Outpatient versus inpatient induction of labour for improving birth outcomes.

PubMed

Kelly, Anthony J; Alfirevic, Zarko; Dowswell, Therese

2009-04-15

More than 20% of women undergo induction of labour in some countries. The different methods used to induce labour have been the focus of previous reviews, but the setting in which induction takes place (hospital versus outpatient settings) may have implications for maternal satisfaction and costs. It is not known whether some methods of induction that are effective and safe in hospital are suitable in outpatient settings. To assess the effects on outcomes for mothers and babies of induction of labour for women managed as outpatients versus inpatients. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (December 2008). Published and unpublished randomised and quasi-randomised trials in which inpatient and outpatient methods of cervical ripening or induction of labour have been compared. Two review authors independently assessed trial reports for inclusion. Two review authors carried out data extraction and assessment of risk of bias independently. We included three trials, with a combined total of 612 women in the review; each examined a different method of induction and we were unable to pool the results from trials.1. Vaginal PGE2 (One study including 201 women). There were no differences between women managed as out- versus inpatients for most review outcomes. Women in the outpatient group were more likely to have instrumental deliveries (risk ratio (RR) 1.74; 95% confidence interval (CI) 1.03 to 2.93). The overall length of hospital stay was similar in the two groups.2. Controlled release PGE2 10mg (one study including 300 women). There was no evidence of differences between groups for most review outcomes, including success of induction. During the induction period itself, women in the outpatient group were more likely to report high levels of satisfaction with their care (satisfaction rated seven or more on a nine-point scale RR 1.42; 95% CI 1.11 to 1.81), but satisfaction scores measured postnatally were similar in the two groups.3. Foley catheter (one study including 111 women). There was no evidence of differences between groups for caesarean section rates, total induction time and the numbers of babies admitted to neonatal intensive care. The data available to evaluate the efficacy or potential hazards of outpatient induction are limited. It is, therefore, not yet possible to determine whether induction of labour is effective and safe in outpatient settings.

Optimizing Immunosuppressive Regimens Among Living-Donor Renal Transplant Recipients.

PubMed

Bakr, Mohamed Adel; Nagib, Ayman Maher; Gheith, Osama Ashry; Hamdy, Ahmed Farouk; Refaie, Ayman Fathi; Donia, Ahmed Farouk; Neamatalla, Ahmed Hassan; Eldahshan, Khaled Farouk; Denewar, Ahmed Abdelfattah; Abbas, Mohamed Hamed; Mostafa, Amany Ismail; Ghoneim, Mohamed Ahmed

2017-02-01

We review different immunosuppressant protocols used for living-donor kidney transplant recipients at our center. Many prospective randomized studies from our center have been reported between March 1976 and 2016, with more than 2700 renal transplant procedures conducted. The first study was a prospective randomized trial of azathioprine versus cyclosporine. The second study compared triple therapy (prednisolone + azathioprine + cyclosporine) versus conventional therapy (prednisolone + azathioprine). The third study was a cost-saving study, in which 100 patients received ketoconazole along with the triple regimen. Another trial demonstrated the advantages of a microemulsion form of cyclosporine. A subsequent trial compared calcineurin inhibitor minimization versus avoidance protocols. Rescue therapies were carried out to intensify immunosuppressive regimens after repeated rejection. In addition, steroid-free regimens were evaluated during both short- and long-term treatment. A recent trial reported a step-forward avoidance protocol with a calcineurin inhibitor and a steroid-free regimen, whereas another current study is the TRANSFORM one. The rationale behind antibody therapy was tho roughly evaluated among living-donor renal trans plant recipients with different agents, including basiliximab, daclizumab, antithymocyte globulin, and alemtuzumab. Earlier studies have demonstrated the efficacy of conventional regimens without induction therapy, especially in longer follow-up. The standard triple therapy has emerged with intensified immunosuppressive and lowered dose of each drug, especially cyclosporine. In minimization studies, no significant differences were encountered regarding patient and graft survival, even in the long-term. Steroid avoidance was safe and effective. Calcineurin inhibitors and steroid-free regimens have shown comparable patient and graft survival. Induction therapy has lowered the incidence and severity of acute rejection. A better 5-year graft survival and less posttransplant complications have been achieved with steroid avoidance after induction with basiliximab. Induction therapy did not affect graft and patient survival rates despite lowered incidence and severity of acute rejections.

Comparative Effectiveness of Mesalamine, Sulfasalazine, Corticosteroids, and Budesonide for the Induction of Remission in Crohn's Disease: A Bayesian Network Meta-analysis.

PubMed

Coward, Stephanie; Kuenzig, M Ellen; Hazlewood, Glen; Clement, Fiona; McBrien, Kerry; Holmes, Rebecca; Panaccione, Remo; Ghosh, Subrata; Seow, Cynthia H; Rezaie, Ali; Kaplan, Gilaad G

2017-03-01

Induction treatment of mild-to-moderate Crohn's disease is controversial. To compare the induction of remission between different doses of mesalamine, sulfasalazine, corticosteroids, and budesonide for active Crohn's disease. We identified randomized controlled trials from existing Cochrane reviews and an updated literature search in Medline, EMBASE, and CENTRAL to November 2015. We included randomized controlled trials (n = 22) in adult patients with Crohn's disease that compared budesonide, sulfasalazine, mesalamine, or corticosteroids with placebo or each other, for the induction of remission (8-17 wks). Mesalamine (above and below 2.4 g/d) and budesonide (above and below 6 mg/d) were stratified into low and high doses. Our primary outcome was remission, defined as a Crohn's Disease Activity Index score <150. A Bayesian random-effects network meta-analysis was performed on the proportion in remission. Corticosteroids (odds ratio [OR] = 3.80; 95% credible interval [CrI]: 2.48-5.66), high-dose budesonide (OR = 2.96; 95% CrI: 2.06-4.30), and high-dose mesalamine (OR = 2.29; 95% CrI: 1.58-3.33) were superior to placebo. Corticosteroids were similar to high-dose budesonide (OR = 1.21; 95% CrI: 0.84-1.76), but more effective than high-dose mesalamine (OR = 1.83; 95% CrI: 1.16-2.88). Sulfasalazine was not significantly superior to any therapy including placebo. Randomized controlled trials that use a strict definition of induction of remission and disease severity at enrollment to assess effectiveness in treating mild-to-moderate Crohn's disease are limited. Corticosteroids and high-dose budesonide were effective treatments for inducing remission in mild-to-moderate Crohn's disease. High-dose mesalamine is an option among patients preferring to avoid steroids.

Induction of labor or serial antenatal fetal monitoring in postterm pregnancy: a randomized controlled trial.

PubMed

Heimstad, Runa; Skogvoll, Eirik; Mattsson, Lars-Ake; Johansen, Ole Jakob; Eik-Nes, Sturla H; Salvesen, Kjell A

2007-03-01

To compare induction of labor at gestational age 41 weeks with expectant management in regard to neonatal morbidity. Secondary aims were to assess the effect of these managements on mode of delivery and maternal complications. Between September 2002 and July 2004, postterm women with singleton cephalic presentation and no prelabor rupture of membranes were randomly assigned to induction of labor at 289 days or antenatal fetal surveillance every third day until spontaneous labor. Main outcome measures were neonatal morbidity, operative delivery rates, and maternal complications. Five hundred eight women were randomly assigned, 254 in each group. No differences of clinical importance were observed in women in whom labor was induced compared with women who were expectantly managed with regard to the following outcomes: neonates whose 5-minute Apgar score was less than 7 (three neonates in the induction group compared with four in the monitoring group, P=.72); neonates whose umbilical cord pH was less than 7 (three compared with two, P=.69); prevalence of cesarean delivery (28 compared with 33, P=.50); or prevalence of operative vaginal delivery (32 compared with 27, P=.49). In the induction group more women had precipitate labors (33 compared with 12, P<.01; number needed to treat was 13), and the duration of second stage of labor was more often less than 15 minutes (94 compared with 56, P<.01; number needed to treat was 7). No differences were found between the induced and monitored groups regarding neonatal morbidity or mode of delivery, and the outcomes were generally good. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00385229. I.

Systematic review with network meta-analysis: the efficacy of anti-tumour necrosis factor-alpha agents for the treatment of ulcerative colitis.

PubMed

Stidham, R W; Lee, T C H; Higgins, P D R; Deshpande, A R; Sussman, D A; Singal, A G; Elmunzer, B J; Saini, S D; Vijan, S; Waljee, A K

2014-04-01

Antibodies against tumour necrosis factor-alpha (anti-TNF) are effective therapies in the treatment of ulcerative colitis (UC), but their comparative efficacy is unknown. To perform a network meta-analysis comparing the efficacy of anti-TNF agents in UC. After screening 506 studies, reviewers extracted information on seven studies. Traditional meta-analysis (TMA) was used to compare each anti-TNF agent to placebo. Bayesian network meta-analysis (NMA) was performed to compare the effects of anti-TNF agents to placebo. In addition, sample sizes for comparative efficacy trials were calculated. Compared to placebo, TMA revealed that anti-TNF agents result in a higher likelihood of induction of remission and response (RR: 2.45, 95% CI: 1.72-3.47 and RR: 1.65, 95% CI: 1.37-1.99 respectively) as well as maintenance of remission and response (RR: 2.00, 95% CI: 1.52-2.62 and RR: 1.76, 95% CI: 1.46-2.14 respectively). Individually, infliximab, adalimumab and goliumumab resulted in a higher likelihood of induction and maintenance for both remission and response. NMA found nonsignificant trends in comparisons of the individual agents. The required sample sizes for direct head-to-head trials between infliximab and adalimumab for induction and maintenance are 174 and 204 subjects respectively. This study demonstrates that, compared to placebo, infliximab, adalimumab and golimumab are all effective for the induction and maintenance of remission in ulcerative colitis. However, network meta-analysis demonstrates that no single agent is clinically superior to the others and therefore, other factors such as cost, safety, route of administration and patient preference should dictate our choice of anti-TNF agents. A randomised comparative efficacy trial between infliximab and adalimumab in UC is of practical size and should be performed. © 2014 John Wiley & Sons Ltd.

Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term.

PubMed

Kelly, Anthony J; Malik, Sidra; Smith, Lee; Kavanagh, Josephine; Thomas, Jane

2009-10-07

Prostaglandins have been used for induction of labour since the 1960s. Initial work focused on prostaglandin F2a as prostaglandin E2 was considered unsuitable for a number of reasons. With the development of alternative routes of administration, comparisons were made between various formulations of vaginal prostaglandins. To determine the effects of vaginal prostaglandins E2 and F2a for third trimester cervical ripening or induction of labour in comparison with placebo/no treatment or other vaginal prostaglandins (except misoprostol). We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May 2009) and bibliographies of relevant papers. Clinical trials comparing vaginal prostaglandins used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods. We assessed studies and extracted data independently. Sixty-three (10,441 women) have been included.Vaginal prostaglandin E2 compared with placebo or no treatment reduced the likelihood of vaginal delivery not being achieved within 24 hours (18.1% versus 98.9%, risk ratio (RR) 0.19, 95% confidence interval (CI) 0.14 to 0.25, two trials, 384 women). The risk of the cervix remaining unfavourable or unchanged was reduced (21.6% versus 40.3%, RR 0.46, 95% CI 0.35 to 0.62, five trials, 467 women); and the risk of oxytocin augmentation reduced (35.1% versus 43.8%, RR 0.83, 95% CI 0.73 to 0.94, 12 trials, 1321 women) when PGE2 was compared to placebo. There was no evidence of a difference between caesarean section rates, although the risk of uterine hyperstimulation with fetal heart rate changes was increased (4.4% versus 0.49%, RR 4.14, 95% CI 1.93 to 8.90, 14 trials, 1259 women).PGE2 tablet, gel and pessary appear to be as efficacious as each other and the use of sustained release PGE2 inserts appear to be associated with a reduction in instrumental vaginal delivery rates (9.9 % versus 19.5%, RR 0.51, 95% CI 0.35 to 0.76, NNT 10 (6.7 to 24.0), five trials, 661 women) when compared to vaginal PGE2 gel or tablet. PGE2 increases successful vaginal delivery rates in 24 hours and cervical favourability with no increase in operative delivery rates. Sustained release vaginal PGE2 is superior to vaginal PGE2 gel with respect to some outcomes studied.Further research is needed to assess the best vehicle for delivering vaginal prostaglandins and this should, where possible, include some examination of the cost-analysis.

Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term.

PubMed

Kelly, A J; Kavanagh, J; Thomas, J

2003-01-01

Prostaglandins have been used for induction of labour since the 1960s. Initial work focused on prostaglandin F2a as prostaglandin E2 was considered unsuitable for a number of reasons. With the development of alternative routes of administration, comparisons were made between various formulations of vaginal prostaglandins. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. To determine the effects of vaginal prostaglandins E2 and F2a for third trimester cervical ripening or induction of labour in comparison with placebo/no treatment or other vaginal prostaglandins (except misoprostol). The Cochrane Pregnancy and Childbirth Group trials register (May 2003) and bibliographies of relevant papers. Clinical trials comparing vaginal prostaglandins used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods. A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. In total, 101 studies were considered: 43 excluded and 57 (10,039 women) included. One study is awaiting assessment. Vaginal prostaglandin E2 compared with placebo or no treatment reduced the likelihood of vaginal delivery not being achieved within 24 hours (18% versus 99%, relative risk (RR) 0.19, 95% confidence interval (CI) 0.14 to 0.25, 2 trials, 384 women), there was no evidence of a difference between caesarean section rates although the risk of uterine hyperstimulation with fetal heart rate changes was increased (4.6% versus 0.51%, RR 4.14, 95% CI 1.93 to 8.90, 13 trials, 1203 women). Comparison of vaginal prostaglandin F2a with placebo showed similar caesarean section rates but the cervical score was more likely to be improved (15% versus 60%, RR 0.25, 95% CI 0.13 to 0.49, 5 trials, 467 women), and the risk of oxytocin augmentation reduced (53.9% versus 89.1%, RR 0.60, 95% CI 0.43 to 0.84, 11 trials, 1265 women) with the use of vaginal PGF2a. There were insufficient data to make meaningful conclusions for the comparison of vaginal PGE2 and PGF2a.PGE2 tablet, gel and pessary appear to be as efficacious as each other. Lower dose regimens, as defined in the review, appear as efficacious as higher dose regimens. The primary aim of this review was to examine the efficacy of vaginal prostaglandin E2 and F2a. This is reflected by an increase in successful vaginal delivery rates in 24 hours, no increase in operative delivery rates and significant improvements in cervical favourability within 24 to 48 hours. Further research is needed to quantify the cost-analysis of induction of labour with vaginal prostaglandins, with special attention to different methods of administration.

Recruiting Unmotivated Smokers into a Smoking Induction Trial

ERIC Educational Resources Information Center

Harris, Kari Jo; Bradley-Ewing, Andrea; Goggin, Kathy; Richter, Kimber P.; Patten, Christi; Williams, Karen; Lee, Hyoung S.; Staggs, Vincent S.; Catley, Delwyn

2016-01-01

Little is known about effective methods to recruit unmotivated smokers into cessation induction trials, the reasons unmotivated smokers agree to participate, and the impact of those reasons on study outcomes. A mixed-method approach was used to examine recruitment data from a randomized controlled cessation induction trial that enrolled 255 adult…

Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A.

PubMed

Závada, J; Sinikka Pesicková, S; Rysavá, R; Horák, P; Hrncír, Z; Lukác, J; Rovensky, J; Vítová, J; Havrda, M; Rychlík, I; Böhmova, J; Vlasáková, V; Slatinská, J; Zadrazil, J; Olejárová, M; Tegzova, D; Tesar, V

2014-01-01

Objective To evaluate the extended follow-up of the CYCLOFA-LUNE trial, a randomized prospective trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide (CPH) or cyclosporine A (CyA). Patients and methods Data for kidney function and adverse events were collected by a cross-sectional survey for 38 of 40 patients initially randomized in the CYCLOFA-LUNE trial. Results The median follow-up time was 7.7 years (range 5.0-10.3). Rates of renal impairment and end-stage renal disease, adverse events (death, cardiovascular event, tumor, premature menopause) did not differ between the CPH and CyA group, nor did mean serum creatinine, 24 h proteinuria and SLICC damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. Conclusion An immunosuppressive regimen based on CyA achieved similar clinical results to that based on CPH in the very long term.

Outcomes of Term Induction in Trial of Labor After Cesarean Delivery: Analysis of a Modern Obstetric Cohort.

PubMed

Lappen, Justin R; Hackney, David N; Bailit, Jennifer L

2015-07-01

To evaluate outcomes of induction of labor, compared with expectant management, in women attempting trial of labor after cesarean delivery (TOLAC) in a large obstetric cohort. We performed a secondary analysis of data from the Consortium on Safe Labor that included women with term (37 weeks of gestation or greater) singleton gestations and a history of one prior cesarean delivery who attempted TOLAC. Induction of labor was compared with expectant management by week of gestation from 37 to 40 weeks in both high- and low-risk cohorts. The primary outcome was failed TOLAC. Secondary outcomes included composite maternal morbidity (hysterectomy, transfusion, intensive care unit (ICU) transfer, venous thromboembolism, death), composite neonatal morbidity (5-minute Apgar score less than 5, cord pH less than 7.0, asphyxia, hypoxic ischemic encephalopathy, neonatal death), and neonatal ICU admission. Multivariate logistic regression was performed with adjustment for confounding factors. We identified 6,033 women attempting TOLAC of whom 1,626 (27.0%) underwent induction of labor and 4,407 (73.0%) did not. Compared with expectant management, induction was associated with an increased risk of failed TOLAC at 37-39 weeks of gestation but not at 40 weeks of gestation (37 weeks of gestation, 48.5% compared with 34.3%, adjusted odds ratio [OR] 1.53, 95% confidence interval [CI] 1.02-2.28]; 38 weeks of gestation, 47.0% compared with 33.0%, adjusted OR 1.74, 95% CI 1.29-2.34; 39 weeks of gestation, 45.6% compared with 29.8%, adjusted OR 2.16, 95% CI 1.76-2.67; 40 weeks of gestation, 37.9% compared with 29.4%, adjusted OR 1.21, 95% CI 0.90-1.66). Induction was associated with an increased risk of composite maternal morbidity at 39 weeks of gestation (adjusted OR 1.87, 95% CI 1.22-2.87) and neonatal ICU admission at 37 weeks of gestation (adjusted OR 2.51, 95% CI 1.62-3.90). Induction was not associated with an increased risk of neonatal morbidity. Induction of labor in women with one prior cesarean delivery, compared with expectant management, is associated with an increased risk of failed TOLAC. Apart from small increases in maternal morbidity at 39 weeks and neonatal ICU admission at 37 weeks of gestation, induction is not associated with an increased risk of severe maternal or neonatal morbidity. II.

Efficacy and Safety of Induction Therapy in Kidney Transplantation: A Network Meta-Analysis.

PubMed

Hwang, S D; Lee, J H; Lee, S W; Park, K-M; Kim, J K; Kim, M-J; Song, J H

2018-05-01

Rejection and infection can occur after kidney transplantation and are important factors in preserving graft kidney function. The use of immunosuppressant agents in transplantation is therefore important, and the question of which induction therapy should be used as an immunosuppressant is controversial. The goal of this study was to assess the comparative benefits and harms of various maintenance immunosuppressive induction agents in adults undergoing kidney transplantation by using a network meta-analysis and to generate rankings of the different immunosuppressive regimens according to their safety and efficacy. CENTRAL, MEDLINE, EMBASE, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trial registers were searched until May 2017 to identify randomized controlled trials on immunosuppression for kidney transplantation. Twenty-seven studies involving 4484 participants were eligible for analysis. Induction and maintenance treatments were administered for 12 months. There was no evidence of differences in outcomes between therapies on all-cause mortality, graft loss, cytomegalovirus, BK virus, neutropenia, thrombocytopenia, and biopsy-proven acute rejection. However, compared with intravenous basiliximab (an interleukin-2 receptor antagonist [IL-2RA]), the most effective treatments to decrease biopsy-proven acute rejection were intravenous alemtuzumab and rabbit antithymocyte globulin (rATG). The odds ratios were 0.45 (95% confidence interval [CI], 0.29-40.78) and 0.63 (95% CI, 0.42-0.95), respectively. As a side effect, rATG was accompanied by more bacterial infection than the IL-2RA (OR, 1.8 [95% CI, 1.01-2.8]). The determination of induction in kidney transplantation is important for future prognosis of the graft kidney. Alemtuzumab and rATG exhibited lower biopsy-proven acute rejection than the IL-2RA. As a side effect, rATG produced frequent bacterial infections. Copyright © 2018 Elsevier Inc. All rights reserved.

Randomized Trial of Labor Induction in Women 35 Years of Age or Older.

PubMed

Walker, Kate F; Bugg, George J; Macpherson, Marion; McCormick, Carol; Grace, Nicky; Wildsmith, Chris; Bradshaw, Lucy; Smith, Gordon C S; Thornton, James G

2016-03-03

The risk of antepartum stillbirth at term is higher among women 35 years of age or older than among younger women. Labor induction may reduce the risk of stillbirth, but it also may increase the risk of cesarean delivery, which already is common in this older age group. We conducted a randomized, controlled trial involving primigravid women who were 35 years of age or older. Women were randomly assigned to labor induction between 39 weeks 0 days and 39 weeks 6 days of gestation or to expectant management (i.e., waiting until the spontaneous onset of labor or until the development of a medical problem that mandated induction). The primary outcome was cesarean delivery. The trial was not designed or powered to assess the effects of labor induction on stillbirth. A total of 619 women underwent randomization. In an intention-to-treat analysis, there were no significant between-group differences in the percentage of women who underwent a cesarean section (98 of 304 women in the induction group [32%] and 103 of 314 women in the expectant-management group [33%]; relative risk, 0.99; 95% confidence interval [CI], 0.87 to 1.14) or in the percentage of women who had a vaginal delivery with the use of forceps or vacuum (115 of 304 women [38%] and 104 of 314 women [33%], respectively; relative risk, 1.30; 95% CI, 0.96 to 1.77). There were no maternal or infant deaths and no significant between-group differences in the women's experience of childbirth or in the frequency of adverse maternal or neonatal outcomes. Among women of advanced maternal age, induction of labor at 39 weeks of gestation, as compared with expectant management, had no significant effect on the rate of cesarean section and no adverse short-term effects on maternal or neonatal outcomes. (Funded by the Research for Patient Benefit Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN11517275.).

Efficacy and safety of native versus pegylated Escherichia coli asparaginase for treatment of adults with high-risk, Philadelphia chromosome-negative acute lymphoblastic leukemia.

PubMed

Ribera, Josep-Maria; Morgades, Mireia; Montesinos, Pau; Martino, Rodrigo; Barba, Pere; Soria, Beatriz; Bermúdez, Arancha; Moreno, María-José; González-Campos, José; Vives, Susana; Gil, Cristina; Abella, Eugenia; Guàrdia, Ramon; Martínez-Carballeira, Daniel; Martínez-Sánchez, Pilar; Amigo, María-Luz; Mercadal, Santiago; Serrano, Alfons; López-Martínez, Aurelio; Vall-Llovera, Ferran; Sánchez-Sánchez, María-José; Peñarrubia, María-Jesús; Calbacho, María; Méndez, Jose-Angel; Bergua, Juan; Cladera, Antonia; Tormo, Mar; García-Belmonte, Daniel; Feliu, Evarist; Ciudad, Juana; Orfao, Alberto

2017-11-22

Native or pegylated (PEG) asparaginase (ASP) are commonly used in treatment of acute lymphoblastic leukemia (ALL), but have been scarcely compared in the same trial in adult patients. Native vs. PEG-ASP administered according to availability in each center were prospectively evaluated in adults with high-risk ALL. Ninety-one patients received native ASP and 35 PEG-ASP in induction. No significant differences were observed in complete remission, minimal residual disease levels after induction and after consolidation, disease-free survival, and overall survival. No significant differences in grades 3-4 toxicity were observed in the induction period, although a trend for higher hepatic toxicity was observed in patients receiving PEG-ASP. In this trial the type of ASP did not influence patient response and outcome.

Labour induction at term--a randomised trial comparing Foley catheter plus titrated oral misoprostol solution, titrated oral misoprostol solution alone, and dinoprostone.

PubMed

Matonhodze, Baron B; Hofmeyr, G Justus; Levin, Jonathan

2003-05-01

To compare three methods of labour induction. Randomised controlled trial. Academic hospitals in Johannesburg, South Africa. Women with intact membranes due for induction of labour. Randomised, sealed opaque envelopes were used to allocate women to labour induction with extra-amniotic Foley catheter/titrated oral misoprostol solution (N = 174), titrated oral misoprostol solution alone (N = 176), or vaginal dinoprostone (N = 176). Misoprostol was dissolved in water and 20-40 g was given 2-hourly. These were failure to deliver vaginally within 24 hours, additional measures for induction or augmentation of labour, analgesia, and maternal and fetal complications. In the Foley catheter group, misoprostol was required in all but 1 case. Failure to deliver vaginally within 24 hours was similar for the three groups (79/174 v. 70/176 v. 70/176 respectively). Labour augmentation, caesarean section and instrumental delivery were used somewhat more frequently in the Foley/misoprostol group than in the misoprostol alone group, but these differences were not statistically significant. More analgesia was used in the Foley catheter/misoprostol group than in the misoprostol group (64/172 v. 46/175). Side-effects and neonatal complications were similar for the three groups. Use of extra-amniotic Foley catheter placement showed no measurable benefits over the use of oral misoprostol alone, or vaginal dinoprostone.

Systematic review with meta-analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis controlled trials.

PubMed

Cholapranee, A; Hazlewood, G S; Kaplan, G G; Peyrin-Biroulet, L; Ananthakrishnan, A N

2017-05-01

Mucosal healing is an important therapeutic endpoint in the management of Crohn's disease (CD) and ulcerative colitis (UC). Limited data exist regarding the comparative efficacy of various therapies in achieving this outcome. To perform a systematic review and meta-analysis of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis. We performed a systematic review and meta-analysis of randomised controlled trials (RCT) examining mucosal healing as an endpoint of immunosuppressives, anti-tumour necrosis factor α (anti-TNF) or anti-integrin monoclonal antibody therapy for moderate-to-severe CD or UC. Pooled effect sizes for induction and maintenance of mucosal healing were calculated and pairwise treatment comparisons evaluated using a Bayesian network meta-analysis. A total of 12 RCTs were included in the meta-analysis (CD - 2 induction, 4 maintenance; UC - 8 induction, 5 maintenance). Duration of follow-up was 6-12 weeks for induction and 32-54 weeks for maintenance trials. In CD, anti-TNFs were more effective than placebo for maintaining mucosal healing [28% vs. 1%, Odds ratio (OR) 19.71, 95% confidence interval (CI) 3.51-110.84]. In UC, anti-TNFs and anti-integrins were more effective than placebo for inducing (45% vs. 30%) and maintaining mucosal healing (33% vs. 18%). In network analysis, adalimumab therapy was inferior to infliximab [OR 0.45, 95% credible interval (CrI) 0.25-0.82] and combination infliximab-azathioprine (OR 0.32, 95% CrI 0.12-0.84) for inducing mucosal healing in UC. There was no statistically significant pairwise difference between vedolizumab and anti-TNF agents in UC. Anti-TNF and anti-integrin biological agents are effective in inducing mucosal healing in UC, with adalimumab being inferior to infliximab or combination therapy. Infliximab and adalimumab were similar in CD. © 2017 John Wiley & Sons Ltd.

Detection of minimal residual disease following induction immunochemotherapy predicts progression free survival in mantle cell lymphoma: final results of CALGB 59909

PubMed Central

Liu, Hongtao; Johnson, Jeffrey L.; Koval, Greg; Malnassy, Greg; Sher, Dorie; Damon, Lloyd E.; Hsi, Eric D.; Bucci, Donna Marie; Linker, Charles A.; Cheson, Bruce D.; Stock, Wendy

2012-01-01

Background In the present study, the prognostic impact of minimal residual disease during treatment on time to progression and overall survival was analyzed prospectively in patients with mantle cell lymphoma treated on the Cancer and Leukemia Group B 59909 clinical trial. Design and Methods Peripheral blood and bone marrow samples were collected during different phases of the Cancer and Leukemia Group B 59909 study for minimal residual disease analysis. Minimal residual disease status was determined by quantitative polymerase chain reaction of IgH and/or BCL-1/JH gene rearrangement. Correlation of minimal residual disease status with time to progression and overall survival was determined. In multivariable analysis, minimal residual disease, and other risk factors were correlated with time to progression. Results Thirty-nine patients had evaluable, sequential peripheral blood and bone marrow samples for minimal residual disease analysis. Using peripheral blood monitoring, 18 of 39 (46%) achieved molecular remission following induction therapy. The molecular remission rate increased from 46 to 74% after one course of intensification therapy. Twelve of 21 minimal residual disease positive patients (57%) progressed within three years of follow up compared to 4 of 18 (22%) molecular remission patients (P=0.049). Detection of minimal residual disease following induction therapy predicted disease progression with a hazard ratio of 3.7 (P=0.016). The 3-year probability of time to progression among those who were in molecular remission after induction chemotherapy was 82% compared to 48% in patients with detectable minimal residual disease. The prediction of time to progression by post-induction minimal residual disease was independent of other prognostic factors in multivariable analysis. Conclusions Detection of minimal residual disease following induction immunochemotherapy was an independent predictor of time to progression following immunochemotherapy and autologous stem cell transplantation for mantle cell lymphoma. The clinical trial was registered at ClinicalTrials.gov: NCT00020943. PMID:22102709

Letrozole versus clomiphene citrate in polycystic ovary syndrome: a meta-analysis of randomized controlled trials.

PubMed

Hu, Shifu; Yu, Qiong; Wang, Yingying; Wang, Mei; Xia, Wei; Zhu, Changhong

2018-05-01

Polycystic ovary syndrome (PCOS) is a common endocrine disturbance affecting women in the reproductive age group. The present study aimed to compare the effects of letrozole (LE) and clomiphene citrate (CC) for ovulation induction in women with PCOS. The PUBMED, Web of Science, and EMBASE databases were screened systematically for randomized controlled trials (RCTs) published from database inception to July 2017. Eleven RCTs involving 2255 patients were included, and data were independently extracted and analyzed using 95% risk ratios (RRs) and confidence intervals (CIs) based on a random- or fixed-effect model (as appropriate). Meta-analyses of nine RCTs comparing LE and CC ovulation induction, followed by timed intercourse, indicated that the former significantly increased the ovulation rate (RR = 1.18; 95% CI 1.03-1.36, P = 0.01), pregnancy rate (RR = 1.34; 95% CI 1.09-1.64, P = 0.006), and live birth rate (RR = 1.55; 95% CI 1.28-1.88, P < 0.00001). However, LE and CC did not differ significantly in terms of the multiple pregnancy and abortion rates. Furthermore, LE for ovulation induction significantly improved the pregnancy rate after IUI. LE is superior to CC for ovulation induction in patients with PCOS.

Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials

PubMed Central

Panés, Julian; Sandborn, William J; Schreiber, Stefan; Sands, Bruce E; Vermeire, Séverine; D'Haens, Geert; Panaccione, Remo; Higgins, Peter D R; Colombel, Jean-Frederic; Feagan, Brian G; Chan, Gary; Moscariello, Michele; Wang, Wenjin; Niezychowski, Wojciech; Marren, Amy; Healey, Paul; Maller, Eric

2017-01-01

Objective Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD). Design We conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks. Those achieving clinical response-100 or remission were re-randomised to maintenance treatment with placebo, tofacitinib 5 or 10 mg twice daily for 26 weeks. Primary endpoints were clinical remission at the end of the induction study, and clinical response-100 or remission at the end of the maintenance study. Results 180/280 patients randomised in the induction study were enrolled in the maintenance study. At week 8 of induction, the proportion of patients with clinical remission was 43.5% and 43.0% with 5 and 10 mg twice daily, respectively, compared with 36.7% in the placebo group (p=0.325 and 0.392 for 5 and 10 mg twice daily vs placebo). At week 26 of maintenance, the proportion of patients with clinical response-100 or remission was 55.8% with tofacitinib 10 mg twice daily compared with 39.5% with tofacitinib 5 mg twice daily and 38.1% with placebo (p=0.130 for 10 mg twice daily vs placebo). Compared with placebo, the change in C-reactive protein from baseline was statistically significant (p<0.0001) with 10 mg twice daily after both induction and maintenance treatments. Conclusions Primary efficacy endpoints were not significantly different from placebo, although there was evidence of a minor treatment effect. No new safety signals were observed for tofacitinib. Trial registration numbers NCT01393626 and NCT01393899. PMID:28209624

Economic analysis comparing induction of labor and expectant management in women with preterm prelabor rupture of membranes between 34 and 37 weeks (PPROMEXIL trial).

PubMed

Vijgen, Sylvia M C; van der Ham, David P; Bijlenga, Denise; van Beek, Johannes J; Bloemenkamp, Kitty W M; Kwee, Anneke; Groenewout, Mariët; Kars, Michael M; Kuppens, Simone; Mantel, Gerald; Molkenboer, Jan F M; Mulder, Antonius L M; Nijhuis, Jan G; Pernet, Paula J M; Porath, Martina; Woiski, Mallory D; Weinans, Martin J N; van Wijngaarden, Wim J; Wildschut, Hajo I J; Akerboom, Bertina; Sikkema, J Marko; Willekes, Christine; Mol, Ben W J; Opmeer, Brent C

2014-04-01

To compare the costs of induction of labor and expectant management in women with preterm prelabor rupture of membranes (PPROM). Economic analysis based on a randomized clinical trial. Obstetric departments of eight academic and 52 non-academic hospitals in the Netherlands. Women with PPROM near term who were not in labor 24 h after PPROM. A cost-minimization analysis was done from a health care provider perspective, using a bottom-up approach to estimate resource utilization, valued with unit-costs reflecting actual costs. Primary health outcome was the incidence of neonatal sepsis. Direct medical costs were estimated from start of randomization to hospital discharge of mother and child. Induction of labor did not significantly reduce the probability of neonatal sepsis [2.6% vs. 4.1%, relative risk 0.64 (95% confidence interval 0.25-1.6)]. Mean costs per woman were €8094 for induction and €7340 for expectant management (difference €754; 95% confidence interval -335 to 1802). This difference predominantly originated in the postpartum period, where the mean costs were €5669 for induction vs. €4801 for expectant management. Delivery costs were higher in women allocated to induction than in women allocated to expectant management (€1777 vs. €1153 per woman). Antepartum costs in the expectant management group were higher because of longer antepartum maternal stays in hospital. In women with pregnancies complicated by PPROM near term, induction of labor does not reduce neonatal sepsis, whereas costs associated with this strategy are probably higher. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Luteal phase clomiphene citrate for ovulation induction in women with polycystic ovary syndrome: a systematic review and meta-analysis.

PubMed

Ding, Nan; Chang, Jianbo; Jian, Qiliang; Liang, Xuefei; Liang, Zhongzhen; Wang, Fang

2016-11-01

To assess the efficacy of late luteal phase clomiphene citrate (CC) administration relative to early follicular phase CC for ovulation induction for polycystic ovary syndrome (PCOS). Review. A complete electronic databases including PubMed, Embase, The Cochrane Library, Web of Science, and CBM were searched for relevant randomized controlled trials (RCTs). The search was not restricted by language and publication time. Two reviewers selected trials and assessed trial quality by the Cochrane Handbook 5.1.0 independently. Four eligible RCT studies involving 708 women (934 cycles) were included. The results of the Meta-analysis: Late luteal phase group was associated with a number of higher total follicles (MD 1.82; 95% CI 0.86-2.78, p < 0.00001) and significant higher endometrial thickness on the day of HCG (MD 0.88; 95% CI 0.78-0.99, p < 0.00001) compared with early follicular group. There were no significant differences in the rate of pregnancy (RR 1.29; 95% CI 0.83-2.01, p = 0.26), ovulation rate (RR 0.99; 95% CI 0.86-1.14, p = 0.87), and abortion rate (RR 1.12; 95% CI 0.38 to 3.29, p = 0.84) between the two groups. It appeared that late luteal phase CC for ovulation induction might be an effective method for ovulation induction in women with PCOS compared to conventional CC administration. Further intensive randomized-controlled studies should be warranted to define the efficacy of CC used in late luteal phase.

Discontinuing Oxytocin Infusion in the Active Phase of Labor: A Systematic Review and Meta-analysis.

PubMed

Saccone, Gabriele; Ciardulli, Andrea; Baxter, Jason K; Quiñones, Joanne N; Diven, Liany C; Pinar, Bor; Maruotti, Giuseppe Maria; Martinelli, Pasquale; Berghella, Vincenzo

2017-11-01

To evaluate the benefits and harms of discontinuation of oxytocin after the active phase of labor is reached. Electronic databases (ie, MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, ScienceDirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) were searched from their inception until April 2017. We included all randomized controlled trials comparing discontinuation (ie, intervention group) and continuation (ie, control group) of oxytocin infusion after the active phase of labor is reached, either after induction or augmentation of labor. Discontinuation of oxytocin infusion was defined as discontinuing oxytocin infusion when the active phase of labor was achieved. Continuation of oxytocin infusion was defined as continuing oxytocin infusion until delivery. Only trials in singleton gestations with vertex presentation at term were included. The primary outcome was the incidence of cesarean delivery. Nine randomized controlled trials, including 1,538 singleton gestations, were identified as relevant and included in the meta-analysis. All nine trials included only women undergoing induction of labor. In the discontinuation group, if arrest of labor occurred, usually defined as no cervical dilation in 2 hours or inadequate uterine contractions for 2 hours or more, oxytocin infusion was restarted. Women in the control group had oxytocin continued until delivery usually at the same dose used at the time the active phase was reached. Women who were randomized to have discontinuation of oxytocin infusion after the active phase of labor was reached had a significantly lower risk of cesarean delivery (9.3% compared with 14.7%; relative risk 0.64, 95% CI 0.48-0.87) and of uterine tachysystole (6.2% compared with 13.1%; relative risk 0.53, 95% CI 0.33-0.84) compared with those who were randomized to have continuation of oxytocin infusion until delivery. Discontinuation of oxytocin infusion was associated with an increase in the duration of the active phase of labor (mean difference 27.65 minutes, 95% CI 3.94-51.36). In singleton gestations with cephalic presentation at term undergoing induction, discontinuation of oxytocin infusion after the active phase of labor at approximately 5 cm is reached reduces the risk of cesarean delivery and of uterine tachysystole compared with continuous oxytocin infusion. Given this evidence, discontinuation of oxytocin infusion once the active stage of labor is established in women being induced should be considered as an alternative management plan.

Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial.

PubMed

Gardin, Claude; Turlure, Pascal; Fagot, Thierry; Thomas, Xavier; Terre, Christine; Contentin, Nathalie; Raffoux, Emmanuel; de Botton, Stephane; Pautas, Cecile; Reman, Oumedaly; Bourhis, Jean-Henri; Fenaux, Pierre; Castaigne, Sylvie; Michallet, Mauricette; Preudhomme, Claude; de Revel, Thierry; Bordessoule, Dominique; Dombret, Herve

2007-06-15

In elderly patients with acute myeloid leukemia (AML) treated intensively, no best postremission strategy has emerged yet. This clinical trial enrolled 416 patients with AML aged 65 years or older who were considered eligible for standard intensive chemotherapy, with a first randomization comparing idarubicin with daunorubicin for all treatment sequences. After induction, an ambulatory postremission strategy based on 6 consolidation cycles administered monthly in outpatients was randomly compared with an intensive strategy with a single intensive consolidation course similar to induction. Complete remission (CR) rate was 57% with 10% induction deaths, and estimated overall survival was 27% at 2 years and 12% at 4 years, without notable differences between anthracycline arms. Among the 236 patients who reached CR, 164 (69%) were randomized for the postremission comparison. In these patients, the multivariate odds ratio in favor of the ambulatory arm was 1.51 for disease-free survival (P.05) and 1.59 for overall survival from CR (P.04). Despite repeated courses of chemotherapy associated with a longer time under treatment, the ambulatory arm was associated with significantly shorter rehospitalization duration and lower red blood cell unit and platelet transfusion requirements than observed in the intensive arm. In conclusion, more prolonged ambulatory treatment should be preferred to intensive chemotherapy as postremission therapy in elderly patients with AML reaching CR after standard intensive remission induction.

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.

Patients with Crohn's Disease Are More Likely to Remain on Biologics than Immunomodulators: A Meta-Analysis of Treatment Durability.

PubMed

Shah, Eric D; Siegel, Corey A; Chong, Kelly; Melmed, Gil Y

2015-08-01

The comparative effectiveness of treatments for moderate-to-severe Crohn's disease can be influenced by the likelihood of remaining on medication. We aimed to clarify this treatment durability by assessing subject discontinuations from clinical trials in the context of treatment efficacy. We conducted a literature search for double-blind RCT of Crohn's disease therapies recommended in international guidelines or with recent positive phase III trial results. Durability was defined through study discontinuation due to adverse events or disease exacerbation represented by number needed to discontinue (NND). Efficacy was defined as clinical remission represented by number needed to treat (NNT). The primary endpoint was NND/NNT, with a higher value representing more durable and effective treatment. Treatment with azathioprine/6-mercaptopurine (AZA/6MP) was associated with more discontinuations than with clinical remission (NND/NNT = 0.92) in maintenance trials. For induction, methotrexate was associated with similar rates of discontinuations and remission (NND/NNT = 1.4). In one maintenance trial, the remission rate for methotrexate was greater than the study discontinuation rate (NND/NNT = 23.3). In contrast, anti-TNF trials revealed greater durability among induction (no excess discontinuation) and maintenance (NND/NNT = 37.9) trials. Trials of anti-trafficking agents had fewer discontinuations in the drug treatment arms than placebo resulting in most favorable NND/NNT ratios. For patients with Crohn's disease, biologic therapies had higher durability than immunomodulators for induction and maintenance therapy. We also report the results of a novel NND/NNT ratio that should be validated in a prospective head-to-head placebo-controlled trial.

Evaluating Study Withdrawal Among Biologics and Immunomodulators in Treating Ulcerative Colitis: A Meta-analysis of Controlled Clinical Trials.

PubMed

Shah, Eric D; Siegel, Corey A; Chong, Kelly; Melmed, Gil Y

2016-04-01

We conducted a systematic review and meta-analysis to evaluate the efficacy and adverse event (AE)-associated tolerability of treatment with immunomodulators and biologics in ulcerative colitis clinical trials. We performed a literature search of PubMed and the Cochrane databases to identify randomized placebo-controlled trials of immunomodulators and biologics. Tolerability was defined through study withdrawal due to AEs and efficacy through clinical response in induction trials and clinical remission in maintenance trials. We performed meta-analyses using a random-effects model to determine relative risks (RRs) of efficacy and study withdrawal. Number needed to treat (NNT) and number needed to stop (NNS) were determined. The ratio of NNS/NNT was calculated, with a higher ratio indicating a greater number of patients in remission for every AE study discontinuation. We examined 13 single-agent trials representing biologics (infliximab, adalimumab, golimumab, and vedolizumab) and immunomodulators (tacrolimus and azathioprine). Induction therapy did not result in excess study withdrawal with immunomodulators (RR = 0.9, 95% CI 0.1-12.0) or biologics (RR = 0.7, 95% CI 0.3-1.8), therefore the NNS/NNT ratio could not be assessed because of high tolerability. Maintenance immunomodulator therapy resulted in a NNS of 14 (RR = 2.8, 95% CI 0.7-10.5) and NNS/NNT ratio of 2.4 in 2 trials. Biologics did not result in excess study withdrawal in maintenance (RR = 0.7, 95% CI 0.3-1.7) or combined induction-and-maintenance (RR = 0.6, 95% CI 0.4-1.0) trials. Biologics were not associated with a higher RR of study withdrawal due to AE than placebo. There were insufficient data to compare these results with immunomodulators.

A cost analysis of inpatient compared with outpatient prostaglandin E2 cervical priming for induction of labour: results from the OPRA trial.

PubMed

Adelson, Pamela L; Wedlock, Garry R; Wilkinson, Chris S; Howard, Kirsten; Bryce, Robert L; Turnbull, Deborah A

2013-09-01

To compare the costs of inpatient (usual care) with outpatient (intervention) care for cervical priming for induction of labour in women with healthy, low-risk pregnancies who are being induced for prolonged pregnancies or for social reasons. Data from a randomised controlled trial at two hospitals in South Australia were matched with hospital financial data. A cost analysis comparing women randomised to inpatient care with those randomised to outpatient care was performed, with an additional analysis focusing on those who received the intervention. Overall, 48% of women randomised into the trial did not receive the intervention. Women randomised to outpatient care had an overall cost saving of $319 per woman (95% CI -$104 to $742) as compared with women randomised to usual care. When restricted to women who actually received the intervention, in-hospital cost savings of $433 (95% CI -$282 to $1148) were demonstrated in the outpatient group. However, these savings were partially offset by the cost of an outpatient priming clinic, reducing the overall cost savings to $156 per woman. Overall cost savings were not statistically significant in women who were randomised to or received the intervention. However, the trend in cost savings favoured outpatient priming.

The relationship between mood state, interpersonal attitudes and psychological distress in stroke patients.

PubMed

Turner, Margaret A; Andrewes, David G

2010-03-01

This study investigated whether increasing positive mood improved interpersonal attitudes and relieved depression in depressed stroke patients despite levels of cognitive and emotional dysfunction. Depressed stroke (n = 30) and rheumatic/orthopaedic controls (n = 30) were compared on the effect of verbal and nonverbal positive and neutral mood induction on mood state, interpersonal attitudes, psychological distress and related cognitive and emotional processing deficits. Compared with the neutral mood induction condition, the positive mood induction significantly improved mood state, interpersonal attitudes and psychological distress, irrespective of cognitive and emotional processing deficits. The nonverbal material was effective for all patients but was more marked for the left hemisphere stroke group. There was no obvious influence of humour appreciation despite reduced understanding in the right hemisphere stroke group. Although the effect is likely to be short-lived, these results support the trial of positive mood induction within therapy programmes to relieve depression.

Mechanical and Pharmacologic Methods of Labor Induction: A Randomized Controlled Trial

PubMed Central

Levine, Lisa D.; Downes, Katheryne L.; Elovitz, Michal A.; Parry, Samuel; Sammel, Mary D.; Srinivas, Sindhu K

2016-01-01

Objective To evaluate the effectiveness of four commonly used induction methods. Methods This randomized trial compared four induction methods: Misoprostol alone, Foley alone, Misoprostol–cervical Foley concurrently, and Foley–oxytocin concurrently,. Women undergoing labor induction with full term (≥37 weeks), singleton, vertex presenting gestations, with no contraindication to vaginal delivery, intact membranes, Bishop score ≤6, and cervical dilation ≤2cm were included. Women were enrolled only once during the study period. Our primary outcome was time to delivery. Neither patients nor providers were blinded to assigned treatment group since examinations are required for placement of all methods; however, research personnel were blinded during data abstraction. A sample size of 123 per group (N=492) was planned to compare the four groups pairwise (P≤.008), with a 4-hour reduction in delivery time considered clinically meaningful. Results From May 2013 through June 2015, 997 women were screened and 491 were randomized and analyzed. Demographic and clinical characteristics were similar among the four treatment groups. When comparing all induction method groups, combination methods achieved a faster median time to delivery than single-agent methods, (misoprostol–Foley: 13.1 hours, Foley–oxytocin: 14.5 hours, misoprostol: 17.6 hours, Foley: 17.7 hours, p<0.001). When censored for cesarean and adjusting for parity, women who received misoprostol–Foley delivered almost twice as likely to deliver before women who received misoprostol alone (hazard ratio (HR, 95% CI) 1.92 [1.42–2.59]) or Foley alone (HR, 95%CI: 1.87 [1.39–2.52]), whereas Foley–oxytocin was not statistically different from single-agent methods. Conclusion After censoring for cesarean and adjusting for parity, misoprostol–cervical Foley resulted in twice the chance of delivering before either single-agent method. PMID:27824758

Relative reward effects on operant behavior: Incentive contrast, induction and variety effects

PubMed Central

Webber, E.S.; Chambers, N. E.; Kostek, J.A.; Mankin, D.E; Cromwell, H.C.

2015-01-01

Comparing different rewards automatically produces dynamic relative outcome effects on behavior. Each new outcome exposure is to an updated version evaluated relative to alternatives. Relative reward effects include incentive contrast, positive induction and variety effects. The present study utilized a novel behavioral design to examine relative reward effects on a chain of operant behavior using auditory cues. Incentive contrast is the most often examined effect and focuses on increases or decreases in behavioral performance after value upshifts (positive) or downshifts (negative) relative to another outcome. We examined the impact of comparing two reward outcomes in a repeated measures design with three sessions: a single outcome and a mixed outcome and a final single outcome session. Relative reward effects should be apparent when comparing trials for the identical outcome between the single and mixed session types. An auditory cue triggered a series of operant responses (nosepoke-leverpress-food retrieval), and we measured possible contrast effects for different reward magnitude combinations. We found positive contrast for trials with the greatest magnitude differential but positive induction or variety effects in other combinations. This behavioral task could be useful for analyzing environmental or neurobiological factors involved in reward comparisons, decision-making and choice during instrumental, goal-directed action. PMID:25979604

Effect of Etomidate Versus Combination of Propofol-Ketamine and Thiopental-Ketamine on Hemodynamic Response to Laryngoscopy and Intubation: A Randomized Double Blind Clinical Trial.

PubMed

Gholipour Baradari, Afshin; Firouzian, Abolfazl; Zamani Kiasari, Alieh; Aarabi, Mohsen; Emadi, Seyed Abdollah; Davanlou, Ali; Motamed, Nima; Yousefi Abdolmaleki, Ensieh

2016-02-01

Laryngoscopy and intubation frequently used for airway management during general anesthesia, is frequently associated with undesirable hemodynamic disturbances. The aim of this study was to compare the effects of etomidate, combination of propofol-ketamine and thiopental-ketamine as induction agents on hemodynamic response to laryngoscopy and intubation. In a double blind, randomized clinical trial a total of 120 adult patients of both sexes, aged 18 - 45 years, scheduled for elective surgery under general anesthesia were randomly assigned into three equally sized groups. Patients in group A received etomidate (0.3 mg/kg) plus normal saline as placebo. Patients in group B and C received propofol (1.5 mg/kg) plus ketamine (0.5 mg/kg) and thiopental sodium (3 mg/kg) plus ketamine (0.5 mg/kg), respectively for anesthesia induction. Before laryngoscopy and tracheal intubation, immediately after, and also one and three minutes after the procedures, hemodynamic values (SBP, DBP, MAP and HR) were measured. A repeated measurement ANOVA showed significant changes in mean SBP and DBP between the time points (P < 0.05). In addition, the main effect of MAP and HR were statistically significant during the course of study (P < 0.05). Furthermore, after induction of anesthesia, the three study groups had significantly different SBP, DBP and MAP changes overtime (P < 0.05). However, HR changes over time were not statistically significant (P > 0.05). Combination of propofol-ketamine had superior hemodynamic stability compared to other induction agents. Combination of propofol-ketamine may be recommended as an effective and safe induction agent for attenuating hemodynamic responses to laryngoscopy and intubation with better hemodynamic stability. Although, further well-designed randomized clinical trials to confirm the safety and efficacy of this combination, especially in critically ill patients or patients with cardiovascular disease, are warranted.

Systematic review with meta-analysis: Comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn’s disease and ulcerative colitis controlled trials

PubMed Central

Cholapranee, Aurada; Hazlewood, Glen S; Kaplan, Gilaad G.; Peyrin-Biroulet, Laurent; Ananthakrishnan, Ashwin N

2017-01-01

Background Mucosal healing is an important therapeutic endpoint in the management of Crohn’s disease (CD) and ulcerative colitis (UC). Limited data exists regarding the comparative efficacy of various therapies in achieving this outcome. Methods We performed a systematic review and meta-analysis of randomized controlled trials (RCT) examining mucosal healing as an endpoint of immunosuppressives, anti-tumor necrosis factor α (anti-TNF) or anti-integrin monoclonal antibody therapy for moderate-to-severe CD or UC. Pooled effect sizes for induction and maintenance of mucosal healing were calculated and pair-wise treatment comparisons evaluated using a Bayesian network meta-analysis. Results A total of 12 RCTs were included in the meta-analysis (CD – 2 induction, 4 maintenance; UC – 8 induction, 5 maintenance). Duration of follow-up was 6–12 weeks for induction and 32–54 weeks for maintenance trials. In CD, anti-TNFs were more effective than placebo for maintaining mucosal healing (28% vs. 1%, Odds ratio (OR) 19.71, 95% confidence interval (CI) 3.51 – 110.84). In UC, anti-TNFs and anti-integrins were more effective than placebo for inducing (45% vs. 30%) and maintaining mucosal healing (33% vs. 18%). In network analysis, adalimumab therapy was inferior to infliximab (OR 0.45, 95% credible interval (CrI) 0.25 – 0.82) and combination infliximab-azathioprine (OR 0.32, 95% CrI 0.12 – 0.84) for inducing mucosal healing in UC. There was no statistically significant pairwise difference between vedolizumab and anti-TNF agents in UC. Conclusion Anti-TNF and anti-integrin biologic agents are effective in inducing mucosal healing in UC with adalimumab being inferior to infliximab or combination therapy. Infliximab and adalimumab were similar in CD. PMID:28326566

Monitoring minimal residual disease in children with high-risk relapses of acute lymphoblastic leukemia: prognostic relevance of early and late assessment.

PubMed

Eckert, C; Hagedorn, N; Sramkova, L; Mann, G; Panzer-Grümayer, R; Peters, C; Bourquin, J-P; Klingebiel, T; Borkhardt, A; Cario, G; Alten, J; Escherich, G; Astrahantseff, K; Seeger, K; Henze, G; von Stackelberg, A

2015-08-01

The prognosis for children with high-risk relapsed acute lymphoblastic leukemia (ALL) is poor. Here, we assessed the prognostic importance of response during induction and consolidation treatment prior to hematopoietic stem cell transplantation (HSCT) aiming to evaluate the best time to assess minimal residual disease (MRD) for intervention strategies and in future trials in high-risk ALL relapse patients. Included patients (n=125) were treated uniformly according to the ALL-REZ BFM (Berlin-Frankfurt-Münster) 2002 relapse trial (median follow-up time=4.8 years). Patients with MRD ⩾10(-3) after induction treatment (76/119, 64%) or immediately preceding HSCT (19/71, 27%) had a significantly worse probability of disease-free survival 10 years after relapse treatment begin, with 26% (±6%) or 23% (±7%), respectively, compared with 58% (±8%) or 48% (±7%) for patients with MRD <10(-3). Conventional intensive consolidation treatment reduced MRD to <10(-3) before HSCT in 63% of patients, whereas MRD remained high or increased in the rest of this patient group. Our data support that MRD after induction treatment can be used to quantify the activity of different induction treatment strategies in phase II trials. MRD persistence at ⩾10(-3) before HSCT reflects a disease highly resistant to conventional intensive chemotherapy and requiring prospective controlled investigation of new treatment strategies and drugs.

Nitric oxide donors for cervical ripening and induction of labour.

PubMed

Ghosh, Arpita; Lattey, Katherine R; Kelly, Anthony J

2016-12-05

Sometimes it is necessary to bring on labour artificially because of safety concerns for the mother or baby. This review is one of a series of reviews of methods of labour induction using a standardised protocol. To determine the effects of NO donors (isosorbide mononitrate (ISMN), isosorbide dinitrate (ISDN), nitroglycerin and sodium nitroprusside) for third trimester cervical ripening or induction of labour, in comparison with placebo or no treatment or other treatments from a predefined hierarchy. We searched Cochrane Pregnancy and Childbirth's Trials Register (15 August 2016) and the reference lists of trial reports. Clinical trials comparing NO donors for cervical ripening or labour induction with other methods listed above it on a predefined list of methods of labour induction. Interventions include NO donors (isosorbide mononitrate, isosorbide dinitrate, nitroglycerin and sodium nitroprusside) compared with other methods listed above it on a predefined list of methods of labour induction. This review is part of a series of reviews focusing on methods of induction of labour, based on a generic protocol. Three review authors independently assessed trials for inclusion, assessed risk of bias and extracted data. In this update, the quality of the evidence for the main comparison was assessed using the GRADE approach. We included 23 trials (including a total of 4777 women). Included studies compared NO donors with placebo, vaginal prostaglandin E2 (PGE2), intracervical PGE2, vaginal misoprostol and intracervical Foley catheter. The majority of the included studies were assessed as being at low risk of bias. Nitric oxide versus placebo There was no evidence of a difference for any of the primary outcomes analysed: vaginal delivery not achieved in 24 hours (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.83 to 1.15; one trial, 238 women; low-quality evidence), uterine hyperstimulation with fetal heart rate (FHR) changes (RR 0.09, 95% CI 0.01 to 1.62; two trials, 300 women; low-quality evidence), caesarean section (RR 0.99, 95% CI 0.88 to 1.11; nine trials, 2624 women; moderate-quality evidence) or serious neonatal morbidity/perinatal death (average RR 1.61, 95% CI 0.08 to 33.26; two trials, 1712 women; low-quality evidence). There were no instances of serious maternal morbidity or death (one study reported this outcome).There was a reduction in an unfavourable cervix at 12 to 24 hours in women treated with NO donors (average RR 0.78, 95% CI 0.67 to 0.90; four trials, 762 women), and this difference was observed in both subgroups of standard release and slow release formulation. Women who received NO donors were less likely to experience uterine hyperstimulation without FHR rate changes (RR 0.05, 95% CI 0.00 to 0.80; one trial, 200 women), and more likely to experience side effects, including nausea, headache and vomiting. Nitric oxide donors versus vaginal prostaglandins There was no evidence of any difference between groups for uterine hyperstimulation with FHR changes or caesarean section (RR 0.97, 95% CI 0.78 to 1.21; three trials, 571 women). Serious neonatal morbidity and serious maternal morbidity were not reported. There were fewer women in the NO donor group who did not achieve a vaginal delivery within 24 hours (RR 0.63, 95% CI 0.47 to 0.86; one trial, 400 primiparae women). Nitric oxide donors versus intracervical prostaglandins One study reported a reduction in the number of women who had not achieved a vaginal delivery within 24 hours with NO donors (RR 0.63, 95% CI 0.47 to 0.86; one trial, 400 women). This result should be interpreted with caution as the information was extracted from an abstract only and a full report of the study is awaited. No differences were observed between groups for uterine hyperstimulation with FHR changes (RR 0.33, 95% CI 0.01 to 7.74; one trial, 42 women) or serious neonatal morbidity/perinatal death (RR 0.33, 95% CI 0.01 to 7.74; one trial, 42 women). Fewer women in the NO donor group underwent a caesarean section in comparison to women who received intracervical prostaglandins (RR 0.63, 95% CI 0.44 to 0.90; two trials, 442 women). No study reported on the outcome serious maternal morbidity or death. Nitric oxide donors versus vaginal misoprostol There was a reduction in the rate of uterine hyperstimulation with FHR changes with NO donors (RR 0.07, 95% CI 0.01 to 0.37; three trials, 281 women). There were no differences in caesarean section rates (RR 1.00, 95% CI 0.82 to 1.21; 761 women; six trials) and no cases of serious neonatal morbidity/perinatal death were reported. One study found that women in the NO donor group were more likely to not deliver within 24 hours (RR 5.33, 95% CI 1.62 to 17.55; one trial, 150 women). Serious maternal morbidity or death was not reported.In terms of secondary outcomes, there was an increase in cervix unchanged/unfavourable with NO (RR 3.43, 95% CI 2.07 to 5.66; two trials, 151 women) and an increase in the need for oxytocin augmentation with NO induction (RR 2.67, 95% CI 1.31 to 5.45; 7 trials; 767 women), although there was evidence of significant heterogeneity which could not be fully explained. Uterine hyperstimulation without FHR was lower in the NO group, as was meconium-stained liquor, Apgar score less than seven at five minutes and analgesia requirements. Nitric oxide donors versus intracervical catheter There was no evidence on any difference between the effects of NO and the use of a Foley catheter for induction of labour for caesarean section (RR 1.00, 95% CI 0.39 to 2.59; one trial, 80 women). No other primary outcomes were reported. One study of 75 participants did not contribute any data to the review.For all comparisons, women who received NO donors were more likely to experience side effects such as headache, nausea or vomiting. Available data suggests that NO donors can be a useful tool in the process of induction of labour causing the cervix to be more favourable in comparison to placebo. However, additional data are needed to assess the true impact of NO donors on all important labour process and delivery outcomes.

The use of altrenogest to avoid hyperestrogenism after eCG-hCG ovulation induction in southern tigrina (Leopardus guttulus).

PubMed

Micheletti, Tatiane; Brown, Janine L; Walker, Susan L; Cubas, Zalmir S; Furtado, Priscila V; Putman, Sarah B; de Moraes, Wanderlei; de Oliveira, Marcos J; de Oliveira, Claudio A; Moreira, Nei

2015-09-01

The goal of this study was to optimize an ovulation induction protocol for use with artificial insemination in the southern tigrina (Leopardus guttulus). The specific aims were to report the efficacy of using altrenogest, an oral progestin (Regumate, MSD Animal Health, Merck Animal Health), to suppress ovarian activity and prevent follicular hyperstimulation and hyperestrogenism after the administration of exogenous eCG and hCG. To monitor ovarian responses, fecal estrogen and progestogen metabolites were quantified by enzyme immunoassay in females before and after intramuscular administration of 200-IU eCG and 150-IU hCG in two trials, 4 months apart. During the first trial, there was no use of altrenogest, only the eCG-hCG ovulation induction protocol. In the second trial, the ovulation induction protocol was preceded by the administration of oral altrenogest for 14 days (minimum of 0.192 mg per kg per day). Altrenogest administration resulted in a suppression of follicular activity in three out of six females before eCG-hCG administration on the basis of lower mean estrogen concentrations (P < 0.05). It also resulted in four out of six females presenting lower fecal estrogen metabolite concentrations (P < 0.05) after ovulation induction, and two out of six individuals showed a reduction (P < 0.05) in postovulatory fecal progestogen metabolite concentrations, all when compared to the same female's cycles without the progestin. Fecal estrogen metabolite concentrations were closer to baseline in 50% of these individuals after altrenogest and eCG-hCG treatments when compared to basal concentrations before gonadotropins without the use of altrenogest. This study reported that use of altrenogest in southern tigrina can suppress ovarian activity and avoid hyperestrogenism after administration of eCG and hCG treatment. However, not all females responded uniformly, so more studies are needed to increase the efficacy of ovulation induction for use with artificial insemination in this species. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of mesalazine and balsalazide in induction and maintenance of remission in patients with ulcerative colitis: a meta-analysis.

PubMed

Rahimi, Roja; Nikfar, Shekoufeh; Rezaie, Ali; Abdollahi, Mohammad

2009-04-01

5-Aminosalicylates are the standard treatment for induction and maintenance of remission in mild-to-moderate ulcerative colitis. In recent years, the 5-aminosalicylic acid-containing pro-drug balsalazide has been the focus of attention. To compare the efficacy and tolerance of balsalazide and mesalazine by meta-analysis. Pubmed, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for studies comparing the efficacy and/or tolerance of balsalazide with mesalazine in the management of UC. The search terms were: "mesalazine" or "5-aminosalicylic acid" and "balsalazide" and "ulcerative colitis." Data were collected from 1966 to 2007 (up to February). There was no language restriction. "Symptomatic remission," "complete remission," "relapse rate," "total adverse events," and "withdrawals because of adverse events" were the key outcomes of interest. Six randomized placebo-controlled clinical trials met our criteria and were included in the meta-analysis. In these "symptomatic remission," "complete remission," "relapse rate," "total adverse events," and "withdrawals because of adverse events" were evaluated in three, three, two, five, and six of the trials, respectively. They included 653 patients consisting of 55.4% men and 44.6% women randomized to receive either balsalazide or mesalazine. Pooling of three trials for symptomatic remission yielded a significant relative risk (RR) of 1.23 (95% confidence interval of 1.03-1.47, P = 0.02). The summary RR for complete remission in three trials was 1.3 (95% CI of 1.002-1.68, P = 0.048). Pooling of two trials for the outcome of relapse yielded a non-significant RR of 0.77 (95% CI of 0.56-1.07, P = 0.12). Pooling five studies from which data for any adverse events were extracted, yielded a non-significant RR of 0.87 (95% CI of 0.75-1.001, P = 0.53). The summary RR for withdrawals because of adverse events in six trials was 0.69, a non-significant RR (95% CI of 0.37-1.29, P = 0.24). Balsalazide is more effective than mesalazine in induction of remission, but balsalazide has no benefit compared with mesalazine in preventing relapse in the population selected. The number of patients with any adverse events and withdrawals because of severe adverse events is similar for mesalazine and balsalazide.

A randomized trial of misoprostol and oxytocin for induction of labor: safety and efficacy.

PubMed

Kramer, R L; Gilson, G J; Morrison, D S; Martin, D; Gonzales, J L; Qualls, C R

1997-03-01

To compare the safety and efficacy of misoprostol and oxytocin for induction of labor. One hundred thirty women requiring induction of labor were randomized to receive either intravenous oxytocin or 100 micrograms misoprostol, administered intravaginally every 4 hours until labor was established. Compared with women receiving oxytocin, a greater percentage of women in the misoprostol group had Bishop scores of 3 or less (58 versus 38%, P < .05). Nonetheless, the median induction-to-delivery interval was significantly shorter (585 versus 885 minutes, P < .001) in the misoprostol group. Women in the misoprostol group were more likely to deliver vaginally within 24 hours of the start of induction (77 versus 55%, P < .002). Epidural analgesia was used more frequently in women receiving oxytocin than in those receiving misoprostol (73 versus 50%, P = .025). The total percentage of cesarean deliveries was not significantly different, although the percentage of cesarean deliveries for dystocia was lower in the misoprostol group (8 versus 21%, P = .02). Uterine tachysystole was significantly more common (70 versus 11%, P < .001) and hospital charges significantly less with misoprostol. Compared with oxytocin for labor induction, misoprostol results in a shorter induction-to-delivery interval, a reduction in the rate of cesarean delivery for dystocia, and a decreased use of epidural analgesia. Uterine tachysystole is significantly more common with the use of misoprostol.

Inositol treatment of anovulation in women with polycystic ovary syndrome: a meta-analysis of randomised trials.

PubMed

Pundir, J; Psaroudakis, D; Savnur, P; Bhide, P; Sabatini, L; Teede, H; Coomarasamy, A; Thangaratinam, S

2018-02-01

Polycystic ovary syndrome is a common cause of anovulation and infertility, and a risk factor for development of metabolic syndrome and endometrial cancer. Systematic review and meta-analysis of randomised controlled trials (RCT) that evaluated the effects of inositol as an ovulation induction agent. We searched MEDLINE, EMBASE, Cochrane and ISI conference proceedings, Register and Meta-register for RCT and WHO trials' search portal. We included studies that compared inositol with placebo or other ovulation induction agents. Quality of studies was assessed for risk of bias. Results were pooled using random effects meta-analysis and findings were reported as relative risk or standardised mean differences. We included ten randomised trials. A total of 362 women were on inositol (257 on myo-inositol; 105 on di-chiro-inositol), 179 were on placebo and 60 were on metformin. Inositol was associated with significantly improved ovulation rate (RR 2.3; 95% CI 1.1-4.7; I 2 = 75%) and increased frequency of menstrual cycles (RR 6.8; 95% CI 2.8-16.6; I 2 = 0%) compared with placebo. One study reported on clinical pregnancy rate with inositol compared with placebo (RR 3.3; 95% CI 0.4-27.1), and one study compared with metformin (RR 1.5; 95% CI 0.7-3.1). No studies evaluated live birth and miscarriage rates. Inositol appears to regulate menstrual cycles, improve ovulation and induce metabolic changes in polycystic ovary syndrome; however, evidence is lacking for pregnancy, miscarriage or live birth. A further, well-designed multicentre trial to address this issue to provide robust evidence of benefit is warranted. Inositols improve menstrual cycles, ovulation and metabolic changes in polycystic ovary syndrome. © 2017 Royal College of Obstetricians and Gynaecologists.

Systematic review with network meta-analysis: comparative efficacy and safety of budesonide and mesalazine (mesalamine) for Crohn's disease.

PubMed

Moja, L; Danese, S; Fiorino, G; Del Giovane, C; Bonovas, S

2015-06-01

Budesonide and mesalazine (mesalamine) are commonly used in the medical management of patients with mild to moderate Crohn's disease. To assess their comparative efficacy and harm using the methodology of network meta-analysis. A comprehensive search of Medline, Embase, the Cochrane Library and ClinicalTrials.gov, through October 2014, was performed to identify randomised controlled trials (RCTs) that recruited adult patients with active or quiescent Crohn's disease, and compared budesonide or mesalazine with placebo, or against each other, or different dosing strategies of one drug. Twenty-five RCTs were combined using Bayesian network meta-analysis. Budesonide 9 mg/day, or at higher doses (15 or 18 mg/day), was shown superior to placebo for induction of remission [odds ratio (OR), 2.93; 95% credible interval (CrI), 1.52-5.39, and OR, 3.28; CrI, 1.46-7.55 respectively] and ranks at the top of the hierarchy of the competing treatments. For maintenance of remission, budesonide 6 mg/day demonstrated superiority over placebo (OR, 1.69; CrI, 1.05-2.75), being also at the best ranking position among all compared treatment strategies. No other comparisons (i.e. different doses of mesalazine vs. placebo or budesonide, for induction or maintenance of remission) reached significance. The occurrence of withdrawals due to adverse events was not shown different between budesonide, mesalazine and placebo, in both the induction and maintenance phases. Budesonide, at the doses of 9 mg/day, or higher, for induction of remission in active mild or moderate Crohn's disease, and at 6 mg/day for maintenance of remission, appears to be the best treatment choice. © 2015 John Wiley & Sons Ltd.

Long-term survival of high-risk melanoma patients immunized with a Hyper-IL-6-modified allogeneic whole-cell vaccine after complete resection.

PubMed

Mackiewicz, Andrzej; Mackiewicz, Jacek; Wysocki, Piotr J; Wiznerowicz, Maciej; Kapcinska, Malgorzata; Laciak, Maria; Rose-John, Stefan; Izycki, Dariusz; Burzykowski, Tomasz; Karczewska-Dzionk, Aldona

2012-06-01

Two single arm, Phase II trials (3 and 5) were undertaken to determine the efficacy and toxicity of an adjuvant treatment using Hyper-IL-6 gene-modified whole-cell allogeneic melanoma vaccine in patients with stage IIIB-IV resected disease. Ninety-seven and 99 patients were enrolled into Trials 3 and 5, respectively. The primary endpoint was disease-free survival (DFS), and the secondary was overall survival (OS). Vaccine was administered eight times every 2 weeks (induction), every month (maintenance) until patient's death. At progression, maintenance was continued or induction was repeated followed by maintenance. Median follow-up was 10.5 and 6.2 years for Trials 3 and 5, respectively. No grade 3 or 4 toxicities were observed. An extension of DFS and OS was observed, when compared with historical non-treated controls. DFS probability at 5 years for Trials 3 and 5 was, respectively, 54.8% and 40.6% for stage IIIB, 25.0% and 24.0% for IIIC, and 8.5% and 17.7% for IV. OS probability at 5 years was, respectively, 66.7% and 56.3% for IIIB, 43.8% and 39.8% for IIIC, and 26.1% and 41.2% for IV. Continuous vaccination, regardless of the disease progression, re-induction, and immunization of patients until death resulted in patients a long-term survival.

Peripheral T-cell lymphoma: autologous hematopoietic cell transplantation as first-line therapy.

PubMed

Laport, Ginna G

2010-09-01

The peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin's lymphomas associated with an unfavorable prognosis compared with the B-cell non-Hodgkin's lymphomas. The PTCLs are characterized by high remission rates after frontline therapy, but relapse inevitably occurs. The impact of high-dose chemotherapy with autologous hematopoietic cell transplantation (AHCT) as early consolidation therapy will be the focus of this review. In several prospective trials, only PTCL patients with responsive disease after induction chemotherapy proceeded to AHCT. The progression-free survivals ranged from 30% to 40% with low toxicity. The outcomes in retrospective trials appear more favorable but such trials were affected by a selection bias because only chemosensitive patients actually proceeded to AHCT, whereas the prospective studies were intention-to-treat analyses. Most of the published trials demonstrated that prognostic models such as the International Prognostic Index and the Prognostic Index for T-cell lymphoma help predict outcome after AHCT. Current data support the use of AHCT as early consolidation therapy for PTCL patients who are chemosensitive after induction chemotherapy. However, approximately one-third of patients are early induction failures and thus are not able to proceed to AHCT. Additionally, disease relapse remains the leading cause of treatment failure after AHCT, and thus more intensive treatment strategies or better noncross-resistant therapies are greatly needed early in the course of the disease.

Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia between 34 and 37 weeks' gestation (HYPITAT-II): a multicentre, open-label randomised controlled trial.

PubMed

Langenveld, Josje; Broekhuijsen, Kim; van Baaren, Gert-Jan; van Pampus, Maria G; van Kaam, Anton H; Groen, Henk; Porath, Martina; Oudijk, Martijn A; Bloemenkamp, Kitty W; Groot, Christianne J de; van Beek, Erik; van Huizen, Marloes E; Oosterbaan, Herman P; Willekes, Christine; Wijnen-Duvekot, Ella J; Franssen, Maureen T M; Perquin, Denise A M; Sporken, Jan M J; Woiski, Mallory D; Bremer, Henk A; Papatsonis, Dimitri N M; Brons, Jozien T J; Kaplan, Mesruwe; Nij Bijvanck, Bas W A; Mol, Ben-Willen J

2011-07-07

Gestational hypertension (GH) and pre-eclampsia (PE) can result in severe complications such as eclampsia, placental abruption, syndrome of Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) and ultimately even neonatal or maternal death. We recently showed that in women with GH or mild PE at term induction of labour reduces both high risk situations for mothers as well as the caesarean section rate. In view of this knowledge, one can raise the question whether women with severe hypertension, pre-eclampsia or deterioration chronic hypertension between 34 and 37 weeks of gestation should be delivered or monitored expectantly. Induction of labour might prevent maternal complications. However, induction of labour in late pre-term pregnancy might increase neonatal morbidity and mortality compared with delivery at term. Pregnant women with severe gestational hypertension, mild pre-eclampsia or deteriorating chronic hypertension at a gestational age between 34+0 and 36+6 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant monitoring. In the expectant monitoring arm, women will be induced only when the maternal or fetal condition detoriates or at 37+0 weeks of gestation. The primary outcome measure is a composite endpoint of maternal mortality, severe maternal complications (eclampsia, HELLP syndrome, pulmonary oedema and thromboembolic disease) and progression to severe pre-eclampsia. Secondary outcomes measures are respiratory distress syndrome (RDS), neonatal morbidity and mortality, caesarean section and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be intention to treat. The power calculation is based on an expectant reduction of the maternal composite endpoint from 5% to 1% for an expected increase in neonatal RDS from 1% at 37 weeks to 10% at 34 weeks. This implies that 680 women have to be randomised. This trial will provide insight as to whether in women with hypertensive disorders late pre-term, induction of labour is an effective treatment to prevent severe maternal complications without compromising the neonatal morbidity. NTR1792 CLINICAL TRIAL REGISTRATION: http://www.trialregister.nl.

Vedolizumab as induction and maintenance therapy for Crohn's disease.

PubMed

Sandborn, William J; Feagan, Brian G; Rutgeerts, Paul; Hanauer, Stephen; Colombel, Jean-Frédéric; Sands, Bruce E; Lukas, Milan; Fedorak, Richard N; Lee, Scott; Bressler, Brian; Fox, Irving; Rosario, Maria; Sankoh, Serap; Xu, Jing; Stephens, Kristin; Milch, Catherine; Parikh, Asit

2013-08-22

The efficacy of vedolizumab, an α4β7 integrin antibody, in Crohn's disease is unknown. In an integrated study with separate induction and maintenance trials, we assessed intravenous vedolizumab therapy (300 mg) in adults with active Crohn's disease. In the induction trial, 368 patients were randomly assigned to receive vedolizumab or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label vedolizumab at weeks 0 and 2 (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461 patients who had had a response to vedolizumab were randomly assigned to receive placebo or vedolizumab every 8 or 4 weeks until week 52. At week 6, a total of 14.5% of the patients in cohort 1 who received vedolizumab and 6.8% who received placebo were in clinical remission (i.e., had a score on the Crohn's Disease Activity Index [CDAI] of ≤150, with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity) (P=0.02); a total of 31.4% and 25.7% of the patients, respectively, had a CDAI-100 response (≥100-point decrease in the CDAI score) (P=0.23). Among patients in cohorts 1 and 2 who had a response to induction therapy, 39.0% and 36.4% of those assigned to vedolizumab every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52, as compared with 21.6% assigned to placebo (P<0.001 and P=0.004 for the two vedolizumab groups, respectively, vs. placebo). Antibodies against vedolizumab developed in 4.0% of the patients. Nasopharyngitis occurred more frequently, and headache and abdominal pain less frequently, in patients receiving vedolizumab than in patients receiving placebo. Vedolizumab, as compared with placebo, was associated with a higher rate of serious adverse events (24.4% vs. 15.3%), infections (44.1% vs. 40.2%), and serious infections (5.5% vs. 3.0%). Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive vedolizumab (rather than switching to placebo) were more likely to be in remission at week 52. Adverse events were more common with vedolizumab. (Funded by Millennium Pharmaceuticals; GEMINI 2 ClinicalTrials.gov number, NCT00783692.).

The M-OVIN study: does switching treatment to FSH and / or IUI lead to higher pregnancy rates in a subset of women with world health organization type II anovulation not conceiving after six ovulatory cycles with clomiphene citrate – a randomised controlled trial

PubMed Central

2013-01-01

Background Clomiphene citrate (CC) is first line treatment in women with World Health Organization (WHO) type II anovulation and polycystic ovary syndrome (PCOS). Whereas 60% to 85% of these women will ovulate on CC, only about one half will have conceived after six cycles. If women do not conceive, treatment can be continued with gonadotropins or intra-uterine insemination (IUI). At present, it is unclear for how many cycles ovulation induction with CC should be repeated, and when to switch to ovulation induction with gonadotropins and/or IUI. Methods/Design We started a multicenter randomised controlled trial in the Netherlands comparing six cycles of CC plus intercourse or six cycles of gonadotrophins plus intercourse or six cycles of CC plus IUI or six cycles of gonadotrophins plus IUI. Women with WHO type II anovulation who ovulate but did not conceive after six ovulatory cycles of CC with a maximum of 150 mg daily for five days will be included. Our primary outcome is birth of a healthy child resulting from a pregnancy that was established in the first eight months after randomisation. Secondary outcomes are clinical pregnancy, miscarriage, multiple pregnancy and treatment costs. The analysis will be performed according to the intention to treat principle. Two comparisons will be made, one in which CC is compared to gonadotrophins and one in which the addition of IUI is compared to ovulation induction only. Assuming a live birth rate of 40% after CC, 55% after addition of IUI and 55% after ovulation induction with gonadotrophins, with an alpha of 5% and a power of 80%, we need to recruit 200 women per arm (800 women in total). An independent Data and Safety Monitoring Committee has criticized the data of the first 150 women and concluded that a sample size re-estimation should be performed after including 320 patients (i.e. 80 per arm). Discussion The trial will provide evidence on the most effective, safest and most cost effective treatment in women with WHO type II anovulation who do not conceive after six ovulatory cycles with CC with a maximum of 150 mg daily for five days. This evidence could imply the need for changing our guidelines, which may cause a shift in large practice variation to evidence based primary treatment for these women. Trial registration number Netherlands Trial register NTR1449 PMID:24160333

[In case of fetal macrosomia, the best strategy is the induction of labor at 38 weeks of gestation].

PubMed

Rozenberg, P

2016-11-01

Macrosomic fetuses are at increased risk of obstetric complications, and notably shoulder dystocia, responsible for a severe neonatal morbidity. In case of fetal macrosomia, three options are: (i) the elective cesarean delivery, but this is recommended only when the estimated fetal weight is≥4500g for diabetic women and 5000g for non-diabetic women; (ii) the expectative management, but children with birth weight≥4500 had significantly increased risk of perinatal mortality, neonatal asphyxia, trauma, and cesarean delivery; (iii) the induction of labor which, reducing the possibility of fetal growth, reduce the risk of cesarean delivery for cephalopelvic disproportion and shoulder dystocia. As 2 former trials did not show maternal or neonatal benefit with induction of labor for fetal macrosomia, it was therefore not recommended. However, these 2 studies had small sample size (273 and 40 women) and a methodology limiting their ability to show a difference, justifying to achieve a large multicentre randomized controlled trial. This trial was performed by Boulvain et al. and the results published in 2015 in the Lancet. Inclusion criteria were: a singleton pregnancy in cephalic presentation and a suspected fetal macrosomia defined by an ultrasound estimated weight>95th percentile between 36 and 38 weeks. Women were randomly assigned to receive induction of labor within 3 days between 37 +0  and 38 +6  weeks of gestation, or expectant management. Expectant management continued until either spontaneous labour or diagnosis of a condition necessitating induction. The primary outcome was a composite of clinically significant shoulder dystocia, fracture of the clavicle, brachial plexus injury, intracranial haemorrhage, or death. Baseline characteristics were similar between groups. The mean birth weight (±SD) was 3831 (±324) g in the induction group 4118 (±392) g in the expectant group. Induction of labor significantly reduced the risk of shoulder dystocia or associated morbidity (8/407; 2 %) compared with expectant management (25/411; 6 %); P=0.004. The number needed to treat was 25 (95 % CI: 15-70). The incidence of caesarean section and operative vaginal delivery did not differ significantly between the groups. The likelihood of spontaneous vaginal delivery increased significantly in the induction of labor group (59 % vs. 52 %, RR: 1.14; 95 % CI: 1.01-1.29). In all, the results of the Boulvain et al. trial justify to propose an induction of labor in cases of suspected macrosomia>95th percentile: the induction of labor reduced the risk of severe shoulder dystocia, and does not increase the risk of cesarean section. It even increases the likelihood of spontaneous vaginal delivery. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Methods for assessing pre-induction cervical ripening

PubMed Central

Ezebialu, Ifeanyichukwu U; Eke, Ahizechukwu C; Eleje, George U; Nwachukwu, Chukwuemeka E

2015-01-01

Background Induction of labour is the artificial initiation of labour in a pregnant woman after the age of fetal viability but without any objective evidence of active phase labour and with intact fetal membranes. The need for induction of labour may arise due to a problem in the mother, her fetus or both, and the procedure may be carried out at or before term. Obstetricians have long known that for this to be successful, it is important that the uterine cervix (the neck of the womb) has favourable characteristics in terms of readiness to go into the labour state. Objectives To compare Bishop score with any other method for assessing pre-induction cervical ripening in women admitted for induction of labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2015) and reference lists of retrieved studies to identify randomised controlled trials (RCTs). Selection criteria All RCTs comparing Bishop score with any other methods of pre-induction cervical assessment in women admitted for induction of labour. Cluster-RCTs were eligible for inclusion but none were identified. Quasi-RCTs and studies using a cross-over design were not eligible for inclusion. Studies published in abstract form were eligible for inclusion if they provided sufficient information. Comparisons could include the following. Bishop score versus transvaginal ultrasound (TVUS). Bishop score versus Insulin-like growth factor binding protein-1 (IGFBP-1). Bishop score versus vaginal fetal fibronectin (fFN). However, we only identified data for a comparison of Bishop score versus TVUS. Data collection and analysis Two review authors independently assessed the trials for inclusion, extracted the data and assessed trial quality. Data were checked for accuracy. Main results We included two trials that recruited a total of 234 women. The overall risk of bias was low for the two studies. Both studies compared Bishop score withTVUS. The two included studies did not show any clear difference between the Bishop score and TVUS groups for the following main outcomes: vaginal birth (RR 1.07, 95% CI 0.92 to 1.25, moderate quality evidence), caesarean delivery (RR 0.81, 95% CI 0.49 to 1.34, moderate quality evidence), neonatal admission into neonatal intensive care unit (RR 1.67, 95% CI 0.41 to 6.71, moderate quality evidence). Both studies only provided median data in relation to induction-delivery interval and reported no clear difference between the Bishop and TVUS groups. Perinatal mortality was not reported in the included studies. For the review's secondary outcomes, the need for misoprostol for cervical ripening was more frequent in the TVUS group compared to the Bishop score group (RR 0.52, 95% CI 0.41 to 0.66, two studies, 234 women, moderate quality evidence). In contrast, there were no clear differences between the Bishop scope and TVUS groups in terms of meconium staining of the amniotic fluid, fetal heart rate abnormality in labour, and Apgar score less than seven. Only one trial reported median data on the induction-delivery interval and induction to active phase interval, the trialist reported no difference between the Bishop group and the TVUS group for this outcome. Neither of the included studies reported on uterine rupture. Authors' conclusions Moderate quality evidence from two small RCTs involving 234 women that compared two different methods for assessing pre-induction cervical ripening (Bishop score and TVUS) did not demonstrate superiority of one method over the other in terms of the main outcomes assessed in this review. We did not identify any data relating to perinatal mortality. Whilst use of TVUS was associated with an increased need for misoprostol for cervical ripening, both methods could be complementary. The choice of a particular method of assessing pre-induction cervical ripening may differ depending on the environment and need where one is practicing since some methods (i.e. TVUS) may not be readily available and affordable in resource-poor settings where the sequelae of labour and its management is prevalent. The evidence in this review is based on two studies that enrolled a small number of women and there is insufficient evidence to support the use of TVUS over the standard digital vaginal assessment in pre-induction cervical ripening. Further adequately powered RCTs involving TVUS and the Bishop score and including other methods of pre-induction cervical ripening assessment are warranted. Such studies need to address uterine rupture, perinatal mortality, optimal cut-off value of the cervical length and Bishop score to classify women as having favourable or unfavourable cervices and cost should be included as an outcome. PLAIN LANGUAGE SUMMARY Methods for assessing pre-induction cervical ripening, the ability of the cervix to open in response to spontaneous uterine contractions In this review, researchers from The Cochrane Collaboration examined a comparison between the Bishop score and any other method for checking pre-induction cervical ripening in women admitted for induction of labour. The Bishop score is the traditional method of determining the readiness of the cervix to open (dilate) before labour induction. It also assesses the position, softening and shortening of the cervix, and the location of the presenting part of the baby. After searching for relevant trials up to 31 March 2015, we included two randomised controlled trials that recruited 234 pregnant women. What are the methods for pre-induction softening of the neck of womb and why is it important to soften the neck of womb before induction of labour? Induction of labour is the non-natural process of starting labour in a pregnant woman after the age the baby is more likely to survive following delivery, when there is no clear evidence of serious onset of labour and the membranes covering the baby are unruptured. Induction of labour may be needed because of a problem in the mother, or her baby or both, and is carried out at or before the ninth (last) month of pregnancy. Obstetricians (specialist caring for pregnant women) have long known that for this to be successful, it is important that the uterine cervix (the neck of the womb) has the favourable characteristics that make it ready to go into the labour. The delivery method and total duration of labour are affected by many factors and cervical readiness (ripeness) is just one of these. What the research says Moderate quality evidence was available from the two included studies which compared the Bishop score with transvaginal ultrasound (TVUS) (ultrasound done through the vagina). The studies were considered to be at a low risk of bias. The need for misoprostol (a drug) for softening the cervix (cervical ripening) was more common in the TVUS arm. No clear difference was seen between the two methods in terms of vaginal birth, caesarean delivery, admission of the newborn into the neonatal intensive care unit, meconium staining of the amniotic fluid, abnormal heart beat of the baby within the womb whilst the mother was in labour and Apgar score less than seven (difficulty of the baby establishing life and other life movements on its own immediately after childbirth). None of the included studies reported on tears of the womb or death of the baby just before, during or immediately after childbirth. We did not find any studies that compared Bishop score with any other methods such as the presence of vaginal fetal fibronectin or insulin-like growth factor binding protein-1. Authors conclusions Although the overall quality of evidence is moderate, there is no difference in outcomes between the two methods (Bishop score and TVUS) apart from the increased need of misoprostol in the TVUS group. Both methods could be useful to each other, or complementary as the Bishop score does not need any special equipment and uses digital examination which is required to induce labour (to insert a cervical ripening agent, rupture the membranes or separate them from the cervix) but TVUS can give additional information that may affect the course and management of the labour. The choice of a particular method may differ depending on the environment and need since TVUS requires training and may not be readily available and affordable in resource-poor countries. Future research The two included studies involved a small number of women and further studies are needed. Such studies should include outcomes such as rupture of the womb, perinatal mortality, most appropriate cut-off value for the cervical length and Bishop score to classify women as having ripe or unripe cervices, and cost. PMID:26068943

Hemodynamic responses to etomidate versus ketamine-thiopental sodium combination for anesthetic induction in coronary artery bypass graft surgery patients with low ejection fraction: a double-blind, randomized, clinical trial.

