral valve surgery for degenerative disease, and percutaneous approaches are being increasingly used in this subgroup of patients. We sought to determine the survival and its predictors after Mitral Valve Surgery in Octogenarians (MiSO) in a multicenter UK study of high-volume specialized centers. Pooled data from 3 centers were collected retrospectively. To identify the predictors of short-term composite outcome of 30 days mortality, acute kidney injury, and cerebrovascular accident, a multivariable logistic regression model was developed. Multiple Cox regression analysis was performed for late mortality. Kaplan-Meier curves were generated for long-term survival in various subsets of patients. Receiver operating characteristic analysis was done to determine the predictive power of the logistic European System for Cardiac Operative Risk Evaluation. A total of 247 patients were included in the study. The median follow-up was 2.9 years (minimum 0, maximum 14 years). A total of 150 patients (60.7%) underwent mitral valve repair, and 97 patients (39.3%) underwent mitral valve replacement. Apart from redo cardiac surgery (mitral valve repair 6 [4%] vs mitral valve replacement 11 [11.3%], P = .04) and preoperative atrial fibrillation (mitral valve repair 79 [52.6%] vs mitral valve replacement 34 [35.1%], P < .01), there was no significant difference in terms of any other preoperative characteristics between the 2 groups. Patient operative risk, as estimated by logistic European System for Cardiac Operative Risk Evaluation, was lower in the mitral valve repair group (10.2 ± 11.8 vs 13.7 ± 15.2 in mitral valve replacement; P = .07). No difference was found between groups for duration of cardiopulmonary bypass and aortic crossclamp times. The 30-day mortality for the whole cohort was 13.8% (mitral valve repair 4.7% vs mitral valve replacement 18.6%; P < .01). No differences were found in terms of postoperative cerebrovascular accident (2% vs 3.1%; P = .9), acute kidney injury requiring dialysis (6.7% vs 13.4%; P = .12), and superficial or deep sternal wound infection (10% vs 16.5%, P = .17; 2% vs 3.1%, P = .67, respectively). The final multiple regression model for short-term composite outcome included previous cardiac surgery (odds ratio [OR], 4.47; 95% confidence interval [CI], 1.37-17.46; P = .02), intra-aortic balloon pump use (OR, 4.77; 95% CI, 1.67-15.79; P < .01), and mitral valve replacement (OR, 7.7; 95% CI, 4.04-14.9; P < .01). Overall survival for the entire cohort at 1, 5, and 10 years was 82.4%, 63.7%, and 45.5% (mitral valve repair vs mitral valve replacement: 89.9% vs 70.7% at 1 year, 69.6% vs 54% at 5 years, and 51.8% vs 35.5% at 10 years; P = .0005). Cox proportional hazard model results showed mitral valve replacement (hazard ratio, 1.88; 95% CI, 1.22-2.89; P < .01) and intra-aortic balloon pump use (hazard ratio, 2.54; 95% CI, 1.26-5.13; P < .01) to be independent predictor factors affecting long-term survival. Logistic European System for Cardiac Operative Risk Evaluation did not perform well in predicting early mortality (area under the curve, 0.57%). In octogenarians, mitral valve repair for degenerative disease is associated with good survival and remains the gold standard, whereas mitral valve replacement is still associated with significant mortality. Logistic European System for Cardiac Operative Risk Evaluation was unable to predict early mortality in our cohort of patients. Larger international multicenter registries are required to optimize the decision-making process in such a high-risk subgroup. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Luminal-like HER2-negative stage IA breast cancer: a multicenter retrospective study on long-term outcome with propensity score analysis

PubMed Central

De Angelis, Carmine; Di Maio, Massimo; Crispo, Anna; Giuliano, Mario; Schettini, Francesco; Bonotto, Marta; Gerratana, Lorenzo; Iacono, Donatella; Cinausero, Marika; Riccardi, Ferdinando; Ciancia, Giuseppe; De Laurentiis, Michelino; Puglisi, Fabio; De Placido, Sabino; Arpino, Grazia

2017-01-01

The benefit of adding chemotherapy (CT) to adjuvant hormone therapy (HT) in stage IA luminal-like HER2-negative breast cancer (BC) is unclear. We retrospectively evaluated predictive factors and clinical outcome of 1,222 patients from 4 oncologic centers. Three hundred and eighty patients received CT and HT (CT-cohort) and 842 received HT alone (HT-cohort). Disease-free survival (DFS) and overall survival (OS) were evaluated with univariate and multivariate analyses. We also applied the propensity score methodology. Compared with the HT-cohort, patients in the CT-cohort were more likely to be younger, have larger tumors of a higher histological grade that were Ki67-positive, and lower estrogen and progesterone receptor expression. At univariate analysis, a higher histological grade and Ki67 were significantly associated to a lower DFS. At multivariable analysis, only histological grade was predictive of DFS. The CT-cohort had a worse outcome than the HT-cohort in terms of DFS and OS, but differences disappeared when matched according to propensity score. In summary, patients with stage IA luminal-like BC had an excellent prognosis, however relapse and mortality were higher in the CT-cohort than in the HT-cohort. Longer use of adjuvant HT or other therapeutic strategies may be needed to improve outcome. PMID:29348868

One Hundred Twenty-One Resected Solid Pseudopapillary Tumors of the Pancreas: An 8-Year Single-Institution Experience at Zhongshan Hospital, Shanghai, China.

PubMed

Xu, Yadong; Zhao, Guochao; Pu, Ning; Nuerxiati, Abulimiti; Ji, Yuan; Zhang, Lei; Rong, Yefei; Lou, Wenhui; Wang, Dansong; Kuang, Tiantao; Xu, Xuefeng; Wu, Wenchuan

2017-09-01

The aims of this study were to introduce our experience with treating patients with pancreatic solid pseudopapillary tumors (SPTs) and to investigate the clinical risk factors for recurrence of SPTs because no consensus has been established to date. One hundred twenty-one patients underwent surgical resection from January 2008 to December 2015 in our institution. Clinical data were collected from the standardized reports. Of the 121 patients, 93 (76.9%) were women, 28 (23.1%) were men, and the mean age at diagnosis was 33.7 years (range, 11-68 years). Sixty patients were subjected to short-term complications, and 8 patients experienced long-term complications, some of whom may require surgery. The tumor located in the distal pancreas (P = 0.02), and a Ki-67 index value > 1.5 (P = 0.01) indicated malignancy according to the World Health Organization 2000 classification. One hundred three patients responded to follow-up, and 3 cases (2.9%) were subject to liver metastases. Recurrence was more frequently observed in tumors classified as high-grade malignancies according to the World Health Organization 2010 classification (P = 0.013), synchronous metastases (P < 0.001), peripancreatic fat infiltration (P = 0.018), and lymphovascular invasion (P < 0.001). Evaluating the risk of the recurrence of SPTs still requires systematic and multicenter trials in the future, even some pathological features showed statistical differences.

A multicenter randomized controlled evaluation of automated home monitoring and telephonic disease management in patients recently hospitalized for congestive heart failure: the SPAN-CHF II trial.

PubMed

Weintraub, Andrew; Gregory, Douglas; Patel, Ayan R; Levine, Daniel; Venesy, David; Perry, Kathleen; Delano, Christine; Konstam, Marvin A

2010-04-01

We performed a prospective, randomized investigation assessing the incremental effect of automated health monitoring (AHM) technology over and above that of a previously described nurse directed heart failure (HF) disease management program. The AHM system measured and transmitted body weight, blood pressure, and heart rate data as well as subjective patient self-assessments via a standard telephone line to a central server. A total of 188 consented and eligible patients were randomized between intervention and control groups in 1:1 ratio. Subjects randomized to the control arm received the Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) heart failure disease management program. Subjects randomized to the intervention arm received the SPAN-CHF disease management program in conjunction with the AHM system. The primary end point was prespecified as the relative event rate of HF hospitalization between intervention and control groups at 90 days. The relative event rate of HF hospitalization for the intervention group compared with controls was 0.50 (95%CI [0.25-0.99], P = .05). Short-term reductions in the heart failure hospitalization rate were associated with the use of automated home monitoring equipment. Long-term benefits in this model remain to be studied. (c) 2010 Elsevier Inc. All rights reserved.

Acute heart failure with and without concomitant acute coronary syndromes: patient characteristics, management, and survival.

PubMed

Tarvasmäki, Tuukka; Harjola, Veli-Pekka; Nieminen, Markku S; Siirilä-Waris, Krista; Tolonen, Jukka; Tolppanen, Heli; Lassus, Johan

2014-10-01

Acute coronary syndromes (ACS) may precipitate up to a third of acute heart failure (AHF) cases. We assessed the characteristics, initial management, and survival of AHF patients with (ACS-AHF) and without (nACS-AHF) concomitant ACS. Data from 620 AHF patients were analyzed in a prospective multicenter study. The ACS-AHF patients (32%) more often presented with de novo AHF (61% vs. 43%; P < .001). Although no differences existed between the 2 groups in mean blood pressure, heart rate, or routine biochemistry on admission, cardiogenic shock and pulmonary edema were more common manifestations in ACS-AHF (P < .01 for both). Use of intravenous nitrates, furosemide, opioids, inotropes, and vasopressors, as well as noninvasive ventilation and invasive coronary procedures (angiography, percutaneous coronary intervention, coronary artery bypass graft surgery), were more frequent in ACS-AHF (P < .001 for all). Although 30-day mortality was significantly higher for ACS-AHF (13% vs. 8%; P = .03), survival in the 2 groups at 5 years was similar. Overall, ACS was an independent predictor of 30-day mortality (adjusted odds ratio 2.0, 95% confidence interval 1.07-3.79; P = .03). Whereas medical history and the manifestation and initial treatment of AHF between ACS-AHF and nACS-AHF patients differ, long-term survival is similar. ACS is, however, independently associated with increased short-term mortality. Copyright © 2014 Elsevier Inc. All rights reserved.

Utilization of Subcutaneous Methotrexate in Rheumatoid Arthritis Patients After Failure or Intolerance to Oral Methotrexate: A Multicenter Cohort Study.

PubMed

Branco, Jaime C; Barcelos, Anabela; de Araújo, Filipe Pombo; Sequeira, Graça; Cunha, Inês; Patto, José Vaz; Oliveira, Margarida; Mateus, Margarida Pratas; Couto, Maura; Nero, Patrícia; Pinto, Patrícia; Monteiro, Paulo; Castelão, Walter; Félix, Jorge; Ferreira, Diana; Almeida, João; Silva, Maria João

2016-01-01

Low-dose weekly methotrexate (MTX) is the mainstay in the therapy of rheumatoid arthritis (RA). It can be given via oral, intramuscular or subcutaneous (SC) route. This study sought to determine the real-world pattern of treatment with SC MTX in Portuguese adult patients with active RA. Utilization of Metoject(®) in Rheumatoid Arthritis (UMAR) was a non-interventional, cohort multicenter study with retrospective data collection. Eligible patients had active RA, at least 18 years of age, and started SC MTX treatment in 2009 or 2010 after failure or intolerance to oral MTX. Data were collected from patient's clinical records. Both non-parametric and parametric survival methods were used to obtain a detailed understanding of SC MTX treatment duration. Fifty patients were included, of which only 9 discontinued SC MTX during the study follow-up period. The probability of discontinuation after 1, 2, and 3 years of treatment of SC MTX treatment is expected to be 6.10%, 8.50%, and 23.20%, respectively. The extrapolated median duration of SC MTX using an exponential model was 106.4 months/8.87 years. Mean dose of SC MTX was 18.36 mg. The reasons for treatment discontinuation were occurrence of adverse events in six patients and lack of efficacy in three. The long treatment duration of SC MTX highlights its excellent tolerability compared to oral MTX, especially concerning the frequent adverse gastrointestinal events of MTX. Furthermore, long MTX treatment duration provides the opportunity to postpone or even avoid expensive therapies with biologics. The results obtained from the UMAR study provide important information for the utilization and public financing of SC MTX in Portugal.

Longitudinal Modeling of Depressive Trajectories Among HIV-Infected Men Using Cocaine.

PubMed

Mukerji, Shibani; Haghighat, Roxanna; Misra, Vikas; Lorenz, David R; Holman, Alex; Dutta, Anupriya; Gabuzda, Dana

2017-07-01

Cocaine use is prevalent among HIV-infected individuals. While cross-sectional studies suggest that cocaine users may be at increased risk for depression, long-term effects of cocaine on depressive symptoms remain unclear. This is a longitudinal study of 341 HIV-infected and uninfected men (135 cocaine users and 206 controls) ages 30-60 enrolled in the Multicenter AIDS Cohort Study during 1996-2009. The median baseline age was 41; 73% were African-American. In mixed-effects models over a median of 4.8 years of observation, cocaine use was associated with higher depressive symptoms independent of age, education level, and smoking (n = 288; p = 0.02); HIV infection modified this association (p = 0.03). Latent class mixed models were used to empirically identify distinct depressive trajectories (n = 160). In adjusted models, cocaine use was associated with threefold increased odds of membership in the class with persistent high depressive symptoms (95% confidence interval (CI) 1.38-6.69) and eightfold increased odds (95% CI (2.73-25.83) when tested among HIV-infected subjects only. Cocaine use is a risk factor for chronic depressive symptoms, particularly among HIV-infected men, highlighting the importance of integrating mental health and substance use treatments to address barriers to well-being and successful HIV-care.