PubMed

Habibi, Mohammad Reza; Baradari, Afshin Gholipour; Soleimani, Aria; Emami Zeydi, Amir; Nia, Hamid Sharif; Habibi, Ali; Onagh, Naser

2014-10-01

During induction of anesthesia and intubation, hemodynamic changes are very important; especially in patients with coronary artery disease (CAD) and left ventricular dysfunction. A little information is available on the hemodynamic effects of a combination of ketamine-thiopental for induction of anesthesia in patients undergoing coronary artery bypass graft (CABG) surgery, with impaired ventricular function. The aim of this study was to compare the hemodynamic responses to etomidate versus ketamine-thiopental sodium combination for anesthetic induction in CABG surgery patients with low ejection fraction (EF<45%). In a double blind randomized clinical trial, a total of 100 patients, scheduled for elective CABG surgery were randomly assigned into two groups. These patients received either etomidate or ketamine-thiopental sodium combination at induction of anesthesia. Hemodynamics variable were measured and recorded at baseline, immediately before and after laryngoscopy and intubation, one, two and three minutes after intubation. Also, muscle twitching incidence among patients in two groups was evaluated. No significant differences between the two groups regarding the changes of hemodynamic variables including systolic and diastolic arterial blood pressure, mean arterial pressure and heart rate, were notice (p>0.05). Muscle twitching was not observed in the two groups. Hemodynamic stability after administration of ketamine-thiopental sodium combination for induction of anesthesia in patients undergoing CABG surgery, with impaired ventricular function, supports the clinical impression that this combination is safe in CABG surgery patients with low EF.

Recruiting unmotivated smokers into a smoking induction trial.

PubMed

Harris, Kari Jo; Bradley-Ewing, Andrea; Goggin, Kathy; Richter, Kimber P; Patten, Christi; Williams, Karen; Lee, Hyoung S; Staggs, Vincent S; Catley, Delwyn

2016-06-01

Little is known about effective methods to recruit unmotivated smokers into cessation induction trials, the reasons unmotivated smokers agree to participate, and the impact of those reasons on study outcomes. A mixed-method approach was used to examine recruitment data from a randomized controlled cessation induction trial that enrolled 255 adult smokers with low motivation to quit. Over 15 months, 33% of smokers who inquired about the study were enrolled. Common recruitment methods included word-of-mouth, print advertisements and clinic referrals. Frequently mentioned reasons for participating included to: gain financial incentives (44.7%), learn about research or help others quit (43%), learn about smoking and risks (40%) and help with future quits (i.e. Quit Assistance, 23.9%). Separate regression models predicting study outcomes at 26 weeks indicated that smokers who said they participated for Quit Assistance reported higher motivation to quit (B 1.26) and were more likely to have made a quit attempt (OR 2.03) compared to those not mentioning this reason, when baseline characteristics were controlled. Understanding reasons for unmotivated smokers' interest in treatment can help practitioners and researchers design effective strategies to engage this population. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Induction regimens for transplant-eligible patients with newly diagnosed multiple myeloma: a network meta-analysis of randomized controlled trials

PubMed Central

Zeng, Zi-Hang; Chen, Jia-Feng; Li, Yi-Xuan; Zhang, Ran; Xiao, Ling-Fei; Meng, Xiang-Yu

2017-01-01

Objective The aim of this study was to compare the early efficacy and survivals of induction regimens for transplant-eligible patients with untreated multiple myeloma. Materials and methods A comprehensive literature search in electronic databases was conducted for relevant randomized controlled trials (RCTs). Eligible studies were selected according to the predefined selection criteria, before they were evaluated for methodological quality. Basic characteristics and data for network meta-analysis (NMA) were extracted from included trials and pooled in our meta-analysis. The end points were the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results A total of 14 RCTs that included 4,763 patients were analyzed. The post-induction ORR was higher with bortezomib plus thalidomide plus dexamethasone (VTD) regimens, and VTD was better than the majority of other regimens. For OS, VTD plus cyclophosphamide (VTDC) regimens showed potential superiority over other regimens, but the difference was not statistically significant. The PFS was longer with thalidomide plus doxorubicin plus dexamethasone (TAD) regimens for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Conclusion The NMA demonstrated that the VTD, VTDC, and TAD regimens are most beneficial in terms of ORR, OS, and PFS for transplant-eligible patients with NDMM, respectively. PMID:28744159

Comparison of clomiphene citrate and letrozole for ovulation induction in women with polycystic ovary syndrome: a prospective randomized trial.

PubMed

Liu, Chang; Feng, Guimei; Huang, Wei; Wang, Qiuyi; Yang, Shiyuan; Tan, Jing; Fu, Jing; Liu, Dong

2017-11-01

To compare the therapeutic efficacy of clomiphene citrate (CC) and letrozole (LE) on ovulation, pregnancy, and live birth in women with polycystic ovary syndrome (PCOS); and to ensure if LE can replace CC as the first-line therapy for ovulation induction in these women. This is a prospectively, randomized, controlled trial in the tertiary hospital. Two-hundred and sixty-eight anovulatory PCOS patients were treated by CC or CC plus metformin and LE or LE plus metformin for three continuous cycles or conception; their ovulation rates, pregnancy rates, and live birth rates were calculated and compared. No significant difference was noted among the four groups regarding to the baseline data of clinical manifestations, serum sex hormone levels, and serum insulin levels. A total of 240 patients completed the therapies. The ovulation rate was significantly higher in the group LE than the group CC; however, no significant difference was noted between the groups LE and CC, CC, and CC + MET, or LE and LE + MET in the pregnancy rate, abortion rate, and live birth rate. No birth defect was found in the total of 63 newborns. CC regimen was still recommended to be the first-line therapy of ovulation induction for PCOS.

Rocuronium versus succinylcholine for rapid sequence induction intubation.

PubMed

Tran, Diem T T; Newton, Ethan K; Mount, Victoria A H; Lee, Jacques S; Wells, George A; Perry, Jeffrey J

2015-10-29

Patients often require a rapid sequence induction (RSI) endotracheal intubation technique during emergencies or electively to protect against aspiration, increased intracranial pressure, or to facilitate intubation. Traditionally succinylcholine has been the most commonly used muscle relaxant for this purpose because of its fast onset and short duration; unfortunately, it can have serious side effects. Rocuronium has been suggested as an alternative to succinylcholine for intubation. This is an update of our Cochrane review published first in 2003 and then updated in 2008 and now in 2015. To determine whether rocuronium creates intubating conditions comparable to those of succinylcholine during RSI intubation. In our initial review we searched all databases until March 2000, followed by an update to June 2007. This latest update included searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 2), MEDLINE (1966 to February Week 2 2015), and EMBASE (1988 to February 14 2015 ) for randomized controlled trials (RCTs) or controlled clinical trials (CCTs) relating to the use of rocuronium and succinylcholine. We included foreign language journals and handsearched the references of identified studies for additional citations. We included any RCT or CCT that reported intubating conditions in comparing the use of rocuronium and succinylcholine for RSI or modified RSI in any age group or clinical setting. The dose of rocuronium was at least 0.6 mg/kg and succinylcholine was at least 1 mg/kg. Two authors (EN and DT) independently extracted data and assessed methodological quality for the 'Risk of bias' tables. We combined the outcomes in Review Manager 5 using a risk ratio (RR) with a random-effects model. The previous update (2008) had identified 53 potential studies and included 37 combined for meta-analysis. In this latest update we identified a further 13 studies and included 11, summarizing the results of 50 trials including 4151 participants. Overall, succinylcholine was superior to rocuronium for achieving excellent intubating conditions: RR 0.86 (95% confidence interval (CI) 0.81 to 0.92; n = 4151) and clinically acceptable intubation conditions (RR 0.97, 95% CI 0.95 to 0.99; n = 3992, 48 trials). A high incidence of detection bias amongst the trials coupled with significant heterogeneity provides moderate-quality evidence for these conclusions, which are unchanged from the previous update. Succinylcholine was more likely to produce excellent intubating conditions when using thiopental as the induction agent: RR 0.81 (95% CI: 0.73 to 0.88; n = 2302, 28 trials). In the previous update, we had concluded that propofol was the superior induction agent with succinylcholine. There were no reported incidences of severe adverse outcomes. We found no statistical difference in intubation conditions when succinylcholine was compared to 1.2 mg/kg rocuronium; however, succinylcholine was clinically superior as it has a shorter duration of action. Succinylcholine created superior intubation conditions to rocuronium in achieving excellent and clinically acceptable intubating conditions.

Efficacy of alfaxalone for intravascular anesthesia and euthanasia in blue crabs (Callinectes sapidus).

PubMed

Minter, Larry J; Harms, Craig A; Archibald, Kate E; Broadhurst, Heather; Bailey, Kate M; Christiansen, Emily F; Lewbart, Gregory A; Posner, Lysa P

2013-09-01

The objective of this study was to characterize the behavioral effects and changes in heart rate of four doses of alfaxalone delivered by intravascular injection to blue crabs (Callinectes sapidus). Thirty (male, n = 27; female, n = 3) blue crabs were randomly assigned to one of four treatment groups of alfaxalone: eight animals were assigned to each of the 5-, 10-, and 15-mg/kg treatment groups, and the remaining six animals were assigned to the 100-mg/kg group. Times for anesthetic induction and recovery periods were recorded. Righting reflex, defensive posturing, and heart rate were evaluated before, during, and after the anesthetic trial. Anesthesia was induced in all 14 animals consolidated into the high-dosage group (15 mg/kg [n = 8] and 100 mg/kg [n = 6]), which was significantly greater than 8 of 16 animals in the low-dosage group (5 mg/kg [n = 2] and 10 mg/kg [n = 6]). Median anesthesia induction time for all crabs was 0.4 min, with no significant difference in induction time between groups observed. Median recovery time was 9.4 min (n = 2), 6.1 min (n = 5), 11.3 min (n = 8), and 66.1 min (n = 5) for the 5-, 10-, 15-, and 100-mg/kg groups, respectively. Recovery times were significantly longer for crabs exposed to an induction dose of 100 mg/kg compared with the 10- and 15-mg/kg induction doses. A significant decrease in the median heart rate was observed between the baseline value and that observed at both induction and 5 min postinjection in the 100-mg/kg dose trial. Two mortalities were observed during the anesthesia trials (n = 1, 10 mg/kg; n = 1, 100 mg/kg), both associated with the autotomization of limbs. In summary, the intravascular administration of alfaxalone at 15 mg/kg provided rapid and reliable sedation, whereas alfaxalone administered at 100 mg/kg produced rapid and long lasting anesthesia.

Evaluation of the use of midazolam as a co-induction agent with ketamine for anaesthesia in sedated ponies undergoing field castration.

PubMed

Allison, A; Robinson, R; Jolliffe, C; Taylor, P M

2018-05-01

There are limited investigations comparing ketamine to a ketamine-midazolam co-induction. To compare quality and safety of general anaesthesia induced using ketamine alone with anaesthesia co-induced using ketamine and midazolam. Randomised, double blinded, placebo controlled trial. After i.v. detomidine (20 μg/kg) thirty-eight ponies undergoing field castration received either 0.06 mg/kg (0.6 mL/50 kg) midazolam (group M) or 0.6 mL/50 kg placebo (group P) with 2.2 mg/kg ketamine i.v. for anaesthetic induction. Quality of anaesthetic induction, endotracheal intubation, surgical relaxation and recovery were scored using combinations of simple descriptive and visual analogue scales. Time of sedation, induction, start of endotracheal intubation, first movement, sternal recumbency and standing were recorded, as were time, number and total quantity of additional i.v. detomidine and ketamine injections. Cardiorespiratory variables were assessed every 5 min. Adverse effects were documented. Data were tested for normality and analysed with a mixed model ANOVA, Fisher's exact test, unpaired Students' t test and Wilcoxon Rank-sum as appropriate; P<0.05 was considered significant. Group M had better scores for induction (P = 0.005), intubation (P<0.001) and surgical relaxation (P<0.001) and required fewer additional injections of detomidine and ketamine (P = 0.04). Time (minutes) from induction to first movement (P<0.001), sternal recumbency (P =< 0.001) and standing was longer (P = 0.05) in group M. Recoveries were uneventful with no difference in quality between groups (P = 0.78). Clinical study with noninvasive monitoring undertaken in field conditions. Ketamine-midazolam co-induction compared to ketamine alone improved quality of induction, ease of intubation and muscle relaxation without impacting recovery quality. © 2017 EVJ Ltd.

Misoprostol administered sublingually at a dose of 12.5 μg versus vaginally at a dose of 25 μg for the induction of full-term labor: a randomized controlled trial protocol.

PubMed

Gattás, Daniele Sofia Moraes Barros; da Silva Junior, José Roberto; Souza, Alex Sandro Rolland; Feitosa, Francisco Edson; de Amorim, Melania Maria Ramos

2018-04-18

Various methods are currently used for the induction of labor. Nevertheless, the most effective method with the fewest side effects remains to be established. Misoprostol, administered vaginally, has been routinely used for this purpose; however, other forms of administration are being proposed, including the use of sublingual tablets. No studies have yet compared the effectiveness and safety of 12.5-μg misoprostol administered sublingually compared to a 25-μg vaginal dose of the drug for the induction of labor. A triple-blind, multicenter, placebo-controlled, randomized clinical trial will be conducted in Brazil at the Instituto de Medicina Integral Prof. Fernando Figueira and at the Assis Chateaubriand Maternity Teaching Hospital of the Federal University of Ceará. A total of 140 patients with full-term pregnancies, a live fetus, a Bishop score ≤ 6 and a recommendation of induction of labor will be randomized to one of two groups. One group will receive 12.5-μg sublingual tablets of misoprostol and placebo vaginal tablets, while the other group will receive placebo sublingual tablets and vaginal tablets containing 25 μg of misoprostol. The principal endpoint is the rate of tachysystole. The secondary endpoints are vaginal delivery within 24 h of induction, uterine hyperstimulation, Cesarean section, severe neonatal morbidity or perinatal death, severe maternal morbidity or maternal death, and maternal preference regarding the route of administration of the drug. Student's t-test, and the chi-square test of association or Fisher's exact test, as appropriate, will be used in the data analysis. Risk ratios and their respective 95% confidence intervals will be calculated. Misoprostol has been identified as a safe, inexpensive, easily administered option for the induction of labor, with satisfactory results. An experimental study has shown that misoprostol administered sublingually at a dose of 25 μg appears to be effective and is associated with greater maternal satisfaction when labor is induced in women with an unfavorable cervix. Nevertheless, the rate of tachysystole remains high; therefore, further studies are required to determine the ideal dose and the ideal interval of time between doses. ClinicalTrial.gov, NCT01406392 .

Adjuvant and induction chemotherapy in non-small cell lung cancer.

PubMed

Pirker, R; Malayeri, R; Huber, H

1999-01-01

About 25%-30% of patients with non-small cell lung cancer can be resected with curative intent. However, systemic relapses occur in up to 70% of these patients. Thus, postoperative adjuvant chemotherapy was evaluated in several randomised trials but the results of these trials were inconclusive with a survival benefit only in some trials. Shortcomings of these trials included low number of patients, poor patient compliance and inadequate chemotherapy protocols. A recent meta-analysis suggested an absolute survival benefit of 5% at five years for postoperative cisplatin-based chemotherapy as compared to surgery alone. Thus adjuvant chemotherapy with both improved chemotherapy protocols and improved anti-emetics is currently re-evaluated in several randomised trials on large patient populations.

Probiotics for induction of remission in ulcerative colitis.

PubMed

Mallon, P; McKay, D; Kirk, S; Gardiner, K

2007-10-17

Ulcerative Colitis (UC) is an inflammatory condition affecting the colon with an incidence of approximately 10-20 per 100,000 per year. No existing intervention is effective in all patients with a proportion requiring colectomy. There are significant proportion of patients who experience adverse effects with current therapies. Consequently, new alternatives for the treatment of UC are constantly being sought. Probiotics are live microbial feed supplements that may beneficially affect the host by improving intestinal microbial balance, enhancing gut barrier function and improving local immune response. To assess the efficacy of probiotics compared with placebo or standard medical treatment (5-aminosalicylates, sulfasalazine or corticosteroids) for the induction of remission in active ulcerative colitis. A comprehensive search for relevant randomised controlled trials (RCT's) was carried out using MEDLINE (1966-January 2006), EMBASE (January 1985- 2006) and CENTRAL. The Cochrane IBD/FBD Review Group Specialised Trials Registrar was also searched. The Australasian Medical Index, Chinese Biomedical Literature Database, Latin American Caribbean Health Sciences Literature (LILACS), and the Japan Information Centre of Science and Technology File on Science, Technology and Medicine (JICST-E) were also used to identify abstracts. Conference proceedings from the Falk Symposium, Digestive Disease Week (DDW) and the United European Digestive Disease week were hand-searched. Authors of relevant studies and drug companies were contacted regarding ongoing or unpublished trials that may be relevant to the review. Randomised controlled trials investigating the effectiveness of probiotics compared to standard treatments in the induction of remission of active ulcerative colitis Two authors independently assessed trial quality and extracted data for analysis. Data were analysed using RevMan 4.2.7. A formal meta-analysis was not preformed due to differences in probiotics, outcomes and trial methodology. None of the included studies reported any statistically significant differences in remission or clinical improvement rates between probiotic and placebo or active comparator groups. Conventional therapy combined with a probiotic does not improve overall remission rates in patients with mild to moderate ulcerative colitis. However, there is limited evidence that probiotics added to standard therapy may provide modest benefits in terms of reduction of disease activity in patients with mild to moderately severe ulcerative colitis. Whether probiotics are as effective in patients with severe and more extensive disease and whether they can be used as an alternative to existing therapies is unknown. Further well designed, larger randomised controlled trials are needed to determine whether probiotics can be used as an alternative to current treatment modalities.

Rising rates of labor induction: present concerns and future strategies.

PubMed

Rayburn, William F; Zhang, Jun

2002-07-01

The rate of labor induction nationwide increased gradually from 9.5% to 19.4% between 1990 and 1998. Reasons for this doubling of inductions relate to widespread availability of cervical ripening agents, pressure from patients, conveniences to physicians, and litigious constraints. The increase in medically indicated inductions was slower than the overall increase, suggesting that induction for marginal or elective reasons has risen more rapidly. Data to support or refute the benefits of marginal or elective inductions are limited. Many trials of inductions for marginal indications are either nonexistent or retrospective with small sample sizes, thereby limiting definitive conclusions. Until prospective clinical trials can better validate reasons for the liberal use of labor induction, it would seem prudent to maintain a cautious approach, especially among nulliparous women. Strategies are proposed for developing evidence-based guidelines to reduce the presumed increase in health care costs, risk of cesarean delivery for nulliparas, and overscheduling in labor and delivery.

Can oral 5-aminosalicylic acid be administered once daily in the treatment of mild-to-moderate ulcerative colitis? A meta-analysis of randomized-controlled trials.

PubMed

Zhu, Ying; Tang, Ren-Kuan; Zhao, Peng; Zhu, Shi-sheng; Li, Yong-guo; Li, Jian-bo

2012-05-01

Several trials have demonstrated that oral delayed-release mesalamine might be administered once daily. We aimed to conduct a meta-analysis to investigate this. A comprehensive and multiple-source literature search was carried out. Only randomized-controlled trials (RCTs) were investigated by comparing a once daily-dosing regime with a divided (twice or thrice daily)-dosing regime of oral delayed-release mesalamine formulations for induction or maintenance of remission in patients with mild-to-moderate ulcerative colitis. The quality of RCTs was assessed using the Jadad scores. Meta-analysis of pooled odds ratios was carried out using Review Manager 5.1. Nine RCTs were finally included. With regard to meta-analyses for induction trials, there were no significant differences for all comparisons between the once daily and the divided groups, including maintenance of just clinical remission (P=0.52) and just endoscopic remission (P=0.23), maintenance of combined clinical and endoscopic remission (P=0.78), and the overall incidence of adverse events (P=0.61). With regard to meta-analyses for maintenance trials, there were also no significant differences for all comparisons between once daily and divided groups, including maintenance of just clinical remission (P=0.73) and just endoscopic remission (P=0.43), maintenance of combined clinical and endoscopic remission (P=0.43), the overall incidence of adverse events (P=0.12) as well as compliance with the prescribed medication (P=0.34). The present work showed that oral delayed-release mesalazine administered as a single or a divided dose demonstrated a good safety profile, which was well tolerated and effective as either maintenance or induction treatment. High clinical and/or endoscopic remission rates can be achieved with once-daily dosing.

Comparative effectiveness of immunosuppressants and biologics for inducing and maintaining remission in Crohn's disease: a network meta-analysis.

PubMed

Hazlewood, Glen S; Rezaie, Ali; Borman, Meredith; Panaccione, Remo; Ghosh, Subrata; Seow, Cynthia H; Kuenzig, Ellen; Tomlinson, George; Siegel, Corey A; Melmed, Gil Y; Kaplan, Gilaad G

2015-02-01

There is controversy regarding the best treatment for patients with Crohn's disease because of the lack of direct comparative trials. We compared therapies for induction and maintenance of remission in patients with Crohn's disease, based on direct and indirect evidence. We performed systematic reviews of MEDLINE, EMBASE, and Cochrane Central databases, through June 2014. We identified randomized controlled trials (N = 39) comparing methotrexate, azathioprine/6-mercaptopurine, infliximab, adalimumab, certolizumab, vedolizumab, or combined therapies with placebo or an active agent for induction and maintenance of remission in adult patients with Crohn's disease. Pairwise treatment effects were estimated through a Bayesian random-effects network meta-analysis and reported as odds ratios (OR) with a 95% credible interval (CrI). Infliximab, the combination of infliximab and azathioprine (infliximab + azathioprine), adalimumab, and vedolizumab were superior to placebo for induction of remission. In pair-wise comparisons of anti-tumor necrosis factor agents, infliximab + azathioprine (OR, 3.1; 95% CrI, 1.4-7.7) and adalimumab (OR, 2.1; 95% CrI, 1.0-4.6) were superior to certolizumab for induction of remission. All treatments were superior to placebo for maintaining remission, except for the combination of infliximab and methotrexate. Adalimumab, infliximab, and infliximab + azathioprine were superior to azathioprine/6-mercaptopurine: adalimumab (OR, 2.9; 95% CrI, 1.6-5.1), infliximab (OR, 1.6; 95% CrI, 1.0-2.5), infliximab + azathioprine (OR, 3.0; 95% CrI, 1.7-5.5) for maintenance of remission. Adalimumab and infliximab + azathioprine were superior to certolizumab: adalimumab (OR, 2.5; 95% CrI, 1.4-4.6) and infliximab + azathioprine (OR, 2.6; 95% CrI, 1.3-6.0). Adalimumab was superior to vedolizumab (OR, 2.4; 95% CrI, 1.2-4.6). Based on a network meta-analysis, adalimumab and infliximab + azathioprine are the most effective therapies for induction and maintenance of remission of Crohn's disease. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Effects of conventional vs high-dose rocuronium on the QTc interval during anesthesia induction and intubation in patients undergoing coronary artery surgery: a randomized, double-blind, parallel trial

PubMed Central

Öztürk, T.; Ağdanlı, D.; Bayturan, Ö.; Çıkrıkcı, C.; Keleş, G.T.

2015-01-01

Myocardial ischemia, as well as the induction agents used in anesthesia, may cause corrected QT interval (QTc) prolongation. The objective of this randomized, double-blind trial was to determine the effects of high- vs conventional-dose bolus rocuronium on QTc duration and the incidence of dysrhythmias following anesthesia induction and intubation. Fifty patients about to undergo coronary artery surgery were randomly allocated to receive conventional-dose (0.6 mg/kg, group C, n=25) or high-dose (1.2 mg/kg, group H, n=25) rocuronium after induction with etomidate and fentanyl. QTc, heart rate, and mean arterial pressure were recorded before induction (T0), after induction (T1), after rocuronium (just before laryngoscopy; T2), 2 min after intubation (T3), and 5 min after intubation (T4). The occurrence of dysrhythmias was recorded. In both groups, QTc was significantly longer at T3 than at baseline [475 vs 429 ms in group C (P=0.001), and 459 vs 434 ms in group H (P=0.005)]. The incidence of dysrhythmias in group C (28%) and in group H (24%) was similar. The QTc after high-dose rocuronium was not significantly longer than after conventional-dose rocuronium in patients about to undergo coronary artery surgery who were induced with etomidate and fentanyl. In both groups, compared with baseline, QTc was most prolonged at 2 min after intubation, suggesting that QTc prolongation may be due to the nociceptive stimulus of intubation. PMID:25714880

Comparative study of titrated oral misoprostol solution and vaginal dinoprostone for labor induction at term pregnancy.

PubMed

Wang, Xiu; Yang, Aijun; Ma, Qingyong; Li, Xuelan; Qin, Li; He, Tongqiang

2016-09-01

To evaluate effectiveness and safety of titrated oral misoprostol solution (OMS) in comparison with vaginal dinoprostone for cervix ripening and labor induction in term pregnant women. A multicenter randomized controlled trial of women with term singleton pregnancy with indications for labor induction; 481 participants were allocated to receive titrated OMS with different doses by hourly administration according to the procedure or insert vaginal dinoprostone for cervix ripening and labor induction to compare maternal outcomes including indication of labor induction, mode of outcome of delivery, maternal morbidity, and neonatal outcomes between two groups for evaluating the efficacy and safety of titrated oral misoprostol induction. Proportion of delivery within 12 h of titrated oral misoprostol is significantly less than vaginal dinoprostone (p = 0.03), but no difference of total vaginal delivery rate (p = 0.93); the mean time of first treatment to vaginal delivery was longer in OMS group (21.3 ± 14.5 h) compared with the vaginal dinoprostone group (15.7 ± 9.6 h). Although the proportion of cesarean section between the two groups showed no statistically significant difference, OMS group showed significantly lower frequency of uterine hyperstimulation, hypertonus, partus precipitatus and non-reassuring fetal heart rate than dinoprostone group. Neonatal outcomes were similar evaluating from Apgar score and NICU admission. Our study also showed that labor induction of women with cervix Bishop score ≤3 needed increased dosage of misoprostol solution. Titrated OMS is as effective as vaginal dinoprostone in labor induction for term pregnant women, with safer effect for its lower rate of adverse effect for women.

Budesonide for induction of remission in Crohn's disease.

PubMed

Rezaie, Ali; Kuenzig, M Ellen; Benchimol, Eric I; Griffiths, Anne Marie; Otley, Anthony R; Steinhart, A Hillary; Kaplan, Gilaad G; Seow, Cynthia H

2015-06-03

Corticosteroids are commonly used for the induction of remission in Crohn's disease. However, traditional corticosteroids can cause significant adverse events. Budesonide is an alternative glucocorticoid with limited systemic bioavailability. The primary objective was to evaluate the efficacy and safety of oral budesonide for the induction of remission in Crohn's disease. The following electronic databases were searched up to June 2014: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane IBD/FBD Group Specialised Trial Register, and ClinicalTrials.gov. Reference lists of articles, as well as conference proceedings were manually searched. Randomised controlled trials comparing budesonide to a placebo or active comparator were considered for inclusion. Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality. Methodological quality was assessed using the Cochrane risk of bias tool The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. Meta-analysis was performed using RevMan 5.3.5 software. The primary outcome was induction of remission (defined by a Crohn's disease activity index (CDAI) < 150) by week 8 to 16 of treatment. Secondary outcomes included: time to remission, mean change in CDAI, clinical, histological or endoscopic improvement, improvement in quality of life, adverse events and early withdrawal. We calculated the relative risk (RR) and corresponding 95% confidence intervals (CIs) for each dichotomous outcome and the mean difference and corresponding 95% CI for each continuous outcome. Data were analyzed on an intention-to-treat basis. A random-effects model was used for the pooled analyses. The overall quality of the evidence supporting the primary outcomes and selected secondary outcomes was evaluated using the GRADE criteria. Fourteen studies (1805 patients) were included: Nine (779 patients) compared budesonide to conventional corticosteroids, three (535 patients) were placebo-controlled, and two (491 patients) compared budesonide to mesalamine. Ten studies were judged to be at low risk of bias. Three studies were judged to be at high risk of bias due to open label design. One study was judged to be at high risk of bias due to selective reporting. After eight weeks of treatment, 9 mg budesonide was significantly more effective than placebo for induction of clinical remission. Forty-seven per cent (115/246) of budesonide patients achieved remission at 8 weeks compared to 22% (29/133) of placebo patients (RR 1.93, 95% CI 1.37 to 2.73; 3 studies, 379 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to sparse data (144 events). Budesonide was significantly less effective than conventional steroids for induction of remission at eight weeks. Fifty-two per cent of budesonide patients achieved remission at week 8 compared to 61% of patients who received conventional steroids (RR 0.85, 95% CI 0.75 to 0.97; 8 studies, 750 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to risk of bias. Budesonide was significantly less effective than conventional steroids among patients with severe disease (CDAI > 300) (RR 0.52, 95% CI 0.28 to 0.95). Studies comparing budesonide to mesalamine were not pooled due to heterogeneity (I(2) = 81%). One study (n = 182) found budesonide to be superior to mesalamine for induction of remission at 8 weeks. Sixty-eight per cent (63/93) of budesonide patients were in remission at 8 weeks compared to 42% (37/89) of mesalamine patients (RR 1.63, 95% CI 1.23 to 2.16). The other study found no statistically significant difference in remission rates at eight weeks. Sixty-nine per cent (107/154) of budesonide patients were in remission at 8 weeks compared to 62% (132/242) of mesalamine patients (RR 1.12, 95% CI 0.95 to 1.32). Fewer adverse events occurred in those treated with budesonide compared to conventional steroids (RR 0.64, 95% CI 0.54 to 0.76) and budesonide was better than conventional steroids in preserving adrenal function (RR for abnormal ACTH test 0.65, 95% CI 0.55 to 0.78). Budesonide is more effective than placebo for induction of remission in Crohn's disease. Although short-term efficacy with budesonide is less than with conventional steroids, particularly in those with severe disease or more extensive colonic involvement, the likelihood of adverse events and adrenal suppression with budesonide is lower. The current evidence does not allow for a firm conclusion on the relative efficacy of budesonide compared to 5-ASA products.

Long-term results of children with acute myeloid leukemia: a report of three consecutive Phase III trials by the Children's Cancer Group: CCG 251, CCG 213 and CCG 2891.

PubMed

Smith, F O; Alonzo, T A; Gerbing, R B; Woods, W G; Arceci, R J

2005-12-01

The Children's Cancer Group (CCG) conducted three Phase III prospective clinical trials for children with de novo acute myeloid leukemia between the years 1979 and 1995. A total of 1903 eligible children ages birth to 21 years of age were enrolled on CCG 251 (n=485), CCG 213 (n=532) and CCG 2891 (n=886). Follow-up is ongoing, with medians of 7.9, 10.9 and 8.6 years, respectively. These three clinical trials developed dose- and time-intensive induction regimens based upon high-dose cytarabine and daunomycin and randomly assigned patients to allogeneic bone marrow transplantation in first remission if an HLA-matched related donor was identified. Despite dose- and time-intensive induction regimens, remission induction rates remained relatively stable at 77-78%. However, overall survival, event-free survival and disease-free survival (DFS) increased for patients receiving intensive-timing induction therapy in comparison to patients who received standard-timing induction, regardless of the type of postremission therapy. Outcomes were best for patients receiving intensive-timing induction followed by matched related donor allogeneic transplantation with DFS of 65+/-9% at 6 years. These three clinical trials have established a strong foundation for the development of future studies focusing on further risk group stratification and the development of novel, molecularly-targeted therapies.

Rapid COJEC Induction Therapy for High-risk Neuroblastoma Patients - Cochrane Review.

PubMed

Peinemann, F; van Dalen, E C; Berthold, F

2016-04-01

Neuroblastoma is a rare malignant disease and patients with high-risk neuroblastoma have a poor prognosis. Rapid COJEC induction chemotherapy means (almost) the same total doses given within a shorter time period. In theory, rapid COJEC could reduce the risk of drug resistance and it has been considered as a potential candidate for improving the outcome. The objective was to evaluate effects of rapid COJEC compared to standard induction chemotherapy in patients with high-risk neuroblastoma. We searched the databases CENTRAL, MEDLINE, and EMBASE from inception to 11 November 2014 and included randomized controlled trials. We identified one relevant randomized controlled trial with 130 participants receiving rapid COJEC and 132 participants receiving standard OPEC/COJEC induction chemotherapy. There was no statistically significant difference between the treatment groups in complete response (risk ratio 0.99, 95% confidence interval 0.71 to 1.38, P=0.94) and treatment-related mortality (risk ratio 1.21, 95% confidence interval 0.33 to 4.39, P=0.77). A statistically significant difference in favor of the standard treatment arm was identified for the following early toxicities: febrile neutropenia, septicemia, and renal toxicity. The differences in complete response and treatment-related mortality between treatment alternatives were not statistically significantly different. Based on the currently available evidence, we are uncertain about the effects of rapid COJEC induction chemotherapy in patients with high-risk neuroblastoma. © Georg Thieme Verlag KG Stuttgart · New York.

Comparison of induction of labor methods for unfavorable cervices in trial of labor after cesarean delivery.

PubMed

Shah, Utsavi; Bellows, Patricia; Drexler, Kathleen; Hawley, Lauren; Davidson, Christina; Sangi-Haghpeykar, Haleh; Gandhi, Manisha

2017-05-01

To compare induction of labor methods in patients attempting a trial of labor after cesarean (TOLAC) with an unfavorable cervix. This is a retrospective cohort study from patients attempting TOLAC from 2009 to 2013. Patients with a simplified Bishop score of three or less where labor was initiated with either a Cook balloon or oxytocin were included. Our primary outcome was mode of delivery. Our secondary outcomes included duration of labor and multiple maternal and neonatal morbidities. Two-hundred and fourteen women met inclusion criteria: 150 received oxytocin and 64 had the Cook balloon placed. The vaginal birth after cesarean delivery rate was significantly higher in the oxytocin group at 70.7% versus 50.0% in the Cook balloon group (p = 0.004). In the multivariable analysis, odds for cesarean delivery were two times higher with the Cook balloon than with oxytocin (Adjusted OR = 2.09, 95% CI = 1.05-4.18, p = 0.036). The duration of labor was longer with the Cook balloon versus oxytocin (21.9 versus 16.3 hours, p = 0.0002). There were no significant differences in maternal and neonatal health outcomes. Oxytocin induction of labor was associated with a higher rate of vaginal delivery and a shorter duration of labor compared to the Cook balloon in women undergoing TOLAC with an unfavorable cervix.

Rationale and design of the German-Speaking Myeloma Multicenter Group (GMMG) trial ReLApsE: a randomized, open, multicenter phase III trial of lenalidomide/dexamethasone versus lenalidomide/dexamethasone plus subsequent autologous stem cell transplantation and lenalidomide maintenance in patients with relapsed multiple myeloma.

PubMed

Baertsch, Marc-Andrea; Schlenzka, Jana; Mai, Elias K; Merz, Maximilian; Hillengaß, Jens; Raab, Marc S; Hose, Dirk; Wuchter, Patrick; Ho, Anthony D; Jauch, Anna; Hielscher, Thomas; Kunz, Christina; Luntz, Steffen; Klein, Stefan; Schmidt-Wolf, Ingo G H; Goerner, Martin; Schmidt-Hieber, Martin; Reimer, Peter; Graeven, Ullrich; Fenk, Roland; Salwender, Hans; Scheid, Christof; Nogai, Axel; Haenel, Mathias; Lindemann, Hans W; Martin, Hans; Noppeney, Richard; Weisel, Katja; Goldschmidt, Hartmut

2016-04-25

Despite novel therapeutic agents, most multiple myeloma (MM) patients eventually relapse. Two large phase III trials have shown significantly improved response rates (RR) of lenalidomide/dexamethasone compared with placebo/dexamethasone in relapsed MM (RMM) patients. These results have led to the approval of lenalidomide for RMM patients and lenalidomide/dexamethasone has since become a widely accepted second-line treatment. Furthermore, in RMM patients consolidation with high-dose chemotherapy plus autologous stem cell transplantation has been shown to significantly increase progression free survival (PFS) as compared to cyclophosphamide in a phase III trial. The randomized prospective ReLApsE trial is designed to evaluate PFS after lenalidomide/dexamethasone induction, high-dose chemotherapy consolidation plus autologous stem cell transplantation and lenalidomide maintenance compared with the well-established lenalidomide/dexamethasone regimen in RMM patients. ReLApsE is a randomized, open, multicenter phase III trial in a planned study population of 282 RMM patients. All patients receive three lenalidomide/dexamethasone cycles and--in absence of available stem cells from earlier harvesting--undergo peripheral blood stem cell mobilization and harvesting. Subsequently, patients in arm A continue on consecutive lenalidomide/dexamethasone cycles, patients in arm B undergo high dose chemotherapy plus autologous stem cell transplantation followed by lenalidomide maintenance until discontinuation criteria are met. Therapeutic response is evaluated after the 3(rd) (arm A + B) and the 5(th) lenalidomide/dexamethasone cycle (arm A) or 2 months after autologous stem cell transplantation (arm B) and every 3 months thereafter (arm A + B). After finishing the study treatment, patients are followed up for survival and subsequent myeloma therapies. The expected trial duration is 6.25 years from first patient in to last patient out. The primary endpoint is PFS, secondary endpoints include overall survival (OS), RR, time to best response and the influence of early versus late salvage high dose chemotherapy plus autologous stem cell transplantation on OS. This phase III trial is designed to evaluate whether high dose chemotherapy plus autologous stem cell transplantation and lenalidomide maintenance after lenalidomide/dexamethasone induction improves PFS compared with the well-established continued lenalidomide/dexamethasone regimen in RMM patients. ISRCTN16345835 (date of registration 2010-08-24).

Safety Profile of Biologic Drugs in the Therapy of Ulcerative Colitis: A Systematic Review and Network Meta-Analysis.

PubMed

Moćko, Paweł; Kawalec, Paweł; Pilc, Andrzej

2016-08-01

We compared the safety profile of biologic drugs in patients with moderately to severely active ulcerative colitis (UC). A systematic literature search was performed using Medline (PubMed), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases through February 9, 2016. We included randomized controlled trials (RCTs) that compared the safety of biologic drugs (infliximab, adalimumab, golimumab, and vedolizumab) with one another or with placebo in patients with UC. Two reviewers independently conducted the search and selection of studies and rated the risk of bias in each trial. The network meta-analysis (NMA) was conducted for an induction phase (6-8 weeks) and maintenance phase (52-54 weeks) with a Bayesian hierarchical random effects model in Aggregate Data Drug Information System (ADDIS) software. The PROSPERO registration number was CRD42016032607. Seven RCTs were included in the systematic review with NMA. In the case of the induction phase, the NMA could be conducted for the assessment of the relative safety profile of adalimumab, golimumab, and vedolizumab, and in the case of the maintenance phase of infliximab, adalimumab, golimumab, and vedolizumab. The methodological quality of the included RCTs was evaluated as low risk of bias, but high risk of bias in the case of attrition bias (incomplete outcome data) according to the Cochrane criteria. No significant differences were found in the rate of adverse events in patients treated with the reviewed biologics. Vedolizumab was most likely to have the most favorable safety profile in the induction phase as was infliximab for the maintenance phase. The assessment of the relative safety profile revealed no significant differences between the biologic drugs. Further studies are needed to confirm our findings including head-to-head comparisons between the analyzed biologics. © 2016 Pharmacotherapy Publications, Inc.

Systematic review: elective induction of labor versus expectant management of pregnancy.

PubMed

Caughey, Aaron B; Sundaram, Vandana; Kaimal, Anjali J; Gienger, Allison; Cheng, Yvonne W; McDonald, Kathryn M; Shaffer, Brian L; Owens, Douglas K; Bravata, Dena M

2009-08-18

The rates of induction of labor and elective induction of labor are increasing. Whether elective induction of labor improves outcomes or simply leads to greater complications and health care costs is commonly debated in the literature. To compare the benefits and harms of elective induction of labor and expectant management of pregnancy. MEDLINE (through February 2009), Web of Science, CINAHL, Cochrane Central Register of Controlled Trials (through March 2009), bibliographies of included studies, and previous systematic reviews. Experimental and observational studies of elective induction of labor reported in English. Two authors abstracted study design; patient characteristics; quality criteria; and outcomes, including cesarean delivery and maternal and neonatal morbidity. Of 6117 potentially relevant articles, 36 met inclusion criteria: 11 randomized, controlled trials (RCTs) and 25 observational studies. Overall, expectant management of pregnancy was associated with a higher odds ratio (OR) of cesarean delivery than was elective induction of labor (OR, 1.22 [95% CI, 1.07 to 1.39]; absolute risk difference, 1.9 percentage points [CI, 0.2 to 3.7 percentage points]) in 9 RCTs. Women at or beyond 41 completed weeks of gestation who were managed expectantly had a higher risk for cesarean delivery (OR, 1.21 [CI, 1.01 to 1.46]), but this difference was not statistically significant in women at less than 41 completed weeks of gestation (OR, 1.73 [CI, 0.67 to 4.5]). Women who were expectantly managed were more likely to have meconium-stained amniotic fluid than those who were electively induced (OR, 2.04 [CI, 1.34 to 3.09]). There were no recent RCTs of elective induction of labor at less than 41 weeks of gestation. The 2 studies conducted at less than 41 weeks of gestation were of poor quality and were not generalizable to current practice. RCTs suggest that elective induction of labor at 41 weeks of gestation and beyond is associated with a decreased risk for cesarean delivery and meconium-stained amniotic fluid. There are concerns about the translation of these findings into actual practice; thus, future studies should examine elective induction of labor in settings where most obstetric care is provided.

Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks' gestation (HYPITAT): a multicentre, open-label randomised controlled trial.

PubMed

Koopmans, Corine M; Bijlenga, Denise; Groen, Henk; Vijgen, Sylvia M C; Aarnoudse, Jan G; Bekedam, Dick J; van den Berg, Paul P; de Boer, Karin; Burggraaff, Jan M; Bloemenkamp, Kitty W M; Drogtrop, Addy P; Franx, Arie; de Groot, Christianne J M; Huisjes, Anjoke J M; Kwee, Anneke; van Loon, Aren J; Lub, Annemiek; Papatsonis, Dimitri N M; van der Post, Joris A M; Roumen, Frans J M E; Scheepers, Hubertina C J; Willekes, Christine; Mol, Ben W J; van Pampus, Maria G

2009-09-19

Robust evidence to direct management of pregnant women with mild hypertensive disease at term is scarce. We investigated whether induction of labour in women with a singleton pregnancy complicated by gestational hypertension or mild pre-eclampsia reduces severe maternal morbidity. We undertook a multicentre, parallel, open-label randomised controlled trial in six academic and 32 non-academic hospitals in the Netherlands between October, 2005, and March, 2008. We enrolled patients with a singleton pregnancy at 36-41 weeks' gestation, and who had gestational hypertension or mild pre-eclampsia. Participants were randomly allocated in a 1:1 ratio by block randomisation with a web-based application system to receive either induction of labour or expectant monitoring. Masking of intervention allocation was not possible. The primary outcome was a composite measure of poor maternal outcome--maternal mortality, maternal morbidity (eclampsia, HELLP syndrome, pulmonary oedema, thromboembolic disease, and placental abruption), progression to severe hypertension or proteinuria, and major post-partum haemorrhage (>1000 mL blood loss). Analysis was by intention to treat and treatment effect is presented as relative risk. This study is registered, number ISRCTN08132825. 756 patients were allocated to receive induction of labour (n=377 patients) or expectant monitoring (n=379). 397 patients refused randomisation but authorised use of their medical records. Of women who were randomised, 117 (31%) allocated to induction of labour developed poor maternal outcome compared with 166 (44%) allocated to expectant monitoring (relative risk 0.71, 95% CI 0.59-0.86, p<0.0001). No cases of maternal or neonatal death or eclampsia were recorded. Induction of labour is associated with improved maternal outcome and should be advised for women with mild hypertensive disease beyond 37 weeks' gestation. ZonMw.

[Comparative study between fast and slow induction of propofol given by target-controlled infusion: expected propofol concentration at the effect site. Randomized controlled trial].

PubMed

Simoni, Ricardo Francisco; Miziara, Luiz Eduardo de Paula Gomes; Esteves, Luis Otávio; Silva, Diógenes de Oliveira; Ribeiro, Cristina Alves; Smith, Mariana Oki; Paula, Leonardo Ferreira de; Cangiani, Luis Henrique

2015-01-01

studies have shown that rate of propofol infusion may influence the predicted propofol concentration at the effect site (Es). The aim of this study was to evaluate the Es predicted by the Marsh pharmacokinetic model (ke0 0.26min(-1)) in loss of consciousness during fast or slow induction. the study included 28 patients randomly divided into two equal groups. In slow induction group (S), target-controlled infusion (TCI) of propofol with plasma, Marsh pharmacokinetic model (ke0 0.26min(-1)) with target concentration (Tc) at 2.0-μg.mL(-1) were administered. When the predicted propofol concentration at the effect site (Es) reached half of Es value, Es was increased to previous Es + 1μg.mL(-1), successively, until loss of consciousness. In rapid induction group (R), patients were induced with TCI of propofol with plasma (6.0μg.ml(-1)) at Es, and waited until loss of consciousness. in rapid induction group, Tc for loss of consciousness was significantly lower compared to slow induction group (1.67±0.76 and 2.50±0.56μg.mL(-1), respectively, p=0.004). the predicted propofol concentration at the effect site for loss of consciousness is different for rapid induction and slow induction, even with the same pharmacokinetic model of propofol and the same balance constant between plasma and effect site. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Biological agents for moderately to severely active ulcerative colitis: a systematic review and network meta-analysis.

PubMed

Danese, Silvio; Fiorino, Gionata; Peyrin-Biroulet, Laurent; Lucenteforte, Ersilia; Virgili, Gianni; Moja, Lorenzo; Bonovas, Stefanos

2014-05-20

Biological agents are emerging treatment options for the management of ulcerative colitis (UC). To assess the comparative efficacy and harm of biological agents in adult patients with moderately to severely active UC who are naive to biological agents. MEDLINE, EMBASE, and Cochrane Library from inception through December 2013, without language restrictions, and ClinicalTrials.gov, European Medicines Agency, and U.S. Food and Drug Administration Web sites. Randomized, placebo-controlled or head-to-head trials assessing biological agents as induction or maintenance therapy for moderately to severely active UC. Two reviewers independently abstracted study data and outcomes and rated each trial's risk of bias. There were no head-to-head trials. There were 7 double-blind, placebo-controlled trials that were rated as low risk of bias and showed that all biological agents (adalimumab, golimumab, infliximab, and vedolizumab) resulted in more clinical responses, clinical remissions, and mucosal healings than placebo for induction therapy. The results of network meta-analysis suggested that infliximab is more effective to induce clinical response (odds ratio, 2.36 [95% credible interval, 1.22 to 4.63]) and mucosal healing (odds ratio, 2.02 [95% credible interval, 1.13 to 3.59]) than adalimumab. No other indirect comparison reached statistical significance. For maintenance, 6 double-blind, placebo-controlled trials that were rated high risk of bias showed that all biological agents have greater clinical efficacy than placebo. The occurrence of adverse events was not different between biological agents and placebo. Few trials, no head-to-head comparisons, and inadequate follow-up in maintenance trials. Biological agents are effective treatments for UC, but head-to-head trials are warranted to establish the best therapeutic option.

Using an electrocautery strategy or recombinant follicle stimulating hormone to induce ovulation in polycystic ovary syndrome: randomised controlled trial

PubMed Central

Bayram, Neriman; van Wely, Madelon; Kaaijk, Eugenie M; Bossuyt, Patrick M M; van der Veen, Fulco

2004-01-01

Objective To compare the effectiveness of an electrocautery strategy with ovulation induction using recombinant follicle stimulating hormone in patients with polycystic ovary syndrome. Design Randomised controlled trial. Setting Secondary and tertiary hospitals in the Netherlands. Participants 168 patients with clomiphene citrate resistant polycystic ovary syndrome: 83 were allocated electrocautery and 85 were allocated recombinant follicle stimulating hormone. Intervention Laparoscopic electrocautery of the ovaries followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted, or induction of ovulation with recombinant follicle stimulating hormone. Main outcome measure Ongoing pregnancy within 12 months. Results. The cumulative rate of ongoing pregnancy after recombinant follicle stimulating hormone was 67%. With only electrocautery it was 34%, which increased to 49% after clomiphene citrate was given. Subsequent recombinant follicle stimulating hormone increased the rate to 67% at 12 months (rate ratio 1.01, 95% confidence interval 0.81 to 1.24). No complications occurred from electrocautery with or without clomiphene citrate. Patients allocated to electrocautery had a significantly lower risk of multiple pregnancy (0.11, 0.01 to 0.86). Conclusion The ongoing pregnancy rate from ovulation induction with laparoscopic electrocautery followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted, or recombinant follicle stimulating hormone, seems equivalent to ovulation induction with recombinant follicle stimulating hormone, but the former procedure carries a lower risk of multiple pregnancy. PMID:14739186

Comparison of the potency of different propofol formulations: a randomized, double-blind trial using closed-loop administration.

PubMed

Le Guen, Morgan; Grassin-Delyle, Stanislas; Cornet, Camille; Genty, Antoine; Chazot, Thierry; Dardelle, Dominique; Liu, Ngai; Dreyfus, Jean-François; Mazoit, Jean-Xavier; Devillier, Philippe; Alvarez, Jean-Claude; Sessler, Daniel I; Fischler, Marc

2014-02-01

Several commercial formulations of propofol are available. The primary outcome of this study was the required dose of propofol alone or combined with lidocaine to achieve induction of general anesthesia. This multicenter, double-blinded trial randomized patients (American Society of Anesthesiologists physical status I-III) just before elective surgery with the use of a computer-generated list. Three different propofol 1% formulations-Diprivan (Astra-Zeneca, Cheshire, United Kingdom), Propoven (Fresenius-Kabi AG, Bad Homburg, Germany), and Lipuro (B-Braun, Melshungen AG, Germany)-were compared with either placebo (saline solution) or lidocaine 1% mixed to the propofol solution. Depth of anesthesia was automatically guided by bispectral index and by a computerized closed-loop system for induction, thus avoiding dosing bias. The authors recorded the total dose of propofol and duration of induction and the patient's discomfort through a behavioral scale (facial expression, verbal response, and arm withdrawal) ranging from 0 to 6. The authors further evaluated postoperative recall of pain using a Visual Analog Scale. Of the 227 patients enrolled, 217 were available for analysis. Demographic characteristics were similar in each group. Propoven required a higher dose for induction (2.2 ± 0.1 mg/kg) than Diprivan (1.8 ± 0.1 mg/kg) or Lipuro (1.7 ± 0.1 mg/kg; P = 0.02). However, induction doses were similar when propofol formulations were mixed with lidocaine. Patient discomfort during injection was significantly reduced with lidocaine for every formulation: Diprivan (0.5 ± 0.3 vs. 2.3 ± 0.3), Propoven (0.4 ± 0.3 vs. 2.4 ± 0.3), and Lipuro (1.1 ± 0.3 vs. 1.4 ± 0.3), all differences significant, with P < 0.0001. No adverse effect was reported. Plain propofol formulations are not equipotent, but comparable doses were required when lidocaine was concomitantly administered.

Use of labour induction and risk of cesarean delivery: a systematic review and meta-analysis

PubMed Central

Mishanina, Ekaterina; Rogozinska, Ewelina; Thatthi, Tej; Uddin-Khan, Rehan; Khan, Khalid S.; Meads, Catherine

2014-01-01

Background: Induction of labour is common, and cesarean delivery is regarded as its major complication. We conducted a systematic review and meta-analysis to investigate whether the risk of cesarean delivery is higher or lower following labour induction compared with expectant management. Methods: We searched 6 electronic databases for relevant articles published through April 2012 to identify randomized controlled trials (RCTs) in which labour induction was compared with placebo or expectant management among women with a viable singleton pregnancy. We assessed risk of bias and obtained data on rates of cesarean delivery. We used regression analysis techniques to explore the effect of patient characteristics, induction methods and study quality on risk of cesarean delivery. Results: We identified 157 eligible RCTs (n = 31 085). Overall, the risk of cesarean delivery was 12% lower with labour induction than with expectant management (pooled relative risk [RR] 0.88, 95% confidence interval [CI] 0.84–0.93; I2 = 0%). The effect was significant in term and post-term gestations but not in preterm gestations. Meta-regression analysis showed that initial cervical score, indication for induction and method of induction did not alter the main result. There was a reduced risk of fetal death (RR 0.50, 95% CI 0.25–0.99; I2 = 0%) and admission to a neonatal intensive care unit (RR 0.86, 95% CI 0.79–0.94), and no impact on maternal death (RR 1.00, 95% CI 0.10–9.57; I2 = 0%) with labour induction. Interpretation: The risk of cesarean delivery was lower among women whose labour was induced than among those managed expectantly in term and post-term gestations. There were benefits for the fetus and no increased risk of maternal death. PMID:24778358

Effect of airway clearance techniques on the efficacy of the sputum induction procedure.

PubMed

Elkins, M R; Lane, T; Goldberg, H; Pagliuso, J; Garske, L A; Hector, E; Marchetto, L; Alison, J A; Bye, P T P

2005-11-01

Sputum induction is used in the early identification of tuberculosis (TB) and pneumocystis infections of the lung. Although manual physiotherapy techniques to clear the airways are often incorporated in the sputum induction procedure, their efficacy in this setting is unknown. This randomised, crossover trial enrolled adults referred for sputum induction for suspected TB and pneumocystis infections of the lung. All participants underwent two sputum induction procedures, inhaling 3% saline via ultrasonic nebuliser. During one randomly allocated procedure, airway clearance techniques (chest wall percussion, vibration, huffing) were incorporated. In total, 59 participants completed the trial. The airway clearance techniques had no significant effect on how the test was tolerated, the volume expectorated or the quality of the sample obtained (assessed by the presence of alveolar macrophages). The techniques did not significantly affect how often the test identified a suspected organism, nor the sensitivity or specificity of sputum induction. In conclusion, the study was unable to demonstrate any effect of airway clearance techniques on the sputum induction procedure. The results provide some justification for not including airway clearance techniques as part of the sputum induction procedure.

Effectiveness, safety and feasibility of extended-release naltrexone for opioid dependence: a 9-month follow-up to a 3-month randomized trial.

PubMed

Solli, Kristin Klemmetsby; Latif, Zill-E-Huma; Opheim, Arild; Krajci, Peter; Sharma-Haase, Kamni; Benth, Jūratė Šaltytė; Tanum, Lars; Kunoe, Nikolaj

2018-05-28

This is a follow-up study of a previously published randomized clinical trial conducted in Norway that compared extended-release naltrexone (XR-NTX) to buprenorphine-naloxone (BP-NLX) over 3 months. At the conclusion of the trial, participants were offered their choice of study medication for an additional 9 months. While BP-NLX was available at no cost through opioid maintenance treatment programmes, XR-NTX was available only through study participation, accounting for why almost all participants chose XR-NTX in the follow-up. The aim of this follow-up study was to compare differences in outcome between adults with opioid dependence continuing XR-NTX and those inducted on XR-NTX for a 9-month period, on measures of effectiveness, safety and feasibility. In this prospective cohort study, participants were either continuing XR-NTX, changed from BP-NLX to XR-NTX or re-included into the study and inducted on XR-NTX treatment. Five urban, out-patient addiction clinics in Norway. Opioid-dependent adults continuing (n = 54) or inducted on (n = 63) XR-NTX. XR-NTX administrated as intramuscular injections (380 mg) every fourth week. Data on retention, use of heroin and other illicit substances, opioid craving, treatment satisfaction, addiction-related problems and adverse events were reported every fourth week. Nine-month follow-up completion rates were 51.9% among participants continuing XR-NTX in the follow-up and 47.6% among those inducted on XR-NTX. Opioid abstinence rates were, respectively, 53.7 and 44.4%. No significant group differences were found in use of heroin and other opioids. Opioid-dependent individuals who elect to switch from buprenorphine-naltrexone treatment after 3 months to extended-release naltrexone treatment for 9 months appear to experience similar treatment completion and abstinence rates and similar adverse event profiles to individuals who had been on extended-release naltrexone from the start of treatment. © 2018 Society for the Study of Addiction.

Systematic Review and Meta-analysis: Placebo Rates in Induction and Maintenance Trials of Ulcerative Colitis

PubMed Central

Zou, Guangyong; Parker, Claire E.; Macdonald, John K.; Mosli, Mahmoud H.; Khanna, Reena; Shackelton, Lisa M.; Vandervoort, Margaret K.; AlAmeel, Turki; Al Beshir, Mohammad; AlMadi, Majid; Al-Taweel, Talal; Atkinson, Nathan S. S.; Biswas, Sujata; Chapman, Thomas P.; Dulai, Parambir S.; Glaire, Mark A.; Hoekman, Daniel; Koutsoumpas, Andreas; Minas, Elizabeth; Samaan, Mark A.; Travis, Simon; D’Haens, Geert; Levesque, Barrett G.; Sandborn, William J.; Feagan, Brian G.

2016-01-01

Background and Aims: Minimisation of the placebo responses in randomised controlled trials [RCTs] is essential for efficient evaluation of new interventions. Placebo rates have been high in ulcerative colitis [UC] clinical trials, and factors influencing this are poorly understood. We quantify placebo response and remission rates in UC RCTs and identify trial design factors influencing them. Methods: MEDLINE, EMBASE, and the Cochrane Library were searched from inception through April 2014 for placebo-controlled trials in adult patients with UC of a biological agent, corticosteroid, immunosuppressant, or aminosalicylate. Data were independently doubly extracted. Quality was assessed using the Cochrane risk of bias tool. Results: In all, 51 trials [48 induction and 10 maintenance phases] were identified. Placebo response and remission rates were pooled according to random-effects models, and mixed-effects meta-regression models were used to evaluate effects of study-level characteristics on these rates. Pooled estimates of placebo remission and response rates for induction trials were 10% (95% confidence interval [CI] 7-13%) and 33% [95% CI 29-37%], respectively. Corresponding values for maintenance trials were 19% [95% CI 11-30%] and 22% [95% CI 17-28%]. Trials enrolling patients with more active disease confirmed by endoscopy [endoscopy subscore ≥ 2] were associated with lower placebo rates. Conversely, placebo rates increased with increasing trial duration and number of study visits. Conclusions: Objective assessment of greater disease activity at trial entry by endoscopy lowered placebo rates, whereas increasing trial duration and more interactions with healthcare providers increased placebo rates. These findings have important implications for design and conduct of clinical trials. PMID:26746169

Vedolizumab for induction and maintenance of remission in ulcerative colitis.

PubMed

Bickston, Stephen J; Behm, Brian W; Tsoulis, David J; Cheng, Jianfeng; MacDonald, John K; Khanna, Reena; Feagan, Brian G

2014-08-08

Cellular adhesion molecules play an important role in the pathogenesis of ulcerative colitis, making selective blockade of these molecules a promising therapeutic strategy. Vedolizumab, a recombinant humanized IgG1 monoclonal antibody, inhibits adhesion and migration of leukocytes into the gastrointestinal tract by binding the alpha4beta7 integrin. Animal studies have suggested that vedolizumab may be a useful therapy for ulcerative colitis. This updated systematic review summarizes the current evidence on the use of vedolizumab for induction and maintenance of remission in ulcerative colitis. The primary objectives were to determine the efficacy and safety of vedolizumab used for induction and maintenance of remission in ulcerative colitis. A computer-assisted search for relevant studies (inception to 15 June 2014) was performed using PubMed, MEDLINE, EMBASE and CENTRAL. References from published articles and conference proceedings were searched to identify additional citations. Randomized controlled trials comparing vedolizumab to placebo or a control therapy for induction or maintenance of remission in ulcerative colitis were included. Two authors independently extracted data and assessed the risk of bias for each trial. The primary outcomes were failure to induce clinical remission and relapse. Secondary outcomes included failure to induce a clinical response, failure to induce endoscopic remission, failure to induce an endoscopic response, quality of life, adverse events, serious adverse events and withdrawal due to adverse events. We calculated the relative risk (RR) and 95% confidence intervals (CI) for each outcome. Data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. Four studies (606 patients) were included. All of the studies were rated as having a low risk of bias. Pooled analyses revealed that vedolizumab was significantly superior to placebo for induction of remission, clinical response, and endoscopic remission and prevention of relapse. After 4 to 6 weeks of therapy 77% (293/382) of vedolizumab patients failed to enter clinical remission compared to 92% (205/224) of placebo patients (RR 0.86, 95% CI 0.80 to 0.91; 4 studies 606 patients). After 6 weeks of therapy 48% of vedolizumab patients failed to have a clinical response compared to 72% of placebo patients (RR 0.68, 95% CI 0.59 to 0.78; 3 studies 601 patients). After 4 to 6 weeks of therapy 68% of vedolizumab patients failed to enter endoscopic remission compared to 81% of placebo patients (RR 0.82, 95% CI 0.75 to 0.91; 3 studies, b583 patients). After 52 weeks of therapy, 54% of vedolizumab patients had a clinical relapse compared to 84% of placebo patients (RR 0.67, 95% CI 0.59 to 0.77; 1 study, 373 patients). One small study (28 patients) found no statistically significant difference in endoscopic response (RR 1.00, 95% CI 0.62 to 1.61). GRADE analyses indicated that the overall quality of the evidence for the primary outcomes was high for induction of remission and moderate for relapse (due to sparse data 246 events). There was no statistically significant difference between vedolizumab and placebo in terms of the risk of any adverse event (RR 0.99, 95% CI 0.93 to 1.07), or serious adverse events (RR 1.01, 95% CI 0.72 to 1.42). There was a statistically significant difference in withdrawals due to adverse events. Six per cent of vedolizumab patients withdrew due to an adverse event compared to 11% of placebo patients (RR 0.55, 95% CI 0.35 to 0.87; 2 studies, 941 patients). Adverse events commonly reported across the studies included: worsening ulcerative colitis, headache, nasopharyngitis, upper respiratory tract infection, nausea, and abdominal pain. Moderate to high quality data from four studies shows that vedolizumab is superior to placebo for induction of clinical remission and response and endoscopic remission in patients with moderate to severely active ulcerative colitis and prevention of relapse in patients with quiescent ulcerative colitis. Moderate quality data from one study suggests that vedolizumab is superior to placebo for prevention of relapse in patients with quiescent ulcerative colitis. Adverse events appear to be similar to placebo. Future trials are needed to define the optimal dose, frequency of administration and long-term efficacy and safety of vedolizumab used for induction and maintenance therapy of ulcerative colitis. Vedolizumab should be compared to other currently approved therapies for ulcerative colitis in these trials.

Immobilization of swift foxes with ketamine hydrochloride-xylazine hydrochloride

USGS Publications Warehouse

Telesco, R.L.; Sovada, Marsha A.

2002-01-01

There is an increasing need to develop field immobilization techniques that allow researchers to handle safely swift foxes (Vulpes velox) with minimal risk of stress or injury. We immobilized captive swift foxes to determine the safety and effectiveness of ketamine hydrochloride and xylazine hydrochloride at different dosages. We attempted to determine appropriate dosages to immobilize swift foxes for an adequate field-handling period based on three anesthesia intervals (induction period, immobilization period, and recovery period) and physiologic responses (rectal temperature, respiration rate, and heart rate). Between October 1998–July 1999, we conducted four trials, evaluating three different dosage ratios of ketamine and xylazine (2.27:1.2, 5.68:1.2, and 11.4:1.2 mg/kg ketamine:mg/kg xylazine, respectively), followed by a fourth trial with a higher dosage at the median ratio (11.4 mg/kg ketamine:2.4 mg/kg xylazine). We found little difference in induction and recovery periods among trials 1–3, but immobilization time increased with increasing dosage (P<0.08). Both the immobilization period and recovery period increased in trial 4 compared with trials 1–3 (P≤0.03). There was a high variation in responses of individual foxes across trials, making it difficult to identify an appropriate dosage for field handling. Heart rate and respiration rates were depressed but all physiologic measures remained within normal parameters established for domestic canids. We recommend a dosage ratio of 10 mg/kg ketamine to 1 mg/kg xylazine to immobilize swift foxes for field handling.

Effects of induction docetaxel, platinum, and fluorouracil chemotherapy in patients with stage III or IVA/B nasopharyngeal cancer treated with concurrent chemoradiation therapy: Final results of 2 parallel phase 2 clinical trials.

PubMed

Kong, Lin; Zhang, Youwang; Hu, Chaosu; Guo, Ye; Lu, Jiade J

2017-06-15

The effects of docetaxel, platinum, and fluorouracil (TPF) induction chemotherapy plus concurrent chemoradiotherapy (CCRT) on locoregionally advanced nasopharyngeal cancer (NPC) are unclear. This study examined the long-term outcomes of the addition of this regimen to CCRT for stage III and IVA/B NPC. Two parallel, single-arm phase 2 trials were performed synchronously to evaluate the efficacy and toxicity of TPF-based induction chemotherapy in patients with stage III or IVA/B NPC. The induction chemotherapy, which preceded standard intensity-modulated radiation therapy/platinum-based chemoradiation, consisted of 3 cycles of docetaxel (75 mg/m 2 on day 1), cisplatin (75 mg/m 2 on day 1), and a continuous infusion of fluorouracil (500 mg/m 2 /d on days 1-5) every 4 weeks. The primary endpoint for both trials was 5-year overall survival (OS). Between January 2007 and July 2010, 52 eligible patients with stage III NPC and 64 eligible patients with nonmetastatic stage IV NPC were accrued to the 2 trials. With a median follow-up of 67 months, the 5-year OS, progression-free survival, distant metastasis-free survival, and local progression-free survival (LPFS) rates were all improved in comparison with historical benchmarks for patients with stage III or IVA/IVB NPC. Multivariate analyses indicated that T and N classifications (T1/T2 vs T3/T4 and N3 vs N0-N2) were the only significant prognosticators for OS. The number of induction chemotherapy cycles was the only significant prognostic factor for predicting LPFS. TPF-based induction chemotherapy appears to significantly improve outcomes in comparison with historical data when it is administered before CCRT for locoregionally advanced NPC. A phase 3 trial is currently being performed to confirm this benefit. Cancer 2017;123:2258-2267. © 2017 American Cancer Society. © 2017 American Cancer Society.

Women's Experiences with and Preference for Induction of Labor with Oral Misoprostol or Foley Catheter at Term.

PubMed

Ten Eikelder, Mieke L G; van de Meent, Marieke M; Mast, Kelly; Rengerink, Katrien Oude; Jozwiak, Marta; de Graaf, Irene M; Scholtenhuis, Marloes A G Holswilder-Olde; Roumen, Frans J M E; Porath, Martina M; van Loon, Aren J; van den Akker, Eline S; Rijnders, Robbert J P; Feitsma, A Hanneke; Adriaanse, Albert H; Muller, Moira A; de Leeuw, Jan W; Visser, Harry; Woiski, Mallory D; Weerd, Sabina Rombout-de; van Unnik, Gijs A; Pernet, Paula J M; Versendaal, Hans; Mol, Ben W; Bloemenkamp, Kitty W M

2017-01-01

Objective  We assessed experience and preferences among term women undergoing induction of labor with oral misoprostol or Foley catheter. Study Design  In 18 of the 29 participating hospitals in the PROBAAT-II trial, women were asked to complete a questionnaire within 24 hours after delivery. We adapted a validated questionnaire about expectancy and experience of labor and asked women whether they would prefer the same method again in a future pregnancy. Results  The questionnaire was completed by 502 (72%) of 695 eligible women; 273 (54%) had been randomly allocated to oral misoprostol and 229 (46%) to Foley catheter. Experience of the duration of labor, pain during labor, general satisfaction with labor, and feelings of control and fear related to their expectation were comparable between both the groups. In the oral misoprostol group, 6% of the women would prefer the other method if induction is necessary in future pregnancy, versus 12% in the Foley catheter group (risk ratio: 0.70; 95% confidence interval: 0.55-0.90; p =  0.02). Conclusion  Women's experiences of labor after induction with oral misoprostol or Foley catheter are comparable. However, women in the Foley catheter group prefer more often to choose a different method for future inductions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Long-Acting Injectable Naltrexone Induction: A Randomized Trial of Outpatient Opioid Detoxification With Naltrexone Versus Buprenorphine.

PubMed

Sullivan, Maria; Bisaga, Adam; Pavlicova, Martina; Choi, C Jean; Mishlen, Kaitlyn; Carpenter, Kenneth M; Levin, Frances R; Dakwar, Elias; Mariani, John J; Nunes, Edward V

2017-05-01

At present there is no established optimal approach for transitioning opioid-dependent adults to extended-release injection naltrexone (XR-naltrexone) while preventing relapse. The authors conducted a trial examining the efficacy of two methods of outpatient opioid detoxification for induction to XR-naltrexone. Participants were 150 opioid-dependent adults randomly assigned 2:1 to one of two outpatient detoxification regimens, naltrexone-assisted detoxification or buprenorphine-assisted detoxification, followed by an injection of XR-naltrexone. Naltrexone-assisted detoxification lasted 7 days and included a single day of buprenorphine followed by ascending doses of oral naltrexone along with clonidine and other adjunctive medications. Buprenorphine-assisted detoxification included a 7-day buprenorphine taper followed by a week-long delay before administration of XR-naltrexone, consistent with official prescribing information for XR-naltrexone. Participants from both groups received behavioral therapy focused on medication adherence and a second dose of XR-naltrexone. Compared with participants in the buprenorphine-assisted detoxification condition, participants assigned to naltrexone-assisted detoxification were significantly more likely to be successfully inducted to XR-naltrexone (56.1% compared with 32.7%) and to receive the second injection at week 5 (50.0% compared with 26.9%). Both models adjusted for primary type of opioid use, route of opioid administration, and morphine equivalents at baseline. These results demonstrate the safety, efficacy, and tolerability of low-dose naltrexone, in conjunction with single-day buprenorphine dosing and adjunctive nonopioid medications, for initiating adults with opioid dependence to XR-naltrexone. This strategy offers a promising alternative to the high rates of attrition and relapse currently observed with agonist tapers in both inpatient and outpatient settings.

Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis

PubMed Central

Stone, John H.; Merkel, Peter A.; Spiera, Robert; Seo, Philip; Langford, Carol A.; Hoffman, Gary S.; Kallenberg, Cees G.M.; St. Clair, E. William; Turkiewicz, Anthony; Tchao, Nadia K.; Webber, Lisa; Ding, Linna; Sejismundo, Lourdes P.; Mieras, Kathleen; Weitzenkamp, David; Ikle, David; Seyfert-Margolis, Vicki; Mueller, Mark; Brunetta, Paul; Allen, Nancy B.; Fervenza, Fernando C.; Geetha, Duvuru; Keogh, Karina A.; Kissin, Eugene Y.; Monach, Paul A.; Peikert, Tobias; Stegeman, Coen; Ytterberg, Steven R.; Specks, Ulrich

2011-01-01

BACKGROUND Cyclophosphamide and glucocorticoids have been the cornerstone of remission-induction therapy for severe antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen. METHODS We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months. RESULTS Nine centers enrolled 197 ANCA-positive patients with either Wegener’s granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P = 0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events. CONCLUSIONS Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number, NCT00104299.) PMID:20647199

Once daily vs multiple daily mesalamine therapy for mild to moderate ulcerative colitis: a meta-analysis.

PubMed

Li, W; Zhang, Z-M; Jiang, X-L

2016-07-01

5-Aminosalicylic acid is the first-line drug for mild to moderate ulcerative colitis (UC). The most commonly used 5-aminosalicylic acid is mesalamine. Several systematic reviews have demonstrated that mesalamine is effective in inducing and maintaining remission. Efficacy, safety and adherence to once daily (OD) and multiple daily (MD) dosing of mesalamine for the induction and maintenance of remission in mild to moderate UC were systematically reviewed and compared. PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched from inception to November 2014. Only randomized controlled trials were considered eligible. STATA software (version 12.0) was used to calculate the pooled risk ratios with 95% confidence interval. Seventeen randomized studies containing 5439 patients were identified. No significant differences were noted in comparisons between OD and MD dosing for maintenance and induction of remission. No significant differences were noted in rates of medication adherence or adverse events between OD and MD dosing. With regard to mesalamine suppository, no significant differences were noted for comparisons between dosing regimens and adverse events for induction of remission. OD dose of mesalamine is as effective and safe as MD doses for the induction and maintenance treatment of mild to moderate UC. OD mesalamine given as a suppository can attain the same effect and safety as MD mesalamine in inducing remission of mild to moderate ulcerative colitis. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

Effects of D2 or combined D1/D2 receptor antagonism on the methamphetamine-induced one-trial and multi-trial behavioral sensitization of preweanling rats

PubMed Central

Mohd-Yusof, Alena; Veliz, Ana; Rudberg, Krista N.; Stone, Michelle J.; Gonzalez, Ashley E.; McDougall, Sanders A.

2015-01-01

Rationale There is suggestive evidence that the neural mechanisms mediating one-trial and multi-trial behavioral sensitization differ, especially when the effects of various classes of dopamine (DA) agonists are examined. Objective The purpose of the present study was to determine the role of the D2 receptor for the induction of one-trial and multi-trial methamphetamine sensitization in preweanling rats. Methods In a series of experiments, rats were injected with saline or raclopride (a selective D2 receptor antagonist), either alone or in combination with SCH23390 (a selective D1 receptor antagonist), 15 min prior to treatment with the indirect DA agonist methamphetamine. Acute control groups were given two injections of saline. This pretreatment regimen occurred on either postnatal days (PD) 13–16 (multi-trial) or PD 16 (one-trial). On PD 17, rats were challenged with methamphetamine and locomotor sensitization was determined. Results Blockade of D2 or D1/D2 receptors reduced or prevented, respectively, the induction of multi-trial methamphetamine sensitization in young rats, while the same manipulations had minimal effects on one-trial behavioral sensitization. Conclusions DA antagonist treatment differentially affected the methamphetamine-induced sensitized responding of preweanling rats depending on whether a one-trial or multi-trial procedure was used. The basis for this effect is uncertain, but there was some evidence that repeated DA antagonist treatment caused nonspecific changes that produced a weakened sensitized response. Importantly, DA antagonist treatment did not prevent the one-trial behavioral sensitization of preweanling rats. The latter result brings into question whether DA receptor stimulation is necessary for the induction of psychostimulant-induced behavioral sensitization during early ontogeny. PMID:26650612

Systematic Review and Meta-analysis: Placebo Rates in Induction and Maintenance Trials of Ulcerative Colitis.

PubMed

Jairath, Vipul; Zou, Guangyong; Parker, Claire E; Macdonald, John K; Mosli, Mahmoud H; Khanna, Reena; Shackelton, Lisa M; Vandervoort, Margaret K; AlAmeel, Turki; Al Beshir, Mohammad; AlMadi, Majid; Al-Taweel, Talal; Atkinson, Nathan S S; Biswas, Sujata; Chapman, Thomas P; Dulai, Parambir S; Glaire, Mark A; Hoekman, Daniel; Koutsoumpas, Andreas; Minas, Elizabeth; Samaan, Mark A; Travis, Simon; D'Haens, Geert; Levesque, Barrett G; Sandborn, William J; Feagan, Brian G

2016-05-01

Minimisation of the placebo responses in randomised controlled trials [RCTs] is essential for efficient evaluation of new interventions. Placebo rates have been high in ulcerative colitis [UC] clinical trials, and factors influencing this are poorly understood. We quantify placebo response and remission rates in UC RCTs and identify trial design factors influencing them. MEDLINE, EMBASE, and the Cochrane Library were searched from inception through April 2014 for placebo-controlled trials in adult patients with UC of a biological agent, corticosteroid, immunosuppressant, or aminosalicylate. Data were independently doubly extracted. Quality was assessed using the Cochrane risk of bias tool. In all, 51 trials [48 induction and 10 maintenance phases] were identified. Placebo response and remission rates were pooled according to random-effects models, and mixed-effects meta-regression models were used to evaluate effects of study-level characteristics on these rates. Pooled estimates of placebo remission and response rates for induction trials were 10% (95% confidence interval [CI] 7-13%) and 33% [95% CI 29-37%], respectively. Corresponding values for maintenance trials were 19% [95% CI 11-30%] and 22% [95% CI 17-28%]. Trials enrolling patients with more active disease confirmed by endoscopy [endoscopy subscore ≥ 2] were associated with lower placebo rates. Conversely, placebo rates increased with increasing trial duration and number of study visits. Objective assessment of greater disease activity at trial entry by endoscopy lowered placebo rates, whereas increasing trial duration and more interactions with healthcare providers increased placebo rates. These findings have important implications for design and conduct of clinical trials. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Further Improvement in Outcomes of Nasopharyngeal Carcinoma With Optimized Radiotherapy and Induction Plus Concomitant Chemotherapy: An Update of the Milan Experience

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

Palazzi, Mauro; Orlandi, Ester; Bossi, Paolo

2009-07-01

Purpose: To report the outcome of a consecutive series of patients with nonmetastatic nasopharyngeal carcinoma (NPC), focusing on the impact of treatment-related factors. Methods and Materials: Between 2000 and 2006, 87 patients with NPC were treated with either conventional (two- or three-dimensional) radiotherapy (RT) or with intensity-modulated RT (IMRT). Of these patients, 81 (93%) received either concomitant CHT (24%) or both induction and concomitant chemotherapy (CHT) (69%). Stage was III in 36% and IV in 39% of patients. Outcomes in this study population were compared with those in the previous series of 171 patients treated during 1990 to 1999. Results:more » With a median follow-up of 46 months, actuarial rates at 3 years were the following: local control, 96%; local-regional control, 93%; distant control (DC), 90%; disease-free survival (DFS), 82%; overall survival, 90%. In Stage III to IV patients, distant control at 3 years was 56% in patients treated with concomitant CHT only and 92% in patients treated with both induction and concomitant CHT (p = 0.014). At multivariate analysis, histology, N-stage, RT technique, and total RT dose had the strongest independent impact on DFS (p < 0.05). Induction CHT had a borderline effect on DC (p = 0.07). Most dosimetric statistics were improved in the group of patients treated with IMRT compared with conventional 3D technique. All outcome endpoints were substantially better in the study population compared with those in the previous series. Conclusions: Outcome of NPC has further improved in the study period compared with the previous decade, with a significant effect of RT technique optimization. The impact of induction CHT remains to be demonstrated in controlled trials.« less

Post-electroconvulsive therapy recovery and reorientation time with methohexital and ketamine: a randomized, longitudinal cross-over design trial

PubMed Central

Yen, Tony; Khafaja, Mohamad; Lam, Nicholas; Crumbacher, James; Schrader, Ronald; Rask, John; Billstrand, Mary; Rothfork, Jacob; Abbott, Christopher C.

2014-01-01

Objectives Methohexital, a barbiturate anesthetic commonly used for electroconvulsive therapy (ECT), possesses dose-dependent anticonvulsant properties, and its use can interfere with effective seizure therapy in patients with high seizure thresholds. Ketamine, a NMDA-antagonist with epileptogenic properties not broadly used for ECT inductions, is a commonly used induction agent for general anesthesia. Recent studies suggest that the use of ketamine is effective in allowing successful ECT treatment in patients with high seizure thresholds without an increase in side-effects. In this preliminary study, we directly compared the recovery and re-orientation times of subjects receiving ketamine and methohexital for ECTs. Methods Twenty patients were randomized in a cross-over design to receive methohexital and ketamine for ECT inductions in alternating fashion for six trials. Primary outcome measures were recovery time (voluntary movement, respiratory effort, blood pressure, consciousness, and O2 saturation) and re-orientation time. Secondary outcome measures were individual recovery variables, side-effect occurrence, and seizure duration. Results: Overall recovery time was not significantly different between the two treatment arms (F(1,17) = 0.72, P = 0.41). Re-orientation time was faster in the methohexital arm (F(1,17) = 9.23, P = 0.007). Conclusion Ketamine inductions resulted in higher number of side-effects, higher subject dropout rates, and a longer reorientation time with respect to methohexital inductions. No significant difference in post-anesthesia recovery time was found between the ketamine and methohexital arms. Intolerability to ketamine affected a significant proportion of subjects, and suggests that ketamine should remain as an alternative or adjunctive agent for patients with high seizure thresholds. PMID:24755722

Effect of etomidate versus thiopental on major depressive disorder in electroconvulsive therapy, a randomized double-blind controlled clinical trial.

PubMed

Abdollahi, Mohammad Hassan; Izadi, Amir; Hajiesmaeili, Mohammad Reza; Ghanizadeh, Ahmad; Dastjerdi, Ghasem; Hosseini, Habib Allah; Ghiamat, Mohammad Mehdi; Abbasi, Hamid Reza

2012-03-01

Although the therapeutic effect of electroconvulsive therapy (ECT) on major depressive disorder is widely investigated, there is a gap in literature regarding the possible effects of the medications used for induction of anesthesia in ECT. To the best of the authors' knowledge, this study is the first randomized double-blind clinical trial comparing the effect of etomidate and sodium thiopental on the depression symptoms in patients who have received ECT. The participants of this study are 60 adult patients with major depressive disorder who were referred for ECT. They were randomly allocated into 1 of the 2 groups. One group received etomidate, and the other group received sodium thiopental, as medication for induction of anesthesia. All the patients received bilateral ECT. The outcomes measures included the Beck Depression Inventory score, seizure duration, and recovery duration after induction of anesthesia. The sex ratio and mean age were not different between the 2 groups. Linear regression analysis showed that etomidate decreased the depression score more than did sodium thiopental. Seizure duration in all of the sessions in the etomidate group was significantly higher than that of sodium thiopental group. In conclusion, etomidate may improve major depressive disorder more than sodium thiopental in patients who are receiving ECT.

Long-term follow-up of the United Kingdom Medical Research Council protocols for childhood acute Lymphoblastic leukaemia, 1980–2001

PubMed Central

Mitchell, Christopher; Richards, Sue; Harrison, Christine J; Eden, Tim

2009-01-01

Between 1980 and 2001, the United Kingdom Medical Research Council Childhood Leukemia Working Party has conducted 4 clinical trial in acute lymphoblastic leukemia, which have recruited a total of 6516 patients. UKALL VIII examined the role of daunorubicin in induction chemotherapy, and UKALL X examined the role of post-induction intensification. Both resulted in major improvement in the outcomes. UKALL XI examined the efficacy of different methods of CNS-directed therapy and the effects of an additional intensification. ALL97, which was initially based on the UKALL X D template (two intensification phases), examined the role of different steroids in induction and different thiopurines through continuing chemotherapy. A reappraisal of results from UKALL XI compared to other cooperative group results led to a redesign in 1999, which subsequently resulted in a major improvement in outcomes. Additionally, ALL97 and 97/99 demonstrated a significant advantage for the use of dexamethasone rather than prednisolone; although the use of 6-thioguanine resulted in fewer relapses, this advantage was offset by an increased incidence of deaths in remission. Over the era encompassed by these four trials there has been a major improvement in both event-free and overall survival for children in the UK with ALL. PMID:20010621

Randomized controlled trial comparing laparoscopic ovarian diathermy with clomiphene citrate as a first-line method of ovulation induction in women with polycystic ovary syndrome.

PubMed

Amer, S A; Li, T C; Metwally, M; Emarh, M; Ledger, W L

2009-01-01

Laparoscopic ovarian diathermy (LOD) is currently accepted as a successful second-line treatment for ovulation induction (OI) in clomiphene citrate (CC)-resistant women with polycystic ovary syndrome (PCOS). The aim of this study was to test the hypothesis that LOD may be superior to CC as a first-line treatment. The study included 72 anovulatory women with PCOS who were randomized to LOD (n = 36) or CC (n = 36). Women who remained anovulatory after LOD were offered CC. Similarly, women receiving CC who failed to ovulate or conceive were offered LOD. Pregnancy rates were compared between the two groups using chi(2) and odds ratio with 95% confidence interval (OR, 95% CI). After randomization, six women conceived before starting treatment and another patient postponed treatment. The remaining 65 women received the treatment (33 underwent LOD and 32 received CC). After the primary treatment, more pregnancies (44%) occurred in women receiving CC than in those undergoing LOD (27%), although the difference did not reach statistical significance [P = 0.13, OR 2.1 (0.7 - 5.8)]. After adding the second treatment, the pregnancy rate was still higher, but to a less extent, in the CC group [63% versus 52%, P = 0.2, OR 1.6 (0.6 - 4.2)]. LOD is not superior to CC as a first-line method of OI in women with PCOS. The trial is registered with ClinicalTrials.gov with an identifier number NCT00220545.

Potential spawn induction and suppression agents in Caribbean Acropora cervicornis corals of the Florida Keys.

PubMed

Flint, Mark; Than, John T

2016-01-01

The enhanced ability to direct sexual reproduction may lead to improved restoration outcomes for Acropora cervicornis. Gravid fragments of A. cervicornis were maintained in a laboratory for two sequential trials in the seven days prior to natural spawning in the Florida Keys. Ten replicates of five chemicals known to affect spawning in various invertebrate taxa were tested. Hydrogen peroxide at 2 mM (70%) and L-5-hydroxytryptophan (5-HTP) at 5 (40%) and 20 µM (30%) induced spawning within 15.4 h, 38.8 h and 26.9 h of dosing at or above the rate of release of the control (30%) within 14.6 h. Serotonin acetate monohydrate at 1 µM (20%) and 10 µM (20%), naloxone hydrochloride dihydrate at 0.01 µM (10%) and potassium phosphate monobasic at 0.25 µM (0%) induced spawning at rates less than the control. Although the greatest number of fragments spawned using hydrogen peroxide, it was with 100% mortality. There was a significantly higher induction rate closer to natural spawn (Trial 2) compared with Trial 1 and no genotype effect. Mechanisms of action causing gamete release were not elucidated. In Caribbean staghorn corals, 5-HTP shows promise as a spawning induction agent if administered within 72 h of natural spawn and it will not result in excessive mortality. Phosphate chemicals may inhibit spawning. This is the first study of its kind on Caribbean acroporid corals and may offer an important conservation tool for biologists currently charged with restoring the imperiled Acropora reefs of the Florida Keys.

Review: aromatase inhibitors for ovulation induction.

PubMed

Casper, Robert F; Mitwally, Mohamed F M

2006-03-01

For the last 40 yr, the first line of treatment for anovulation in infertile women has been clomiphene citrate (CC). CC is a safe, effective oral agent but is known to have relatively common antiestrogenic endometrial and cervical mucous side effects that could prevent pregnancy in the face of successful ovulation. In addition, there is a significant risk of multiple pregnancy with CC, compared with natural cycles. Because of these problems, we proposed the concept of aromatase inhibition as a new method of ovulation induction that could avoid many of the adverse effects of CC. The objective of this review was to describe the different physiological mechanisms of action for CC and aromatase inhibitors (AIs) and compare studies of efficacy for both agents for ovulation induction. We conducted a systematic review of all the published studies, both controlled and noncontrolled, comparing CC and AI treatment, either alone or in combination with gonadotropins, for ovulation induction or augmentation, identified through the Entrez-PubMed search engine. Because of the recent acceptance of the concept of using AIs for ovulation induction, few controlled studies were identified, and the rest of the studies were pilot or preliminary comparisons. Based on these studies, it appears that AIs are as effective as CC in inducing ovulation, are devoid of any antiestrogenic side effects, result in lower serum estrogen concentrations, and are associated with good pregnancy rates with a lower incidence of multiple pregnancy than CC. When combined with gonadotropins for assisted reproductive technologies, AIs reduce the dose of FSH required for optimal follicle recruitment and improve the response to FSH in poor responders. Preliminary evidence suggests that AIs may replace CC in the future because of similar efficacy with a reduced side effect profile. Although worldwide experience with AIs for ovulation induction is increasing, at present, definitive studies in the form of randomized controlled trials comparing CC with AIs are lacking.

Aminosalicylates for induction of remission or response in Crohn's disease.