Optimizing Outcome Assessment in Multicenter TBI Trials: Perspectives From TRACK-TBI and the TBI Endpoints Development Initiative.

PubMed

Bodien, Yelena G; McCrea, Michael; Dikmen, Sureyya; Temkin, Nancy; Boase, Kim; Machamer, Joan; Taylor, Sabrina R; Sherer, Mark; Levin, Harvey; Kramer, Joel H; Corrigan, John D; McAllister, Thomas W; Whyte, John; Manley, Geoffrey T; Giacino, Joseph T

Traumatic brain injury (TBI) is a global public health problem that affects the long-term cognitive, physical, and psychological health of patients, while also having a major impact on family and caregivers. In stark contrast to the effective trials that have been conducted in other neurological diseases, nearly 30 studies of interventions employed during acute hospital care for TBI have failed to identify treatments that improve outcome. Many factors may confound the ability to detect true and meaningful treatment effects. One promising area for improving the precision of intervention studies is to optimize the validity of the outcome assessment battery by using well-designed tools and data collection strategies to reduce variability in the outcome data. The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, conducted at 18 sites across the United States, implemented a multidimensional outcome assessment battery with 22 measures aimed at characterizing TBI outcome up to 1 year postinjury. In parallel, through the TBI Endpoints Development (TED) Initiative, federal agencies and investigators have partnered to identify the most valid, reliable, and sensitive outcome assessments for TBI. Here, we present lessons learned from the TRACK-TBI and TED initiatives aimed at optimizing the validity of outcome assessment in TBI.

Hormone therapy in menopausal women with cognitive complaints: a randomized, double-blind trial.

PubMed

Maki, P M; Gast, M J; Vieweg, A J; Burriss, S W; Yaffe, K

2007-09-25

To evaluate the effects of hormone therapy (HT) on cognition and subjective quality of life (QoL) in recently postmenopausal women with cognitive complaints. Cognitive Complaints in Early Menopause Trial (COGENT) was a randomized, double-blind, placebo-controlled, multicenter, pilot study of 180 healthy postmenopausal women aged 45 to 55 years, randomly assigned to receive either placebo or conjugated equine estrogen 0.625 mg/medroxyprogesterone acetate 2.5 mg for 4 months. Outcome measures included memory, subjective cognition, QoL, sexuality, and sleep, which were assessed at baseline and month 4. The study was terminated before the expected final sample size of 275 due to a decrease in enrollment coinciding with the publication of findings from the Women's Health Initiative. There were no differences between groups on any cognitive or QoL measures, except for an increase in sexual interest and thoughts with HT. Modest negative effects on short- and long-term verbal memory approached significance (p < 0.10). Women with baseline vasomotor symptoms (VMS) showed a decrease in VMS and an improvement in general QoL, but no cognitive benefit vs placebo. With the power to detect an effect size of >or=0.45, this study suggests potential modest negative effects on verbal memory that are consistent with previous hormone therapy trials in older women.

Multicenter Clinical Trial of the Nucleus® Hybrid™ S8 Cochlear Implant: Final Outcomes

PubMed Central

Gantz, Bruce J; Dunn, Camille; Oleson, Jacob; Hansen, Marlan; Parkinson, Aaron; Turner, Christopher

2015-01-01

Objective The concept expanding electrical speech processing to those with more residual acoustic hearing with a less invasive shorter cochlear implant has been ongoing since 1999. A multi-center study of the Nucleus Hybrid S8 CI took place between 2002–11. This report describes the final outcomes of this clinical trial. Study Design Multi-Center longitudinal single subject design Methods Eighty-seven subjects received a Nucleus® Hybrid™ S8 implant in their poorer ear. Speech perception in quiet (CNC words) and in noise (BKB-SIN) was collected pre- and post-operatively at 3, 6, and 12 months. Subjective questionnaire data using the APHAB was also collected. Results Some level of hearing preservation was accomplished in 98% subjects with 90% maintaining a functional low-frequency pure-tone average (LFPTA) at initial activation. By 12 months, 5 subjects had total hearing loss and 80% of subjects maintained functional hearing. CNC words demonstrated that 82.5% and 87.5% of subjects had significant improvements in the Hybrid and Combined conditions. The majority of had improvements with BKB-SIN. Results also indicated that as long as subjects maintained at least a severe LFPTA, there was significant improvement in speech understanding. Furthermore, all subjects reported positive improvements in hearing in three of the 4 subscales of the APHAB. Conclusion The concept of hybrid speech processing has significant advantages for subjects with residual low-frequency hearing. In this study, the Nucleus® Hybrid™ S8 provided improved word understanding in quiet and noise. Additionally, there appears to be stability of the residual hearing after initial activation of the device. Level of evidence 2c PMID:26756395

Proposal for a sub-classification of hepato-biliary-pancreatic operations for surgical site infection surveillance following assessment of results of prospective multicenter data.

PubMed

Nakahira, Shin; Shimizu, Junzo; Miyamoto, Atsushi; Kobayashi, Shogo; Umeshita, Koji; Ito, Toshinori; Monden, Morito; Doki, Yuichiro; Mori, Masaki

2013-06-01

Surgical site infection (SSI) surveillance in Japan is based on the National Nosocomial Infection Surveillance system, which categorizes all hepato-biliary-pancreatic surgeries, except for cholecystectomy, into "BILI." We evaluated differences among BILI procedures to determine the optimal subdivision for SSI surveillance. We conducted multicenter SSI surveillance at 20 hospitals. BILI was subdivided into choledochectomy, pancreatoduodenectomy, hepatectomy, hepatectomy with biliary reconstruction, pancreatoduodenectomy with hepatectomy, distal pancreatectomy and total pancreatectomy to determine the optimal subdivision. The outcome of interest was SSI. Univariate and multivariate analyses were performed to determine the predictive significance of variables in each type of surgery. 1,926 BILI cases were included in this study. SSI rates were 23.2 % for all BILI; for choledochectomy 23.6 %, pancreatoduodenectomy 39.3 %, hepatectomy 12.8 %, hepatectomy with biliary reconstruction 41.9 %, pancreatoduodenectomy with hepatectomy 27.3 %, distal pancreatectomy 31.8 %, and total pancreatectomy 20.0 %. SSI rates for hepatectomy were significantly lower than those for non-hepatectomy BILI. Risk factors for developing SSI with hepatectomy were drain placement and long operative duration, while for non-hepatectomy BILI, risk factors were use of intra-abdominal silk sutures, SSI risk index and long operative duration. Hepatectomy and non-hepatectomy BILI differ with regard to the incidence of and risk factors for developing SSI. These surgeries should be assessed separately when conducting SSI surveillance.

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

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.

Disease-modifying and symptomatic treatment of amyotrophic lateral sclerosis

PubMed Central

Dorst, Johannes; Ludolph, Albert C.; Huebers, Annemarie

2017-01-01

In this review, we summarize the most important recent developments in the treatment of amyotrophic lateral sclerosis (ALS). In terms of disease-modifying treatment options, several drugs such as dexpramipexole, pioglitazone, lithium, and many others have been tested in large multicenter trials, albeit with disappointing results. Therefore, riluzole remains the only directly disease-modifying drug. In addition, we discuss antisense oligonucleotides (ASOs) as a new and potentially causal treatment option. Progress in symptomatic treatments has been more important. Nutrition and ventilation are now an important focus of ALS therapy. Several studies have firmly established that noninvasive ventilation improves patients’ quality of life and prolongs survival. On the other hand, there is still no consensus regarding best nutritional management, but big multicenter trials addressing this issue are currently ongoing. Evidence regarding secondary symptoms like spasticity, muscle cramps or sialorrhea remains generally scarce, but some new insights will also be discussed. Growing evidence suggests that multidisciplinary care in specialized clinics improves survival. PMID:29399045

Three-year patient-related and stent-related outcomes of second-generation everolimus-eluting Xience V stents versus zotarolimus-eluting resolute stents in real-world practice (from the Multicenter Prospective EXCELLENT and RESOLUTE-Korea Registries).

PubMed

Lee, Joo Myung; Park, Kyung Woo; Han, Jung-Kyu; Yang, Han-Mo; Kang, Hyun-Jae; Koo, Bon-Kwon; Bae, Jang-Whan; Woo, Sung-Il; Park, Jin Sik; Jin, Dong-Kyu; Jeon, Dong Woon; Oh, Seok Kyu; Park, Jong-Seon; Kim, Doo-Il; Hyon, Min Su; Jeon, Hui-Kyung; Lim, Do-Sun; Kim, Myeong-Gon; Rha, Seung-Woon; Her, Sung-Ho; Hwang, Jin-Yong; Kim, Sanghyun; Choi, Young Jin; Kang, Jin Ho; Moon, Keon-Woong; Jang, Yangsoo; Kim, Hyo-Soo

2014-11-01

Long-term outcomes are imperative to confirm safety of drug-eluting stents. There have been 2 randomized controlled trials comparing everolimus-eluting stents (EESs) and Resolute zotarolimus-eluting stents (ZES-Rs). To date, long-term clinical outcomes of these stents were limited to only 1 report, which has recently reported 4-year comparisons of these stents. Therefore, more evidence is needed regarding long-term clinical outcomes of the second-generation stents. This study compared the long-term clinical outcomes of EES with ZES-R in "all-comer" cohorts up to 3-year follow-up. The EXCELLENT and RESOLUTE-Korea registries prospectively enrolled 3,056 patients treated with EES and 1,998 with ZES-R, respectively, without exclusions. Stent-related composite outcomes (target lesion failure) and patient-related composite events up to 3-year follow-up were compared in crude and propensity score-matched analyses. Of 5,054 patients, 3,830 patients (75.8%) had off-label indication (2,217 treated with EES and 1,613 treated with ZES-R). The stent-related outcome (189 [6.2%] vs 127 [6.4%], p = 0.812) and the patient-related outcome (420 [13.7%] vs 250 [12.5%], p = 0.581) did not differ between EES and ZES-R, respectively, at 3 years, which was corroborated by similar results from the propensity score-matched cohort (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.70 to 1.20, p = 0.523 and 0.85, 95% CI 0.70 to 1.02, p = 0.081, for stent- and patient-related outcomes, respectively). The rate of definite or probable stent thrombosis up to 3 years (22 [0.7%] vs 10 [0.5%], p = 0.370) was also similar. The rate of very late definite or probable stent thrombosis was very low and comparable between the 2 stents (3 [0.1%] vs 1 [0.1%], p = 0.657). In multivariate analysis, chronic renal failure (adjusted HR 3.615, 95% CI 2.440 to 5.354, p <0.001) and off-label indication (adjusted HR 1.782, 95% CI 1.169 to 2.718, p = 0.007) were the strongest predictors of target lesion failure at 3 years. In conclusion, both stents showed comparable safety and efficacy at 3-year follow-up in this robust real-world registry with unrestricted use of EES and ZES-R. Overall incidences of target lesion failure and definite stent thrombosis, including very late stent thrombosis, were low, even in the patients with off-label indications, suggesting excellent long-term safety and sustained efficacy of both types of second-generation drug-eluting stents. Copyright © 2014 Elsevier Inc. All rights reserved.

78 FR 66945 - Proposed Collection; 60-Day Comment request: Gulf Long-Term Follow-Up Study (GuLF STUDY)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-07

... Comment request: Gulf Long-Term Follow-Up Study (GuLF STUDY) Summary: In compliance with the requirement... days of the date of this publication. Proposed Collection: Gulf Long-Term Follow-Up Study (GuLF STUDY... GuLF STUDY is to investigate potential short- and long-term health effects associated with oil spill...

Fourier transform of the multicenter product of 1s hydrogenic orbitals and Coulomb or Yukawa potentials and the analytically reduced form for subsequent integrals that include plane waves

NASA Technical Reports Server (NTRS)

Straton, Jack C.

1989-01-01

The Fourier transform of the multicenter product of N 1s hydrogenic orbitals and M Coulomb or Yukawa potentials is given as an (M+N-1)-dimensional Feynman integral with external momenta and shifted coordinates. This is accomplished through the introduction of an integral transformation, in addition to the standard Feynman transformation for the denominators of the momentum representation of the terms in the product, which moves the resulting denominator into an exponential. This allows the angular dependence of the denominator to be combined with the angular dependence in the plane waves.