PubMed

Lim, Wee-Chian; Hanauer, Stephen

2010-12-08

Controlled clinical trials investigating the efficacy of aminosalicylates for the treatment of mildly to moderately active Crohn's disease have yielded conflicting results. A systematic review was conducted to critically examine current available data on the efficacy of sulfasalazine and mesalamine for inducing remission or clinical response in patients with mildly to moderately active Crohn's disease. To evaluate the efficacy of aminosalicylates compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) for the treatment of mildly to moderately active Crohn's disease. Separate MEDLINE (1966-July 2010), Cochrane Central Register of Controlled Trials (CENTRAL; Issue 3, 2010) and EMBASE database searches (1985-July 2010) of all relevant English and non-English language articles were performed, followed by manual searches of the reference list from potentially relevant papers and review articles, as well as proceedings from annual meetings (1991-2010) of the American Gastroenterological Association (AGA) and American College of Gastroenterology (ACG). Randomized controlled trials that evaluated the efficacy of sulfasalazine or mesalamine in the treatment of mildly to moderately active Crohn's disease compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) were included. Data extraction and assessment of methodological quality of each selected study was independently performed by the investigators and any disagreement was resolved by discussion and consensus. The primary outcome measure was a well defined clinical endpoint of induction of remission or response to treatment. Nineteen studies met the inclusion criteria and were analyzed. Pooled relative risks (RR) for inducing remission or clinical response and their 95% confidence intervals were calculated (random effects model) where appropriate. Sulfasalazine was more likely to induce remission (RR 1.38; 95% CI 1.02 to 1.87; n = 263) compared to placebo with benefit confined mainly to patients with colitis. Sulfasalazine was less effective than corticosteroids (RR 0.66; 95% CI 0.53 to 0.81; n = 260). Olsalazine was less effective than placebo in a single trial. Low dose mesalamine (1 to 2 g/day) was not superior to placebo (RR = 1.46, 95% CI 0.89-2.40; n = 302) and was less effective than corticosteroids. High dose mesalamine (3 to 4.5 g/day) was not superior to placebo for induction of remission (RR 2.02; 95% CI 0.75 to 5.45) or response (Weighted Mean Difference -19.8 points; 95% CI -46.2 to 6.7; n = 615). In a single randomized controlled trial, 5-ASA was inferior to budesonide (RR 0.56; 95% CI 0.40 to 0.78). No statistically significant difference was found between high dose mesalamine and conventional corticosteroids (RR 1.04; 95% CI 0.79 to 1.36; n = 178). However, relatively few patients were available for analysis. There was a lack of good quality clinical trials comparing sulfasalazine with other mesalamine formulations. Sulfasalazine has modest efficacy compared to placebo and is inferior to corticosteroids for the treatment of mild to moderately active Crohn's disease. Olsalazine and low dose mesalamine (1 to 2 g/day) are not superior to placebo. High dose mesalamine (3 to 4.5 g/day) is not more effective than placebo for inducing response or remission. High dose mesalamine was inferior to budesonide for inducing remission in a single trial. In conclusion, sulfasalazine shows modest efficacy for the treatment of active Crohn's disease. However, the existing data show little benefit for 5-aminosalicylates.

Interpreting clinical trial results by deductive reasoning: In search of improved trial design.

PubMed

Kurbel, Sven; Mihaljević, Slobodan

2017-10-01

Clinical trial results are often interpreted by inductive reasoning, in a trial design-limited manner, directed toward modifications of the current clinical practice. Deductive reasoning is an alternative in which results of relevant trials are combined in indisputable premises that lead to a conclusion easily testable in future trials. © 2017 WILEY Periodicals, Inc.

A clinical trial of supervised exercise for adult inpatients with acute myeloid leukemia (AML) undergoing induction chemotherapy☆

PubMed Central

Alibhai, Shabbir M.H.; O’Neill, Sara; Fisher-Schlombs, Karla; Breunis, Henriette; Brandwein, Joseph M.; Timilshina, Narhari; Tomlinson, George A.; Klepin, Heidi D.; Culos-Reed, S. Nicole

2013-01-01

Patients with acute myeloid leukemia (AML) receiving induction chemotherapy (IC) were enrolled in a supervised exercise intervention to determine safety, feasibility, and efficacy. Physical fitness measures, quality of life (QOL) and fatigue were assessed using standardized measures at baseline, post-induction, and post first consolidation. Retention was excellent, the intervention was safe, and efficacy estimates suggested benefits in physical fitness and QOL outcomes. Exercise is a safe, promising intervention for improving fitness and QOL in this patient population. These results provide a foundation for a randomized trial to better understand the impact of exercise during IC on clinically important outcomes. PMID:22726923

Shortening the induction delivery interval with prostaglandins: a randomized controlled trial of solo or in combination

PubMed Central

Mahendru, Rajiv; Yadav, Shweta

2011-01-01

Objective To compare the efficacy and safety of misoprostol alone with dinoprostone followed by misoprostol, all inserted intravaginally in induction of labor at term and the obstetrical outcome. Material and Methods A pilot study comprising 111 primigravidae, >37 gestational weeks with singleton pregnancy in cephalic presentation having an unfavorable Bishop score admitted for labor induction, were considered and randomly allocated into two groups. In group I (n=55) with intravaginal 25mcg misoprostol 4 hourly (six doses at the most) and and group II (n=56), with dinoprostone 0.5mg followed eight hours later by 25mcg misoprostol induction to vaginal delivery time was found to be significantly different, being 14.8 h in group-I and shorter in group-II with a mean of 11.6 h. Vaginal delivery rates within 12 h (groups-I and −II: 47.2%, as compared to 60.7%, respectively) were found to be higher with dinoprostone-misoprostol induction, as well as vaginal delivery rates in 24 h, 80.0% and 91.1%. The need for oxytocin augmentation was more frequent in the misoprostol than in the dinoprostone-misoprostol group, (61.8%, and 39.3%), and all these observations were statistically significant. Abnormal foetal heart rate pattern occurred more frequently (18.2%) in group-I in contrast to 5.3% in group-II, as was the incidence rate of (18.2%) who had passage of meconium in group-I, this rate being significantly different from group-II having meconium passage in 3 cases, a rate of 5.3%. Conclusion Using dinoprostone followed by vaginal misoprostol is safe and effective for induction of labor with less need for oxytocin augmentation and shorter induction delivery interval. PMID:24591967

Comparison effect of oral propranolol and oxytocin versus oxytocin only on induction of labour in nulliparous women (a double blind randomized trial).

PubMed

Moghadam, Ashraf Direkvand; Jaafarpour, Molouk; Khani, Ali

2013-11-01

Today, research on new methods for preventing caesarean sections owing to labour induction, have been requested in obstetric practice, because of the increased morbidity related to caesarean section. Therefore, the aim of this study was to compare the effect of Oral Propranolol and Oxytocin versus Oxytocin only on induction of labour in nulliparous women. A double blind randomized controlled trial was performed at the Ilam Mostafa Hospital, Ilam, Iran, from March 2010 to March 2011 on 146 nulliparous pregnant women who had gestational age of 40-42 weeks of pregnancy and a Bishop score of ≤5. Participants were divided in two groups (with 73 participants in each group). In the first group (placebo plus Oxytocin group = 73), Oxytocin was used for the induction of labour. In the second group (Propranolol plus Oxytocin group = 73 cases), before the use of Oxytocin, 20 mg Propranolol was administrated orally and then the Oxytocin was initiated. Twenty mg Propranolol was repeated after 8 hours if good contraction was not obtained. The mean duration for obtaining good contractions was significantly shorter in the Propranolol group than in the placebo group, on both the first and second day of induction (p<.05). The mean duration of latent phase was shorter in the first in Propranolol group (p<.05). In Propranolol plus Oxytocine group, frequency of cesarean deliveries significantly decreased than in the placebo plus Oxytocin group (21% versus 39.7%). No significant differences in neonate outcome, such as Apgar scores of minutes 1 and 5 and need of admissions to NICU, were found between the groups (p>.05) DISCUSSION AND CONCLUSION: Our study showed that oral Propranolol was effective for labour induction and that it could decrease the frequency of caesarean deliveries without producing any adverse effects on mothers or neonates.

A review of the evidence for use of thymoglobulin induction in renal transplantation.

PubMed

Gaber, A Osama; Knight, R J; Patel, S; Gaber, L W

2010-06-01

Depleting antilymphocyte, or antithymocyte antibodies, have long been an integral part of induction regimens and continue today to be used in the management of patients at risk of early rejection or those in whom the introduction of calcineurins or other immune suppressants must be delayed. Registry data demonstrate that the most commonly used depleting antibody, rabbit anti-human thymocyte globulin (rATG), is associated with improved outcomes following renal transplantation in high-risk patients, particularly in conjunction with steroid-avoidance regimens. Two prospective randomized trials in high-risk renal allograft patients have also demonstrated an advantage of r-ATG induction compared to the nondepleting interleukin receptor (IL2RA) antibodies. In low-immunologic-risk patients, however, r-ATG induction and IL2RA induction appear to be equivalent in terms of rejection prophylaxis and long-term function. Other studies have shown that sequential rATG-containing regimens were superior to no induction and allowed for successful late introduction of calcineurin inhibitors. The side effect profile of the depleting antibody included increased incidence of fever, hematologic abnormalities, cytomegalovirus infections when prophylaxis was not employed, and in some studies, increased incidence of posttransplant lymphoproliferative disease. This review describes the evidence supporting the use of depleting ATGs in kidney transplantation.

A prospective pilot study of Dilapan-S compared with Propess for induction of labour at 41+ weeks in nulliparous pregnancy.

PubMed

Crosby, David A; O'Reilly, Claire; McHale, Helen; McAuliffe, Fionnuala M; Mahony, Rhona

2017-12-21

The incidence of labour induction has risen worldwide over the past decade, and this may contribute to the rising caesarean delivery rate. The mechanisms for induction of labour are generally divided into two categories: mechanical and pharmacological. The objective of this study was to determine if mechanical induction with Dilapan-S is an acceptable, safe method of induction of labour in post-dates uncomplicated nulliparous pregnancy. This was a single-centre prospective observational pilot study trial. Fifty-two low-risk nulliparous women with an unfavourable cervix, scheduled for induction of labour for post-dates ≥ 41 weeks gestation, were offered induction of labour with Dilapan-S or Propess from May 2016 until November 2016. The primary outcomes measured were compliance to study protocol and maternal (infection, hyperstimulation) and neonatal outcomes (Apgar score at birth). The secondary outcome measures included change in Bishop's score and caesarean delivery rate. Compliance to study protocol was 25/26 (96%); it was possible to insert Dilapan-S in all but one woman. There were no differences in maternal and neonatal primary outcomes between the groups. There were no cases in either arm of hyperstimulation with either induction method. No difference between the groups was noted in the caesarean delivery rate nor in the mean change in Bishop's score. Dilapan-S is an acceptable, safe form of induction of labour in post-dates uncomplicated nulliparous pregnancy. No cases of hyperstimulation were found, and therefore, Dilapan-S may be a suitable option for outpatient induction of labour in low-risk post-dates nulliparas.

Meta-analysis of letrozole versus clomiphene citrate in polycystic ovary syndrome.

PubMed

He, Donghong; Jiang, Fengyan

2011-07-01

The aim of this study was to systematically compare the clinical efficacy and safety of letrozole with clomiphene citrate for ovulation induction in women with polycystic ovary syndrome (PCOS). The Cochrane Central Register of Controlled Trials, PubMed, EMbase, CBMdisc and CNKI were searched for eligible randomized controlled trials (RCT) comparing letrozole with clomiphene citrate in PCOS patients. Two reviewers independently extracted information and evaluated methodological quality according to the Cochrane Handbook 5.0. Meta-analysis was performed with the fixed-effects model or random-effects model according to the heterogeneity. Six eligible RCT involving 841 patients were included. Letrozole was associated with a number of lower mature follicles per cycle (standardized mean difference (SMD) -1.41; 95% confidence intervales (CI) -1.54 to -1.28; P<0.00001) compared with clomiphene citrate. There were no significant differences in pregnancy rate (relative risk (RR) 0.97; 95% CI 0.79 to 1.18), abortion rate (RR 1.38; 95% CI 0.48 to -3.96) and multiple pregnancy rate (RR 0.34; 95% CI 0.07 to -1.72) between the two groups. The evidence from ovulation rates was not enough to support either letrozole or clomiphene citrate. In conclusion, letrozole is as effective as clomiphene citrate for ovulation induction in patients with PCOS. Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Clove oil as an anaesthetic for adult sockeye salmon: Field trials

USGS Publications Warehouse

Woody, C.A.; Nelson, Jack L.; Ramstad, K.

2002-01-01

Wild migrating sockeye salmon Oncorhynchus nerka exposed to 20, 50 and 80 mg 1-1 of clove oil could be handled within 3 min, recovered within 10 min, and survived 15 min exposure trials. Fish tested at 110 mg 1-1 did not recover from 15 min exposure trials. Response curves developed for induction and recovery time considered the following predictors: clove oil concentration, sex, fish length and depth. A significant positive dependence was observed between induction time and fish length for 20, 50 and 80 mg 1-1 test concentrations; no dependence was observed between induction time and length at 110 and 140 mg 1-1. Recovery time differed as a function of clove oil concentration, but not fish size. A concentration of 50 mg 1-1 is recommended for anaesthetizing sockeye salmon ranging in length from 400 to 550 mm at water temperatures averaging 9-10??C.

Dissociated control as a signature of typological variability in high hypnotic suggestibility.

PubMed

Terhune, Devin Blair; Cardeña, Etzel; Lindgren, Magnus

2011-09-01

This study tested the prediction that dissociative tendencies modulate the impact of a hypnotic induction on cognitive control in different subtypes of highly suggestible individuals. Low suggestible (LS), low dissociative highly suggestible (LDHS), and high dissociative highly suggestible (HDHS) participants completed the Stroop color-naming task in control and hypnosis conditions. The magnitude of conflict adaptation (faster response times on incongruent trials preceded by an incongruent trial than those preceded by a congruent trial) was used as a measure of cognitive control. LS and LDHS participants displayed marginally superior up-regulation of cognitive control following a hypnotic induction, whereas HDHS participants' performance declined. These findings indicate that dissociative tendencies modulate the influence of a hypnotic induction on cognitive control in high hypnotic suggestibility and suggest that HS individuals are comprised of distinct subtypes with dissimilar cognitive profiles. Copyright © 2010 Elsevier Inc. All rights reserved.

Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials.

PubMed

Hills, Robert K; Castaigne, Sylvie; Appelbaum, Frederick R; Delaunay, Jacques; Petersdorf, Stephen; Othus, Megan; Estey, Elihu H; Dombret, Hervé; Chevret, Sylvie; Ifrah, Norbert; Cahn, Jean-Yves; Récher, Christian; Chilton, Lucy; Moorman, Anthony V; Burnett, Alan K

2014-08-01

Gemtuzumab ozogamicin was the first example of antibody-directed chemotherapy in cancer, and was developed for acute myeloid leukaemia. However, randomised trials in which it was combined with standard induction chemotherapy in adults have produced conflicting results. We did a meta-analysis of individual patient data to assess the efficacy of adding gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia. We searched PubMed for reports of randomised controlled trials published in any language up to May 1, 2013, that included an assessment of gemtuzumab ozogamicin given to adults (aged 15 years and older) in conjunction with the first course of intensive induction chemotherapy for acute myeloid leukaemia (excluding acute promyelocytic leukaemia) compared with chemotherapy alone. Published data were supplemented with additional data obtained by contacting individual trialists. The primary endpoint of interest was overall survival. We used standard meta-analytic techniques, with an assumption-free (or fixed-effect) method. We also did exploratory stratified analyses to investigate whether any baseline features predicted a greater or lesser benefit from gemtuzumab ozogamicin. We obtained data from five randomised controlled trials (3325 patients); all trials were centrally randomised and open label, with overall survival as the primary endpoint. The addition of gemtuzumab ozogamicin did not increase the proportion of patients achieving complete remission with or without complete peripheral count recovery (odds ratio [OR] 0·91, 95% CI 0·77-1·07; p=0·3). However, the addition of gemtuzumab ozogamicin significantly reduced the risk of relapse (OR 0·81, 0·73-0·90; p=0·0001), and improved overall survival at 5 years (OR 0·90, 0·82-0·98; p=0·01). At 6 years, the absolute survival benefit was especially apparent in patients with favourable cytogenetic characteristics (20·7%; OR 0·47, 0·31-0·73; p=0·0006), but was also seen in those with intermediate characteristics (5·7%; OR 0·84, 0·75-0·95; p=0·005). Patients with adverse cytogenetic characteristics did not benefit (2·2%; OR 0·99, 0·83-1·18; p=0·9). Doses of 3 mg/m(2) were associated with fewer early deaths than doses of 6 mg/m(2), with equal efficacy. Gemtuzumab ozogamicin can be safely added to conventional induction therapy and provides a significant survival benefit for patients without adverse cytogenetic characteristics. These data suggest that the use of gemtuzumab ozogamicin should be reassessed and its licence status might need to be reviewed. None. Copyright © 2014 Elsevier Ltd. All rights reserved.

Transdermal nicotine for induction of remission in ulcerative colitis.

PubMed

McGrath, J; McDonald, J W D; Macdonald, J K

2004-10-18

Ulcerative colitis is largely a disease of nonsmokers. Intermittent smokers often experience improvement in their symptoms while smoking. Nonsmokers with ulcerative colitis who begin smoking may go into remission. Randomized controlled trials were developed to test the efficacy of transdermal nicotine for the induction of remission in ulcerative colitis. (1) To determine the efficacy of transdermal nicotine for induction of remission in ulcerative colitis. (2) To assess adverse events associated with transdermal nicotine therapy for ulcerative colitis The MEDLINE (via PubMed) and EMBASE databases were searched using the search criteria "ulcerative colitis" and "transdermal nicotine" or "nicotine" to identify relevant papers published between 1970 and December 2003. Manual searches of reference lists from potentially relevant papers were performed to identify additional studies. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. The Cochrane Central Register of Controlled Trials and the Cochrane Inflammatory Bowel Disease Group Specialized Trials Register were also searched. We included only randomized controlled trials in which patients with active mild to moderate ulcerative colitis were randomly allocated to receive transdermal nicotine (15 to 25 mg/day) or a placebo or another treatment (corticosteroids or mesalamine). Data extraction and assessment of the methodological quality of each trial were independently performed by each author. Any disagreement among reviewers was resolved by consensus. The primary outcome measure was the number of patients achieving clinical or sigmoidoscopic remission as defined by the primary studies (e.g. no symptoms of ulcerative colitis), and expressed as a percentage of the patients randomized (intention to treat analysis). Secondary outcomes included clinical response, adverse events and withdrawal because of adverse events. Seven studies were identified, five of which met the inclusion criteria. A meta-analysis of two trials in which 71 patients were randomized to nicotine and 70 to placebo showed a statistically significant benefit for nicotine treatment. After four to six weeks of treatment 19 of 71 patients treated with transdermal nicotine were in clinical remission compared to 9 of 70 treated with placebo (OR=2.56, 95% CI 1.02-6.45). In the same group of patients improvement or remission was noted in 29 of the 71 patients assigned to nicotine compared to 14 of 70 patients assigned to placebo (OR=2.72, 95% CI 1.28 - 5.81). For patients with left sided colitis the odds ratio was 2.31 (95% CI 1.05-5.10). When transdermal nicotine was compared to standard medical therapy no significant benefit for nicotine was observed. After four to six weeks of standard therapy (oral prednisone or mesalamine), 34 of 63 patients were in clinical or sigmoidoscopic remission compared to 33 of 66 patients treated with transdermal nicotine (OR=0.77, 95% CI 0.37-1.60). A meta-analysis of all five studies which included 137 patients treated with transdermal nicotine and 133 patients treated with a placebo or standard therapy demonstrated no statistically significant benefit of nicotine therapy (OR=1.23; 95% CI 0.71-2.14). Patients treated with transdermal nicotine were significantly more likely to withdrawal due to adverse events than patients treated with placebo or standard medical therapy (OR=5.82, 95% CI, 1.66 - 20.47) and were significantly more likely to suffer from an adverse event than patients treated with placebo or standard medical therapy (OR=3.54, 95% CI, 2.07 - 6.08). The results of this review provide evidence that transdermal nicotine is superior to placebo for the induction of remission in patient's with ulcerative colitis. The review did not identify any significant advantage for transdermal nicotine therapy compared to standard medical therapy. Adverse events associated with transdermal nicotine are significant and limit its use in some patients.

A randomized trial of Foley balloon induction of labor trial in nulliparas (FIAT-N).

PubMed

Connolly, Katherine A; Kohari, Katherine S; Rekawek, Patricia; Smilen, Brooke S; Miller, Meredith R; Moshier, Erin; Factor, Stephanie H; Stone, Joanne L; Bianco, Angela T

2016-09-01

With an increasing rate of induction of labor, it is important to choose induction methods that are safe and efficient in achieving a vaginal delivery. The optimal method for inducing nulliparous women with an unfavorable cervix is not known. We sought to determine if induction of labor with simultaneous use of oxytocin and Foley balloon vs sequential use of Foley balloon followed by oxytocin decreases the time to delivery in nulliparous women. We conducted a randomized controlled trial of nulliparous women presenting for induction at a single institution from December 2013 through March 2015. After decision for induction was made by their primary provider, women with gestational age ≥24 weeks with a nonanomalous, singleton fetus in vertex presentation with intact membranes were offered participation. Exclusion criteria included history of uterine surgery, unexplained vaginal bleeding, latex allergy, or contraindication to vaginal delivery. Participants were randomized to either simultaneous (oxytocin and Foley balloon) or sequential (oxytocin after expulsion of Foley balloon) induction group. The primary outcome was time from induction to delivery. Secondary outcomes included mode of delivery, estimated blood loss, postpartum hemorrhage, chorioamnionitis, and composite neonatal outcome. Maternal and neonatal outcomes were collected via chart review. Analyses were done on an intention-to-treat basis. A total of 166 patients were enrolled; 82 in the simultaneous and 84 in the sequential group. There were no differences in baseline characteristics in the 2 groups. Patients who received simultaneous oxytocin with insertion of a Foley balloon delivered significantly earlier (15.92 vs 18.87 hours, P = .004) than those in the sequential group. There was no difference in rate of cesarean delivery, estimated blood loss, postpartum hemorrhage, chorioamnionitis, or composite neonatal outcome. Simultaneous use of oxytocin and Foley balloon for induction of labor results in a significantly shorter interval to delivery in nulliparas. Copyright © 2016 Elsevier Inc. All rights reserved.

Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study.

PubMed

Zavada, J; Pesickova, Ss; Rysava, R; Olejarova, M; Horák, P; Hrncír, Z; Rychlík, I; Havrda, M; Vítova, J; Lukác, J; Rovensky, J; Tegzova, D; Böhmova, J; Zadrazil, J; Hána, J; Dostál, C; Tesar, V

2010-10-01

Intravenous cyclophosphamide is considered to be the standard of care for the treatment of proliferative lupus nephritis. However, its use is limited by potentially severe toxic effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative to cyclophosphamide. Forty patients with clinically active proliferative lupus nephritis were randomly assigned to one of two sequential induction and maintenance treatment regimens based either on cyclophosphamide or Cyclosporine A. The primary outcomes were remission (defined as normal urinary sediment, proteinuria <0.3 g/24 h, and stable s-creatinine) and response to therapy (defined as stable s-creatinine, 50% reduction in proteinuria, and either normalization of urinary sediment or significant improvement in C3) at the end of induction and maintenance phase. Secondary outcomes were incidence of adverse events, and relapse-free survival. At the end of the induction phase, 24% of the 21 patients treated by cyclophosphamide achieved remission, and 52% achieved response, as compared with 26% and 43%, respectively of the 19 patients treated by the Cyclosporine A. At the end of the maintenance phase, 14% of patients in cyclophosphamide group, and 37% in Cyclosporine A group had remission, and 38% and 58% respectively response. Treatment with Cyclosporine A was associated with transient increase in blood pressure and reversible decrease in glomerular filtration rate. There was no significant difference in median relapse-free survival. In conclusion, Cyclosporine A was as effective as cyclophosphamide in the trial of sequential induction and maintenance treatment in patients with proliferative lupus nephritis and preserved renal function.(ClinicalTrials.gov identifier: NCT00976300)

Baseline AMH Level Associated With Ovulation Following Ovulation Induction in Women With Polycystic Ovary Syndrome.

PubMed

Mumford, Sunni L; Legro, Richard S; Diamond, Michael P; Coutifaris, Christos; Steiner, Anne Z; Schlaff, William D; Alvero, Ruben; Christman, Gregory M; Casson, Peter R; Huang, Hao; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping; Cedars, Marcelle I

2016-09-01

Anti-Müllerian hormone (AMH) reduces aromatase activity and sensitivity of follicles to FSH stimulation. Therefore, elevated serum AMH may indicate a higher threshold for response to ovulation induction in women with polycystic ovary syndrome (PCOS). This study sought to determine the association between AMH levels and ovulatory response to treatment among the women enrolled into the Pregnancy in PCOS II (PPCOS II) trial. This was a secondary analysis of data from a randomized clinical trial in academic health centers throughout the United States Participants: A total of 748 women age 18-40 years, with PCOS and measured AMH levels at baseline, were included in this study. Couples were followed for up to five treatment cycles to determine ovulation (midluteal serum progesterone > 5 ng/mL) and the dose required to achieve ovulation. A lower mean AMH and AMH per follicle was observed among women who ovulated compared with women who never achieved ovulation during the study (geometric mean AMH, 5.54 vs 7.35 ng/mL; P = .0001; geometric mean AMH per follicle, 0.14 vs 0.18; P = .01) after adjustment for age, body mass index, T, and insulin level. As AMH levels increased, the dose of ovulation induction medication needed to achieve ovulation also increased. No associations were observed between antral follicle count and ovulation. These results suggest that high serum AMH is associated with a reduced response to ovulation induction among women with PCOS. Women with higher AMH levels may require higher doses of medication to achieve ovulation.

A clinical trial of supervised exercise for adult inpatients with acute myeloid leukemia (AML) undergoing induction chemotherapy.

PubMed

Alibhai, Shabbir M H; O'Neill, Sara; Fisher-Schlombs, Karla; Breunis, Henriette; Brandwein, Joseph M; Timilshina, Narhari; Tomlinson, George A; Klepin, Heidi D; Culos-Reed, S Nicole

2012-10-01

Patients with acute myeloid leukemia (AML) receiving induction chemotherapy (IC) were enrolled in a supervised exercise intervention to determine safety, feasibility, and efficacy. Physical fitness measures, quality of life (QOL) and fatigue were assessed using standardized measures at baseline, post-induction, and post first consolidation. Retention was excellent, the intervention was safe, and efficacy estimates suggested benefits in physical fitness and QOL outcomes. Exercise is a safe, promising intervention for improving fitness and QOL in this patient population. These results provide a foundation for a randomized trial to better understand the impact of exercise during IC on clinically important outcomes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Rapid COJEC versus standard induction therapies for high-risk neuroblastoma.

PubMed

Peinemann, Frank; Tushabe, Doreen A; van Dalen, Elvira C; Berthold, Frank

2015-05-19

Neuroblastoma is a rare malignant disease and mainly affects infants and very young children. The tumors mainly develop in the adrenal medullary tissue and an abdominal mass is the most common presentation. The high-risk group is characterized by metastasis and other characteristics that increase the risk for an adverse outcome. In the rapid COJEC induction schedule, higher single doses of selected drugs than standard induction schedules are administered over a substantially shorter treatment period, with shorter intervals between cycles. Shorter intervals and higher doses increase the dose intensity of chemotherapy and might improve survival. The aim of this study was to evaluate the efficacy and adverse events of the rapid COJEC induction schedule as compared to standard induction schedules in patients with high-risk neuroblastoma (as defined by the International Neuroblastoma Risk Group (INRG) classification system). Outcomes of interest were complete response, early toxicity and treatment-related mortality as primary endpoints and overall survival, progression- and event-free survival, late non-hematological toxicity, and health-related quality of life as secondary endpoints. We searched the electronic databases CENTRAL (2014, Issue 11), MEDLINE (PubMed), and EMBASE (Ovid) for articles from inception to 11 November 2014. Further searches included trial registries, conference proceedings, and reference lists of recent reviews and relevant articles. We did not apply limits on publication year or languages. Randomized controlled trials evaluating the rapid COJEC induction schedule for high-risk neuroblastoma patients compared to standard induction schedules. Two review authors performed study selection, abstracted data on study and patient characteristics, and assessed risk of bias independently. We resolved differences by discussion or by appeal to a third review author. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. We used the five GRADE considerations, study limitations, consistency of effect, imprecision, indirectness, and publication bias, to judge the quality of the evidence. We downgraded for risk of bias and imprecision We identified one randomized controlled trial (CCLG-ENSG-5) that included 262 patients with high-risk neuroblastoma who were randomized to receive either rapid COJEC (N = 130) or standard OPEC/COJEC (N = 132) induction chemotherapy. We graded the evidence as low quality; we downgraded for risk of bias and imprecision.There was no clear evidence of a difference between the treatment groups in complete response (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.71 to 1.38), treatment-related mortality (RR 1.21, 95% CI 0.33 to 4.39), overall survival (hazard ratio (HR) 0.83, 95% CI 0.63 to 1.10), and event-free survival (HR 0.86, 95% CI 0.65 to 1.13). We calculated the HRs using the complete follow-up period of the trial.Febrile neutropenia (two or more episodes), proven fungal infections, septicemia (one or more episodes), gastrointestinal toxicity (grade 3 or 4), renal toxicity (glomerular filtration rate < 80 ml/min per body surface area of 1.73 m(2)), neurological toxicity (grade 3 or 4), and ototoxicity (Brock grade 2 to 4) were addressed as early toxicities (during pre-operative chemotherapy). For febrile neutropenia, septicemia, and renal toxicity, a statistically significant difference in favor of the standard treatment arm was identified; for all other early toxicities no clear evidence of a difference between treatment groups was identified. With regard to late non-hematological toxicities (median follow-up 12.7 years; range 6.9 to 16.5 years), the study provided data on any complication, renal toxicity (glomerular filtration rate < 80 ml/min per body surface area of 1.73m(2)), ototoxicity (Brock grade 1 to 4), endocrine complications, neurocognitive complications (i.e. behavioral, speech, or learning difficulties), and second malignancies. For endocrine complications and neurocognitive complications, a statistically significant difference in favor of the rapid COJEC arm was found; for all other late non-hematological toxicities no clear evidence of a difference between treatment groups was identified.Data on progression-free survival and health-related quality of life were not reported. We identified one randomized controlled trial that evaluated rapid COJEC versus standard induction therapy in patients with high-risk neuroblastoma. No clear evidence of a difference in complete response, treatment-related mortality, overall survival, and event-free survival between the treatment alternatives was found. This could be the result of low power or too short a follow-up period. Results of both early and late toxicities were ambiguous. Information on progression-free survival and health-related quality of life were not available. This trial was performed in the 1990s. Since then, many changes in, for example, treatment and risk classification have occurred. Therefore, based on the currently available evidence, we are uncertain about the effects of rapid COJEC and standard induction therapy in patients with high-risk neuroblastoma. More research is needed for a definitive conclusion.

Reduction in resource use with the misoprostol vaginal insert vs the dinoprostone vaginal insert for labour induction: a model-based analysis from a United Kingdom healthcare perspective.

PubMed

Draycott, T; van der Nelson, H; Montouchet, C; Ruff, L; Andersson, F

2016-02-10

In view of the increasing pressure on the UK's maternity units, new methods of labour induction are required to alleviate the burden on the National Health Service, while maintaining the quality of care for women during delivery. A model was developed to evaluate the resource use associated with misoprostol vaginal inserts (MVIs) and dinoprostone vaginal inserts (DVIs) for the induction of labour at term. The one-year Markov model estimated clinical outcomes in a hypothetical cohort of 1397 pregnant women (parous and nulliparous) induced with either MVI or DVI at Southmead Hospital, Bristol, UK. Efficacy and safety data were based on published and unpublished results from a phase III, double-blind, multicentre, randomised controlled trial. Resource use was modelled using data from labour induction during antenatal admission to patient discharge from Southmead Hospital. The model's sensitivity to key parameters was explored in deterministic multi-way and scenario-based analyses. Over one year, the model results indicated MVI use could lead to a reduction of 10,201 h (28.9%) in the time to vaginal delivery, and an increase of 121% and 52% in the proportion of women achieving vaginal delivery at 12 and 24 h, respectively, compared with DVI use. Inducing women with the MVI could lead to a 25.2% reduction in the number of midwife shifts spent managing labour induction and 451 fewer hospital bed days. These resource utilisation reductions may equate to a potential 27.4% increase in birthing capacity at Southmead Hospital, when using the MVI instead of the DVI. Resource use, in addition to clinical considerations, should be considered when making decisions about labour induction methods. Our model analysis suggests the MVI is an effective method for labour induction, and could lead to a considerable reduction in resource use compared with the DVI, thereby alleviating the increasing burden of labour induction in UK hospitals.

Clomiphene citrate before and after withdrawal bleeding for induction of ovulation in women with polycystic ovary syndrome: Randomized cross-over trial.

PubMed

Elbohoty, Ahmed E H; Amer, Mohamed; Abdelmoaz, Mohamed

2016-08-01

To compare the ovarian response to early versus late clomiphene citrate (CC) in women with polycystic ovary syndrome (PCOS). This cross-over randomized controlled clinical trial included 90 infertile amenorrheic women with PCOS. After inducing withdrawal bleeding, patients were randomly divided into two equal groups to receive ovulation induction with CC 100 mg/day for 5 days. Group I started treatment the next day after finishing medroxyprogesterone acetate course for a menstrual cycle, and after a washout period of another menstrual cycle, the treatment was shifted to start on day 2 of withdrawal bleeding. Group II received a reversed protocol: late then early treatment. Women were followed up on transvaginal ultrasonography to monitor follicular growth, endometrial thickness and evidence of ovulation. Human chorionic gonadotropin 10 000 IU was given i.m. to trigger ovulation when at least one mature follicle measured ≥18 mm at day 14. In all cases, early induction protocol resulted in significantly higher proportion of ovulating patients, thicker endometrium and higher number of follicles 14-17 mm in diameter, ≥ 18 mm in diameter and total number of follicles (P < 0.001 for all comparisons). In women with PCOS, early initiation of CC before withdrawal bleeding or during the last days of the luteal phase can achieve a better ovulatory response. © 2016 Japan Society of Obstetrics and Gynecology.

Reduced medical costs and hospital days when using oral arsenic plus ATRA as the first-line treatment of acute promyelocytic leukemia.

PubMed

Jiang, Hao; Liang, Gong-Wen; Huang, Xiao-Jun; Jiang, Qian; Han, Sheng; Shi, Lu-Wen; Zhu, Hong-Hu

2015-12-01

We have demonstrated that oral arsenic (Realgar-Indigo naturalis formula, RIF) plus all-trans retinoic acid (ATRA) is not inferior to intravenous arsenic trioxide (ATO) plus ATRA as the first-line treatment of acute promyelocytic leukemia (APL). To compare the cost-effectiveness of oral and intravenous arsenic, we analyzed the results of 30 patients in each group involved in a randomized controlled trial at our center. The median total medical costs were $13,183.49 in the RIF group compared with $24136.98 in the ATO group (p<0.0001). This difference primarily resulted from the different costs of induction therapy (p=0.016) and maintenance treatment (p<0.0001). The length of hospitalization for the RIF group was significantly lower than that for the ATO group (24 vs. 31 days, p<0.0001) during induction therapy. During maintenance treatment, the estimated medical costs were $2047.14 for each patient in the RIF group treated at home compared with $11273.81 for each patient in the ATO group treated in an outpatient setting (p<0.0001). We conclude that oral RIF plus ATRA significantly reduced the medical costs and length of hospital stay during induction and remission therapy compared with ATO plus ATRA in APL patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Methods of term labour induction for women with a previous caesarean section.

PubMed

West, Helen M; Jozwiak, Marta; Dodd, Jodie M

2017-06-09

Women with a prior caesarean delivery have an increased risk of uterine rupture and for women subsequently requiring induction of labour it is unclear which method is preferable to avoid adverse outcomes. This is an update of a review that was published in 2013. To assess the benefits and harms associated with different methods used to induce labour in women who have had a previous caesarean birth. We searched Cochrane Pregnancy and Childbirth's Trials Register (31 August 2016) and reference lists of retrieved studies. Randomised controlled trials (RCTs) comparing any method of third trimester cervical ripening or labour induction, with placebo/no treatment or other methods in women with prior caesarean section requiring labour induction in a subsequent pregnancy. Two review authors independently assessed studies for inclusion and trial quality, extracted data, and checked them for accuracy. Eight studies (data from 707 women and babies) are included in this updated review. Meta-analysis was not possible because studies compared different methods of labour induction. All included studies had at least one design limitation (i.e. lack of blinding, sample attrition, other bias, or reporting bias). One study stopped prematurely due to safety concerns. Vaginal PGE2 versus intravenous oxytocin (one trial, 42 women): no clear differences for caesarean section (risk ratio (RR) 0.67, 95% confidence interval (CI) 0.22 to 2.03, evidence graded low), serious neonatal morbidity or perinatal death (RR 3.00, 95% CI 0.13 to 69.70, evidence graded low), serious maternal morbidity or death (RR 3.00, 95% CI 0.13 to 69.70, evidence graded low). Also no clear differences between groups for the reported secondary outcomes. The GRADE outcomes vaginal delivery not achieved within 24 hours, and uterine hyperstimulation with fetal heart rate changes were not reported. Vaginal misoprostol versus intravenous oxytocin (one trial, 38 women): this trial stopped early because one woman who received misoprostol had a uterine rupture (RR 3.67, 95% CI 0.16 to 84.66) and one had uterine dehiscence. No other outcomes (including GRADE outcomes) were reported. Foley catheter versus intravenous oxytocin (one trial, subgroup of 53 women): no clear difference between groups for vaginal delivery not achieved within 24 hours (RR 1.47, 95% CI 0.89 to 2.44, evidence graded low), uterine hyperstimulation with fetal heart rate changes (RR 3.11, 95% CI 0.13 to 73.09, evidence graded low), and caesarean section (RR 0.93, 95% CI 0.45 to 1.92, evidence graded low). There were also no clear differences between groups for the reported secondary outcomes. The following GRADE outcomes were not reported: serious neonatal morbidity or perinatal death, and serious maternal morbidity or death. Double-balloon catheter versus vaginal PGE2 (one trial, subgroup of 26 women): no clear difference in caesarean section (RR 0.97, 95% CI 0.41 to 2.32, evidence graded very low). Vaginal delivery not achieved within 24 hours, uterine hyperstimulation with fetal heart rate changes, serious neonatal morbidity or perinatal death, and serious maternal morbidity or death were not reported. Oral mifepristone versus Foley catheter (one trial, 107 women): no primary/GRADE outcomes were reported. Fewer women induced with mifepristone required oxytocin augmentation (RR 0.54, 95% CI 0.38 to 0.76). There were slightly fewer cases of uterine rupture among women who received mifepristone, however this was not a clear difference between groups (RR 0.29, 95% CI 0.08 to 1.02). No other secondary outcomes were reported. Vaginal isosorbide mononitrate (IMN) versus Foley catheter (one trial, 80 women): fewer women induced with IMN achieved a vaginal delivery within 24 hours (RR 2.62, 95% CI 1.32 to 5.21, evidence graded low). There was no difference between groups in the number of women who had a caesarean section (RR 1.00, 95% CI 0.39 to 2.59, evidence graded very low). More women induced with IMN required oxytocin augmentation (RR 1.65, 95% CI 1.17 to 2.32). There were no clear differences in the other reported secondary outcomes. The following GRADE outcomes were not reported: uterine hyperstimulation with fetal heart rate changes, serious neonatal morbidity or perinatal death, and serious maternal morbidity or death. 80 mL versus 30 mL Foley catheter (one trial, 154 women): no clear difference between groups for the primary outcomes: vaginal delivery not achieved within 24 hours (RR 1.05, 95% CI 0.91 to 1.20, evidence graded moderate) and caesarean section (RR 1.05, 95% CI 0.89 to 1.24, evidence graded moderate). However, more women induced using a 30 mL Foley catheter required oxytocin augmentation (RR 0.81, 95% CI 0.66 to 0.98). There were no clear differences between groups for other secondary outcomes reported. Several GRADE outcomes were not reported: uterine hyperstimulation with fetal heart rate changes, serious neonatal morbidity or perinatal death, and serious maternal morbidity or death. Vaginal PGE2 pessary versus vaginal PGE2 tablet (one trial, 200 women): no difference between groups for caesarean section (RR 1.09, 95% CI 0.74 to 1.60, evidence graded very low), or any of the reported secondary outcomes. Several GRADE outcomes were not reported: vaginal delivery not achieved within 24 hours, uterine hyperstimulation with fetal heart rate changes, serious neonatal morbidity or perinatal death, and serious maternal morbidity or death. RCT evidence on methods of induction of labour for women with a prior caesarean section is inadequate, and studies are underpowered to detect clinically relevant differences for many outcomes. Several studies reported few of our prespecified outcomes and reporting of infant outcomes was especially scarce. The GRADE level for quality of evidence was moderate to very low, due to imprecision and study design limitations.High-quality, adequately-powered RCTs would be the best approach to determine the optimal method for induction of labour in women with a prior caesarean birth. However, such trials are unlikely to be undertaken due to the very large numbers needed to investigate the risk of infrequent but serious adverse outcomes (e.g. uterine rupture). Observational studies (cohort studies), including different methods of cervical ripening, may be the best alternative. Studies could compare methods believed to provide effective induction of labour with low risk of serious harm, and report the outcomes listed in this review.

Pressure-dependent changes in haematocrit and plasma volume during anaesthesia, a randomised clinical trial.

PubMed

Damén, T; Reinsfelt, B; Redfors, B; Nygren, A

2016-05-01

Induction of general anaesthesia has been shown to cause haemodilution and an increase in plasma volume. The aim of this study was to evaluate whether prevention of hypotension during anaesthesia induction could avoid haemodilution. Twenty-four cardiac surgery patients, 66 ± 10 years, were randomised to receive either norepinephrine in a dose needed to maintain mean arterial blood pressure (MAP) at pre-anaesthesia levels after induction or to a control group that received vasopressor if MAP decreased below 60 mmHg. No fluids were infused. Changes in plasma volume were calculated with standard formula: 100 × (Hct(pre)/Hct(post) - 1)/(1 - Hct(pre)). Arterial blood gas was analysed every 10 minutes and non-invasive continuous haemoglobin (SpHb) was continuously measured. Pre-anaesthesia MAP was 98 ± 7 mmHg. Ten minutes after anaesthesia induction, the haematocrit decreased by 5.0 ± 2.5% in the control group compared with 1.2 ± 1.4% in the intervention group, which corresponds to increases in plasma volume by 310 ml and 85 ml respectively. MAP decreased to 69 ± 15 mmHg compared to 92 ± 10 mmHg in the intervention group. The difference maintained throughout the 70 min intervention period. The change in haemoglobin level measured by blood gas analysis could not be detected by SpHb measurement. The mean bias between the SpHb and blood gas haemoglobin was 15 g/l. During anaesthesia induction, haematocrit decreases and plasma volume increases early and parallel to a decrease in blood pressure. This autotransfusion is blunted when blood pressure is maintained at pre-induction levels with norepinephrine. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Does a hypnosis session reduce the required propofol dose during closed-loop anaesthesia induction?: A randomised controlled trial.

PubMed

Bataille, Aurélien; Guirimand, Avit; Szekely, Barbara; Michel-Cherqui, Mireille; Dumans, Virginie; Liu, Ngai; Chazot, Thierry; Fischler, Marc; Le Guen, Morgan

2017-11-27

Hypnosis has a positive effect on peri-operative anxiety and pain. The objective of this study was to assess the impact of a formal deep hypnosis session on the consumption of propofol for anaesthetic induction using automated administration of propofol guided by the bispectral index (BIS) in a closed loop. A 1 : 1 randomised, usual-care-controlled, single-centre trial. Tertiary care centre in France from April 2014 to December 2015. Female adult patients scheduled for outpatient gynaecological surgery under general anaesthesia. Before surgery, patients were randomised to receive either a deep hypnosis session or routine care. Anaesthetic induction was performed automatically by propofol without opioids and was assisted by the BIS in a closed loop. The primary endpoint was the propofol dose required for anaesthesia induction, defined as a BIS less than 60 for at least 30 s. Data for 31 patients in the hypnosis group and 35 in the control group were analysed. There was no evidence of a difference in the mean required propofol dose for anaesthetic induction between the hypnosis and the control groups (2.06 mg kg (95% confidence interval [1.68 to 2.43]) versus 1.79 mg kg (95% CI [1.54 to 2.03]), P = 0.25, respectively). The current study, which was designed to determine the effect of a deep hypnosis session on anaesthesia induction using an automated tool for propofol administration, failed to detect a difference in the required dose of propofol. ClinicalTrials.gov, NCT02249364.

Progress in HIV vaccine development

PubMed Central

Hsu, Denise C.; O'Connell, Robert J.

2017-01-01

ABSTRACT An HIV-1 vaccine is needed to curtail the HIV epidemic. Only one (RV144) out of the 6 HIV-1 vaccine efficacy trials performed showed efficacy. A potential mechanism of protection is the induction of functional antibodies to V1V2 region of HIV envelope. The 2 main current approaches to the generation of protective immunity are through broadly neutralizing antibodies (bnAb) and induction of functional antibodies (non-neutralizing Abs with other potential anti-viral functions). Passive immunization using bnAb has advanced into phase II clinical trials. The induction of bnAb using mimics of the natural Env trimer or B-cell lineage vaccine design is still in pre-clinical phase. An attempt at optimization of protective functional antibodies will be assessed next with the efficacy trial (HVTN702) about to start. With on-going optimization of prime/boost strategies, the development of mosaic immunogens, replication competent vectors, and emergence of new strategies designed to induce bnAb, the prospects for a preventive HIV vaccine have never been more promising. PMID:28281871

Induction of fetal demise before abortion.

PubMed

Diedrich, Justin; Drey, Eleanor

2010-06-01

For decades, the induction of fetal demise has been used before both surgical and medical second-trimester abortion. Intracardiac potassium chloride and intrafetal or intra-amniotic digoxin injections are the pharmacologic agents used most often to induce fetal demise. In the last several years, induction of fetal demise has become more common before second-trimester abortion. The only randomized, placebo-controlled trial of induced fetal demise before surgical abortion used a 1 mg injection of intra-amniotic digoxin before surgical abortion at 20-23 weeks' gestation and found no difference in procedure duration, difficulty, estimated blood loss, pain scores or complications between groups. Inducing demise before induction terminations at near viable gestational ages to avoid signs of life at delivery is practiced widely. The role of inducing demise before dilation and evacuation (D&E) remains unclear, except for legal considerations in the United States when an intact delivery is intended. There is a discrepancy between the one published randomized trial that used 1 mg intra-amniotic digoxin that showed no improvement in D&E outcomes and observational studies using different routes, doses and pre-abortion intervals that have made claims for its use. Additional randomized trials might provide clearer evidence upon which to make further recommendations about any role of inducing demise before surgical abortion. At the current time, the Society of Family Planning recommends that pharmacokinetic studies followed by randomized controlled trials be conducted to assess the safety and efficacy of feticidal agents to improve abortion safety.

Remission induction and maintenance effect of probiotics on ulcerative colitis: A meta-analysis

PubMed Central

Sang, Li-Xuan; Chang, Bing; Zhang, Wen-Liang; Wu, Xiao-Mei; Li, Xiao-Hang; Jiang, Min

2010-01-01

AIM: To evaluate the induction of remission and maintenance effects of probiotics for ulcerative colitis. METHODS: Information was retrieved from MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The induction of remission and promotion of maintenance were compared between probiotics treatment and non-probiotics treatment in ulcerative colitis. RESULTS: Thirteen randomized controlled studies met the selection criteria. Seven studies evaluated the remission rate, and eight studies estimated the recurrence rate; two studies evaluated both remission and recurrence rates. Compared with the non-probiotics group, the remission rate for ulcerative colitis patients who received probiotics was 1.35 (95% CI: 0.98-1.85). Compared with the placebo group, the remission rate of ulcerative colitis who received probiotics was 2.00 (95% CI: 1.35-2.96). During the course of treatment, in patients who received probiotics for less than 12 mo compared with the group treated by non-probiotics, the remission rate of ulcerative colitis was 1.36 (95% CI: 1.07-1.73). Compared with the non-probiotics group, the recurrence rate of ulcerative colitis patients who received probiotics was 0.69 (95% CI: 2.47-1.01). In the mild to moderate group who received probiotics, compared to the group who did not receive probiotics, the recurrence rate was 0.25 (95% CI: 0.12-0.51). The group who received Bifidobacterium bifidum treatment had a recurrence rate of 0.25 (95% CI: 0.12-0.50) compared with the non-probiotics group. CONCLUSION: Probiotic treatment was more effective than placebo in maintaining remission in ulcerative colitis. PMID:20397271

Remission induction and maintenance effect of probiotics on ulcerative colitis: a meta-analysis.

PubMed

Sang, Li-Xuan; Chang, Bing; Zhang, Wen-Liang; Wu, Xiao-Mei; Li, Xiao-Hang; Jiang, Min

2010-04-21

To evaluate the induction of remission and maintenance effects of probiotics for ulcerative colitis. Information was retrieved from MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The induction of remission and promotion of maintenance were compared between probiotics treatment and non-probiotics treatment in ulcerative colitis. Thirteen randomized controlled studies met the selection criteria. Seven studies evaluated the remission rate, and eight studies estimated the recurrence rate; two studies evaluated both remission and recurrence rates. Compared with the non-probiotics group, the remission rate for ulcerative colitis patients who received probiotics was 1.35 (95% CI: 0.98-1.85). Compared with the placebo group, the remission rate of ulcerative colitis who received probiotics was 2.00 (95% CI: 1.35-2.96). During the course of treatment, in patients who received probiotics for less than 12 mo compared with the group treated by non-probiotics, the remission rate of ulcerative colitis was 1.36 (95% CI: 1.07-1.73). Compared with the non-probiotics group, the recurrence rate of ulcerative colitis patients who received probiotics was 0.69 (95% CI: 2.47-1.01). In the mild to moderate group who received probiotics, compared to the group who did not receive probiotics, the recurrence rate was 0.25 (95% CI: 0.12-0.51). The group who received Bifidobacterium bifidum treatment had a recurrence rate of 0.25 (95% CI: 0.12-0.50) compared with the non-probiotics group. Probiotic treatment was more effective than placebo in maintaining remission in ulcerative colitis.

Elective induction of labor.

PubMed

Moore, Lisa E; Rayburn, William F

2006-09-01

Induction of labor rates have more than doubled nationwide in the past 15 years. The increase in medically induced inductions was slower than the overall increase, suggesting that inductions for marginal or elective reasons rose more rapidly. Elective inductions seem to account for at least half of all inductions and 10% of all deliveries. Whether the experience of an elective induction is satisfactory to the patient, obstetrician, and intrapartum crew warrants more widespread attention. Cesarean rates are high for nulliparas undergoing an induction with an unfavorable cervix. Prospective studies are limited or nonexistent to recommend induction of labor for elective or marginal indications. Until more prospective work is performed, it will be difficult to evaluate the true impact of the elective induction of labor on population-wide cesarean delivery rates. Strategies for increased obstetrician awareness are proposed through practice guidelines and through clinical research trials.

Induction Chemotherapy plus Concurrent Chemoradiotherapy in Endemic Nasopharyngeal Carcinoma: Individual Patient Data Pooled Analysis of Four Randomized Trials.

PubMed

Chen, Yu-Pei; Tang, Ling-Long; Yang, Qi; Poh, Sharon-Shuxian; Hui, Edwin P; Chan, Anthony T C; Ong, Whee-Sze; Tan, Terence; Wee, Joseph; Li, Wen-Fei; Chen, Lei; Ma, Brigette B Y; Tong, Macy; Tan, Sze-Huey; Cheah, Shie-Lee; Fong, Kam-Weng; Sommat, Kiattisa; Soong, Yoke Lim; Guo, Ying; Lin, Ai-Hua; Sun, Ying; Hong, Ming-Huang; Cao, Su-Mei; Chen, Ming-Yuan; Ma, Jun

2018-04-15

Purpose: Because of the uneven geographic distribution and small number of randomized trials available, the value of additional induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) remains controversial. This study performed an individual patient data (IPD) pooled analysis to better assess the precise role of IC + CCRT in locoregionally advanced NPC. Experimental Design: Four randomized trials in endemic areas were identified, representing 1,193 patients; updated IPD were obtained. Progression-free survival (PFS) and overall survival (OS) were the primary and secondary endpoints, respectively. Results: Median follow-up was 5.0 years. The HR for PFS was 0.70 [95% confidence interval (CI), 0.56-0.86; P = 0.0009; 9.3% absolute benefit at 5 years] in favor of IC + CCRT versus CCRT alone. IC + CCRT also improved OS (HR = 0.75; 95% CI, 0.57-0.99; P = 0.04) and reduced distant failure (HR = 0.68; 95% CI, 0.51-0.90; P = 0.008). IC + CCRT had a tendency to improve locoregional control compared with CCRT alone (HR = 0.70; 95% CI, 0.48-1.01; P = 0.06). There was no heterogeneity between trials in any analysis. No interactions between patient characteristics and treatment effects on PFS or OS were found. After adding two supplementary trials to provide a more comprehensive overview, the conclusions remained valid and were strengthened. In a supplementary Bayesian network analysis, no statistically significant differences in survival between different IC regimens were detected. Conclusions: This IPD pooled analysis demonstrates the superiority of additional IC over CCRT alone in locoregionally advanced NPC, with the survival benefit mainly associated with improved distant control. Clin Cancer Res; 24(8); 1824-33. ©2018 AACR . ©2018 American Association for Cancer Research.

Misoprostol for labor induction in women with term premature rupture of membranes: a meta-analysis.

PubMed

Lin, Monique G; Nuthalapaty, Francis S; Carver, Alissa R; Case, Ashley S; Ramsey, Patrick S

2005-09-01

To systematically review published data evaluating the comparative use of misoprostol with placebo/expectant management or oxytocin for labor induction in women with term (> or = 36 weeks of gestation) premature rupture of membranes. PubMed (1966-2005), Ovid (1966-2005), CINAHL, The Cochrane Library, ACP Journal Club, OCLC, abstracts from scientific forums, and bibliographies of published articles were searched using the following keywords: premature rupture of membranes, misoprostol, labor induction, and cervical ripening. Primary authors were contacted directly if the data sought were unavailable or only published in abstract form. Only randomized controlled trials evaluating the efficacy and safety of misoprostol in comparison with placebo or expectant management (n = 6) and oxytocin (n = 9) published in either article or abstract form were analyzed and included in the meta-analysis. Studies were reviewed independently by all authors. Meta-analysis was performed, and the relative risks (RRs) were calculated and pooled for each study outcome. Misoprostol, compared with placebo, significantly increased vaginal delivery less than 12 hours (RR 2.71, 95% confidence interval [CI] 1.87-3.92, P < .001). Misoprostol was similar to oxytocin with respect to vaginal delivery less than 24 hours (RR 1.07, 95% CI 0.88-1.31, P = .50) and less than 12 hours (RR 0.98, 95% CI 0.71-1.35, P = .90). Misoprostol was not associated with an increased risk of tachysystole, hypertonus, or hyperstimulation syndrome when compared with oxytocin and had similar risks for adverse neonatal and maternal outcomes. Misoprostol is an effective and safe agent for induction of labor in women with term premature rupture of membranes. When compared with oxytocin, the risk of contraction abnormalities and the rate of maternal and neonatal complications were similar among the 2 groups.

Pulsatile gonadotrophin releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome.

PubMed

Bayram, N; van Wely, M; van der Veen, F

2004-01-01

In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intravenous or subcutaneous route using a portable pump has been used successfully in patients with hypogonadotrophic hypogonadism. Assuming that the results would be similar in women with polycystic ovary syndrome (PCOS), pulsatile GnRH has been used to induce ovulation in these women. Although ovulation and pregnancy have been achieved, the effectiveness of pulsatile GnRH in women with PCOS has not been clearly demonstrated. To assess the effectiveness of pulsatile GnRH administration in women with polycystic ovary syndrome (PCOS), in terms of ongoing pregnancy, ovulation, clinical pregnancy, ovarian hyperstimulation syndrome (OHSS), multiple pregnancy, miscarriage, and multifollicular growth. We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (searched 13 August 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 2, August 2001), MEDLINE (January 1966 to August 2003), EMBASE (January 1985 to August 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. All relevant published randomised clinical trials were selected for inclusion if treatment consisted of pulsatile GnRH administration versus another treatment for ovulation induction in subfertile women with PCOS. Relevant data were extracted independently by two reviewers (NB, MW). Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention. All trials were screened and analysed for predetermined quality criteria. 2X2 tables were generated for all the relevant outcomes. Odds ratios were generated using the Peto method. Four randomised clinical trials involving 57 women were identified comparing four different treatments: GnRH versus HMG, GnRH and FSH versus FSH, GnRH following pretreatment with GnRH agonist (GnRHa) versus GnRH only, GnRH following pretreatment with GnRHa versus clomiphene citrate. This means that there was only one trial in any one comparison. In two studies, data of pre- and post-crossover were not described separately. All trials were small and of too short duration to show any significant differences in pregnancy results. The odds ratio for ongoing pregnancy, only described in one trial, was 7.5 (95% CI 0.44 to 127) in the comparison GnRH following pretreatment with GnRHa versus GnRH only in favour of the first group. Multiple pregnancies were not seen. Ovarian hyperstimulation syndrome was seen only in women allocated to ovulation induction with HMG. The four trials describing four different comparisons with a short follow up (1 to 3 cycles) were too small to either prove or discard the value of pulsatile GnRH treatment in patients with polycystic ovary syndrome.

Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial.

PubMed

Moll, Etelka; Bossuyt, Patrick M M; Korevaar, Johanna C; Lambalk, Cornelis B; van der Veen, Fulco

2006-06-24

To compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome. Randomised clinical trial. Multicentre trial in 20 Dutch hospitals. 228 women with polycystic ovary syndrome. Clomifene citrate plus metformin or clomifene citrate plus placebo. The primary outcome measure was ovulation. Secondary outcome measures were ongoing pregnancy, spontaneous abortion, and clomifene resistance. 111 women were allocated to clomifene citrate plus metformin (metformin group) and 114 women were allocated to clomifene citrate plus placebo (placebo group). The ovulation rate in the metformin group was 64% compared with 72% in the placebo group, a non-significant difference (risk difference - 8%, 95% confidence interval - 20% to 4%). There were no significant differences in either rate of ongoing pregnancy (40% v 46%; - 6%, - 20% to 7%) or rate of spontaneous abortion (12% v 11%; 1%, - 7% to 10%). A significantly larger proportion of women in the metformin group discontinued treatment because of side effects (16% v 5%; 11%, 5% to 16%). Metformin is not an effective addition to clomifene citrate as the primary method of inducing ovulation in women with polycystic ovary syndrome. Current Controlled Trials ISRCTN55906981 [controlled-trials.com].

Titrated oral misoprostol solution for induction of labour: a multi-centre, randomised trial.

PubMed

Hofmeyr, G J; Alfirevic, Z; Matonhodze, B; Brocklehurst, P; Campbell, E; Nikodem, V C

2001-09-01

To determine the effects of titrated oral misoprostol solution, compared with vaginal dinoprostone. Open, randomised clinical trial. Academic hospitals in South Africa and Liverpool, UK. Women undergoing induction of labour after 34 weeks of pregnancy were allocated by randomised, sealed opaque envelopes, to induction of labour with titrated oral misoprostol solution, or two doses of vaginal dinoprostone (2mg) administered six hours apart. Failure to deliver within 24 hours of randomisation was the primary outcome on which the sample size was based. The data were analysed by intention-to-treat. Six hundred and ninety-five women were randomly allocated: 346 to oral misoprostol and 349 to vaginal dinoprostone. There were no significant differences in substantive outcomes. Vaginal delivery within 24 hours was not achieved in 38% of women in the oral misoprostol group and 36% in the vaginal dinoprostone group (RR 1.08; 95% CI 0.89-1.31). The caesarean section rates were 16% and 20%, respectively (RR 0.80; 95% CI 0.58-1.11). Hyperstimulation with fetal heart rate changes occurred in 4% of women in the oral misoprostol group and 3% after vaginal dinoprostone (RR 1.32, 95% CI 0.59-2.98). The response to induction of labour in women with unfavourable cervices was somewhat slower with misoprostol when membranes were intact, and with dinoprostone when membranes were ruptured. There were no differences in neonatal outcome between the two groups. This new approach to oral misoprostol administration was successful in minimising the risk of uterine hyperstimulation, which has been a feature of misoprostol use for induction of labour, at the expense of a somewhat slower response in women with intact membranes and unfavourable cervices. Misoprostol is not registered for use in pregnant women, and further research is needed to confirm optimal and safe dosages.

Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials.

PubMed

Panés, Julian; Sandborn, William J; Schreiber, Stefan; Sands, Bruce E; Vermeire, Séverine; D'Haens, Geert; Panaccione, Remo; Higgins, Peter D R; Colombel, Jean-Frederic; Feagan, Brian G; Chan, Gary; Moscariello, Michele; Wang, Wenjin; Niezychowski, Wojciech; Marren, Amy; Healey, Paul; Maller, Eric

2017-06-01

Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD). We conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks. Those achieving clinical response-100 or remission were re-randomised to maintenance treatment with placebo, tofacitinib 5 or 10 mg twice daily for 26 weeks. Primary endpoints were clinical remission at the end of the induction study, and clinical response-100 or remission at the end of the maintenance study. 180/280 patients randomised in the induction study were enrolled in the maintenance study. At week 8 of induction, the proportion of patients with clinical remission was 43.5% and 43.0% with 5 and 10 mg twice daily, respectively, compared with 36.7% in the placebo group (p=0.325 and 0.392 for 5 and 10 mg twice daily vs placebo). At week 26 of maintenance, the proportion of patients with clinical response-100 or remission was 55.8% with tofacitinib 10 mg twice daily compared with 39.5% with tofacitinib 5 mg twice daily and 38.1% with placebo (p=0.130 for 10 mg twice daily vs placebo). Compared with placebo, the change in C-reactive protein from baseline was statistically significant (p<0.0001) with 10 mg twice daily after both induction and maintenance treatments. Primary efficacy endpoints were not significantly different from placebo, although there was evidence of a minor treatment effect. No new safety signals were observed for tofacitinib. NCT01393626 and NCT01393899. 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/.

Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710

PubMed Central

Moser, Barry; Stock, Wendy; Gallagher, Robert E.; Willman, Cheryl L.; Stone, Richard M.; Rowe, Jacob M.; Coutre, Steven; Feusner, James H.; Gregory, John; Couban, Stephen; Appelbaum, Frederick R.; Tallman, Martin S.; Larson, Richard A.

2010-01-01

Arsenic trioxide (As2O3) is a highly effective treatment for patients with relapsed acute promyelocytic leukemia (APL); its role as consolidation treatment for patients in first remission has not been defined. We randomized 481 patients (age ≥ 15 years) with untreated APL to either a standard induction regimen of tretinoin, cytarabine, and daunorubicin, followed by 2 courses of consolidation therapy with tretinoin plus daunorubicin, or to the same induction and consolidation regimen plus two 25-day courses of As2O3 consolidation immediately after induction. After consolidation, patients were randomly assigned to one year of maintenance therapy with either tretinoin alone or in combination with methotrexate and mercaptopurine. Ninety percent of patients on each arm achieved remission and were eligible to receive their assigned consolidation therapy. Event-free survival, the primary end point, was significantly better for patients assigned to receive As2O3 consolidation, 80% compared with 63% at 3 years (stratified log-rank test, P < .0001). Survival, a secondary end point, was better in the As2O3 arm, 86% compared with 81% at 3 years (P = .059). Disease-free survival, a secondary end point, was significantly better in the As2O3 arm, 90% compared with 70% at 3 years (P < .0001). The addition of As2O3 consolidation to standard induction and consolidation therapy significantly improves event-free and disease-free survival in adults with newly diagnosed APL. This trial was registered at clinicaltrials.gov (NCT00003934). PMID:20705755

Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial

PubMed Central

Moll, Etelka; Bossuyt, Patrick M M; Korevaar, Johanna C; Lambalk, Cornelis B; van der Veen, Fulco

2006-01-01

Objective To compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome. Design Randomised clinical trial. Setting Multicentre trial in 20 Dutch hospitals. Participants 228 women with polycystic ovary syndrome. Interventions Clomifene citrate plus metformin or clomifene citrate plus placebo. Main outcome measure The primary outcome measure was ovulation. Secondary outcome measures were ongoing pregnancy, spontaneous abortion, and clomifene resistance. Results 111 women were allocated to clomifene citrate plus metformin (metformin group) and 114 women were allocated to clomifene citrate plus placebo (placebo group). The ovulation rate in the metformin group was 64% compared with 72% in the placebo group, a non-significant difference (risk difference - 8%, 95% confidence interval - 20% to 4%). There were no significant differences in either rate of ongoing pregnancy (40% v 46%; - 6%, - 20% to 7%) or rate of spontaneous abortion (12% v 11%; 1%, - 7% to 10%). A significantly larger proportion of women in the metformin group discontinued treatment because of side effects (16% v 5%; 11%, 5% to 16%). Conclusion Metformin is not an effective addition to clomifene citrate as the primary method of inducing ovulation in women with polycystic ovary syndrome. Trial registration Current Controlled Trials ISRCTN55906981 [controlled-trials.com]. PMID:16769748

Puzzles in modern biology. V. Why are genomes overwired?

PubMed

Frank, Steven A

2017-01-01

Many factors affect eukaryotic gene expression. Transcription factors, histone codes, DNA folding, and noncoding RNA modulate expression. Those factors interact in large, broadly connected regulatory control networks. An engineer following classical principles of control theory would design a simpler regulatory network. Why are genomes overwired? Neutrality or enhanced robustness may lead to the accumulation of additional factors that complicate network architecture. Dynamics progresses like a ratchet. New factors get added. Genomes adapt to the additional complexity. The newly added factors can no longer be removed without significant loss of fitness. Alternatively, highly wired genomes may be more malleable. In large networks, most genomic variants tend to have a relatively small effect on gene expression and trait values. Many small effects lead to a smooth gradient, in which traits may change steadily with respect to underlying regulatory changes. A smooth gradient may provide a continuous path from a starting point up to the highest peak of performance. A potential path of increasing performance promotes adaptability and learning. Genomes gain by the inductive process of natural selection, a trial and error learning algorithm that discovers general solutions for adapting to environmental challenge. Similarly, deeply and densely connected computational networks gain by various inductive trial and error learning procedures, in which the networks learn to reduce the errors in sequential trials. Overwiring alters the geometry of induction by smoothing the gradient along the inductive pathways of improving performance. Those overwiring benefits for induction apply to both natural biological networks and artificial deep learning networks.

Intensified High-Dose Chemoradiotherapy With Induction Chemotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer-Safety and Toxicity Results Within a Prospective Trial

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

Poettgen, Christoph, E-mail: christoph.poettgen@uk-essen.d; Eberhardt, Wilfried E.; Gauler, Thomas

2010-03-01

Purpose: To analyze the toxicity profile of an intensified definitive chemoradiotherapy (CRT) schedule in patients with locally advanced non-small-cell lung cancer (Stage IIIA N2/selected IIIB) treated within a prospective multicenter trial. Patients and Methods: After mediastinoscopy and routine staging procedures, three cycles of induction chemotherapy (cisplatin 50 mg/m{sup 2}, Days 1 and 8; paclitaxel 175 mg/m{sup 2} Day 1, every 21 days) were planned, followed by concurrent CRT (accelerated-hyperfractionated regimen, 45 Gy, 2 x 1.5 Gy/d, cisplatin 50 mg/m{sup 2}, Days 64 and 71, vinorelbine 20 mg/m{sup 2}, Days 64 and 71). At 45 Gy, a multidisciplinary panel decision wasmore » made regarding operability. Inoperable patients received definitive radiotherapy (total dose 65 or 71 Gy, depending on the mean lung dose) with additional concurrent chemotherapy (cisplatin 40 mg/m{sup 2}, Day 85; vinorelbine 15 mg/m{sup 2}, Days 85 and 92). Results: A total of 28 patients (23 men and 5 women; median age, 58 years; range 41-73; Stage IIIA in 3 and Stage IIIB in 25) were judged ineligible for surgery by the multidisciplinary panel and underwent definitive CRT (75% of the patients received 71 Gy). The maximum toxicity (Grade 3 or greater) during induction chemotherapy included leukopenia (11%) and anemia (4%). During concurrent CRT, leukopenia (Grade 3 or greater) was observed in 39% of the patients. The maximal nonhematologic toxicity during concurrent CRT included esophagitis (Grade 3 or greater) in 18% and pneumonitis (Grade 3 or greater) in 4% of the patients. At 3 years, the locoregional control rate was 52% (95% confidence interval, 29-75%) and the overall survival rate was 31% (95% confidence interval, 12-50%). Conclusion: This intensified treatment protocol with induction chemotherapy and concurrent CRT, including hyperfractionated-accelerated RT, showed only moderate toxicity and proved feasible. This treatment represents the definitive CRT arm of our ongoing multicenter randomized trial comparing definitive CRT and trimodality treatment.« less

Systematic review with network meta-analysis: comparative assessment of tofacitinib and biological therapies for moderate-to-severe ulcerative colitis.

PubMed

Bonovas, S; Lytras, T; Nikolopoulos, G; Peyrin-Biroulet, L; Danese, S

2018-02-01

Biological therapies have improved the care of patients with ulcerative colitis (UC). Tofacitinib, an oral small-molecule Janus kinase inhibitor, is potentially a new treatment option. To comparatively assess efficacy and harm of tofacitinib and biologics (infliximab, adalimumab, golimumab and vedolizumab) in adult patients not previously exposed to TNF antagonists. We performed a comprehensive search of PubMed, Embase, Scopus, clinical trial registries, regulatory authorities' websites and major conference proceedings, through August 2017, to identify randomised, placebo-controlled or head-to-head trials assessing tofacitinib or biologics as induction and/or maintenance therapy in moderate-to-severe UC. Two reviewers independently extracted study data and outcomes, and investigated each trial's risk-of-bias. We used conventional meta-analysis to synthesise direct evidence, and network meta-analysis for adjusted indirect treatment comparisons. Fifteen randomised, double-blind, placebo-controlled trials (n = 3130) contributed data for induction: All treatments are superior to placebo. Indirect treatment comparisons showed that infliximab is better than adalimumab (OR: 2.01, 95% CI: 1.36-2.98) and golimumab (1.67, 1.08-2.59) in clinical response, better than adalimumab (2.10, 1.21-3.64) in clinical remission, and better than adalimumab (1.87, 1.26-2.79) and golimumab (1.75, 1.13-2.73) in mucosal healing. No indirect comparisons between tofacitinib and biologics reached statistical significance. Nine studies (n = 1776) contributed maintenance data showing that all treatments have higher clinical efficacy than placebo. Safety analyses indicated no increased rates of adverse events for the treatments under evaluation (except for infliximab), while vedolizumab may have an advantage regarding the occurrence of serious adverse events. Tofacitinib and biologics are efficacious and safe for UC. Further high-quality research is warranted to establish the best therapeutic option. © 2017 John Wiley & Sons Ltd.

Women's experiences of outpatient induction of labour with remote continuous monitoring.

PubMed

O'Brien, Ediri; Rauf, Zubair; Alfirevic, Zarko; Lavender, Tina

2013-04-01

to gain insight into women's experiences and preferences for induction in the home as part of a trial investigating the feasibility and acceptability of outpatient induction of labour with remote monitoring. a qualitative study using semi-structured individual interviews. Interview transcripts were subjected to thematic analysis to identify the dominant themes regarding women's experiences of outpatient induction. a large maternity hospital in the North West of England. fifteen women who participated in the main trial of outpatient induction of labour with remote continuous monitoring. three main themes were identified; the need for women to 'labour within their comfort zone'; their desire to achieve 'the next best thing to a normal labour' and the importance of a 'virtual presence' to offer remote reassurance. women's preference for the outpatient setting of induction of labour is dominated by their need to labour within their comfort zone. Outpatient induction offered women the familiarity and freedom of the home environment, and the resulting physical and emotional comforts helped women cope better with their labour and improved their birth experiences. While remote monitoring offered some reassurance, women still depended on effective communication from hospital staff to provide the virtual presence of a health professional in the home. the combination of slow-release prostaglandin and a remote monitoring device may provide low risk women with an improved induction and labour experience. While ongoing studies continue to explore further the safety of interventions at home, this study has importantly considered women's views and confirmed that induction at home is not only acceptable to women but also that the outpatient experience is preferable to long inpatient inductions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Methotrexate versus cyclophosphamide for remission maintenance in ANCA-associated vasculitis: A randomised trial.

PubMed

Maritati, Federica; Alberici, Federico; Oliva, Elena; Urban, Maria L; Palmisano, Alessandra; Santarsia, Francesca; Andrulli, Simeone; Pavone, Laura; Pesci, Alberto; Grasselli, Chiara; Santi, Rosaria; Tumiati, Bruno; Manenti, Lucio; Buzio, Carlo; Vaglio, Augusto

2017-01-01

The treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is based on remission-induction and remission-maintenance. Methotrexate is a widely used immunosuppressant but only a few studies explored its role for maintenance in AAV. This trial investigated the efficacy and safety of methotrexate as maintenance therapy for AAV. In this single-centre, open-label, randomised trial we compared methotrexate and cyclophosphamide for maintenance in AAV. We enrolled patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), the latter with poor-prognosis factors and/or peripheral neuropathy. Remission was induced with cyclophosphamide. At remission, the patients were randomised to receive methotrexate or to continue with cyclophosphamide for 12 months; after treatment, they were followed for another 12 months. The primary end-point was relapse; secondary end-points included renal outcomes and treatment-related toxicity. Of the 94 enrolled patients, 23 were excluded during remission-induction or did not achieve remission; the remaining 71 were randomised to cyclophosphamide (n = 33) or methotrexate (n = 38). Relapse frequencies at months 12 and 24 after randomisation were not different between the two groups (p = 1.00 and 1.00). Relapse-free survival was also comparable (log-rank test p = 0.99). No differences in relapses were detected between the two treatments when GPA+MPA and EGPA were analysed separately. There were no differences in eGFR at months 12 and 24; proteinuria declined significantly (from diagnosis to month 24) only in the cyclophosphamide group (p = 0.0007). No significant differences in adverse event frequencies were observed. MTX may be effective and safe for remission-maintenance in AAV. clinicaltrials.gov NCT00751517.

Update on the use of meningococcal serogroup C CRM₁₉₇-conjugate vaccine (Meningitec) against meningitis.

PubMed

Badahdah, Al-Mamoon; Rashid, Harunor; Khatami, Ameneh

2016-01-01

Meningitec is a CRM197-conjugated meningococcal serogroup C (MenC) vaccine, first licensed in 1999. It has been used as a primary and booster vaccine in infants, toddlers, older children and adults, and has been shown to be immunogenic and well-tolerated in all age groups, including premature infants. Vaccine effectiveness has been demonstrated using combined data on all three licensed MenC conjugate vaccines. Evidence from clinical trials, however, suggests that the different MenC conjugate vaccines behave differently with respect to the induction and persistence of bactericidal antibody and generation of immune memory. It appears that Meningitec has a less favorable immunologic profile compared particularly to tetanus toxoid (TT) MenC conjugate vaccines. Data from comparative trials have raised interesting questions on priming of the immune system by conjugate vaccines, particularly in infants. The results from these and other studies are reviewed here with specific focus on Meningitec.

Biomarkers in Advanced Larynx Cancer

PubMed Central

Bradford, Carol R.; Kumar, Bhavna; Bellile, Emily; Lee, Julia; Taylor, Jeremy; D’Silva, Nisha; Cordell, Kitrina; Kleer, Celina; Kupfer, Robbi; Kumar, Pawan; Urba, Susan; Worden, Francis; Eisbruch, Avraham; Wolf, Gregory T.; Teknos, Theodoros N.; Prince, Mark E.P.; Chepeha, Douglas B.; Hogikyan, Norman D.; Moyer, Jeffrey S.; Carey, Thomas E.

2014-01-01

Objectives/Hypothesis To determine if tumor biomarkers were predictive of outcome in a prospective cohort of patients with advanced larynx cancer treated in a phase II clinical trial. Study Design Prospectively collected biopsy specimens from 58 patients entered into a Phase II trial of organ preservation in advanced laryngeal cancer were evaluated for expression of a large panel of biomarkers and correlations with outcome were determined. Methods Tissue microarrays were constructed from pretreatment biopsies and stained for cyclin D1, CD24, EGFR, MDM2, PCNA, p53, survivin, Bcl-xL, Bcl-2, BAK, rhoC, and NFκB. Pattern of invasion and p53 mutations were assessed. Correlations with overall survival (OS), disease-specific survival (DSS), time free from indication of surgery, induction chemotherapy response, and chemoradiation response were determined. Cox models were used to assess combinations of these biomarkers. Results Low expression of BAK was associated with response to induction chemotherapy. Low expression of BAK and cytoplasmic NFκB was associated with chemoradiation response. Aggressive histologic growth pattern was associated with response induction chemotherapy. Expression of cyclin D1 was predictive of overall and disease-specific survival. Overexpression of EGFR was also associated with an increased risk of death from disease. Bcl-xL expression increased significantly in persistent/recurrent tumors specimens when compared to pretreatment specimens derived from the same patient (p = 0.0003). Conclusions Evaluation of biomarker expression in pretreatment biopsy specimens can lend important predictive and prognostic information for patients with advanced larynx cancer. PMID:23775802

Results and conclusions of the European Intergroup EURO-LB02 trial in children and adolescents with lymphoblastic lymphoma.

PubMed

Landmann, Eva; Burkhardt, Birgit; Zimmermann, Martin; Meyer, Ulrike; Woessmann, Wilhelm; Klapper, Wolfram; Wrobel, Grazyna; Rosolen, Angelo; Pillon, Marta; Escherich, Gabriele; Attarbaschi, Andishe; Beishuizen, Auke; Mellgren, Karin; Wynn, Robert; Ratei, Richard; Plesa, Adriana; Schrappe, Martin; Reiter, Alfred; Bergeron, Christophe; Patte, Catherine; Bertrand, Yves

2017-12-01

In the European Intergroup EURO-LB02 trial, children and adolescents with lymphoblastic lymphoma underwent the non-Hodgkin lymphoma Berlin-Frankfurt-Münster protocol without prophylactic cranial radiotherapy. The primary aims of this trial were to test whether replacing prednisone with dexamethasone during induction increases event-free survival in the subgroups with T-cell lymphoblastic lymphoma and whether therapy duration could be reduced from 24 to 18 months (factorial design, randomizations). These questions could not be answered due to premature closure of the trial. Here we report on the secondary aims of the trial: whether the results of the NHL-BFM90 study could be reproduced and evaluation of disease features and prognostic factors. Three hundred and nineteen patients (66 with precursor B-cell lymphoblastic lymphoma, 233 with T-cell lymphoblastic lymphoma, 12 with mixed phenotype, 8 not classifiable) were enrolled. In induction, 215 patients received prednisone and 104 patients received dexamethasone. The median follow-up was 6.8 years (range, 3.0-10.3). The 5-year event-free survival was 82±2% [12 toxic deaths, 5 secondary malignancies, 43 non-response/relapse (central nervous system n=9; all received prednisone during induction)]. The event-free survival rate was 80±5% for patients with precursor B-cell lymphoblastic lymphoma, 82±3% for those with T-cell lymphoblastic lymphoma, and 100% for patients with a mixed phenotype. During induction, significantly more grade III/IV toxicities were observed in patients receiving dexamethasone, resulting in significant treatment delays. The number of toxic deaths did not differ significantly. The only variable associated with outcome was performance status at diagnosis. The 90% event-free survival rate for patients with T-cell lymphoblastic lymphoma shown in study NHL-BFM90 was not replicated, mainly due to more toxic deaths and central nervous system relapses. Dexamethasone in induction may prevent central nervous system relapse more effectively than prednisone but produces a higher burden of toxicity. (#NCT00275106). Copyright© 2017 Ferrata Storti Foundation.

Succinylcholine versus rocuronium for rapid sequence intubation in intensive care: a prospective, randomized controlled trial

PubMed Central

2011-01-01

Introduction Succinylcholine and rocuronium are widely used to facilitate rapid sequence induction (RSI) intubation in intensive care. Concerns relate to the side effects of succinylcholine and to slower onset and inferior intubation conditions associated with rocuronium. So far, succinylcholine and rocuronium have not been compared in an adequately powered randomized trial in intensive care. Accordingly, the aim of the present study was to compare the incidence of hypoxemia after rocuronium or succinylcholine in critically ill patients requiring an emergent RSI. Methods This was a prospective randomized controlled single-blind trial conducted from 2006 to 2010 at the University Hospital of Basel. Participants were 401 critically ill patients requiring emergent RSI. Patients were randomized to receive 1 mg/kg succinylcholine or 0.6 mg/kg rocuronium for neuromuscular blockade. The primary outcome was the incidence of oxygen desaturations defined as a decrease in oxygen saturation ≥ 5%, assessed by continuous pulse oxymetry, at any time between the start of the induction sequence and two minutes after the completion of the intubation. A severe oxygen desaturation was defined as a decrease in oxygen saturation ≥ 5% leading to a saturation value of ≤ 80%. Results There was no difference between succinylcholine and rocuronium regarding oxygen desaturations (succinylcholine 73/196; rocuronium 66/195; P = 0.67); severe oxygen desaturations (succinylcholine 20/196; rocuronium 20/195; P = 1.0); and extent of oxygen desaturations (succinylcholine -14 ± 12%; rocuronium -16 ± 13%; P = 0.77). The duration of the intubation sequence was shorter after succinycholine than after rocuronium (81 ± 38 sec versus 95 ± 48 sec; P = 0.002). Intubation conditions (succinylcholine 8.3 ± 0.8; rocuronium 8.2 ± 0.9; P = 0.7) and failed first intubation attempts (succinylcholine 32/200; rocuronium 36/201; P = 1.0) did not differ between the groups. Conclusions In critically ill patients undergoing emergent RSI, incidence and severity of oxygen desaturations, the quality of intubation conditions, and incidence of failed intubation attempts did not differ between succinylcholine and rocuronium. Trial Registration ClinicalTrials.gov, number NCT00355368. PMID:21846380

Equivalence Class Formation in a Trace Stimulus Pairing Two-Response Format: Effects of Response Labels and Prior Programmed Transitivity Induction

ERIC Educational Resources Information Center

Fields, Lanny; Doran, Erica; Marroquin, Michael

2009-01-01

Three experiments identified factors that did and did not enhance the formation of two-node four-member equivalence classes when training and testing were conducted with trials presented in a trace stimulus pairing two-response (SP2R) format. All trials contained two separately presented stimuli. Half of the trials, called within-class trials,…

A randomized 2×2 factorial trial, part 1: single-dose rabbit antithymocyte globulin induction may improve renal transplantation outcomes.

PubMed

Stevens, R Brian; Foster, Kirk W; Miles, Clifford D; Lane, James T; Kalil, Andre C; Florescu, Diana F; Sandoz, John P; Rigley, Theodore H; Nielsen, Kathleen J; Skorupa, Jill Y; Kellogg, Anna M; Malik, Tamer; Wrenshall, Lucile E

2015-01-01

We conducted a randomized and unblinded 2 × 2 sequential-factorial trial, composed of an induction arm (part 1) comparing single-dose (SD) versus divided-dose rabbit antithymocyte globulin (rATG), and a maintenance arm (part 2) comparing tacrolimus minimization versus withdrawal. We report the long-term safety and efficacy of SD-rATG induction in the context of early steroid withdrawal and tacrolimus minimization or withdrawal. Patients (n=180) received 6 mg/kg rATG, SD or four alternate-day doses (1.5 mg/kg/dose), with early steroid withdrawal and tacrolimus or sirolimus maintenance. After 6 months targeted maintenance levels were tacrolimus, 2 to 4 ng/mL and sirolimus, 4 to 6 ng/mL or, if calcineurin inhibitor-withdrawn, sirolimus 8 to 12 ng/mL with mycophenolate mofetil 2 g two times per day. Primary endpoints were renal function (abbreviated modification of diet in renal disease) and chronic graft histopathology (Banff). Secondary endpoints included patient survival, graft survival, biopsy-proven rejection, and infectious or noninfectious complications. Follow-up averaged longer than 4 years. Tacrolimus or sirolimus and mycophenolate mofetil exposure was identical between groups. The SD-rATG associated with improved renal function (2-36 months; P<0.001) in deceased donor recipients. The SD-rATG associated with quicker lymphocyte, CD4 T cell, and CD4-CD8 recovery and fewer infections. Cox multivariate hazard modeling showed divided-dose-rATG (P=0.019), deceased donor (P=0.003), serious infection (P=0.0.018), and lower lymphocyte count (P=0.001) associated with increased mortality. Patients with all four covariates showed a 27-fold increased likelihood of death (P=0.00002). Chronic graft histopathology, rejection rates, and death-censored graft survival were not significantly different between groups. The SD-rATG induction improves the 3-year renal function in recipients of deceased donor kidneys. This benefit, along with possibly improved patient survival and fewer infections suggest that how rATG is administered may impact its efficacy and safety.

A Randomized 2×2 Factorial Trial, Part 1: Single-Dose Rabbit Antithymocyte Globulin Induction May Improve Renal Transplantation Outcomes

PubMed Central

Stevens, R. Brian; Foster, Kirk W.; Miles, Clifford D.; Lane, James T.; Kalil, Andre C.; Florescu, Diana F.; Sandoz, John P.; Rigley, Theodore H.; Nielsen, Kathleen J.; Skorupa, Jill Y.; Kellogg, Anna M.; Malik, Tamer; Wrenshall, Lucile E.

2015-01-01

Background We conducted a randomized and unblinded 2×2 sequential-factorial trial, composed of an induction arm (part 1) comparing single-dose (SD) versus divided-dose rabbit antithymocyte globulin (rATG), and a maintenance arm (part 2) comparing tacrolimus minimization versus withdrawal. We report the long-term safety and efficacy of SD-rATG induction in the context of early steroid withdrawal and tacrolimus minimization or withdrawal. Methods Patients (n=180) received 6 mg/kg rATG, SD or four alternate-day doses (1.5 mg/kg/dose), with early steroid withdrawal and tacrolimus or sirolimus maintenance. After 6 months targeted maintenance levels were tacrolimus, 2 to 4 ng/mL and sirolimus, 4 to 6 ng/mL or, if calcineurin inhibitor–withdrawn, sirolimus 8 to 12 ng/mL with mycophenolate mofetil 2 g two times per day. Primary endpoints were renal function (abbreviated modification of diet in renal disease) and chronic graft histopathology (Banff). Secondary endpoints included patient survival, graft survival, biopsy-proven rejection, and infectious or noninfectious complications. Results Follow-up averaged longer than 4 years. Tacrolimus or sirolimus and mycophenolate mofetil exposure was identical between groups. The SD-rATG associated with improved renal function (2-36 months; P<0.001) in deceased donor recipients. The SD-rATG associated with quicker lymphocyte, CD4 T cell, and CD4-CD8 recovery and fewer infections. Cox multivariate hazard modeling showed divided-dose–rATG (P=0.019), deceased donor (P=0.003), serious infection (P=0.0.018), and lower lymphocyte count (P=0.001) associated with increased mortality. Patients with all four covariates showed a 27-fold increased likelihood of death (P=0.00002). Chronic graft histopathology, rejection rates, and death-censored graft survival were not significantly different between groups. Conclusion The SD-rATG induction improves the 3-year renal function in recipients of deceased donor kidneys. This benefit, along with possibly improved patient survival and fewer infections suggest that how rATG is administered may impact its efficacy and safety. PMID:25083614

Avacopan in the treatment of ANCA-associated vasculitis.