Effect of bardoxolone methyl on kidney function in patients with T2D and Stage 3b-4 CKD.

PubMed

Pergola, Pablo E; Krauth, Melissa; Huff, J Warren; Ferguson, Deborah A; Ruiz, Stacey; Meyer, Colin J; Warnock, David G

2011-01-01

Bardoxolone methyl, a novel synthetic triterpenoid, induces Nrf2, a transcription factor known to play a key role in decreasing oxidative stress and the production of pro-inflammatory molecules. This exploratory multi-center, open-label study assessed the clinical activity and safety of bardoxolone methyl in 20 patients with moderate to severe chronic kidney disease and type 2 diabetes. Patients received 25 mg of bardoxolone methyl daily for 28 days, followed by 75 mg daily for another 28 days. The study achieved its primary efficacy endpoint, as demonstrated by a significant increase from baseline in estimated glomerular filtration rate (eGFR) of 7.2 ml/min/1.73 m2 (p < 0.001). Improvements were seen in approximately 90% of patients and showed a dose- and time-dependent increase in eGFR. The eGFR change paralleled a significant reduction in serum creatinine (-0.3 mg/dl) and blood urea nitrogen (-4.9 mg/dl), along with an increase in creatinine clearance (+14.6 ml/min/1.73 m2), without a change in the 24-hour creatinine excretion rate. Markers of vascular injury and inflammation were improved by treatment with bardoxolone. No life-threatening adverse events or drug-related serious adverse events were reported. The results describe an apparent increase in kidney function following relatively short-term treatment with bardoxolone methyl, a promising new agent that warrants placebo-controlled studies to define its long-term effects on renal function. Copyright © 2011 S. Karger AG, Basel.

Prospective, randomized multicenter study of cervical arthroplasty versus anterior cervical discectomy and fusion: 5-year results with a metal-on-metal artificial disc.

PubMed

Coric, Domagoj; Guyer, Richard D; Nunley, Pierce D; Musante, David; Carmody, Cameron; Gordon, Charles; Lauryssen, Carl; Boltes, Margaret O; Ohnmeiss, Donna D

2018-03-01

OBJECTIVE Seven cervical total disc replacement (TDR) devices have received FDA approval since 2006. These devices represent a heterogeneous assortment of implants made from various biomaterials with different biomechanical properties. The majority of these devices are composed of metallic endplates with a polymer core. In this prospective, randomized multicenter study, the authors evaluate the safety and efficacy of a metal-on-metal (MoM) TDR (Kineflex|C) versus anterior cervical discectomy and fusion (ACDF) in the treatment of single-level spondylosis with radiculopathy through a long-term (5-year) follow-up. METHODS An FDA-regulated investigational device exemption (IDE) pivotal trial was conducted at 21 centers across the United States. Standard validated outcome measures including the Neck Disability Index (NDI) and visual analog scale (VAS) for assessing pain were used. Patients were randomized to undergo TDR using the Kineflex|C cervical artificial disc or anterior cervical fusion using structural allograft and an anterior plate. Patients were evaluated preoperatively and at 6 weeks and 3, 6, 12, 24, 36, 48, and 60 months after surgery. Serum ion analysis was performed on a subset of patients randomized to receive the MoM TDR. RESULTS A total of 269 patients were enrolled and randomly assigned to undergo either TDR (136 patients) or ACDF (133 patients). There were no significant differences between the TDR and ACDF groups in terms of operative time, blood loss, or length of hospital stay. In both groups, the mean NDI scores improved significantly by 6 weeks after surgery and remained significantly improved throughout the 60-month follow-up (both p < 0.01). Similarly, VAS pain scores improved significantly by 6 weeks and remained significantly improved through the 60-month follow-up (both p < 0.01). There were no significant changes in outcomes between the 24- and 60-month follow-ups in either group. Range of motion in the TDR group decreased at 3 months but was significantly greater than the preoperative mean value at the 12- and 24-month follow-ups and remained significantly improved through the 60-month period. There were no significant differences between the 2 groups in terms of reoperation/revision surgery or device-/surgery-related adverse events. The serum ion analysis revealed cobalt and chromium levels significantly lower than the levels that merit monitoring. CONCLUSIONS Cervical TDR with an MoM device is safe and efficacious at the 5-year follow-up. These results from a prospective randomized study support that Kineflex|C TDR as a viable alternative to ACDF in appropriately selected patients with cervical radiculopathy. Clinical trial registration no.: NCT00374413 (clinicaltrials.gov).

Business Students' Choice of Short-Term or Long-Term Study Abroad Opportunities

ERIC Educational Resources Information Center

Fitzsimmons, Stacey R.; Flanagan, David J.; Wang, Xiaodan

2013-01-01

Recent years have seen a proliferation of short-term study abroad opportunities. Although they are both supplementing and replacing semester-long study abroad programs, research has focused primarily on semester (long-term) programs. We draw on the theory of planned behavior (TPB) to explore factors that predict why students choose long-term and…

A multicenter randomised, 1-year comparative effectiveness, parallel-group trial protocol of a physical therapy approach compared to corticosteroid injection on pain and function related to knee osteoarthritis (PTA Trial)

PubMed

Deyle, Gail D; Gill, Norman W; Rhon, Daniel I; Allen, Chris S; Allison, Stephen C; Hando, Ben R; Petersen, Evan J; Dusenberry, Douglas I; Bellamy, Nicholas

2016-03-31

Corticosteroid injections (CSIs) are commonly used as an initial or a primary intervention for knee osteoarthritis (OA). Consistent evidence indicates CSIs offer symptom relief with conflicting reports regarding long-term efficacy. Physical therapy (PT) offers a non-invasive alternative. There is moderate evidence suggesting short-term and long-term symptom relief and functional improvement with PT interventions. Patients with knee OA are more commonly prescribed CSI than PT prior to total joint replacement. UnitedHealthcare and Military Health System data show substantially more total knee replacement patients receive preoperative CSI than PT. There are no studies comparing CSI to a PT approach in individuals with knee OA. The primary objective of this study is to compare the effectiveness of CSI to PT in individuals with knee OA at 1, 2 and 12 months. We plan to recruit 156 participants meeting established knee OA criteria. Following informed consent, participants will be randomised to receive either CSI or PT. All participants will receive instruction on recommended exercise and weight control strategies plus usual medical care. The CSI intervention consisting of 3 injections and the PT intervention consisting of 8-12 sessions will be spaced over 12 months. Measures of the dependent variables (DVs) will occur at baseline, 4 weeks, 8 weeks, 6 months and 12 months post enrolment. This pragmatic, randomised clinical trial will be a mixed-model 2×5 factorial design. The independent variables are treatment (CSI and PT) and time with five levels from baseline to 1 year. The primary DV is the Western Ontario & McMaster Universities Arthritis Index (WOMAC). We will also compare healthcare utilisation between the 2 groups. The protocol was approved by the Madigan Army Medical Center Institutional Review Board. The authors intend to publish the results in a peer-reviewed source. NCT01427153. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Weight loss, weight regain, and conversions to Roux-en-Y gastric bypass: 10-year results of laparoscopic sleeve gastrectomy.