PubMed

Tesar, Vladimir; Hruskova, Zdenka

2018-05-08

ANCA-associated vasculitis (AAV) is a rare but potentially life-threatening disease. Currently used induction treatment (cyclophosphamide or rituximab with high-dose corticosteroids) has significantly improved outcome of AAV, but is associated with high toxicity. Alternative complement pathway activation was shown to play a role in the pathogenesis of AAV, thus providing rationale for the use of avacopan, a selective inhibitor of C5a receptor, in the treatment of AAV. Areas covered: Pharmacokinetic and pharmocodynamic properties of avacopan, clinical efficacy and safety and tolerability of avacopan in so far performed clinical trials in patients with AAV are reviewed and discussed. Expert opinion: Avacopan was shown to have at least similar efficacy compared to high dose corticosteroids in patients with active AAV with renal involvement, while there were no major safety issues reported. Replacement of corticosteroids should decrease the corticosteroid-related toxicity and improve long-term outcome of patients with AAV even though this still needs to be confirmed in a larger trial. Data on long-term outcome of avacopan-treated patients are currently lacking and will be eagerly awaited. In the future, avacopan could replace corticosteroids not only in the induction phase, but also in the maintenance treatment of AAV.

The influence of empathic concern on prosocial behavior in children.

PubMed

Williams, Amanda; O'Driscoll, Kelly; Moore, Chris

2014-01-01

This research explored the influence of empathic distress on prosocial behavior in a resource allocation task with children. Children were randomly assigned to one of two conditions before engaging in a sticker sharing task; watching either a video of a girl upset that her dog had gone missing (emotion induction condition), or a video of the same girl preparing for a yard sale (control condition). In study one, 5-6 year old children in the emotion induction condition rated the emotional state of both the protagonist and the self more negatively, and also exhibited more prosocial behavior; sharing more in advantageous inequity (AI) trials, and less often withholding a benefit in disadvantageous inequity trials, than the control group. Prosocial behavior was significantly correlated with ratings of the emotional state of the protagonist but not with own emotional state, suggesting that empathic concern rather than personal distress was the primary influence on prosocial behavior. In study two, 3-year-olds were tested on AI trials alone, and like the 5 and 6-year-olds, showed more prosocial behavior in the emotion induction condition than the control.

The influence of empathic concern on prosocial behavior in children

PubMed Central

Williams, Amanda; O’Driscoll, Kelly; Moore, Chris

2014-01-01

This research explored the influence of empathic distress on prosocial behavior in a resource allocation task with children. Children were randomly assigned to one of two conditions before engaging in a sticker sharing task; watching either a video of a girl upset that her dog had gone missing (emotion induction condition), or a video of the same girl preparing for a yard sale (control condition). In study one, 5–6 year old children in the emotion induction condition rated the emotional state of both the protagonist and the self more negatively, and also exhibited more prosocial behavior; sharing more in advantageous inequity (AI) trials, and less often withholding a benefit in disadvantageous inequity trials, than the control group. Prosocial behavior was significantly correlated with ratings of the emotional state of the protagonist but not with own emotional state, suggesting that empathic concern rather than personal distress was the primary influence on prosocial behavior. In study two, 3-year-olds were tested on AI trials alone, and like the 5 and 6-year-olds, showed more prosocial behavior in the emotion induction condition than the control. PMID:24860537

[Locally advanced head and neck cancers: recommendations of an expert panel and perspectives for the use of TPF regimen (docetaxel, cisplatin and fluoro-uracil) as induction therapy].

PubMed

Bardet, E; Bourhis, J; Cals, L; Fayette, J; Guigay, J; Hans, S; Saint-Guily, J Lacau; Lagarde, F; Lallemant, B; Milano, G; Rolland, F; Lefebvre, J-L

2009-10-01

The purpose of the present article was to evaluate indications, regimens, treatment modalities, and predictive factors of response to treatment in locally advanced squamous cell carcinoma of the head and neck (SCCHN). An expert panel including otolaryngology and head and neck surgery specialists, oncologists, radiotherapists and biologists analyzed the literature providing a synthesis and giving some recommendations. Findings from the main randomized phase III trials highlight that the TPF regimen (docetaxel, cisplatin, fluorouracil) represent a preferential option when induction chemotherapy is indicated in either operable or non-operable patients. Given the potential fragility of patients presenting with SCCHN, treatment modalities in routine use require applying preventive measures and tailored follow-up according to each patient's profile. As regards predictive factors of response to TPF regimen, no factor is currently validated, but ongoing trials should provide better knowledge. Progresses in induction chemotherapy have allowed improving the prognosis of patients with locally advanced SCCHN. The TPF regimen represents a major improvement in this indication, and ongoing strategic clinical trials should refine its indications.

Induction of labor using prostaglandin vaginal gel: cost analysis comparing early amniotomy with repeat prostaglandin gel.

PubMed

Beckmann, Michael; Merollini, Katharina; Kumar, Sailesh; Flenady, Vicki

2016-04-01

In a randomized controlled trial of two policies for induction of labor (IOL) using Prostaglandin E2 (PGE2) vaginal gel, women who had an earlier amniotomy experienced a shorter IOL-to-birth time. To report the cost analysis of this trial and determine if there are differences in healthcare costs when an early amniotomy is performed as opposed to giving more PGE2 vaginal gel, for women undergoing IOL at term. Following an evening dose of PGE2 vaginal gel, 245 women with live singleton pregnancies, ≥37+0 weeks, were randomized into an amniotomy or repeat-PGE2 group. Healthcare costs were a secondary outcome measure, sourced from hospital finance systems and included staff costs, equipment and consumables, pharmacy, pathology, hotel services and business overheads. A decision analytic model, specifically a Markov chain, was developed to further investigate costs, and a Monte Carlo simulation was performed to confirm the robustness of these findings. Mean and median costs and cost differences between the two groups are reported, from the hospital perspective. The healthcare costs associated with IOL were available for all 245 trial participants. A 1000-patient cohort simulation demonstrated that performing an early amniotomy was associated with a cost-saving of $AUD289 ($AUD7094 vs $AUD7338) per woman induced, compared with administering more PGE2. Propagating the uncertainty through the model 10,000 times, early amniotomy was associated with a median cost savings of $AUD487 (IQR -$AUD573, +$AUD1498). After an initial dose of PGE2 vaginal gel, a policy of administering more PGE2 when the Modified Bishop's score is <7 was associated with increased healthcare costs compared with a policy of performing an amniotomy, if technically possible. Length of stay was the main driver of healthcare costs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Vedolizumab as induction and maintenance therapy for ulcerative colitis.

PubMed

Feagan, Brian G; Rutgeerts, Paul; Sands, Bruce E; Hanauer, Stephen; Colombel, Jean-Frédéric; Sandborn, William J; Van Assche, Gert; Axler, Jeffrey; Kim, Hyo-Jong; Danese, Silvio; Fox, Irving; Milch, Catherine; Sankoh, Serap; Wyant, Tim; Xu, Jing; Parikh, Asit

2013-08-22

Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis. We conducted two integrated randomized, double-blind, placebo-controlled trials of vedolizumab in patients with active disease. In the trial of induction therapy, 374 patients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to vedolizumab at week 6 were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. Response rates at week 6 were 47.1% and 25.5% among patients in the vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval [CI], 11.6 to 31.7; P<0.001). At week 52, 41.8% of patients who continued to receive vedolizumab every 8 weeks and 44.8% of patients who continued to receive vedolizumab every 4 weeks were in clinical remission (Mayo Clinic score ≤2 and no subscore >1), as compared with 15.9% of patients who switched to placebo (adjusted difference, 26.1 percentage points for vedolizumab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P<0.001] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [95% CI, 17.9 to 40.4; P<0.001]). The frequency of adverse events was similar in the vedolizumab and placebo groups. Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.).

High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European Neuroblastoma Study Group.

PubMed

Pritchard, Jon; Cotterill, Simon J; Germond, Shirley M; Imeson, John; de Kraker, Jan; Jones, David R

2005-04-01

High dose myeloablative chemotherapy ("megatherapy"), with haematopoietic stem cell support, is now widely used to consolidate response to induction chemotherapy in patients with advanced neuroblastoma. In this study (European Neuroblastoma Study Group, ENSG1), the value of melphalan myeloablative "megatherapy" was evaluated in a randomised, multi-centre trial. Between 1982 and 1985, 167 children with stages IV and III neuroblastoma (123 stage IV > 1 year old at diagnosis and 44 stage III and stage IV from 6 to 12 months old at diagnosis) were treated with oncovin, cisplatin, epipodophyllotoxin, and cyclophosphamide (OPEC) induction chemotherapy every 3 weeks. After surgical excision of primary tumour, the 90 patients (69% of the total) who achieved complete response (CR) or good partial response (GPR) were eligible for randomisation either to high dose melphalan (180 mg per square meter) with autologous bone marrow support or to no further treatment. Sixty-five (72%) of eligible children were actually randomised and 21 of these patients were surviving at time of this analysis, with median follow-up from randomisation of 14.3 years. Five year event-free survival (EFS) was 38% (95% confidence interval (CI) 21-54%) in the melphalan-treated group and 27% (95% CI 12-42%) in the "no-melphalan" group. This difference was not statistically significant (P = 0.08, log rank test) but for the 48 randomised stage IV patients aged >1 year at diagnosis outcome was significantly better in the melphalan-treated group-5 year EFS 33% versus 17% (P = 0.01, log rank test). In this trial, high dose melphalan improved the length of EFS and overall survival of children with stage IV neuroblastoma >1 year of age who achieved CR or GPR after OPEC induction therapy and surgery. Multi-agent myeloablative regimens are now widely used as consolidation therapy for children with stage IV disease and in those with other disease stages when the MYCN gene copy number in tumour cells is amplified. Because they are more toxic, complex, and costly these combination megatherapy regimens should be compared with single agent melphalan in randomised clinical trials.

Comparison of single-use and reusable metal laryngoscope blades for orotracheal intubation during rapid sequence induction of anesthesia: a multicenter cluster randomized study.

PubMed

Amour, Julien; Le Manach, Yannick Le; Borel, Marie; Lenfant, François; Nicolas-Robin, Armelle; Carillion, Aude; Ripart, Jacques; Riou, Bruno; Langeron, Olivier

2010-02-01

Single-use metal laryngoscope blades are cheaper and carry a lower risk of infection than reusable metal blades. The authors compared single-use and reusable metal blades during rapid sequence induction of anesthesia in a multicenter cluster randomized trial. One thousand seventy-two adult patients undergoing general anesthesia under emergency conditions and requiring rapid sequence induction were randomly assigned on a weekly basis to either single-use or reusable metal blades (cluster randomization). After induction, a 60-s period was allowed to complete intubation. In the case of failed intubation, a second attempt was performed using the opposite type of blade. The primary endpoint was the rate of failed intubation, and the secondary endpoints were the incidence of complications (oxygen desaturation, lung aspiration, and/or oropharynx trauma) and the Cormack and Lehane score. Both groups were similar in their main characteristics, including the risk factors for difficult intubation. The rate of failed intubation was significantly decreased with single-use metal blades at the first attempt compared with reusable blades (2.8 vs. 5.4%, P < 0.05). In addition, the proportion of grades III and IV in Cormack and Lehane score were also significantly decreased with single-use metal blades (6 vs. 10%, P < 0.05). The global complication rate did not reach statistical significance, although the same trend was noted (6.8% vs. 11.5%, P = not significant). An investigator survey and a measure of illumination pointed that illumination might have been responsible for this result. The single-use metal blade was more efficient than a reusable metal blade in rapid sequence induction of anesthesia.

Repeated Induction of Inattentional Blindness in a Simulated Aviation Environment

NASA Technical Reports Server (NTRS)

Kennedy, Kellie D.; Stephens, Chad L.; Williams, Ralph A.; Schutte, Paul C.

2017-01-01

The study reported herein is a subset of a larger investigation on the role of automation in the context of the flight deck and used a fixed-based, human-in-the-loop simulator. This paper explored the relationship between automation and inattentional blindness (IB) occurrences in a repeated induction paradigm using two types of runway incursions. The critical stimuli for both runway incursions were directly relevant to primary task performance. Sixty non-pilot participants performed the final five minutes of a landing scenario twice in one of three automation conditions: full automation (FA), partial automation (PA), and no automation (NA). The first induction resulted in a 70 percent (42 of 60) detection failure rate with those in the PA condition significantly more likely to detect the incursion compared to the FA condition or the NA condition. The second induction yielded a 50 percent detection failure rate. Although detection improved (detection failure rates declined) in all conditions, those in the FA condition demonstrated the greatest improvement with doubled detection rates. The detection behavior in the first trial did not preclude a failed detection in the second induction. Group membership (IB vs. Detection) in the FA condition showed a greater improvement than those in the NA condition and rated the Mental Demand and Effort subscales of the NASA-TLX (NASA Task Load Index) significantly higher for Time 2 compared Time 1. Participants in the FA condition used the experience of IB exposure to improve task performance whereas those in the NA condition did not, indicating the availability and reallocation of attentional resources in the FA condition. These findings support the role of engagement in operational attention detriment and the consideration of attentional failure causation to determine appropriate mitigation strategies.

Natalizumab for induction of remission in Crohn's disease.

PubMed

Macdonald, J K; McDonald, J W D

2006-07-19

The pathogenesis of Crohn's disease involves migration of leukocytes into gut tissue and subsequent inflammation. Natalizumab (Tysabri, Elan Pharmaceuticals and Biogen Idec) a recombinant humanized IgG4 monoclonal antibody that blocks adhesion and subsequent migration of leukocytes into the gut by binding the alpha4 integrin is a member of a new class of molecules known as selective adhesion molecule (SAM) inhibitors. The results of animal studies suggest that alpha4 integrin blockade could be a useful therapy for inflammatory bowel disease. The results of randomized controlled trials suggest that natalizumab may be an effective therapy for active Crohn's disease. This systematic review summarizes the current evidence on the use of natalizumab for the induction of remission in Crohn's disease. To determine the efficacy and safety of natalizumab for induction of remission in Crohn's disease. A computer assisted search of the Cochrane Central Register of Controlled Trials, the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Review Group Specialized Trials Register, MEDLINE and EMBASE was performed to identify relevant publications between 1966 and June 2005. The medical subject heading (MeSH) terms "Crohn disease" or "inflammatory bowel disease", "Natalizumab" or "Antegren" or "Tysabri" and "Antibodies, Monoclonal" were used to perform key word searches of each database. Manual searches of reference lists from potentially relevant papers were performed in order to identify additional studies that may have been missed using the computer-assisted search strategy. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. Personal contacts, leaders in the field, and the manufacturers were contacted to identify other studies which may not be published. We included only randomized controlled trials comparing natalizumab to a placebo or control therapy for the induction of remission in Crohn's disease. Data were analyzed using Review Manager (RevMan 4.2.8). All data were analyzed on an intention-to-treat basis. For pooled data, summary test statistics were derived using the relative risk and 95% confidence intervals. Fixed and random effects models were used where appropriate. The definitions of treatment success, remission and clinical improvement were set by the authors of each paper, and the data were combined for analysis only if these definitions were sufficiently similar. Pooled data from the three included studies suggest that natalizumab (3 to 4 mg/kg) may be effective for induction of clinical response and remission in patients with moderately to severely active Crohn's disease. This benefit is statistically significant for one, two and three infusion treatments. There was a trend toward increased benefit with additional infusions of natalizumab. Natalizumab appears to provide greater benefit for patient subgroups characterized by objective confirmation of active inflammation or chronically active disease despite conventional therapies. These subgroup analyses demonstrated significantly greater clinical response and remission rates for natalizumab compared with placebo in patients with elevated C-reactive protein levels, active disease despite the use of immunosuppressants, or prior anti-tumor necrosis factor therapy. These benefits were apparent for both short term (one infusion) and longer term treatment (two or three infusions). Natalizumab was generally well tolerated and the safety profile observed in the three included studies was similar. Adverse events occurred infrequently and were experienced by a similar proportion of natalizumab and placebo treated patients. There were no statistically significant differences between natalizumab and placebo treated patients in the proportions of patients who withdrew due to adverse events or those who experienced serious adverse events. The included trials lacked adequate power to detect serious adverse events that occur infrequently. Recently, two patients with multiple sclerosis treated with natalizumab in combination with interferon beta-1a and one patient with Crohn's disease treated with natalizumab in combination with azathioprine developed progressive multifocal leukoencephalopathy (PML) resulting in two patient deaths. As a result all dosing in clinical trials and commercial use of natalizumab has been suspended. A retrospective investigation was conducted to assess the risk of PML in natalizumab treated patients and no new cases were identified. Pooled data and the results of an ongoing study suggest that natalizumab may be effective for induction of clinical response and remission in patients with moderately to severely active Crohn's disease. The clinical benefit of induction therapy with natalizumab in Crohn's disease should be weighed against the potential risk of serious adverse events. Currently natalizumab is not available on the market for routine clinical use as a consequence of the unexpected association with PML. However, preliminary data from the retrospective investigation of adverse events associated with natalizumab suggest that it may be possible to identify patients at risk for PML by testing for the appearance of JC virus in plasma.

Comparing the Effect of Metformin and Acarbose Accompanying Clomiphene on the Successful Ovulation Induction in Infertile Women with Polycystic Ovary Syndrome.

PubMed

Rezai, Masomeh; Jamshidi, Mohmmad; Mohammadbeigi, Robabeh; Seyedoshohadaei, Fariba; Mohammadipour, Somaye; Moradi, Ghobad

2016-09-01

The aim of this study was to compare the effects of Metformin and Acarbose accompanying Clomiphene on the successful ovulation induction in infertile women with polycystic ovary syndrome.This randomized double blind clinical trial study was performed on 60 women with polycystic ovary syndrome. Women were selected and randomly divided in two control and intervention groups. Intervention group received Acarbose 100 mg/day for 3 months. In the first, second, and third weeks, they received 1 tablet, 2 tablets, and 3 tablets per day respectively. In addition, they received 100 mg Clomiphene from third to seventh day of menstruation, during the 3 month treatment period. The control group received Metformin 500 mg/day for 3 months. In the first, second, and third weeks, they received 1 tablet, 2 tablets, and 3 tablets per day respectively. In addition, they received 100 mg Clomiphene from third to seventh day of menstruation, during the 3 month treatment period. All the subjects in both groups before and after the treatment were examined for hirsutism, acne, oral glucose tolerance test, serum triglycerides, cholesterol, LDL, HDL. Also, induction of ovulation was assessed by vaginal ultrasound. The Mean of BMI and fasting glucose tolerance test in Acarbose group was less than Metformin group (P = 0.05). The mean of triglycerides, LDL and HDL levels did not differ between the two groups after the intervention (P > 0.05). The mean of cholesterol levels were different in the two groups after the intervention (P = 0.04). Frequency of ovulation induction in those who received Acarbose (78.5%) was more than those who received Metformin (46.6) (P = 0.012). Comparing with Metformin, Acarbose accompanying Clomiphene was more effective in ovulation induction and decreasing body mass index in infertile women with polycystic ovary syndrome.

Effects of preemptive analgesia with parecoxib sodium on haemodynamics and plasma stress hormones in surgical patients with thyroid carcinoma.

PubMed

Wang, Lian-Dong; Gao, Xia; Li, Jun-Ying; Yu, Hong-Yan; Su, Hai-Wen; Liu, Lian-Zhong; Qi, Jun

2015-01-01

To investigate the effects of preemptive analgesia with parecoxib sodium on haemodynamics and plasma stress hormones in surgical patients with thyroid carcinoma. Fifty-seven patients with thyroid carcinoma who underwent thyroidectomy selectively in Laiwu Hospital Affiliated to Taishan Medical University and Binzhou People's Hospital were selected and randomly divided into three groups, 19 cases in each group. The control group was intravenously injected 0.9% sodium chloride injection before anesthesia induction; trial group I was intravenously injected with parecoxib sodium 20 min before anesthesia induction; based on trial group I, trial group II was injected with parecoxib sodium again 12 h after surgery. The levels of plasma norepinephrine (NE), cortisol (Cor) and blood glucose before, 12 and 24 h after surgery and changes of haemodynamics before surgery, at the end of surgery and 12, 24 and 48 h after surgery were compared in the three groups. Besides, visual analogue scale (VAS) scores were recorded 4, 8, 12 and 24 h after surgery. 12 and 24 h after surgery, the levels of plasma NE and Cor in three groups rose dramatically (P<0.05 or (P<0.01); The levels of plasma NE and Cor in trial groups I and II were evidently lower than in control group (P<0.05 or P<0.01), and those in trial group II slightly lower than in trial group I. 12 h after surgery, the heart rates (HR) and systolic pressures (SBP) in trial groups I and II increased obviously by comparison to surgery before (P<0.05 or P<0.01), but gradually returned to the preoperative level. HR, SBP and diastolic pressures (DBP) in trial groups I and II at the end of surgery and 12 h after surgery were all lower than in the control group, and significant differences were present (P<0.05 or (P<0.01). At 4, 8, 12 and 24 h after surgery, VAS scores in trial groups I and II were markedly lower than in the control group ((P<0.05 or (P<0.01), the scores in trial group II being the lowest. Combined application of parecoxib sodium for preemptive analgesia before anesthesia and after surgery can effectively reduce the levels of plasma stress hormones and improve analgesic effects in surgical patients with thyroid carcinoma, and without conspicuous impact on haemodynamics.

Effects of dexmedetomidine on heart arrhythmia prevention in off-pump coronary artery bypass surgery: A randomized clinical trial

PubMed Central

Soltani, Ghasem; Jahanbakhsh, Saeed; Tashnizi, Mohammad Abbasi; Fathi, Mehdi; Amini, Shahram; Zirak, Nahid; Sheybani, Shima

2017-01-01

Background Arrhythmia occurring during and after surgery is one of the major complications in open-heart surgery. Dexmedetomidine is an intravenous alpha-2 agonist and very specific short-acting drug to protect the various organs against ischemic injuries and blood reflow. However, the effect of dexmedetomidine for preventing intraoperative heart arrhythmias has not been recognized. Objective This study aimed to determine the effect of dexmedetomidine on the incidence rate of heart arrhythmias and anesthetic required in off-pump coronary artery bypass surgery. Methods This randomized clinical trial was conducted on patients who were candidates for off-pump coronary artery bypass referring to Imam Reza Hospital of Mashhad, Iran, from July 2016 through January 2017. The patients were randomly assigned to two groups of intervention (infusion of 0.5 mcg/kg/h dexmedetomidine together with induction followed by infusion of 0.5 mcg/kg/h by the end of the surgery) or control (saline infusion). Mean arterial pressure (MAP) and heart rate (HR) were measured before induction, during surgery operation and ICU admission. Data were analyzed by SPSS version 18 using Chi Square and independent-samples t-test. Results A total of 76 patients with a mean age of 59.8 ± 8.2 years (in two groups of 38) were studied. The two groups had no statistically significant difference in terms of background variables. The MAP and HR values before induction, during surgery and ICU admission were significantly higher in the control group than in the intervention group (p=0.001). Out of the studied arrhythmias, the values of PAC (55.2% vs. 15.7%), PVC (81.5% vs. 21.0%), AF (26.3% vs. 7.8%), VTAC (21.0% vs. 2.6%) were significantly lower in dexmedetomidine group (p=0.001). Conclusion It seems that dexmedetomidine administration during induction and surgery can cause significant reduction in most of the common arrhythmias in off-pump coronary bypass surgery. The use of dexmedetomidine maintains MAP and HR at significantly lower values, and changes compared to the control group as well as reduces the need for anesthetic compounds. Trial Registration The present study has been registered at the Iranian Registry of Clinical Trials (www.IRCT.IR) with a code of IRCT2016072413159N9 before starting the study. Founding This study was fully sponsored by the Research Deputy at Mashhad University of Medical Sciences, Iran (grant number 941413). PMID:29238500

EFFECTIVENESS OF THE ANESTHETIC AQUI-S® 20E IN MARINE FINFISH AND ELASMOBRANCHS.

PubMed

Silbernagel, Constance; Yochem, Pamela

2016-04-01

Immersion anesthetics are used in hatchery settings by veterinarians, field biologists, and laboratory researchers to aid in handling finfish for medical procedures, research purposes, and moderating perceived stress responses. The only Food and Drug Administration- (FDA) approved anesthetic for food fish, tricaine methanesulfonate, requires a 21-d withdrawal period prior to harvest. Ten percent eugenol (AQUI-S® 20E) has been gaining momentum for FDA approval because of its 0-d withdrawal time if fish are not of harvestable size within 72 h of exposure. We performed two trials to determine appropriate anesthetic doses for two cultured marine finfish: Atractoscion nobilis (white seabass, WSB) and Seriola lalandi (California yellowtail, YT). Fish were held in a treated water bath for 10 min or until opercular beat rate slowed to a rate of <2 beats/min. Based on these results, we conducted a field trial with wild Paralabrax maculatofasciatus (spotted bay bass), Paralabrax nebulifer (barred sand bass), Paralichthys californicus (California halibut), Triakis semifasciata (leopard shark), and Mustelus californicus (grey smooth-hound) at a single dosing regime, with animals held 5-10 min in anesthetic baths. Anesthetic dosing of 35-55 mg L(-1) provided relatively fast induction and good anesthetic maintenance in cultured and wild finfish. Anesthetic induction times were comparable among S. lalandi and A. nobilis at 35-mg L(-1) to 75-mg L(-1) doses, but recovery times were variable. Mortality rates of 20-90% were observed at higher doses (75 mg L(-1) and 100 mg L(-1), A. nobilis; 55 mg L(-1) and 75 mg L(-1), S. lalandi). The apparent increase in sensitivity of S. lalandi may have been associated with nutritional stress in the fish tested. There were no differences in time to anesthesia or recovery among wild finfish species tested at a single dose. Anesthetic induction, maintenance, and recovery were less predictable in the elasmobranch species tested and additional trials are needed to determine optimal dosing.

Clinical evaluation of endocervical prostaglandin E2-triacetin-gel for preinduction cervical softening in pregnant women at term.

PubMed

Kieback, D G; Zahradnik, H P; Quaas, L; Kröner-Fehmel, E E; Lippert, T H

1986-07-01

In an open randomized clinical trial 100 pregnant women with low Bishop Scores at term were treated either with intracervical Prostaglandin (PG) E2 (0.5 mg in 2.5 ml triacetin-gel) 12 hours before labor induction with intravenous oxytocin or with oxytocin infusion alone. In 46 of the 50 pretreated patients (92%) the Bishop Score progressed at least 3 points, in four cases only 2 points. The mean Bishop score in the untreated patients increased insignificantly. After PGE2-gel administration 16 patients delivered during the 12 hour interval compared to 3 in the group without pretreatment. The first induction attempt was successful in 14 (64%) of the 22 patients that were left to be induced after cervical softening and in 26 (57%) of the 47 women without cervical priming. The Cesarean section rate was 10% (n = 5) in the PGE2-gel group and 12% (n = 6) in the control group. Dosage of oxytocin required for labor induction was significantly lower after cervical softening. No serious fetal or maternal side effects were observed after PGE2 pretreatment.

Failure of a new protocol to improve treatment results in paediatric lymphoblastic leukaemia: lessons from the UK Medical Research Council trials UKALL X and UKALL XI.

PubMed

Chessells, Judith M; Harrison, Georgina; Richards, Susan M; Gibson, Brenda E; Bailey, Clifford C; Hill, Frank G H; Hann, Ian M

2002-08-01

The impact of various types of intensification therapy was examined in a cohort of 3617 children aged 1-14 years with acute lymphoblastic leukaemia (ALL) enrolled in the Medical Research Council (MRC) UKALL X (1985-90) and UKALL XI (1990-97) trials. UKALL XI was modified in 1992 to incorporate the "best arm" of UKALL X with two 5-d intensification blocks at 5 and 20 weeks, and an additional randomization in respect of a third intensification at 35 weeks but omission of two consecutive injections of daunorubicin during induction. All children were eligible for randomization irrespective of risk group. The impact of the various types of intensification therapy was examined in a stratified analysis. At a median follow up of 102 months, both trials had an identical event-free survival of 61% (95% CI 58-63%) at 8 years. Survival at 8 years in UKALL XI was significantly better in than in UKALL X, 81% (79-83%) compared with 74% (72-76%) (P = < 0.001), owing to improved management of relapse. There was a highly significant trend in reduction of the number of relapses and deaths with increased intensity of therapy both for children with initial leucocyte count < 50 x 10(9)/l (P = < 0.001) and > or = 50 x 10(9)/l (P = 0.002). Introduction of a third late intensification block compensated for omission of anthracyclines during induction but produced little additional benefit. These results show, in a large cohort of patients, that minor modifications of therapy may influence relapse rate and obviate the benefit of previous randomized trials. The failure to adapt treatment for higher risk children contributed to these disappointing results.

Determinants of health-related quality of life in the postpartum period after obstetric complications.

PubMed

Prick, Babette W; Bijlenga, Denise; Jansen, A J Gerard; Boers, Kim E; Scherjon, Sicco A; Koopmans, Corine M; van Pampus, Marielle G; Essink-Bot, Marie-Louise; van Rhenen, Dick J; Mol, Ben W; Duvekot, Johannes J

2015-02-01

To determine the influence of socio-demographic, clinical parameters and obstetric complications on postpartum health-related quality of life (HRQoL). We used data of three randomized controlled trials to investigate HRQoL determinants in women after an obstetric complication. The DIGITAT and HYPITAT trials compared induction of labor and expectant management in women with intra-uterine growth restriction (IUGR) and hypertensive disorders. The WOMB trial randomized anemic women after postpartum hemorrhage to red blood cell transfusion or expectant management. The HRQoL-measure Short-Form36 was completed at six weeks postpartum. Multivariable analyses were used to identify which parameters affected the Short-Form36 physical component score (PCS) and mental component score (MCS). HRQoL analyses included 1391 women (60%) of the 2310 trial participants. HYPITAT and DIGITAT participants had significantly lower MCS than WOMB participants. In multivariable analysis, PCS after elective and emergency cesarean section was 5-6 points lower than after vaginal delivery. Gestational hypertension, neonatal admission and delivery in an academic hospital had a small negative effect on PCS. No effect was found for randomization status, maternal age, BMI, country of birth, education, parity, induction of labor, analgesics, birth weight, perineal laceration, delivery of placenta, postpartum hemorrhage, congenital anomaly, urinary tract infection, thromboembolic event or endometritis. MCS was influenced only mildly by these parameters. IUGR and hypertensive disorders lead to lower HRQoL scores postpartum than PPH. In a heterogeneous obstetric population, only mode of delivery by cesarean section has a profound, negative impact, on physical HRQoL (PCS). No profound impacts on MCS were detected. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Emotion Recognition from Single-Trial EEG Based on Kernel Fisher's Emotion Pattern and Imbalanced Quasiconformal Kernel Support Vector Machine

PubMed Central

Liu, Yi-Hung; Wu, Chien-Te; Cheng, Wei-Teng; Hsiao, Yu-Tsung; Chen, Po-Ming; Teng, Jyh-Tong

2014-01-01

Electroencephalogram-based emotion recognition (EEG-ER) has received increasing attention in the fields of health care, affective computing, and brain-computer interface (BCI). However, satisfactory ER performance within a bi-dimensional and non-discrete emotional space using single-trial EEG data remains a challenging task. To address this issue, we propose a three-layer scheme for single-trial EEG-ER. In the first layer, a set of spectral powers of different EEG frequency bands are extracted from multi-channel single-trial EEG signals. In the second layer, the kernel Fisher's discriminant analysis method is applied to further extract features with better discrimination ability from the EEG spectral powers. The feature vector produced by layer 2 is called a kernel Fisher's emotion pattern (KFEP), and is sent into layer 3 for further classification where the proposed imbalanced quasiconformal kernel support vector machine (IQK-SVM) serves as the emotion classifier. The outputs of the three layer EEG-ER system include labels of emotional valence and arousal. Furthermore, to collect effective training and testing datasets for the current EEG-ER system, we also use an emotion-induction paradigm in which a set of pictures selected from the International Affective Picture System (IAPS) are employed as emotion induction stimuli. The performance of the proposed three-layer solution is compared with that of other EEG spectral power-based features and emotion classifiers. Results on 10 healthy participants indicate that the proposed KFEP feature performs better than other spectral power features, and IQK-SVM outperforms traditional SVM in terms of the EEG-ER accuracy. Our findings also show that the proposed EEG-ER scheme achieves the highest classification accuracies of valence (82.68%) and arousal (84.79%) among all testing methods. PMID:25061837

Emotion recognition from single-trial EEG based on kernel Fisher's emotion pattern and imbalanced quasiconformal kernel support vector machine.

PubMed

Liu, Yi-Hung; Wu, Chien-Te; Cheng, Wei-Teng; Hsiao, Yu-Tsung; Chen, Po-Ming; Teng, Jyh-Tong

2014-07-24

Electroencephalogram-based emotion recognition (EEG-ER) has received increasing attention in the fields of health care, affective computing, and brain-computer interface (BCI). However, satisfactory ER performance within a bi-dimensional and non-discrete emotional space using single-trial EEG data remains a challenging task. To address this issue, we propose a three-layer scheme for single-trial EEG-ER. In the first layer, a set of spectral powers of different EEG frequency bands are extracted from multi-channel single-trial EEG signals. In the second layer, the kernel Fisher's discriminant analysis method is applied to further extract features with better discrimination ability from the EEG spectral powers. The feature vector produced by layer 2 is called a kernel Fisher's emotion pattern (KFEP), and is sent into layer 3 for further classification where the proposed imbalanced quasiconformal kernel support vector machine (IQK-SVM) serves as the emotion classifier. The outputs of the three layer EEG-ER system include labels of emotional valence and arousal. Furthermore, to collect effective training and testing datasets for the current EEG-ER system, we also use an emotion-induction paradigm in which a set of pictures selected from the International Affective Picture System (IAPS) are employed as emotion induction stimuli. The performance of the proposed three-layer solution is compared with that of other EEG spectral power-based features and emotion classifiers. Results on 10 healthy participants indicate that the proposed KFEP feature performs better than other spectral power features, and IQK-SVM outperforms traditional SVM in terms of the EEG-ER accuracy. Our findings also show that the proposed EEG-ER scheme achieves the highest classification accuracies of valence (82.68%) and arousal (84.79%) among all testing methods.

Timing of birth for women with a twin pregnancy at term: a randomised controlled trial

PubMed Central

2010-01-01

Background There is a well recognized risk of complications for both women and infants of a twin pregnancy, increasing beyond 37 weeks gestation. Preterm birth prior to 37 weeks gestation is a recognized complication of a twin pregnancy, however, up to 50% of twins will be born after this time. The aims of this randomised trial are to assess whether elective birth at 37 weeks gestation compared with standard care in women with a twin pregnancy affects the risk of perinatal death, and serious infant complications. Methods/Design Design: Multicentred randomised trial. Inclusion Criteria: women with a twin pregnancy at 366 weeks or more without contraindication to continuation of pregnancy. Trial Entry & Randomisation: Following written informed consent, eligible women will be randomised from 36+6 weeks gestation. The randomisation schedule uses balanced variable blocks, with stratification for centre of birth and planned mode of birth. Women will be randomised to either elective birth or standard care. Treatment Schedules: Women allocated to the elective birth group will be planned for elective birth from 37 weeks gestation. Where the plan is for vaginal birth, this will involve induction of labour. Where the plan is for caesarean birth, this will involve elective caesarean section. For women allocated to standard care, birth will be planned for 38 weeks gestation or later. Where the plan is for vaginal birth, this will involve either awaiting the spontaneous onset of labour, or induction of labour if required. Where the plan is for caesarean birth, this will involve elective caesarean section (after 38 and as close to 39 weeks as possible). Primary Study Outcome: A composite of perinatal mortality or serious neonatal morbidity. Sample Size: 460 women with a twin pregnancy to show a reduction in the composite outcome from 16.3% to 6.7% with adjustment for the clustering of twin infants within mothers (p = 0.05, 80% power). Discussion This is a protocol for a randomised trial, the findings of which will contribute information about the optimal time of birth for women with an uncomplicated multiple pregnancy at and beyond 37 weeks gestation. Clinical Trial Registration Current Controlled Trials ISRCTN15761056 PMID:20973989

Pulsatile luteinising hormone releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome.

PubMed

Bayram, N; van Wely, M; Vandekerckhove, P; Lilford, R; van Der Veen, F

2000-01-01

In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intra-venous or subcutaneous route using a portable pump has been used successfully in patients with hypogonadotrophic hypogonadism. Assuming that the results would be similar in polycystic ovary syndrome (PCOS), pulsatile GnRH has been used to induce ovulation in patients with PCOS. But, although ovulation and pregnancy has been achieved, the use of pulsatile GnRH in PCOS patients is controversial. To assess the effectiveness of pulsatile GnRH administration in women with clomiphene-resistant polycystic ovary syndrome (PCOS), in terms of ovulation induction, pregnancy, miscarriage, multiple pregnancy and ovarian hyperstimulation syndrome (OHSS). The search strategy of the Menstrual Disorders and Subfertility review group was used to identify all relevant trials. Please see Review Group details. All relevant published RCTs were selected. Non-randomised controlled trials were eligible for inclusion if treatment consisted of GnRH administration versus another treatment to induce ovulation in subfertile women with PCOS. A computerised MEDLINE and EMBASE search was used to identify randomised and non randomised controlled trials. The reference lists of all studies found were checked for relevant articles. One RCT (Bringer 1985a) and one abstract (Coelingh 1983) were identified this way. Relevant data were extracted independently by two reviewers (NB, MW). Validity was assessed in terms of method of randomization, completeness of follow-up, presence or absence of cross-over and co-intervention. All trials were screened and analysed for predetermined quality criteria. 2X2 tables were generated for all the relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Three RCTs and one non-randomised comparative trial were identified comparing four different treatments: GnRH versus HMG, GnRH following GnRHa pre-treatment versus no pre-treatment, GnRH and FSH versus FSH, and GnRH following GnRHa pre-treatment versus GnRH following oral contraceptive pre-treatment. This means that there was only one trial in any one comparison. In the first two studies, data of pre- and post-cross-over were not described separately. Therefore, these results could not be included in the MetaView analysis. The odds ratio for ovulation rate was 16 (95 % CI: 1.1-239) in the study comparing GnRH and FSH with FSH. When GnRH after GnRHa pre-treatment was compared with GnRH after oral contraceptive pre-treatment, an odds ratio of 7.5 (95 % CI: 1.2-46) was obtained. All trials were small and of too short duration to show any significance in pregnancy results. Per study only one to four pregnancies occurred. Multiple pregnancies were not seen. OHSS was seen only in the patients stimulated with HMG. The four trials describing four different comparisons with a short follow up (1 to 3 cycles) were too small to either prove or discard the value of pulsatile GnRH treatment in patients with polycystic ovary syndrome.

Which method is best for the induction of labour? A systematic review, network meta-analysis and cost-effectiveness analysis.

PubMed

Alfirevic, Zarko; Keeney, Edna; Dowswell, Therese; Welton, Nicky J; Medley, Nancy; Dias, Sofia; Jones, Leanne V; Gyte, Gillian; Caldwell, Deborah M

2016-08-01

More than 150,000 pregnant women in England and Wales have their labour induced each year. Multiple pharmacological, mechanical and complementary methods are available to induce labour. To assess the relative effectiveness, safety and cost-effectiveness of labour induction methods and, data permitting, effects in different clinical subgroups. We carried out a systematic review using Cochrane methods. The Cochrane Pregnancy and Childbirth Group's Trials Register was searched (March 2014). This contains over 22,000 reports of controlled trials (published from 1923 onwards) retrieved from weekly searches of OVID MEDLINE (1966 to current); Cochrane Central Register of Controlled Trials (The Cochrane Library); EMBASE (1982 to current); Cumulative Index to Nursing and Allied Health Literature (1984 to current); ClinicalTrials.gov; the World Health Organization International Clinical Trials Registry Portal; and hand-searching of relevant conference proceedings and journals. We included randomised controlled trials examining interventions to induce labour compared with placebo, no treatment or other interventions in women eligible for third-trimester induction. We included outcomes relating to efficacy, safety and acceptability to women. In addition, for the economic analysis we searched the Database of Abstracts of Reviews of Effects, and Economic Evaluations Databases, NHS Economic Evaluation Database and the Health Technology Assessment database. We carried out a network meta-analysis (NMA) using all of the available evidence, both direct and indirect, to produce estimates of the relative effects of each treatment compared with others in a network. We developed a de novo decision tree model to estimate the cost-effectiveness of various methods. The costs included were the intervention and other hospital costs incurred (price year 2012-13). We reviewed the literature to identify preference-based utilities for the health-related outcomes in the model. We calculated incremental cost-effectiveness ratios, expected costs, utilities and net benefit. We represent uncertainty in the optimal intervention using cost-effectiveness acceptability curves. We identified 1190 studies; 611 were eligible for inclusion. The interventions most likely to achieve vaginal delivery (VD) within 24 hours were intravenous oxytocin with amniotomy [posterior rank 2; 95% credible intervals (CrIs) 1 to 9] and higher-dose (≥ 50 µg) vaginal misoprostol (rank 3; 95% CrI 1 to 6). Compared with placebo, several treatments reduced the odds of caesarean section, but we observed considerable uncertainty in treatment rankings. For uterine hyperstimulation, double-balloon catheter had the highest probability of being among the best three treatments, whereas vaginal misoprostol (≥ 50 µg) was most likely to increase the odds of excessive uterine activity. For other safety outcomes there were insufficient data or there was too much uncertainty to identify which treatments performed 'best'. Few studies collected information on women's views. Owing to incomplete reporting of the VD within 24 hours outcome, the cost-effectiveness analysis could compare only 20 interventions. The analysis suggested that most interventions have similar utility and differ mainly in cost. With a caveat of considerable uncertainty, titrated (low-dose) misoprostol solution and buccal/sublingual misoprostol had the highest likelihood of being cost-effective. There was considerable uncertainty in findings and there were insufficient data for some planned subgroup analyses. Overall, misoprostol and oxytocin with amniotomy (for women with favourable cervix) is more successful than other agents in achieving VD within 24 hours. The ranking according to safety of different methods was less clear. The cost-effectiveness analysis suggested that titrated (low-dose) oral misoprostol solution resulted in the highest utility, whereas buccal/sublingual misoprostol had the lowest cost. There was a high degree of uncertainty as to the most cost-effective intervention. Future trials should be powered to detect a method that is more cost-effective than misoprostol solution and report outcomes included in this NMA. This study is registered as PROSPERO CRD42013005116. The National Institute for Health Research Health Technology Assessment programme.

Methodology of clinical trials evaluating the incorporation of new drugs in the first-line treatment of patients with diffuse large B-cell lymphoma (DLBCL): a critical review.

PubMed

Iacoboni, G; Zucca, E; Ghielmini, M; Stathis, A

2018-05-01

The first-line treatment of diffuse large B-cell lymphoma (DLBCL) is the combination of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, curing approximately 60% of patients. Many clinical trials have been carried out over the last 10 years trying to improve the results of this treatment, but the appropriateness of their planning strategies could be rediscussed. Reports of phase III trials evaluating the addition of molecularly targeted agents or new monoclonal antibodies to the classic R-CHOP backbone in first-line induction or maintenance treatment were reviewed. The trial design, primary end point, number of patients enrolled, patient selection criteria, treatment schedule and results were registered for each one. In addition, the phases I and II trials which preceded these phase III trials were also reviewed. Among six phase III trials with results, only one trial evaluating lenalidomide maintenance after response to R-CHOP induction was positive and reached its primary end point. The other five trials did not show an improved outcome with the addition of the new agent. The preceding phases I and II trials were very heterogeneous in their end points and design. Even though most of these trials were considered positive, thus encouraging further investigation, so far they failed to predict the results of the subsequent phase III trials. The standard of care for DLBCL is still R-CHOP. Phase I/II trials failed to predict the results of subsequent phase III trials evaluating non-chemotherapeutic agents added to R-CHOP. The methodology of phase II trials evaluating new agents in DLBCL needs to be better defined in the future.

A TAD better for myeloma therapy?

PubMed

Giralt, Sergio

2010-02-11

In this issue of Blood, Lokhorst and colleagues report on the results of HOVON-50, a phase 3 randomized trial designed to evaluate the effects of thalidomide during induction treatment and as maintenance in patients with multiple myeloma. There were 556 patients randomly assigned either to 3 cycles of VAD or to TAD. All patients were to receive high-dose melphalan with autologous stem cell support followed by maintenance with interferon for the VAD arm or thalidomide for the TAD arm.(1) This study together with other randomized and nonrandomized trials establish a definitive role for thalidomide as induction therapy in conjunction with dexamethasone, anthracyclines, and alkylating agents.

Ways of encoding somatic information and their effects on retrospective symptom reporting.

PubMed

Walentynowicz, Marta; Van Diest, Ilse; Raes, Filip; Van den Bergh, Omer

2017-05-01

Retrospective symptom reports tend to overestimate actual symptom intensity. This study explored how focusing on sensory-perceptual or on affective-motivational aspects of a somatic experience influenced retrospective symptom reports in high and low habitual symptom reporters (HSR). We hypothesized that a focus on affective-motivational aspects of somatic episodes contributes to retrospective overestimation compared to a focus on sensory-perceptual aspects. Dyspnoea (rebreathing) and pain (cold pain) were induced during two experimental sessions in healthy women: 21 high and 24 low HSR, selected using cut-off scores on a symptom checklist. Within-subject manipulation of sensory and affective processing focus (PF) took place at the encoding phase before symptom induction. Dyspnoea and pain ratings were collected immediately after the symptom inductions and after 2 weeks. Breathing behaviour was recorded during dyspnoea trials, while affective state and symptom measures were collected after each trial. Compared to pain, dyspnoea induction was perceived as more unpleasant, arousing, and threatening (ps < .001). Affective PF led to higher arousal (p < .01) and threat ratings (p = .01) than sensory PF. Affective PF also led to an increase in retrospective dyspnoea ratings over the course of 2 weeks (p = .039), which was not observed for pain, nor for dyspnoea after sensory PF. The effects of PF on symptom ratings were independent of the HSR levels. The PF during symptom encoding may explain previously observed bias in retrospective symptom reporting. The results are relevant to understand the mechanisms underlying symptom overreporting. Statement of contribution What is already known on this subject? Retrospective symptom ratings are often biased when compared to the momentary assessments. Attending to either sensory or affective aspects of the somatic experience is one of the factors affecting self-reported symptoms. What does this study add? Focusing on affective aspects elicited by the somatic experience led to an increase in retrospective symptom ratings over time. This is particularly so for more aversive somatic experiences. Directing the processing focus to sensory aspects during symptom encoding can attenuate bias in retrospective symptom reporting. © 2017 The British Psychological Society.

Comparison of acupuncture pretreatment followed by letrozole versus letrozole alone on live birth in anovulatory infertile women with polycystic ovary syndrome: a study protocol for a randomised controlled trial

PubMed Central

Li, Juan; Ng, Ernest Hung Yu; Stener-Victorin, Elisabet; Hu, Zhenxing; Wu, Wanting; Lai, Maohua; Wu, Taixiang; Ma, Hongxia

2016-01-01

Introduction The high prevalence of insulin resistance in women with polycystic ovary syndrome (PCOS) is considered to be one of the major pathophysiological changes in PCOS that leads to anovulatory infertility. We hypothesise that electroacupuncture pretreatment improves insulin sensitivity and leads to a higher ovulation rate and greater chances of live birth after the induction of ovulation. The effect of electroacupuncture pretreatment followed by ovulation induction in women with anovulatory PCOS has not been investigated before, and we present here a randomised controlled trial to test this hypothesis by comparing electroacupuncture pretreatment followed by letrozole versus letrozole alone in anovulatory women with PCOS. Methods/analysis This is a multicentre, randomised,and controlled trial. A total of 384 patients will be enrolled in this study and will be randomly allocated by a central randomisation system to the treatment group or the control group in a 1:1 ratio. The treatment group will undergo 16 weeks of electroacupuncture pretreatment followed by 4 cycles of letrozole, and the control group will only undergo 4 cycles of letrozole. The primary outcome will be the live birth rate. All statistical analyses will be performed using the SPSS program V.21.0 (SPSS, Chicago, Illinois, USA), and a p value <0.05 will be considered statistically significant. Ethics/dissemination This study has been approved by the ethics committees of each participating centre. Written consent will be obtained from each patient and her husband before any study procedure is performed. Adverse events will be categorised, and the percentage of patients experiencing adverse events or serious adverse events during the treatment period will be documented. The results of this trial will be disseminated in peer-reviewed journals and presented at international meetings. Trial registration number NCT02491333. PMID:27855085

Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial

PubMed Central

Lee, Joshua D; Nunes, Edward V; Novo, Patricia; Bachrach, Ken; Bailey, Genie L; Bhatt, Snehal; Farkas, Sarah; Fishman, Marc; Gauthier, Phoebe; Hodgkins, Candace C; King, Jacquie; Lindblad, Robert; Liu, David; Matthews, Abigail G; May, Jeanine; Peavy, K Michelle; Ross, Stephen; Salazar, Dagmar; Schkolnik, Paul; Shmueli-Blumberg, Dikla; Stablein, Don; Subramaniam, Geetha; Rotrosen, John

2018-01-01

Summary Background Extended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX. Methods We initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433. Findings Between Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10–1·68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0·44). Opioid-negative urine samples (p<0·0001) and opioid-abstinent days (p<0·0001) favoured BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0·0012), then converged by week 24 (p=0·20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group). Interpretation In this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications. PMID:29150198

Surgical versus medical methods for second trimester induced abortion.

PubMed

Lohr, P A; Hayes, J L; Gemzell-Danielsson, K

2008-01-23

Determining the optimal method of performing second-trimester abortions is important, since they account for a disproportionate amount of abortion-related morbidity and mortality. To compare surgical and medical methods of inducing abortion in the second trimester of pregnancy with regard to efficacy, side effects, adverse events, and acceptability. We identified trials using Pub Med, EMBASE, POPLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL). We also searched the reference lists of identified studies, relevant review articles, book chapters, and conference proceedings for additional, previously unidentified studies. We contacted experts in the field for information on other published or unpublished research. Randomised trials comparing any surgical to any medical method of inducing abortion at >/= 13 weeks' gestation were included. We assessed the validity of each study using the methods suggested in the Cochrane Handbook. Investigators were contacted as needed to provide additional information regarding trial conduct or outcomes. Two reviewers abstracted the data. Odds ratios and 95% confidence intervals were calculated for dichotomous variables using RevMan 4.2. The trials did not have uniform interventions, therefore, we were unable to combine them into a meta-analysis. Two studies met criteria for this review. One compared dilation and evacuation (D&E) to intra-amniotic instillation of prostaglandin F(2) (alpha). The second study compared D&E to induction with mifepristone and misoprostol. Compared with prostaglandin instillation, the combined incidence of minor complications was lower with D&E (OR 0.17, 95% CI 0.04-0.65) as was the total number of minor and major complications (OR 0.12, 95% CI 0.03-0.46). The number of women experiencing adverse events was also lower with D&E than with mifepristone and misoprostol (OR 0.06, 95% CI 0.01-0.76). Although women treated with mifepristone and misoprostol reported significantly more pain than those undergoing D&E, efficacy and acceptability were the same in both groups. In both trials, fewer subjects randomised to D&E required overnight hospitalisation. Dilation and evacuation is superior to instillation of prostaglandin F(2) (alpha). The current evidence also appears to favour D&E over mifepristone and misoprostol, however larger randomised trials are needed.

Effects of dexmedetomidine on heart arrhythmia prevention in off-pump coronary artery bypass surgery: A randomized clinical trial.

PubMed

Soltani, Ghasem; Jahanbakhsh, Saeed; Tashnizi, Mohammad Abbasi; Fathi, Mehdi; Amini, Shahram; Zirak, Nahid; Sheybani, Shima

2017-10-01

Arrhythmia occurring during and after surgery is one of the major complications in open-heart surgery. Dexmedetomidine is an intravenous alpha-2 agonist and very specific short-acting drug to protect the various organs against ischemic injuries and blood reflow. However, the effect of dexmedetomidine for preventing intraoperative heart arrhythmias has not been recognized. This study aimed to determine the effect of dexmedetomidine on the incidence rate of heart arrhythmias and anesthetic required in off-pump coronary artery bypass surgery. This randomized clinical trial was conducted on patients who were candidates for off-pump coronary artery bypass referring to Imam Reza Hospital of Mashhad, Iran, from July 2016 through January 2017. The patients were randomly assigned to two groups of intervention (infusion of 0.5 mcg/kg/h dexmedetomidine together with induction followed by infusion of 0.5 mcg/kg/h by the end of the surgery) or control (saline infusion). Mean arterial pressure (MAP) and heart rate (HR) were measured before induction, during surgery operation and ICU admission. Data were analyzed by SPSS version 18 using Chi Square and independent-samples t-test. A total of 76 patients with a mean age of 59.8 ± 8.2 years (in two groups of 38) were studied. The two groups had no statistically significant difference in terms of background variables. The MAP and HR values before induction, during surgery and ICU admission were significantly higher in the control group than in the intervention group (p=0.001). Out of the studied arrhythmias, the values of PAC (55.2% vs. 15.7%), PVC (81.5% vs. 21.0%), AF (26.3% vs. 7.8%), VTAC (21.0% vs. 2.6%) were significantly lower in dexmedetomidine group (p=0.001). It seems that dexmedetomidine administration during induction and surgery can cause significant reduction in most of the common arrhythmias in off-pump coronary bypass surgery. The use of dexmedetomidine maintains MAP and HR at significantly lower values, and changes compared to the control group as well as reduces the need for anesthetic compounds. The present study has been registered at the Iranian Registry of Clinical Trials (www.IRCT.IR) with a code of IRCT2016072413159N9 before starting the study. This study was fully sponsored by the Research Deputy at Mashhad University of Medical Sciences, Iran (grant number 941413).

Comparison of propofol with pentobarbital/midazolam/fentanyl sedation for magnetic resonance imaging of the brain in children.

PubMed

Pershad, Jay; Wan, Jim; Anghelescu, Doralina L

2007-09-01

Propofol and pentobarbital, alone or combined with other agents, are frequently used to induce deep sedation in children for MRI. However, we are unaware of a previous comparison of these 2 agents as part of a randomized, controlled trial. We compared the recovery time of children after deep sedation with single-agent propofol with a pentobarbital-based regimen for MRI and considered additional variables of safety and efficacy. This prospective, randomized trial at a tertiary children's hospital enrolled 60 patients 1 to 17 years old who required intravenous sedation for elective cranial MRI. Patients were assigned randomly to receive a loading dose of propofol followed by continuous intravenous infusion of propofol or to receive sequential doses of midazolam, pentobarbital, and fentanyl until a modified Ramsay score of >4 was attained. A nurse who was blind to group assignment assessed discharge readiness (Aldrete score > 8) and administered a follow-up questionnaire. We compared recovery time, time to induction of sedation, total sedation time, quality of imaging, number of repeat-image sequences, adverse events, caregiver satisfaction, and time to return to presedation functional status. The groups were similar in age, gender, race, American Society of Anesthesiology physical status class, and frequency of cognitive impairment. No sedation failure or significant adverse events were observed. Propofol offered significantly shorter sedation induction time, recovery time, total sedation time, and time to return to baseline functional status. Caregiver satisfaction scores were also significantly higher in the patients in the propofol group. Propofol permits faster onset and recovery than, and comparable efficacy to, a pentobarbital/midazolam/fentanyl regimen for sedation of children for MRI.

[Comparison of two antimicrobial prophylaxis regimens in biliary tract surgery: a randomized controlled clinical trial].

PubMed

Orozco, H; Sifuentes Osornio, J; Prado, E; Takahashi, T; López Graniel, C M; Anaya, E; Canto, J

1993-01-01

The aim of this study was to analyze the efficacy in prophylaxis during biliary tract and gallbladder surgery with amoxicillin/clavulanate and to compare it with the combination of cephalothin and clindamycin. A randomized nonblinded clinical trial with a blind independent observer. Tertiary-care center. Forty-two patients were included. All had undergone biliary tract and/or gallbladder surgery. They were divided in two groups: 22 in group A (cephalothin and clindamycin), and 20 in group B (amoxicillin/clavulanate). Patients from group A were intravenously treated with three doses of cephalothin (2 g at anesthetic induction and two additional doses of 1 g at six-hour intervals), and three of clindamycin (600 mg every six hours). Patients from group B received three doses of amoxicillin/clavulanate (1000/200 mg IV, one during the induction of the anesthesia followed by two more at six-hour intervals). In group A six wound infections were recorded, one of them with secondary bacteremia. In group B we did not record any infection (Fisher p < 0.01). One case of phlebitis was recorded in each group. Our results indicate that amoxicillin/clavulanate is useful in the prophylaxis of gallbladder and biliary tract surgery, and more effective than the combination of cephalothin and clindamycin.

Efficacy of oral vs. topical, or combined oral and topical 5-aminosalicylates, in Ulcerative Colitis: systematic review and meta-analysis.

PubMed

Ford, Alexander C; Khan, Khurram J; Achkar, Jean-Paul; Moayyedi, Paul

2012-02-01

Efficacy of 5-aminosalicylic acids (5-ASAs) in ulcerative colitis (UC) has been studied previously in meta-analyses. However, no recent meta-analysis has studied the relative efficacies of differing routes of administration. MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through May 2011). Eligible trials recruited adults with mildly to moderately active UC, or quiescent UC, and compared oral 5-ASAs with either topical 5-ASAs or a combination of oral and topical 5-ASAs. Dichotomous data were pooled to obtain relative risk (RR) of failure to achieve remission in active UC, and RR of relapse of disease activity in quiescent UC, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. The search identified 3,061 citations, and 12 randomized controlled trials (RCTs) were eligible. Four compared topical with oral 5-ASAs in active UC remission, with an RR of no remission with topical 5-ASAs of 0.82 (95% CI=0.52-1.28). Four trials compared combined with oral 5-ASAs in active UC (RR of no remission=0.65; 95% CI=0.47-0.91; NNT=5). Three RCTs compared intermittent topical with oral 5-ASAs in preventing relapse of quiescent UC (RR=0.64; 95% CI=0.43-0.95; NNT=4), and two compared combined with oral 5-ASAs (RR of relapse=0.48; 95% CI=0.17-1.38). Combined 5-ASA therapy appeared superior to oral 5-ASAs for induction of remission of mildly to moderately active UC. Intermittent topical 5-ASAs appeared superior to oral 5-ASAs for preventing relapse of quiescent UC.

The current role of systemic chemotherapy in the primary treatment of head and neck cancer.

PubMed

Busch, C-J; Tribius, S; Schafhausen, P; Knecht, R

2015-03-01

The treatment of patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) is still evolving into the perfect combination of the different multidisciplinary approaches. Induction chemotherapy (ICT) prior to planned definitive local therapy is widely used in this patient population for over 30 years but it is still unclear how to incorporate ICT into multimodality treatment the best. It appears to have a role in selected clinical situations especially for those patients with high risk for distant metastasis. However, since ICT protocols in different studies varies a lot, a comparative and consistent statement of benefits is difficult. We show the recent developments including randomized trials comparing radiochemotherapy (RCT) and ICT followed by definitive RCT here. This review summarizes how ICT has developed over the years, provides critical remarks of recent developments, and discusses how clinical trials including ICT should be conducted in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial.

PubMed

Sandborn, William J; Rutgeerts, Paul; Enns, Robert; Hanauer, Stephen B; Colombel, Jean-Frédéric; Panaccione, Remo; D'Haens, Geert; Li, Ju; Rosenfeld, Marie R; Kent, Jeffrey D; Pollack, Paul F

2007-06-19

Adalimumab, a fully human tumor necrosis factor (TNF) antagonist, is an effective treatment for patients with Crohn disease who are naive to the chimeric TNF antagonist, infliximab. No anti-TNF agent has been evaluated prospectively in patients with Crohn disease who had responded to another anti-TNF agent and then lost that response or were intolerant of the agent. To determine whether adalimumab induces remissions more frequently than placebo in adult patients with Crohn disease who have symptoms despite infliximab therapy or who cannot take infliximab because of adverse events. 4-week, randomized, double-blind, placebo-controlled trial (November 2004 to December 2005). 52 sites in the United States, Canada, and Europe. 325 adults 18 to 75 years of age who had a history of Crohn disease for 4 months or more that was moderate to severe at baseline (Crohn's Disease Activity Index [CDAI] score, 220 to 450 points). Patients were randomly assigned to receive induction doses of adalimumab, 160 mg and 80 mg, at weeks 0 and 2, respectively, or placebo at the same time points. The primary end point was induction of remission at week 4. Decreases in CDAI score by 70 or more and 100 or more points (secondary end points) were also measured. A total of 301 patients completed the trial. Twenty-one percent (34 of 159) of patients in the adalimumab group versus 7% (12 of 166) of those in the placebo group achieved remission at week 4 (P < 0.001). The absolute difference in clinical remission rates was 14.2 percentage points (95% CI, 6.7 to 21.6 percentage points). A 70-point response occurred at week 4 in 52% (82 of 159) of patients in the adalimumab group versus 34% (56 of 166) of patients in the placebo group (P = 0.001). The absolute difference in 70-point response rates was 17.8 percentage points (CI, 7.3 to 28.4 percentage points). Two of 159 patients in the adalimumab group and 4 of 166 patients in the placebo group discontinued treatment because of adverse events. No patients in the adalimumab group and 4 of 166 patients in the placebo group had a serious infection. The trial did not directly compare alternative active treatments and did not evaluate maintenance of response or long-term immunogenicity of adalimumab. Adalimumab induces remissions more frequently than placebo in adult patients with Crohn disease who cannot tolerate infliximab or have symptoms despite receiving infliximab therapy. For more information on adalimumab in Crohn disease, click here. ClinicalTrials.gov registration number: NCT00105300.

Induction of a T-Helper 1 (Th1) Immune Response in Mice by an Extract from the Pleurotus eryngii (Eringi) Mushroom

PubMed Central

Kameyama, Natsuko; Ito, Akira; Imai, Soichi

2012-01-01

Abstract To assess the effect of edible mushroom extracts on the induction of T-helper 1 (Th1) immunity, we examined differences in interferon-gamma (IFN-γ) and interleukin (IL)-4 production in mice induced by hot-water extracts of 15 species of edible mushroom. Extracts from Agaricus bisporus, Flammulina velutipes, Hypsizigus marmoreus, Lentinula edodes, and Lyophyllum decastes induced both IFN-γ and IL-4 production in mice, whereas extracts from Pleurotus ostreatus only induced IL-4. In contrast, extracts from Agaricus blazei, Grifola frondosa, Morchella esculenta, Pholiota nameko, Pleurotus citrinopileatus, and Pleurotus eryngii induced only IFN-γ production. In particular, the extract from P. eryngii induced high levels of IFN-γ and reduced levels of IL-4. We further investigated the use of a trial immunogen using the P. eryngii extract as a Th1 immunostimulator. An oil-in-water emulsion of the hot-water extract from P. eryngii (immunostimulator) and ovalbumin (OVA; antigen) was used as a trial immunogen. This immunogen induced strong OVA-specific IgG2a antibody production in mice compared with the negative controls. In addition, OVA-specific IgG1 antibody levels were lower than those for the negative controls. Marked increases in serum IFN-γ levels and high-level production of IFN-γ in the culture supernatant from the CD4+ spleen cells in the trial immunogen group mice were observed. Our results suggested that the hot-water extract from P. eryngii induced Th1 immunity by acting as an immunostimulator. PMID:23134464

Rifaximin: The Revolutionary Antibiotic Approach for Irritable Bowel Syndrome.

PubMed

Triantafyllou, Konstantinos; Sioulas, Athanasios D; Giamarellos-Bourboulis, Evangelos J

2015-01-01

A large number of clinical studies using breath testing and a smaller number of studies using quantitative cultures of the upper small intestine established a link between irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO). A series of 12 studies both prospective and retrospective in design in a population of patients with SIBO without IBS showed that the non-absorbable antibiotic rifaximin can eradicate SIBO as proved through decrease of the exhaled hydrogen and methane in breath tests. The efficacy of rifaximin was superior over the comparator treatment in most of these studies. Based on these findings, short course rifaximin was tested in various concentrations in eight open-label trials in patients with IBS and proven SIBO by breath test. Similar efficacy of rifaximin was shown in SIBO eradication; this was accompanied by improvement of the global score for IBS symptoms. Finally, five double-blind randomized clinical trials were conducted in patients with IBS; four were placebo-controlled. The larger trials were TARGET 1 and TARGET 2 studies testing rifaximin at a regimen of 550 mg tid for 14 days. All trials showed a significant superiority of rifaximin over comparator for the improvement of global symptoms of IBS and bloating. Although the aforementioned results render rifaximin a revolutionary therapeutic approach for IBS, several concerns on induction of antimicrobial resistant flora remain.

Prevention of catheter-related bladder discomfort - pudendal nerve block with ropivacaine versus intravenous tramadol: study protocol for a randomized controlled trial.

PubMed

Li, Jing-Yi; Liao, Ren

2016-09-13

Catheter-related bladder discomfort (CRBD) is a common distressing symptom complex during the postoperative period, especially after urologic procedures with a relatively greater size urinary catheter. In this study, we will enroll male patients undergoing elective prostate surgery with urinary catheterization under general anesthesia, and we will compare the efficacy of pudendal nerve block (PNB) and intravenous tramadol in CRBD prevention. This trial is a prospective, randomized controlled trial that will test the superiority of bilateral PNB with 0.33 % ropivacaine compared with intravenous tramadol 1.5 mg/kg for CRBD prevention. A total of 94 male patients undergoing elective prostate surgery with urinary catheterization after anesthesia induction will be randomized to receive either bilateral PNB with 0.33 % ropivacaine (the PNB group) or intravenous tramadol 1.5 mg/kg (the tramadol group) after the completion of surgery. The primary outcome is the incidence of CRBD. The most important secondary outcome is the severity of postoperative CRBD, and other secondary outcomes include Numeric Rating Scale (NRS) score for postoperative pain; incidence of postoperative side effects such as postoperative nausea/vomiting, sedation, dizziness, and dry mouth; postoperative requirement for tramadol as a rescue treatment for CRBD and sufentanil as a rescue analgesic for postoperative pain; and NRS score for acceptance of an indwelling urinary catheter. This trial is planned to test the superiority of PNB with 0.33 % ropivacaine compared with intravenous tramadol 1.5 mg/kg. It may provide a basis for a new clinical practice for the prevention of CRBD. ClinicalTrials.gov identifier NCT02683070 . Registered on 11 February 2016.

Chinese herbal medicine for subfertile women with polycystic ovarian syndrome.

PubMed

Zhou, Kunyan; Zhang, Jing; Xu, Liangzhi; Wu, Taixiang; Lim, Chi Eung Danforn

2016-10-12

Polycystic ovarian syndrome (PCOS) is one of the most common reproductive endocrinology abnormalities, and affects 5% to 10% of women of reproductive age. Western medicines, such as oral contraceptives, insulin sensitizers and laparoscopic ovarian drilling (LOD), have been used to treat PCOS. Recently, many studies have been published that consider Chinese herbal medicine (CHM) as an alternative treatment for women with PCOS. To assess the efficacy and safety of CHM for subfertile women with PCOS. We searched sources, including the following databases, from inception to 9 June 2016: the Cochrane Gynaecology and Fertility Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Allied and Complementary Medicine (AMED), PsycINFO, Chinese National Knowledge Infrastructure (CNKI), VIP, Wanfang and trial registries. In addition, we searched the reference lists of included trials and contacted experts in the field to locate trials. Randomized controlled trials (RCTs) that considered the use of CHM for the treatment of subfertile women with PCOS. Two review authors independently screened appropriate trials for inclusion, assessed the risk of bias in included studies and extracted data. We contacted primary study authors for additional information. We conducted meta-analyses. We used the odds ratios (ORs) to report dichotomous data, with 95% confidence intervals (CI). We assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. We included five RCTs with 414 participants. The comparisons in the included trials were as follows: CHM versus clomiphene, CHM plus clomiphene versus clomiphene (with or without ethinyloestradiol cyproterone acetate (CEA)), CHM plus follicle aspiration plus ovulation induction versus follicle aspiration plus ovulation induction alone, and CHM plus laparoscopic ovarian drilling (LOD) versus LOD alone. The overall quality of the evidence for most comparisons was very low.None of the included studies reported live birth rate, and only one study reported data on adverse events.When CHM was compared with clomiphene (with or without LOD in both arms), there was no evidence of a difference between the groups in pregnancy rates (odds ratio (OR) 1.98, 95% confidence interval (CI) 0.78 to 5.06; two studies, 90 participants, I² statistic = 0%, very low quality evidence). No study reported data on adverse events. When CHM plus clomiphene was compared with clomiphene (with or without CEA), there was low quality evidence of a higher pregnancy rate in the CHM plus clomiphene group (OR 2.62, 95% CI 1.65 to 4.14; three RCTs, 300 women, I² statistic = 0%,low quality evidence). No data were reported on adverse events.When CHM with follicle aspiration and ovulation induction was compared with follicle aspiration and ovulation induction alone, there was no evidence of a difference between the groups in pregnancy rates (OR 1.60, 95% CI 0.46 to 5.52; one study, 44 women, very low quality evidence), severe luteinized unruptured follicle syndrome (LUFS) (OR 0.60, 95% CI 0.06 to 6.14; one study, 44 women, very low quality evidence), ovarian hyperstimulation syndrome (OHSS) (OR 0.16, 95% CI 0.00 to 8.19; one study, 44 women, very low quality evidence) or multiple pregnancy (OR 0.60, 95% CI 0.06 to 6.14; one study, 44 women, very low quality evidence).When CHM with LOD was compared with LOD alone, there was no evidence of a difference between the groups in rates of pregnancy (OR 3.50, 95% CI 0.72 to 17.09; one study, 30 women, very low quality evidence), No data were reported on adverse events.There was no evidence of a difference between any of the comparison groups for any other outcomes. The quality of the evidence for all other comparisons and outcomes was very low. The main limitations in the evidence were failure to report live birth or adverse events, failure to describe study methods in adequate detail and imprecision due to very low event rates and wide CIs. There is insufficient evidence to support the use of CHM for women with PCOS and subfertility. No data are available on live birth, and there is no consistent evidence to indicate that CHM influences fertility outcomes. However there is very limited low quality evidence to suggest that the addition of CHM to clomiphene may improve pregnancy rates. There is insufficient evidence on adverse effects to indicate whether CHM is safe.

Tinnitus after Simultaneous and Sequential Bilateral Cochlear Implantation.

PubMed

Ramakers, Geerte G J; Kraaijenga, Véronique J C; Smulders, Yvette E; van Zon, Alice; Stegeman, Inge; Stokroos, Robert J; Free, Rolien H; Frijns, Johan H M; Huinck, Wendy J; Van Zanten, Gijsbert A; Grolman, Wilko

2017-01-01

There is an ongoing global discussion on whether or not bilateral cochlear implantation should be standard care for bilateral deafness. Contrary to unilateral cochlear implantation, however, little is known about the effect of bilateral cochlear implantation on tinnitus. To investigate tinnitus outcomes 1 year after bilateral cochlear implantation. Secondarily, to compare tinnitus outcomes between simultaneous and sequential bilateral cochlear implantation and to investigate long-term follow-up (3 years). This study is a secondary analysis as part of a multicenter randomized controlled trial. Thirty-eight postlingually deafened adults were included in the original trial, in which the presence of tinnitus was not an inclusion criterion. All participants received cochlear implants (CIs) because of profound hearing loss. Nineteen participants received bilateral CIs simultaneously and 19 participants received bilateral CIs sequentially with an inter-implant interval of 2 years. The prevalence and severity of tinnitus before and after simultaneous and sequential bilateral cochlear implantation were measured preoperatively and each year after implantation with the Tinnitus Handicap Inventory (THI) and Tinnitus Questionnaire (TQ). The prevalence of preoperative tinnitus was 42% (16/38). One year after bilateral implantation, there was a median difference of -8 (inter-quartile range (IQR): -28 to 4) in THI score and -9 (IQR: -17 to -9) in TQ score in the participants with preoperative tinnitus. Induction of tinnitus occurred in five participants, all in the simultaneous group, in the year after bilateral implantation. Although the preoperative and also the postoperative median THI and TQ scores were higher in the simultaneous group, the median difference scores were equal in both groups. In the simultaneous group, tinnitus scores fluctuated in the 3 years after implantation. In the sequential group, four patients had an additional benefit of the second CI: a total suppression of tinnitus compared with their unilateral situation. While bilateral cochlear implantation can have a positive effect on preoperative tinnitus complaints, the induction of (temporary or permanent) tinnitus was also reported. Dutch Trial Register NTR1722.

Efficacy of prophylactic doses of intravenous nitroglycerin in preventing myocardial ischemia under general anesthesia: A systematic review and meta-analysis with trial sequential analysis.

PubMed

Hoshijima, Hiroshi; Denawa, Yohei; Mihara, Takahiro; Takeuchi, Risa; Kuratani, Norifumi; Mieda, Tsutomu; Iwase, Yoshinori; Shiga, Toshiya; Wajima, Zen'ichiro; Nagasaka, Hiroshi

2017-08-01

To evaluate the efficacy of intravenous nitroglycerin (TNG) in preventing intraoperative myocardial ischemia (MI) under general anesthesia. Moreover, we analyzed the hemodynamic changes in heart rate (HR), mean blood pressure (MBP), and pulmonary capillary wedge pressure (PCWP) associated with TNG administration both before and after the induction of anesthesia. Meta-analysis. Operating room, cardiac surgery or non-cardiac surgery, all surgeries were elective measurements. We performed a computerized search of articles on PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. Meta-analysis was performed using Review Manager. The data from the individual trials were combined using a random-effects model to calculate either the pooled relative risk (RR) or the weighted mean difference (WMD) with 95% confidence interval (CI). We conducted trial sequential analysis (TSA). The primary outcome was the incidence of MI and the secondary outcomes were hemodynamic changes (HR, MBP, and PCWP). Using electronic databases, we selected 10 trials with a total of 353 patients for our review. Prophylactic intravenous TNG did not significantly decrease the incidence of MI (RR=0.61; CI, 0.33 to 1.13; P=0.12; I 2 =55). TSA corrected the CI to 0.05 to 7.39 and showed that 9.5% of the required information size was achieved. In terms of hemodynamic changes, intravenous TNG significantly reduced MBP in comparison with the placebo (MBP pre-induction: WMD=-7.27; 95% CI -14.2 to -0.33; P=0.04; I 2 =97%; MBP post-induction: WMD=-5.13; 95% CI -9.17 to -1.09; P=0.01; I 2 =73%). Our analyses showed that prophylactic intravenous TNG does not reduce the incidence of intraoperative MI. Moreover, TSA suggests that further studies are necessary to confirm the results (GRADE: very low). Prophylactic doses of intravenous TNG significantly reduced the MBP both pre and post anesthesia induction (GRADE: very low). Copyright © 2017 Elsevier Inc. All rights reserved.

The cost-effectiveness of immediate treatment or watch and wait with deferred chemotherapy for advanced asymptomatic follicular lymphoma.

PubMed

Prettyjohns, Matthew; Hoskin, Peter; McNamara, Christopher; Linch, David

2018-01-01

Recent evidence has shown that immediate treatment with rituximab induction, with and without maintenance, substantially reduces the need for further treatment in patients with advanced asymptomatic follicular lymphoma. This analysis estimates the cost-effectiveness of immediate treatment approaches in comparison to a watch and wait approach from the perspective of the UK National Health Service. A Markov decision model was developed to estimate the cost-effectiveness of treatment strategies in patients with asymptomatic follicular lymphoma. The model was populated using effectiveness data from a systematic literature review with the key clinical data sourced from a randomised trial, in which the treatment strategies were compared. Costs were estimated using UK national sources. In comparison to watchful waiting, both rituximab strategies were found to be more effective and cost saving. In comparison to rituximab induction, the addition of rituximab maintenance marginally increased effectiveness but substantially increased costs, resulting in an incremental cost-effectiveness ratio (ICER) of £69 406 per quality-adjusted life year (QALY). In probabilistic sensitivity analysis, rituximab induction was found to have a 68% probability of being cost-effective at a threshold of £20 000 per QALY. In conclusion, active treatment with rituximab induction is a cost-effective strategy to adopt in patients with asymptomatic follicular lymphoma. © 2017 John Wiley & Sons Ltd.

Randomized trial of single-dose versus divided-dose rabbit anti-thymocyte globulin induction in renal transplantation: an interim report.

PubMed

Stevens, R Brian; Mercer, David F; Grant, Wendy J; Freifeld, Alison G; Lane, James T; Groggel, Gerald C; Rigley, Theodore H; Nielsen, Kathleen J; Henning, Megan E; Skorupa, Jill Y; Skorupa, Anna J; Christensen, Kecia A; Sandoz, John P; Kellogg, Anna M; Langnas, Alan N; Wrenshall, Lucile E

2008-05-27

The optimal dosing protocol for rabbit anti-thymocyte globulin (rATG) induction in renal transplantation has not been determined, but evidence exists that rATG infusion before renal allograft reperfusion improves early graft function. Infusing a large rATG dose over a short interval has not previously been evaluated for its effect on renal function and allograft nephropathy in a prospective, randomized comparison against conventional rATG induction. Between April 20, 2004 and December 26, 2007 we enrolled renal transplant patients into a prospective, randomized, nonblinded trial of two rATG dosing protocols (single dose, 6 mg/kg vs. divided doses, 1.5 mg/kg every other day x 4; target enrollment=160) followed after 6 months by calcineurin-inhibitor withdrawal. Primary endpoints are renal function by calculated glomerular filtration rate (GFR) and chronic allograft nephropathy at protocol biopsy. We now present the early GFR data of all 160 patients and safety and efficacy data of the first 142 patients with 6 months follow up and before calcineurin inhibitor withdrawal (average follow up=23.3+/-11.6 months). There were no differences between groups in rATG-related adverse events, patient and graft survival, acute rejection, or chronic allograft nephropathy rate at 6 months. Calculated DeltaGFR (POD 1-4) was significantly better in the single-dose group (P=0.02), with a trend toward improved renal function from months 2 to 6 in recipients of deceased donor kidneys (P=0.08). This study demonstrates that administering 6 mg/kg of rATG over 24 hr is safe and is associated with improved early renal function compared with administering rATG in alternate-day doses.

An economic evaluation of laparoscopic ovarian diathermy versus gonadotrophin therapy for women with clomiphene citrate-resistant polycystic ovarian syndrome.

PubMed

Farquhar, Cynthia M

2005-08-01

Women with polycystic ovarian syndrome are typically anovulatory and require ovulation induction. Ovarian wedge resection was the first treatment for anovulation but was eventually abandoned because of the increased risk of postsurgical adhesions and as medical ovulation induction with clomiphene and gonadotrophins was introduced. However, with the advent of laparoscopy, there has been a return to surgical approaches. The potential advantages of laparoscopic surgery include avoidance of hyperstimulation and the lowered costs make ovarian surgery an attractive alternative to gonadotrophins. Clinical trials in New Zealand and the Netherlands have compared costs of laparoscopic ovarian drilling with gonadotrophins. The total cost of treatment in the Netherlands study for the ovarian drilling group was euro 4664 and for the gonadotrophins group was euro 5418. Without the cost of monitoring and the diagnostic laparoscopy then the difference was euro 2110 in favour of ovarian drilling. It was estimated that the cost per term pregnancy would be euro 14,489 for gonadotrophin and euro 11,301 for ovarian drilling (22% lower). The higher rates of multiple pregnancy in the gonadotrophin group were considered to be responsible for the increased costs. In the New Zealand trial the costs of a live birth were one-third lower in the group that underwent laparoscopic ovarian diathermy compared with those women who received gonadotrophins (NZ$19,640 and 29,836, respectively). Treating women with clomiphene-resistant polycystic ovarian syndrome with laparoscopic ovarian diathermy results in reduced direct and indirect costs. The reduction in multiple pregnancies makes the alternative of surgery particularly attractive.

Effects of oral carbohydrate with amino acid solution on the metabolic status of patients in the preoperative period: a randomized, prospective clinical trial.

PubMed

Tsutsumi, Rie; Kakuta, Nami; Kadota, Takako; Oyama, Takuro; Kume, Katsuyoshi; Hamaguchi, Eisuke; Niki, Noriko; Tanaka, Katsuya; Tsutsumi, Yasuo M

2016-10-01

Enhanced recovery after surgery is increasingly desired nowadays, and preoperative nutrient intake may be beneficial for this purpose. In this study, we investigated whether the intake of preoperative carbohydrate with amino acid (ONS) solution can improve starvation status and lipid catabolism before the induction of anesthesia. This randomized, prospective clinical trial included 24 patients who were divided into two groups before surgery under general anesthesia: a control group, comprising patients who fasted after their last meal the day before surgery (permitted to drink only water), and an ONS group, comprising patients who consumed ONS solution 2 h before surgery. Biochemical markers, the respiratory quotient, and psychosomatic scores were assessed at the initiation of anesthesia. Compared with the control group, the ONS group showed significantly lower serum free fatty acid levels [control group: 828 (729, 1004) µEq/L, ONS group: 479 (408, 610) µEq/L, P = 0.0002, median (25th, 75th percentile)] and total ketone bodies [control group: 119 (68, 440) µmol/L, ONS group: 40 [27, 64] µmol/L, P = 0.037]. In addition, analysis using the Visual Analog Scale showed higher preoperative scores for anxiety, hunger, and thirst for the control group, with no differences in any other measure of subjective well-being between groups. The results of this study suggest that preoperative ONS intake improves lipid catabolism and starvation status before the induction of anesthesia. Furthermore, it can provide better preoperative mental health compared with complete fasting.

Decreased morbidity and mortality of autologous hematopoietic transplants for children with malignant central nervous system tumors: the 'Head Start' trials, 1991-2009.

PubMed

Altshuler, C; Haley, K; Dhall, G; Vasquez, L; Gardner, S L; Stanek, J; Finlay, J L

2016-07-01

Since 1991, three sequential prospective clinical trials have been conducted by the 'Head Start' (HS) Consortium in which young children with newly-diagnosed malignant central nervous system (CNS) tumors were treated with induction chemotherapy followed by single-cycle marrow-ablative chemotherapy and autologous hematopoietic rescue as a means of improving disease cure rate and quality of survival through avoidance (<6 years old at diagnosis) or reduction (6-10 years old) of brain irradiation. Bone Marrow (HS I) or filgrastim-mobilized peripheral hematopoietic cells (HS II and III) were obtained following recovery from the first and/or second induction cycles. Radiotherapy was administered following all chemotherapy only for patients with residual tumor following completion of induction or with age greater than 6 years at diagnosis. Two hundred and twenty-six children were enrolled on three consecutive HS trials with primary malignant CNS tumors and underwent marrow-ablative chemotherapy. The 100-day treatment-related mortality (TRM) steadily declined as did grade IV transplant-related oropharyngeal mucositis. Factors most likely associated with the decrease in TRM and morbidity are increasing experience with the marrow-ablative chemotherapy regimen combined with improved leukapheresis and post-reinfusion supportive care techniques, contributing toward improved overall survival.

Comparing the cost-effectiveness of rituximab maintenance and radioimmunotherapy consolidation versus observation following first-line therapy in patients with follicular lymphoma.

PubMed

Chen, Qiushi; Ayer, Turgay; Nastoupil, Loretta J; Rose, Adam C; Flowers, Christopher R

2015-03-01

Phase 3 randomized trials have shown that maintenance rituximab (MR) therapy or radioimmunotherapy (RIT) consolidation following frontline therapy can improve progression-free survival for patients with follicular lymphoma (FL), but the cost-effectiveness of these approaches with respect to observation has not been examined using a common modeling framework. To evaluate and compare the economic impact of MR and RIT consolidation versus observation, respectively, following the first-line induction therapy for patients with advanced-stage FL. We developed Markov models to estimate patients' lifetime costs, quality-adjusted life-years (QALYs), and life-years (LYs) after MR, RIT, and observation following frontline FL treatment from the US payer's perspective. Progression risks, adverse event probabilities, costs, and utilities were estimated from clinical data of Primary RItuximab and MAintenance (PRIMA) trial, Eastern Cooperative Oncology Group (ECOG) trial (for MR), and First-line Indolent Trial (for RIT) and the published literature. We evaluated the incremental cost-effectiveness ratio for direct comparisons between MR/RIT and observation. Model robustness was addressed by one-way and probabilistic sensitivity analyses. Compared with observation, MR provided an additional 1.089 QALYs (1.099 LYs) and 1.399 QALYs (1.391 LYs) on the basis of the PRIMA trial and the ECOG trial, respectively, and RIT provided an additional 1.026 QALYs (1.034 LYs). The incremental cost per QALY gained was $40,335 (PRIMA) or $37,412 (ECOG) for MR and $40,851 for RIT. MR and RIT had comparable incremental QALYs before first progression, whereas RIT had higher incremental costs of adverse events due to higher incidences of cytopenias. MR and RIT following frontline FL therapy demonstrated favorable and similar cost-effectiveness profiles. The model results should be interpreted within the specific clinical settings of each trial. Selection of MR, RIT, or observation should be based on patient characteristics and expected trade-offs for these alternatives. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Concurrent Chemo-Radiation With or Without Induction Gemcitabine, Carboplatin, and Paclitaxel: A Randomized, Phase 2/3 Trial in Locally Advanced Nasopharyngeal Carcinoma

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

Tan, Terence, E-mail: trdtwk@nccs.com.sg; Lim, Wan-Teck; Fong, Kam-Weng

Purpose: To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation (CCRT), against CCRT alone. Patients and Methods: Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m{sup 2}, carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m{sup 2} given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m{sup 2}), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5%more » significance level and 80% power. Results: Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P=.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases–free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms. Conclusion: Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.« less

Effect of clomiphene citrate on endometrial thickness, ovulation, pregnancy and live birth in anovulatory women: systematic review and meta-analysis.

PubMed

Gadalla, M A; Huang, S; Wang, R; Norman, R J; Abdullah, S A; El Saman, A M; Ismail, A M; van Wely, M; Mol, B W J

2018-01-01

To compare the impact of clomiphene citrate (CC) vs other drug regimens on mid-cycle endometrial thickness (EMT), ovulation, pregnancy and live birth rates in women with World Health Organization (WHO) group II ovulatory disorders. We searched MEDLINE, EMBASE, Scopus, Web of Science, The Cochrane Central Register of Clinical Trials (CENTRAL) and the non-MEDLINE subset of PubMed from inception to December 2016 and cross-checked references of relevant articles. We included only randomized controlled trials (RCTs) comparing CC used alone vs other drug regimens for ovulation induction in women with WHO group II anovulation. Outcomes were mid-cycle EMT, ovulation, pregnancy and live birth rates. We pooled weighted mean differences (WMD) with 95% confidence intervals (CI) for continuous variables (EMT) and risk ratios (RR) with 95% CI for binary variables (ovulation, pregnancy and live birth rates). We retrieved 1718 articles of which 33 RCTs (4349 women, 7210 ovulation induction cycles) were included. In 15 RCTs that compared CC with letrozole, EMT was lower in the CC group (1957 women, 3892 cycles; WMD, -1.39; 95% CI, -2.27 to -0.51; I 2  = 100%), ovulation rates after CC and letrozole were comparable (1710 women, 3217 cycles; RR, 0.97; 95% CI, 0.90-1.04; I 2  = 47%), while CC led to a lower pregnancy rate (1957 women, 3892 cycles; RR, 0.78; 95% CI, 0.63-0.95; I 2  = 43%) and a lower live birth rate (RR, 0.70; 95% CI, 0.49-0.98; I 2  = 35%). In two RCTs that compared CC with CC plus metformin, EMT, ovulation and pregnancy rates were comparable (101 women, 140 cycles; WMD, -0.23; 95% CI, -0.92 to 0.45; I 2  = 78%; RR, 0.84; 95% CI, 0.67-1.06; I 2  = 0%; and RR, 0.79; 95% CI, 0.33-1.87; I 2  = 0%). In three studies that compared CC with CC plus N-acetyl cysteine (NAC), EMT was lower in the CC group (340 women, 300 cycles; WMD, -1.51; 95% CI, -1.98 to -1.04; I 2  = 45%). In two studies that compared CC with CC + nitric oxide (NO) donor, EMT was lower in the CC group (120 women, 304 cycles; WMD, -1.75; 95% CI, -2.08 to -1.41; I 2  = 0%). Compared with CC plus NO donor or NAC, CC showed statistically significant lower ovulation and pregnancy rates. Compared with tamoxifen in three studies, CC showed a tendency towards lower EMT (571 women, 844 cycles; WMD, -1.34; 95% CI, -2.70 to 0.01; I 2  = 96%) with comparable ovulation and pregnancy rates. In women with WHO group II ovulatory disorders, ovulation induction with CC might result in lower EMT than other ovulation induction regimens. Whether the lower EMT caused the lower pregnancy and live birth rates remains to be elucidated. Letrozole seems to be beneficial for these women. However, our findings should be interpreted with caution as the quality of evidence was very low. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Type I interferons for induction of remission in ulcerative colitis.