PubMed

Felsenreich, Daniel M; Langer, Felix B; Kefurt, Ronald; Panhofer, Peter; Schermann, Martin; Beckerhinn, Philipp; Sperker, Christoph; Prager, Gerhard

2016-11-01

With promising short-term results, laparoscopic sleeve gastrectomy (SG) has become the second most frequently performed bariatric procedure worldwide. Aside from a growing number of reports covering up to 10 years of follow-up, only limited data have been published so far on long-term results. The aim of the study was to present a 10-year follow-up for SG. University hospital setting, Austria. We present the first complete 10-year follow-up of 53 consecutive patients who underwent SG before 2006. In this multicenter study, weight loss success, weight regain, and revisional surgery were analyzed beside Bariatric Analysis and Reporting Outcome System (BAROS) scores. A mean maximum percent excess weight loss of 71±25% (percent total weight loss: 28±15%) was reached at a median of 12 (range 12-120) months after SG. At 10 years, a mean percent excess weight loss of 53±25% was achieved by 32 patients, corresponding to a percent total weight loss of 26.3±13.4%. Nineteen of the 53 patients (36%) were converted to Roux-en-Y gastric bypass (n = 18) or duodenal switch (n = 1) due to significant weight regain (n = 11), reflux (n = 6), or acute revision (n = 2) at a median of 36 months. Two patients died at 3 and 101 months postoperatively, unrelated to SG. A total of 31 patients (59%) suffered from weight regain of 10 kg or more, among them 24 patients (45%) with 15 kg or more, 16 patients (30%) with 20 kg or more, and 7 patients (13%) with 25 kg or more weight regain from nadir. Mean BAROS score was 2.4±2.2 at 10 years follow-up, classifying SG as "fairly efficient." Within a long-term follow-up of 10 years or more after SG, a high incidence of both significant weight regain and intractable reflux was observed, leading to conversion, most commonly to Roux-en-Y gastric bypass. Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Blocking and reversing hepatic fibrosis in patients with chronic hepatitis B treated by traditional Chinese medicine (tablets of biejia ruangan or RGT): study protocol for a randomized controlled trial.

PubMed

Qu, Jianhui; Yu, Zujiang; Li, Qin; Chen, Yongping; Xiang, Dedong; Tan, Lin; Lei, Chunliang; Bai, Wenlin; Li, Hongyan; Shang, Qinghua; Chen, Liang; Hu, Xiaoyu; Lu, Wei; Li, Zhiqin; Chen, Da; Wang, Xiaodong; Zhang, Changjiang; Xiao, Guangming; Qi, Xun; Chen, Jing; Zhou, Li; Chen, Guofeng; Li, Yonggang; Zeng, Zhen; Rong, Guanghua; Dong, Zheng; Chen, Yan; Lou, Min; Wang, Chunping; Lu, Yinying; Zhang, Cuihong; Yang, Yongping

2014-11-10

Chronic hepatitis B (CHB) can progress to cirrhosis, hepatocellular carcinoma (HCC) and ultimately liver-related death. Although oral antiviral therapy for patients with CHB reduces the risk of such complications, once cirrhosis is established, the benefits of antiviral therapy are not robustly demonstrated. According to traditional Chinese medicine (TCM), some Chinese herbal medicines promote blood circulation and soften hard masses, and therefore they may block and reverse hepatic fibrosis. The aim of this study is to evaluate the effects of TCM tablets of the compound biejia ruangan (RGT) administered for fibrosis, and entecavir (ETV), on the development of HCC in patients with CHB or hepatitis B virus (HBV)-related compensated cirrhosis. This multicenter, centrally randomized, double-blind, placebo-controlled, parallel-group study is planned to complete within 5 years. For the study, 1,000 with CHB or HBV-related compensated cirrhosis are randomly assigned in a 1:1 ratio to a treatment group (0.5 mg ETV once daily; 2 g RGT three times daily) or a control group (0.5 mg ETV once daily; 2 g RGT dummy agent three times daily). The primary end points are the development of HCC and liver-related death. Secondary end points include disease progression and overall survival. Although antiviral therapy can achieve sustained suppression of HBV replication, thereby preventing cirrhosis, patients with CHB treated with nucleos(t)ide analogs (NUCs) retain a higher risk for HCC compared with patients with inactive disease. Although previous clinical trials with RGT have confirmed the efficacy of blocking and reversing hepatic fibrosis in patients with CHB or compensated cirrhosis, the long-term risk for HCC or disease progression in these patients treated with combination of RGT and NUCs compared with NUCs alone is unclear. Therefore, it is necessary to investigate the effects of the RGT blockade and reversal of hepatic fibrosis on the development of HCC in patients with CHB or HBV-related compensated cirrhosis in large, prospective, multicenter, double-blind, randomized, controlled trials in China. ClinicalTrials.gov Identifier: NCT01965418. Date registered: 17 October 2013.