PubMed

Wang, Yongjun; MacDonald, John K; Benchimol, Eric I; Griffiths, Anne Marie; Steinhart, A Hillary; Panaccione, Remo; Seow, Cynthia H

2015-09-14

Interferons (IFNs) are cytokines which possess immunoregulatory properties and have been used to successfully treat a number of chronic inflammatory disorders. It has been postulated that Type I IFNs may be able to re-establish the Th1/Th2 balance in Th2 predominant diseases like ulcerative colitis. To systematically evaluate the efficacy and safety of type I IFN therapy for induction of remission in ulcerative colitis. We searched MEDLINE, EMBASE, CENTRAL, the Cochrane IBD/FBD group specialised register, and ClinicalTrials.gov from inception to August 8, 2014. Reference lists of trials and review articles, as well as recent proceedings from major gastroenterology meetings were manually searched. Randomised controlled trials of type I IFNs for induction of remission in UC were included. The study population included patients of any age with active ulcerative colitis. There were no exclusions based on type, dose or duration of IFN treatment. Two independent authors reviewed studies for eligibility, extracted the data and assessed study quality using the Cochrane risk of bias tool. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. The primary outcome was induction of remission of ulcerative colitis. Secondary outcomes included: time to remission, mean change in disease activity index score, clinical, histological or endoscopic improvement, improvement in quality of life, and adverse events. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes. We calculated the mean difference and corresponding 95% confidence interval for continuous outcomes. Meta-analysis was performed using RevMan 5.3.5 software. Six studies were eligible for inclusion (517 patients). Five studies compared type I IFNs to placebo injections (485 patients) and a single study compared IFNs to prednisolone enemas in patients with left-sided colitis (32 patients). The active comparator study was rated as high risk of bias due to an open-label design. Three studies were rated as unclear risk of bias for random sequence generation and allocation concealment. Two studies described as double blind were rated as unclear risk of bias for blinding. There was no significant benefit of type I IFNs over placebo for inducing clinical remission or improvement in patients with active ulcerative colitis. Thirty-six per cent (87/242) of patients in the type I IFNs group achieved clinical remission by 8 to 12 weeks compared to 30% (36/120) of placebo patients (RR 1.16, 95% CI 0.84 to 1.58; 4 studies, 362 patients). A GRADE analysis indicated that the overall quality of the evidence supporting the outcome clinical remission was moderate due to sparse data (123 events). Fifty-six per cent (149/264) of patients in the type I IFNs group improved clinically by 8 to 12 weeks compared to 48% (77/161) of placebo patients (RR 1.16, 95% CI 0.96 to 1.40; 4 studies, 425 patients). A GRADE analysis indicated that the overall quality of the evidence supporting the outcome clinical improvement was moderate due to sparse data (226 events). Patients who received type I IFNs were significantly more likely to withdraw from the studies due to adverse events than those who received placebo. Seven per cent (18/42) of type I IFNs patients withdrew due to adverse events compared to 2% (3/152) of placebo patients (RR 3.16, 95% CI 1.06 to 9.40). A GRADE analysis indicated that the overall quality of the evidence supporting the outcome withdrawal due to adverse events was low due to very sparse data (21 events). The study comparing type I IFNs to prednisolone enemas found no difference between the treatment groups in quality of life or disease activity scores. Common adverse events included headaches, arthralgias, myalgias, fatigue, back pain, nausea, application site reactions, rigors, and fevers. There were no statistically significant differences in the other secondary outcomes. Moderate quality evidence suggests that type I IFNs are not effective for the induction of remission in UC. In addition, there are concerns regarding the tolerability of this class of treatment.

Induction chemotherapy in metastatic neuroblastoma--does dose influence response? A critical review of published data standards, options and recommendations (SOR) project of the National Federation of French Cancer Centres (FNCLCC).

PubMed

Pinkerton, C R; Blanc Vincent, M P; Bergeron, C; Fervers, B; Philip, T

2000-09-01

The purpose of this study was to determine, from a review of published data, whether in stage 4 neuroblastoma in children over 1 year of age, the dose or scheduling of induction chemotherapy influenced the response rate in distant metastases. Publications relating to induction chemotherapy since the introduction of cisplatin/epipodophyllotoxin combinations were identified using Medline, Current Contents and personal reference lists. Thirteen publications were identified which described 17 regimens involving 948 children. The doses and the scheduling of the various regimens were compared with a standard regimen OPEC (vincristine, cisplatin, teniposide, cyclophosphamide). These were correlated with the reported response rates in the bone marrow. Due to a lack of standardisation in the nature of restaging investigations, timing of restaging and definitions of response it was difficult to compare all studies. The complete response rate at distant metastases ranged from less than 40% to over 90%. For individual drugs; the comparative doses given in each course ranged up to 4.2 g/m(2) for cyclophosphamide, 280 mg/m(2) for cisplatin, 600 mg/m(2) for etoposide and 4.5 mg/m(2) for vincristine. There was no evidence of any positive correlation between response rate in the marrow and either the dose of any individual drug or the schedule used. In contrast to a previous study which included a number of older studies where disease assessment was even more variable, this analysis has failed to show any justification for the routine use of very intensive induction regimens in this disease. Such an approach should only be taken in the context of randomised trials in which timing and methods of reassessment can be standardised. Until such studies demonstrate superiority either in terms of response rate or progression-free survival lower morbidity regimens should remain the standard therapy.

Efficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis

PubMed Central

Specks, Ulrich; Merkel, Peter A.; Seo, Philip; Spiera, Robert; Langford, Carol A.; Hoffman, Gary S.; Kallenberg, Cees G.M.; St. Clair, E. William; Fessler, Barri J.; Ding, Linna; Viviano, Lisa; Tchao, Nadia K.; Phippard, Deborah J.; Asare, Adam L.; Lim, Noha; Ikle, David; Jepson, Brett; Brunetta, Paul; Allen, Nancy B.; Fervenza, Fernando C.; Geetha, Duvuru; Keogh, Karina; Kissin, Eugene Y.; Monach, Paul A.; Peikert, Tobias; Stegeman, Coen; Ytterberg, Steven R.; Mueller, Mark; Sejismundo, Lourdes P.; Mieras, Kathleen; Stone, John H.

2018-01-01

Background The 18-month efficacy of a single course of rituximab as compared with conventional immunosuppression with cyclophosphamide followed by azathioprine in patients with severe (organ-threatening) antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is unknown. Methods In a multicenter, randomized, double-blind, double-dummy, noninferiority trial, we compared rituximab (375 mg per square meter of body-surface area administered once a week for 4 weeks) followed by placebo with cyclophosphamide administered for 3 to 6 months followed by azathioprine for 12 to 15 months. The primary outcome measure was complete remission of disease by 6 months, with the remission maintained through 18 months. Results A total of 197 patients were enrolled. As reported previously, 64% of the patients in the rituximab group, as compared with 53% of the patients in the cyclophosphamide–azathioprine group, had a complete remission by 6 months. At 12 and 18 months, 48% and 39%, respectively, of the patients in the rituximab group had maintained the complete remissions, as compared with 39% and 33%, respectively, in the comparison group. Rituximab met the prespecified criteria for noninferiority (P<0.001, with a noninferiority margin of 20%). There was no significant difference between the groups in any efficacy measure, including the duration of complete remission and the frequency or severity of relapses. Among the 101 patients who had relapsing disease at baseline, rituximab was superior to conventional immunosuppression at 6 months (P = 0.01) and at 12 months (P = 0.009) but not at 18 months (P = 0.06), at which time most patients in the rituximab group had reconstituted B cells. There was no significant between-group difference in adverse events. Conclusions In patients with severe ANCA-associated vasculitis, a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction and maintenance of remissions over the course of 18 months. (Funded by the National Institute of Allergy and Infectious Diseases and others; RAVE ClinicalTrials.gov number, NCT00104299.) PMID:23902481

Evaluation Effect of Shiatsu Technique on Labor Induction in Post-Term Pregnancy

PubMed Central

Batool, Teimoori; Shahin-Dokht, Navvabi-Rigi; Shahnaz, Rajabi; Azizollah, Arbabisarjou

2015-01-01

Objective: Labor induction in post-term pregnancy is considered as a conventional process of mothers’ care. Shiatsu technique is one of the complementary methods which use for post-term pregnancy induction. Therefore, the researchers decided to examine the effect of Shiatsu technique on the induction of post-term pregnancy. Materials and Methods: This is a randomized control trials which conducted on 288 women with post-term pregnancy who referred to consulting clinic at Ali- Ibn- Abi -Talib Hospital, in Zahedan-Iran in 2010-2011. Participants were selected based on random table. The participants divided into two groups: the first was shiatsu technique and the second group was control group (routine procedure). Shiatsu technique was conducted on the participants of intervention group for 30s on three points by an experienced midwife. The gathered data analyzed by SPSS version 15.00 and comparing tests were t-students tests, chi-square. Results: Mothers ages range were between 16 to 42 yr (mean 26.5-5.7) in shiatsu and 17 to 43 yr (mean 24.5-5.1) in control group. Regarding spontaneous initiation of labor, 82 women (56.9%) in Shiatsu group had spontaneous initiation of labor, whereas the number of women was only 12 (8.3%) in control group. Women who have used Shiatsu technique were significantly more likely to have spontaneous labour than those women who did not. Conclusions: Results of the study showed that shiatsu technique can be used as one of safe complementary methods for post-term pregnancy induction. PMID:25948426

Efficacy and Safety Outcomes in Patients With Advanced Melanoma Who Discontinued Treatment With Nivolumab and Ipilimumab Because of Adverse Events: A Pooled Analysis of Randomized Phase II and III Trials.

PubMed

Schadendorf, Dirk; Wolchok, Jedd D; Hodi, F Stephen; Chiarion-Sileni, Vanna; Gonzalez, Rene; Rutkowski, Piotr; Grob, Jean-Jacques; Cowey, C Lance; Lao, Christopher D; Chesney, Jason; Robert, Caroline; Grossmann, Kenneth; McDermott, David; Walker, Dana; Bhore, Rafia; Larkin, James; Postow, Michael A

2017-12-01

Purpose Approximately 40% of patients with advanced melanoma who received nivolumab combined with ipilimumab in clinical trials discontinued treatment because of adverse events (AEs). We conducted a retrospective analysis to assess the efficacy and safety of nivolumab plus ipilimumab in patients who discontinued treatment because of AEs. Methods Data were pooled from phase II and III trials of patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, every 3 weeks for four doses, followed by nivolumab monotherapy 3 mg/kg every 2 weeks (N = 409). Efficacy was assessed in all randomly assigned patients who discontinued because of AEs during the induction phase (n = 96) and in those who did not discontinue because of AEs (n = 233). Safety was assessed in treated patients who discontinued because of AEs (n = 176) at any time and in those who did not discontinue because of AEs (n = 231). Results At a minimum follow-up of 18 months, median progression-free survival was 8.4 months for patients who discontinued treatment because of AEs during the induction phase and 10.8 months for patients who did not discontinue because of AEs ( P = .97). Median overall survival had not been reached in either group ( P = .23). The objective response rate was 58.3% for patients who discontinued because of AEs during the induction phase and 50.2% for patients who did not discontinue. The vast majority of grade 3 or 4 AEs occurred during the induction phase, with most resolving after appropriate management. Conclusion Efficacy outcomes seemed similar between patients who discontinued nivolumab plus ipilimumab treatment because of AEs during the induction phase and those who did not discontinue because of AEs. Therefore, even after discontinuation, many patients may continue to derive benefit from combination therapy.

Efficacy and Safety Outcomes in Patients With Advanced Melanoma Who Discontinued Treatment With Nivolumab and Ipilimumab Because of Adverse Events: A Pooled Analysis of Randomized Phase II and III Trials

PubMed Central

Schadendorf, Dirk; Wolchok, Jedd D.; Hodi, F. Stephen; Chiarion-Sileni, Vanna; Gonzalez, Rene; Rutkowski, Piotr; Grob, Jean-Jacques; Cowey, C. Lance; Lao, Christopher D.; Chesney, Jason; Robert, Caroline; Grossmann, Kenneth; McDermott, David; Walker, Dana; Bhore, Rafia; Larkin, James

2017-01-01

Purpose Approximately 40% of patients with advanced melanoma who received nivolumab combined with ipilimumab in clinical trials discontinued treatment because of adverse events (AEs). We conducted a retrospective analysis to assess the efficacy and safety of nivolumab plus ipilimumab in patients who discontinued treatment because of AEs. Methods Data were pooled from phase II and III trials of patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, every 3 weeks for four doses, followed by nivolumab monotherapy 3 mg/kg every 2 weeks (N = 409). Efficacy was assessed in all randomly assigned patients who discontinued because of AEs during the induction phase (n = 96) and in those who did not discontinue because of AEs (n = 233). Safety was assessed in treated patients who discontinued because of AEs (n = 176) at any time and in those who did not discontinue because of AEs (n = 231). Results At a minimum follow-up of 18 months, median progression-free survival was 8.4 months for patients who discontinued treatment because of AEs during the induction phase and 10.8 months for patients who did not discontinue because of AEs (P = .97). Median overall survival had not been reached in either group (P = .23). The objective response rate was 58.3% for patients who discontinued because of AEs during the induction phase and 50.2% for patients who did not discontinue. The vast majority of grade 3 or 4 AEs occurred during the induction phase, with most resolving after appropriate management. Conclusion Efficacy outcomes seemed similar between patients who discontinued nivolumab plus ipilimumab treatment because of AEs during the induction phase and those who did not discontinue because of AEs. Therefore, even after discontinuation, many patients may continue to derive benefit from combination therapy. PMID:28841387

Oral intake of phenylbutyrate with or without vitamin D3 upregulates the cathelicidin LL-37 in human macrophages: a dose finding study for treatment of tuberculosis

PubMed Central

2013-01-01

Background We earlier showed that 4-phenylbutyrate (PB) can induce cathelicidin LL-37 expression synergistically with 1,25-dihydroxyvitamin D3 in a lung epithelial cell line. We aimed to evaluate a therapeutic dose of PB alone or in combination with vitamin D3 for induction of LL-37 expression in immune cells and enhancement of antimycobacterial activity in monocyte-derived macrophages (MDM). Methods Healthy volunteers were enrolled in an 8-days open trial with three doses of PB [250 mg (Group-I), 500 mg (Group-II) or 1000 mg (Group-III)] twice daily (b.d.) together with vitamin D3 {5000 IU once daily (o.d.)}, PB (500 mg b.d.) (Group-IV) or vitamin D3 (5000 IU o.d.) (Group-V), given orally for 4 days. Blood was collected on day-0, day-4 and day-8; plasma was separated, peripheral blood mononuclear cells (PBMC), non-adherent lymphocytes (NAL) and MDM were cultured. LL-37 transcript in cells and peptide concentrations in supernatant were determined by qPCR and ELISA, respectively. In plasma, 25-hydorxyvitamin D3 levels were determined by ELISA. MDM-mediated killing of Mycobacterium tuberculosis (Mtb) (H37Rv) was performed by conventional culture method. Results MDM from Group-II had increased concentration of LL-37 peptide and transcript at day-4, while Group-I showed increased transcript at day-4 and day-8 compared to day-0 (p < 0.05). Both Group-I and -II exhibited higher levels of transcript on day-4 compared to Group-III and Group-V (p < 0.035). Increased induction of peptide was observed in lymphocytes from Group-II on day-4 compared to Group-I and Group-IV (p < 0.05), while Group-IV showed increased levels on day-8 compared to Group-I and Group-III (p < 0.04). Intracellular killing of Mtb on day-4 was significantly increased compared to day-0 in Group-I, -II and -V (p < 0.05). Conclusion The results demonstrate that 500 mg b.d. PB with 5000 IU o.d. vitamin D3 is the optimal dose for the induction of LL-37 in macrophages and lymphocytes and intracellular killing of Mtb by macrophages. Hence, this dose has potential application in the treatment of TB and is now being used in a clinical trial of adults with active pulmonary TB (NCT01580007). PMID:23590701

Combined metformin-clomiphene in clomiphene-resistant polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Abu Hashim, Hatem; Foda, Osama; Ghayaty, Essam

2015-09-01

Our objective was to compare the effectiveness of metformin plus clomiphene citrate vs. gonadotrophins, laparoscopic ovarian diathermy, aromatase inhibitors, N-acetyl-cysteine and other insulin sensitizers+clomiphene for improving fertility outcomes in women with clomiphene-resistant polycystic ovary syndrome. PubMed, SCOPUS and CENTRAL databases were searched until April 2014 with the key words: PCOS, polycystic ovary syndrome, metformin, clomiphene citrate, ovulation induction and pregnancy. The search was limited to articles conducted with humans and published in English. The PRISMA statement was followed. Twelve randomized controlled trials (n = 1411 women) were included. Ovulation and clinical pregnancy rates per woman randomized. Compared with gonadotrophins, the metformin+clomiphene combination resulted in significantly fewer ovulations (odds ratio 0.25; 95% confidence interval 0.15-0.41; p < 0.00001, 3 trials, I(2) = 85%, n = 323) and pregnancies (odds ratio 0.45; 95% confidence interval 0.27-0.75; p = 0.002, 3 trials, I(2) = 0%, n = 323). No significant differences were found when metformin+clomiphene was compared with laparoscopic ovarian diathermy (odds ratio 0.88; 95% confidence interval 0.53-1.47; p = 0.62, 1 trial, n = 282; odds ratio 0.96; 95% confidence interval 0.60-1.54; p = 0.88, 2 trials, I(2) = 0%, n = 332, for ovulation and pregnancy rates, respectively). Likewise, no differences were observed in comparison with aromatase inhibitors (odds ratio 0.88; 95% confidence interval 0.58-1.34; p = 0.55, 3 trials, I(2) = 3%, n = 409; odds ratio 0.85; 95% confidence interval 0.53-1.36; p = 0.50, 2 trials, n = 309, for ovulation and pregnancy rates, respectively). There is evidence for the superiority of gonadotrophins, but the metformin+clomiphene combination is mainly relevant for clomiphene-resistant polycystic ovary syndrome patients and, if not effective, a next step could be gonadotrophins. More attempts with metformin+clomiphene are only relevant if there is limited access to gonadotrophins. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Preoperative carbohydrate loading for elective surgery: a systematic review and meta-analysis.

PubMed

Li, Lun; Wang, Zehao; Ying, Xiangji; Tian, Jinhui; Sun, Tiantian; Yi, Kang; Zhang, Peng; Jing, Zhang; Yang, Kehu

2012-07-01

It is unclear whether the preoperative administration of oral carbohydrates (CHO) is safe and effective, and therefore we herein evaluated the efficacy and adverse events associated with CHO for elective surgery. Comprehensive searches were conducted to identify randomized controlled trials (RCTs), which evaluated preoperative CHO for elective surgery. Two reviewers independently selected the trials, extracted data, and assessed the methodological qualities and evidence levels. The data were analyzed by the RevMan 5.0 software program. CHO increased the insulin and glucose levels on the first day after surgery higher than those in overnight fasting group (fifteen RCTs) and i.v. glucose infusion group (three RCTs). The pooled results of thirteen RCTs showed greater declines in the insulin level at the induction of anesthesia and a smaller increase in the glucose level at the end of surgery, and fewer decreases in the postoperative insulin sensitivity index in the CHO group were observed as compared to the placebo group. No aspiration was observed in any of the included studies. CHO appears to be safe, and may attenuate postoperative insulin resistance as compared to placebo. However, the quality of most of the published trials has been poor, and the evidence levels for most outcomes were low, so rigorous and larger RCTs are needed in the future.

Evaluating the addition of oxaliplatin to single agent fluoropyrimidine in the treatment of locally advanced rectal cancer: a systematic review and meta-analysis.

PubMed

Thavaneswaran, Subotheni; Kok, Peey Sei; Price, Timothy

2017-10-01

Multimodality treatment of patients with locally advanced rectal cancer (LARC) has significantly improved local disease control, however the unaltered overall survival (OS) implicates an inability to further control micrometastases, providing rationale for intensified systemic treatment. A systematic review was conducted to evaluate the efficacy and toxicity of adding oxaliplatin to a fluoropyrimidine (intervention) compared with fluoropyrimidine alone (control) in the treatment of LARC. We searched CENTRAL, Medline Ovid, PubMed and EMBASE databases. Randomised trials comparing the intervention and control delivered either pre- or post-operatively were included. Seven trials involving 4444 patients were identified; five studies evaluated the intervention vs control preoperatively; one study peri-operatively; and one, post-operatively. There was no significant difference in OS with oxaliplatin addition, HR 0.89, 95% CI, 0.75 to 1.06. There was however an improvement in disease free survival, 3-year local and distant recurrence rates (RR) favouring oxaliplatin. Preoperative oxaliplatin improved pathological complete response (pCR), but with a greater toxicity and reduced compliance with radiation. There is no OS benefit with oxaliplatin, despite improved pCR, local and distant RR. Before drawing definitive conclusions, longer follow-up in included trials and availability of published data from other eligible studies, including the induction setting, are needed.

Induction gemcitabine in standard dose or prolonged low-dose with cisplatin followed by concurrent radiochemotherapy in locally advanced non-small cell lung cancer: a randomized phase II clinical trial

PubMed Central

Vrankar, Martina; Zwitter, Matjaz; Bavcar, Tanja; Milic, Ana; Kovac, Viljem

2014-01-01

Background The optimal combination of chemotherapy with radiation therapy for treatment locally advanced non-small cell lung cancer (NSCLC) remains an open issue. This randomized phase II study compared gemcitabine in two different schedules and cisplatin - as induction chemotherapy, followed by radiation therapy concurrent with cisplatin and etoposid. Patients and methods. Eligible patients had microscopically confirmed inoperable non-metastatic non-small cell lung cancer; fulfilled the standard criteria for platin-based chemotherapy; and signed informed consent. Patients were treated with 3 cycles of induction chemotherapy with gemcitabine and cisplatin. Two different aplications of gemcitabine were compared: patients in arm A received gemcitabine at 1250 mg/m2 in a standard half hour i.v. infusion on days 1 and 8; patients in arm B received gemcitabine at 250 mg/m2 in prolonged 6-hours i.v. infusion on days 1 and 8. In both arms, cisplatin 75 mg/m2 on day 2 was administered. All patients continued treatment with radiation therapy with 60–66 Gy concurrent with cisplatin 50 mg/m2 on days 1, 8, 29 and 36 and etoposid 50 mg/m2 on days 1–5 and 29–33. The primary endpoint was response rate (RR) after induction chemotherapy; secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). Results From September 2005 to November 2010, 106 patients were recruited to this study. No statistically signifficant differences were found in RR after induction chemotherapy between the two arms (48.1% and 57.4%, p = 0.34). Toxicity profile was comparable and mild with grade 3/4 neutropenia as primary toxicity in both arms. One patient in arm B suffered from acute peripheral ischemia grade 4 and an amputation of lower limb was needed. With a median follow-up of 69.3 months, progression-free survival and median survival in arm A were 15.7 and 24.8 months compared to 18.9 and 28.6 months in arm B. The figures for 1- and 3-year overall survival were 73.1% and 30.8% in arm A, and 81.5 % and 44.4% in arm B, respectively. Conclusions Among the two cisplatin-based doublets of induction chemotherapy for inoperable NSCLC, both schedules of gemcitabine have a comparable toxicity profile. Figures for RR, PFS and OS are among the best reported in current literature. While there is a trend towards better efficacy of the treament with prolonged infusion of gemcitabine, the difference between the two arms did not reach statistical significance. PMID:25435850

Adding the phytoestrogen Cimicifugae Racemosae to clomiphene induction cycles with timed intercourse in polycystic ovary syndrome improves cycle outcomes and pregnancy rates - a randomized trial.

PubMed

Shahin, Ahmed Y; Mohammed, Safwat A

2014-07-01

Owing to their potential to act as estrogen receptor modulators and interfere with aromatase enzyme in animal studies, phytoestrogens (PE) may be useful as part of ovulation induction for polycystic ovary syndrome (PCOS). Patients <35 years, presenting with infertility and PCOS, were included and randomly allocated to either group I (clomiphene citrate; CC) or group II (CC plus Cimicifugae racemosae; CR). Primary outcome was pregnancy rate. Secondary outcomes included ovulation, midcycle serum estradiol and luteinizing hormone (LH) as well as mid-luteal serum progesterone. Analysis included 98 patients in group I versus 96 patients in group II. Both groups were matched regarding demographics and basic data. Significant differences were elicited when comparing days until HCG injection (15.0 ± 1.7 versus 12.0 ± 1.9, p=0.91), endometrial thickness (mm) (8.5 ± 1.9 versus 12.5 ± 1.9, p<0.001), serum levels of mid-luteal and midcycle estradiol (p<0.001; Figure 2), LH (IU/ml) (p<0.001) as well as mid-luteal progesterone (p<0.001). PE plus CC group had significantly higher clinical pregnancies per cycle (33/192 (17.2%) versus 71/204 (34.8%), p<0.01), compared to the CC only group. Adding CR to clomiphene-induction cycles with timed intercourse in polycystic ovarian syndrome improves cycle outcomes and pregnancy rates.

Propofol Requirement for Induction of Unconsciousness Is Reduced in Patients with Parkinson's Disease: A Case Control Study

PubMed Central

Xu, Xiao-ping; Yu, Xi-ya; Wu, Xi; Hu, Xiao-wu; Chen, Jian-chun; Li, Jin-bao; Deng, Xiao-ming

2015-01-01

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, but whether the neurodegenerative process influences the pharmacodynamics of propofol remains unclear. We aimed to evaluate the effect of PD on pharmacodynamics of propofol. A total of 31 PD patients undergoing surgical treatment (PD group) and 31 pair-controlled non-PD patients undergoing intracranial surgery (NPD group) were recruited to investigate the propofol requirement for unconsciousness induction. Unconsciousness was induced in all patients with target-controlled infusion of propofol. The propofol concentration at which unconsciousness was induced was compared between the two groups. EC50 and EC95 were calculated as well. Demographic data, bispectral index, and hemodynamic values were comparable between PD and NPD groups. The mean target concentration of propofol when unconsciousness was achieved was 2.32 ± 0.38 μg/mL in PD group, which was significantly lower than that in NPD group (2.90 ± 0.35 μg/mL). The EC50 was 2.05 μg/mL (95% CI: 1.85–2.19 μg/mL) in PD group, much lower than the 2.72 μg/mL (95% CI: 2.53–2.88 μg/mL) in NPD group. In conclusion, the effective propofol concentration needed for induction of unconsciousness in 50% of patients is reduced in PD patients. (This trial is registered with NCT01998204.) PMID:26495319

Optimisation of antiretroviral therapy in HIV-infected children under 3 years of age.

PubMed

Penazzato, Martina; Prendergast, Andrew J; Muhe, Lulu M; Tindyebwa, Denis; Abrams, Elaine

2014-05-22

In the absence of antiretroviral therapy (ART), over 50% of HIV-infected infants progress to AIDS and death by 2 years of age. However, there are challenges to initiation of ART in early life, including the possibility of drug resistance in the context of prevention of mother-to-child transmission (PMTCT) programs, a paucity of drug choices , uncertain dosing for some medications and long-term toxicities. Key management decisions include when to start ART, what regimen to start, and whether and when to substitute drugs or interrupt therapy. This review, an update of a previous review, aims to summarize the currently available evidence on this topic and inform the ART management in HIV-infected children less than 3 years of age. To evaluate 1) when to start ART in young children (less than 3 years); 2) what ART to start with, comparing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI)-based regimens; and 3) whether alternative strategies should be used to optimize antiretroviral treatment in this population: induction (initiation with 4 drugs rather than 3 drugs) followed by maintenance ART, interruption of ART and substitution of PI with NNRTI drugs once virological suppression is achieved on a PI-based regimen. Search methodsWe searched for published studies in the Cochrane HIV/AIDS Review Group Trials Register, The Cochrane Library, Pubmed, EMBASE and CENTRAL. We screened abstracts from relevant conference proceedings and searched for unpublished and ongoing trials in clinical trial registries (ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform). We identified RCTs that recruited perinatally HIV-infected children under 3 years of age without restriction of setting. We rejected trials that did not include children less than 3 years of age, did not provide stratified outcomes for those less than 3 years or did not evaluate either timing of ART initiation, choice of drug regimen or treatment switch/interruption strategy. Two reviewers independently applied study selection criteria, assessed study quality and extracted data. Effects were assessed using the hazard ratio (HR) for time-to-event outcomes, relative risk for dichotomous outcomes and weighted mean difference for continuous outcomes. A search of the databases identified a total of 735 unique, previously unreviewed studies, of which 731 were excluded to leave 4 new studies to incorporate into the review. Four additional studies were identified in conference proceedings, for a total of 8 studies addressing when to start treatment (n=2), what to start (n=3), whether to substitute lopinavir/ritonavir (LPV/r) with nevirapine (NVP) (n=1), whether to use an induction-maintenance ART strategy (n=1) and whether to interrupt treatment (n=1).Treatment initiation in asymptomatic infants with good immunological status was associated with a 75% reduction (HR=0.25; 95%CI 0.12-0.51; p=0.0002) in mortality or disease progression in the one trial with sufficient power to address this question. In a smaller pilot trial, median CD4 cell count was not significantly different between early and deferred treatment groups 12 months after ART.Regardless of previous exposure to nevirapine for PMTCT, the hazard for treatment failure at 24 weeks was 1.79 (95%CI 1.33, 2.41) times higher in children starting ART with a NVP-based regimen compared to those starting with a LPV/r-based regimen (p=0.0001) with no clear difference in the effect observed for children younger or older than 1 year. The hazard for virological failure at 24 weeks was overall 1.84 (95%CI 1.29, 2.63) times higher for children starting ART with a NVP-based regimen compared to those starting with a LPV/r-based regimen (p=0.0008) with a larger difference in time to virological failure (or death) between the NVP and LPV/r-based regimens when ART was initiated in the first year of life.Infants starting a LPV/r regimen and achieving sustained virological suppression who then substituted LPV/r with NVP after median 9 months on LPV/r were less likely to develop virological failure (defined as at least one VL greater than 50 copies/mL) compared with infants who started and stayed on LPV/r (HR=0.62, 95%CI 0.41, 0.92, p=0.02). However the hazard for confirmed failure at a higher viral load (>1000 copies/mL) was greater among children who switched to NVP compared to those who remained on LPV/r (HR=10.19, 95% CI 2.36, 43.94, p=0.002).Children undergoing an induction-maintenance ART approach with a 4-drug NNRTI-based regimen for 36 weeks, followed by 3-drug ART, had significantly greater CD4 rise than children receiving a standard 3-drug NNRTI-based ART at 36 weeks (mean difference 1.70 [95%CI 0.61, 2.79] p=0.002) and significantly better viral load response at 24 weeks (OR 1.99 [95%CI 1.09, 3.62] p=0.02). However, the immunological and virological benefits were short-term.The one trial of treatment interruption that compared children initiating continuous ART from infancy with children interrupting ART was terminated early because the duration of treatment interruption was less than 3 months in most infants. Children interrupting treatment had similar growth and occurrence of serious adverse events as those in the continuous arm. ART initiation in asymptomatic children under 1 year of age reduces morbidity and mortality, but it remains unclear whether there are clinical benefits to starting ART in asymptomatic children diagnosed with HIV infection between 1-3 years.The available evidence shows that a LPV/r-based first-line regimen is more efficacious than a NVP-based regimen, regardless of PMTCT exposure status. New formulations of LPV/r are urgently required to enable new WHO recommendations to be implemented. An alternative approach to long-term LPV/r is substituting LPV/r with NVP once virological suppression is achieved. This strategy looked promising in the one trial undertaken, but may be difficult to implement in the absence of routine viral load testing.A 4-drug induction-maintenance approach showed short-term virological and immunological benefits during the induction phase but, in the absence of sustained benefits, is not recommended as a routine treatment strategy. Treatment interruption following early ART initiation in infancy was challenging for children who were severely immunocompromised in the context of poor clinical immunological condition at ART initiation due to the short duration of interruption, and is therefore not practical in ART treatment programmes where close monitoring is not feasible.

[Reduction of omalgia in laparoscopic cholecystectomy: clinical randomized trial ketorolac vs ketorolac and acetazolamide].

PubMed

Figueroa-Balderas, Lorena; Franco-López, Francisco; Flores-Álvarez, Efrén; López-Rodríguez, Jorge Luis; Vázquez-García, José Antonio; Barba-Valadez, Claudia Teresa

2013-01-01

Laparoscopy cholecystectomy for the surgical treatment of cholelithiasis has been considered the gold standard. The referred pain to the shoulder (omalgia) may be present to 63% of the patients and limits outpatient management. The study was to evaluate the usefulness of acetazolamide associated with ketorolac for reduction of the omalgia to minimally invasive treatment. We performed a clinical trial, randomized, double blind in patients undergoing laparoscopic cholecystectomy to assess the reduction of post-operative omalgia comparing ketorolac and ketorolaco+acetazolamida. 31 patients in each group were studied. The study group: 250 mg of acetazolamide before anesthetic induction and 30 mg of ketorolac in the immediate postoperative period. one tablet of placebo prior to the anesthetic induction and 30 mg of ketorolac in the immediate postoperative. The presence of omalgia was assessed using the analog visual scale. The variables recorded included: age, sex, flow of carbon dioxide intra-abdominal pressure, surgical time, urgent or elective surgery, omalgia, severity of pain evaluated by analog visual scale, addition analgesia. Both groups were homogeneous and statistical analysis showed no differences in the variables studied. The omalgia in the study group was presented at 9.67% and in the group control was the 58.06% (p < 0.001). 250 mg oral acetazolamide associated 30 mg of ketorolac reduces significantly the development of omalgia in patients undergoing laparoscopic cholecystectomy.

Comparison of acupuncture pretreatment followed by letrozole versus letrozole alone on live birth in anovulatory infertile women with polycystic ovary syndrome: a study protocol for a randomised controlled trial.

PubMed

Li, Juan; Ng, Ernest Hung Yu; Stener-Victorin, Elisabet; Hu, Zhenxing; Wu, Wanting; Lai, Maohua; Wu, Taixiang; Ma, Hongxia

2016-10-07

The high prevalence of insulin resistance in women with polycystic ovary syndrome (PCOS) is considered to be one of the major pathophysiological changes in PCOS that leads to anovulatory infertility. We hypothesise that electroacupuncture pretreatment improves insulin sensitivity and leads to a higher ovulation rate and greater chances of live birth after the induction of ovulation. The effect of electroacupuncture pretreatment followed by ovulation induction in women with anovulatory PCOS has not been investigated before, and we present here a randomised controlled trial to test this hypothesis by comparing electroacupuncture pretreatment followed by letrozole versus letrozole alone in anovulatory women with PCOS. This is a multicentre, randomised,and controlled trial. A total of 384 patients will be enrolled in this study and will be randomly allocated by a central randomisation system to the treatment group or the control group in a 1:1 ratio. The treatment group will undergo 16 weeks of electroacupuncture pretreatment followed by 4 cycles of letrozole, and the control group will only undergo 4 cycles of letrozole. The primary outcome will be the live birth rate. All statistical analyses will be performed using the SPSS program V.21.0 (SPSS, Chicago, Illinois, USA), and a p value <0.05 will be considered statistically significant. This study has been approved by the ethics committees of each participating centre. Written consent will be obtained from each patient and her husband before any study procedure is performed. Adverse events will be categorised, and the percentage of patients experiencing adverse events or serious adverse events during the treatment period will be documented. The results of this trial will be disseminated in peer-reviewed journals and presented at international meetings. NCT02491320. 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/.

Acute rejection characteristics from a prospective, randomized, double-blind, placebo-controlled multicenter trial of early corticosteroid withdrawal.

PubMed

Gaber, A Osama; Moore, Linda W; Alloway, Rita R; Woodle, E Steve; Pirsch, John; Shihab, Fuad; Henning, Alice; Fitzsimmons, William; Holman, John; Reisfield, Robin; First, M Roy

2013-02-27

This report characterizes acute rejection and rejection outcomes in subjects randomized to continuous corticosteroid therapy (CCS) or early corticosteroid withdrawal (CSWD; 7 days after transplantation) in the Astellas Blinded CSWD Trial. The Astellas Blinded CSWD Trial was a 5-year, prospective, multicenter, randomized, double-blind trial of early CCS withdrawal in 386 kidney transplant recipients (195 CCS and 191 CSWD). Tacrolimus and mycophenolate mofetil were required as well as either rabbit antithymocyte globulin or interleukin-2 receptor antibody induction. Biopsy-confirmed acute rejection (BCAR) was grade 1A or higher by Banff criteria. This report also provides borderline changes (BL) that did not meet Banff grade 1A included with BCAR (BCAR+BL). BCAR+BL was 25 (12.8%) in CCS group and 42 (22.0%) in CSWD group (P=0.022). Early BCAR+BL (first 90 days after transplantation) was less frequent in CCS (n=5 [2.6%]) than in CSWD (n=22 [11.5%]; P<0.001). Among non-African-American subjects, early BCAR+BL occurred more often in CSWD (n=20 [12.7%]) versus CCS (n=2 [1.3%]; P<0.001). Late acute rejection (>2 years) occurred more often in African-American subjects in CCS (n=5 [13.9%]) than in CSWD (n=0; P=0.056). Risk factors were CSWD (hazard ratio [HR], 4.72; P<0.002) and human leukocyte antigen mismatch (HR, 1.48; P<0.005) for early BCAR+BL and CSWD (HR, 1.9; P<0.02), human leukocyte antigen mismatch (HR, 1.2; P<0.01), and age (HR, 0.97; P<0.002) for 5-year rejection. The HR for graft loss associated with BCAR+BL was 8.8. BCAR+BL may occur more frequently during the early period after transplantation under an early CSWD regimen with tacrolimus plus induction compared with CCS, particularly among non-African-Americans.

Randomized Controlled Trial of Use of the Peanut Ball During Labor.

PubMed

Roth, Cheryl; Dent, Sarah A; Parfitt, Sheryl E; Hering, Sandra L; Bay, R Curtis

2016-01-01

The purpose of this study was to evaluate the efficacy of peanut ball use on duration of first stage labor and pushing time in women who were scheduled for elective induction of labor at ≥39 weeks gestation and planning an epidural. In this randomized controlled trial, women having labor induction and planning a labor epidural were assigned (1:1) to one of two groups: one group used a peanut ball and one group did not. Outcome variables were time spent in first stage labor and time spent pushing. Factors included group assignment (peanut ball, no peanut ball), parity (primiparous, multiparous), and race. Age and maximum oxytocin dose served as covariates. Among women having elective induction with epidural analgesia, use of a peanut ball reduced first stage labor duration for primiparous patients significantly more than multiparous patients, p = 0.018. There was no significant difference in the reduction of length of first stage labor for multiparous women, p = 0.057 with use of the peanut ball. Peanut ball use did not alter length of pushing time for either group, p > 0.05. Use of peanut balls may reduce total labor time to a greater degree in primiparous patients than multiparous patients having elective induction at ≥39 weeks with epidural analgesia.

Pegylated-asparaginase during induction therapy for adult acute lymphoblastic leukaemia: toxicity data from the UKALL14 trial.

PubMed

Patel, B; Kirkwood, A A; Dey, A; Marks, D I; McMillan, A K; Menne, T F; Micklewright, L; Patrick, P; Purnell, S; Rowntree, C J; Smith, P; Fielding, A K

2017-01-01

Safety and efficacy data on pegylated asparaginase (PEG-ASP) in adult acute lymphoblastic leukaemia (ALL) induction regimens are limited. The UK National Cancer Research Institute UKALL14 trial NCT01085617 prospectively evaluated the tolerability of 1000 IU/m 2 PEG-ASP administered on days 4 and 18 as part of a five-drug induction regimen in adults aged 25-65 years with de novo ALL. Median age was 46.5 years. Sixteen of the 90 patients (median age 56 years) suffered treatment-related mortality during initial induction therapy. Eight of the 16 died of sepsis in combination with hepatotoxicity. Age and Philadelphia (Ph) status were independent variables predicting induction death >40 versus ⩽40 years, odds ratio (OR) 18.5 (2.02-169.0), P=0.01; Ph- versus Ph+ disease, OR 13.60 (3.52-52.36), P<0.001. Of the 74 patients who did not die, 37 (50.0%) experienced at least one grade 3/4 PEG-ASP-related adverse event, most commonly hepatotoxicity (36.5%, n=27). A single dose of PEG-ASP achieved trough therapeutic enzyme levels in 42/49 (86%) of the patients tested. Although PEG-ASP delivered prolonged asparaginase activity in adults, it was difficult to administer safely as part of the UKALL14 intensive multiagent regimen to those aged >40 years. It proved extremely toxic in patients with Ph+ ALL, possibly owing to interaction with imatinib.

Pegylated-asparaginase during induction therapy for adult acute lymphoblastic leukaemia: toxicity data from the UKALL14 trial

PubMed Central

Patel, B; Kirkwood, A A; Dey, A; Marks, D I; McMillan, A K; Menne, T F; Micklewright, L; Patrick, P; Purnell, S; Rowntree, C J; Smith, P; Fielding, A K

2017-01-01

Safety and efficacy data on pegylated asparaginase (PEG-ASP) in adult acute lymphoblastic leukaemia (ALL) induction regimens are limited. The UK National Cancer Research Institute UKALL14 trial NCT01085617 prospectively evaluated the tolerability of 1000 IU/m2 PEG-ASP administered on days 4 and 18 as part of a five-drug induction regimen in adults aged 25–65 years with de novo ALL. Median age was 46.5 years. Sixteen of the 90 patients (median age 56 years) suffered treatment-related mortality during initial induction therapy. Eight of the 16 died of sepsis in combination with hepatotoxicity. Age and Philadelphia (Ph) status were independent variables predicting induction death >40 versus ⩽40 years, odds ratio (OR) 18.5 (2.02–169.0), P=0.01; Ph− versus Ph+ disease, OR 13.60 (3.52–52.36), P<0.001. Of the 74 patients who did not die, 37 (50.0%) experienced at least one grade 3/4 PEG-ASP-related adverse event, most commonly hepatotoxicity (36.5%, n=27). A single dose of PEG-ASP achieved trough therapeutic enzyme levels in 42/49 (86%) of the patients tested. Although PEG-ASP delivered prolonged asparaginase activity in adults, it was difficult to administer safely as part of the UKALL14 intensive multiagent regimen to those aged >40 years. It proved extremely toxic in patients with Ph+ ALL, possibly owing to interaction with imatinib. PMID:27480385

Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia

PubMed Central

Ramos, Nestor R.; Mo, Clifton C.; Karp, Judith E.; Hourigan, Christopher S.

2015-01-01

The limited sensitivity of the historical treatment response criteria for acute myeloid leukemia (AML) has resulted in a different paradigm for treatment compared with most other cancers presenting with widely disseminated disease. Initial cytotoxic induction chemotherapy is often able to reduce tumor burden to a level sufficient to meet the current criteria for “complete” remission. Nevertheless, most AML patients ultimately die from their disease, most commonly as clinically evident relapsed AML. Despite a variety of available salvage therapy options, prognosis in patients with relapsed or refractory AML is generally poor. In this review, we outline the commonly utilized salvage cytotoxic therapy interventions and then highlight novel investigational efforts currently in clinical trials using both pathway-targeted agents and immunotherapy based approaches. We conclude that there is no current standard of care for adult relapsed or refractory AML other than offering referral to an appropriate clinical trial. PMID:25932335

Health-Related Quality of Life in SCALOP, a Randomized Phase 2 Trial Comparing Chemoradiation Therapy Regimens in Locally Advanced Pancreatic Cancer

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

Hurt, Christopher N., E-mail: hurtcn@cardiff.ac.uk; Mukherjee, Somnath; Bridgewater, John

Purpose: Chemoradiation therapy (CRT) for patients with locally advanced pancreatic cancer (LAPC) provides survival benefits but may result in considerable toxicity. Health-related quality of life (HRQL) measurements during CRT have not been widely reported. This paper reports HRQL data from the Selective Chemoradiation in Advanced Localised Pancreatic Cancer (SCALOP) trial, including validation of the QLQ-PAN26 tool in CRT. Methods and Materials: Patients with locally advanced, inoperable, nonmetastatic carcinoma of the pancreas were eligible. Following 12 weeks of induction gemcitabine plus capecitabine (GEMCAP) chemotherapy, patients with stable and responding disease were randomized to a further cycle of GEMCAP followed by capecitabine- or gemcitabine-basedmore » CRT. HRQL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Pancreatic Cancer module (PAN26). Results: A total of 114 patients from 28 UK centers were registered and 74 patients randomized. There was improvement in the majority of HRQL scales during induction chemotherapy. Patients with significant deterioration in fatigue, appetite loss, and gastrointestinal symptoms during CRT recovered within 3 weeks following CRT. Differences in changes in HRQL scores between trial arms rarely reached statistical significance; however, where they did, they favored capecitabine therapy. PAN26 scales had good internal consistency and were able to distinguish between subgroups of patients experiencing toxicity. Conclusions: Although there is deterioration in HRQL following CRT, this resolves within 3 weeks. HRQL data support the use of capecitabine- over gemcitabine-based chemoradiation. The QLQ-PAN26 is a reliable and valid tool for use in patients receiving CRT.« less

Deep peeling using phenol versus percutaneous collagen induction combined with trichloroacetic acid 20% in atrophic post-acne scars; a randomized controlled trial.

PubMed

Leheta, Tahra Mohamed; Abdel Hay, Rania Mounir; El Garem, Yehia Farouk

2014-04-01

Deep peeling using phenol and percutaneous collagen induction (PCI) are used in treating acne scars. To compare deep peeling using phenol and PCI combined with trichloroacetic acid (TCA) 20% in treating atrophic acne scars. 24 patients with post-acne atrophic scars were randomly divided into two groups; group 1 was subjected to one session of deep peeling using phenol, and group 2 was subjected to four sessions of PCI combined with TCA 20%. As a secondary outcome measure, side effects were recorded and patients were asked to assess their % of improvement by a questionnaire completed 8 months after the procedure. Scar severity scores improved by a mean of 75.12% (p < 0.001) in group 1 and a mean of 69.43% (p < 0.001) in group 2. Comparing the degree of improvement in different types of scars, within the same group after treatment, revealed a significant highest degree of improvement in the rolling type (p = 0.005) in group 2. Deep peeling using phenol and PCI with TCA 20% were effective in treating post-acne atrophic scars.

Specific oral tolerance induction in childhood.

PubMed

Peters, Rachel L; Dang, Thanh D; Allen, Katrina J

2016-12-01

Food allergy continues to be a significant public health concern for which there are no approved treatments and management strategies primarily include allergen avoidance and pharmacological measures for accidental exposures. Food allergy is thought to result from either a failure to establish oral tolerance or the breakdown of existing oral tolerance, and therefore, experimental preventative and treatment strategies are now aimed at inducing specific oral tolerance. This may occur in infancy prior to the development of food allergy through the optimal timing of dietary exposure (primary oral tolerance induction) or as a treatment for established food allergy through oral immunotherapy (secondary oral tolerance induction). Trials examining the effectiveness of early dietary allergen exposure to prevent food allergy have yielded promising results for peanut allergy but not so for other allergens, although the results of several trials are yet to be published. Although infant feeding guidelines no longer advise to avoid allergenic foods and exposure to food allergens orally is an important step in inducing food tolerance by the immune system, evidence regarding the optimal timing, dose and form of these foods into the infant's diet is lacking. Likewise, oral immunotherapy trials appear promising for inducing desensitization; however, the long-term efficacy in achieving sustained desensitization and optimal protocols to achieve this is unknown. More research is needed in this emerging field. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Low-dose fotemustine as second-line chemotherapy for recurrent glioblastoma multiforme.

PubMed

De Felice, Francesca; Bulzonetti, Nadia; Musio, Daniela; D'Elia, Alessandro; Salvati, Maurizio; Tombolini, Vincenzo

2013-09-01

To test if fotemustine administrated at low doses during the maintenance phase of gioblastoma therapy could improve the toxicity profile, without reducing progression-free survival at six months (PFS-6). Patients enrolled were affected by recurrent glioblastoma multiforme, proven by magnetic resonance imaging (MRI), at least six months after radiochemotherapy completion. Fotemustine was administered at an induction dose of 100 mg/m(2) followed by a maintenance dose of 75 mg/m(2). All 15 patients completed the induction phase. Eight patients began maintenance-phase therapy and received a median of three cycles (range=2-6). Grade 3 or more haematological toxicity was not documented. The PFS-6 was 5/15 and the median overall survival was 7.5 months. Haematological toxicity compares favourably with trials using the conventional scheme: no grade 3-4 adverse effects were recorded. This low-dose approach could be considered a compromise treatment whilst waiting for definitive standardization of second-line therapy, in order to reduce severe hematological toxicity.

Quantitative structure-activity relationships by neural networks and inductive logic programming. I. The inhibition of dihydrofolate reductase by pyrimidines

NASA Astrophysics Data System (ADS)

Hirst, Jonathan D.; King, Ross D.; Sternberg, Michael J. E.

1994-08-01

Neural networks and inductive logic programming (ILP) have been compared to linear regression for modelling the QSAR of the inhibition of E. coli dihydrofolate reductase (DHFR) by 2,4-diamino-5-(substitured benzyl)pyrimidines, and, in the subsequent paper [Hirst, J.D., King, R.D. and Sternberg, M.J.E., J. Comput.-Aided Mol. Design, 8 (1994) 421], the inhibition of rodent DHFR by 2,4-diamino-6,6-dimethyl-5-phenyl-dihydrotriazines. Cross-validation trials provide a statistically rigorous assessment of the predictive capabilities of the methods, with training and testing data selected randomly and all the methods developed using identical training data. For the ILP analysis, molecules are represented by attributes other than Hansch parameters. Neural networks and ILP perform better than linear regression using the attribute representation, but the difference is not statistically significant. The major benefit from the ILP analysis is the formulation of understandable rules relating the activity of the inhibitors to their chemical structure.

How to select among available options for the treatment of multiple myeloma.

PubMed

Harousseau, J L

2012-09-01

The introduction of novel agents (thalidomide, bortezomib and lenalidomide) in the frontline therapy of multiple myeloma has markedly improved the outcome both in younger patients who are candidates for high-dose therapy plus autologous stem-cell transplantation (HDT/ASCT) and in elderly patients. In the HDT/ASCT paradigm, novel agents may be used as induction therapy or after HDT/ASCT as consolidation and/or maintenance therapy. It is now possible to achieve up to 70% complete plus very good partial remission after HDT/ASCT and 70% 3-year progression-free survival (PFS). However long-term non-intensive therapy may also yield high response rates and prolonged PFS. Randomized trials comparing these two strategies are underway. In elderly patients, six randomized studies show the benefit of adding thalidomide to melphalan-prednisone (MP). a large randomized trial has also shown that the combination of bortezomib-MP is superior to MP for all parameters measuring the response and outcome. Finally, the role of maintenance is currently evaluated and a randomized trial shows that low-dose lenalidomide maintenance prolongs PFS.

Tumor necrosis factor alpha blocking agents as treatment for ulcerative colitis intolerant or refractory to conventional medical therapy: a meta-analysis.

PubMed

Lv, Ruxi; Qiao, Weiguang; Wu, Zhiyong; Wang, Yinjun; Dai, Shixue; Liu, Qiang; Zheng, Xuebao

2014-01-01

Efficacy of tumor necrosis factor alpha (TNF-α) blockers for treatment of ulcerative colitis that is unresponsive to conventional therapy is unclear due to recent studies yielding conflicting results. To assess the efficacy and safety of anti-TNF-α agents for treatment of ulcerative colitis patients who were intolerant or refractory to conventional medical therapy. Pubmed, Embase, and the Cochrane database were searched. Analysis was performed on randomized controlled trials that assessed anti-TNF-α therapy on ulcerative colitis patients that had previously failed therapy with corticosteroids and/or immunosuppressants. The primary outcome focused on was the frequency of patients that achieved clinical remission. Further trial outcomes of interest included rates of remission without patient use of corticosteroids during the trial, extent of mucosal healing, and the number of cases that resulted in colectomy and serious side effects. Eight trials from seven studies (n = 2122) met the inclusion criteria and were thus included during analysis. TNF-α blockers demonstrated clinical benefit as compared to placebo control as evidenced by an increased frequency of clinical remission (p<0.00001), steroid-free remission (p = 0.01), endoscopic remission (p<0.00001) and a decrease in frequency of colectomy (p = 0.03). No difference was found concerning serious side effects (p = 0.05). Three small trials (n = 57) comparing infliximab to corticosteroid treatment, showed no difference in frequency of clinical remission (p = 0.93), mucosal healing (p = 0.80), and requirement for a colectomy (p = 0.49). One trial compared infliximab to cyclosporine (n = 115), wherein no difference was found in terms of mucosal healing (p = 0.85), colectomy frequency (p = 0.60) and serious side effects (p = 0.23). TNF-α blockers are effective and safe therapies for the induction and maintenance of long-term remission and prevention of treatment by colectomy for patients with refractory ulcerative colitis where conventional treatment was previously ineffective. Furthermore, infliximab and cyclosporine were found to be comparable for treating acute severe steroid-refractory ulcerative colitis.

Phase II clinical trial of combination chemotherapy with dexamethasone for lymphoma in dogs.

PubMed

Greenberg, Chelsea B; Boria, Pedro A; Borgatti-Jeffreys, Antonella; Raskin, Rose E; Lucroy, Michael D

2007-01-01

Dogs with histologically confirmed lymphoma were treated with a 14-week induction chemotherapy protocol that included dexamethasone. A phase II clinical trial was done using a standard two-stage design. Complete remission occurred in 21 (88%) dogs, with a median initial progression-free interval of 186 days. Toxicity was mild and self-limiting in the majority of dogs.

Pregnancy complications and metabolic disease in women with clomiphene citrate-resistant anovulation randomized to receive laparoscopic electrocautery of the ovaries or ovulation induction with gonadotropins: a 10-year follow-up.

PubMed

Nahuis, Marleen J; Oude Lohuis, Eefje J; Bayram, Neriman; Hompes, Peter G A; Oosterhuis, G Jurjen E; van der Veen, Fulco; Mol, Ben Willem J; van Wely, Madelon

2014-01-01

To assess long-term effects of laparoscopic electrocautery of the ovaries compared with ovulation induction with gonadotropins in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS) on the incidence of pregnancy complications like gestational diabetes, hypertensive disorders, and metabolic or cardiovascular disease. Long-term follow-up study. Twenty-eight hospitals within the Netherlands. One hundred sixty-eight CC-resistant women who had participated in a randomized controlled trial between 1998 and 2001 comparing electrocautery and gonadotropins. Postal questionnaire, search in medical files. Pregnancy complications, metabolic or cardiovascular disease. Eighty-two percent of follow-up data were obtained. Thirteen of 68 women (19%) allocated to electrocautery, and 14 of 63 women (22%) allocated to gonadotropins had evidence for pregnancy complications (relative risk 0.86; 95% confidence interval 0.43-1.7). At follow-up, 12 of 69 (17%) women allocated to electrocautery, and 13 of 69 (19%) women allocated to gonadotropins had evidence for metabolic or cardiovascular disease (relative risk 0.90; 95% confidence interval 0.39-2.1). The risk of these was modified by body mass index (BMI), but not by female age or treatment allocation. This study is based on questionnaires and data from medical files. In the absence of routine screening, under-reporting in our follow-up study is likely. Electrocautery in women with CC-resistant PCOS does not affect pregnancy complications or metabolic or cardiovascular disease later in life compared with ovulation induction with gonadotropins. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Lectin of Bacillus subtilis sp. as overinducer of gamma-interferonogenesis.

PubMed

Kishko, Ia H; Vasylenko, M I; Pidhors'kyĭ, V S; Kovalenko, E O

1997-01-01

It has been demonstrated experimentally that lectin of Bacillus subtilis sp. in comparison with generally accepted Con A, PHA and lectin of "gold rain" grass--Laburnum anagyroides M e d i k in trials on white mice of CBA line gave in 4 hours of induction maximal titers of gamma-IFN in blood serum of animals--153.6 +/- 17.0 IU/ml. Practically identical titers had been obtained after induction by lectin "gold rain", some lower--after Con A and PHA. At swine gamma-IFN synthesis optimal density of cell suspension must contain 2.5 + 10(7) immunocytes in 1 ml, owing to which it is possible to obtain the titer equal 1 : 2150. Materials with using of bacterial lectins at various degree of purification had shown that maximal titers in blood serum of mongrel white mice were registered at administration to animals of non-purified lectin, 4 times lower--at using of half-purified and purified lectins. Data of these trials in vivo were confirmed by materials of gamma-IFN induction by immunocytes of swine, cattle and even man.

Impact of induction treatment before autologous stem cell transplantation on long-term outcome in patients with newly diagnosed multiple myeloma.

PubMed

Gassiot, Susanna; Motlló, Cristina; Llombart, Inuska; Morgades, Mireia; González, Yolanda; Garcia-Caro, Montse; Ribera, Josep-Maria; Oriol, Albert

2017-06-01

Clinical trials for patients with multiple myeloma (MM) using novel agent (NA)-based regimens before autologous stem cell transplantation (SCT) have shown improvement in response rates and progression-free survival (PFS); however they have failed to identify a significant overall survival (OS) benefit. The aim of this study was to analyze the potential impact of initial induction on the feasibility and outcome of subsequent treatment lines in a real clinical practice setting. Patients with consecutive MM <70 years of age diagnosed between 1999 and 2009 were prospectively registered and classified as having received conventional chemotherapy induction regimens with new agents available at relapse (CC cohort, 89 patients) or as treated with NAs upfront (NA cohort, 65 patients). Patients in the NA cohort demonstrated a superior median PFS (2.8 years vs 1.6 years, P=.03) and also a median PFS from diagnosis to second progression (5.2 years vs 2.7 years, P=.003). After a median follow-up of 7 years, clear differences in OS were observed (7.97 years in NA cohort compared to 3.35 years in CC cohort, P<.001). New agent-based first-line induction treatments provide benefits in both PFS and beyond that point, contributing to a significant improvement in OS. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intrauterine insemination versus timed intercourse with clomiphene citrate in polycystic ovary syndrome: a randomized controlled trial.

PubMed

Abu Hashim, Hatem; Ombar, Osama; Abd Elaal, Ibrahim

2011-04-01

To compare the efficacy of intrauterine insemination vs. timed intercourse with clomiphene citrate as a first-line treatment for anovulatory infertility associated with polycystic ovary syndrome. A randomized controlled trial following the CONSORT criteria. A university hospital and a private practice setting. 188 women (525 cycles) with polycystic ovary syndrome. Women received three consecutive cycles of ovulation induction with clomiphene citrate and intrauterine insemination (n=93, 259 cycles) or three consecutive cycles of clomiphene citrate with timed intercourse (n=95, 266 cycles). Clinical pregnancy rate per cycle, number of growing and mature follicles, serum estradiol, endometrial thickness at the hCG day, serum progesterone, ovulation, miscarriage and live birth rates. There were no differences between the two groups regarding the clinical pregnancy rate per cycle or per woman (8.49 vs. 7.89% and 23.6 vs. 22.1%; p=0.26 and p=0.33, respectively). Two twin pregnancies occurred in each group. Miscarriage and live birth rates were comparable (18.1 vs. 19% and 19.35 vs. 17.89%; p=0.31 and p=0.33, respectively). No ectopic, higher-order pregnancies or cases of ovarian hyperstimulation syndrome occurred. No differences were found regarding the number of follicles, serum progesterone, ovulation rates, estradiol levels or endometrial thickness at the hCG day (7.7±0.4 vs. 7.5±0.6mm; p=0.54). Ovulation induction with clomiphene citrate and timed intercourse is as effective as that with intrauterine insemination for achieving pregnancy in polycystic ovary syndrome and could represent the initial treatment option, being less invasive and less expensive than intrauterine insemination. © 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

Once daily oral mesalamine compared to conventional dosing for induction and maintenance of remission in ulcerative colitis: a systematic review and meta-analysis.

PubMed

Feagan, Brian G; MacDonald, John K

2012-09-01

We systematically reviewed and compared the efficacy and safety of once daily (OD) mesalamine to conventional dosing for induction and maintenance of remission in ulcerative colitis (UC). A literature search to January 2012 identified all applicable randomized trials. Study quality was evaluated using the Cochrane risk of bias tool. The GRADE criteria were used to assess the overall quality of the evidence. Studies were subgrouped by formulation for meta-analysis. Eleven studies that evaluated 4070 patients were identified. The risk of bias was low for most factors, although five studies were single-blind and one was open-label. No difference was observed between the dosing strategies in the proportion of patients with clinical remission (relative risk [RR] 0.95; 95% confidence interval [CI] 0.82-1.10), clinical improvement (RR 0.87 95% CI 0.68-1.10), or relapse at 6 (RR 1.10; 95% CI 0.83-1.46) or 12 months (RR 0.92; 95% CI 0.83-1.03). Subgroup analyses showed no important differences in efficacy. No significant difference was demonstrated in rates of medication adherence or adverse events between OD and conventional dosing. OD mesalamine appears to be as effective and safe as conventional dosing for both the treatment of mild to moderately active UC and for maintenance of remission in quiescent UC. The failure to demonstrate a superior rate of adherence to OD dosing may be due to the high rate of adherence observed in the clinical trials environment. Future research should assess the value of OD dosing in community settings. Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.

Tolerance in Nonhuman Primates by Delayed Mixed Chimerism

DTIC Science & Technology

2017-12-01

person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control ...induction of mixed chimerism in a non -human primate (NHP) model. This approach, in contrast to protocols which have already reached clinical trials...principle of delayed induction of mixed chimerism in a non -human primate (NHP) model. This approach, in contrast to protocols which have already reached

Effects of Low-dose Selenium on the Inflammatory Response in Coronary Artery Bypass Graft Surgery: A Clinical Trial

PubMed Central

Sedighinejad, Abbas; Imantalab, Vali; Mirmansouri, Ali; Mohammadzadeh Jouryabi, Ali; Kanani, Gholamreza; Nassiri Sheikhani, Nassir; Haghighi, Mohammad; Atrkarroushan, Zahra; Biazar, Gelareh

2016-01-01

Background Coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB) triggers an inflammatory reaction, leading to the development of myocardial damage and dysfunction. It is suggested that selenium (Se), an essential trace element, has a protective role against oxidative stress. Decreased intraoperative Se levels might be an independent predictive factor for postoperative multiorgan failure. In spite of its proposed advantages, however, the optimal timing and dosage are not well known. Objectives To determine whether 600 µg of intravenous Se administration before induction of anesthesia for CABG surgery could attenuate inflammatory reactions in an Iranian population. Methods This randomized triple-blind clinical trial took place in the department of cardiac surgery of an academic hospital affiliated with Guilan University of Medical Sciences (GUMS) from May 2015 to September 2015. Eighty-eight eligible patients scheduled for elective on-pump CABG surgery were divided into two groups using randomized fixed quadripartite blocks. They received either an intravenous bolus of 600 µg Se before induction of anesthesia, or normal saline as a placebo. We had four measurement time-points: just before induction of anesthesia (T0), immediately after the end of CPB (T1), 24 hours after surgery (T2), and 48 hours after surgery (T3). Interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) serum levels were measured using the enzyme-linked immunosorbent assay (ELISA). Results Data from a total of 81 patients were analyzed: group S (n = 41) and group C (n = 40). There was no significant difference between the two groups with regard to baseline characteristics. In both groups, CPB caused markedly increased IL-6, TNF-α, and CRP plasma concentrations compared with baseline (P = 0.0001). However, the pattern of changes was not significantly different between group S (P = 0.068) and group C (P = 0.26). The IL-6 and TNF-α change trends were significant in each group (P=0.0001). However, comparing the two groups showed no significant difference. With regard to IL-6, there was no significant difference between the two groups at the time-points of T1 (P = 0.34), T2 (P = 0.17), and T3 (P = 0.056), and the same was found for TNF-α at T1 (P = 0.34), T2 (P = 0.17), and T3 (P = 0.056). With regard to CRP, the trend of the changes was significant in each group (P = 0.0001). However, comparing two groups showed a borderline significant difference between them at T1 (P = 0.039), but not at T2 (P = 0.075) or T3 (P = 0.11). Conclusions This study revealed that the administration of 600 μg of intravenous Se immediately before induction of anesthesia was safe, but when compared to a placebo, no predominant clinical effects or modifications in the systemic inflammatory response induced by on-pump CABG were observed. PMID:27795837

Enteric-coated budesonide for the induction and maintenance of remission of Crohn's disease in children.

PubMed

Cohen, Stanley A; Aloi, Marina; Arumugam, Ramalingam; Baker, Robert; Bax, Kevin; Kierkuś, Jaroslaw; Koletzko, Sibylle; Lionetti, Paolo; Persson, Tore; Eklund, Stefan

2017-07-01

These studies evaluated the safety and efficacy of enteric-coated budesonide for the induction and maintenance of remission of mild-to-moderate Crohn's disease (CD) in children. The consecutive, multicenter, open-label, non-comparative studies enrolled patients aged 6-17 years. In the induction study, patients with active CD of the ileum and/or ascending colon received budesonide 9 mg or 6 mg once daily for 8 weeks; in the maintenance study, patients in remission received budesonide 6 mg once daily for 12 weeks. The primary objective was assessment of safety, including glucocorticosteroid-related side effects and serum cortisol levels. Efficacy was assessed using the Pediatric Crohn's Disease Activity Index (PCDAI), and health-related quality of life (HRQoL) using the IMPACT-III questionnaire. In the induction study (n = 108), most adverse events were related to CD, commonly abdominal pain; possible glucocorticosteroid-related effects included acne and increased appetite but without significant weight gain. Subnormal morning cortisol levels were observed in 32 of 103 patients after 8 weeks. Budesonide reduced disease activity from baseline (mean ± standard deviation, 9.1 ± 8.5 vs. 19.1 ± 10.1, p < .001) with 58.1% of patients reaching remission (PCDAI <10); HRQoL improved (p < .001). In the maintenance study (n = 50), mean disease activity worsened (p = .047) with HRQoL unchanged (p = .33). Budesonide treatment was generally well tolerated, although the potential for adrenal suppression was noted. Budesonide was effective for induction of remission in children with mild-to-moderate CD but not for maintaining remission (ClinicalTrials.gov identifiers: NCT01444092, NCT01453946).

An embedded checklist in the Anesthesia Information Management System improves pre-anaesthetic induction setup: a randomised controlled trial in a simulation setting.

PubMed

Wetmore, Douglas; Goldberg, Andrew; Gandhi, Nishant; Spivack, John; McCormick, Patrick; DeMaria, Samuel

2016-10-01

Anaesthesiologists work in a high stress, high consequence environment in which missed steps in preparation may lead to medical errors and potential patient harm. The pre-anaesthetic induction period has been identified as a time in which medical errors can occur. The Anesthesia Patient Safety Foundation has developed a Pre-Anesthetic Induction Patient Safety (PIPS) checklist. We conducted this study to test the effectiveness of this checklist, when embedded in our institutional Anesthesia Information Management System (AIMS), on resident performance in a simulated environment. Using a randomised, controlled, observer-blinded design, we compared performance of anaesthesiology residents in a simulated operating room under production pressure using a checklist in completing a thorough pre-anaesthetic induction evaluation and setup with that of residents with no checklist. The checklist was embedded in the simulated operating room's electronic medical record. Data for 38 anaesthesiology residents shows a statistically significant difference in performance in pre-anaesthetic setup and evaluation as scored by blinded raters (maximum score 22 points), with the checklist group performing better by 7.8 points (p<0.01). The effects of gender and year of residency on total score were not significant. Simulation duration (time to anaesthetic agent administration) was increased significantly by the use of the checklist. Required use of a pre-induction checklist improves anaesthesiology resident performance in a simulated environment. The PIPS checklist as an integrated part of a departmental AIMS warrant further investigation as a quality measure. 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/

Costs and consequences of treatment for mild gestational diabetes mellitus – evaluation from the ACHOIS randomised trial

PubMed Central

Moss, John R; Crowther, Caroline A; Hiller, Janet E; Willson, Kristyn J; Robinson, Jeffrey S

2007-01-01

Background Recommended best practice is that economic evaluation of health care interventions should be integral with randomised clinical trials. We performed a cost-consequence analysis of treating women with mild gestational diabetes mellitus by dietary advice, blood glucose monitoring and insulin therapy as needed compared with routine pregnancy care, using patient-level data from a multi-centre randomised clinical trial. Methods Women with a singleton pregnancy who had mild gestational diabetes diagnosed by an oral glucose-tolerance test between 24 and 34 weeks' gestation and their infants were included. Clinical outcomes and outpatient costs derived from all women and infants in the trial. Inpatient costs derived from women and infants attending the hospital contributing the largest number of enrolments (26.1%), and charges to women and their families derived from a subsample of participants from that hospital (in 2002 Australian dollars). Occasions of service and health outcomes were adjusted for maternal age, ethnicity and parity. Analysis of variance was used with bootstrapping to confirm results. Primary clinical outcomes were serious perinatal complications; admission to neonatal nursery; jaundice requiring phototherapy; induction of labour and caesarean delivery. Economic outcome measures were outpatient and inpatient costs, and charges to women and their families. Results For every 100 women with a singleton pregnancy and positive oral glucose tolerance test who were offered treatment for mild gestational diabetes mellitus in addition to routine obstetric care, $53,985 additional direct costs were incurred at the obstetric hospital, $6,521 additional charges were incurred by women and their families, 9.7 additional women experienced induction of labour, and 8.6 more babies were admitted to a neonatal nursery. However, 2.2 fewer babies experienced serious perinatal complication and 1.0 fewer babies experienced perinatal death. The incremental cost per additional serious perinatal complication prevented was $27,503, per perinatal death prevented was $60,506 and per discounted life-year gained was $2,988. Conclusion It is likely that the general public in high-income countries such as Australia would find reductions in perinatal mortality and in serious perinatal complications sufficient to justify additional health service and personal monetary charges. Over the whole lifespan, the incremental cost per extra life-year gained is highly favourable. Trial Registration Australian Clinical Trials Registry ACTRN12606000294550 PMID:17963528

Twenty years of ovulation induction with metformin for PCOS; what is the best available evidence?

PubMed

Abu Hashim, Hatem

2016-01-01

The potential reproductive benefits of metformin, a drug endowed with the capacity to ameliorate insulin resistance in polycystic ovary syndrome (PCOS), has garnered much interest over the past 2 decades. In this review, randomized-controlled trials (RCT) and meta-analyses of RCT comparing metformin are critically appraised and summarized. PubMed and CENTRAL databases were consulted. Evidence is insufficient to favour the use of metformin or metformin plus clomiphene citrate instead of clomiphene citrate for ovulation induction in women with newly diagnosed PCOS. Evidence is also insufficient to recommend metformin as a primary treatment for non-obese women with PCOS. Metformin plus clomiphene citrate should be considered as an effective option in clomiphene citrate-resistant PCOS. In women with PCOS undergoing gonadotrophin ovulation induction, metformin significantly increased pregnancy and live birth rates (P < 0.0001 and P = 0.020, respectively) with reduced risk of cancelled cycles. A beneficial effect of metformin co-treatment in increasing clinical pregnancy rates and reducing the risk of OHSS in PCOS patients undergoing assisted reproduction techniques has been shown. No evidence was found of reduced risk of spontaneous abortion or increased risk of major anomalies in women with PCOS taking metformin during the first trimester. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

The Feasibility of Hypnotic Analgesia in Ameliorating Pain and Anxiety Among Adults Undergoing Needle Electromyography

PubMed Central

Slack, David; Nelson, Lonnie; Patterson, David; Burns, Stephen; Hakimi, Kevin; Robinson, Lawrence

2017-01-01

Objective Our hypothesis was that hypnotic analgesia reduces pain and anxiety during electromyography [EMG]. Design Prospective randomized controlled clinical trial at outpatient electrodiagnostic clinics in teaching hospitals. Just prior to EMG, 26 subjects were randomized to one of three 20 minute audio programs: (EDU) education about EMG (n=8); (HYP-C) hypnotic induction without analgesic suggestion (n=10) or; (HYP-ANLG) hypnotic induction with analgesic suggestion (n=8). The blinded electromyographer provided a post-hypnotic suggestion at the start of EMG. After EMG, subjects rated worst and average pain, and anxiety using visual analog scales. Results Mean values for the EDU, HYP-C and HYP-ANLG groups were not significantly different (mean ± sd): worst pain 67 ± 25, 42 ± 18, 49 ± 30: average pain 35 ± 26, 27 ± 14, 25 ± 22; anxiety 44 ± 41, 42 ± 23, 22 ± 24. When hypnosis groups were merged [n=18] and compared with the EDU condition [n=8], average and worst pain and anxiety were less for the hypnosis group than EDU, but this was statistically significant only for worst pain [hypnosis - 46 ± 24 vs. EDU - 67 ± 35, p=0.049] with a 31% average reduction. Conclusions A short hypnotic induction appears to reduce worst pain during EMG. PMID:18971768

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

Hatton, Matthew; Nankivell, Matthew, E-mail: mn@ctu.mrc.ac.uk; Lyn, Ethan

Purpose: Recent clinical trials and meta-analyses have shown that both CHART (continuous hyperfractionated accelerated radiation therapy) and induction chemotherapy offer a survival advantage over conventional radical radiotherapy for patients with inoperable non-small cell-lung cancer (NSCLC). This multicenter randomized controlled trial (INCH) was set up to assess the value of giving induction chemotherapy before CHART. Methods and Materials: Patients with histologically confirmed, inoperable, Stage I-III NSCLC were randomized to induction chemotherapy (ICT) (three cycles of cisplatin-based chemotherapy followed by CHART) or CHART alone. Results: Forty-six patients were randomized (23 in each treatment arm) from 9 UK centers. As a result ofmore » poor accrual, the trial was closed in December 2007. Twenty-eight patients were male, 28 had squamous cell histology, 34 were Stage IIIA or IIIB, and all baseline characteristics were well balanced between the two treatment arms. Seventeen (74%) of the 23 ICT patients completed the three cycles of chemotherapy. All 42 (22 CHART + 20 ICT) patients who received CHART completed the prescribed treatment. Median survival was 17 months in the CHART arm and 25 months in the ICT arm (hazard ratio of 0.60 [95% CI 0.31-1.16], p = 0.127). Grade 3 or 4 adverse events (mainly fatigue, dysphagia, breathlessness, and anorexia) were reported for 13 (57%) CHART and 13 (65%) ICT patients. Conclusions: This small randomized trial indicates that ICT followed by CHART is feasible and well tolerated. Despite closing early because of poor accrual, and so failing to show clear evidence of a survival benefit for the additional chemotherapy, the results suggest that CHART, and ICT before CHART, remain important options for the treatment of inoperable NSCLC and deserve further study.« less

Results of a phase II trial for high-risk neuroblastoma treatment protocol JN-H-07: a report from the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG).

PubMed

Hishiki, Tomoro; Matsumoto, Kimikazu; Ohira, Miki; Kamijo, Takehiko; Shichino, Hiroyuki; Kuroda, Tatsuo; Yoneda, Akihiro; Soejima, Toshinori; Nakazawa, Atsuko; Takimoto, Tetsuya; Yokota, Isao; Teramukai, Satoshi; Takahashi, Hideto; Fukushima, Takashi; Kaneko, Takashi; Hara, Junichi; Kaneko, Michio; Ikeda, Hitoshi; Tajiri, Tatsuro; Nakagawara, Akira

2018-04-26

The Japanese Children's Cancer Group (JCCG) Neuroblastoma Committee (JNBSG) conducted a phase II clinical trial for high-risk neuroblastoma treatment. We report the result of the protocol treatment and associated genomic aberration studies. JN-H-07 was a single-arm, late phase II trial for high-risk neuroblastoma treatment with open enrollment from June 2007 to February 2009. Eligible patients underwent five courses of induction chemotherapy followed by high-dose chemotherapy with hematopoietic stem cell rescue. Surgery for the primary tumor was scheduled after three or four courses of induction chemotherapy. Radiotherapy was administered to the primary tumor site and to any bone metastases present at the end of induction chemotherapy. The estimated 3-year progression-free and overall survival rates of the 50 patients enrolled were 36.5 ± 7.0 and 69.5 ± 6.6%, respectively. High-dose chemotherapy caused severe toxicity including three treatment-related deaths. In response to this, the high-dose chemotherapy regimen was modified during the trial by infusing melphalan before administering carboplatin and etoposide. The modified high-dose chemotherapy regimen was less toxic. Univariate analysis revealed that patients younger than 547 days and patients whose tumor showed a whole chromosomal gains / losses pattern had a significantly poor prognosis. Notably, the progression-free survival of cases with MYCN amplification were not inferior to those without MYCN amplification. The outcome of patients treated with the JN-H-07 protocol showed improvement over the results reported by previous studies conducted in Japan. Molecular and genetic profiling may enable a more precise stratification of the high-risk cohort.

Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model.

PubMed

Jones-Hughes, Tracey; Snowsill, Tristan; Haasova, Marcela; Coelho, Helen; Crathorne, Louise; Cooper, Chris; Mujica-Mota, Ruben; Peters, Jaime; Varley-Campbell, Jo; Huxley, Nicola; Moore, Jason; Allwood, Matt; Lowe, Jenny; Hyde, Chris; Hoyle, Martin; Bond, Mary; Anderson, Rob

2016-08-01

End-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy: kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation, followed by immunosuppressive therapy (induction and maintenance therapy) to reduce the risk of kidney rejection and prolong graft survival. To review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect(®), Novartis Pharmaceuticals UK Ltd) and rabbit anti-human thymocyte immunoglobulin (rATG) (Thymoglobulin(®), Sanofi) as induction therapy, and immediate-release tacrolimus (TAC) (Adoport(®), Sandoz; Capexion(®), Mylan; Modigraf(®), Astellas Pharma; Perixis(®), Accord Healthcare; Prograf(®), Astellas Pharma; Tacni(®), Teva; Vivadex(®), Dexcel Pharma), prolonged-release tacrolimus (Advagraf(®) Astellas Pharma), belatacept (BEL) (Nulojix(®), Bristol-Myers Squibb), mycophenolate mofetil (MMF) (Arzip(®), Zentiva; CellCept(®), Roche Products; Myfenax(®), Teva), mycophenolate sodium (MPS) (Myfortic(®), Novartis Pharmaceuticals UK Ltd), sirolimus (SRL) (Rapamune(®), Pfizer) and everolimus (EVL) (Certican(®), Novartis) as maintenance therapy in adult renal transplantation. Clinical effectiveness searches were conducted until 18 November 2014 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science (via ISI), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted until 18 November 2014 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Database (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and the American Economic Association's electronic bibliography (via EconLit, EBSCOhost). Included studies were selected according to predefined methods and criteria. A random-effects model was used to analyse clinical effectiveness data (odds ratios for binary data and mean differences for continuous data). Network meta-analyses were undertaken within a Bayesian framework. A new discrete time-state transition economic model (semi-Markov) was developed, with acute rejection, graft function (GRF) and new-onset diabetes mellitus used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death. Eighty-nine randomised controlled trials (RCTs), of variable quality, were included. For induction therapy, no treatment appeared more effective than another in reducing graft loss or mortality. Compared with placebo/no induction, rATG and BAS appeared more effective in reducing biopsy-proven acute rejection (BPAR) and BAS appeared more effective at improving GRF. For maintenance therapy, no treatment was better for all outcomes and no treatment appeared most effective at reducing graft loss. BEL + MMF appeared more effective than TAC + MMF and SRL + MMF at reducing mortality. MMF + CSA (ciclosporin), TAC + MMF, SRL + TAC, TAC + AZA (azathioprine) and EVL + CSA appeared more effective than CSA + AZA and EVL + MPS at reducing BPAR. SRL + AZA, TAC + AZA, TAC + MMF and BEL + MMF appeared to improve GRF compared with CSA + AZA and MMF + CSA. In the base-case deterministic and probabilistic analyses, BAS, MMF and TAC were predicted to be cost-effective at £20,000 and £30,000 per quality-adjusted life-year (QALY). When comparing all regimens, only BAS + TAC + MMF was cost-effective at £20,000 and £30,000 per QALY. For included trials, there was substantial methodological heterogeneity, few trials reported follow-up beyond 1 year, and there were insufficient data to perform subgroup analysis. Treatment discontinuation and switching were not modelled. High-quality, better-reported, longer-term RCTs are needed. Ideally, these would be sufficiently powered for subgroup analysis and include health-related quality of life as an outcome. Only a regimen of BAS induction followed by maintenance with TAC and MMF is likely to be cost-effective at £20,000-30,000 per QALY. This study is registered as PROSPERO CRD42014013189. The National Institute for Health Research Health Technology Assessment programme.

Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model.

PubMed Central

Jones-Hughes, Tracey; Snowsill, Tristan; Haasova, Marcela; Coelho, Helen; Crathorne, Louise; Cooper, Chris; Mujica-Mota, Ruben; Peters, Jaime; Varley-Campbell, Jo; Huxley, Nicola; Moore, Jason; Allwood, Matt; Lowe, Jenny; Hyde, Chris; Hoyle, Martin; Bond, Mary; Anderson, Rob

2016-01-01

BACKGROUND End-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy: kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation, followed by immunosuppressive therapy (induction and maintenance therapy) to reduce the risk of kidney rejection and prolong graft survival. OBJECTIVES To review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect(®), Novartis Pharmaceuticals UK Ltd) and rabbit anti-human thymocyte immunoglobulin (rATG) (Thymoglobulin(®), Sanofi) as induction therapy, and immediate-release tacrolimus (TAC) (Adoport(®), Sandoz; Capexion(®), Mylan; Modigraf(®), Astellas Pharma; Perixis(®), Accord Healthcare; Prograf(®), Astellas Pharma; Tacni(®), Teva; Vivadex(®), Dexcel Pharma), prolonged-release tacrolimus (Advagraf(®) Astellas Pharma), belatacept (BEL) (Nulojix(®), Bristol-Myers Squibb), mycophenolate mofetil (MMF) (Arzip(®), Zentiva; CellCept(®), Roche Products; Myfenax(®), Teva), mycophenolate sodium (MPS) (Myfortic(®), Novartis Pharmaceuticals UK Ltd), sirolimus (SRL) (Rapamune(®), Pfizer) and everolimus (EVL) (Certican(®), Novartis) as maintenance therapy in adult renal transplantation. METHODS Clinical effectiveness searches were conducted until 18 November 2014 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science (via ISI), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted until 18 November 2014 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Database (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and the American Economic Association's electronic bibliography (via EconLit, EBSCOhost). Included studies were selected according to predefined methods and criteria. A random-effects model was used to analyse clinical effectiveness data (odds ratios for binary data and mean differences for continuous data). Network meta-analyses were undertaken within a Bayesian framework. A new discrete time-state transition economic model (semi-Markov) was developed, with acute rejection, graft function (GRF) and new-onset diabetes mellitus used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death. RESULTS Eighty-nine randomised controlled trials (RCTs), of variable quality, were included. For induction therapy, no treatment appeared more effective than another in reducing graft loss or mortality. Compared with placebo/no induction, rATG and BAS appeared more effective in reducing biopsy-proven acute rejection (BPAR) and BAS appeared more effective at improving GRF. For maintenance therapy, no treatment was better for all outcomes and no treatment appeared most effective at reducing graft loss. BEL + MMF appeared more effective than TAC + MMF and SRL + MMF at reducing mortality. MMF + CSA (ciclosporin), TAC + MMF, SRL + TAC, TAC + AZA (azathioprine) and EVL + CSA appeared more effective than CSA + AZA and EVL + MPS at reducing BPAR. SRL + AZA, TAC + AZA, TAC + MMF and BEL + MMF appeared to improve GRF compared with CSA + AZA and MMF + CSA. In the base-case deterministic and probabilistic analyses, BAS, MMF and TAC were predicted to be cost-effective at £20,000 and £30,000 per quality-adjusted life-year (QALY). When comparing all regimens, only BAS + TAC + MMF was cost-effective at £20,000 and £30,000 per QALY. LIMITATIONS For included trials, there was substantial methodological heterogeneity, few trials reported follow-up beyond 1 year, and there were insufficient data to perform subgroup analysis. Treatment discontinuation and switching were not modelled. FUTURE WORK High-quality, better-reported, longer-term RCTs are needed. Ideally, these would be sufficiently powered for subgroup analysis and include health-related quality of life as an outcome. CONCLUSION Only a regimen of BAS induction followed by maintenance with TAC and MMF is likely to be cost-effective at £20,000-30,000 per QALY. STUDY REGISTRATION This study is registered as PROSPERO CRD42014013189. FUNDING The National Institute for Health Research Health Technology Assessment programme. PMID:27578428

Phase II Trial of Induction Chemotherapy Followed by Surgery for Squamous Cell Carcinoma of the Oral Tongue in Young Adults

PubMed Central

Kies, Merrill S.; Boatright, Dowin H.; Li, Guojun; Blumenschein, George; El-Naggar, Adel K.; Lewin, Jan S.; Steinhaus, Ganene; Sturgis, Erich M.

2013-01-01

Background We conducted a phase II clinical trial of induction chemotherapy followed by surgery ± radiotherapy for squamous cell carcinoma of the oral tongue (SCCOT) in young adults. Methods From September 2001 to October 2004, 23 patients aged 18–49 years with clinical T2-3N0-2M0 SCCOT and no prior radiotherapy, chemotherapy, or neck dissection underwent induction chemotherapy (paclitaxel, ifosfamide, and carboplatin) followed by glossectomy and neck dissection ± radiotherapy and chemotherapy. Results On final surgical pathology, 9 (39%) patients had a complete/major (2 complete) histologic response at the primary tumor site; 8 (35%) had no response or progression. Similarly, 9 (39%) patients had a complete response in the neck or remained node negative; 6 (26%) had an increase in nodal category. No treatment-associated deaths occurred, and toxicity was modest. At a median follow-up from the end of treatment of 52 months (minimum, 23 months), 10 (43%) patients developed recurrence, and all 10 died of cancer. Crude recurrence/cancer death rates were associated with ≤ a partial response at the tongue (P = .029), poor histologic differentiation (P = .012), and multiple adverse features on final surgical pathology (P = .040). Conclusions Response rates and overall survival with this induction chemotherapy regimen were limited, but complete/major response at the tongue was associated with excellent prognosis. Additionally, improved patient selection and predictive tumor biomarkers will be needed for induction chemotherapy to be routinely incorporated into the treatment of oral tongue cancer in young adults. PMID:22009800

Phase II trial of induction chemotherapy followed by surgery for squamous cell carcinoma of the oral tongue in young adults.

PubMed

Kies, Merrill S; Boatright, Dowin H; Li, Guojun; Blumenschein, George; El-Naggar, Adel K; Brandon Gunn, G; Lewin, Jan S; Steinhaus, Ganene D; Sturgis, Erich M

2012-09-01

We conducted a phase II clinical trial of induction chemotherapy followed by surgery ± radiotherapy for squamous cell carcinoma of the oral tongue (SCCOT) in young adults. From September 2001 to October 2004, 23 patients aged 18 to 49 years with clinical T2-3 N0-2 M0 SCCOT and no prior radiotherapy, chemotherapy, or neck dissection underwent induction chemotherapy (paclitaxel, ifosfamide, and carboplatin) followed by glossectomy and neck dissection ± radiotherapy and chemotherapy. On final surgical pathology, 9 patients (39%) had a complete/major (2 complete) histologic response at the primary tumor site; 8 patients (35%) had no response or progression. Similarly, 9 patients (39%) had a complete response in the neck or remained node negative; 6 patients (26%) had an increase in nodal category. No treatment-associated deaths occurred, and toxicity was modest. At a median follow-up from the end of treatment of 52 months (minimum, 23 months), 10 patients (43%) developed recurrence, and all 10 died of cancer. Crude recurrence/cancer death rates were associated with ≤ a partial response at the tongue (p = .029), poor histologic differentiation (p = .012), and multiple adverse features on final surgical pathology (p = .040). Response rates and overall survival with this induction chemotherapy regimen were limited, but complete/major response at the tongue was associated with excellent prognosis. Additionally, improved patient selection and predictive tumor biomarkers will be needed for induction chemotherapy to be routinely incorporated into the treatment of oral tongue cancer in young adults. Copyright © 2011 Wiley Periodicals, Inc.

Induction therapy with carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal radiotherapy in the treatment of locally advanced, unresectable non-small cell lung cancer: preliminary report of a phase I trial.

PubMed

Socinski, M A; Clark, J A; Halle, J; Steagall, A; Kaluzny, B; Rosenman, J G

1997-08-01

Locally advanced non-small cell lung cancer is optimally managed with chemotherapy and thoracic irradiation, although the most appropriate strategy is not yet defined. In this phase I trial, we use two 21-day cycles of induction chemotherapy with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (225 mg/m2 over 3 hours) and carboplatin (area under the concentration-time curve = 6) followed by concurrent weekly paclitaxel (45 mg/m2/wk x 6) and carboplatin (area under the concentration-time curve = 2/wk x 6) and thoracic irradiation. Patients undergo three-dimensional treatment planning (conformal radiotherapy) to define the cancer target volume precisely. The phase I question being addressed in this study is the maximum tolerated radiation dose given concurrently with low-dose paclitaxel and carboplatin. The initial radiation dose is 60 Gy, with dose escalations to 66 Gy, 70 Gy, and 74 Gy being planned. Ten patients have been entered thus far (eight men and two women). Their median age is 67 years (range, 59 to 78 years), and none of the patients has had greater than 5% pretreatment weight loss. Seven of 10 are evaluable for response to induction carboplatin and paclitaxel, with a response rate of 57% (three partial responses and one minor response). Three patients had stable disease and none of the patients had evidence of progressive disease during induction chemotherapy. Three patients have completed all treatment at 60 Gy and one has completed all treatment at 66 Gy. Three of the four patients have had partial responses (75%), with the remaining patient having stable disease. Toxicity in the concurrent chemoradiotherapy portion of the trial thus far has consisted of grade 3 neutropenia in one patient and grade 4 lymphocytopenia in all four patients. No grade 3 or 4 nonhematologic toxicity has been seen. The trial data are not yet mature enough to report on survival. Accrual and treatment is continuing at the 66 Gy radiation dose level.

[Effect of external abdominal aorta compression on circulation during anesthesia induction in elderly patients].

PubMed

Li, Xiuman; Wang, Lixiang

2017-07-01

To investigate the effect of external abdominal aorta compression on circulation during anesthetic induction in elderly patients. A prospective randomized controlled trial was conducted. Patients with age of 60-75 years old, requiring a general anesthesia for non-abdominal surgery, and with II-III class of American Society of Anesthesiologists (ASA) physical status classification, and admitted to General Hospital of Chinese People's Armed Police Forces from January to April in 2017 were enrolled. They were divided into abdominal aorta pressure group and control group according to random number method, with 20 patients in each group. In both groups, anesthesia was induced with midazolam, propofol, fentanyl and cisatracurium, and was maintained with propofol, remifentanil and cisatracurium. After successful intubation, the anesthesia machine was changed into mechanical ventilation. The patients in abdominal aorta pressure group were given abdominal aorta pressure 1 minute after induction of general anesthesia with midazolam till 5 minutes after intubation. The mean arterial pressure (MAP), heart rate (HR) and blood oxygen saturation (SpO 2 ) were observed before anesthesia induction, immediately after anesthesia induction, immediately after intubation, 5 minutes and 10 minutes after intubation, respectively. The incidence of hypotension or bradycardia, and usage of ephedrine or atropine were recorded. There were no significant differences in MAP [mmHg (1 mmHg = 0.133 kPa): 83.6±4.7 vs. 82.9±4.7], HR (bpm: 67.3±5.9 vs. 65.9±5.7) and SpO 2 (0.962±0.007 vs. 0.960±0.009) before anesthesia induction between abdominal aorta pressure group and control group (all P > 0.05). Immediately after anesthesia induction, the MAP and HR in control group were significantly decreased as compared with those before anesthesia induction [MAP (mmHg): 70.0±8.7 vs. 82.9±4.7, HR (bpm): 60.7±6.7 vs. 65.9±5.7, both P < 0.05], and they were also significantly lower than those of abdominal aorta pressure group [MAP (mmHg): 83.1±3.9, HR (bpm): 66.8±4.9, both P < 0.05]. Immediately after intubation, the MAP and HR in control group were significantly increased as compared with those immediately after anesthesia induction [MAP (mmHg): 78.9±7.9 vs. 70.0±8.7, HR (bpm): 67.3±2.7 vs. 60.7±6.7, both P < 0.05], but the changes in MAP and HR in abdominal aorta pressure group were not obvious. During the anesthesia induction period, there was no statistical difference in SpO 2 change between the two groups. During induction of anesthesia, no adverse reaction was found in the abdominal aorta pressure group, but 4 patients with hypotension and 2 patients with bradycardia were found in the control group. Two patients with hypotension were treated with ephedrine, and 2 patients with bradycardia were treated with atropine. Anesthesia induction of elderly patients with abdominal aorta pressure can help maintain hemodynamic stability.

Culturally Targeted Strategies for Diabetes Prevention in Minority Populations: A Systematic Review and Framework

PubMed Central

Lagisetty, Pooja A.; Priyadarshini, Shubadra; Terrell, Stephanie; Hamati, Mary; Landgraf, Jessica; Chopra, Vineet; Heisler, Michele

2017-01-01

Purpose The purpose of this study is to (a) assess the effectiveness of culturally tailored diabetes prevention interventions in minority populations and (b) develop a novel framework to characterize four key domains of culturally tailored interventions. Prevention strategies specifically tailored to the culture of ethnic minority patients may help reduce the incidence of diabetes. Methods We searched PubMed, EMBASE, and CINAHL for English-language, randomized controlled trials (RCTs) or quasi-experimental (QE) trials testing culturally tailored interventions to prevent diabetes in minority populations. Two reviewers independently extracted data and assessed risk of bias. Inductive thematic analysis was used to develop a framework with four domains (FiLLM: Facilitating [i.e., delivering] Interventions through Language, Location and Message). The framework was used to assess the overall effectiveness of culturally tailored interventions. Results Thirty-four trials met eligibility criteria. Twelve studies were randomized controlled trials, and 22 were quasi-experimental trials. Twenty-five out of 34 studies (74%) that used cultural tailoring demonstrated significantly improved Hemoglobin A1C, fasting glucose, and/or weight loss. Of the 25 successful interventions, 21 (84%) incorporated at least three culturally targeted domains. Seven studies used all four domains and were all successful. The least utilized domain was delivery (4/34) of the intervention’s key educational message. Conclusions Culturally tailoring interventions across the four domains of facilitators, language, location, and messaging can be effective in improving risk factors for progression to diabetes among ethnic minority groups. Future studies should evaluate how specific tailoring approaches work compared to usual care as well as comparative effectiveness of each tailoring domain. Registration (PROSPERO registration: CRD42015016914) PMID:28118127

Cost-effectiveness of vedolizumab compared with conventional therapy for ulcerative colitis patients in the UK.

PubMed

Wilson, Michele R; Azzabi Zouraq, Ismail; Chevrou-Severac, Helene; Selby, Ross; Kerrigan, Matthew C

2017-01-01

To examine the clinical and economic impact of vedolizumab compared with conventional therapy in the treatment of moderately-to-severely active ulcerative colitis (UC) in the UK based on results of the GEMINI I trial. A decision-analytic model in Microsoft Excel was used to compare vedolizumab with conventional therapy (aminosalicylates, corticosteroids, immunomodulators) for the treatment of patients with UC in the UK. We considered the following three populations: the overall intent-to-treat population from the GEMINI I trial, patients naïve to anti-TNF therapy, and those who had failed anti-TNF-therapy. Population characteristics and efficacy data were obtained from the GEMINI I trial. Other inputs (eg, unit costs, probability of surgery, mortality) were obtained from published literature. Time horizon was a lifetime horizon, with costs and outcomes discounted by 3.5% per year. One-way and probabilistic sensitivity analyses were conducted to measure the impact of parameter uncertainty. Vedolizumab had incremental cost-effectiveness ratios of £4,095/quality-adjusted life-year (QALY), £4,423/QALY, and £5,972/QALY compared with conventional therapy in the intent-to-treat, anti-TNF-naïve, and anti-TNF-failure populations, respectively. Patients on vedolizumab accrued more QALYs while incurring more costs than patients on conventional therapy. The sensitivity analyses showed that the results were most sensitive to induction response and transition probabilities for each treatment. The results suggest that vedolizumab results in more QALYs and may be a cost-effective treatment option compared with conventional therapy for both anti-TNF-naïve and anti-TNF-failure patients with moderately-to-severely active UC.

Infection prevention for patients with acute leukemia using laminar air flow rooms.

PubMed

Masaoka, T

1986-01-01

Infection prevention using laminar air flow (LAF) rooms was studied. For the effective and economical usage of LAF rooms, our trials with ozone decontamination were deemed very convenient and effective. In maintaining LAF clean, insects were found to be a critical factor regarding fungus contamination of LAF. As to its efficacy of infection prevention, LAF decreased infection during remission induction from 113/100 to 28/100. The infections reduced by LAF were pneumonia, upper respiratory infection and skin abscess, while sepsis and perianal infection were not affected. Treatment in LAF rooms also seemed to have comparable influence on interstitial pneumonitis after bone marrow transplantation.

Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis.

PubMed

Costello, S P; Soo, W; Bryant, R V; Jairath, V; Hart, A L; Andrews, J M

2017-08-01

Faecal microbiota transplantation (FMT) is emerging as a novel therapy for ulcerative colitis (UC). Interpretation of efficacy of FMT for UC is complicated by differences among studies in blinding, FMT administration procedures, intensity of therapy and donor stool processing methods. To determine whether FMT is effective and safe for the induction of remission in active UC. Medline (Ovid), Embase and the Cochrane Library were searched from inception through February 2017. Original studies reporting remission rates following FMT for active UC were included. All study designs were included in the systematic review and a meta-analysis performed including only randomised controlled trials (RCTs). There were 14 cohort studies and four RCTs that used markedly different protocols. In the meta-analysis of RCTs, clinical remission was achieved in 39 of 140 (28%) patients in the donor FMT groups compared with 13 of 137 (9%) patients in the placebo groups; odds ratio 3.67 (95% CI: 1.82-7.39, P<.01). Clinical response was achieved in 69 of 140 (49%) donor FMT patients compared to 38 of 137 (28%) placebo patients; odds ratio 2.48 (95% CI: 1.18-5.21, P=.02). In cohort studies, 39 of 168 (24%; 95% CI: 11%-40%) achieved clinical remission. Despite variation in processes, FMT appears to be effective for induction of remission in UC, with no major short-term safety signals. Further studies are needed to better define dose frequency and preparation methods, and to explore its feasibility, efficacy and safety as a maintenance agent. © 2017 John Wiley & Sons Ltd.

Chemical induction of resinosis in southern pines. Final report

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

Stubbs, J.; Outcalt, K.W.

1982-01-01

Research studies in the use of paraquat, a contact herbicide, for lightwood induction; i.e., the accumulation of oleoresin in the boles of living southern pine trees are summarized. The objectives of this research were to determine oleoresin yields as influenced by treatment factors, to estimate treatment costs, to uncover technical problems, both in the field and processng plants, and to assess the problem of bark beetle attacks on treated trees. Two pulp and paper mill trials using paraquat-treated wood were conducted, one with loblolly and one with slash pine. The loblolly trial yielded 40 percent more tall oil, or anmore » extra 27.2 pounds/cord of wood. Due to limited turpentine condenser capacity, no additional turpentine was recovered. However, there is evidence to believe that an additional one gal./cord could have been realized.« less

Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the Study Alliance Leukemia.

PubMed

Müller-Tidow, C; Tschanter, P; Röllig, C; Thiede, C; Koschmieder, A; Stelljes, M; Koschmieder, S; Dugas, M; Gerss, J; Butterfaß-Bahloul, T; Wagner, R; Eveslage, M; Thiem, U; Krause, S W; Kaiser, U; Kunzmann, V; Steffen, B; Noppeney, R; Herr, W; Baldus, C D; Schmitz, N; Götze, K; Reichle, A; Kaufmann, M; Neubauer, A; Schäfer-Eckart, K; Hänel, M; Peceny, R; Frickhofen, N; Kiehl, M; Giagounidis, A; Görner, M; Repp, R; Link, H; Kiani, A; Naumann, R; Brümmendorf, T H; Serve, H; Ehninger, G; Berdel, W E; Krug, U

2016-03-01

DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P=0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P=0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P=0.76). Median EFS was 6 months in both arms (P=0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P=0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.

Letrozole versus clomiphene citrate in polycystic ovary syndrome: systematic review and meta-analysis.

PubMed

Roque, Matheus; Tostes, Ana C I; Valle, Marcello; Sampaio, Marcos; Geber, Selmo

2015-01-01

The objective of the present systematic review and meta-analysis was to examine the literature and to identify the results of randomized controlled trials (RCTs) comparing the use of letrozole to clomiphene citrate (CC) for ovulation induction in patients with polycystic ovary syndrome (PCOS). An exhaustive electronic literature search was performed using the MEDLINE and EMBASE databases until October 2014. Seven prospective RCTs comparing the use of letrozole to CC in PCOS patients met the inclusion criteria. Overall, the seven included studies accounted for 1833 patients (906 in the letrozole group and 927 in the CC group) and for 4999 ovulation induction cycles (2455 in the letrozole group and 2544 in the CC group). Five of the included studies reported data on live birth rates. There was a statistically significant increase in the live birth and pregnancy rates in the letrozole group when compared to the CC group, with a relative risk (RR) = 1.55 (95% confidence interval (CI): 1.26-1.90; I(2) = 0%) and RR = 1.38 (95% CI: 1.05-1.83; I(2) = 61%), respectively. There were no differences in the multiple pregnancy, miscarriage and ovulation rates between the two groups. Our study found that letrozole is superior to CC when considering the live birth and pregnancy rates in patients with PCOS.

Flai (fludarabine, cytarabine, idarubicin) plus low-dose Gemtuzumab Ozogamicin as induction therapy in CD33-positive AML: Final results and long term outcome of a phase II multicenter clinical trial.

PubMed

Candoni, Anna; Papayannidis, Cristina; Martinelli, Giovanni; Simeone, Erica; Gottardi, Michele; Iacobucci, Ilaria; Gherlinzoni, Filippo; Visani, Giuseppe; Baccarani, Michele; Fanin, Renato

2018-05-01

The aim of this prospective clinical trial was to evaluate the efficacy and safety of a combination of Gemtuzumab-Ozogamicin (GO) and FLAI scheme (fludarabine, cytarabine, idarubicin) as a first-line therapy in CD33 positive AML. We treated 130 patients, aged <65, with a median age of 52 years. FLAI-GO induction regimen included fludarabine (30 mg/sqm) and cytarabine (2 g/sqm) on days 1-5; idarubicin (10 mg/sqm) on days 1, 3, and 5; and GO (3 mg/sqm) on day 6. SCT was planned for all high-risk AML patients, after consolidation with intermediate doses of cytarabine and idarubicin and a high dose of cytarabine. CD33 expression exceeded 20% in all cases. Primary endpoints of the study included feasibility, overall response rate (ORR) and toxicity. Secondary endpoints included the evaluation of MRD by WT1 expression, feasibility and outcome of consolidation with SCT, overall survival (OS) and disease-free survival (DFS). After induction with FLAI-GO, complete remission (CR) rate was 82%. Four patients achieved partial remission (PR) and 12% were resistant (ORR 85%); death during induction (DDI) was 3%. The hematological and extra hematological toxicity of FLAI-GO was manageable; 45% of patients experienced transient and reversible GO infusion related adverse events. In the setting of patients who achieved a cytological CR after FLAI-GO, the mean of WT1 copies dropped from 8337±9936 copies/10 4 ABL (diagnosis) to 182 ± 436 copies after induction therapy (p = 0.0001) showing a very good disease debulking. After a median follow-up of 54 months, 67/130 (52%) patients were alive. The probability of 1, 2, and 5-year OS was 80%, 63%, and 52%, respectively. The probability of 1, 2, and 5-year DFS was 77%, 58%, and 52%, respectively. Allogeneic and autologous SCT was performed in 60 (46%) and 23 (18%) patients, respectively. In summary, the final results of this trial confirm that FLAI-GO is an active and safe treatment strategy for CD33-positive AML patients aged ≤ 65 years, allowing a high ORR, a good disease debulking, favorable safety profile, low DDI, and subsequent high SCT rate. The encouraging results of this trial, consolidated by a long follow-up, support the reintroduction of GO in clinical practice. © 2018 Wiley Periodicals, Inc.

Combined metformin and clomiphene citrate versus laparoscopic ovarian diathermy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial.

PubMed

Abu Hashim, Hatem; El Lakany, Naser; Sherief, Lotfy

2011-03-01

To compare the effect of combined metformin and clomiphene citrate (CC) with laparoscopic ovarian diathermy (LOD) meant for ovulation induction in CC-resistant women with polycystic ovary syndrome (PCOS). Two-hundred and eighty-two anovulatory women with CC-resistant PCOS were selected in this randomized controlled trial. Patients (n = 138) received combined metformin-CC for up to six cycles or underwent LOD (n = 144) with six months follow up. The outcome measures were: ovulation rate, midcycle endometrial thickness, pregnancy and miscarriage rates. Ovulation occurred in 386/576 cycles (67%) in the combined metformin-CC group and 381/558 cycles (68.2%) in LOD group without a significant difference between the groups. Resumption of regular menstruation was similar in both groups. A significant increase in midcycle endometrial thickness was observed in the combined metformin-CC group (9.2 ± 1.2 mm vs 7.6 ± 1.1 mm) (P < 0.05). The pregnancy rate was similar in both groups (15.4% vs 17%), and there were no statistically significant differences regarding the miscarriage rate between both groups. Four twin pregnancies occurred in the metformin-CC group. No ovarian hyperstimulation occurred in either group. Combined metformin-CC and LOD are equally effective for inducing ovulation and achieving pregnancy in CC-resistant PCOS patients. © 2010 The Authors. Journal of Obstetrics and Gynaecology Research © 2010 Japan Society of Obstetrics and Gynecology.

Sequential chemoimmunotherapy of fludarabine, mitoxantrone, and cyclophosphamide induction followed by alemtuzumab consolidation is effective in T-cell prolymphocytic leukemia.

PubMed

Hopfinger, Georg; Busch, Raymonde; Pflug, Natali; Weit, Nicole; Westermann, Anne; Fink, Anna-Maria; Cramer, Paula; Reinart, Nina; Winkler, Dirk; Fingerle-Rowson, Günter; Stilgenbauer, Stephan; Döhner, Hartmut; Kandler, Gabriele; Eichhorst, Barbara; Hallek, Michael; Herling, Marco

2013-06-15

Scarce systematic trial data have prevented uniform therapeutic guidelines for T-cell prolymphocytic leukemia (T-PLL). A central need in this historically refractory tumor is the controlled evaluation of multiagent chemotherapy and its combination with the currently most active single agent, alemtuzumab. This prospective multicenter phase 2 trial assessed response, survival, and toxicity of a novel regimen in previously treated (n = 9) and treatment-naive (n = 16) patients with T-PLL. Induction by fludarabine, mitoxantrone, and cyclophosphamide (FMC), for up to 4 cycles, was followed by alemtuzumab (A) consolidation, up to 12 weeks. Of the 25 patients treated with FMC, 21 subsequently received alemtuzumab. Overall response rate to FMC was 68%, comprising 6 complete remissions (all bone-marrow confirmed) and 11 partial remissions. Alemtuzumab consolidation increased the intent-to-treat overall response rate to 92% (12 complete remissions; 11 partial remissions). Median overall survival after FMC-A was 17.1 months and median progression-free survival was 11.9 months. Progression-free survival tended to be shorter for patients with high-level T-cell leukemia 1 oncoprotein expression. Hematologic toxicities were the most frequent grade 3/4 side effects under FMC-A. Exclusively in the 21 alemtuzumab-consolidated patients, 13 cytomegalovirus reactivations were observed; 9 of these 13 represented a clinically relevant infection. FMC-A is a safe and efficient protocol in T-PLL, which compares favorably to published data. Copyright © 2013 American Cancer Society.

Impact of post-remission therapy in patients aged 65–70 years with de novo acute myeloid leukemia: a comparison of two concomitant randomized ALFA trials with overlapping age inclusion criteria

PubMed Central

Itzykson, Raphael; Gardin, Claude; Pautas, Cécile; Thomas, Xavier; Turlure, Pascal; Raffoux, Emmanuel; Terré, Christine; Fenaux, Pierre; Castaigne, Sylvie; Dombret, Hervé; Boissel, Nicolas

2011-01-01

Background There is no standard post-remission therapy in older patients with acute myeloid leukemia. Design and Methods From 1999 to 2006, the Acute Leukemia French Association group ran two concurrent randomized trials with overlapping inclusion criteria for patients aged 65 to 70 with acute myeloid leukemia, with different post-remission strategies: two intensive courses in the 9801 trial, one intensive course or six outpatient courses in the 9803 trial. We analyzed the outcome of these patients per protocol and per post-remission therapy. Results Two hundred and eleven patients aged 65 to 70 years with de novo acute myeloid leukemia were enrolled in trial 9801 (n=76) or 9803 (n=135). The patients in the two trials had comparable white blood cell counts (P=0.3), cytogenetics (P=0.49), and complete remission rates (70% and 57%, respectively; P=0.17). Overall survival was identical in both trials (32% and 34% at 2 years, respectively; P=0.71). Overall survival after complete remission was identical in the 103 of 130 patients who received the planned post-remission courses (n=44 with two intensive courses, n=28 with one intensive course, n=31 with six outpatient courses; 41%, 55%, and 58% at 2 years, respectively; P=0.34). Even in patients with favorable or normal karyotype (n=97), overall survival from complete remission was not improved by more intensive post-remission therapy. Conclusions In patients aged 65 to 70 years with de novo acute myeloid leukemia in complete remission after standard intensive induction chemotherapy, there is no apparent benefit from intensive post-remission therapy. (ClinicalTrials.gov Identifiers: NCT00931138 and NCT00363025) PMID:21459791

Impact of post-remission therapy in patients aged 65-70 years with de novo acute myeloid leukemia: a comparison of two concomitant randomized ALFA trials with overlapping age inclusion criteria.

PubMed

Itzykson, Raphael; Gardin, Claude; Pautas, Cécile; Thomas, Xavier; Turlure, Pascal; Raffoux, Emmanuel; Terré, Christine; Fenaux, Pierre; Castaigne, Sylvie; Dombret, Hervé; Boissel, Nicolas

2011-06-01

There is no standard post-remission therapy in older patients with acute myeloid leukemia. From 1999 to 2006, the Acute Leukemia French Association group ran two concurrent randomized trials with overlapping inclusion criteria for patients aged 65 to 70 with acute myeloid leukemia, with different post-remission strategies: two intensive courses in the 9801 trial, one intensive course or six outpatient courses in the 9803 trial. We analyzed the outcome of these patients per protocol and per post-remission therapy. Two hundred and eleven patients aged 65 to 70 years with de novo acute myeloid leukemia were enrolled in trial 9801 (n=76) or 9803 (n=135). The patients in the two trials had comparable white blood cell counts (P=0.3), cytogenetics (P=0.49), and complete remission rates (70% and 57%, respectively; P=0.17). Overall survival was identical in both trials (32% and 34% at 2 years, respectively; P=0.71). Overall survival after complete remission was identical in the 103 of 130 patients who received the planned post-remission courses (n=44 with two intensive courses, n=28 with one intensive course, n=31 with six outpatient courses; 41%, 55%, and 58% at 2 years, respectively; P=0.34). Even in patients with favorable or normal karyotype (n=97), overall survival from complete remission was not improved by more intensive post-remission therapy. In patients aged 65 to 70 years with de novo acute myeloid leukemia in complete remission after standard intensive induction chemotherapy, there is no apparent benefit from intensive post-remission therapy. (ClinicalTrials.gov Identifiers: NCT00931138 and NCT00363025).

Reducing youth internalizing symptoms: Effects of a family-based preventive intervention on parental guilt induction and youth cognitive style

PubMed Central

McKEE, LAURA G.; PARENT, JUSTIN; FOREHAND, REX; RAKOW, AARON; WATSON, KELLY H.; DUNBAR, JENNIFER P.; REISING, MICHELLE M.; HARDCASTLE, EMILY; COMPAS, BRUCE E.

2014-01-01

This study utilized structural equation modeling to examine the associations among parental guilt induction (a form of psychological control), youth cognitive style, and youth internalizing symptoms, with parents and youth participating in a randomized controlled trial of a family-based group cognitive–behavioral preventive intervention targeting families with a history of caregiver depression. The authors present separate models utilizing parent report and youth report of internalizing symptoms. Findings suggest that families in the active condition (family-based group cognitive–behavioral group) relative to the comparison condition showed a significant decline in parent use of guilt induction at the conclusion of the intervention (6 months postbaseline). Furthermore, reductions in parental guilt induction at 6 months were associated with significantly lower levels of youth negative cognitive style at 12 months. Finally, reductions in parental use of guilt induction were associated with lower youth internalizing symptoms 1 year following the conclusion of the intervention (18 months postbaseline). PMID:24438999

Culturally Targeted Strategies for Diabetes Prevention in Minority Population.

PubMed

Lagisetty, Pooja A; Priyadarshini, Shubadra; Terrell, Stephanie; Hamati, Mary; Landgraf, Jessica; Chopra, Vineet; Heisler, Michele

2017-02-01

Purpose The purpose of this study is to (a) assess the effectiveness of culturally tailored diabetes prevention interventions in minority populations and (b) develop a novel framework to characterize 4 key domains of culturally tailored interventions. Prevention strategies specifically tailored to the culture of ethnic minority patients may help reduce the incidence of diabetes. Methods We searched PubMed, EMBASE, and CINAHL for English-language, randomized controlled trials (RCTs) or quasi-experimental (QE) trials testing culturally tailored interventions to prevent diabetes in minority populations. Two reviewers independently extracted data and assessed risk of bias. Inductive thematic analysis was used to develop a framework with 4 domains (FiLLM: Facilitating [ie, delivering] Interventions Through Language, Location, and Message). The framework was used to assess the overall effectiveness of culturally tailored interventions. Results Thirty-four trials met eligibility criteria. Twelve studies were RCTs, and 22 were QE trials. Twenty-five out of 34 studies (74%) that used cultural tailoring demonstrated significantly improved A1C, fasting glucose, and/or weight loss. Of the 25 successful interventions, 21 (84%) incorporated at least 3 culturally targeted domains. Seven studies used all 4 domains and were all successful. The least utilized domain was delivery (4/34) of the intervention's key educational message. Conclusions Culturally tailoring interventions across the 4 domains of facilitators, language, location, and messaging can be effective in improving risk factors for progression to diabetes among ethnic minority groups. Future studies should evaluate how specific tailoring approaches work compared to usual care as well as comparative effectiveness of each tailoring domain.

Long-term outcome of older patients with newly diagnosed de novo acute promyelocytic leukemia treated with ATRA plus anthracycline-based therapy.

PubMed

Martínez-Cuadrón, D; Montesinos, P; Vellenga, E; Bernal, T; Salamero, O; Holowiecka, A; Brunet, S; Gil, C; Benavente, C; Ribera, J M; Pérez-Encinas, M; De la Serna, J; Esteve, J; Rubio, V; González-Campos, J; Escoda, L; Amutio, M E; Arnan, M; Arias, J; Negri, S; Lowënberg, B; Sanz, M A

2018-01-01

Treatment outcome in older patients with acute promyelocytic leukemia (APL) is lower compared with younger patients, mainly because of a higher induction death rate and postremission non-relapse mortality (NRM). This prompted us to design a risk- and age-adapted protocol (Programa Español de Tratamientos en Hematología (PETHEMA)/HOVON LPA2005), with dose reduction of consolidation chemotherapy. Patients aged ⩾60 years reported to the PETHEMA registry and were treated with all-trans retinoic acid (ATRA) plus anthracycline-based regimens according to three consecutive PETHEMA trials that were included. We compared the long-term outcomes of the LPA2005 trial with the preceding PETHEMA trials using non-age-adapted schedules (LPA96&LPA99). From 1996 to 2012, 389 older patients were registered, of whom 268 patients (69%) were eligible. Causes of ineligibility were secondary APL (19%), and unfit for chemotherapy (11%). Median age was 67 years, without relevant differences between LPA2005 and LPA96&LPA99 cohorts. Overall, 216 patients (81%) achieved complete remission with no differences between trials. The 5-year NRM, cumulative incidence of relapse, disease-free survival and overall survival in the LPA2005 vs the LPA96&99 were 5 vs 18% (P=0.15), 7 vs 12% (P=0.23), 87 vs 69% (P=0.04) and 74 vs 60% (P=0.06). A less intensive front-line regimen with ATRA and anthracycline monochemotherapy resulted in improved outcomes in older APL patients.

The Pittsburgh Randomized Trial of Tacrolimus Compared to Cyclosporine for Hepatic Transplantation

PubMed Central

Fung, John J.; Eliasziw, Michael; Todo, Satoru; Jain, Ashok; Demetris, Anthony J.; McMichael, John P.; Starzl, Thomas E.; Meier, Paul; Donner, Allan

2009-01-01

Background Tacrolimus (formerly FK 506) was first used clinically in 1989 to successfully replace cyclosporine in hepatic transplant recipients who were experiencing intractable rejection or as the baseline drug from the time of operation. After extensive pilot experience, an institutional review board-mandated clinical trial comparing cyclosporine with tacrolimus was performed. Study Design From February 16, 1990 to December 26, 1991, 154 patients were recruited. The competing drugs were combined with equal induction doses of prednisone in both arms of the study for the first 81 patients and with subsequently higher doses of prednisone in the remaining 35 patients who received cyclosporine and were entered into the trial. Drug crossover was permitted for lack of efficacy or adverse events. End points were rejection confirmed by biopsy and treatment failure leading to retransplantation or death. Results Seventy-nine patients were randomized to the tacrolimus arm and 75 to the cyclosporine arm during 1990 and 1991. All patients were available for follow-up throughout the trial, which terminated on May 30, 1995. The mean duration of follow-up was four years. Patients randomized to the tacrolimus arm were less likely to experience acute rejection than were those receiving cyclosporine, with 36.2 percent of the patients receiving tacrolimus and 16.8 percent of the patients receiving cyclosporine showing freedom from rejection at one year (p=0.003, likelihood ratio test). Survival of patients over the course of the study was virtually the same in the two groups. Conclusions Tacrolimus was more effective than cyclosporine in preventing acute rejection. PMID:8696542

Treatment outcomes of reduced-dose intravitreal ganciclovir for cytomegalovirus retinitis.

PubMed

Choopong, Pitipol; Vivittaworn, Kamolporn; Konlakij, Duanphen; Thoongsuwan, Somanus; Pituksung, Auengporn; Tesavibul, Nattaporn

2016-04-18

Cytomegalovirus retinitis (CMVR) is one of the most common opportunistic infection in immunocompromised individuals. Intravitreal ganciclovir injection has been used successfully but no standard regimen was established. Risks of drug toxicity, endophthalmitis, and injection-related complications increased with number and frequency of injection. The aim of this study is to evaluate the outcomes of reduced-dose intravitreal ganciclovir (2 mg/0.04 mL) for the treatment of CMVR. A prospective observational cohort study involving 67 eyes of 49 patients with CMVR was performed. Induction therapy involved intravenous ganciclovir (10 mg/kg/day) for 2 weeks unless contraindicated or patients refused. Patients were then treated with reduced-dose intravitreal ganciclovir every week for 4 weeks, and then every other week until the lesion healed. The patients' demographic data were recorded, and vision parameters were examined every visit. Twenty eyes (29.9 %) presented with initial visual acuities less than 6/60. The majority of patients were diagnosed with CMVR in zones 1 or 2 (63 eyes, 94 %), and, at least, one quadrant of the retina was involved (56 eyes, 83.6 %). Forty-one eyes (61.2 %) completely resolved after treatment within the 6-month follow-up. There was no significant difference in healing time, whether or not patients received induction treatment with intravenous ganciclovir (111.00 ± 12.96 vs 105.00 ± 28.32 days, p = 0.8). Five eyes (12.2 %) of patients with healed CMVR had visual acuities less than 6/60. Reduced-dose intravitreal ganciclovir is a safe and effective treatment option. It provides comparable results to other weekly regimens. Induction with intravenous ganciclovir is not crucial in a resolution of retinitis, although it may be necessary to reduce systemic cytomegalovirus loads and mortality rates. The trial was registered with Thai Clinical Trials Registry (TCTR) on 16 March 2016 - TCTR20160316001 .

Oral Sulforaphane increases Phase II antioxidant enzymes in the human upper airway

PubMed Central

Riedl, Marc A.; Saxon, Andrew; Diaz-Sanchez, David

2009-01-01

Background Cellular oxidative stress is an important factor in asthma and is thought to be the principle mechanism by which oxidant pollutants such as ozone and particulates mediate their pro-inflammatory effects. Endogenous Phase II enzymes abrogate oxidative stress through the scavenging of reactive oxygen species and metabolism of reactive chemicals. Objective We conducted a placebo-controlled dose escalation trial to investigate the in vivo effects of sulforaphane, a naturally occurring potent inducer of Phase II enzymes, on the expression of glutathione-s-transferase M1 (GSTM1), glutathione-s-transferase P1 (GSTP1), NADPH quinone oxidoreductase (NQO1), and hemoxygenase-1 (HO-1) in the upper airway of human subjects. Methods Study subjects consumed oral sulforaphane doses contained in a standardized broccoli sprout homogenate (BSH). RNA expression for selected Phase II enzymes was measured in nasal lavage cells by RT-PCR before and after sulforaphane dosing. Results All subjects tolerated oral sulforaphane dosing without significant adverse events. Increased Phase II enzyme expression in nasal lavage cells occurred in a dose-dependent manner with maximal enzyme induction observed at the highest dose of 200 grams broccoli sprouts prepared as BSH. Significant increases were seen in all sentinel Phase II enzymes RNA expression compared to baseline. Phase II enzyme induction was not seen with ingestion of non-sulforaphane containing alfalfa sprouts. Conclusion Oral sulforaphane safely and effectively induces mucosal Phase II enzyme expression in the upper airway of human subjects. This study demonstrates the potential of antioxidant Phase II enzymes induction in the human airway as a strategy to reduce the inflammatory effects of oxidative stress. Clinical Implications This study demonstrates the potential of enhancement of Phase II enzyme expression as a novel therapeutic strategy for oxidant induced airway disease. Capsule Summary A placebo-controlled dose escalation trial demonstrated that naturally occurring sulforaphane from broccoli sprouts can induce a potent increase in antioxidant Phase II enzymes in airway cells. PMID:19028145

Outcome of children with acute myeloid leukaemia (AML) experiencing primary induction failure in the AIEOP AML 2002/01 clinical trial.

PubMed

Quarello, Paola; Fagioli, Franca; Basso, Giuseppe; Putti, Maria C; Berger, Massimo; Luciani, Matteo; Rizzari, Carmelo; Menna, Giuseppe; Masetti, Riccardo; Locatelli, Franco

2015-11-01

Paediatric patients with acute myeloid leukaemia (AML) who fail induction due to primary resistance to chemotherapy account for a significant proportion of cases and have a particularly dismal prognosis. We report the clinical and biological data, and final outcome of 48 paediatric patients with primary-resistant AML enrolled in the Associazione Italiana di Ematologia e Oncologia Pediatrica AML 2002/01 clinical trial. These patients had a significantly higher white blood cell count at diagnosis compared to other AML patients. Cytogenetic and molecular features did not differ between patients with primary induction failure and patients allocated to the high-risk group. For the whole patient population, the probability of overall survival, event-free survival (EFS) and disease-free survival (DFS) was 21·8% ± 6·2, 20·4% ± 5·9, and 49·5% ± 11·3, respectively. Twenty-eight (58%) patients received haematopoietic stem cell transplantation (HSCT); 3 were autologous and 25 were allogeneic. Patients who underwent HSCT had improved EFS (31·2% vs. 5%, P < 0·0001). Only one of the 20 patients who did not receive HSCT is alive and disease free. The 19 patients in complete remission at time of HSCT showed significantly better DFS than the 9 with active disease (46% vs. 0%, P = 0·02). This study represents one of the largest series with long-term follow up of paediatric AML patients with primary refractory disease. Children who underwent transplantation had an encouraging long-term outcome. Disease recurrence remains the major cause of treatment failure; a better understanding of the disease biology is desirable to develop more effective treatment strategies. © 2015 John Wiley & Sons Ltd.

Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results

PubMed Central

Morgan, Gareth J.; Davies, Faith E.; Gregory, Walter M.; Bell, Sue E.; Szubert, Alexander J.; Navarro Coy, Nuria; Cook, Gordon; Feyler, Sylvia; Johnson, Peter R.E.; Rudin, Claudius; Drayson, Mark T.; Owen, Roger G.; Ross, Fiona M.; Russell, Nigel H.; Jackson, Graham H.; Child, J. Anthony

2012-01-01

Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation. Design and Methods Oral cyclophosphamide, thalidomide, and dexamethasone was compared with infusional cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma. Results The post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with cyclophosphamide-thalidomide-dexamethasone (n=555) versus cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44–2.55; P<0.0001. The complete response rates were 13.0% with cyclophosphamide-thalidomide-dexamethasone and 8.1% with cyclophos-phamide-vincristine-doxorubicin-dexamethasone (P=0.0083), with this differential response being maintained in patients who received autologous stem-cell transplantation (post-transplant complete response 50.0% versus 37.2%, respectively; P=0.00052). Cyclophosphamide-thalidomide-dexamethasone was non-inferior to cyclophosphamide-vincristine-doxorubicin-dexamethasone for progression-free and overall survival, and there was a trend toward a late survival benefit with cyclophosphamide-thalidomide-dexamethasone in responders. A trend toward an overall survival advantage for cyclophosphamide-thalidomide-dexamethasone over cyclophosphamide-vincristine-doxorubicin-dexamethasone was also observed in a subgroup of patients with favorable interphase fluorescence in situ hybridization. Compared with cyclophosphamide-vincristine-doxorubicin-dexamethasone, cyclophosphamide-thalidomide-dexamethasone was associated with more constipation and somnolence, but a lower incidence of cytopenias. Conclusions The cyclophosphamide-thalidomide-dexamethasone regimen showed improved response rates and was not inferior in terms of survival outcomes to the standard infusional regimen of cyclophosphamide-vincristine-doxorubicin-dexamethasone. Based on its oral administration and the reduced incidence of infection and cytopenia, cyclophosphamide-thalidomide-dexa-methasone may be considered an effective induction therapy option for patients with newly diagnosed multiple myeloma. (ISRCTN: 68454111) PMID:22058209

HIMALAIA (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA): a randomized single-blind controlled trial of induced hypertension vs. no induced hypertension in the treatment of delayed cerebral ischemia after subarachnoid hemorrhage.

PubMed

Gathier, C S; van den Bergh, W M; Slooter, A J C

2014-04-01

Delayed cerebral ischemia (DCI) is a major complication after aneurysmal subarachnoid hemorrhage (SAH). One option to treat delayed cerebral ischemia is to use induced hypertension, but its efficacy on the eventual outcome has not been proven in a randomized clinical trial. This article describes the design of the HIMALAIA trial (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA), designed to assess the effectiveness of induced hypertension on neurological outcome in patients with DCI after SAH. To investigate whether induced hypertension improves the functional outcome in patients with delayed cerebral ischemia after SAH. The HIMALAIA trial is a multicenter, singe-blinded, randomized controlled trial in patients with DCI after a recent SAH. Eligible patients will be randomized to either induced hypertension (n = 120) or to no induced hypertension (n = 120). In selected centers, the efficacy of induced hypertension in augmenting cerebral blood flow will be measured by means of cerebral perfusion computerized tomography scanning. Follow-up assessments will be performed at 3 and 12 months after randomization by trial nurses who are blinded to the treatment allocation and management. We will include patients during five years. The primary outcome is the proportion of subarachnoid hemorrhage patients with delayed cerebral ischemia with poor outcome three-months after randomization, defined as a modified Rankin scale of more than 3. Secondary outcome measures are related to treatment failure, functional outcome, adverse events, and cerebral hemodynamics. The HIMALAIA trial is registered at clinicaltrials.gov under identifier NCT01613235. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Cognitive predictors of everyday functioning in older adults: results from the ACTIVE Cognitive Intervention Trial.

PubMed

Gross, Alden L; Rebok, George W; Unverzagt, Frederick W; Willis, Sherry L; Brandt, Jason

2011-09-01

The present study sought to predict changes in everyday functioning using cognitive tests. Data from the Advanced Cognitive Training for Independent and Vital Elderly trial were used to examine the extent to which competence in different cognitive domains--memory, inductive reasoning, processing speed, and global mental status--predicts prospectively measured everyday functioning among older adults. Coefficients of determination for baseline levels and trajectories of everyday functioning were estimated using parallel process latent growth models. Each cognitive domain independently predicts a significant proportion of the variance in baseline and trajectory change of everyday functioning, with inductive reasoning explaining the most variance (R2 = .175) in baseline functioning and memory explaining the most variance (R2 = .057) in changes in everyday functioning. Inductive reasoning is an important determinant of current everyday functioning in community-dwelling older adults, suggesting that successful performance in daily tasks is critically dependent on executive cognitive function. On the other hand, baseline memory function is more important in determining change over time in everyday functioning, suggesting that some participants with low baseline memory function may reflect a subgroup with incipient progressive neurologic disease.

Nonlinear Electrostatic Properties of Lunar Dust

NASA Technical Reports Server (NTRS)

Irwin, Stacy A.

2012-01-01

A laboratory experiment was designed to study the induction charging and charge decay characteristics of small dielectric particles, or glass beads. Initially, the goal of the experiment was further understanding of induction charging of lunar dust particles. However, the mechanism of charging became a point of greater interest as the project continued. Within an environmentally-controlled acrylic glove box was placed a large parallel plate capacitor at high-voltage (HV) power supply with reversible polarity. Spherical 1-mm and 0.5-mm glass beads, singly, were placed between the plates, and their behaviors recorded on video and quantified. Nearly a hundred trials at various humidities were performed. The analysis of the results indicated a non-linear relationship between humidity and particle charge exchange time (CET), for both sizes of beads. Further, a difference in CET for top-resting beads and bottom-resting beads hinted at a different charging mechanism than that of simple induction. Results from the I-mm bead trials were presented at several space science and physics conferences in 2008 and 2009, and were published as a Master's thesis in August 2009. Tangential work stemming from this project resulted in presentations at other international conferences in 2010, and selection to attend workshop on granular matter flow 2011.

Castor oil as a natural alternative to labor induction: A retrospective descriptive study.

PubMed

DeMaria, Andrea L; Sundstrom, Beth; Moxley, Grace E; Banks, Kendall; Bishop, Ashlan; Rathbun, Lesley

2018-04-01

To describe birthing outcomes among women who consumed castor oil cocktail as part of a freestanding birth center labor induction protocol. De-identified data from birth logs and electronic medical records were entered into SPSS Statistics 22.0 for analysis for all women who received the castor oil cocktail (n=323) to induce labor between January 2008 and May 2015 at a birth center in the United States. Descriptive statistics were analyzed for trends in safety and birthing outcomes. Of the women who utilized the castor oil cocktail to stimulate labor, 293 (90.7%) birthed vaginally at the birth center or hospital. The incidence of maternal adverse effects (e.g., nausea, vomiting, extreme diarrhea) was less than 7%, and adverse effects of any kind were reported in less than 15% of births. An independent sample t-test revealed that parous women were more likely to birth vaginally at the birth center after using the castor oil cocktail than their nulliparous counterparts (p<.010), while gestational age (p=.26), woman's age (p=.23), and body mass index (p=.28) were not significantly associated. Nearly 91% of women in the study who consumed the castor oil cocktail to induce labor were able to give birth vaginally with little to no maternal or fetal complications. Findings indicate further research is needed to compare the safety and effectiveness of natural labor induction methodologies, including castor oil, to commonly used labor induction techniques in a prospective study or clinical trial. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Survival follow-up and ipilimumab retreatment of patients with advanced melanoma who received ipilimumab in prior phase II studies

PubMed Central

Lebbé, C.; Weber, J. S.; Maio, M.; Neyns, B.; Harmankaya, K.; Hamid, O.; O'Day, S. J.; Konto, C.; Cykowski, L.; McHenry, M. B.; Wolchok, J. D.

2014-01-01

Background This report provides a survival update at a follow-up of >5 years (5.5–6 years) for patients with advanced melanoma who previously received ipilimumab in phase II clinical trials. Safety and efficacy data following ipilimumab retreatment are also reported. Patients and methods Patients who previously received ipilimumab 0.3, 3, or 10 mg/kg in one of six phase II trials (CA184-004, CA184-007, CA184-008, CA184-022, MDX010-08, and MDX010-15) were eligible to enroll in the companion study, CA184-025. Upon enrollment, patients initially received ipilimumab retreatment, extended maintenance therapy, or were followed for survival only. Overall survival (OS) rates were evaluated in patients from studies CA184-004, CA184-007, CA184-008, and CA184-022. Safety and best overall response during ipilimumab retreatment at 10 mg/kg were assessed in study CA184-025. Results Five-year OS rates for previously treated patients who received ipilimumab induction at 0.3, 3, or 10 mg/kg were 12.3%, 12.3%–16.5%, and 15.5%–28.4%, respectively. Five-year OS rates for treatment-naive patients who received ipilimumab induction at 3 or 10 mg/kg were 26.8% and 21.4%–49.5%, respectively. Little to no change in OS was observed from year 5 up to year 6. The objective response rate among retreated patients was 23%. Grade 3/4 immune-related adverse events occurred in 25%, 5.9%, and 13.2% of retreated patients who initially received ipilimumab 0.3, 3, and 10 mg/kg, with the most common being observed in the skin (4.2%, 2.9%, 3.8%) and gastrointestinal tract (12.5%, 2.9%, 3.8%), respectively. Conclusions At a follow-up of 5–6 years, ipilimumab continues to demonstrate durable, long-term survival in a proportion of patients with advanced melanoma. In some patients, ipilimumab retreatment can re-establish disease control with a safety profile that is comparable with that observed during ipilimumab induction. Further studies are needed to determine the contribution of ipilimumab retreatment to OS. ClinicalTrials.gov NCT00162123. PMID:25210016

Does Response to Induction Chemotherapy Predict Survival for Locally Advanced Non-Small-Cell Lung Cancer? Secondary Analysis of RTOG 8804/8808

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

McAleer, Mary Frances, E-mail: mfmcalee@mdanderson.or; Moughan, Jennifer M.S.; Byhardt, Roger W.

2010-03-01

Purpose: Induction chemotherapy (ICT) improves survival compared with radiotherapy (RT) alone in locally advanced non-small-cell lung cancer (LANSCLC) patients with good prognostic factors. Concurrent chemoradiotherapy (CCRT) is superior to ICT followed by RT. The question arises whether ICT response predicts the outcome of patients subsequently treated with CCRT or RT. Methods and Materials: Between 1988 and 1992, 194 LANSCLC patients were treated prospectively with ICT (two cycles of vinblastine and cisplatin) and then CCRT (cisplatin plus 63 Gy for 7 weeks) in the Radiation Therapy Oncology Group 8804 trial (n = 30) or ICT and then RT (60 Gy/6 wk)more » on Radiation Therapy Oncology Group 8808 trial (n = 164). Of the 194 patients, 183 were evaluable and 141 had undergone a postinduction assessment. The overall survival (OS) of those with complete remission (CR) or partial remission (PR) was compared with that of patients with stable disease (SD) or progressive disease (PD) after ICT. Results: Of the 141 patients, 6, 30, 99, and 6 had CR, PR, SD, and PD, respectively. The log-rank test showed a significant difference (p <0.0001) in OS when the response groups were compared (CR/PR vs. SD/PD). On univariate and multivariate analyses, a trend was seen toward a response to ICT with OS (p = 0.097 and p = 0.06, respectively). A squamous histologic type was associated with worse OS on univariate and multivariate analyses (p = 0.031 and p = 0.018, respectively). SD/PD plus a squamous histologic type had a hazard ratio of 2.25 vs. CR/PR plus a nonsquamous histologic type (p = 0.007) on covariate analysis. Conclusion: The response to ICT was associated with a significant survival difference when the response groups were compared. A response to ICT showed a trend toward, but was not predictive of, improved OS in LANSCLC patients. Patients with SD/PD after ICT and a squamous histologic type had the poorest OS. These data suggest that patients with squamous LANSCLC might benefit from immediate RT or CCRT.« less

Randomised controlled trial comparing oral and intravenous paracetamol (acetaminophen) plasma levels when given as preoperative analgesia.

PubMed

van der Westhuizen, J; Kuo, P Y; Reed, P W; Holder, K

2011-03-01

Gastric absorption of oral paracetamol (acetaminophen) may be unreliable perioperatively in the starved and stressed patient. We compared plasma concentrations of parenteral paracetamol given preoperatively and oral paracetamol when given as premedication. Patients scheduled for elective ear; nose and throat surgery or orthopaedic surgery were randomised to receive either oral or intravenous paracetamol as preoperative medication. The oral dose was given 30 minutes before induction of anaesthesia and the intravenous dose given pre-induction. All patients were given a standardised anaesthetic by the same specialist anaesthetist who took blood for paracetamol concentrations 30 minutes after the first dose and then at 30 minute intervals for 240 minutes. Therapeutic concentrations of paracetamol were reached in 96% of patients who had received the drug parenterally, and 67% of patients who had received it orally. Maximum median plasma concentrations were 19 mg.l(-1) (interquartile range 15 to 23 mg.l(-1)) and 13 mg.l(-1) (interquartile range 0 to 18 mg.l(-1)) for the intravenous and oral group respectively. The difference between intravenous and oral groups was less marked after 150 minutes but the intravenous preparation gave higher plasma concentrations throughout the study period. It can be concluded that paracetamol gives more reliable therapeutic plasma concentrations when given intravenously.

Phase I Trial Using Induction Ciplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib With Concurrent Radiotherapy for Advanced Head and Neck Cancer.

PubMed

Ahn, Peter H; Machtay, Mitchell; Anne, Pramila R; Cognetti, David; Keane, William M; Wuthrick, Evan; Dicker, Adam P; Axelrod, Rita S

2018-05-01

Bevacizumab (avastin) and erlotinib (tarceva) had shown early clinical activity against head and neck cancer (HNC). We initiated a phase I trial of induction cisplatin, docetaxel, 5-fluorouracil and erlotinib (TPF-E) followed by cisplatin, bevacizumab and erlotinib (PA-E) with radiotherapy (XRT) for advanced HNC. The goal was to determine maximum tolerated erlotinib dose. Eligible patients had stage IVA or higher HNC with good performance status, hematologic, and renal reserve. Two cycles of induction TPF-E were administered. XRT was administered with concurrent weekly cisplatin and bevacizumab every 2 weeks. Initial erlotinib dose was 50 mg daily from start of induction chemotherapy until radiotherapy completion. Erlotinib dose escalations to 100 and 150 mg were planned. Thirteen patients with previously untreated locoregional disease (11 patients) or oligometastatic (2 patients) HNC were enrolled. Totally, 11 of 13 patients completed XRT as planned. Four of 8 patients in cohort 1 (erlotinib 50 mg), 3 of 4 patients in cohort 2 (100 mg), and 0 of 1 patients in cohort 3 (150 mg) completed the regimen. Two patients had significant gastrointestinal complications (bleeding and perforation), and 1 had dose-limiting diarrhea. Maximum tolerated dose was reached at 50 mg erlotinib. At median 23.4 months follow-up, 5 patients (38%) have no evidence of disease, and 2 (15%) have stable but measurable disease. Erlotinib in combination with induction TPF followed by erlotinib, cisplatin, and bevacizumab with XRT is active but toxic. Gastrointestinal toxicities partly caused high rates of study withdrawal. All doses studied in this protocol caused unexpected toxicities and we do not recommend advancement to phase II.

Induction-related cost of patients with acute myeloid leukaemia in France.

PubMed

Nerich, Virginie; Lioure, Bruno; Rave, Maryline; Recher, Christian; Pigneux, Arnaud; Witz, Brigitte; Escoffre-Barbe, Martine; Moles, Marie-Pierre; Jourdan, Eric; Cahn, Jean Yves; Woronoff-Lemsi, Marie-Christine

2011-04-01

The economic profile of acute myeloid leukaemia (AML) is badly known. The few studies published on this disease are now relatively old and include small numbers of patients. The purpose of this retrospective study was to evaluate the induction-related cost of 500 patients included in the AML 2001 trial, and to determine the explanatory factors of cost. "Induction" patient's hospital stay from admission for "induction" to discharge after induction. The study was performed from the French Public Health insurance perspective, restrictive to hospital institution costs. The average management of a hospital stay for "induction" was evaluated according to the analytical accounting of Besançon University Teaching Hospital and the French public Diagnosis-Related Group database. Multiple linear regression was used to search for explanatory factors. Only direct medical costs were included: treatment and hospitalisation. Mean induction-related direct medical cost was estimated at €41,852 ± 6,037, with a mean length of hospital stay estimated at 36.2 ± 10.7 days. After adjustment for age, sex and performance status, only two explanatory factors were found: an additional induction course and salvage course increased induction-related cost by 38% (± 4) and 15% (± 1) respectively, in comparison to one induction. These explanatory factors were associated with a significant increase in the mean length of hospital stay: 45.8 ± 11.6 days for 2 inductions and 38.5 ± 15.5 if the patient had a salvage course, in comparison to 32.9 ± 7.7 for one induction (P < 10⁻⁴). This result is robust and was confirmed by sensitivity analysis. Consideration of economic constraints in health care is now a reality. Only the control of length of hospital stay may lead to a decrease in induction-related cost for patients with AML.

Polycystic Ovary Syndrome: Effect and Mechanisms of Acupuncture for Ovulation Induction

PubMed Central

Johansson, Julia; Stener-Victorin, Elisabet

2013-01-01

Polycystic ovary syndrome (PCOS), the most common endocrine disorder among women of reproductive age, is characterized by the coexistence of hyperandrogenism, ovulatory dysfunction, and polycystic ovaries (PCO). PCOS also represents the largest part of female oligoovulatory infertility, and the management of ovulatory and menstrual dysfunction, comprises a third of the high costs of PCOS treatment. Current pharmacological and surgical treatments for reproductive symptoms are effective, however, associated with negative side effects, such as cardiovascular complications and multiple pregnancies. For menstrual irregularities and ovulation induction in women with PCOS, acupuncture has indicated beneficial effects. This review will focus on the results from randomized controlled acupuncture trials for regulation of menstrual dysfunction and for inducing ovulation in women with PCOS although there are uncontrolled trials with nonetheless interesting results. Animal experimental studies will be further discussed when they can provide a more mechanistic explanatory view. PMID:24073009

A brief history of the global effort to develop a preventive HIV vaccine.

PubMed

Esparza, José

2013-08-02

Soon after HIV was discovered as the cause of AIDS in 1983-1984, there was an expectation that a preventive vaccine would be rapidly developed. In trying to achieve that goal, three successive scientific paradigms have been explored: induction of neutralizing antibodies, induction of cell mediated immunity, and exploration of combination approaches and novel concepts. Although major progress has been made in understanding the scientific basis for HIV vaccine development, efficacy trials have been critical in moving the field forward. In 2009, the field was reinvigorated with the modest results obtained from the RV144 trial conducted in Thailand. Here, we review those vaccine development efforts, with an emphasis on events that occurred during the earlier years. The goal is to provide younger generations of scientists with information and inspiration to continue the search for an HIV vaccine. Copyright © 2013 The Author. Published by Elsevier Ltd.. All rights reserved.

Oral or vaginal misoprostol administration for induction of labor: a randomized, double-blind trial.

PubMed

Adair, C D; Weeks, J W; Barrilleaux, S; Edwards, M; Burlison, K; Lewis, D F

1998-11-01

To compare the efficacy and vaginal birth intervals after intravaginal or oral misoprostol for labor induction. One hundred seventy-eight women were randomized to one of two double-blind groups: 1) oral misoprostol 200 microg and one-half tablet placebo intravaginal or 2) oral placebo tablet and one-half tablet of a 100-microg misoprostol intravaginal (dose 50 microg). Doses were repeated every 6 hours until labor was established (maximum of three doses). Ninety-three subjects were assigned to oral misoprostol and 85 to intravaginal administration. Oral administration was accompanied by significantly shorter intervals to the onset of uterine contractility (133+/-78 minutes versus 168+/-93, P < .01) but a higher incidence of abnormal uterine contractile activity (tachysystole 38.7% versus 20.0%, P < .01; hyperstimulation syndrome 44.1% versus 21.2%, P < .01). No adverse maternal or neonatal outcomes were noted, nor were there differences in cesarean delivery rates or total lengths of labor. Oral administration of 200 microg misoprostol has similar efficacy to intravaginal administration of 50 microg but is associated with more frequent abnormal uterine contractility.

Clomiphene citrate combined with metformin versus letrozole for induction of ovulation in clomiphene-resistant polycystic ovary syndrome: a randomized clinical trial.

PubMed

Rezk, Mohamed; Shaheen, Abd-Elhamid; Saif El-Nasr, Ibrahim

2018-04-01

A total of 202 patients with clomiphene citrate (CC) -resistant polycystic ovary syndrome (PCOS) were randomly allocated into two arms of induction of ovulation; the first group (n = 102) received CC 100 mg and metformin 500 mg while the second group (n = 100) received letrozole 2.5 mg with ovulation rate, clinical pregnancy rate, adverse effects, and acceptability were assessed. Patients in the letrozole arm experienced higher rate of ovulation (82% versus 43.1%, p < .001), more dominant follicles (p < .05), better endometrial thickness (p < .001), higher clinical pregnancy rate (36% versus 9.8%, p < .001), higher multiple pregnancy rate (p < .05), lesser adverse effects (p < .05) and higher acceptability (p < .001) compared to patients in the CC and metformin arm. In conclusion; letrozole is better and more acceptable than combined CC and metformin for inducing ovulation in patients with CC-resistant PCOS with higher clinical pregnancy rate and unexpectedly higher multiple pregnancy rate.

[Secondary osteoporosis induced by anticoagulants?].

PubMed

Riess, H; Loew, A; Himmelreich, G

2001-07-01

Generalized osteoporosis is a result of different causes and pathogenic mechanisms, which often combine forces to become clinically relevant. Among the different exogenic factors, drugs play an important role, frequently in connection with other factors such as immobilization or pregnancy. It has been suggested that anticoagulation therapy with heparins or coumarins may induce osteoporotic changes or enhance the development of osteoporosis for other reasons. According to in vitro experiments, preclinical trials, and clinical investigations, it seems reasonable to assume that heparins induce increased bone loss in a time- and dose-related manner. Low-molecular-weight heparins most likely have less effect on bone turnover when compared to unfractionated heparin. Oral anticoagulation therapy with vitamin K-antagonists is believed to have a weak effect on induction of osteoporosis, but clinical studies are contradictory. In spite of the fact that a relevant effect of these drugs on the induction of osteoporosis is questionable, it must be taken into consideration that anticoagulant drugs may enhance the negative effects on bone density of other risk factors capable of inducing osteoporosis such as immobilization, pregnancy, or endocrinological disorders.

Does acupuncture used in nulliparous women reduce time from prelabour rupture of membranes at term to active phase of labour? A randomised controlled trial.

PubMed

Selmer-Olsen, Tone; Lydersen, Stian; Mørkved, Siv

2007-01-01

To assess if acupuncture influences the onset of labour and the need for induction after prelabour rupture of membranes (PROM) in nulliparous women. Further, to investigate a possible effect of acupuncture on the woman's wellbeing. In a randomised controlled trial (RCT), 106 nulliparous women with PROM were allocated to an acupuncture group (AG) or a control group (CG). The outcome measures were time from PROM to onset of active phase of labour, and rate of inductions if labour was absent after 2 days. The women's self-reported wellbeing was registered on a Visual Analogue Scale (VAS). There was no statistically significant difference between the 2 groups regarding time from PROM to active phase (median times in AG versus CG: 15 versus 20.5 h, p=0.34). Additionally, there was no difference between the 2 groups in the need for induction. We found no significant differences in self-reported wellbeing, but the women receiving acupuncture considered their treatment to be more positive than the controls (p=0.003). No adverse effects were reported. Acupuncture treatment used in nulliparas after PROM showed no significant effect in reducing time to active labour or in reducing rate of inductions. There was no change in wellbeing as a result of acupuncture, but it was considered positive to receive this kind of treatment while waiting for labour to begin.

MRD assessed by WT1 and NPM1 transcript levels identifies distinct outcomes in AML patients and is influenced by gemtuzumab ozogamicin

PubMed Central

Lambert, Juliette; Lambert, Jérôme; Nibourel, Olivier; Pautas, Cécile; Hayette, Sandrine; Cayuela, Jean-Michel; Terré, Christine; Rousselot, Philippe; Dombret, Hervé; Chevret, Sylvie; Preudhomme, Claude; Castaigne, Sylvie; Renneville, Aline

2014-01-01

We analysed the prognostic significance of minimal residual disease (MRD) level in adult patients with acute myeloid leukemia (AML) treated in the randomized gemtuzumab ozogamicin (GO) ALFA-0701 trial. Levels of WT1 and NPM1 gene transcripts were assessed using cDNA-based real-time quantitative PCR in 183 patients with WT1 overexpression and in 77 patients with NMP1 mutation (NPM1mut) at diagnosis. Positive WT1 MRD (defined as > 0.5% in the peripheral blood) after induction and at the end of treatment were both significantly associated with a higher risk of relapse and a shorter overall survival (OS). Positive NPM1mut MRD (defined as > 0.1% in the bone marrow) after induction and at the end of treatment also predicted a higher risk of relapse, but did not influence OS. Interestingly, the achievement of a negative NPM1mut MRD was significantly more frequent in patients treated in the GO arm compared to those treated in control arm (39% versus 7% (p=0.006) after induction and 91% versus 61% (p=0.028) at the end of treatment). However, GO did not influence WT1 MRD levels. Our study supports the prognostic significance of MRD assessed by WT1 and NPM1mut transcript levels and show that NPM1 MRD is decreased by GO treatment. PMID:25026287

MRD assessed by WT1 and NPM1 transcript levels identifies distinct outcomes in AML patients and is influenced by gemtuzumab ozogamicin.

PubMed

Lambert, Juliette; Lambert, Jérôme; Nibourel, Olivier; Pautas, Cécile; Hayette, Sandrine; Cayuela, Jean-Michel; Terré, Christine; Rousselot, Philippe; Dombret, Hervé; Chevret, Sylvie; Preudhomme, Claude; Castaigne, Sylvie; Renneville, Aline

2014-08-15

We analysed the prognostic significance of minimal residual disease (MRD) level in adult patients with acute myeloid leukemia (AML) treated in the randomized gemtuzumab ozogamicin (GO) ALFA-0701 trial. Levels of WT1 and NPM1 gene transcripts were assessed using cDNA-based real-time quantitative PCR in 183 patients with WT1 overexpression and in 77 patients with NMP1 mutation (NPM1mut) at diagnosis. Positive WT1 MRD (defined as > 0.5% in the peripheral blood) after induction and at the end of treatment were both significantly associated with a higher risk of relapse and a shorter overall survival (OS). Positive NPM1mut MRD (defined as > 0.1% in the bone marrow) after induction and at the end of treatment also predicted a higher risk of relapse, but did not influence OS. Interestingly, the achievement of a negative NPM1mut MRD was significantly more frequent in patients treated in the GO arm compared to those treated in control arm (39 % versus 7% (p=0.006) after induction and 91% versus 61% (p=0.028) at the end of treatment). However, GO did not influence WT1 MRD levels. Our study supports the prognostic significance of MRD assessed by WT1 and NPM1mut transcript levels and show that NPM1 MRD is decreased by GO treatment.

Bayesian randomized clinical trials: From fixed to adaptive design.

PubMed

Yin, Guosheng; Lam, Chi Kin; Shi, Haolun

2017-08-01

Randomized controlled studies are the gold standard for phase III clinical trials. Using α-spending functions to control the overall type I error rate, group sequential methods are well established and have been dominating phase III studies. Bayesian randomized design, on the other hand, can be viewed as a complement instead of competitive approach to the frequentist methods. For the fixed Bayesian design, the hypothesis testing can be cast in the posterior probability or Bayes factor framework, which has a direct link to the frequentist type I error rate. Bayesian group sequential design relies upon Bayesian decision-theoretic approaches based on backward induction, which is often computationally intensive. Compared with the frequentist approaches, Bayesian methods have several advantages. The posterior predictive probability serves as a useful and convenient tool for trial monitoring, and can be updated at any time as the data accrue during the trial. The Bayesian decision-theoretic framework possesses a direct link to the decision making in the practical setting, and can be modeled more realistically to reflect the actual cost-benefit analysis during the drug development process. Other merits include the possibility of hierarchical modeling and the use of informative priors, which would lead to a more comprehensive utilization of information from both historical and longitudinal data. From fixed to adaptive design, we focus on Bayesian randomized controlled clinical trials and make extensive comparisons with frequentist counterparts through numerical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative Analysis of Resource Utilization and Safety of Outpatient Management Following Intensive AML Induction/Salvage Chemotherapy

PubMed Central

Vaughn, Jennifer E.; Othus, Megan; Powell, Morgan A.; Gardner, Kelda M.; Rizzuto, Donelle L.; Hendrie, Paul C.; Becker, Pamela S.; Pottinger, Paul S.; Estey, Elihu H.; Walter, Roland B.

2016-01-01

Importance Adults with acute myeloid leukemia (AML) typically remain hospitalized after induction or salvage chemotherapy until blood count recovery, with resulting prolonged inpatient stays being a primary driver of healthcare cost. Pilot studies suggest that outpatient management following chemotherapy might be safe and could reduce cost for these patients. Objective To compare safety, resource utilization, infections and cost between adults discharged early following AML induction or salvage chemotherapy and inpatient controls. Design Non-randomized phase 2 study. Setting Single center study conducted at the University of Washington Medical Center in Seattle, WA. Participants Over a 43-month period (January 1, 2011 – July 31, 2014), 178 adults receiving intensive AML chemotherapy were enrolled. After completion of chemotherapy, 107 met pre-designated medical and logistical criteria for early discharge (ED), while 29 met medical criteria only and served as inpatient controls. Interventions for Clinical Trials ED patients were discharged from the hospital at the completion of chemotherapy, and supportive care was provided in the outpatient setting until count recovery (median 21 days, range 2–45 days). Controls received inpatient supportive care (median 16 days, range 3–42 days). Main Outcome Measures 1) differences in early mortality 2) differences in resource utilization (ICU days, transfusions/study-day and IV antibiotics/study-day) 3) numbers of infections and 3) total and inpatient charges/study-day between early discharge patients and controls. Results Four patients discharged early (4%) but no controls died within 30 days of enrollment (p=0.58). Nine patients discharged early (8%) but no controls required intensive care unit-level care (p=0.20). No differences were noted in the average daily number of red blood cell (p=0.55) or platelet (p=0.31) transfusions. Patients discharged early did have more positive blood cultures (p=0.04) but required fewer days of IV antibiotics (p=0.007). Overall, daily charges among discharged patients were significantly lower (median $3,840 vs. $5,852; p<0.001) despite increased charges per inpatient day when readmitted (median $7,405 vs. $6,267; p<0.001). Conclusions and Relevance Early dischargefollowing intensive AML chemotherapy can reduce cost and use of IV antibiotics, but attention should be paid to complications that may occur in the outpatient setting. This study was registered at www.ClinicalTrials.gov (NCT01235572). PMID:26355382

Phase II study. Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer.

PubMed

Arrieta, Oscar; Blake, Mónika; de la Mata-Moya, María Dolores; Corona, Francisco; Turcott, Jenny; Orta, David; Alexander-Alatorre, Jorge; Gallardo-Rincón, Dolores

2014-05-01

Nitroglycerin, a nitric oxide donor agent, reduces the expression of hypoxia-inducible factor-1α (HIF-1α) and could be a normalizer of the tumor microenvironment. Both factors are associated with chemo-radio-resistance. The aim of this study was to determine the safety profile and efficacy of nitroglycerin administration with chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). This is a phase II trial of locally advanced NSCLC patients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy. A 25-mg NTG patch was administered to the patients for 5 days (1 day before and 4 days after chemotherapy induction and consolidation) and all day during chemo-radiotherapy. VEGF plasmatic level was determined before and after two cycles of chemotherapy. Thirty-five patients were enrolled in this trial. Sixty-three percent of patients achieved an overall response after induction of chemotherapy, and 75% achieved an overall response after chemo-radiotherapy. The median progression-free survival was 13.5 months (95% CI, 8.8-18.2), and the median overall survival was 26.9 months (95% CI, 15.3-38.5). Reduction of VEGF level was associated with better OS. The toxicity profile related to nitroglycerin included headache (20%) and hypotension (2.9%). The addition of nitroglycerin to induction chemotherapy and concurrent chemoradiotherapy in patients with locally advanced NSCLC has an acceptable toxicity profile and supports the possibility to add nitroglycerin to chemotherapy and radiotherapy. A randomized trial is warranted to confirm these findings. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

THE EFFECTS OF DRONABINOL DURING DETOXIFICATION AND THE INITIATION OF TREATMENT WITH EXTENDED RELEASE NALTREXONE

PubMed Central

Bisaga, Adam; Sullivan, Maria A.; Glass, Andrew; Mishlen, Kaitlyn; Pavlicova, Martina; Haney, Margaret; Raby, Wilfrid N.; Levin, Frances R.; Carpenter, Kenneth M.; Mariani, John J.; Nunes, Edward V.

2015-01-01

Background Evidence suggests that the cannabinoid system is involved in the maintenance of opioid dependence. We examined whether dronabinol, a cannabinoid receptor type 1 partial agonist, reduces opioid withdrawal and increases retention in treatment with extended release naltrexone (XR-naltrexone). Methods Opioid dependent participants were randomized to receive dronabinol 30 mg/d (n=40) or placebo (n=20), under double-blind conditions, while they underwent inpatient detoxification and naltrexone induction. Before discharge all participants received an injection of XR-naltrexone, with an additional dose given four weeks later. Dronabinol or placebo was given while inpatient and for 5 weeks afterwards. The primary outcomes were the severity of opioid withdrawal, measured with the Subjective Opioid Withdrawal Scale, and retention in treatment at the end of the inpatient phase and at the end of the 8-week trial. Results The severity of opioid withdrawal during inpatient phase was lower in the dronabinol group relative to placebo group (p=0.006). Rates of successful induction onto XR-naltrexone (dronabinol 66%, placebo 55%) and completion of treatment (dronabinol 35%, placebo 35%) were not significantly different. Post-hoc analysis showed that the 32% of participants who smoked marijuana regularly during the outpatient phase had significantly lower ratings of insomnia and anxiety and were more likely to complete the 8-week trial. Conclusion Dronabinol reduced the severity of opiate withdrawal during acute detoxification but had no effect on rates of XR-naltrexone treatment induction and retention. Participants who elected to smoke marijuana during the trial were more likely to complete treatment regardless of treatment group assignment. PMID:26187456

Letrozole pretreatment prior to medical termination of pregnancy: a systematic review.

PubMed

Nash, Christopher M; Philp, Lauren; Shah, Prakesh; Murphy, Kellie E

2018-06-01

The purpose of this systematic review was to evaluate the efficacy of pretreatment with letrozole prior to either a first- or second-trimester medical termination of pregnancy. We searched letrozole, femara, aromatase inhibitors, abortifacient agents, termination of pregnancy and labor induction in MEDLINE, EMBASE, Cochrane Database, Google Scholar and PubMed from inception of each database until September 2015 with no language limitation. A systematic review of all randomized controlled trials (RCTs) was performed where women received either letrozole and misoprostol or placebo and misoprostol for termination of pregnancy. The primary outcome was complete abortion rate, defined as complete evacuation of the products of conception from the uterus. Relative risk with 95% confidence intervals was used to report data. Our systematic review identified 7 studies; 4 RCTs were included in the review. Two RCTs evaluated terminations of pregnancy up to 9 weeks' gestation, while 2 evaluated terminations over 9 weeks' gestation. For each gestational age group, one trial supported an increase in complete abortion rate, while the other showed no difference, with letrozole and misoprostol compared with placebo and misoprostol. Time-to-abortion interval for terminations up to 9 weeks' gestation was not improved with the addition of letrozole to misoprostol. For terminations over 9 weeks' gestation, one trial supported and one trial refuted a decrease in time-to-abortion interval with letrozole and misoprostol. Similarly, for each gestational age group, one study supported a decrease and one study showed no difference in rate of dilation and curettage (D&C) with letrozole and misoprosol. Medication side effects were similar between both treatment groups. There was significant heterogeneity between the trials, and therefore, the results were not meta-analyzed. Some studies and trials report better outcomes (i.e., complete abortion rates, time-to-abortion and D&C rates) in women exposed to letrozole and misoprostol compared to placebo and misoprostol, while other trials demonstrate no difference. Further research exploring letrozole pretreatment prior to medical abortion is required. This systematic review demonstrated that a combination of letrozole and misoprostol increased the rate of complete abortion compared to misoprostol alone in some studies but not in others; additional well-designed RCT's are needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Different types of dietary advice for women with gestational diabetes mellitus.

PubMed

Han, Shanshan; Middleton, Philippa; Shepherd, Emily; Van Ryswyk, Emer; Crowther, Caroline A

2017-02-25

Dietary advice is the main strategy for managing gestational diabetes mellitus (GDM). It remains unclear what type of advice is best. To assess the effects of different types of dietary advice for women with GDM for improving health outcomes for women and babies. We searched Cochrane Pregnancy and Childbirth's Trials Register (8 March 2016), PSANZ's Trials Registry (22 March 2016) and reference lists of retrieved studies. Randomised controlled trials comparing the effects of different types of dietary advice for women with GDM. Two authors independently assessed study eligibility, risk of bias, and extracted data. Evidence quality for two comparisons was assessed using GRADE, for primary outcomes for the mother: hypertensive disorders of pregnancy; caesarean section; type 2 diabetes mellitus; and child: large-for-gestational age; perinatal mortality; neonatal mortality or morbidity composite; neurosensory disability; secondary outcomes for the mother: induction of labour; perineal trauma; postnatal depression; postnatal weight retention or return to pre-pregnancy weight; and child: hypoglycaemia; childhood/adulthood adiposity; childhood/adulthood type 2 diabetes mellitus. In this update, we included 19 trials randomising 1398 women with GDM, at an overall unclear to moderate risk of bias (10 comparisons). For outcomes assessed using GRADE, downgrading was based on study limitations, imprecision and inconsistency. Where no findings are reported below for primary outcomes or pre-specified GRADE outcomes, no data were provided by included trials. Primary outcomes Low-moderate glycaemic index (GI) versus moderate-high GI diet (four trials): no clear differences observed for: large-for-gestational age (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.22 to 2.34; two trials, 89 infants; low-quality evidence); severe hypertension or pre-eclampsia (RR 1.02, 95% CI 0.07 to 15.86; one trial, 95 women; very low-quality evidence); eclampsia (RR 0.34, 95% CI 0.01 to 8.14; one trial, 83 women; very low-quality evidence) or caesarean section (RR 0.66, 95% CI 0.29 to 1.47; one trial, 63 women; low-quality evidence). Energy-restricted versus no energy-restricted diet (three trials): no clear differences seen for: large-for-gestational age (RR 1.17, 95% CI 0.65 to 2.12; one trial, 123 infants; low-quality evidence); perinatal mortality (no events; two trials, 423 infants; low-quality evidence); pre-eclampsia (RR 1.00, 95% CI 0.51 to 1.97; one trial, 117 women; low-quality evidence); or caesarean section (RR 1.12, 95% CI 0.80 to 1.56; two trials, 420 women; low-quality evidence). DASH (Dietary Approaches to Stop Hypertension) diet versus control diet (three trials): no clear differences observed for: pre-eclampsia (RR 1.00, 95% CI 0.31 to 3.26; three trials, 136 women); however there were fewer caesarean sections in the DASH diet group (RR 0.53, 95% CI 0.37 to 0.76; two trials, 86 women). Low-carbohydrate versus high-carbohydrate diet (two trials): no clear differences seen for: large-for-gestational age (RR 0.51, 95% CI 0.13 to 1.95; one trial, 149 infants); perinatal mortality (RR 3.00, 95% CI 0.12 to 72.49; one trial, 150 infants); maternal hypertension (RR 0.40, 95% CI 0.13 to 1.22; one trial, 150 women); or caesarean section (RR 1.29, 95% CI 0.84 to 1.99; two trials, 179 women). High unsaturated fat versus low unsaturated fat diet (two trials): no clear differences observed for: large-for-gestational age (RR 0.54, 95% CI 0.21 to 1.37; one trial, 27 infants); pre-eclampsia (no cases; one trial, 27 women); hypertension in pregnancy (RR 0.54, 95% CI 0.06 to 5.26; one trial, 27 women); caesarean section (RR 1.08, 95% CI 0.07 to 15.50; one trial, 27 women); diabetes at one to two weeks (RR 2.00, 95% CI 0.45 to 8.94; one trial, 24 women) or four to 13 months postpartum (RR 1.00, 95% CI 0.10 to 9.61; one trial, six women). Low-GI versus high-fibre moderate-GI diet (one trial): no clear differences seen for: large-for-gestational age (RR 2.87, 95% CI 0.61 to 13.50; 92 infants); caesarean section (RR 1.91, 95% CI 0.91 to 4.03; 92 women); or type 2 diabetes at three months postpartum (RR 0.76, 95% CI 0.11 to 5.01; 58 women). Diet recommendation plus diet-related behavioural advice versus diet recommendation only (one trial): no clear differences observed for: large-for-gestational age (RR 0.73, 95% CI 0.25 to 2.14; 99 infants); or caesarean section (RR 0.78, 95% CI 0.38 to 1.62; 99 women). Soy protein-enriched versus no soy protein diet (one trial): no clear differences seen for: pre-eclampsia (RR 2.00, 95% CI 0.19 to 21.03; 68 women); or caesarean section (RR 1.00, 95% CI 0.57 to 1.77; 68 women). High-fibre versus standard-fibre diet (one trial): no primary outcomes reported. Ethnic-specific versus standard healthy diet (one trial): no clear differences observed for: large-for-gestational age (RR 0.14, 95% CI 0.01 to 2.45; 20 infants); neonatal composite adverse outcome (no events; 20 infants); gestational hypertension (RR 0.33, 95% CI 0.02 to 7.32; 20 women); or caesarean birth (RR 1.20, 95% CI 0.54 to 2.67; 20 women). Secondary outcomes For secondary outcomes assessed using GRADE no differences were observed: between a low-moderate and moderate-high GI diet for induction of labour (RR 0.88, 95% CI 0.33 to 2.34; one trial, 63 women; low-quality evidence); or an energy-restricted and no energy-restricted diet for induction of labour (RR 1.02, 95% CI 0.68 to 1.53; one trial, 114 women, low-quality evidence) and neonatal hypoglycaemia (average RR 1.06, 95% CI 0.48 to 2.32; two trials, 408 infants; very low-quality evidence).Few other clear differences were observed for reported outcomes. Longer-term health outcomes and health services use and costs were largely not reported. Evidence from 19 trials assessing different types of dietary advice for women with GDM suggests no clear differences for primary outcomes and secondary outcomes assessed using GRADE, except for a possible reduction in caesarean section for women receiving a DASH diet compared with a control diet. Few differences were observed for secondary outcomes.Current evidence is limited by the small number of trials in each comparison, small sample sizes, and variable methodological quality. More evidence is needed to assess the effects of different types of dietary advice for women with GDM. Future trials should be adequately powered to evaluate short- and long-term outcomes.

The effects of nicardipine or esmolol on the onset time of rocuronium and intubation conditions during rapid sequence induction: a randomized double-blind trial.

PubMed

Lee, Ji Heui; Kim, Yunkwang; Lee, Kye Hyeok; Rim, Sung Kyu; Lee, Ji Yeon; Lee, Cheong

2015-06-01

The main aims of rapid sequence induction (RSI) are prompt and adequate muscle relaxation for tracheal intubation and hemodynamic stability during and after intubation. The purpose of the present study was to investigate the effects of nicardipine and esmolol on the action of rocuronium and intubation conditions during RSI. Adult patients (n = 82) were randomly allocated to one of three groups. One minute prior to the induction of sevoflurane-based general anesthesia, patients received 20 μg/kg of nicardipine (N group; n = 27) or 0.5 mg/kg of esmolol (E group; n = 27), or 5 ml of saline (C group; n = 28). Patients were assessed according to intubation conditions, the onset time of rocuronium, mean arterial pressure (MAP), and heart rate (HR) during RSI. The intubation conditions and score were significantly better in the C and N groups than in the E group (P < 0.001). The onset time of rocuronium was shortened in the N group and prolonged in the E group when compared to the C group (P < 0.001). A significant attenuation in the increase of MAP immediately after intubation was observed in the N group as compared with the C and E groups (P < 0.008). HR was significantly lower in the E group than in the N and C groups (P < 0.01). Pretreatment with nicardipine for RSI improved intubation conditions and shortened the onset time of rocuronium and attenuated changes in MAP after intubation. Esmolol may disturb intubation conditions and the onset of action of rocuronium, despite being effective in alleviating responses of HR after RSI.

Safety profile of biologic drugs in the therapy of Crohn disease: A systematic review and network meta-analysis.

PubMed

Moćko, Paweł; Kawalec, Paweł; Pilc, Andrzej

2016-12-01

Crohn disease (CD) is an inflammatory bowel disease which occurs especially in developed countries of Western Europe and North America. The aim of the study was to compare the safety profile of biologic drugs in patients with CD. A systematic literature search was performed using PubMed, Embase, and CENTRAL databases, until April 27, 2016. We included randomized controlled trials (RCTs) that compared the safety of biologic drugs (infliximab, adalimumab, vedolizumab, certolizumab pegol, and ustekinumab) with one another or with placebo in patients with CD. The network meta-analysis (NMA) was conducted for an induction phase (6-10 weeks) and maintenance phase (52-56 weeks) with a Bayesian hierarchical random effects model in the ADDIS ® software. The PROSPERO registration number was CRD42016032606. Ten RCTs were included in the systematic review with NMA. In the case of the induction phase, the NMA could be conducted for the assessment of the relative safety profile of adalimumab, vedolizumab, certolizumab pegol, and ustekinumab, and in the case of the maintenance phase-of infliximab, adalimumab, and vedolizumab. There were no significant differences in the rate of adverse events in patients treated with biologics. Statistical analysis revealed that vedolizumab had the greatest probability of being the safest treatment in most endpoints in the induction phase and adalimumab-in the maintenance phase. No significant differences between the biologics in the relative safety profile analysis were observed. Further studies are needed to confirm our findings, including head-to-head comparisons between the analyzed biologics. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Ultrasound for fetal assessment in early pregnancy

PubMed Central

Whitworth, Melissa; Bricker, Leanne; Neilson, James P; Dowswell, Therese

2014-01-01

Background Diagnostic ultrasound is a sophisticated electronic technology, which utilises pulses of high frequency sound to produce an image. Diagnostic ultrasound examination may be employed in a variety of specific circumstances during pregnancy such as after clinical complications, or where there are concerns about fetal growth. Because adverse outcomes may also occur in pregnancies without clear risk factors, assumptions have been made that routine ultrasound in all pregnancies will prove beneficial by enabling earlier detection and improved management of pregnancy complications. Routine screening may be planned for early pregnancy, late gestation, or both. The focus of this review is routine early pregnancy ultrasound. Objectives To assess whether routine early pregnancy ultrasound for fetal assessment (i.e. its use as a screening technique) influences the diagnosis of fetal malformations, multiple pregnancies, the rate of clinical interventions, and the incidence of adverse fetal outcome when compared with the selective use of early pregnancy ultrasound (for specific indications). Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (September 2009). Selection criteria Published, unpublished, and ongoing randomised controlled trials that compared outcomes in women who experienced routine versus selective early pregnancy ultrasound (i.e. less than 24 weeks’ gestation). We have included quasi-randomised trials. Data collection and analysis Two review authors independently extracted data for each included study. We used the Review Manager software to enter and analyse data. Main results Routine/revealed ultrasound versus selective ultrasound/concealed: 11 trials including 37505 women. Ultrasound for fetal assessment in early pregnancy reduces the failure to detect multiple pregnancy by 24 weeks’ gestation (risk ratio (RR) 0.07, 95% confidence interval (CI) 0.03 to 0.17). Routine scan is associated with a reduction in inductions of labour for ‘post term’ pregnancy (RR 0.59, 95% CI 0.42 to 0.83). Routine scans do not seem to be associated with reductions in adverse outcomes for babies or in health service use by mothers and babies. Long-term follow up of children exposed to scan in utero does not indicate that scans have a detrimental effect on children’s physical or cognitive development. Authors’ conclusions Early ultrasound improves the early detection of multiple pregnancies and improved gestational dating may result in fewer inductions for post maturity. Caution needs to be exercised in interpreting the results of aspects of this review in view of the fact that there is considerable variability in both the timing and the number of scans women received. PMID:20393955

Treatment strategies for women with WHO group II anovulation: systematic review and network meta-analysis

PubMed Central

Kim, Bobae V; van Wely, Madelon; Johnson, Neil P; Costello, Michael F; Zhang, Hanwang; Ng, Ernest Hung Yu; Legro, Richard S; Bhattacharya, Siladitya; Norman, Robert J; Mol, Ben Willem J

2017-01-01

Objective To compare the effectiveness of alternative first line treatment options for women with WHO group II anovulation wishing to conceive. Design Systematic review and network meta-analysis. Data sources Cochrane Central Register of Controlled Trials, Medline, and Embase, up to 11 April 2016. Study selection Randomised controlled trials comparing eight ovulation induction treatments in women with WHO group II anovulation: clomiphene, letrozole, metformin, clomiphene and metformin combined, tamoxifen, gonadotropins, laparoscopic ovarian drilling, and placebo or no treatment. Study quality was measured on the basis of the methodology and categories described in the Cochrane Collaboration Handbook. Pregnancy, defined preferably as clinical pregnancy, was the primary outcome; live birth, ovulation, miscarriage, and multiple pregnancy were secondary outcomes. Results Of 2631 titles and abstracts initially identified, 57 trials reporting on 8082 women were included. All pharmacological treatments were superior to placebo or no intervention in terms of pregnancy and ovulation. Compared with clomiphene alone, both letrozole and the combination of clomiphene and metformin showed higher pregnancy rates (odds ratio 1.58, 95% confidence interval 1.25 to 2.00; 1.81, 1.35 to 2.42; respectively) and ovulation rates (1.99, 1.38 to 2.87; 1.55, 1.02 to 2.36; respectively). Letrozole led to higher live birth rates when compared with clomiphene alone (1.67, 1.11 to 2.49). Both letrozole and metformin led to lower multiple pregnancy rates compared with clomiphene alone (0.46, 0.23 to 0.92; 0.22, 0.05 to 0.92; respectively). Conclusions In women with WHO group II anovulation, letrozole and the combination of clomiphene and metformin are superior to clomiphene alone in terms of ovulation and pregnancy. Compared with clomiphene alone, letrozole is the only treatment showing a significantly higher rate of live birth. Systematic review registration PROSPERO CRD42015027579. PMID:28143834

Inability to induce consistent T-cell responses recognizing conserved regions within HIIV-1 antigens: a potential mechanism for lack of vaccine efficacy in the step study

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

Korber, Bette; Szinger, James

2009-01-01

T cell based vaccines are based upon the induction of CD8+ T cell memory responses that would be effective in inhibiting infection and subsequent replication of an infecting HIV-1 strain, a process that requires a high probability of matching the epitope induced by vaccination with the infecting viral strain. We compared the frequency and specificity of the CTL epitopes elicited by the replication defective AdS gag/pol/nef vaccine used in the STEP trial with the likelihood of encountering those epitopes among recently sequenced Clade B isolates of HIV-1. On average vaccination elicited only one epitope per gene. Importantly, the highly conservedmore » epitopes in gag, pol, and nef (> 80% of strains in the current collection of the Los Alamos database [www.hiv.lanl.gov]) were rarely elicited by vaccination. Moreover there was a statistically significant skewing of the T cell response to relative variable epitopes of each gene; only 20% of persons possessed > 3 T cell responses to epitopes likely to be found in circulating strains in the CladeB populations in which the Step trial was conducted. This inability to elicit T cell responses likely to be found in circulating viral strains is a likely factor in the lack of efficacy of the vaccine utilized in the STEP trial. Modeling of the epitope specific responses elicited by vaccination, we project that a median of 8-10 CD8+ T cell epitopes are required to provide >80% likelihood of eliciting at least 3 CD8+ T cell epitopes that would be found on a circulating population of viruses. Development of vaccine regimens which elicit either a greater breadth of responses or elicit responses to conserved regions of the HIV-1 genome are needed to fully evaluate the concept of whether induction of T cell immunity can alter HIV-1 in vivo.« less

Altering Hirsutism Through Ovulation Induction in Women With Polycystic Ovary Syndrome

PubMed Central

Roth, Lauren W.; Huang, Hao; Legro, Richard S.; Diamond, Michael P.; Coutifaris, Christos; Carson, Sandra A.; Steinkampf, Michael P.; Carr, Bruce R.; McGovern, Peter G.; Cataldo, Nicholas A.; Gosman, Gabriella G.; Nestler, John E.; Myers, Evan R.; Zhang, Heping; Schlaff, William D.