Meniscal Repair with Concurrent Anterior Cruciate Ligament Reconstruction: Operative Success and Patient Outcomes at 6-Year Follow-up

PubMed Central

Westermann, RW; Wright, RW; Huston, LJ; Wolf, BR

2015-01-01

BACKGROUND Meniscus repairs are commonly performed concurrently with anterior cruciate ligament reconstruction (ACLR) in the acutely injured knee. No large-scale, prospective, multicenter studies have evaluated long-term success and patient-oriented outcomes after combined ACLR and meniscus repair. PURPOSE To define operative success and patient-oriented outcome scores 6 years after combined meniscus repair and ACLR. STUDY DESIGN Cohort study; Level of evidence, 3. METHODS All ipsilateral primary ACLR and meniscus repair cases from a multicenter study group between 2002 and 2004 were selected. Validated patient-oriented outcome instruments were completed at 3 time points: preoperatively, 2 years and 6 years following the index procedure. Subsequent ipsilateral knee re-operation was confirmed by operative reports to evaluate for failure of meniscal repairs. RESULTS In total, 286 patients of 1440 primary ACLR’s underwent concurrent meniscus repair (298 meniscal repairs). 235/286 (82.2%) were available for follow-up at 6 years (154 medial, 72 lateral and 9 both lateral and medial meniscal repairs). Repaired menisci most commonly involved the peripheral 1/3 of the meniscus (84%); patterns were typically longitudinal (84%) or displaced bucket-handle (10%), with mean length of 16.5 ±5.8mm. Overall, the meniscal repair failure rate was 14% (medial, 21/154; lateral, 10/72; both 2/9) at 6 years. Medial repairs failed earlier than lateral repairs (2.1 versus 3.7 years; p=0.01). Significant improvements in outcome instruments were sustained at 6-year follow-up. No differences in suture number or type were detected between repair failures and successes. Meniscal reoperation was higher in patients who underwent repair compared to those who did have an identified meniscal injury at the time of ACLR (p<0.01). CONCLUSIONS Concurrent meniscal repair with ACLR is associated with failure rates approximating 14% at 6-year follow-up. Improvements in patient-oriented outcome instruments were sustained at 6-year follow-up. Surgeons may expect good clinical outcomes 6 years after combined ACLR and meniscus repairs. PMID:25023440

Early versus late Gamma Knife radiosurgery following transsphenoidal surgery for nonfunctioning pituitary macroadenomas: a multicenter matched-cohort study.

PubMed

Pomeraniec, I Jonathan; Kano, Hideyuki; Xu, Zhiyuan; Nguyen, Brandon; Siddiqui, Zaid A; Silva, Danilo; Sharma, Mayur; Radwan, Hesham; Cohen, Jonathan A; Dallapiazza, Robert F; Iorio-Morin, Christian; Wolf, Amparo; Jane, John A; Grills, Inga S; Mathieu, David; Kondziolka, Douglas; Lee, Cheng-Chia; Wu, Chih-Chun; Cifarelli, Christopher P; Chytka, Tomas; Barnett, Gene H; Lunsford, L Dade; Sheehan, Jason P

2017-10-27

OBJECTIVE Gamma Knife radiosurgery (GKRS) is frequently used to treat residual or recurrent nonfunctioning pituitary macroadenomas. There is no consensus as to whether GKRS should be used early after surgery or if radiosurgery should be withheld until there is evidence of imaging-defined progression of tumor. Given the high incidence of adenoma progression after subtotal resection over time, the present study intended to evaluate the effect of timing of radiosurgery on outcome. METHODS This is a multicenter retrospective review of patients with nonfunctioning pituitary macroadenomas who underwent transsphenoidal surgery followed by GKRS from 1987 to 2015 at 9 institutions affiliated with the International Gamma Knife Research Foundation. Patients were matched by adenoma and radiosurgical parameters and stratified based on the interval between last resection and radiosurgery. Operative results, imaging data, and clinical outcomes were compared across groups following early (≤ 6 months after resection) or late (> 6 months after resection) radiosurgery. RESULTS After matching, 222 patients met the authors' study criteria (from an initial collection of 496 patients) and were grouped based on early (n = 111) or late (n = 111) GKRS following transsphenoidal surgery. There was a greater risk of tumor progression after GKRS (p = 0.013) and residual tumor (p = 0.038) in the late radiosurgical group over a median imaging follow-up period of 68.5 months. No significant difference in the occurrence of post-GKRS endocrinopathy was observed (p = 0.68). Thirty percent of patients without endocrinopathy in the early cohort developed new endocrinopathies during the follow-up period versus 27% in the late cohort (p = 0.84). Fourteen percent of the patients in the early group and 25% of the patients in the late group experienced the resolution of endocrine dysfunction after original presentation (p = 0.32). CONCLUSIONS In this study, early GKRS was associated with a lower risk of radiological progression of subtotally resected nonfunctioning pituitary macroadenomas compared with expectant management followed by late radiosurgery. Delaying radiosurgery may increase patient risk for long-term adenoma progression. The timing of radiosurgery does not appear to significantly affect the rate of delayed endocrinopathy.

Incidence and predictors of myocardial recovery on long-term left ventricular assist device support: Results from the United Network for Organ Sharing database.

PubMed

Pan, Stephen; Aksut, Baran; Wever-Pinzon, Omar E; Rao, Shaline D; Levin, Allison P; Garan, Arthur R; Fried, Justin A; Takeda, Koji; Hiroo, Takayama; Yuzefpolskaya, Melana; Uriel, Nir; Jorde, Ulrich P; Mancini, Donna M; Naka, Yoshifumi; Colombo, Paolo C; Topkara, Veli K

2015-12-01

Mechanical circulatory support (MCS) leads to favorable changes in the failing heart at the molecular, cellular, and structural levels. However, myocardial recovery leading to device explantation is rare. We reasoned that the multicenter United Network for Organ Sharing (UNOS) registry might provide insights into clinical predictors and outcomes of the recovery process. The MCS device data set of the UNOS registry was queried for patients with long-term continuous-flow left ventricular assist devices (CF-LVADs) that were explanted for heart transplantation or indication of recovery. Analysis was restricted to adult patients (≥18 years old) who were listed for an initial heart transplantation. Patients with CF-LVADs that were explanted because of recovery were compared with patients with CF-LVADs who underwent transplantation. We identified 594 patients with HeartMate II devices and 92 patients with HeartWare devices. Duration of support was on average 500.4 ± 325.3 days. In 34 (5.0%) patients, devices were explanted secondary to myocardial recovery. Univariate predictors of recovery in patients with long-term LVADs included younger age (40 years vs 53 years), female sex, lower body mass index (25.7 kg/m(2) vs 27.9 kg/m(2)), non-ischemic etiology (91% vs 59%), lack of implantable cardioverter defibrillator at the time of listing (44% vs 79%), and lower serum creatinine (0.97 mg/dl vs 1.28 mg/dl) (all p < 0.05). In the post-explantation period, freedom from death or transplantation was 66% at 1 year. The incidence of recovery on device support is low in the current MCS era and limited to a select cohort of predominantly young patients with non-ischemic myopathy. Given the high incidence of disease recurrence, patients should be closely followed after device explantation. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Identifying the potential long-term survivors among breast cancer patients with distant metastasis.