2012-01-01

Objective Many women with polycystic ovary syndrome (PCOS) experience infertility and hirsutism and often seek treatment for both concurrently. We investigated whether women who ovulate in response to treatment with clomiphene citrate), metformin, or both would have greater improvement in hirsutism compared to those who did not ovulate. Methods This is a secondary analysis evaluating the change in Ferriman-Gallwey score for the hirsute women (n = 505, 80.7%) from the Pregnancy in Polycystic Ovary Syndrome 1 study. This was a prospective, randomized, doubled-blind trial of 626 women with PCOS and infertility recruited from 12 university sites. They were treated with clomiphene citrate, metformin, or both (combination) for up to six cycles, and hirsutism evaluators were blinded to group assignment. Results There was a significant decrease in the Ferriman-Gallwey score between baseline and completion of the study in each of the three individual groups (clomiphene citrate, p=0.024; metformin, p=0.005; combination, p<0.001). There was no significant difference in the degree to which the hirsutism score changed when comparing the three groups (p=0.44). The change in hirsutism was not associated with the duration of treatment or with the presence or absence of ovulation. Conclusions In infertile hirsute women with PCOS, treatment with clomiphene citrate, metformin, or both for up to 6 cycles does not alter hirsutism. Clinical Trial Registration ClinicalTrials.gov, www.clinicaltrials.gov, NCT00068861. PMID:22617579

A Phase 2 Open Label, Single-Arm Trial to Evaluate the Combination of Cetuximab Plus Taxotere, Cisplatin, and 5-Flurouracil as an Induction Regimen in Patients With Unresectable Squamous Cell Carcinoma of the Head and Neck

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

Mesía, Ricard, E-mail: rmesia@iconcologia.net; Vázquez, Silvia; Grau, Juan J.

Purpose: Despite treatment, prognosis of unresectable squamous cell carcinoma of the head and neck (SCCHC) is dismal. Cetuximab therapy has proven to increase the clinical activity of radiation therapy and chemotherapy in patients with locoregional advanced disease with an acceptable toxicity profile. We designed a phase 2 trial to evaluate the efficacy of docetaxel, cisplatin, and 5-fluorouracil (TPF) plus cetuximab (C-TPF) as an induction regimen in patients with unresectable SCCHN. Methods and Materials: A single-arm phase 2 trial was conducted. Eligible patients included those with untreated unresectable SCCHC, World Health Organization performance status of 0 to 1, 18 to 70 yearsmore » of age. Treatment consisted of four 21-day cycles of TPF (docetaxel, 75 mg/m{sup 2} day 1; cisplatin, 75 mg/m{sup 2} day 1; 5-fluorouracil [5-FU], 750 mg/m{sup 2} day 1-5) and cetuximab, 250 mg/m{sup 2} weekly (loading dose of 400 mg/m{sup 2}). Prophylactic granulocyte colony-stimulating factor and antibiotic support were given. After induction, sequential accelerated radiation therapy with concomitant boost (69.9 Gy) and weekly cetuximab therapy were delivered in the absence of disease progression. The primary endpoint was objective response rate (ORR) to C-TPF. Results: Fifty patients were enrolled across 8 centers. Median age was 54 years; disease was stage IV; oropharynx and hypopharynx were the most common primary sites. Eighty-two percent received 4 cycles of C-TPF, and 86% started sequential treatment based on radiation therapy and cetuximab. ORR after C-TPF was 86% (95% confidence interval [CI]: 73%-94%) and 24% had complete response (CR). With a median follow-up of 40.7 months, median overall survival (OS) was 40.7 months. The 2-year actuarial locoregional control (LRC) rate was 57%. The most common drug-related grade 3 or 4 toxicities during induction were neutropenia (24%), neutropenic fever (24%), and diarrhea (20%). There were 3 treatment-related deaths (6%). Conclusions: C-TPF yields high ORR and CR as induction treatment in unresectable SCCHN. However, hematologic toxicity is too high to recommend this regimen at the current dose.« less

Anesthesia maintenance with 'induction dose only' sevoflurane during pediatric ophthalmic examination: comparison with standard low-flow technique through a randomized controlled trial.

PubMed

Datta, Priyankar K; Sinha, Renu; Ray, Bikash Ranjan; Jambunathan, Venkateswaran; Kundu, Riddhi

2017-02-01

Sevoflurane is preferred for pediatric day care procedures. However, financial and environmental costs remain major limitations. Induction dose of sevoflurane could itself be sufficient for maintaining anesthesia with low fresh gas flow during short noninvasive procedures. Fifty children, aged 1-5 years, scheduled for ophthalmic examination under anesthesia, were randomized into two groups. All children were induced with 8% sevoflurane in O 2 : N 2 O (40 : 60). In the Group S, anesthesia was maintained with 2% sevoflurane at 1 l·min -1 fresh gas flow [O 2 : N 2 O = 50 : 50]. In Group L, the sevoflurane vaporizer was turned off and fresh gas flow was reduced to 0.5 l·min -1 [O 2 : N 2 O = 50 : 50]. HR, BP, MAC, BIS, total sevoflurane consumption, ocular deviation, body movement, time to laryngeal mask airway removal (T WO ), and airway complications were compared between the groups. Rescue propofol bolus was used, if needed. Median duration of examination was 14 min (IQR = 9-17) in Group S and 15 min (IQR = 10-17) in Group L. Sevoflurane consumption was lower in the Group L (7 ml) compared to Group S (9 ml) [median difference = 2 ml, P < 0.001, 95% CI = 0.96-3.04]. T WO was lower in Group L (86 s) compared to Group S (131 s) [median difference = 45 s, P = 0.002, 95% CI = 19.85-70.15]. There was no difference in hemodynamic parameters, incidence of ocular deviation, movement or airway complications, and need for rescue propofol. Induction dose of sevoflurane is, in itself, adequate for maintaining anesthesia for short noninvasive ophthalmic examinations lasting approximately 15 min. This method significantly reduces sevoflurane consumption and cost. © 2016 John Wiley & Sons Ltd.

Comparison of In-Patient Costs for Children Treated on the AAML0531 Clinical Trial: A Report From the Children’s Oncology Group

PubMed Central

Getz, Kelly D.; Li, Yimei; Alonzo, Todd A.; Hall, Matthew; Gerbing, Robert B.; Sung, Lillian; Huang, Yuan-Shung; Arnold, Staci; Seif, Alix E.; Miller, Tamara P.; Bagatell, Rochelle; Fisher, Brian T.; Adamson, Peter C.; Gamis, Alan; Keren, Ron; Aplenc, Richard

2015-01-01

Background A better understanding of drivers of treatment costs may help identify effective cost containment strategies and prioritize resources. We aimed to develop a method for estimating inpatient costs for pediatric patients with acute myeloid leukemia (AML) enrolled on NCI-funded Phase III trials, compare costs between AAML0531 treatment arms (standard chemotherapy ± gemtuzumab ozogamicin (GMTZ)), and evaluate primary drivers of costs for newly diagnosed pediatric AML. Procedure Patients from the AAML0531 trial were matched on hospital, sex, and dates of birth and diagnosis to the Pediatric Health Information Systems (PHIS) database to obtain daily billing data. Inpatient treatment costs were calculated as adjusted charges multiplied by hospital-specific cost-to-charge ratios. Generalized linear models were used to compare costs between treatment arms and courses, and by patient characteristics. Results Inpatient costs did not differ by randomized treatment arm. Costs varied by course with stem cell transplant being most expensive, followed by Intensification II (cytarabine/mitoxantrone) and Induction I (cytarabine/daunorubicin/etoposide). Room/board and pharmacy were the largest contributors to inpatient treatment cost, representing 74% of the total cost. Higher AML risk group (P = 0.0003) and older age (P < 0.0001) were associated with significantly higher daily inpatient cost. Conclusions Costs from external data sources can be successfully integrated into NCI-funded Phase III clinical trials. Inpatient treatment costs did not differ by GMTZ exposure but varied by chemotherapy course. Variation in cost by course was driven by differences in duration of hospitalization through room/board charges as well as increased clinical and pharmacy charges in specific courses. Pediatr Blood Cancer PMID:25946708

Single induction dose of etomidate versus other induction agents for endotracheal intubation in critically ill patients.

PubMed

Bruder, Eric A; Ball, Ian M; Ridi, Stacy; Pickett, William; Hohl, Corinne

2015-01-08

The use of etomidate for emergency airway interventions in critically ill patients is very common. In one large registry trial, etomidate was the most commonly used agent for this indication. Etomidate is known to suppress adrenal gland function, but it remains unclear whether or not this adrenal gland dysfunction affects mortality. The primary objective was to assess, in populations of critically ill patients, whether a single induction dose of etomidate for emergency airway intervention affects mortality.The secondary objectives were to address, in populations of critically ill patients, whether a single induction dose of etomidate for emergency airway intervention affects adrenal gland function, organ dysfunction, or health services utilization (as measured by intensive care unit (ICU) length of stay (LOS), duration of mechanical ventilation, or vasopressor requirements).We repeated analyses within subgroups defined by the aetiologies of critical illness, timing of adrenal gland function measurement, and the type of comparator drug used. We searched the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; CINAHL; EMBASE; LILACS; International Pharmaceutical Abstracts; Web of Science; the Database of Abstracts of Reviews of Effects (DARE); and ISI BIOSIS Citation index(SM) on 8 February 2013. We reran the searches in August 2014. We will deal with any studies of interest when we update the review.We also searched the Scopus database of dissertations and conference proceedings and the US Food and Drug Administration Database. We handsearched major emergency medicine, critical care, and anaesthesiology journals.We handsearched the conference proceedings of major emergency medicine, anaesthesia, and critical care conferences from 1990 to current, and performed a grey literature search of the following: Current Controlled Trials; National Health Service - The National Research Register; ClinicalTrials.gov; NEAR website. We included randomized controlled trials in patients undergoing emergency endotracheal intubation for critical illness, including but not limited to trauma, stroke, myocardial infarction, arrhythmia, septic shock, hypovolaemic or haemorrhagic shock, and undifferentiated shock states. We included single (bolus) dose etomidate for emergency airway intervention compared to any other rapid-acting intravenous bolus single-dose induction agent. Refinement of our initial search results by title review, and then by abstract review was carried out by three review authors. Full-text review of potential studies was based on their adherence to our inclusion and exclusion criteria. This was decided by three independent review authors. We reported the decisions regarding inclusion and exclusion in accordance with the PRISMA statement.Electronic database searching yielded 1635 potential titles, and our grey literature search yielded an additional 31 potential titles. Duplicate titles were filtered leaving 1395 titles which underwent review of their titles and abstracts by three review authors. Sixty seven titles were judged to be relevant to our review, however only eight met our inclusion criteria and seven were included in our analysis. We included eight studies in the review and seven in the meta-analysis. Of those seven studies, only two were judged to be at low risk of bias. Overall, no strong evidence exists that etomidate increases mortality in critically ill patients when compared to other bolus dose induction agents (odds ratio (OR) 1.17; 95% confidence interval (CI) 0.86 to 1.60, 6 studies, 772 participants, moderate quality evidence). Due to a large number of participants lost to follow-up, we performed a post hoc sensitivity analysis. This gave a similar result (OR 1.15; 95% CI 0.86 to 1.53). There was evidence that the use of etomidate in critically ill patients was associated with a positive adrenocorticotropic hormone (ACTH) stimulation test, and this difference was more pronounced at between 4 to 6 hours (OR 19.98; 95% CI 3.95 to 101.11) than after 12 hours (OR 2.37; 95% CI 1.61 to 3.47) post-dosing. Etomidate's use in critically ill patients was associated with a small increase in SOFA score, indicating a higher risk of multisystem organ failure (mean difference (MD) 0.70; 95% CI 0.01 to 1.39, 2 studies, 591 participants, high quality evidence), but this difference was not clinically meaningful. Etomidate use did not have an effect on ICU LOS (MD 1.70 days; 95% CI -2.00 to 5.40, 4 studies, 621 participants, moderate quality evidence), hospital LOS (MD 2.41 days; 95% CI -7.08 to 11.91, 3 studies, 152 participants, moderate quality evidence), duration of mechanical ventilation (MD 2.14 days; 95% CI -1.67 to 5.95, 3 studies, 621 participants, moderate quality evidence), or duration of vasopressor use (MD 1.00 day; 95% CI -0.53 to 2.53, 1 study, 469 participants). Although we have not found conclusive evidence that etomidate increases mortality or healthcare resource utilization in critically ill patients, it does seem to increase the risk of adrenal gland dysfunction and multi-organ system dysfunction by a small amount. The clinical significance of this finding is unknown. This evidence is judged to be of moderate quality, owing mainly to significant attrition bias in some of the smaller studies, and new research may influence the outcomes of our review. The applicability of these data may be limited by the fact that 42% of the patients in our review were intubated for "being comatose", a population less likely to benefit from the haemodynamic stability inherent in etomidate use, and less at risk from its potential negative downstream effects of adrenal suppression.

The effect of acupressure on the initiation of labor: A randomized controlled trial.

PubMed

Torkzahrani, Shahnaz; Mahmoudikohani, Fatemeh; Saatchi, Kiarash; Sefidkar, Reyhaneh; Banaei, Mojdeh

2017-02-01

Induction of labor is a common obstetric procedure. Acupressure is a natural method that is used for inducing uterine contractions. Nevertheless, few studies have examined the impact of acupressure on the induction of labor. The aim of this study was to evaluate the effect of acupressure on the initiation of labor. In this randomized clinical trial, 162 nulliparous pregnant women were admitted to the hospital. They were categorized into 3 groups; acupressure, sham acupressure and control. Acupressure points SP6, BL 60 and BL 32 were pressured bilaterally. The intervention was done by the researcher every other day between 9 am and 11 am. The intervention was carried out on women in the afternoon and the following day. Subjects were examined to determine the initiation of labor symptoms48 and 96h after the start of intervention and at the time of hospitalization. Data were analyzed using the ANOVA, Kruskal-Wallis and Chi-square tests (p<0.05). There was no significant difference among the groups for spontaneous initiation of labor within 48h (P=0.464), and 49-96h after beginning the intervention (P=0.111) and 97h after beginning the intervention to the time of hospitalization for the spontaneous initiation of labor (P=0.897). There were no significant differences in the secondary outcomes between the groups. According to the finding of this study, it seems that acupressure treatment was not effective in initiating labor as compared with the sham acupressure and the routine care groups. Copyright © 2016 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Costo- Efectividad Del Uso Profiláctico Del Factor Estimulante De Colonias De Granulocitos En Adultos Con Leucemia Linfoblástica Aguda en Colombia.

PubMed

Casadiego Rincón, Elkin Javier; Díaz Rojas, Jorge Augusto; Bermúdez, Carlos Daniel; Martínez, Víctor Prieto

2016-12-01

To assess the cost-effectiveness of prophylactic administration of Granulocyte Colony-Stimulating Factor (G-CSF) compared with no use of it, during the induction phase of chemotherapy in Adults with Acute Lymphoblastic Leukemia (ALL) in Colombia. A decision tree with a time horizon of 30 days was built under colombian health system perspective including only direct costs. The costs of procedures and medications were taken from official sources and an institution of national reference of oncology services. The safety and effectiveness data were taken from the literature and two Colombian cohorts with patients older than 15 years. The unit of outcome was the proportion of deaths avoided. Base-case results on a clinical trial indicate that using factor is a dominant strategy. The variable that most impacted the outcome was the incidence of febrile neutropenia. Considering a threshold of $22.228 USD in 80% of cases using factor was cost effective. However, the use of factor is not cost-effective for the country for incidences of febrile neutropenia > 48%. It was not possible to establish cost-effectiveness of pegfilgrastim because no information was found. As per Colombian data, the use of prophylactic factor under chemotherapeutic induction in adults with ALL, turns out to be not cost effective. The difference in the results suggests the need of a careful extrapolation of information from clinical trials (ideal world) for developing economic evaluations in Colombia. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

ATG-Fresenius or daclizumab induction therapy in immunologically high risk kidney recipients: a prospective randomized pilot trial.

PubMed

Kim, Min Jeong; Tsinalis, Dimitrios; Franz, Stefan; Binet, Isabelle; Gürke, Lorenz; Mihatsch, Michael J; Steiger, Jürg; Thiel, Gilbert; Dickenmann, Michael

2008-01-01

Despite all the advantages in the immunosuppressive therapy, kidney transplantation in immunologically high risk patients remains a challenge. Ideally, an induction therapy should provide maximal graft protection, while adverse events rate and costs remain as low as possible. Immunologically high risk kidney recipients with CDC-PRA ł 25% within the last 3 years, a positive B-cell CDC-crossmatch or graft loss due to rejection within 3 years following a prior transplantation, were randomized 1:1 to receive ATG-Fresenius (ATG-F) (9 mg/kg day 0; 3 mg/kg day 1-4) or Daclizumab therapy (1 mg/kg day 0, 14, 28, 42, 56) in a pilot study. Additional immunosuppression consisted of cyclosporine, mycophenolate mofetil, and steroids. 11 patients were included in each group. The patient (90% in ATG-F; 100% in Daclizumab) and graft survival (censored for death) (100% in ATG-F; 90% in Daclizumab) and the mean creatinine concentration at 24 months (139+/-68 mol/l in ATG-F; 176+/-103 mol/l in Daclizumab) were similar in both groups. More severe graft rejections (3 vascular rejections in Daclizumab) and adverse events (5.3/patient in ATG-F; 6.7/patient in Daclizumab) were observed in the Daclizumab group. The costs for hospitalization/ day within 24 months were lower in ATG-F (2.32+/-3.51 USD vs. 12.25+/-9.75 USD; p=0.02) resulting in an average cost-difference of more than 10'435 USD /patient. In this pilot trial, both treatments were comparably successful regarding graft and patient outcome.

Long-Term Outcomes Among Patients Who Achieve Complete or Near-Complete Responses After the Induction Phase of Bladder-Preserving Combined-Modality Therapy for Muscle-Invasive Bladder Cancer: A Pooled Analysis of NRG Oncology/RTOG 9906 and 0233

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

Mitin, Timur, E-mail: mitin@ohsu.edu; George, Asha; Zietman, Anthony L.

Purpose: To investigate the differences in outcomes among patients with muscle-invasive bladder cancer on NRG Oncology Radiation Therapy Oncology Group protocols 9906 and 0233 who achieved complete response and near-complete response after induction chemoradiation and then completed bladder-preserving therapy with chemoradiation therapy (chemo-RT) to full dose (60-64 Gy). Patients and Methods: A pooled analysis was performed on 119 eligible patients with muscle-invasive bladder cancer enrolled on NRG Oncology Radiation Therapy Oncology Group trials 9906 and 0233, who were classified as having a complete (T0) or near-complete (Ta or Tis) response after induction chemo-RT and completed consolidation with a total RT dose ofmore » at least 60 Gy. Bladder recurrence, salvage cystectomy rates, and disease-specific survival were estimated by the cumulative incidence method and bladder-intact and overall survivals by the Kaplan-Meier method. Results: Among the 119 eligible patients, 101 (85%) achieved T0, and 18 (15%) achieved Ta or Tis after induction chemo-RT and proceeded to consolidation. After a median follow-up of 5.9 years, 36 of 101 T0 patients (36%) versus 5 of 18 Ta or Tis patients (28%) experienced bladder recurrence (P=.52). Thirteen patients among complete responders eventually required late salvage cystectomy for tumor recurrence, compared with 1 patient among near-complete responders (P=.63). Disease-specific, bladder-intact, and overall survivals were not significantly different between T0 and Ta/Tis cases. Conclusions: The bladder recurrence and salvage cystectomy rates of the complete and the near-complete responders were similar. Therefore it is reasonable to recommend that patients with Ta or Tis after induction chemo-RT continue with bladder-sparing therapy with consolidation chemo-RT to full dose (60-64 Gy).« less

Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial

PubMed Central

Clifton, Guy L; Valadka, Alex; Zygun, David; Coffey, Christopher S; Drever, Pamala; Fourwinds, Sierra; Janis, L Scott; Wilde, Elizabeth; Taylor, Pauline; Harshman, Kathy; Conley, Adam; Puccio, Ava; Levin, Harvey S; McCauley, Stephen R; Bucholz, Richard D; Smith, Kenneth R; Schmidt, John H; Scott, James N; Yonas, Howard; Okonkwo, David O

2013-01-01

Summary Background The inconsistent effect of hypothermia treatment on severe brain injury in previous trials might be because hypothermia was induced too late after injury. We aimed to assess whether very early induction of hypothermia improves outcome in patients with severe brain injury. Methods The National Acute Brain Injury Study: Hypothermia II (NABIS: H II) was a randomised, multicentre clinical trial of patients with severe brain injury who were enrolled within 2·5 h of injury at six sites in the USA and Canada. Patients with non-penetrating brain injury who were 16–45 years old and were not responsive to instructions were randomly assigned (1:1) by a random number generator to hypothermia or normothermia. Patients randomly assigned to hypothermia were cooled to 35°C until their trauma assessment was completed. Patients who had none of a second set of exclusion criteria were either cooled to 33°C for 48 h and then gradually rewarmed or treated at normothermia, depending upon their initial treatment assignment. Investigators who assessed the outcome measures were masked to treatment allocation. The primary outcome was the Glasgow outcome scale score at 6 months. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, NCT00178711. Findings Enrolment occurred from December, 2005, to June, 2009, when the trial was terminated for futility. Follow-up was from June, 2006, to December, 2009. 232 patients were initially randomised a mean of 1·6 h (SD 0·5) after injury: 119 to hypothermia and 113 to normothermia. 97 patients (52 in the hypothermia group and 45 in the normothermia group) did not meet any of the second set of exclusion criteria. The mean time to 35°C for the 52 patients in the hypothermia group was 2·6 h (SD 1·2) and to 33°C was 4·4 h (1·5). Outcome was poor (severe disability, vegetative state, or death) in 31 of 52 patients in the hypothermia group and 25 of 56 in the normothermia group (relative risk [RR] 1·08, 95% CI 0·76–1·53; p=0·67). 12 patients in the hypothermia group died compared with eight in the normothermia group (RR 1·30, 95% CI 0·58–2·52; p=0·52). Interpretation This trial did not confirm the utility of hypothermia as a primary neuroprotective strategy in patients with severe traumatic brain injury. Funding National Institute of Neurological Disorders and Stroke. PMID:21169065

Extended release naltrexone injection is performed in the majority of opioid dependent patients receiving outpatient induction: a very low dose naltrexone and buprenorphine open label trial.

PubMed

Mannelli, Paolo; Wu, Li-Tzy; Peindl, Kathleen S; Swartz, Marvin S; Woody, George E

2014-05-01

The approval of extended release injectable naltrexone (XR-NTX; Vivitrol(®)) has introduced a new option for treating opioid addiction, but studies are needed to identify its place within the spectrum of available therapies. The absence of physiological opioid dependence is a necessary and challenging first step for starting XR-NTX. Outpatient detoxification gives poor results and inpatient detoxification is either unavailable or too brief for the physiological effects of opioids to resolve. Here we present findings from an open label study that tested whether the transition from opioid addiction to XR-NTX can be safely and effectively performed in an outpatient setting using very low dose naltrexone and buprenorphine. Twenty treatment seeking opioid addicted individuals were given increasing doses of naltrexone starting at 0.25mg with decreasing doses of buprenorphine starting at 4 mg during a 7-day outpatient XR-NTX induction procedure. Withdrawal discomfort, craving, drug use, and adverse events were assessed daily until the XR-NTX injection, then weekly over the next month. Fourteen of the 20 participants received XR-NTX and 13 completed weekly assessments. Withdrawal, craving, and opioid or other drug use were significantly lower during induction and after XR-NTX administration compared with baseline, and no serious adverse events were recorded. Outpatient transition to XR-NTX combining upward titration of very low dose naltrexone with downward titration of low dose buprenorphine was safe, well tolerated, and completed by most participants. Further studies with larger numbers of subjects are needed to see if this approach is useful for naltrexone induction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Assessing renal function with daclizumab induction and delayed tacrolimus introduction in liver transplant recipients.

PubMed

Calmus, Yvon; Kamar, Nassim; Gugenheim, Jean; Duvoux, Christophe; Ducerf, Christian; Wolf, Philippe; Samuel, Didier; Vanlemmens, Claire; Neau-Cransac, Martine; Salamé, Ephrem; Chazouillères, Olivier; Declerck, Nicole; Pageaux, Georges-Philippe; Dubel, Laurence; Rostaing, Lionel

2010-06-27

Calcineurin inhibitor-induced renal dysfunction is a major problem in liver transplantation. Interleukin-2 receptor antagonist induction followed by delayed tacrolimus (Tac) administration may minimize the renal insult without compromising immunoprotection. This open, randomized, multicenter trial evaluated the benefit of daclizumab induction with delayed Tac on renal function at 6 months; an observational study was continued for 18 months. Liver transplant patients with a 12-hr serum creatinine (SrC) level less than 180 micromol/L received either delayed Tac with daclizumab induction (n=98) or standard Tac (n=101) both combined with mycophenolate mofetil and steroids. The primary endpoint was the incidence of SrC level more than 130 micrommol/L at 6 months. The incidence was 22.4% with delayed Tac and 29.7% with standard Tac (P=ns), which remained unchanged at 12 months (21.6% and 23.9%) but increasing slightly at 24 months (29.0% and 32.9%), respectively. A post hoc analysis of renal function was done based on patients stratification by SrC at 12 hr (100 micromol/L) showing no difference in SrC values at 6 months regardless of the 12-hr values despite a trend toward better estimated glomerular filtration rate for patients with 12-hr value less than 100 micromol/L in the delayed Tac group. Biopsy-proven acute rejection was similar at 6 months (17.5% and 18.75%), 12 months (23.5% and 23.8%), and 24 months (24.5% and 25.7%), respectively. Patient and graft survival in both groups were comparable and good. Similar types and incidences of adverse events were reported in both groups at all time. Delay of Tac does not benefit renal function in liver transplant recipients with a good renal function at baseline.

Long-term follow-up of laparoscopic electrocautery of the ovaries versus ovulation induction with recombinant FSH in clomiphene citrate-resistant women with polycystic ovary syndrome: an economic evaluation.

PubMed

Nahuis, M J; Oude Lohuis, E; Kose, N; Bayram, N; Hompes, P; Oosterhuis, G J E; Kaaijk, E M; Cohlen, B J; Bossuyt, P P M; van der Veen, F; Mol, B W; van Wely, M

2012-12-01

Laparoscopic electrocautery of the ovaries and ovulation induction with gonadotrophins are both second line treatments for women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). Long-term follow-up after electrocautery versus ovulation induction with gonadotrophins has demonstrated at least comparable chances for a first live born child with a reduced need for ovulation induction or assisted reproduction treatment and increased chances for a second live born child. In this study, we report on the long-term economic consequences of both treatment modalities. Between February 1998 and October 2001, we performed a multi-centre randomized controlled trial (RCT) comparing a strategy of laparoscopic electrocautery of the ovaries, followed by clomiphene citrate and gonadotrophins when anovulation persisted, and a strategy of ovulation induction with gonadotrophins in women with clomiphene citrate-resistant PCOS. Eight to twelve years after randomization we performed a follow-up study on reproductive outcome in these women and the fertility treatments they had needed including data on direct medical costs of pregnancy and delivery. Clinical data included number of treatment cycles, live births, miscarriages, ectopic pregnancies and multiple pregnancies. We calculated mean costs per woman after randomization until the first live birth. Confidence intervals (CIs) were estimated by bootstrapping. We obtained data for an economic analysis on 159 of the 168 randomized women (95%). In total, 71 of 83 women (86%) allocated to the electrocautery strategy and 69 of 85 women (81%) allocated to the gonadotrophin strategy had at least one live birth. Given the equivalence between the two treatment strategies in terms of a first live birth-the primary outcome measure-our analysis focused on the cost difference between the two strategies within a mean follow-up time of 8-12 years. The mean costs per first live birth after randomization were €11 176 (95% CI: €9689-€12 549) for the electrocautery group and €14 423 (95% CI: €12 239-€16 606) for the recombinant FSH group, resulting in significantly lower costs (P < 0.05) per first live birth for women allocated to the electrocautery group (mean difference €3247; 95% CI: €650-€5814). In women with clomiphene-resistant PCOS, laparoscopic electrocautery of the ovaries results in significantly lower costs per live birth than ovulation induction with gonadotrophins for an at least equal effectiveness.

Double-blind randomized controlled trial of letrozole versus clomiphene citrate in subfertile women with polycystic ovarian syndrome.

PubMed

Amer, S A; Smith, J; Mahran, A; Fox, P; Fakis, A

2017-08-01

Would letrozole as a primary ovulation induction agent generate better pregnancy rates than clomiphene citrate (CC) in subfertile women with anovulatory polycystic ovarian syndrome (PCOS)? Participants receiving letrozole as a primary treatment achieved a significantly (P = 0.022) higher clinical pregnancy rate per patient (61.2%) compared to CC (43.0%). According to a recent Cochrane systematic review (2014), letrozole appears to improve live-birth (LB) and pregnancy rates in anovulatory women with PCOS, compared to CC. However, the review concluded that the quality of evidence was low due to poor reporting of study methods and possible publication bias. This double-blind randomized controlled trial (RCT) included 159 participants between April 2007 and June 2014. Subjects were randomly allocated to either CC (n = 79) or letrozole (n = 80) in a 1:1 ratio. Both drugs were encapsulated to look identical. Randomization was performed in mixed blocks and stratified by patients' BMI (<30 and 30-35 kg/m2). The trial included subfertile women diagnosed with PCOS. Treatment started with one tablet (CC 50 mg, letrozole 2.5 mg) increasing to two in non-responders and continuing until pregnancy or for up to six ovulatory cycles. Non-responders were crossed over to the other treatment after a 6-week break. Cycles were initially monitored with ultrasound follicle tracking then mid-luteal serum progesterone measurement in subsequent cycles. Amongst the 159 participants included in the intention-to-treat analysis, four women conceived before treatment and six were lost-to-follow-up. The remaining 149 participants (74 on CC and 75 on letrozole) completed at least the first treatment. Women receiving letrozole achieved a significantly (P = 0.022; absolute difference [95% confidence interval] 18% [3-33%]) higher pregnancy rate (61.%) than those on CC (43%). The median number of treatment cycles received until pregnancy was significantly (log rank P = 0.038) smaller with letrozole (4[3-5] cycles) compared to CC (6[4-7] cycles). LB rates were not statistically (P = 0.089) different between the two groups, although there was a trend towards higher rates on letrozole (48.8%) compared to CC (35.4%). After the crossover, pregnancy and LB rates on letrozole (n = 45; 28.9 and 24.4%, respectively) were not statistically (P = 0.539 and P = 0.601) different from CC (n = 31; 22.6 and 19.4%). One possible limitation of this trial may be the exclusion of PCOS women with BMI > 35 kg/m2, which would limit the applicability of the results in this subgroup of PCOS. However, this group of women are generally excluded from treatment in the majority of fertility centres, especially in Europe, due to the associated challenges and risks. The results of this trial are consistent with the recent Cochrane systematic review. However, with its robust design, the current RCT provides more valid and compelling evidence for the superiority of letrozole over CC as a primary ovulation induction agent in PCOS women with 40% increase in pregnancy rates and with a shorter time-to-pregnancy. Furthermore, the participants in this RCT are a good representation of subfertile PCOS population receiving fertility treatment in Europe and worldwide. The results are therefore globally generalizable for clinical practice. This RCT was mainly funded by the R&D Funding Scheme of Derby Hospitals NHS Foundation Trust. The study also received funds from School of Medicine, University of Nottingham. The Trust R&D department was involved in the development of the protocol and the running of the trial. The trial was sponsored and monitored by the University of Nottingham. The authors have no conflicts of interest. www.Clinicaltrials.gov: NCT00478504. Registration was verified on 23/05/2007. 25/04/2007. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer.

PubMed

Cohen, Ezra E W; Karrison, Theodore G; Kocherginsky, Masha; Mueller, Jeffrey; Egan, Robyn; Huang, Chao H; Brockstein, Bruce E; Agulnik, Mark B; Mittal, Bharat B; Yunus, Furhan; Samant, Sandeep; Raez, Luis E; Mehra, Ranee; Kumar, Priya; Ondrey, Frank; Marchand, Patrice; Braegas, Bettina; Seiwert, Tanguy Y; Villaflor, Victoria M; Haraf, Daniel J; Vokes, Everett E

2014-09-01

Induction chemotherapy (IC) before radiotherapy lowers distant failure (DF) rates in locally advanced squamous cell carcinoma of the head and neck (SCCHN). The goal of this phase III trial was to determine whether IC before chemoradiotherapy (CRT) further improves survival compared with CRT alone in patients with N2 or N3 disease. Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm; docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week) versus two 21-day cycles of IC (docetaxel 75 mg/m(2) on day 1, cisplatin 75 mg/m(2) on day 1, and fluorouracil 750 mg/m(2) on days 1 to 5) followed by the same CRT regimen (IC + CRT arm). The primary end point was overall survival (OS). Secondary end points included DF-free survival, failure pattern, and recurrence-free survival (RFS). A total of 285 patients were randomly assigned. The most common grade 3 to 4 toxicities during IC were febrile neutropenia (11%) and mucositis (9%); during CRT (both arms combined), they were mucositis (49%), dermatitis (21%), and leukopenia (18%). Serious adverse events were more common in the IC arm (47% v 28%; P = .002). With a minimum follow-up of 30 months, there were no statistically significant differences in OS (hazard ratio, 0.91; 95% CI, 0.59 to 1.41), RFS, or DF-free survival. IC did not translate into improved OS compared with CRT alone. However, the study was underpowered because it did not meet the planned accrual target, and OS was higher than predicted in both arms. IC cannot be recommended routinely in patients with N2 or N3 locally advanced SCCHN. © 2014 by American Society of Clinical Oncology.

Phase III Randomized Trial of Induction Chemotherapy in Patients With N2 or N3 Locally Advanced Head and Neck Cancer

PubMed Central

Cohen, Ezra E.W.; Karrison, Theodore G.; Kocherginsky, Masha; Mueller, Jeffrey; Egan, Robyn; Huang, Chao H.; Brockstein, Bruce E.; Agulnik, Mark B.; Mittal, Bharat B.; Yunus, Furhan; Samant, Sandeep; Raez, Luis E.; Mehra, Ranee; Kumar, Priya; Ondrey, Frank; Marchand, Patrice; Braegas, Bettina; Seiwert, Tanguy Y.; Villaflor, Victoria M.; Haraf, Daniel J.; Vokes, Everett E.

2014-01-01

Purpose Induction chemotherapy (IC) before radiotherapy lowers distant failure (DF) rates in locally advanced squamous cell carcinoma of the head and neck (SCCHN). The goal of this phase III trial was to determine whether IC before chemoradiotherapy (CRT) further improves survival compared with CRT alone in patients with N2 or N3 disease. Patients and Methods Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm; docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week) versus two 21-day cycles of IC (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2 on days 1 to 5) followed by the same CRT regimen (IC + CRT arm). The primary end point was overall survival (OS). Secondary end points included DF-free survival, failure pattern, and recurrence-free survival (RFS). Results A total of 285 patients were randomly assigned. The most common grade 3 to 4 toxicities during IC were febrile neutropenia (11%) and mucositis (9%); during CRT (both arms combined), they were mucositis (49%), dermatitis (21%), and leukopenia (18%). Serious adverse events were more common in the IC arm (47% v 28%; P = .002). With a minimum follow-up of 30 months, there were no statistically significant differences in OS (hazard ratio, 0.91; 95% CI, 0.59 to 1.41), RFS, or DF-free survival. Conclusion IC did not translate into improved OS compared with CRT alone. However, the study was underpowered because it did not meet the planned accrual target, and OS was higher than predicted in both arms. IC cannot be recommended routinely in patients with N2 or N3 locally advanced SCCHN. PMID:25049329

miR-21 expression and clinical outcome in locally advanced pancreatic cancer: exploratory analysis of the pancreatic cancer Erbitux, radiotherapy and UFT (PERU) trial

PubMed Central

Khan, Khurum; Cunningham, David; Peckitt, Clare; Barton, Sarah; Tait, Diana; Hawkins, Maria; Watkins, David; Starling, Naureen; Rao, Sheela; Begum, Ruwaida; Thomas, Janet; Oates, Jacqui; Guzzardo, Vincenza; Fassan, Matteo; Braconi, Chiara; Chau, Ian

2016-01-01

Background Locally advanced pancreatic cancer (LAPC) is associated with high mortality, and biomarker-driven treatment approach is currently lacking. This study evaluated safety and efficacy of a combination approach of chemotherapy followed by chemo-radiotherapy (CRT) +/− cetuximab, and the prognostic role of miR-21 in patients with LAPC treated with a multimodality approach. Patients and Methods This was a randomised phase II trial in which patients with inoperable LAPC were offered gemcitabine and capecitabine (GEM-CAP) for 16 weeks. Patients with stable disease or response after GEM-CAP were randomised to capecitabine or UFT plus radiotherapy (RT) (A), or capecitabine or UFT plus cetuximab plus RT (B). The primary outcome of the study was overall survival (OS). Clinical outcome was compared according to baseline circulating miR-21 levels. Results 17 patients were enrolled and treated with GEM-CAP, with 13 patients achieving disease control and being randomised to arms A (n:7) and B (n:6). After a median follow-up of 61.2 months, median progression free survival (PFS) was 10.4 months and 12.7 months, median OS was 15.8 months and 22.0 months in arms A and B respectively (p > 0.05). Patients with high baseline plasma miR-21 had worse PFS (3.5 vs. 12.7 months; p:0.032) and OS (5.1 vs 15.3 months; p:0.5) compared to patients with low miR-21. Circulating miR-21 levels reflected miR-21 expression within the tissues. Conclusions Addition of Cetuximab to CRT following induction chemotherapy did not improve survival. High miR-21 baseline plasma expression was associated with poor clinical outcome in LAPC patients treated with induction chemotherapy followed by chemo-radiotherapy. PMID:26862857

Comparative study of labour induced by oral prostaglandin E2 and intravenous syntocinon.

PubMed

Murray, C P; Clinch, J

1975-03-22

The use of prostaglandin E2 for the induction of labor with intact membranes is described and its effectiveness is compared to intravenous syntocinon. 40 primigravida and 60 multigravid patients with previous medical and obstetrical histories were studied. The patients were numbered as they entered the trial, with the odd numbers in each group being given oral prostaglandin and the even numbers intravenous syntocinon. In no case was the pregnancy less than 38 weeks maturity. No patient was in labor prior to being given either drug. Prostaglandin E2 (PGE2) was supplied in ampoules containing 5 milligrams in 0.5 milliliter of ethanol. This was added to 49.5 milliliters of sterile water to produce a concentration of the drug of 0.1 milligrams per ml. The syntocinon infusion was prepared by putting 20 units of syntocinon into 1 liter of 5% dextrose in water to produce a solution concentration of 20 mu/ml. The accepted criteria for diagnosing established labor for both groups of patients was the presence of uterine contractions occurring once every 3 minutes, associated with progressive dilatation of the cervix. For both groups of patients it was decided that cervical dilatation should be at least 6 cm within 18 hours of the infusion starting. Using this criterion there was only 1 failure, occurring in the 1st primigravid patient given PGE2, the labor in this instance being completed with intravenous syntocinon. A further 8 patients failed to complete the trial as they had to be delivered by cesarian section. Syntocin was considerably more efficient than PGE2 in inducing labor in the remaining 91 patients particularly in primigravida. This was the case whether judged by the length of labor or by the induction delivery interval. Toco-dynamometric studies showed that the contractions produced by prostaglandin more closely resembled those of normal labor and were less painful.

Delivery outcome after trial of labor in nulliparous women over 40 years of age - a population-based study.

PubMed

Ankarcrona, Victoria; Altman, Daniel; Wikström, Anna-Karin; Jacobsson, Bo; Brismar Wendel, Sophia

2018-05-17

An increasing proportion of nulliparous women are over 40 years and labor is more often induced. The aim of this study was to assess delivery outcome in women over 40 years, accounting for the interaction between age and induction. Population-based study of 1 644 598 nulliparous women with live singleton cephalic term deliveries 1992 to 2011. Risks of intrapartum cesarean section, operative vaginal delivery, obstetric anal sphincter injury (OASIS), and 5-minutes Apgar score <7 were calculated in women ≥40 years with induced or spontaneous labor, and women <40 years with induced labor by unconditional logistic regression, and presented with crude and adjusted odds ratios (aOR) with 95% confidence intervals (95%CI). Women <40 years with spontaneous labor were used as reference. Intrapartum cesarean section was performed in 19.2% (aOR 3.14, 95%CI 2.94-3.35) of women ≥40 years with induced labor, 7.3% (aOR 1.51, 95%CI 1.44-1.58) with spontaneous labor, and 15.6% (aOR 2.48, 95%CI 2.43-2.53) of induced women <40 years, compared to 4.4% in the reference group. Operative vaginal delivery occurred in 9.8% (aOR 1.05, 95%CI 0.96-1.14) of women ≥40 years with induced labor and in 7.3% (aOR 0.94, 95%CI 0.90-0.99) with spontaneous labor. Obstetric anal sphincter injury was not increased in women ≥40 years. Apgar <7 at 5 minutes was similar in all groups. Trial of labor was successful in most women ≥40 years, even after induction of labor. Intrapartum cesarean section was more common compared to women <40, while operative vaginal delivery, obstetric anal sphincter injury, and low Apgar was not. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Double-blind randomized controlled trial of letrozole versus clomiphene citrate in subfertile women with polycystic ovarian syndrome

PubMed Central

Smith, J.; Mahran, A.; Fox, P.; Fakis, A.

2017-01-01

Abstract STUDY QUESTION Would letrozole as a primary ovulation induction agent generate better pregnancy rates than clomiphene citrate (CC) in subfertile women with anovulatory polycystic ovarian syndrome (PCOS)? SUMMARY ANSWER Participants receiving letrozole as a primary treatment achieved a significantly (P = 0.022) higher clinical pregnancy rate per patient (61.2%) compared to CC (43.0%). WHAT IS KNOWN ALREADY According to a recent Cochrane systematic review (2014), letrozole appears to improve live-birth (LB) and pregnancy rates in anovulatory women with PCOS, compared to CC. However, the review concluded that the quality of evidence was low due to poor reporting of study methods and possible publication bias. STUDY DESIGN, SIZE, DURATION This double-blind randomized controlled trial (RCT) included 159 participants between April 2007 and June 2014. Subjects were randomly allocated to either CC (n = 79) or letrozole (n = 80) in a 1:1 ratio. Both drugs were encapsulated to look identical. Randomization was performed in mixed blocks and stratified by patients’ BMI (<30 and 30–35 kg/m2). PARTICIPANTS/MATERIALS, SETTING, METHODS The trial included subfertile women diagnosed with PCOS. Treatment started with one tablet (CC 50 mg, letrozole 2.5 mg) increasing to two in non-responders and continuing until pregnancy or for up to six ovulatory cycles. Non-responders were crossed over to the other treatment after a 6-week break. Cycles were initially monitored with ultrasound follicle tracking then mid-luteal serum progesterone measurement in subsequent cycles. MAIN RESULTS AND THE ROLE OF CHANCE Amongst the 159 participants included in the intention-to-treat analysis, four women conceived before treatment and six were lost-to-follow-up. The remaining 149 participants (74 on CC and 75 on letrozole) completed at least the first treatment. Women receiving letrozole achieved a significantly (P = 0.022; absolute difference [95% confidence interval] 18% [3–33%]) higher pregnancy rate (61.%) than those on CC (43%). The median number of treatment cycles received until pregnancy was significantly (log rank P = 0.038) smaller with letrozole (4[3–5] cycles) compared to CC (6[4–7] cycles). LB rates were not statistically (P = 0.089) different between the two groups, although there was a trend towards higher rates on letrozole (48.8%) compared to CC (35.4%). After the crossover, pregnancy and LB rates on letrozole (n = 45; 28.9 and 24.4%, respectively) were not statistically (P = 0.539 and P = 0.601) different from CC (n = 31; 22.6 and 19.4%). LIMITATIONS, REASONS FOR CAUTION One possible limitation of this trial may be the exclusion of PCOS women with BMI > 35 kg/m2, which would limit the applicability of the results in this subgroup of PCOS. However, this group of women are generally excluded from treatment in the majority of fertility centres, especially in Europe, due to the associated challenges and risks. WIDER IMPLICATIONS OF THE FINDINGS The results of this trial are consistent with the recent Cochrane systematic review. However, with its robust design, the current RCT provides more valid and compelling evidence for the superiority of letrozole over CC as a primary ovulation induction agent in PCOS women with 40% increase in pregnancy rates and with a shorter time-to-pregnancy. Furthermore, the participants in this RCT are a good representation of subfertile PCOS population receiving fertility treatment in Europe and worldwide. The results are therefore globally generalizable for clinical practice. STUDY FUNDING/COMPETING INTEREST(S) This RCT was mainly funded by the R&D Funding Scheme of Derby Hospitals NHS Foundation Trust. The study also received funds from School of Medicine, University of Nottingham. The Trust R&D department was involved in the development of the protocol and the running of the trial. The trial was sponsored and monitored by the University of Nottingham. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER www.Clinicaltrials.gov: NCT00478504. TRIAL REGISTRATION DATE Registration was verified on 23/05/2007. DATE OF FIRST PATIENT'S ENROLMENT 25/04/2007. PMID:28854590

TRIBE-2: a phase III, randomized, open-label, strategy trial in unresectable metastatic colorectal cancer patients by the GONO group.

PubMed

Cremolini, Chiara; Marmorino, Federica; Loupakis, Fotios; Masi, Gianluca; Antoniotti, Carlotta; Salvatore, Lisa; Schirripa, Marta; Boni, Luca; Zagonel, Vittorina; Lonardi, Sara; Aprile, Giuseppe; Tamburini, Emiliano; Ricci, Vincenzo; Ronzoni, Monica; Pietrantonio, Filippo; Valsuani, Chiara; Tomasello, Gianluca; Passardi, Alessandro; Allegrini, Giacomo; Di Donato, Samantha; Santini, Daniele; Falcone, Alfredo

2017-06-09

Chemotherapy plus bevacizumab is a standard first-line treatment for unresectable metastatic colorectal cancer patients. Different chemotherapy backbones may be chosen, including one to three drugs, based on patients' general conditions and comorbidities, treatments' objectives, and disease characteristics. TRIBE trial demonstrated a significant advantage in terms of progression-free survival and overall survival for FOLFOXIRI plus bevacizumab as compared with FOLFIRI plus bevacizumab. Based on recent evidence, the de-intensification of the upfront regimen after 4-6 months of treatment is nowadays regarded as a valuable option. Moreover, the prolonged inhibition of angiogenesis, and in particular the continuation of bevacizumab beyond the evidence of disease progression, is an efficacious strategy in the treatment of metastatic colorectal cancer patients. TRIBE-2 is a prospective, open-label, multicentric phase III randomized trial in which unresectable and previously untreated metastatic colorectal cancer patients are randomized to receive first-line FOLFOX plus bevacizumab followed by FOLFIRI plus bevacizumab after disease progression or FOLFOXIRI plus bevacizumab followed by the re-introduction of the same regimen after disease progression. The primary endpoint is to compare the efficacy of the two proposed treatment strategies in terms of Progression Free Survival 2. The TRIBE-2 study aims at answering the question whether the upfront use of FOLFOXIRI improves the clinical outcome of metastatic colorectal cancer patients, when compared with the pre-planned, sequential use of oxaliplatin-based and irinotecan-based doublets. Both proposed treatment strategies are designed to exploit the effectiveness of the prolonged inhibition of angiogenesis, alternating short (up to 4 months) induction periods and less intensive maintenance phases. TRIBE2 is registered at Clinicaltrials.gov: NCT02339116 . January 12, 2015. TRIBE-2 is registered at EUDRACT 2014-004436-19, October 10, 2014.

Immunomodulatory drugs and the risk of serious infection in multiple myeloma: systematic review and meta-analysis of randomized and observational studies.

PubMed

Chen, Min; Zhao, Yongfeng; Xu, Chuanxin; Wang, Xian; Zhang, Xianping; Mao, Benyu

2018-06-01

The effect of immunomodulatory drugs (IMiDs) on serious infection remains uncertain. We therefore conducted a systematic review and meta-analysis to assess the possible impact of IMiDs on serious infection in patients with multiple myeloma (MM). We searched randomized controlled trials (RCTs) and observational studies from databases that addressed the effect of IMiDs on serious infection in patients with MM. We pooled data from RCTs and observational studies separately and used the GRADE approach to rate the quality of evidence. Rates in patients with individual IMiDs at different treatment status ranged from 7.00 to 23.00%. The use of thalidomide- or lenalidomide-based regimen induction therapy for autologous stem cell transplantation (ASCT)-ineligible patients suggests increase in serious infection (RR = 1.59, 95% CI 1.31-1.93, p < 0.01). Compared to conventional therapy, IMiDs' induction in ASCT-eligible patients significantly decreases the risk of serious infection (RR = 0.82, 95% CI 0.72-0.94, p < 0.01). Lenalidomide-based therapy was associated with a significant increase in risk of serious infection in patients treated compared with conventional therapy (RR = 2.45, 95% CI 1.57-3.83, p < 0.01). The current evidence suggests that patients with MM treated with IMiDs are at a high risk of serious infection.

Near-Infrared Spectroscopy in Adult Cardiac Surgery Patients: A Systematic Review and Meta-Analysis.

PubMed

Chan, Matthew J; Chung, Tricia; Glassford, Neil J; Bellomo, Rinaldo

2017-08-01

To identify the normal baseline preoperative range of cerebral tissue oxygen saturation (SctO 2 ) derived using near-infrared spectroscopy (NIRS) and the efficacy of perioperative interventions designed to modulate SctO 2 in cardiac surgical patients. Systematic review and meta-analysis of relevant randomized controlled trials (RCTs) extracted from the Medline, Embase, and Cochrane Central Register of Controlled Trials databases. Hospitals performing cardiac surgery. The study comprised 953 participants from 11 RCTs. Interventions included the following: (1) SctO 2 monitoring protocol compared with no monitoring; (2) use of cardiopulmonary bypass (CPB) compared with no CPB; (3) normothermic CPB compared with hypothermic CPB; (4) glyceryl trinitrate during surgery compared with placebo; (5) midazolam during induction of anesthesia compared with propofol; (6) sevoflurane anesthesia compared with total intravenous anesthesia; (7) sevoflurane anesthesia compared with propofol-based anesthesia; and (8) norepinephrine during CPB compared with phenylephrine. Eleven RCTs with 953 participants measured baseline preoperative SctO 2 using NIRS. The pooled mean baseline SctO 2 was 66.4% (95% CI 65.0-67.7), generating a reference range of 51.0% to 81.8%. Four interventions (1, 3, 4, and 6 described in the Interventions section above) increased intraoperative SctO 2 across the majority of reported time points. Postoperative follow-up of SctO 2 occurred in only 1 study, and postoperative cognitive assessment correlating SctO 2 with cognitive function was applied in only 4 studies using variable methodology. The authors have established that reference values for baseline NIRS-derived SctO 2 in cardiac surgery patients are varied and have identified interventions that modulate SctO 2 . This information opens the door to standardized research and interventional studies in this field. Copyright © 2017. Published by Elsevier Inc.

Cetuximab Combined With Induction Oxaliplatin and Capecitabine, Followed by Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer: SWOG 0713.

PubMed

Leichman, Cynthia Gail; McDonough, Shannon L; Smalley, Stephen R; Billingsley, Kevin G; Lenz, Heinz-Josef; Beldner, Matthew A; Hezel, Aram F; Velasco, Mario R; Guthrie, Katherine A; Blanke, Charles D; Hochster, Howard S

2018-03-01

Neoadjuvant chemoradiation (NCRT) is standard treatment for locally advanced rectal cancer. Pathologic complete response (pCR) has associated with improved survival. In modern phase III trials of NCRT, pCR ranges from 10% to 20%. Cetuximab improves response in KRAS (KRAS proto-oncogene) wild type (wt) metastatic colorectal cancer. S0713 was designed to assess improvement in pCR with additional use of cetuximab with induction chemotherapy and NCRT for locally advanced, KRAS-wt rectal cancer. Patient eligibility: stage II to III biopsy-proven, KRAS-wt rectal adenocarcinoma; no bowel obstruction; adequate hematologic, hepatic and renal function; performance status of 0 to 2. Target enrollment: 80 patients. induction chemotherapy with wCAPOX (weekly capecitabine and oxaliplatin) and cetuximab followed by the same regimen concurrent with radiation (omitting day 15 oxaliplatin). If fewer than 7 pCRs were observed at planned interim analysis after 40 patients received all therapy, the study would close. Eighty eligible patients would provide 90% power given a true pCR rate > 35% at a significance of 0.04. The regimen would lack future interest if pCR probability was ≤ 20%. Between February 2009 and April 2013, 83 patients registered. Four were ineligible and 4 not treated, leaving 75 evaluable for clinical outcomes and toxicity, of whom 65 had surgery. Of 75 patients, 20 had pCR (27%; 95% confidence interval [CI], 17%-38%); 19 (25%) had microscopic cancer; 36 (48%) had minor/no response (including 10 without surgery). Three-year disease-free survival was 73% (95% CI, 63%-83%). Our trial did not meet the pCR target of 35%. Toxicity was generally acceptable. This regimen cannot be recommended outside the clinical trial setting. Copyright © 2017 Elsevier Inc. All rights reserved.

Cognitive Skill and Traditional Trance Hypnotic Inductions: A Within-Subjects Comparison.

ERIC Educational Resources Information Center

Vickery, Anne R.; And Others

1985-01-01

Compared a traditional trance hypnotic induction and a cognitive skill induction using a within-subjects design with college students (N=40). The skill induction enhanced responses to suggestions and produced marginally significant increments in behavioral responses when preceded by the trance induction, but there were no significant differences…

Decreased invasive fungal disease but no impact on overall survival by posaconazole compared to fluconazole prophylaxis: a retrospective cohort study in patients receiving induction therapy for acute myeloid leukaemia/myelodysplastic syndromes.

PubMed

Dahlén, Torsten; Kalin, Mats; Cederlund, Kerstin; Nordlander, Anna; Björkholm, Magnus; Ljungman, Per; Blennow, Ola

2016-02-01

Posaconazole prophylaxis during induction chemotherapy for acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) has been shown to significantly decrease the incidence of invasive fungal disease (IFD) and increase overall survival in a trial setting, but only small real-life studies have been published. This was a retrospective cohort study including consecutive patients with AML/MDS treated with intensive induction chemotherapy; 176 patients received fluconazole prophylaxis 2008-2011 and 107 patients received posaconazole prophylaxis 2011-2013. Only proven and probable IFD according to the revised EORTC/MSG criteria were included in the analysis. The two cohorts were well matched without significant differences in patient characteristics. At day 100, patients receiving posaconazole had a significantly lower incidence of total IFD (0.9% vs. 10.8%, P < 0.01), invasive aspergillosis (0% vs. 5.7%, P = 0.02) and invasive candidiasis (0% vs. 4.0%, P < 0.05). There was no significant difference in overall survival, neither at day 100 (87% in the posaconazole group vs. 85% in the fluconazole group) nor at end of follow-up (78% vs. 77%). Posaconazole prophylaxis decreased the incidence of IFD but did not improve short-term overall survival. Improved treatment efficacy of manifest IFD is likely to explain the lack of survival benefit. © 2015 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.

Intravenous rocuronium 0.3 mg/kg improves the conditions for tracheal intubation in cats: a randomized, placebo-controlled trial.

PubMed

Sakai, Daniel M; Zornow, Kailee Anne; Campoy, Luis; Cable, Christina; Appel, Leslie D; Putnam, Holly J; Martin-Flores, Manuel

2018-01-01

Objectives We evaluated the use of rocuronium 0.3 mg/kg intravenously (IV) to facilitate tracheal intubation in cats anesthetized for elective ovariohysterectomy. Methods Thirty female cats were randomly allocated to receive rocuronium 0.3 mg/kg IV or an equal volume of normal saline, following induction of anesthesia with ketamine and midazolam. Thirty seconds after induction, a single investigator, unaware of treatment allocation, attempted tracheal intubation. The number of attempts and the time to complete intubation were measured. Intubating conditions were assessed as acceptable or unacceptable based on a composite score consisting of five different components. Duration of apnea after induction was measured and cases of hemoglobin desaturation (SpO 2 <90%) were identified. Results Intubation was completed faster (rocuronium 12 s [range 8-75 s]; saline 60 s [range 9-120 s]) and with fewer attempts (rocuronium 1 [range 1-2]; saline 2 [range 1-3], both P = 0.006) in cats receiving rocuronium. Unacceptable intubating conditions on the first attempt occurred in 3/15 cats with rocuronium and in 10/15 with saline ( P = 0.01). Apnea lasted 4 ± 1.6 mins with rocuronium and 2.3 ± 0.5 mins with saline ( P = 0.0007). No cases of desaturation were observed. Conclusions and relevance Rocuronium 0.3 mg/kg IV improves intubating conditions compared with saline and reduces the time and number of attempts to intubate with only a short period of apnea in cats.

Neurophysiological mechanisms of emotion regulation for subtypes of externalizing children.

PubMed

Stieben, Jim; Lewis, Marc D; Granic, Isabela; Zelazo, Philip David; Segalowitz, Sidney; Pepler, Debra

2007-01-01

Children referred for externalizing behavior problems may not represent a homogeneous population. Our objective was to assess neural mechanisms of emotion regulation that might distinguish subtypes of externalizing children from each other and from their normal age mates. Children with pure externalizing (EXT) problems were compared with children comorbid for externalizing and internalizing (MIXED) problems and with age-matched controls. Only boys were included in the analysis because so few girls were referred for treatment. We used a go/no-go task with a negative emotion induction, and we examined dense-array EEG data together with behavioral measures of performance. We investigated two event-related potential (ERP) components tapping inhibitory control or self-monitoring - the inhibitory N2 and error-related negativity (ERN) - and we constructed source models estimating their cortical generators. The MIXED children's N2s increased in response to the emotion induction, resulting in greater amplitudes than EXT children in the following trial block. ERN amplitudes were greatest for control children and smallest for EXT children with MIXED children in between, but only prior to the emotion induction. These results were paralleled by behavioral differences in response time and performance monitoring. ERP activity was localized to cortical sources suggestive of the dorsal anterior cingulate for control children, posterior cingulate areas for the EXT children, and both posterior cingulate and ventral cingulate/prefrontal regions for the MIXED children. These findings highlight different mechanisms of self-regulation underlying externalizing subtypes and point toward distinct developmental pathways and treatment strategies.

Thiopurines and inflammatory bowel disease: Current evidence and a historical perspective.

PubMed

Axelrad, Jordan E; Roy, Abhik; Lawlor, Garrett; Korelitz, Burton; Lichtiger, Simon

2016-12-14

The use of thiopurines in inflammatory bowel disease (IBD) has been examined in numerous prospective, controlled trials, with a majority demonstrating a clinical benefit. We conducted this review to describe the historical and current evidence in the use of thiopurines in IBD. A systematic search was performed on MEDLINE between 1965 and 2016 to identify studies on thiopurines in IBD. The most robust evidence for thiopurines in IBD includes induction of remission in combination with anti-tumor necrosis factor (anti-TNF) agents, and maintenance of remission and post-operative maintenance in Crohn's disease. Less evidence exists for thiopurine monotherapy in induction of remission, maintenance of ulcerative colitis, chemoprevention of colorectal cancer, and in preventing immunogenicity to anti-TNF. Evidence was often limited by trial design. Overall, thiopurines have demonstrated efficacy in a broad range of presentations of IBD. With more efficacious novel therapeutic agents, the positioning of thiopurines in the management of IBD will change and future studies will analyze the benefit of thiopurines alone and in conjunction with these new medications.

A mixed method pilot study: the researchers' experiences.

PubMed

Secomb, Jacinta M; Smith, Colleen

2011-08-01

This paper reports on the outcomes of a small well designed pilot study. Pilot studies often disseminate limited or statistically meaningless results without adding to the body knowledge on the comparative research benefits. The design a pre-test post-test group parallel randomised control trial and inductive content analysis of focus group transcripts was tested specifically to increase outcomes in a proposed larger study. Strategies are now in place to overcome operational barriers and recruitment difficulties. Links between the qualitative and quantitative arms of the proposed larger study have been made; it is anticipated that this will add depth to the final report. More extensive reporting on the outcomes of pilot studies would assist researchers and increase the body of knowledge in this area.

Biomarkers for Allergen Immunotherapy: A "Panoromic" View.

PubMed

Moingeon, Philippe

2016-02-01

Biomarkers (BMKs) are biological parameters that can be measured to predict or monitor disease severity or treatment efficacy. The induction of regulatory dendritic cells (DCs) concomitantly with a downregulation of proallergic DC2s (ie, DCs supporting the differentiation of T-helper lymphocyte type 2 cells) in the blood of patients allergic to grass pollen has been correlated with the early onset of allergen immunotherapy efficacy. The combined use of omics technologies to compare biological samples from clinical responders and nonresponders is being implemented in the context of nonhypothesis-driven approaches. Such comprehensive "panoromic" strategies help identify completely novel candidate BMKs, to be subsequently validated as companion diagnostics in large-scale clinical trials. Copyright © 2016 Elsevier Inc. All rights reserved.

Battered women who kill: the impact of expert testimony and empathy induction in the courtroom.

PubMed

Plumm, Karyn M; Terrance, Cheryl A

2009-02-01

Mock jurors (N = 312) viewed a simulated trial involving a woman, charged with the murder of her abusive husband, entering a plea of not guilty by reason of self-defense. Expert testimony was varied using battered woman syndrome, social agency framework, or no expert testimony. Within expert testimony conditions, jurors were presented with opening and closing statements either including or not including instructions aimed at inducing empathy. Results indicate differences in gender and expert testimony for ratings of guilt as well as differences in gender, expert testimony, and empathy induction for perceptions of the defendant.

Quantitative structure-activity relationships by neural networks and inductive logic programming. II. The inhibition of dihydrofolate reductase by triazines

NASA Astrophysics Data System (ADS)

Hirst, Jonathan D.; King, Ross D.; Sternberg, Michael J. E.

1994-08-01

One of the largest available data sets for developing a quantitative structure-activity relationship (QSAR) — the inhibition of dihydrofolate reductase (DHFR) by 2,4-diamino-6,6-dimethyl-5-phenyl-dihydrotriazine derivatives — has been used for a sixfold cross-validation trial of neural networks, inductive logic programming (ILP) and linear regression. No statistically significant difference was found between the predictive capabilities of the methods. However, the representation of molecules by attributes, which is integral to the ILP approach, provides understandable rules about drug-receptor interactions.

Effects of fentanyl administration before induction of anesthesia and placement of the Laryngeal Mask Airway: a randomized, placebo-controlled trial.

PubMed

Joshi, Girish P; Kamali, Amin; Meng, Jin; Rosero, Eric; Gasanova, Irina

2014-03-01

To assess the effects of fentanyl administered before induction of anesthesia on movement and airway responses during desflurane anesthesia via the Laryngeal Mask Airway (LMA). Randomized, double-blinded, controlled trial. Tertiary-care academic center. 100 adult, ASA physical status 1, 2, and 3 patients undergoing ambulatory surgery. Patients were administered fentanyl 1 μg/kg (n=51) or saline (n=49) 3 to 5 minutes before induction with propofol 2-2.5 mg/kg intravenously (IV), followed by LMA placement. Anesthesia was maintained with desflurane titrated to a bispectral index (BIS) of 50-60 and 50% nitrous oxide in oxygen, and fentanyl 25 μg boluses were titrated to respiratory rate. Apnea occurrence and duration of manual ventilation, as well as frequency and severity of movement, coughing, breath holding, and laryngospasm were recorded. Two patients in each group were excluded from analysis. The fentanyl pretreatment group had a higher frequency of apnea (94% vs 64%; P=0.0003) and longer duration of manual ventilation (3 [interquartile range (IQR), 1.5-5] min vs 1 [0-1.5] min; P<0.0001) at induction. In contrast, the fentanyl pretreatment group had a lower frequency of movements (16% vs 51%;P=0.0001). The rates of intraoperative breath holding (6.1% vs 8.5%) and laryngospasm (2% vs 4.3%) in the two groups were similar. All subjects experiencing laryngospasm were smokers. Adjusting for smoking status did not affect the differences noted in apnea, duration of manual ventilation, or movement between groups; however, coughing occurrence was statistically higher in the placebo group (P=0.043). Preinduction fentanyl increased the frequency of apnea at induction and duration of manual ventilation, but reduced the frequency of movements. In addition, it reduced intraoperative coughing in smokers. Copyright © 2014 Elsevier Inc. All rights reserved.

NEOSCOPE: A randomised phase II study of induction chemotherapy followed by oxaliplatin/capecitabine or carboplatin/paclitaxel based pre-operative chemoradiation for resectable oesophageal adenocarcinoma.

PubMed

Mukherjee, Somnath; Hurt, Christopher Nicholas; Gwynne, Sarah; Sebag-Montefiore, David; Radhakrishna, Ganesh; Gollins, Simon; Hawkins, Maria; Grabsch, Heike I; Jones, Gareth; Falk, Stephen; Sharma, Ricky; Bateman, Andrew; Roy, Rajarshi; Ray, Ruby; Canham, Jo; Griffiths, Gareth; Maughan, Tim; Crosby, Tom

2017-03-01

Oxaliplatin-capecitabine (OxCap) and carboplatin-paclitaxel (CarPac) based neo-adjuvant chemoradiotherapy (nCRT) have shown promising activity in localised, resectable oesophageal cancer. A non-blinded, randomised (1:1 via a centralised computer system), 'pick a winner' phase II trial. Patients with resectable oesophageal adenocarcinoma ≥ cT3 and/or ≥ cN1 were randomised to OxCapRT (oxaliplatin 85 mg/m 2  day 1, 15, 29; capecitabine 625 mg/m 2 bd on days of radiotherapy) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m 2  day 1, 8, 15, 22, 29). Radiotherapy dose was 45 Gy/25 fractions/5 weeks. Both arms received induction OxCap chemotherapy (2 × 3 week cycles of oxaliplatin 130 mg/m 2  day 1, capecitabine 625 mg/m 2 bd days 1-21). Surgery was performed 6-8 weeks after nCRT. Primary end-point was pathological complete response (pCR). Secondary end-points included toxicity, surgical morbidity/mortality, resection rate and overall survival. Based on pCR ≤ 15% not warranting future investigation, but pCR ≥ 35% would, 76 patients (38/arm) gave 90% power (one-sided alpha 10%), implying that arm(s) having ≥10 pCR out of first 38 patients could be considered for phase III trials. ClinicalTrials.gov: NCT01843829. Funder: Cancer Research UK (C44694/A14614). Eighty five patients were randomised between October 2013 and February 2015 from 17 UK centres. Three of 85 (3.5%) died during induction chemotherapy. Seventy-seven patients (OxCapRT = 36; CarPacRT = 41) underwent surgery. The 30-d post-operative mortality was 2/77 (2.6%). Grade III/IV toxicity was comparable between arms, although neutropenia was higher in the CarPacRT arm (21.4% versus 2.6%, p = 0.01). Twelve of 41 (29.3%) (10 of first 38 patients) and 4/36 (11.1%) achieved pCR in the CarPacRT and OxcapRT arms, respectively. Corresponding R0 resection rates were 33/41 (80.5%) and 26/36 (72.2%), respectively. Both regimens were well tolerated. Only CarPacRT passed the predefined pCR criteria for further investigation. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

[Induction chemotherapy with docetaxel plus cisplatin (TP regimen) followed by concurrent chemoradiotherapy with TP regimen versus cisplatin in treating locally advanced nasopharyngeal carcinoma].

PubMed

Xie, Fang-Yun; Zou, Guo-Rong; Hu, Wei-Han; Qi, Shu-Nan; Peng, Miao; Li, Ji-Shi

2009-03-01

Clinical trials on docetaxel plus cisplatin (DDP) (TP regimen) in treating nasopharyngeal carcinoma (NPC) are still uncertain due to limited samples. This study was to compare the short-term efficacy and toxicity of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen versus DDP in treating locally advanced NPC. Fifty-seven patients with stage T3-4N2-3M0 NPC diagnosed pathologically from December 2005 to December 2006 were randomized into TP group (30 patients) and DDP group (27 patients). Both groups received TP regimen as induction chemotherapy with docetaxel (70 mg/m(2)) on Day 1 and DDP (80 mg/m(2)) on Day 2, repeating every 21 days for 2 cycles. For concurrent chemotherapy, TP group were administered docetaxel (60 mg/m(2)) on Day 1 and DDP (80 mg/m(2)) on Day 2; DDP group were administered DDP (80 mg/m(2)) on Day 1. Both schedules were repeated every 21 days for 2 cycles. Linear accelerator was used as radioactive source. Irradiation field was designed with CT-simulation and conventional fractions. The 57 patients received 111 cycles of induction chemotherapy, and 53 of them received 103 cycles of concurrent chemotherapy; four patients ceased induction chemotherapy and three ceased concurrent chemotherapy. All patients completed radiotherapy. The major toxicity of induction chemotherapy was hematologic toxicity; the main toxicities of concurrent chemoradiotherapy were hematologic toxicity and mucositis. The occurrence rates of Grade 3-4 leucopenia and Grade 3-4 neutropenia were significantly higher in TP group than in DDP groups (p <0.05). In concurrent chemoradiotherapy, the application rate of granulocyte colony stimulating factor (G-CSF) was significantly higher in TP group than in DDP group (100% vs. 72.0%, p<0.05). After concurrent chemoradiotherapy, the complete remission (CR) rates of the nasopharynx and regional lymph nodes were 93.3% and 92.9% in TP group, and were 96.3% and 91.3% in DDP group (p>0.05). The short-term efficacy of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen on locally advanced NPC is similar to that of TP regimen followed by concurrent chemoradiotherapy with DDP. The toxicity of the former schedule is severer than that of the latter, but it is tolerable with the use of G-CSF. The long-term efficacy of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen need to be further studied.

The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial.

PubMed

Burnett, Alan K; Milligan, Donald; Goldstone, Anthony; Prentice, Archibald; McMullin, Mary-Frances; Dennis, Michael; Sellwood, Elizabeth; Pallis, Monica; Russell, Nigel; Hills, Robert K; Wheatley, Keith

2009-05-01

The acute myeloid leukaemia (AML)14 trial addressed four therapeutic questions in patients predominantly aged over 60 years with AML and High Risk Myelodysplastic Syndrome: (i) Daunorubicin 50 mg/m(2) vs. 35 mg/m(2); (ii) Cytarabine 200 mg/m(2) vs. 400 mg/m(2) in two courses of DA induction; (iii) for part of the trial, patients allocated Daunorubicin 35 mg/m(2) were also randomized to receive, or not, the multidrug resistance modulator PSC-833 in a 1:1:1 randomization; and (iv) a total of three versus four courses of treatment. A total of 1273 patients were recruited. The response rate was 62% (complete remission 54%, complete remission without platelet/neutrophil recovery 8%); 5-year survival was 12%. No benefits were observed in either dose escalation randomization, or from a fourth course of treatment. There was a trend for inferior response in the PSC-833 arm due to deaths in induction. Multivariable analysis identified cytogenetics, presenting white blood count, age and secondary disease as the main predictors of outcome. Although patients with high Pgp expression and function had worse response and survival, this was not an independent prognostic factor, and was not modified by PSC-833. In conclusion, these four interventions have not improved outcomes in older patients. New agents need to be explored and novel trial designs are required to maximise prospects of achieving timely progress.

Porcine spine finite element model: a complementary tool to experimental scoliosis fusionless instrumentation.

PubMed

Hachem, Bahe; Aubin, Carl-Eric; Parent, Stefan

2017-06-01

Developing fusionless devices to treat pediatric scoliosis necessitates lengthy and expensive animal trials. The objective was to develop and validate a porcine spine numerical model as an alternative platform to assess fusionless devices. A parametric finite element model (FEM) of an osseoligamentous porcine spine and rib cage, including the epiphyseal growth plates, was developed. A follower-type load replicated physiological and gravitational loads. Vertebral growth and its modulation were programmed based on the Hueter-Volkmann principle, stipulating growth reduction/promotion due to increased compressive/tensile stresses. Scoliosis induction via a posterior tether and 5-level rib tethering, was simulated over 10 weeks along with its subsequent correction via a contralateral anterior custom tether (20 weeks). Scoliosis induction was also simulated using two experimentally tested compression-based fusionless implants (hemi- and rigid staples) over 12- and 8-weeks growth, respectively. Resulting simulated Cobb and sagittal angles, apical vertebral wedging, and left/right height alterations were compared to reported studies. Simulated induced Cobb and vertebral wedging were 48.4° and 7.6° and corrected to 21° and 5.4°, respectively, with the contralateral anterior tether. Apical rotation (15.6°) was corrected to 7.4°. With the hemi- and rigid staples, Cobb angle was 11.2° and 11.8°, respectively, with 3.7° and 2.0° vertebral wedging. Sagittal plane was within the published range. Convex/concave-side vertebral height difference was 3.1 mm with the induction posterior tether and reduced to 2.3 with the contralateral anterior tether, with 1.4 and 0.8 for the hemi- and rigid staples. The FEM represented growth-restraining effects and growth modulation with Cobb and vertebral wedging within 0.6° and 1.9° of experimental animal results, while it was within 5° for the two simulated staples. Ultimately, the model would serve as a time- and cost-effective tool to assess the biomechanics and long-term effect of compression-based fusionless devices prior to animal trials, assisting the transfer towards treating scoliosis in the growing spine.

Relative Effectiveness of Reappraisal and Distraction in Regulating Emotion in Late-Life Depression

PubMed Central

Smoski, Moria J.; LaBar, Kevin S.; Steffens, David C.

2013-01-01

Objectives The present study compares the effectiveness of two strategies, reappraisal and distraction, in reducing negative affect in older adults induced by focusing on personally relevant negative events and stressors. Participants included 30 adults with MDD and 40 never-depressed (ND) comparison participants ages 60 and over (mean age = 69.7 years). Design and Measurements Participants underwent three affect induction trials, each followed by a different emotion regulation strategy: distraction, reappraisal, and a no-instruction control condition. Self-reported affect was recorded pre- and post-affect induction, and at one-minute intervals during regulation. Results Across groups, participants reported greater reductions in negative affect with distraction than reappraisal or the no-instruction control condition. An interaction between group and regulation condition indicated that distraction was more effective in reducing negative affect in the MDD group than the ND group. Conclusions These results suggest that distraction is an especially effective strategy for reducing negative affect in older adults with MDD. Finding ways to incorporate distraction skills into psychotherapeutic interventions for late-life MDD may improve their effectiveness, especially for short-term improvement of affect following rumination. PMID:24021222

Induction of a shorter compression phase is correlated with a deeper chest compression during metronome-guided cardiopulmonary resuscitation: a manikin study.

PubMed

Chung, Tae Nyoung; Bae, Jinkun; Kim, Eui Chung; Cho, Yun Kyung; You, Je Sung; Choi, Sung Wook; Kim, Ok Jun

2013-07-01

Recent studies have shown that there may be an interaction between duty cycle and other factors related to the quality of chest compression. Duty cycle represents the fraction of compression phase. We aimed to investigate the effect of shorter compression phase on average chest compression depth during metronome-guided cardiopulmonary resuscitation. Senior medical students performed 12 sets of chest compressions following the guiding sounds, with three down-stroke patterns (normal, fast and very fast) and four rates (80, 100, 120 and 140 compressions/min) in random sequence. Repeated-measures analysis of variance was used to compare the average chest compression depth and duty cycle among the trials. The average chest compression depth increased and the duty cycle decreased in a linear fashion as the down-stroke pattern shifted from normal to very fast (p<0.001 for both). Linear increase of average chest compression depth following the increase of the rate of chest compression was observed only with normal down-stroke pattern (p=0.004). Induction of a shorter compression phase is correlated with a deeper chest compression during metronome-guided cardiopulmonary resuscitation.

Comparative Study of Oral and Vaginal Misoprostol for Induction of Labour, Maternal and Foetal Outcome

PubMed Central

Komala, Kambhampati; Reddy, Meherlatha; Quadri, Iqbal Jehan; B., Suneetha; V., Ramya

2013-01-01

Background: Misoprostol is a new promising agent for cervical ripening and induction of labour .The ideal dose, route and frequency of administration of misoprostol are still under investigation. Although, vaginal application of misoprostol has been validated as a reasonable mean of induction, there is a patient resistance to digital examination and there is a risk of ascending infection. For this reason, oral administration of misoprostol for cervical ripening and labour induction has been tried. Aims and Objectives: To compare 50μg of oral misoprostol versus 25μg of intravaginal misoprostol for induction of labour at term and maternal, foetal outcomes. Methods: Two hundred women who were at term, with indication for induction of labour and Bishop scores of ≤5 were randomly assigned to receive misoprostol 50μg or 25μg intravaginal, every 4-6 hours, for a maximum of 5 doses. In either group, pregnant females with inadequate uterine contractions despite being given maximum 5 doses of misoprostol, were augmented using oxytocin. The primary outcome measure was time-interval from induction to vaginal delivery and vaginal delivery rate within 24 hours. Results: The median induction to vaginal delivery time in oral group (12.92h) and vaginal group (14.04 h) was not significant. Oral misoprostol resulted in more number of vaginal deliveries as compared to vaginal misoprostol (94% as compared to 86%), which was not significant. There was a significantly higher incidence of uterine tachysystole in the vaginal group, as compared to oral group. There were no significant differences between the groups with respect to oxytocin augmentation, caesarean section rate, analgesic requirement and neonatal outcome. Conclusion: Oral misoprostol is as efficacious as vaginal misoprostol because of shorter induction delivery interval, lower caesarean section rates, and lower incidence of failed induction rates. Lower incidence of foetal distress and easy intake are observed if the drug is administered orally. PMID:24551660

The home as an appropriate setting for women undertaking cervical ripening before the induction of labour.

PubMed

Reid, Margaret; Lorimer, Karen; Norman, Jane E; Bollapragada, Shrikant S; Norrie, John

2011-02-01

to explore women's experiences of cervical ripening using isosorbide mononitrate (IMN) in the home as part of the main randomised controlled trial. qualitative study with semi-structured interviews carried out at three weeks post partum. Interview transcripts were analysed to identify recurrent themes, focusing on why women became involved in the study, their views about both the self-medication and the home setting, and whether they would repeat the experience. the home. twenty women enrolled in the main randomised controlled trial. the study is part of a double-blind randomised controlled trial with 350 patients investigating whether a nitric oxide donor (IMN) used in cervical ripening improves the process of induction of labour. women liked the opportunity to remain at home during the cervical ripening process. Timing and setting were central issues; women hoped that it would hasten labour, while the home was seen as a setting offering freedom, security and reassurance, as opposed to the hospital, seen as constraining. Two women reported problems with IMN but the remainder reported that they would repeat the experience. women were very positive about the opportunity to undertake cervical ripening at home. It is important to explore this setting further for appropriate interventions. Copyright © 2009 Elsevier Ltd. All rights reserved.

Effect of exposure to second-hand smoke from husbands on biochemical hyperandrogenism, metabolic syndrome and conception rates in women with polycystic ovary syndrome undergoing ovulation induction.

PubMed

Li, Jian; Wu, Q; Wu, Xiao-Ke; Zhou, Zhong-Ming; Fu, Ping; Chen, Xiu-Hua; Yan, Ying; Wang, Xin; Yang, Zheng-Wang; Li, Wei-Li; Stener-Victorin, Elisabet; Legro, Richard S; Ng, Ernest Hung-Yu; Zhang, Heping; Mol, Ben Willem J; Wang, Chi Chiu

2018-04-01

Does second-hand smoke (SHS) exposure from husbands have adverse effects on sex hormones, metabolic profiles, clinical phenotypes and fertility outcomes in women with polycystic ovary syndrome (PCOS) undergoing ovulation induction? SHS exposure is associated with worsened biochemical hyperandrogenism, higher incidence of metabolic syndrome and reduced conception rates in women with PCOS. Smoking in women impairs fecundity at some stages of the reproductive process including folliculogenesis, embryo transport, endometrial angiogenesis and uterine blood flow. Yet little is known about the hazard of SHS exposure in women with PCOS. This study was a secondary analysis of the Polycystic Ovary Syndrome Acupuncture and Clomiphene Trial (PCOSAct), a large randomized controlled trial conducted at 27 hospitals from 2012 to 2015 in mainland China. Out of 1000 women with PCOS, SHS exposure status were available in 500 women, of whom 271 women were non-exposed and 229 exposed to cigarette smoke (170 women ≤10 cigarettes per day as low-SHS exposed and 59 women >10 cigarettes per day as high-SHS exposed). We compared circulating sex steroids, glucose and lipid metabolism, metabolic syndrome and phenotypes, fertility and obstetric outcomes between non-exposed and exposed women. Women exposed to SHS, compared to non-exposed women, had a higher serum total testosterone (1.7 vs 1.5 nmol/L, P = 0.01), free androgen index (5.7 vs 4.0, P = 0.001) and lower sex hormone binding globulin (30.1 vs 35.6 nmol/L, P = 0.03). Metabolic syndrome, but not other phenotypes, was more frequent in exposed women as compared to non-exposed women (21.8 vs 13.3%, adjusted odds ratio (OR)=1.66; 95% CI, 1.02-2.71, P = 0.04). Ovulation rates between exposed and non-exposed groups were not significantly different (76.9 vs 82.9%, adjusted OR=0.72; 95% CI, 0.45-1.15, P = 0.17). Conception rates were significant lower in the exposed group (26.6 vs 36.9%; adjusted OR=0.61; 95% CI, 0.41-0.91; P = 0.01), while clinical pregnancy and live birth rates showed a similar trend that was not statistically significant. Gestational age, birth weight and other obstetric outcomes were not affected by SHS exposure. Data on SHS exposure were missing in 50% of the women. We did not assay serum nicotine or cotinine levels to quantify the SHS exposure status. These data suggest that smoking partners of infertile women with PCOS who seek treatment should be advised to quit smoking. Funding was provided by the National Public Welfare Projects for Chinese Medicine (201107005 and 200807002) and the National Clinical Trial Base in Chinese Medicine Special Projects (JDZX2012036 and 2015B009). There are no conflicts of interest. ClinicalTrial.gov number: NCT01573858 and chictr.org.cn number: ChiCTR-TRC-12002081.

Tumor-Preferential Induction of Immune Responses and Epidermal Cell Death in Actinic Keratoses by Ingenol Mebutate

PubMed Central

Zibert, John R.; Schön, Margarete; Hald, Andreas; Hansen, Maria H.; Litman, Thomas; Schön, Michael P.

2016-01-01

The rapid and strong clinical efficacy of the first-in-class, ingenol mebutate, against actinic keratosis (AK) has resulted in its recent approval. We conducted the first comprehensive analysis of the cellular and molecular mode of action of topical ingenol mebutate 0.05% gel in both AK and uninvolved skin of 26 patients in a phase I, single-center, open-label, within-patient comparison. As early as 1 day after application, ingenol mebutate induced profound epidermal cell death, along with a strong infiltrate of CD4+ and CD8+ T-cells, neutrophils, and macrophages. Endothelial ICAM-1 activation became evident after 2 days. The reaction pattern was significantly more pronounced in AK compared with uninvolved skin, suggesting a tumor-preferential mode of action. Extensive molecular analyses and transcriptomic profiling of mRNAs and microRNAs demonstrated alterations in gene clusters functionally associated with epidermal development, inflammation, innate immunity, and response to wounding. Ingenol mebutate reveals a unique mode of action linking directly to anti-tumoral effects. Trial Registration: ClinicalTrials.gov NCT01387711 PMID:27612149

Effect of Silicon on the Desulfurization of Al-Killed Steels: Part II. Experimental Results and Plant Trials

NASA Astrophysics Data System (ADS)

Roy, Debdutta; Pistorius, Petrus Christiaan; Fruehan, Richard J.

2013-10-01

Recent observations suggest that increased silicon levels improve ladle desulfurization of aluminum-killed steel. A kinetic model was developed and presented in part I of this paper, demonstrating that increased silicon levels in steel suppress the consumption of aluminum by parasitic reactions like silica reduction and FeO/MnO reduction, thus making more aluminum available at the interface for desulfurization. The results are increases in the rate and the extent of desulfurization. Predictions were compared with laboratory induction furnace melts using 1 kg of steel and 0.1 kg slag. The experimental results demonstrate the beneficial effect of silicon on the desulfurization reaction and that alumina can be reduced out of the slag and aluminum picked up by the steel, if the silicon content in the steel is high enough. The experimental results are in close agreement with the model predictions. Plant trials also show that with increased silicon content, both the rate and extent of desulfurization increase; incorporating silicon early into the ladle desulfurization process leads to considerable savings in aluminum consumption.

Stability and broad-sense heritaibility of mineral content in potato: copper and sulfur

USDA-ARS?s Scientific Manuscript database

Potato breeding lines and varieties in two separate trials were evaluated for copper and sulfur content by wet ashing and Inductively Coupled Argon Plasma Emission Spectrophotometer analysis. Stability and broad-sense heritability were determined. Copper contents ranged among genotypes between 2.0...

Effect of psychological therapy on disease activity, psychological comorbidity, and quality of life in inflammatory bowel disease: a systematic review and meta-analysis.

PubMed

Gracie, David J; Irvine, Andrew J; Sood, Ruchit; Mikocka-Walus, Antonina; Hamlin, P John; Ford, Alexander C

2017-03-01

Inflammatory bowel disease is associated with psychological comorbidity and impaired quality of life. Psychological comorbidity could affect the natural history of inflammatory bowel disease. Psychological therapies might therefore have beneficial effects on disease activity, mood, and quality of life in patients with inflammatory bowel disease. We did a systematic review and meta-analysis examining these issues. In this systematic review and meta-analysis, we searched MEDLINE, Embase, Embase Classic, PsychINFO, and the Cochrane Central Register of Controlled Trials for articles published between 1947 and Sept 22, 2016. Randomised controlled trials (RCTs) recruiting patients with inflammatory bowel disease aged at least 16 years that compared psychological therapy with a control intervention or usual treatment were eligible. We pooled dichotomous data to obtain relative risks of induction of remission in active disease or prevention of relapse of quiescent disease, with 95% CIs. We pooled continuous data to estimate standardised mean differences in disease activity indices, anxiety, depression, perceived stress, and quality-of-life scores in patients dichotomised into those with clinically active or quiescent disease, with 95% CIs. We extracted data from published reports and contacted the original investigators of studies for which the required data were not available. We pooled all data using a random-effects model. The search identified 1824 studies, with 14 RCTs of 1196 patients eligible for inclusion. The relative risk of relapse of quiescent inflammatory bowel disease with psychological therapy versus control was 0·98 (95% CI 0·77-1·24; p=0·87; I 2 =50%; six trials; 518 patients). We observed a significant difference in depression scores (standardised mean difference -0·17 [-0·33 to -0·01]; p=0·04; I 2 =0%; seven trials; 605 patients) and quality of life (0·30 [0·07-0·52]; p=0·01; I 2 =42%; nine trials; 578 patients) with psychological therapy versus control at the end of therapy for patients with quiescent disease. However, these beneficial effects were lost at final point of follow-up (depression scores -0·11 [-0·27 to 0·05], p=0·17, I 2 =0%, eight trials, 593 patients; quality of life 0·15 [-0·05 to 0·34], p=0·14, I 2 =22%, ten trials, 577 patients). When we assessed the effect of individual physiological therapies on quality of life, only cognitive behavioural therapy had any significant beneficial effect (0·37 [0·02-0·72]). We noted no effect on disease activity indices or other psychological wellbeing scores when compared with control in patients with quiescent disease. Dichotomous data for induction of remission and continuous data for change in clinical disease activity indices, depression, anxiety, and perceived stress scores were only reported in one RCT of patients with active disease. Quality of life was assessed in two RCTs of patients with active disease, but was not significantly different between intervention and control groups (0·27 [-0·05 to 0·59]). Psychological therapies, and cognitive behavioural therapy in particular, might have small short-term beneficial effects on depression scores and quality of life in patients with inflammatory bowel disease. Further RCTs of these interventions in patients with coexistent psychological distress are required. None. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Risk of uterine rupture in vaginal birth after cesarean: Systematic review].