PubMed

Lee, E S; Jung, S Y; Kim, J Y; Kim, J J; Yoo, T K; Kim, Y G; Lee, K S; Lee, E S; Kim, E K; Min, J W; Han, W; Noh, D Y; Moon, H G

2016-05-01

We aimed to develop a prediction model to identify long-term survivors after developing distant metastasis from breast cancer. From the institution's database, we collected data of 547 patients who developed distant metastasis during their follow-ups. We developed a model that predicts the post-metastasis overall survival (PMOS) based on the clinicopathologic factors of the primary tumors and the characteristics of the distant metastasis. For validation, the survival data of 254 patients from four independent institutions were used. The median duration of the PMOS was 31.0 months. The characteristics of the initial primary tumor, such as tumor stage, hormone receptor status, and Ki-67 expression level, and the characteristics of the distant metastasis presentation including the duration of disease-free interval, the site of metastasis, and the presence of metastasis-related symptoms were independent prognostic factors determining the PMOS. The association between tumor stage and the PMOS was only seen in tumors with early relapses. The PMOS score, which was developed based on the above six factors, successfully identified patients with superior survival after metastasis. The median PMOS for patients with a PMOS score of <2 and for patients with a PMOS score of >5 were 71.0 and 12 months, respectively. The clinical significance of the PMOS score was further validated using independent multicenter datasets. We have developed a novel prediction model that can classify breast cancer patients with distant metastasis according to their survival after metastasis. Our model can be a valuable tool to identify long-term survivors who can be potential candidates for more intensive multidisciplinary approaches. Furthermore, our model can provide a more reliable survival information for both physicians and patients during their informed decision-making process. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

OK-432 sclerotherapy in head and neck lymphangiomas: long-term follow-up result.

PubMed

Yoo, Jae Chul; Ahn, Youngjin; Lim, Yune Syung; Hah, J Hun; Kwon, Tack-Kyun; Sung, Myung-Whun; Kim, Kwang Hyun

2009-01-01

Nonsurgical treatments, such as sclerotherapy have been attempted for head and neck lymphagiomas. Of the available sclerosing agents, picibanil has shown satisfactory short-term treatment results in many studies, but no study has presented long-term treatment results. Accordingly, in the present study, the authors retrospectively reviewed the long-term treatment results of picibanil sclerotherapy. Fifty-five lymphangioma patients who underwent picibanil sclerotherapy were enrolled. Data about initial and long-term response, recurrence, and excision rate were collected. Initial response rates were 83.5 percent and long-term response rates were 76.3 percent. Initial and the long-term response rate were equally good for lymphangioma.

Chronic lateral ankle instability surgical repairs: the long term prospective.

PubMed

Mabit, C; Tourné, Y; Besse, J-L; Bonnel, F; Toullec, E; Giraud, F; Proust, J; Khiami, F; Chaussard, C; Genty, C

2010-06-01

The present study sought to assess the clinical and radiological results and long-term joint impact of different techniques of lateral ankle ligament reconstruction. A multicenter retrospective review was performed on 310 lateral ankle ligament reconstructions, with a mean 13-year-follow-up (minimum FU: 5 years). Male subjects (53%) and sports trauma (78%) predominated. Mean duration of instability was 92 months; mean age at surgery was 28 years. Twenty-eight percent of cases showed subtalar joint involvement. Four classes of surgical technique were distinguished: C1, direct capsular ligamentous complex reattachment; C2, augmented repair; C3, ligamentoplasty using part of the peroneus brevis tendon and C4, ligamentoplasty using the whole peroneus brevis tendon. Clinical and functional assessment used Karlsson and Good-Jones-Livingstone scores; radiologic assessment combined centered AP and lateral views, hindfoot weight-bearing Méary views and dynamic views (manual technique, Telos or self-imposed varus). The majority of results (92%) were satisfactory. The mean Karlsson score of 90 [19-100] (i.e., 87% good and very good results) correlated with the subjective assessment, and did not evolve over time. Postoperative complications (20%), particularly when neurologic, were associated with poorer results. Control X-ray confirmed the very minor progression in degenerative changes, with improved stability; there was, however, no correlation between functional result and residual laxity on X-ray. Unstable and painful ankles showed poorer clinical results and more secondary osteoarthritis. Analysis by class of technique found poorer results in C4-type plasties and poorer control of laxity on X-ray in C1-type tension restoration. The present results confirm the interest of lateral ankle ligamentoplasty in the management of instability and protection against secondary osteoarthritis, and of precise lesion assessment (CT-scan/MRI) to adapt surgery to the ligamentary and associated lesions. Level IV. Retrospective therapeutic study. Copyright 2010 Elsevier Masson SAS. All rights reserved.

Five-year safety and performance results from the Argus II Retinal Prosthesis System clinical trial

PubMed Central

da Cruz, Lyndon; Dorn, Jessy D.; Humayun, Mark S.; Dagnelie, Gislin; Handa, James; Barale, Pierre-Olivier; Sahel, José-Alain; Stanga, Paulo E.; Hafezi, Farhad; Safran, Avinoam B.; Salzmann, Joel; Santos, Arturo; Birch, David; Spencer, Rand; Cideciyan, Artur V.; de Juan, Eugene; Duncan, Jacque L.; Eliott, Dean; Fawzi, Amani; Olmos de Koo, Lisa C.; Ho, Allen C.; Brown, Gary; Haller, Julia; Regillo, Carl; Del Priore, Lucian V.; Arditi, Aries; Greenberg, Robert J.

2016-01-01

Purpose The Argus® II Retinal Prosthesis System (Second Sight Medical Products, Inc., Sylmar, CA) was developed to restore some vision to patients blind from retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception due to end-stage RP. Design The study is a prospective, multicenter, single-arm, clinical trial. Within-patient controls included the non-implanted fellow eye and patients' native residual vision compared to their vision when using the System. Subjects There were 30 subjects in 10 centers in the U.S. and Europe. Methods The worse-seeing eye of blind patients was implanted with the Argus II System. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. Main Outcome Measures The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by three computer-based, objective tests. Secondary measures included functional vision performance on objectively-scored real-world tasks. Results Twenty-four out of 30 patients remained implanted with functioning Argus II Systems at 5 years post-implant. Only one additional serious adverse event was experienced since the 3-year time point. Patients performed significantly better with the System ON than OFF on all visual function tests and functional vision tasks. Conclusions The five-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada. PMID:27453256