PubMed

Hidalgo-Lopezosa, Pedro; Hidalgo-Maestre, María

To assess the risk of uterine rupture (UR) in attempted vaginal birth after cesarean and to identify risk factors. Systematic review by consulting the following databases: PubMed (MEDLINE), Cochrane Library Plus, Embase, Nursing@Ovid, Cuidatge and Dialnet. The search was conducted between January and March 2015. MeSH descriptors used were: vaginal birth after cesarean; uterine rupture; labor induced and labor obstetric or trial of labor. There were no restrictions on date or language. The selection of articles was performed by 2 independent reviewers, standardized and unblinded. A critical review of the summary was conducted, and if was necessary, the full text was consulted. Prospective and retrospective documents were included. A total of 39 documents were included for their relevance and interest. Few clinical trials were found. The UR incidence on the results of the studies analyzed ranged from 0.15-0.98% in spontaneous labor; 0.3-1.5% in stimulation and induction with oxytocin, and 0.68-2.3% in prostaglandin inductions. The success of vaginal birth after cesarean is important and improves when conditions are optimal. However it is not without risks, the main one being UR. Induction of labor with oxytocin and/or prostaglandins appears as the main risk factor, while the spontaneous onset of labor and a prior vaginal birth are protective factors. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Are there any differences in the efficacy and safety of different formulations of Oral 5-ASA used for induction and maintenance of remission in ulcerative colitis? evidence from cochrane reviews.

PubMed

Feagan, Brian G; Chande, Nilesh; MacDonald, John K

2013-08-01

We systematically reviewed and compared the efficacy and safety of oral mesalamine formulations (sustained release, delayed release, and prodrugs) used for induction and maintenance of remission in ulcerative colitis. The main objective of this review was to determine if there are any differences in efficacy or safety among the oral 5-ASA drugs. A literature search in February 2013 identified all applicable randomized trials. Study quality was evaluated using the Cochrane risk of bias tool. The Grading of Recommendations Assessment, Development and Evaluation criteria were used to assess the overall quality of the evidence. Studies were subgrouped by common mesalamine comparators for meta-analysis. Studies were pooled for analysis if they compared equimolar doses of oral 5-ASA. Seventeen studies that evaluated 2925 patients were identified. The risk of bias was low for most factors, although 1 study was single blind and 3 were open label. No difference was observed between oral 5-ASA and comparator 5-ASA formulations in the proportion of patients with clinical remission (relative risk, 0.94; 95% confidence interval, 0.86-1.02), clinical improvement (relative risk, 0.89; 95% confidence interval, 0.77-1.01), or relapse at 12 months (relative risk, 1.01; 95% confidence interval, 0.80-1.28). Subgroup analyses showed no important differences in efficacy. No significant difference was demonstrated in rates of adverse events or withdrawal due to adverse events. There does not seem to be any difference in efficacy or safety among the various formulations of oral 5-ASA. Oral mesalamine is an effective and safe treatment of mild-to-moderate or quiescent ulcerative colitis regardless of the chosen formulation.

Safety of oral glutamine in the abbreviation of preoperative fasting: a double-blind, controlled, randomized clinical trial.

PubMed

Borges Dock-Nascimento, D; Aguilar-Nascimento, J E D; Caporossi, C; Sepulveda Magalhães Faria, M; Bragagnolo, R; Caporossi, F Stephan; Linetzky Waitzberg, D

2011-01-01

No study so far has tested a beverage containing glutamine 2 h before anesthesia in patients undergoing surgery. The aim of the study was to investigate: 1) the safety of the abbreviation of preoperative fasting to 2 h with a carbohydrate-L-glutamine-rich drink; and 2) the residual gastric volume (RGV) measured after the induction of anesthesia for laparoscopic cholecystectomies. Randomized controlled trial with 56 women (42 (17-65) years-old) submitted to elective laparoscopic cholecystectomy. Patients were randomized to receive either conventional preoperative fasting of 8 hours (fasted group, n = 12) or one of three different beverages drunk in the evening before surgery (400 mL) and 2 hours before the initiation of anesthesia (200 mL). The beverages were water (placebo group, n = 12), 12.5% (240 mOsm/L) maltodextrine (carbohydrate group, n = 12) or the latter in addition to 50 g (40 g in the evening drink and 10 g in the morning drink) of L-glutamine (glutamine group, n = 14). A 20 F nasogastric tube was inserted immediately after the induction of general anesthesia to aspirate and measure the RGV. Fifty patients completed the study. None of the patients had either regurgitation during the induction of anesthesia or postoperative complications. The median (range) of RGV was 6 (0-80) mL. The RGV was similar (p = 0.29) between glutamine group (4.5 [0-15] mL), carbohydrate group (7.0 [0-80] mL), placebo group (8.5 [0-50] mL), and fasted group (5.0 [0-50] mL). The abbreviation of preoperative fasting to 2 h with carbohydrate and L-glutamine is safe and does not increase the RGV during induction of anesthesia.

Streamed video clips to reduce anxiety in children during inhaled induction of anesthesia.

PubMed

Mifflin, Katherine A; Hackmann, Thomas; Chorney, Jill Maclaren

2012-11-01

Anesthesia induction in children is frequently achieved by inhalation of nitrous oxide and sevoflurane. Pediatric anesthesiologists commonly use distraction techniques such as humor or nonprocedural talk to reduce anxiety and facilitate a smooth transition at this critical phase. There is a large body of successful distraction research that explores the use of video and television distraction methods for minor medical and dental procedures, but little research on the use of this method for ambulatory surgery. In this randomized control trial study we examined whether video distraction is effective in reducing the anxiety of children undergoing inhaled induction before ambulatory surgery. Children (control = 47, video = 42) between 2 and 10 years old undergoing ambulatory surgery were randomly assigned to a video distraction or control group. In the video distraction group a video clip of the child's preference was played during induction, and the control group received traditional distraction methods during induction. The modified Yale Preoperative Anxiety Scale was used to assess the children's anxiety before and during the process of receiving inhalation anesthetics. All subjects were similar in their age and anxiety scores before entering the operating rooms. Children in the video distraction group were significantly less anxious at induction and showed a significantly smaller change in anxiety from holding to induction than did children in the control group. Playing video clips during the inhaled induction of children undergoing ambulatory surgery is an effective method of reducing anxiety. Therefore, pediatric anesthesiologists may consider using video distraction as a useful, valid, alternative strategy for achieving a smooth transition to the anesthetized state.

Buprenorphine dose induction in non-opioid-tolerant pre-release prisoners.

PubMed

Vocci, Frank J; Schwartz, Robert P; Wilson, Monique E; Gordon, Michael S; Kinlock, Timothy W; Fitzgerald, Terrence T; O'Grady, Kevin E; Jaffe, Jerome H

2015-11-01

In a previously reported randomized controlled trial, formerly opioid-dependent prisoners were more likely to enter community drug abuse treatment when they were inducted in prison onto buprenorphine/naloxone (hereafter called buprenorphine) than when they received counseling without buprenorphine in prison (47.5% vs. 33.7%, p=0.012) (Gordon et al., 2014). In this communication we report on the results of the induction schedule and the adverse event profile seen in pre-release prisoners inducted onto buprenorphine. This paper examines the dose induction procedure, a comparison of the proposed versus actual doses given per week, and side effects reported for 104 adult participants who were randomized to buprenorphine treatment in prison. Self-reported side effects were analyzed using generalized estimated equations to determine changes over time in side effects. Study participants were inducted onto buprenorphine at a rate faster than the induction schedule. Of the 104 (72 males, 32 females) buprenorphine recipients, 64 (37 males, 27 females) remained on medication at release from prison. Nine participants (8.6%) discontinued buprenorphine because of unpleasant opioid side effects. There were no serious adverse events reported during the in-prison phase of the study. Constipation was the most frequent symptom reported (69 percent). Our findings suggest that buprenorphine administered to non-opioid-tolerant adults should be started at a lower, individualized dose than customarily used for adults actively using opioids, and that non-opioid-tolerant pre-release prisoners can be successfully inducted onto therapeutic doses prior to release. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Divergent creative thinking in young and older adults: Extending the effects of an episodic specificity induction

PubMed Central

Madore, Kevin P.; Jing, Helen G.; Schacter, Daniel L.

2016-01-01

Recent research has suggested that an episodic specificity induction- brief training in recollecting the details of a past experience- enhances divergent creative thinking on the Alternate Uses Task (AUT) in young adults without affecting performance on tasks thought to involve little divergent thinking, but the generalizability of these results to other populations and tasks is unknown. The present experiments examined whether effects of an episodic specificity induction extend to older adults and a different index of divergent thinking, the Consequences Task. In Experiment 1, the specificity induction significantly enhanced divergent thinking on the AUT in both young and older adults compared with a control induction not requiring specific episodic retrieval; performance on a task involving little divergent thinking did not vary as a function of induction (generating associates for common objects). No overall age-related differences were observed on either task. In Experiment 2, the specificity induction significantly enhanced divergent thinking (generating consequences of novel scenarios) in young adults compared with another control induction not requiring episodic retrieval. To examine the types of creative ideas affected by the induction, participants in both experiments also labeled each of their divergent thinking responses as an old idea from memory or new idea from imagination. New and to some extent old ideas were significantly boosted following the specificity induction compared with the control. These experiments provide novel evidence that an episodic specificity induction can boost divergent thinking in young and older adults, and indicate that episodic memory is involved in multiple divergent thinking tasks. PMID:27001170

Induction chemoradiation in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial.

PubMed

Pless, Miklos; Stupp, Roger; Ris, Hans-Beat; Stahel, Rolf A; Weder, Walter; Thierstein, Sandra; Gerard, Marie-Aline; Xyrafas, Alexandros; Früh, Martin; Cathomas, Richard; Zippelius, Alfred; Roth, Arnaud; Bijelovic, Milorad; Ochsenbein, Adrian; Meier, Urs R; Mamot, Christoph; Rauch, Daniel; Gautschi, Oliver; Betticher, Daniel C; Mirimanoff, René-Olivier; Peters, Solange

2015-09-12

One of the standard options in the treatment of stage IIIA/N2 non-small-cell lung cancer is neoadjuvant chemotherapy and surgery. We did a randomised trial to investigate whether the addition of neoadjuvant radiotherapy improves outcomes. We enrolled patients in 23 centres in Switzerland, Germany and Serbia. Eligible patients had pathologically proven, stage IIIA/N2 non-small-cell lung cancer and were randomly assigned to treatment groups in a 1:1 ratio. Those in the chemoradiotherapy group received three cycles of neoadjuvant chemotherapy (100 mg/m(2) cisplatin and 85 mg/m(2) docetaxel) followed by radiotherapy with 44 Gy in 22 fractions over 3 weeks, and those in the control group received neoadjuvant chemotherapy alone. All patients were scheduled to undergo surgery. Randomisation was stratified by centre, mediastinal bulk (less than 5 cm vs 5 cm or more), and weight loss (5% or more vs less than 5% in the previous 6 months). The primary endpoint was event-free survival. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00030771. From 2001 to 2012, 232 patients were enrolled, of whom 117 were allocated to the chemoradiotherapy group and 115 to the chemotherapy group. Median event-free survival was similar in the two groups at 12·8 months (95% CI 9·7-22·9) in the chemoradiotherapy group and 11·6 months (8·4-15·2) in the chemotherapy group (p=0·67). Median overall survival was 37·1 months (95% CI 22·6-50·0) with radiotherapy, compared with 26·2 months (19·9-52·1) in the control group. Chemotherapy-related toxic effects were reported in most patients, but 91% of patients completed three cycles of chemotherapy. Radiotherapy-induced grade 3 dysphagia was seen in seven (7%) patients. Three patients died in the control group within 30 days after surgery. Radiotherapy did not add any benefit to induction chemotherapy followed by surgery. We suggest that one definitive local treatment modality combined with neoadjuvant chemotherapy is adequate to treat resectable stage IIIA/N2 non-small-cell lung cancer. Swiss State Secretariat for Education, Research and Innovation (SERI), Swiss Cancer League, and Sanofi. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multicenter phase II study of weekly docetaxel, cisplatin, and S-1 (TPS) induction chemotherapy for locally advanced squamous cell cancer of the head and neck.

PubMed

Bae, Woo Kyun; Hwang, Jun Eul; Shim, Hyun Jeong; Cho, Sang Hee; Lee, Ki Hyeong; Han, Hye Suk; Song, Eun-Kee; Yun, Hwan Jung; Cho, In Sung; Lee, Joon Kyoo; Lim, Sang-Chul; Chung, Woong-Ki; Chung, Ik-Joo

2013-03-06

The purpose of this study was to evaluate the efficacy and tolerability of weekly docetaxel, cisplatin, and S-1 (weekly TPS) as induction chemotherapy for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). A total of 35 patients with previously untreated, locally advanced HNSCC were enrolled. Seven patients (20%) were diagnosed with stage III HNSCC and 28 patients (80%) were diagnosed with stage IV. Induction treatment included 30 mg/m(2) docetaxel on day 1 and 8, 60 mg/m(2) cisplatin on day 1, and 70 mg/m(2) S-1 on days 1 to 14. The regimen was repeated every 21 days. After three courses of induction chemotherapy, patients received concurrent chemoradiotherapy. Among the 35 patients, 30 (85.7%) completed induction chemotherapy. The response to induction chemotherapy was as follows: nine patients (25.7%) achieved a complete response (CR) and the overall response rate (ORR) was 85.7%. Grades 3-4 toxicity during induction therapy included neutropenia (28.5%), neutropenic fever (8.5%), and diarrhea (17.1%). After completion of concurrent chemoradiotherapy, the CR rate was 62.8% and the partial response (PR) was 22.8%. Estimates of progression-free and overall survival at 2 years were 73.2% and 79.3%, respectively. Weekly TPS is a promising regimen that is well-tolerated, causes minimal myelosuppression and is effective as an outpatient regimen for locally advanced HNSCC. ClinicalTrials.gov: NCT01645748.

Parental presence during induction of anesthesia: physiological effects on parents.

PubMed

Kain, Zeev N; Caldwell-Andrews, Alison A; Mayes, Linda C; Wang, Shu-Ming; Krivutza, Dawn M; LoDolce, Megan E

2003-01-01

The authors conducted a randomized controlled trial to determine whether parental presence during induction of anesthesia (PPIA) is associated with parental physiologic and behavioral manifestations of stress. Children and their parents (N = 80) were randomly assigned to one of three groups: (1) PPIA; (2) PPIA plus 0.5 mg/kg oral midazolam; and (3) control (no PPIA or midazolam). The effect of the group assignment on parental heart rate (HR), parental blood pressure, and parental skin conductance level (SCL) were assessed. Both parental HR and parental SCL were monitored continually. Anxiety of the parent and child was also assessed. Parental HR increased from baseline until the induction of anesthesia (P = 0.001). A group-by-time effect ( P= 0.005) was also found. That is, throughout the induction period there were several time points at which parents in the two PPIA groups had a significantly higher HR than did parents in the control group (P < 0.05). Similarly, SCL was found to increase in all parents from baseline until induction of anesthesia (P = 0.001). Significant group differences in SCL changes over time were found as well (P = 0.009). State anxiety and blood pressure following induction of anesthesia did not differ significantly between groups ( P= nonsignificant). Examination of parental Holter data revealed no rhythm abnormalities and no electrocardiogram changes indicating ischemia. The authors found that PPIA is associated with increased parental HR and SCL. However, no increased incidence of electrocardiogram abnormalities were found in parents present during induction of anesthesia.

Antifibrinolytics (lysine analogues) for the prevention of bleeding in people with haematological disorders

PubMed Central

Estcourt, Lise J; Desborough, Michael; Brunskill, Susan J; Doree, Carolyn; Hopewell, Sally; Murphy, Michael F; Stanworth, Simon J

2016-01-01

Background People with haematological disorders are frequently at risk of severe or life-threatening bleeding as a result of thrombocytopenia (reduced platelet count). This is despite the routine use of prophylactic platelet transfusions to prevent bleeding once the platelet count falls below a certain threshold. Platelet transfusions are not without risk and adverse events may be life-threatening. A possible adjunct to prophylactic platelet transfusions is the use of antifibrinolytics, specifically the lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA). This is an update of a Cochrane review first published in 2013. Objectives To determine the efficacy and safety of antifibrinolytics (lysine analogues) in preventing bleeding in people with haematological disorders. Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (The Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 07 March 2016. Selection criteria We included RCTs involving participants with haematological disorders, who would routinely require prophylactic platelet transfusions to prevent bleeding. We only included trials involving the use of the lysine analogues TXA and EACA. Data collection and analysis Two review authors independently screened all electronically-derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two review authors independently assessed the full text of all potentially relevant trials for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration’s ‘Risk of bias’ tool. We requested missing data from one author but the data were no longer available. The outcomes are reported narratively: we performed no meta-analyses because of the heterogeneity of the available data. Main results We identified three new studies in this update of the review. In total seven studies were eligible for inclusion, three were ongoing RCTs and four were completed studies. The four completed studies were included in the original review and the three ongoing studies were included in this update. We did not identify any RCTs that compared TXA with EACA. Of the four completed studies, one cross-over TXA study (eight participants) was excluded from the outcome analysis because it had very flawed study methodology. Data from the other three studies were all at unclear risk of bias due to lack of reporting of study methodology. Three studies (two TXA (12 to 56 participants), one EACA (18 participants) reported in four articles (published 1983 to 1995) were included in the narrative review. All three studies compared the drug with placebo. All three studies included adults with acute leukaemia receiving chemotherapy. One study (12 participants) only included participants with acute promyelocytic leukaemia. None of the studies included children. One of the three studies reported funding sources and this study was funded by a charity. We are uncertain whether antifibrinolytics reduce the risk of bleeding (three studies; 86 participants; very low-quality evidence). Only one study reported the number of bleeding events per participant and there was no difference in the number of bleeding events seen during induction or consolidation chemotherapy between TXA and placebo (induction; 38 participants; mean difference (MD) 1.70 bleeding events, 95% confidence interval (CI) −0.37 to 3.77: consolidation; 18 participants; MD −1.50 bleeding events, 95% CI −3.25 to 0.25; very low-quality evidence). The two other studies suggested bleeding was reduced in the antifibrinolytic study arm, but this was statistically significant in only one of these two studies. Two studies reported thromboembolism and no events occurred (68 participants, very low-quality evidence). All three studies reported a reduction in platelet transfusion usage (three studies, 86 participants; very low-quality evidence), but this was reported in different ways and no meta-analysis could be performed. No trials reported the number of platelet transfusions per participant. Only one study reported the number of platelet components per participant and there was a reduction in the number of platelet components per participant during consolidation chemotherapy but not during induction chemotherapy (consolidation; 18 participants; MD −5.60 platelet units, 95% CI −9.02 to −2.18: induction; 38 participants, MD −1.00 platelet units, 95% CI −9.11 to 7.11; very low-quality evidence). Only one study reported adverse events of TXA as an outcome measure and none occurred. One study stated side effects of EACA were minimal but no further information was provided (two studies, 74 participants, very low-quality evidence). None of the studies reported on the following pre-specified outcomes: overall mortality, adverse events of transfusion, disseminated intravascular coagulation (DIC) or quality of life (QoL). Authors’ conclusions Our results indicate that the evidence available for the use of antifibrinolytics in haematology patients is very limited. The trials were too small to assess whether or not antifibrinolytics decrease bleeding. No trials reported the number of platelet transfusions per participant. The trials were too small to assess whether or not antifibrinolytics increased the risk of thromboembolic events or other adverse events. There are three ongoing RCTs (1276 participants) due to be completed in 2017 and 2020. PMID:26978005

Low-Dose or High-Dose Rocuronium Reversed with Neostigmine or Sugammadex for Cesarean Delivery Anesthesia: A Randomized Controlled Noninferiority Trial of Time to Tracheal Intubation and Extubation.

PubMed

Stourac, Petr; Adamus, Milan; Seidlova, Dagmar; Pavlik, Tomas; Janku, Petr; Krikava, Ivo; Mrozek, Zdenek; Prochazka, Martin; Klucka, Jozef; Stoudek, Roman; Bartikova, Ivana; Kosinova, Martina; Harazim, Hana; Robotkova, Hana; Hejduk, Karel; Hodicka, Zuzana; Kirchnerova, Martina; Francakova, Jana; Obare Pyszkova, Lenka; Hlozkova, Jarmila; Sevcik, Pavel

2016-05-01

Rocuronium for cesarean delivery under general anesthesia is an alternative to succinylcholine for rapid-sequence induction of anesthesia because of the availability of sugammadex for reversal of neuromuscular blockade. However, there are no large well-controlled studies in women undergoing general anesthesia for cesarean delivery. The aim of this noninferiority trial was to determine whether rocuronium and sugammadex confer benefit in time to tracheal intubation (primary outcome) and other neuromuscular blockade outcomes compared with succinylcholine, rocuronium, and neostigmine in women undergoing general anesthesia for cesarean delivery. We aimed to enroll all women undergoing general anesthesia for cesarean delivery in the 2 participating university hospitals (Brno, Olomouc, Czech Republic) in this single-blinded, randomized, controlled study. Women were randomly assigned to the ROC group (muscle relaxation induced with rocuronium 1 mg/kg and reversed with sugammadex 2-4 mg/kg) or the SUX group (succinylcholine 1 mg/kg for induction, rocuronium 0.3 mg/kg for maintenance, and neostigmine 0.03 mg/kg for reversal of the neuromuscular blockade). The interval from the end of propofol administration to tracheal intubation was the primary end point with a noninferiority margin of 20 seconds. We recorded intubating conditions (modified Viby-Mogensen score), neonatal outcome (Apgar score <7; umbilical artery pH), anesthesia complications, and subjective patient complaints 24 hours after surgery. We enrolled 240 parturients. The mean time to tracheal intubation was 2.9 seconds longer in the ROC group (95% confidence interval, -5.3 to 11.2 seconds), noninferior compared with the SUX group. Absence of laryngoscopy resistance was greater in the ROC than in the SUX groups (ROC, 87.5%; SUX, 74.2%; P = 0.019), but there were no differences in vocal cord position (P = 0.45) or intubation response (P = 0.31) between groups. No statistically significant differences in incidence of anesthesia complications or in neonatal outcome were found (10-minute Apgar score <7, P = 0.07; umbilical artery pH, P = 0.43). The incidence of postpartum myalgia was greater in the SUX group (ROC 0%; SUX 6.7%; P = 0.007). The incidence of subjective complaints was lower in the ROC group (ROC, 21.4%; SUX, 37.5%; P = 0.007). We conclude that rocuronium for rapid-sequence induction is noninferior for time to tracheal intubation and is accompanied by more frequent absence of laryngoscopy resistance and lower incidence of myalgia in comparison with succinylcholine for cesarean delivery under general anesthesia.

Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial.

PubMed

Ferreri, Andrés J M; Cwynarski, Kate; Pulczynski, Elisa; Fox, Christopher P; Schorb, Elisabeth; La Rosée, Paul; Binder, Mascha; Fabbri, Alberto; Torri, Valter; Minacapelli, Eleonora; Falautano, Monica; Ilariucci, Fiorella; Ambrosetti, Achille; Roth, Alexander; Hemmaway, Claire; Johnson, Peter; Linton, Kim M; Pukrop, Tobias; Sønderskov Gørløv, Jette; Balzarotti, Monica; Hess, Georg; Keller, Ulrich; Stilgenbauer, Stephan; Panse, Jens; Tucci, Alessandra; Orsucci, Lorella; Pisani, Francesco; Levis, Alessandro; Krause, Stefan W; Schmoll, Hans J; Hertenstein, Bernd; Rummel, Mathias; Smith, Jeffery; Pfreundschuh, Michael; Cabras, Giuseppina; Angrilli, Francesco; Ponzoni, Maurilio; Deckert, Martina; Politi, Letterio S; Finke, Jürgen; Reni, Michele; Cavalli, Franco; Zucca, Emanuele; Illerhaus, Gerald

2017-11-01

The International Extranodal Lymphoma Study Group-32 (IELSG32) trial is an international randomised phase 2 study that addresses two key clinical questions in the treatment of patients with newly diagnosed primary CNS lymphoma. Results of the first randomisation have demonstrated that methotrexate, cytarabine, thiotepa, and rituximab (called the MATRix regimen) is the induction combination associated with significantly better outcome compared with the other induction combinations tested. Here, we report the results of the second randomisation that addresses the efficacy of myeloablative chemotherapy supported by autologous stem-cell transplantation (ASCT), as an alternative to whole-brain radiotherapy (WBRT), as consolidation after high-dose-methotrexate-based chemoimmunotherapy. HIV-negative patients (aged 18-70 years) with newly diagnosed primary CNS lymphoma and an Eastern Cooperative Oncology Group performance status of 0-3 were randomly assigned to receive four courses of methotrexate 3·5 g/m 2 on day 1 plus cytarabine 2 g/m 2 twice daily on days 2 and 3 (group A); or the same combination plus two doses of rituximab 375 mg/m 2 on days -5 and 0 (group B); or the same methotrexate-cytarabine-rituximab combination plus thiotepa 30 mg/m 2 on day 4 (group C), with the three groups repeating treatment every 3 weeks. Patients with responsive or stable disease after induction treatment, with adequate autologous peripheral blood stem-cell collection, and without persistent iatrogenic side-effects, were eligible for the second randomisation between WBRT (photons of 4-10 MeV; five fractions per week; fraction size 180 cGy; started within 4 weeks from the last induction course; group D) and carmustine-thiotepa conditioned ASCT (carmustine 400 mg/m 2 on day -6, and thiotepa 5 mg/kg every 12 h on days -5 and -4, followed by reinfusion of autologous peripheral blood stem cells; group E). A permuted block randomised design was adopted for both randomisations, and a computer-generated randomisation list was used within each stratum. No masking after assignment to intervention was adopted. The primary endpoint was 2-year progression-free survival, with induction group and response to induction chemotherapy as stratification parameters. Analyses were done on a modified intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT01011920. Between Feb 19, 2010, and Aug 27, 2014, 227 patients were recruited from 53 centres in five countries. 219 of 227 enrolled patients were assessable. Of the 122 patients eligible for the second randomisation, 118 patients were randomly assigned to WBRT or ASCT (59 patients per group) and constitute the study population. WBRT and ASCT were both effective, and achieved the predetermined efficacy threshold of at least 40 progression-free survivors at 2 years among the first 52 patients in both groups D and E. There were no significant differences in 2-year progression-free survival between WBRT and ASCT: 80% (95% CI 70-90) in group D and 69% (59-79) in group E (hazard ratio 1·50, 95% CI 0·83-2·71; p=0·17). Both consolidation therapies were well tolerated. Grade 4 non-haematological toxicity was uncommon; as expected, haematological toxicity was more common in patients treated with ASCT than in those who received WBRT. Two toxic deaths (infections) were recorded, both in patients who received ASCT. WBRT and ASCT are both feasible and effective as consolidation therapies after high-dose methotrexate-based chemoimmunotherapy in patients aged 70 years or younger with primary CNS lymphoma. The risks and implications of cognitive impairment after WBRT should be considered at the time of therapeutic decision. Agenzia Italiana del Farmaco, Cancer Research UK, Oncosuisse, and Swiss National Science Foundation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Stepping Up to Motherhood among Inner-City Teens

ERIC Educational Resources Information Center

Shanok, Arielle F.; Miller, Lisa

2007-01-01

This mixed-methods, context-oriented study explored transitions to motherhood among pregnant and newly parenting inner-city teenagers (n = 80) attending an alternative public school. Additionally, a novel research approach was assessed. Using data from a 2-year psychotherapy trial, inductive content analyses of therapy sessions and post hoc…

Loss of long term protection with the inclusion of HIV pol to a DNA vaccine encoding gag.

PubMed

Garrod, Tamsin J; Gargett, Tessa; Yu, Wenbo; Major, Lee; Burrell, Christopher J; Wesselingh, Steven; Suhrbier, Andreas; Grubor-Bauk, Branka; Gowans, Eric J

2014-11-04

Traditional vaccine strategies that induce antibody responses have failed to protect against HIV infection in clinical trials, and thus cell-mediated immunity is now an additional criterion. Recent clinical trials that aimed to induce strong T cell responses failed to do so. Therefore, to enhance induction of protective T cell responses, it is crucial that the optimum antigen combination is chosen. Limited research has been performed into the number of antigens selected for an HIV vaccine. This study aimed to compare DNA vaccines encoding either a single HIV antigen or a combination of two antigens, using intradermal vaccination of C57BL/6 mice. Immune assays were performed on splenocytes, and in vivo protection was examined by challenge with a chimeric virus, EcoHIV, able to infect mouse but not human leukocytes, at 10 days (short term) and 60 days (long term) post final vaccination. At 60 days there was significantly lower frequency of induced antigen-specific CD8(+) T cells in the spleens of pCMVgag-pol-vaccinated mice compared with mice which received pCMVgag only. Most importantly, short term viral control of EcoHIV was similar for pCMVgag and pCMVgag-pol-vaccinated mice at day 10, but only the pCMVgag-vaccinated significantly controlled EcoHIV at day 60 compared with pCMV-vaccinated mice, showing that control was reduced with the inclusion of the HIV pol gene. Copyright © 2014 Elsevier B.V. All rights reserved.

Skills-demands compatibility as a determinant of flow experience in an inductive reasoning task.

PubMed

Schiefele, Ulrich; Raabe, Andreas

2011-10-01

The skills-demands fit hypothesis of flow theory was examined. Based on the earlier finding that high demands in a game situation do not reduce the experience of flow, a cognitive task paradigm was used. The effect of skills-demands compatibility on the experience of flow but not of other, similar psychological states (i.e., concentration, negative and positive activation) was also investigated. Participants were 89 undergraduate students who worked on a number of inductive reasoning tasks in four successive trials with or without skills-demands compatibility. The results clearly supported the skills-demands fit hypothesis; concentration and activation were affected only by the tasks' difficulty. Inductive reasoning tasks are a useful tool for the experimental analysis of flow, and skills-demands compatibility is a significant and powerful condition of flow, but not of other, similar psychological states.

Feasibility Study of Sequentially Alternating EGFR-TKIs and Chemotherapy for Patients with Non-small Cell Lung Cancer.

PubMed

Takemura, Yoshizumi; Chihara, Yusuke; Morimoto, Yoshie; Tanimura, Keiko; Imabayashi, Tatsuya; Seko, Yurie; Kaneko, Yoshiko; Date, Koji; Ueda, Mikio; Arimoto, Taichiro; Iwasaki, Yoshinobu; Takayama, Koichi

2018-04-01

The purpose of this trial was to evaluate the feasibility and efficacy of alternating platinum-based doublet chemotherapy with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant non-small cell lung cancer (NSCLC). Chemotherapy-naive patients with advanced NSCLC harboring an EGFR mutation were enrolled. All patients underwent induction chemotherapy by sequentially alternating pemetrexed/cisplatin/bevacizumab and EGFR-TKIs followed by maintenance therapy with pemetrexed/bevacizumab and EGFR-TKIs. The primary outcome was the completion rate of the induction therapy. Eighteen eligible patients were enrolled between May 2011 and March 2016. The completion rate of induction therapy was 72.2% (13/18). Unfortunately, one patient developed grade 4 acute renal injury, but no other serious complications concerning this protocol were observed. Furthermore, diarrhea, rashes, and hematological adverse effects were mild. The completion rate of induction therapy was promising. Alternating chemotherapy and EGFR-TKIs should be further investigated regarding feasibility and efficacy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Neoadjuvant therapy for organ preservation in head and neck cancer.

PubMed

Urba, S G; Wolf, G T; Bradford, C R; Thornton, A F; Eisbruch, A; Terrell, J E; Carpenter, V; Miller, T; Tang, G; Strawderman, M

2000-12-01

We designed two sequential trials of induction chemotherapy followed by definitive radiation in patients with potentially resectable head and neck cancer to determine whether organ preservation is feasible without apparent compromise of survival Study Design Both trials were Phase II studies. Two clinical trials were conducted sequentially at the University of Michigan. Fifty-two patients enrolled in the first study and were treated with a planned three cycles of carboplatin and 5-fluorouracil. Patients who achieved at least 50% reduction in the size of the primary tumor received definitive radiation therapy, to a dose of 6600 to 7380 cGy. Patients with minimal response or progression had immediate salvage surgery. Thirty-seven patients enrolled in the second trial, in which the chemotherapy consisted of carboplatin, 5-fluororuracil, and leukovorin. Responders were treated with accelerated radiation therapy, to a total dose of 7120 cGy delivered in 41 fractions over 5.5 weeks. Toxicity and response were similar in both trials; therefore, the results are reported first separately and then combined for all 89 patients. Tumor sites included: oropharynx, 55 patients; hypopharynx, 34 patients. Eighty-three percent of patients tolerated all three cycles of chemotherapy and toxicity was mild. Response to chemotherapy was: 48% complete response at the primary tumor site, and 34% partial response at the primary tumor site. Initial organ preservation at individual tumor sites was: oropharynx, 58%; hypopharynx, 59%. Median survival was 28 months, and survival at 3 and 5 years was 40% and 24%, respectively. These two regimens were well tolerated, and survival did not appear to be compromised by organ preservation treatment compared with historical controls. This approach warrants further investigation, particularly in those patients for whom surgery could be functionally debilitating.

Preinduction incentive spirometry versus deep breathing to improve apnea tolerance during induction of anesthesia in patients of abdominal sepsis: A randomized trial.

PubMed

Tripathi, M; Subedi, A; Raimajhi, A; Pokharel, K; Pandey, M

2013-01-01

Abdominal sepsis is associated with varied degree of hypoxemia and atelactasis in the lung and can enhance the onset of desaturation of arterial blood during apnea. This study looked at methods to improve safety margin of apnea during induction of anesthesia in these high-risk patients. It was a randomized, single blind study on adult patients presenting for emergency laparotomy due to peritonitis in a university teaching hospital setting. In group 1 (IS) (n = 32), three sessions of incentive spirometry (IS) were performed within one hour before induction of anesthesia. In group 2 (DB) (n = 34), patients were subjected to deep breathing sessions in a similar manner. All patients received preoxygenation (100%) by mask for 3 min, followed by rapid-sequence induction of anesthesia using fentanyl, thiopental, and suxamethonium and endotracheal intubation. Patients were subjected to a period of apnea by keeping the end of the endotracheal tube open to air till they developed 95% hemoglobin saturation (SpO 2) by pulse oxymetry. Positive pressure ventilation was resumed at the end. We observed for hemodynamic changes, apnea time, and SpO 2 (100%) recovery time on resuming ventilation. Arterial blood gas samples were taken before intervention, after IS or DB, after preoxygenation, and at the end of apnea. One-way analysis of variance (ANOVA), X 2 test, Kaplan-Meier graph, and log-rank tests were applied to compare the two study groups. Oxygenation level in group 1 (265 ± 76.7 mmHg) patients was significantly (P < 0.001) higher than in group 2 (221 ± 61.8 mmHg)at the end of preoxygenation. The apnea time (median: lower bound - upper bound Confidence Interval apnea time) (272:240-279 s) in group 1 (IS) patients was significantly higher P < 0.05) than in group 2 (180:163-209 s) patients. Saturation recovery time (35:34-46 s) in group 1 (IS) patients was also quicker than in group 2 patients (48:44-58 s). IS in the preoperative period is superior to deep breathing sessions for improving apnea tolerance during induction of anesthesia in abdominal sepsis patients.

Conventional and high-dose daunorubicin and idarubicin in acute myeloid leukaemia remission induction treatment: a mixed treatment comparison meta-analysis of 7258 patients.

PubMed

Sekine, Leo; Morais, Vinícius Daudt; Lima, Karine Margarites; Onsten, Tor Gunnar Hugo; Ziegelmann, Patrícia Klarmann; Ribeiro, Rodrigo Antonini

2015-12-01

Previous meta-analyses suggested that acute myeloid leukaemia induction regimens containing idarubicin (IDA) or high-dose daunorubicin (HDD) induce higher rates of complete remission (CR) than conventional-dose daunorubicin (CDD), with a possible benefit in overall survival. However, robust comparisons between these regimens are still lacking. We conducted a mixed treatment comparison meta-analysis regarding these three regimens. Mixed treatment comparison is a statistical method of data summarization that aggregates data from both direct and indirect effect estimates. Literature search strategy included MEDLINE, EMBASE, Cochrane, Scielo and LILACS, from inception until August 2013 and resulted in the inclusion of 17 trials enrolling 7258 adult patients. HDD [relative risk (RR) 1.13; 95% credible interval (CrI) 1.02-1.26] and IDA (RR 1.13; 95% CrI 1.05-1.23) showed higher CR rates than CDD. IDA also led to lower long-term overall mortality rates when compared with CDD (RR 0.93, 95% CrI 0.86-0.99), whereas HDD and CDD were no different (RR 0.94, 95% CrI 0.85-1.02). HDD and IDA comparison did not reach statistically significant differences in CR (RR 1.00; 95% CrI 0.89-1.11) and in long-term mortality (RR 1.01, 95% CrI 0.91-1.11). IDA and HDD are consistently superior to CDD in inducing CR, and IDA was associated with lower long-term mortality. On the basis of these findings, we recommend incorporation of IDA and HDD instead of the traditional CDD as standard treatments for acute myeloid leukaemia induction. The lack of HDD benefit on mortality, when compared with CDD in this study, should be cautiously addressed, because it may have been susceptible to underestimation because of statistical power limitations. Copyright © 2014 John Wiley & Sons, Ltd.

Balancing the efficacy and safety of misoprostol: a meta-analysis comparing 25 versus 50 micrograms of intravaginal misoprostol for the induction of labour.

PubMed

McMaster, K; Sanchez-Ramos, L; Kaunitz, A M

2015-03-01

The optimal dose of misoprostol for the induction of labour remains uncertain. To compare the efficacy and safety of 25 versus 50 micrograms of intravaginal misoprostol tablets for the induction of labour and cervical ripening. We performed electronic and manual searches to identify relevant randomised trials. The efficacy outcomes assessed were rates of vaginal delivery within 24 hours, delivery within one dose, and oxytocin augmentation, and interval to delivery. The safety outcomes assessed were incidences of tachysystole, hyperstimulation, caesarean delivery, cesarean delivery for non-reassuring fetal heart rate (FHR), operative vaginal delivery, abnormal 5-minute Apgar score, abnormal cord gas values, admission to a neonatal intensive care unit (NICU), and meconium passage. Thirteen studies (1945 women) were included. Relative risk (RR) and 95% confidence intervals (CI) were calculated using fixed-effects and random-effects models. We found that 25 micrograms was less efficacious, with lower rates of delivery after one dose (RR 0.59; 95% CI 0.39-0.88) and vaginal delivery within 24 hours (RR 0.88; 95% CI 0.79-0.96), and with increased rates of oxytocin augmentation (RR 1.54, 95% CI 1.36-1.75). We noted an improved safety profile with 25 micrograms, however, with decreased rates of tachysystole (RR 0.46; 95% CI 0.35-0.61), hyperstimulation (RR 0.5; 95% CI 0.31-0.78), caesarean deliveries for non-reassuring FHR (RR 0.67; 95% CI 0.52-0.87), NICU admissions (RR 0.63; 95% CI 0.4-0.98), and meconium passage (RR 0.65; 95% CI 0.45-0.96). Although 50 micrograms of intravaginal misoprostol may be more efficacious, safety concerns make the 25-microgram dose preferable. © 2014 Royal College of Obstetricians and Gynaecologists.

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

PubMed Central

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

2010-01-01

Background: Mesalamine is the first-line drug for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two mesalamine formulations for the induction of remission in patients with UC. Methods: In a multicenter, double-blind, randomized study, 229 patients with mild-to-moderate active UC were assigned to 4 groups: 66 and 65 received a pH-dependent release formulation of 2.4 g/day (pH-2.4 g) or 3.6 g/day (pH-3.6 g), respectively; 65 received a time-dependent release formulation of 2.25 g/day (Time-2.25 g), and 33 received placebo (Placebo). The drugs were administered three times daily for eight weeks. The primary endpoint was a decrease in the UC disease activity index (UC-DAI). Results: In the full analysis set (n = 225) the decrease in UC-DAI in each group was 1.5 in pH-2.4 g, 2.9 in pH-3.6 g, 1.3 in Time-2.25 g and 0.3 in Placebo, respectively. These results demonstrate the superiority of pH-3.6 g over Time-2.25 g (P = 0.003) and the noninferiority of pH-2.4 g to Time-2.25 g. Among the patients with proctitis-type UC, a significant decrease in UC-DAI was observed in pH-2.4 g and pH-3.6 g as compared to Placebo, but not in Time-2.25 g. No differences were observed in the safety profiles. Conclusions: Higher dose of the pH-dependent release formulation was more effective for induction of remission in patients with mild-to-moderate active UC. Additionally, the pH-dependent release formulation was preferable to the time-dependent release formulation for patients with proctitis-type UC (UMIN Clinical Trials Registry, no. C000000288). (Inflamm Bowel Dis 2010) PMID:20049950

Taxane-cisplatin-fluorouracil as induction chemotherapy for advanced head and neck cancer: a meta-analysis of the 5-year efficacy and safety.

PubMed

Qian, Xu; Ma, Chenming; Hoffmann, Thomas K; Kaufmann, Andreas M; Albers, Andreas E

2015-01-01

The objective of this study was to compare the efficacy and safety of taxane (docetaxel or paclitaxel), cisplatin, and fluorouracil (Tax-PF) with cisplatin plus fluorouracil (PF) regimen by a meta-analysis of data retrieved from the literature. Seven randomized clinical trials were identified, which included patients with advanced head and neck cancer who underwent induction chemotherapy with either a Tax-PF or PF protocol. The outcomes included the 3-year and 5-year overall survival (OS) and progression-free survival (PFS), overall response rate (ORR) and different types of adverse events. The 3-year OS rate (HR: 1.14; 95% CI: 1.03 to 1.25; P = 0.008), 3-year PFS rate (HR: 1.24; 95% CI: 1.08 to 1.43; P = 0.002), 5-year OS rate (HR: 1.30; 95% CI, 1.09 to 1.55;P = 0.003), 5-year PFS rate (HR: 1.39; 95% CI, 1.14 to 1.70; P = 0.001) and ORR to chemotherapy (OR 1.66; 95% CI, 1.35 to 2.05; P < 0.001) of the patients in the Tax-PF group were statistically superior to those in the PF group. In terms of toxicities, the incidence of febrile neutropenia (OR 2.36; 95% CI, 1.62 to 3.46; P < 0.001), alopecia (OR 8.22; 95% CI, 3.99 to 16.92; P < 0.001), diarrhea (OR 1.57; 95% CI, 1.05 to 2.36; P = 0.03) and leukopenia (OR 2.79; 95% CI, 1.86 to 4.21; P < 0.001) was higher in the Tax-PF group. The Tax-PF induction chemotherapy improved PFS and OS, and the ORR was better as compared to PF-based therapy regimens at the cost of a higher incidence of adverse events.

An evaluation of prostaglandin E2 vaginal gel use in practice.

PubMed

Taylor, S J; Peat, J K; Armour, C L

1999-08-01

The purpose of this study was to investigate the effectiveness of prostaglandin E2 vaginal gel as used in practice, rather than its efficacy as assessed in randomised, controlled, clinical trials. This product is used to ripen the cervix prior to induction of labour, sometimes making unnecessary the use of the standard treatment for induction, artificial rupture of the membranes (ARM) plus oxytocin. In this study, effectiveness of the gel was assessed in terms of changes in mode of delivery, and in particular the risk of Caesarean section. An historical control was used and the risk of Caesarean section for women induced in the 1990/91 (before the introduction of the gel) was compared with that for women induced in 1992/93 (after the introduction of the gel). Maternal characteristics which may have been different in the two groups and factors which might influence the risk of Caesarean section were controlled for statistically using logistic regression, thus reducing any bias towards one group. After adjusting for the factors which had a significant effect on the process of labour from induction to birth, it was found that the risk of Caesarean section was not significantly lower in the 1992/93-time period, when the gel was in regular use, from that in the 2 years prior to its introduction (Odds ratio 1.09, CI95% 0.88, 1.36). Following the introduction of PGE2 gel, no difference in effectiveness, as measured in terms of mode of delivery, was detected in this study of practice, which included patients with more complex obstetric problems.

Tofacitinib induction and maintenance therapy in East Asian patients with active ulcerative colitis: subgroup analyses from three phase 3 multinational studies.

PubMed

Motoya, Satoshi; Watanabe, Mamoru; Kim, Hyo Jong; Kim, Young Ho; Han, Dong Soo; Yuasa, Hirotoshi; Tabira, Junichi; Isogawa, Naoki; Arai, Shoko; Kawaguchi, Isao; Hibi, Toshifumi

2018-04-01

Tofacitinib is an oral, small-molecule Janus kinase inhibitor being investigated for ulcerative colitis (UC). In OCTAVE Induction 1 and 2, patients with moderately to severely active UC received placebo or tofacitinib 10 mg twice daily (BID) for 8 weeks. Clinical responders in OCTAVE Induction were re-randomized to 52 weeks' therapy with placebo, tofacitinib 5 mg BID, or tofacitinib 10 mg BID. We conducted post-hoc efficacy and safety analyses of East Asian patients in OCTAVE Induction 1 and 2 and OCTAVE Sustain. A total of 121 East Asian (Japan, Korea, and Taiwan) patients were randomized in OCTAVE Induction 1 and 2 (placebo, n=26; tofacitinib 10 mg BID, n=95), and 63 in OCTAVE Sustain (placebo, n=20; tofacitinib 5 mg BID, n=22; tofacitinib 10 mg BID, n=21). At week 8 of OCTAVE Induction 1 and 2, 18.9% of patients (18/95) achieved remission with tofacitinib 10 mg BID versus 3.8% (1/26) with placebo. In OCTAVE Sustain, the week 52 remission rates were 45.5% (10/22), 47.6% (10/21), and 15.0% (3/20) with 5 mg BID, 10 mg BID, and placebo, respectively. Adverse event rates were similar between groups in OCTAVE Induction and numerically higher with tofacitinib in OCTAVE Sustain. Serious adverse event rates were similar across groups in all studies. Infections were numerically more frequent with tofacitinib than placebo. Increases in serum lipid levels were observed with tofacitinib. In East Asian patients with UC, tofacitinib demonstrated numerically greater efficacy versus placebo as induction and maintenance therapy, with a safety profile consistent with the global study population. ClinicalTrials.gov: NCT01465763; NCT01458951; NCT01458574.

Outcomes of elective induction of labour compared with expectant management: population based study

PubMed Central

Ferguson, Evelyn; Duffy, Andrew; Ford, Ian; Chalmers, James; Norman, Jane E

2012-01-01

Objective To determine neonatal outcomes (perinatal mortality and special care unit admission) and maternal outcomes (mode of delivery, delivery complications) of elective induction of labour compared with expectant management. Design Retrospective cohort study using an unselected population database. Setting Consultant and midwife led obstetric units in Scotland 1981-2007. Participants 1 271 549 women with singleton pregnancies of 37 weeks or more gestation. Interventions Outcomes of elective induction of labour (induction of labour with no recognised medical indication) at 37, 38, 39, 40, and 41 weeks’ gestation compared with those of expectant management (continuation of pregnancy to either spontaneous labour, induction of labour or caesarean section at a later gestation). Main outcome measures Extended perinatal mortality, mode of delivery, postpartum haemorrhage, obstetric anal sphincter injury, and admission to a neonatal or special care baby unit. Outcomes were adjusted for age at delivery, parity, year of birth, birth weight, deprivation category, and, where appropriate, mode of delivery. Results At each gestation between 37 and 41 completed weeks, elective induction of labour was associated with a decreased odds of perinatal mortality compared with expectant management (at 40 weeks’ gestation 0.08% (37/44 764) in the induction of labour group versus 0.18% (627/350 643) in the expectant management group; adjusted odds ratio 0.39, 99% confidence interval 0.24 to 0.63), without a reduction in the odds of spontaneous vertex delivery (at 40 weeks’ gestation 79.9% (35 775/44 778) in the induction of labour group versus 73.7% (258 665/350 791) in the expectant management group; adjusted odds ratio 1.26, 1.22 to 1.31). Admission to a neonatal unit was, however, increased in association with elective induction of labour at all gestations before 41 weeks (at 40 weeks’ gestation 8.0% (3605/44 778) in the induction of labour group compared with 7.3% (25 572/350 791) in the expectant management group; adjusted odds ratio 1.14, 1.09 to 1.20). Conclusion Although residual confounding may remain, our findings indicate that elective induction of labour at term gestation can reduce perinatal mortality in developed countries without increasing the risk of operative delivery. PMID:22577197

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.

Evaluation of two carrier protein–angiotensin I conjugate vaccines to assess their future potential to control high blood pressure (hypertension) in man

PubMed Central

Downham, M R; Auton, T R; Rosul, A; Sharp, H L; Sjöström, L; Rushton, A; Richards, J P; Mant, T G K; Gardiner, S M; Bennett, T; Glover, J F

2003-01-01

Aims We aim to modulate the renin–angiotensin system (RAS) by active immunization against angiotensin I hormone (AI), potentially providing a novel conjugate vaccine treatment for hypertension in man. Methods Immunization studies in rat and human subjects compare the effectiveness of tetanus toxoid (TT) and keyhole limpet haemocyanin (KLH) vaccines for immunotherapy following conjugation with an AI peptide analogue (AI). Cardiovascular responses were assessed in immunized rats and human subjects (two-dose trial only), following increasing i.v. infusions of either AI or angiotensin II hormone (AII). Results The AI–TT and AI–KLH conjugate vaccines induced an equivalent immune response, and inhibition of the pressor effects to exogenous AI in rats. Single-dose clinical trials with both conjugate vaccines only resulted in an immune response to the KLH carrier protein. A two-dose clinical trial of AI–KLH conjugate vaccine resulted in a significant immune response to AI. A shift in diastolic blood pressure (DBP) dose–response was demonstrated following challenge with AI and AII for the study volunteer showing the largest anti-AI IgG induction. Conclusion KLH was shown to be a suitable alternative to TT as a carrier protein for AI, thus supporting continued evaluation of our AI–KLH conjugate vaccine for treatment of hypertension in man. PMID:14651724

A wearable respiratory monitoring device--the between-days variability of calibration.

PubMed

Heyde, C; Mahler, H; Roecker, K; Gollhofer, A

2015-01-01

The between-days variability in ascertained gain factors for calibration of a wearable respiratory inductance plethysmograph (RIP) and validity thereof for the repeated use during exercise were examined. Consecutive 5-min periods of standing still, slow running at 8 km·h(-1), fast running at 14 km·h(-1) (male) or 12 km·h(-1) (female) and recovery were repeated by 10 healthy subjects on 5 days. Breath-by-breath data were recorded simultaneously by flow meter and RIP. Gain factors were determined individually for each trial (CALIND) via least square regression. Reliability and variability in gain factors were quantified respectively by intraclass correlation coefficients (ICC) and limits of agreement. Within a predefined error range of ±20% the amount of RIP-derived tidal volumes after CALIND was compared to corresponding amounts when gain factors of the first trial were applied on the following 4 trials (CALFIRST). ICC ranged within 0.96 and 0.98. The variability in gain factors (up to ± 24.06%) was reduced compensatively by their sum. Amounts of breaths within the predefined error range did not differ between CALIND and (CALFIRST) (P>0.32). The between-days variability of gain factors for a wearable RIP-device does not show impaired reliability in further derived tidal volumes. © Georg Thieme Verlag KG Stuttgart · New York.

VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial.

PubMed

Moreau, Philippe; Hulin, Cyrille; Macro, Margaret; Caillot, Denis; Chaleteix, Carine; Roussel, Murielle; Garderet, Laurent; Royer, Bruno; Brechignac, Sabine; Tiab, Mourad; Puyade, Mathieu; Escoffre, Martine; Stoppa, Anne-Marie; Facon, Thierry; Pegourie, Brigitte; Chaoui, Driss; Jaccard, Arnaud; Slama, Borhane; Marit, Gerald; Laribi, Karim; Godmer, Pascal; Luycx, Odile; Eisenmann, Jean-Claude; Allangba, Olivier; Dib, Mamoun; Araujo, Carla; Fontan, Jean; Belhadj, Karim; Wetterwald, Marc; Dorvaux, Véronique; Fermand, Jean-Paul; Rodon, Philippe; Kolb, Brigitte; Glaisner, Sylvie; Malfuson, Jean-Valere; Lenain, Pascal; Biron, Laetitia; Planche, Lucie; Caillon, Helene; Avet-Loiseau, Herve; Dejoie, Thomas; Attal, Michel

2016-05-26

The Intergroupe Francophone du Myélome conducted a randomized trial to compare bortezomib-thalidomide-dexamethasone (VTD) with bortezomib-cyclophosphamide-dexamethasone (VCD) as induction before high-dose therapy and autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma. Overall, a total of 340 patients were centrally randomly assigned to receive VTD or VCD. After 4 cycles, on an intent-to-treat basis, 66.3% of the patients in the VTD arm achieved at least a very good partial response (primary end point) vs 56.2% in the VCD arm (P = .05). In addition, the overall response rate was significantly higher in the VTD arm (92.3% vs 83.4% in the VCD arm; P = .01). Hematologic toxicity was higher in the VCD arm, with significantly increased rates of grade 3 and 4 anemia, thrombocytopenia, and neutropenia. On the other hand, the rate of peripheral neuropathy (PN) was significantly higher in the VTD arm. With the exception of hematologic adverse events and PN, other grade 3 or 4 toxicities were rare, with no significant differences between the VTD and VCD arms. Our data support the preferential use of VTD rather than VCD in preparation for ASCT. This trial was registered at www.clinicaltrials.gov as #NCT01564537 and at EudraCT as #2013-003174-27. © 2016 by The American Society of Hematology.

Dopaminergic Modulation of the Persistence of One-Trial Hippocampus-Dependent Memory

ERIC Educational Resources Information Center

O'Carroll, Colin M.; Martin, Stephen J.; Sandin, Johan; Frenguelli, Bruno; Morris, Richard G. M.

2006-01-01

The persistence of new memory traces in the hippocampus, encoded following appropriate activation of glutamatergic receptors and the induction of synaptic plasticity, can be influenced by heterosynaptic activation of neuromodulatory brain systems. We therefore investigated the effects of a hippocampus-specific blockade of dopamine D1/D5 receptors…

Unexpected Effects of a System-Distributed Mobile Application in Maternity Care: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Ledford, Christy J. W.; Womack, Jasmyne J.; Rider, Heather A.; Seehusen, Angela B.; Conner, Stephen J.; Lauters, Rebecca A.; Hodge, Joshua A.

2018-01-01

Background: As pregnant mothers increasingly engage in shared decision making regarding prenatal decisions, such as induction of labor, the patient's level of activation may influence pregnancy outcomes. One potential tool to increase patient activation in the clinical setting is mobile applications. However, research is limited in comparing…

Improving Teacher Induction

ERIC Educational Resources Information Center

Wayne, Andrew J.; Youngs, Peter; Fleischman, Steve

2005-01-01

A common problem faced by new teachers is lack of supervisory support and learning on the job through trial and error can often dishearten the rookie enough to abandon the job and often the profession. Suggestions are offered on how to redress this problem and a starting point could be the implementation of what the Alliance for Excellent…

Thiopurines and inflammatory bowel disease: Current evidence and a historical perspective

PubMed Central

Axelrad, Jordan E; Roy, Abhik; Lawlor, Garrett; Korelitz, Burton; Lichtiger, Simon

2016-01-01

The use of thiopurines in inflammatory bowel disease (IBD) has been examined in numerous prospective, controlled trials, with a majority demonstrating a clinical benefit. We conducted this review to describe the historical and current evidence in the use of thiopurines in IBD. A systematic search was performed on MEDLINE between 1965 and 2016 to identify studies on thiopurines in IBD. The most robust evidence for thiopurines in IBD includes induction of remission in combination with anti-tumor necrosis factor (anti-TNF) agents, and maintenance of remission and post-operative maintenance in Crohn’s disease. Less evidence exists for thiopurine monotherapy in induction of remission, maintenance of ulcerative colitis, chemoprevention of colorectal cancer, and in preventing immunogenicity to anti-TNF. Evidence was often limited by trial design. Overall, thiopurines have demonstrated efficacy in a broad range of presentations of IBD. With more efficacious novel therapeutic agents, the positioning of thiopurines in the management of IBD will change and future studies will analyze the benefit of thiopurines alone and in conjunction with these new medications. PMID:28028358

Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (including a review of TA140 and TA262): clinical effectiveness systematic review and economic model.

PubMed

Archer, Rachel; Tappenden, Paul; Ren, Shijie; Martyn-St James, Marrissa; Harvey, Rebecca; Basarir, Hasan; Stevens, John; Carroll, Christopher; Cantrell, Anna; Lobo, Alan; Hoque, Sami

2016-05-01

Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the UK. UC can have a considerable impact on patients' quality of life. The burden for the NHS is substantial. To evaluate the clinical effectiveness and safety of interventions, to evaluate the incremental cost-effectiveness of all interventions and comparators (including medical and surgical options), to estimate the expected net budget impact of each intervention, and to identify key research priorities. Peer-reviewed publications, European Public Assessment Reports and manufacturers' submissions. The following databases were searched from inception to December 2013 for clinical effectiveness searches and from inception to January 2014 for cost-effectiveness searches for published and unpublished research evidence: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effects, the Health Technology Assessment database and NHS Economic Evaluation Database; ISI Web of Science, including Science Citation Index, and the Conference Proceedings Citation Index-Science and Bioscience Information Service Previews. The US Food and Drug Administration website and the European Medicines Agency website were also searched, as were research registers, conference proceedings and key journals. A systematic review [including network meta-analysis (NMA)] was conducted to evaluate the clinical effectiveness and safety of named interventions. The health economic analysis included a review of published economic evaluations and the development of a de novo model. Ten randomised controlled trials were included in the systematic review. The trials suggest that adult patients receiving infliximab (IFX) [Remicade(®), Merck Sharp & Dohme Ltd (MSD)], adalimumab (ADA) (Humira(®), AbbVie) or golimumab (GOL) (Simponi(®), MSD) were more likely to achieve clinical response and remission than those receiving placebo (PBO). Hospitalisation data were limited, but suggested more favourable outcomes for ADA- and IFX-treated patients. Data on the use of surgical intervention were sparse, with a potential benefit for intervention-treated patients. Data were available from one trial to support the use of IFX in paediatric patients. Safety issues identified included serious infections, malignancies and administration site reactions. Based on the NMA, in the induction phase, all biological treatments were associated with statistically significant beneficial effects relative to PBO, with the greatest effect associated with IFX. For patients in response following induction, all treatments except ADA and GOL 100 mg at 32-52 weeks were associated with beneficial effects when compared with PBO, although these were not significant. The greatest effects at 8-32 and 32-52 weeks were associated with 100 mg of GOL and 5 mg/kg of IFX, respectively. For patients in remission following induction, all treatments except ADA at 8-32 weeks and GOL 50 mg at 32-52 weeks were associated with beneficial effects when compared with PBO, although only the effect of ADA at 32-52 weeks was significant. The greatest effects were associated with GOL (at 8-32 weeks) and ADA (at 32-52 weeks). The economic analysis suggests that colectomy is expected to dominate drug therapies, but for some patients, colectomy may not be considered acceptable. In circumstances in which only drug options are considered, IFX and GOL are expected to be ruled out because of dominance, while the incremental cost-effectiveness ratio for ADA versus conventional treatment is approximately £50,300 per QALY gained. The health economic model is subject to several limitations: uncertainty associated with extrapolating trial data over a lifetime horizon, the model does not consider explicit sequential pathways of non-biological treatments, and evidence relating to complications of colectomy was identified through consideration of approaches used within previous models rather than a full systematic review. Adult patients receiving IFX, ADA or GOL were more likely to achieve clinical response and remission than those receiving PBO. Further data are required to conclusively demonstrate the effect of interventions on hospitalisation and surgical outcomes. The economic analysis indicates that colectomy is expected to dominate medical treatments for moderate to severe UC. This study is registered as PROSPERO CRD42013006883. The National Institute for Health Research Health Technology Assessment programme.

Improved Outcomes With Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non-High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial.

PubMed

Platzbecker, Uwe; Avvisati, Giuseppe; Cicconi, Laura; Thiede, Christian; Paoloni, Francesca; Vignetti, Marco; Ferrara, Felicetto; Divona, Mariadomenica; Albano, Francesco; Efficace, Fabio; Fazi, Paola; Sborgia, Marco; Di Bona, Eros; Breccia, Massimo; Borlenghi, Erika; Cairoli, Roberto; Rambaldi, Alessandro; Melillo, Lorella; La Nasa, Giorgio; Fiedler, Walter; Brossart, Peter; Hertenstein, Bernd; Salih, Helmut R; Wattad, Mohammed; Lübbert, Michael; Brandts, Christian H; Hänel, Mathias; Röllig, Christoph; Schmitz, Norbert; Link, Hartmut; Frairia, Chiara; Pogliani, Enrico Maria; Fozza, Claudio; D'Arco, Alfonso Maria; Di Renzo, Nicola; Cortelezzi, Agostino; Fabbiano, Francesco; Döhner, Konstanze; Ganser, Arnold; Döhner, Hartmut; Amadori, Sergio; Mandelli, Franco; Ehninger, Gerhard; Schlenk, Richard F; Lo-Coco, Francesco

2017-02-20

Purpose The initial results of the APL0406 trial showed that the combination of all- trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series of patients enrolled onto this trial. Patients and Methods The APL0406 study was a prospective, randomized, multicenter, open-label, phase III noninferiority trial. Eligible patients were adults between 18 and 71 years of age with newly diagnosed, low- or intermediate-risk APL (WBC at diagnosis ≤ 10 × 10 9 /L). Overall, 276 patients were randomly assigned to receive ATRA-ATO or ATRA-CHT between October 2007 and January 2013. Results Of 263 patients evaluable for response to induction, 127 (100%) of 127 patients and 132 (97%) of 136 patients achieved complete remission (CR) in the ATRA-ATO and ATRA-CHT arms, respectively ( P = .12). After a median follow-up of 40.6 months, the event-free survival, cumulative incidence of relapse, and overall survival at 50 months for patients in the ATRA-ATO versus ATRA-CHT arms were 97.3% v 80%, 1.9% v 13.9%, and 99.2% v 92.6%, respectively ( P < .001, P = .0013, and P = .0073, respectively). Postinduction events included two relapses and one death in CR in the ATRA-ATO arm and two instances of molecular resistance after third consolidation, 15 relapses, and five deaths in CR in the ATRA-CHT arm. Two patients in the ATRA-CHT arm developed a therapy-related myeloid neoplasm. Conclusion These results show that the advantages of ATRA-ATO over ATRA-CHT increase over time and that there is significantly greater and more sustained antileukemic efficacy of ATO-ATRA compared with ATRA-CHT in low- and intermediate-risk APL.

Intesive fludarabine-high dose cytarabine-idarubicin combination as induction therapy with risk-adapted consolidation may improve treatment efficacy in younger Acute Myeloid Leukemia (AML) patients: Rationales, evidences and future perspectives.

PubMed

Guolo, Fabio; Minetto, Paola; Clavio, Marino; Miglino, Maurizio; Lemoli, Roberto Massimo; Gobbi, Marco

2017-03-22

Acute Myeloid Leukemia (AML) is the commonest form of leukemia in the adults, with an incidence of 3-4 cases per 100,000 people/year. After the first description of the effective cytarabine + antracycline (3+7) induction regimen, in the last 3 decades, no effective targeted drug has been included in the standard treatment of AML. Many efforts of modifying 3+7 adding a third drug or increasing the dose of anthracycline, cytarabine or both did not lead to substantial improvements, mainly due to increased toxicity. Many in vitro and in vivo evidences suggested that fludarabine may increase efficacy of cytarabine through a synergistic effect. Considering the continuous improvements in supportive care and management of infectious complications the feasibility of more intensive induction strategies have increased and a renewed interest in fludarabine-containing induction strategies arose. The recent MRC AML 15 trial has shown that a fludarabine-containing induction, FLAG-Ida, resulted superior to conventional 3+7 in terms of complete remission rates, relapse incidence and survival, although only a minority of patients could complete the whole planned consolidation program due to an excessive hematological toxicity. Our group recently published a 10-year experience with a fludarabine-containing induction that slightly differed from the MRC one and resulted in good efficacy and higher feasibility. In this commentary we review the major evidences supporting the employ of a fludarabine-containing induction in AML, and discuss the future perspectives.

Clinical and economic outcomes of rabbit antithymocyte globulin induction in adults who received kidney transplants from living unrelated donors and received cyclosporine-based immunosuppression.

PubMed

Miller, James T; Collins, Curtis D; Stuckey, Linda J; Luan, Fu L; Englesbe, Michael J; Magee, John C; Park, Jeong M

2009-10-01

To evaluate the efficacy, safety, and costs of rabbit antithymocyte globulin (TMG) induction in patients who received kidney transplants from living unrelated donors. Retrospective cohort study. Large academic medical center. Eighty-seven patients who received kidney transplants from living unrelated donors: 40 of the recipients underwent transplantation between January 1, 2003, and December 31, 2004, and did not receive TMG induction (no induction group); 47 underwent transplantation between January 1, 2005, and June 30, 2006, and received TMG induction (induction group). All patients received cyclosporine-based immunosuppression. Biopsy-proven acute rejection, posttransplantation complications, and inpatient hospital costs for the first 12 months after transplantation were compared between groups using standard univariate statistical analyses. Induction significantly decreased the occurrence of biopsy-proven acute rejection versus no induction (2% vs 48%, p<0.001). Fifty percent of rejection episodes in the no induction group required hospitalization, and 46% of rejection episodes required TMG treatment. Slightly elevated initial costs associated with TMG induction were offset by lower costs related to rejection treatment. Total inpatient costs for the 12 months after transplantation were comparable between the groups (no induction $66,038 vs induction $74,183, p>0.05). For the no induction versus induction groups, no significant differences in cytomegalovirus disease (5% vs 6%), malignancy (3% vs 2%), graft failures (5% vs 6%), mortality (5% vs 4%), and serum creatinine concentrations (mean +/- SD 1.4 +/- 0.3 vs 1.5 +/- 0.3 mg/dl) were observed at 12 months (p>0.05 for all comparisons). Five-day TMG induction effectively reduced the 1-year acute rejection rate without significantly increasing total inpatient costs or posttransplantation complications among recipients of kidney transplants from living unrelated donors.

Minimal stimulation or clomiphene citrate as first-line therapy in women with polycystic ovary syndrome: a randomized controlled trial.

PubMed

Abu Hashim, Hatem; Bazeed, Mohamed; Abd Elaal, Ibrahim

2012-02-01

To compare the efficacy of minimal stimulation and clomiphene citrate (CC) as a first-line treatment for anovulatory infertility associated with polycystic ovary syndrome (PCOS). One hundred and thirteen women with PCOS were selected in this randomized controlled trial. Patients received minimal stimulation protocol consisted of 5 days CC (100 mg/day) then 150 IU of highly purified uFSH on cycle day 9 (n = 58, 159 cycles) or CC only (n = 55, 153 cycles) for up to three cycles. Outcome measures were: clinical pregnancy rate per cycle, number of growing and mature follicles, serum E2, endometrial thickness at the hCG day, serum P, ovulation and miscarriage rates. There were no differences between both groups regarding the clinical pregnancy rate per cycle and per woman (8.8% vs. 7.8 % and 24.1% vs. 21.8%; p = 0.23, p = 0.36, respectively). One twin pregnancy occurred in each group. Miscarriage rate was comparable (14.3% vs. 16.7%; p = 0.38). No differences were found regarding the number of follicles, serum P, ovulation rate, E2 and endometrial thickness at the hCG day (7.8 ± 0.5 vs. 7.6 ± 0.6 mm; p = 0.52). Ovulation induction with minimal stimulation is not more effective than CC alone for achieving pregnancy when used as initial treatment in PCOS patients.

Accuracy of Cardiac Output by Nine Different Pulse Contour Algorithms in Cardiac Surgery Patients: A Comparison with Transpulmonary Thermodilution.

PubMed

Broch, Ole; Bein, Berthold; Gruenewald, Matthias; Masing, Sarah; Huenges, Katharina; Haneya, Assad; Steinfath, Markus; Renner, Jochen

2016-01-01

Objective. Today, there exist several different pulse contour algorithms for calculation of cardiac output (CO). The aim of the present study was to compare the accuracy of nine different pulse contour algorithms with transpulmonary thermodilution before and after cardiopulmonary bypass (CPB). Methods. Thirty patients scheduled for elective coronary surgery were studied before and after CPB. A passive leg raising maneuver was also performed. Measurements included CO obtained by transpulmonary thermodilution (CO TPTD ) and by nine pulse contour algorithms (CO X1-9 ). Calibration of pulse contour algorithms was performed by esophageal Doppler ultrasound after induction of anesthesia and 15 min after CPB. Correlations, Bland-Altman analysis, four-quadrant, and polar analysis were also calculated. Results. There was only a poor correlation between CO TPTD and CO X1-9 during passive leg raising and in the period before and after CPB. Percentage error exceeded the required 30% limit. Four-quadrant and polar analysis revealed poor trending ability for most algorithms before and after CPB. The Liljestrand-Zander algorithm revealed the best reliability. Conclusions. Estimation of CO by nine different pulse contour algorithms revealed poor accuracy compared with transpulmonary thermodilution. Furthermore, the less-invasive algorithms showed an insufficient capability for trending hemodynamic changes before and after CPB. The Liljestrand-Zander algorithm demonstrated the highest reliability. This trial is registered with NCT02438228 (ClinicalTrials.gov).

A randomized trial of one versus three doses of Augmentin as wound prophylaxis in at-risk abdominal surgery.

PubMed Central

Bates, T.; Roberts, J. V.; Smith, K.; German, K. A.

1992-01-01

In a randomized prospective trial of prophylactic antibiotics in at-risk abdominal surgery, one dose of intravenous Augmentin (amoxycillin 250 mg and clavulanic acid 125 mg) on induction has been compared with three 8 hourly doses in 900 patients. Wound infection rates which included minor and delayed infections were very similar in those given one dose: 48/449 (10.7%) compared with those given three doses: 49/451 (10.9%) 95% confidence limits - 4.25% + 3.9%. There were more septic and sepsis-related deaths in those patients given one dose (14 deaths) than in those given three doses (7 deaths) P > 0.1 95% CL - 0.4% + 3.0%. However, there were more very elderly patients in the one dose group: 64% of the deaths were aged over 80 and all but one had an emergency operation. There was no difference in the other outcome measures studied which included non-fatal deep sepsis, length of postoperative hospital stay, duration of postoperative fever or the use of antibiotics for postoperative infection. One dose of a suitable intravenous antibiotic gives prophylaxis against wound infection in at-risk abdominal surgery which is at least as effective as multiple doses. However, there may be a risk of overwhelming systemic sepsis in very elderly patients having emergency surgery. PMID:1461853

Influence of Dietary Selenium Species on Selenoamino Acid Levels in Rainbow Trout.

PubMed

Godin, Simon; Fontagné-Dicharry, Stéphanie; Bueno, Maïté; Tacon, Philippe; Prabhu, Philip Antony Jesu; Kaushik, Sachi; Médale, Françoise; Bouyssiere, Brice

2015-07-22

Two forms of selenium (Se) supplementation of fish feeds were compared in two different basal diets. A 12-week feeding trial was performed with rainbow trout fry using either a plant-based or a fish meal-based diet. Se yeast and selenite were used for Se supplementation. Total Se and Se speciation were determined in both diets and whole body of trout fry using inductively coupled plasma mass spectrometry (ICP MS) and high-performance liquid chromatography (HPLC). The two selenoamino acids, selenomethionine (SeMet) and selenocysteine (SeCys), were determined in whole body of fry after enzymatic digestion using protease type XIV with a prior derivatization step in the case of SeCys. The plant-based basal diet was found to have a much lower total Se than the fish meal-based basal diet with concentrations of 496 and 1222 μg(Se) kg(-1), respectively. Dietary Se yeast had a higher ability to raise whole body Se compared to selenite. SeMet concentration in the fry was increased only in the case of Se yeast supplementation, whereas SeCys levels were similar at the end of the feeding trial for both Se supplemented forms. The results show that the fate of dietary Se in fry is highly dependent on the form brought through supplementation and that a plant-based diet clearly benefits from Se supplementation.

Use of arsenic trioxide in remission induction and consolidation therapy for acute promyelocytic leukaemia in the Australasian Leukaemia and Lymphoma Group (ALLG) APML4 study: a non-randomised phase 2 trial.

PubMed

Iland, Harry J; Collins, Marnie; Bradstock, Ken; Supple, Shane G; Catalano, Alberto; Hertzberg, Mark; Browett, Peter; Grigg, Andrew; Firkin, Frank; Campbell, Lynda J; Hugman, Amanda; Reynolds, John; Di Iulio, Juliana; Tiley, Campbell; Taylor, Kerry; Filshie, Robin; Seldon, Michael; Taper, John; Szer, Jeff; Moore, John; Bashford, John; Seymour, John F

2015-09-01

Initial treatment of acute promyelocytic leukaemia traditionally involves tretinoin (all-trans retinoic acid) combined with anthracycline-based risk-adapted chemotherapy, with arsenic trioxide being the treatment of choice at relapse. To try to reduce the relapse rate, we combined arsenic trioxide with tretinoin and idarubicin in induction therapy, and used arsenic trioxide with tretinoin as consolidation therapy. Patients with previously untreated genetically confirmed acute promyelocytic leukaemia were eligible for this study. Eligibilty also required Eastern Cooperative Oncology Group performance status 0-3, age older than 1 year, normal left ventricular ejection fraction, Q-Tc interval less than 500 ms, absence of serious comorbidity, and written informed consent. Patients with genetic variants of acute promyelocytic leukaemia (fusion of genes other than PML with RARA) were ineligible. Induction comprised 45 mg/m(2) oral tretinoin in four divided doses daily on days 1-36, 6-12 mg/m(2) intravenous idarubicin on days 2, 4, 6, and 8, adjusted for age, and 0·15 mg/kg intravenous arsenic trioxide once daily on days 9-36. Supportive therapy included blood products for protocol-specified haemostatic targets, and 1 mg/kg prednisone daily as prophylaxis against differentiation syndrome. Two consolidation cycles with tretinoin and arsenic trioxide were followed by maintenance therapy with oral tretinoin, 6-mercaptopurine, and methotrexate for 2 years. The primary endpoints of the study were freedom from relapse and early death (within 36 days of treatment start) and we assessed improvement compared with the 2 year interim results. To assess durability of remission we compared the primary endpoints and disease-free and overall survival at 5 years in APML4 with the 2 year interim APML4 data and the APML3 treatment protocol that excluded arsenic trioxide. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12605000070639. 124 patients were enrolled between Nov 10, 2004, and Sept 23, 2009, with data cutoff of March 15, 2012. Four (3%) patients died early. After a median follow-up of 4·2 years (IQR, 3·2-5·2), the 5 year freedom from relapse was 95% (95% CI 89-98), disease-free survival was 95% (89-98), event-free survival was 90% (83-94), and overall survival was 94% (89-97). The comparison with APML3 data showed that hazard ratios were 0·23 (95% CI 0·08-0·64, p=0·002) for freedom from relapse, 0·21 (0·07-0·59, p=0·001) for disease-free survival, 0·34 (0·16-0·69, p=0·002) for event-free survival, and 0·35 (0·14-0·91, p=0·02) for overall survival. Incorporation of arsenic trioxide in initial therapy induction and consolidation for acute promyelocytic leukaemia reduced the risk of relapse when compared with historical controls. This improvement, together with a non-significant reduction in early deaths and absence of deaths in remission, translated into better event-free and overall survival. Phebra. Copyright © 2015 Elsevier Ltd. All rights reserved.

Popliteal block for lower limb surgery in children with cerebral palsy: effect on sevoflurane consumption and postoperative pain (a randomized, double-blinded, controlled trial).

PubMed

Ozkan, Derya; Gonen, Emel; Akkaya, Taylan; Bakir, Mesut

2017-06-01

The aim of this study was to evaluate the effects of a preoperative popliteal block on sevoflurane consumption, postoperative pain, and analgesic consumption in children with cerebral palsy (CP) following lower limb surgery. Fifty-four patients undergoing lower limb surgery were randomized to receive either a popliteal block + general anaesthesia (group P, n = 27) or general anaesthesia without a popliteal block (group C, n = 27). After anesthesia induction with 50% N 2 O, O 2 , and 8% sevoflurane, a popliteal block was given to group P patients with ultrasound guidance as a single dose of 0.3 ml/kg body weight of 0.25% bupivacaine. Group C patients received the same regimen of anesthesia induction but no preoperative popliteal block. Both the conductance fluctuation (SCF) peak numbers per second and the Wong-Baker FACES® Pain Rating Scale (WBFS) values of the patients were recorded upon arrival at the PACU, at 10 and 20 min after arrival at the PACU, and at postoperative hours 1, 4, 8, 12, and 24 when they were in the ward. The total paracetamol consumption of the patients was also recorded. The end-tidal sevoflurane concentration values were significantly higher in group C patients than in group P patients, except for at 5 min after induction of anaesthesia (p < 0.001). The SCF peak numbers per second and WBFS scores were significantly higher in group C patients than in group P patients, except at Tp24h (p < 0.001). The total paracetamol consumption was 489.7 ± 122.7 mg in group P patients and 816.6 ± 166.5 in group C patients (p < 0.001). Popliteal block is effective for postoperative analgesia, decreasing the paracetamol consumption and sevoflurane requirement in children with CP undergoing lower limb surgery. Trial registration ClinicalTrial.gov identifier: NCT02507700.

Scenarios of Mentor Education in Romania--Towards Improving Teacher Induction

ERIC Educational Resources Information Center

Stîngu, Mihaela; Eisenschmidt, Eve; Iucu, Romi?a

2016-01-01

The aim of this paper is to examine the induction programme for newly qualified teachers and mentor education in Estonia, providing a comparative analysis of existing Estonian and possible Romanian models of mentoring. While the Estonian induction programme has been in place for more than ten years, induction in Romania is a relatively new and has…

Starting time for induction of labor and the risk for night-time delivery.

PubMed

Thorsell, M; Lyrenäs, S; Andolf, E; Kaijser, M

2011-08-01

To analyze if starting time for labor induction affected the risk of night-time delivery, and to evaluate to what extent the risk was influenced by Bishop score at start of induction, mode of induction, and parity. A retrospective cohort study of women who delivered at Danderyd Hospital, Stockholm, Sweden, 2002-2006, comprising 1940 women induced by Dinoprostone (PGE(2)) or transcervical balloon catheter (BARD). Risks for night-time delivery were calculated as absolute risk and Odds Ratios by unconditional logistic regression using induction of labor in the morning as reference. For nulliparae with Bishop score 0-3 induced by BARD, odds ratios for night-time delivery were 0.42 (95% C.I. 0.19-0.93) and 0.09 (95% C.I. 0.02-0.47) when inductions started in the afternoon and evening, respectively, compared to inductions starting in the morning For multiparae, however, the risk of night-time delivery was highest if induction started in the evening. Compared to inductions started in the morning, odds ratios for night-time delivery were 3.53 (95% C.I. 2.57-4.83) and 8.49 (95% C.I. 4.45-16.19) for induction starting in the afternoon and evening, respectively. Starting time of labor induction affects the risk of giving birth at night. For nulliparae induced by BARD, starting the induction in the evening instead of during the day may reduce the number of night-time deliveries substantially. For multiparae, however, our data suggest that induction of labor should take place in the morning. Copyright © 2011 Elsevier B.V. All rights reserved.

The Influence of Two Different Doses of Magnesium Sulfate on Intraocular Pressure Variations after Injection of Succinylcholine and Endotracheal Intubation: A Prospective, Randomized, Parallel Three-Arm, Double-blind, Placebo-controlled Clinical Trial.

PubMed

Yassin, Hany Mahmoud; Abdel Moneim, Ahmed Tohamy; Mostafa Bayoumy, Ahmed Sherin; Bayoumy, Hasan Metwally; Taher, Sameh Galal

2017-01-01

The use of succinylcholine for rapid sequence induction in patients with open globe injuries may be detrimental to the eye. The aim of this study is to determine if the premedication with magnesium sulfate (MgSO 4 ) could attenuate the increase in intraocular pressure (IOP) associated with succinylcholine injection and intubation. Operation theaters in a tertiary care University Hospital between December 2014 and July 215. This was a prospective, randomized, parallel three-arm, double-blind, placebo-controlled clinical trial. One hundred and thirteen patients' physical status ASA Classes I and II underwent elective cataract surgery under general anesthesia. These patients allocated into three groups: Group C (control group) received 100 ml normal saline, Group M1 received 30 mg/kg MgSO 4 in 100 ml normal saline, and Group M2 received 50 mg/kg MgSO 4 in 100 ml normal saline. IOP, mean arterial pressure (MAP), and heart rate (HR) reported at 5-time points related to study drug administration. In addition, any adverse effects related to MgSO 4 were recorded. Intragroup and between-groups differences were examined by analysis of variance test. We noticed a significant decrease in IOP in M1 ( n = 38) and M2 ( n = 37) groups as compared with C group ( n = 38) after study drugs infusion, 2 and 5 min after intubation, P < 0.001. While the difference between M1 and M2 groups was insignificant, P = 0.296 and P = 0.647, respectively. There was a significant decrease in MAP and HR in M1 and M2 groups as compared with C group 2 and 5 min after intubation, P = 0.01. While the difference between M1 and M2 groups was insignificant, P = 1. MgSO 4 30 mg/kg as well as 50 mg/kg effectively prevented the rise in IOP, MAP, and HR associated with rapid sequence induction by succinylcholine and endotracheal intubation.

Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management.

PubMed

Smith, J Joshua; Chow, Oliver S; Gollub, Marc J; Nash, Garrett M; Temple, Larissa K; Weiser, Martin R; Guillem, José G; Paty, Philip B; Avila, Karin; Garcia-Aguilar, Julio

2015-10-23

Treatment of patients with non-metastatic, locally advanced rectal cancer (LARC) includes pre-operative chemoradiation, total mesorectal excision (TME) and post-operative adjuvant chemotherapy. This trimodality treatment provides local tumor control in most patients; but almost one-third ultimately die from distant metastasis. Most survivors experience significant impairment in quality of life (QoL), due primarily to removal of the rectum. A current challenge lies in identifying patients who could safely undergo rectal preservation without sacrificing survival benefit and QoL. This multi-institutional, phase II study investigates the efficacy of total neoadjuvant therapy (TNT) and selective non-operative management (NOM) in LARC. Patients with MRI-staged Stage II or III rectal cancer amenable to TME will be randomized to receive FOLFOX/CAPEOX: a) before induction neoadjuvant chemotherapy (INCT); or b) after consolidation neoadjuvant chemotherapy (CNCT), with 5-FU or capecitabine-based chemoradiation. Patients in both arms will be re-staged after completing all neoadjuvant therapy. Those with residual tumor at the primary site will undergo TME. Patients with clinical complete response (cCR) will receive non-operative management (NOM). NOM patients will be followed every 3 months for 2 years, and every 6 months thereafter. TME patients will be followed according to NCCN guidelines. All will be followed for at least 5 years from the date of surgery or--in patients treated with NOM--the last day of treatment. The studies published thus far on the safety of NOM in LARC have compared survival between select groups of patients with a cCR after NOM, to patients with a pathologic complete response (pCR) after TME. The current study compares 3-year disease-free survival (DFS) in an entire population of patients with LARC, including those with cCR and those with pCR. We will compare the two arms of the study with respect to organ preservation at 3 years, treatment compliance, adverse events and surgical complications. We will measure QoL in both groups. We will analyze molecular indications that may lead to more individually tailored treatments in the future. This will be the first NOM trial utilizing a regression schema for response assessment in a prospective fashion. NCT02008656.

Randomized prospective trial of ganciclovir maintenance therapy for cytomegalovirus retinitis.

PubMed

Jacobson, M A; O'Donnell, J J; Brodie, H R; Wofsy, C; Mills, J

1988-07-01

We report the first randomized prospective comparative study of long-term maintenance ganciclovir (9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine, BW759U, DHPG) therapy for cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS). Eleven retinitis patients who received a 10-day course of ganciclovir induction therapy and then were randomized to receive either immediate daily ganciclovir maintenance therapy or deferred maintenance (eight deferred maintenance, three immediate maintenance) were evaluated for drug efficacy. Median time to retinitis progression was 42 days for the immediate maintenance group compared with 16 days for the deferred maintenance group, (P = 0.07). After crossing over to maintenance therapy, patients in the deferred group had a median time to retinitis progression of 58 days compared to 16 days while not on maintenance therapy (P = 0.13). Only 9% of cultures obtained while patients received maintenance therapy were positive for cytomegalovirus, vs 40% of those obtained off maintenance (P less than 0.001). We can state then that maintenance therapy with ganciclovir delays, but does not halt, progression of cytomegalovirus retinitis and suppresses, but does not eradicate, cytomegalovirus shedding in patients with AIDS.

Etoposide and cisplatin versus irinotecan and cisplatin in patients with limited-stage small-cell lung cancer treated with etoposide and cisplatin plus concurrent accelerated hyperfractionated thoracic radiotherapy (JCOG0202): a randomised phase 3 study.

PubMed

Kubota, Kaoru; Hida, Toyoaki; Ishikura, Satoshi; Mizusawa, Junki; Nishio, Makoto; Kawahara, Masaaki; Yokoyama, Akira; Imamura, Fumio; Takeda, Koji; Negoro, Shunichi; Harada, Masao; Okamoto, Hiroaki; Yamamoto, Nobuyuki; Shinkai, Tetsu; Sakai, Hiroshi; Matsui, Kaoru; Nakagawa, Kazuhiko; Shibata, Taro; Saijo, Nagahiro; Tamura, Tomohide

2014-01-01

Four cycles of etoposide plus cisplatin and accelerated hyperfractionated thoracic radiotherapy (AHTRT) is the standard of care for limited-stage small-cell lung cancer (SCLC). Irinotecan plus cisplatin significantly improved overall survival compared with etoposide plus cisplatin for extensive-stage SCLC. We compared these regimens for overall survival of patients with limited-stage SCLC. We did this phase 3 study in 36 institutions in Japan. Eligibility criteria included age 20-70 years, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and adequate organ functions. Eligible patients with previously untreated limited-stage SCLC received one cycle of etoposide plus cisplatin (intravenous etoposide 100 mg/m(2) on days 1-3; intravenous cisplatin 80 mg/m(2) on day 1) plus AHTRT (1.5 Gy twice daily, 5 days a week, total 45 Gy over 3 weeks). Patients without progressive disease following induction therapy were randomised (1:1 ratio, using a minimisation method with biased-coin assignment balancing on ECOG performance status [0 vs 1], response to induction chemoradiotherapy [complete response plus near complete response vs partial response and stable disease], and institution) to receive either three further cycles of consolidation etoposide plus cisplatin or irinotecan plus cisplatin (intravenous irinotecan 60 mg/m(2) on days 1, 8, 15; intravenous cisplatin 60 mg/m(2) on day 1). Patients, physicians, and investigators were aware of allocation. The primary endpoint was overall survival after randomisation; primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00144989, and the UMIN Clinical Trials Registry, number C000000095. 281 patients were enrolled between Sept 1, 2002, and Oct 2, 2006. After induction etoposide plus cisplatin and AHTRT, 258 patients were randomised to consolidation etoposide plus cisplatin (n=129) or irinotecan plus cisplatin (n=129). In the etoposide plus cisplatin group, median overall survival was 3.2 years (95% CI 2.4-4.1). In the irinotecan and cisplatin group, median overall survival was 2.8 years (95% CI 2.4-3.6); overall survival did not differ between the two groups (hazard ratio 1.09 [95% CI 0.80-1.46], one-sided stratified log-rank p=0.70). The most common adverse events of grade 3 or 4 were neutropenia (120 [95%] in the etoposide plus cisplatin group vs 101 [78%] in the irinotecan plus cisplatin group), anaemia (44 [35%] vs 50 [39%]), thrombocytopenia (26 [21%] vs six [5%]), febrile neutropenia (21 [17%] vs 18 [14%]), and diarrhoea (two [2%] vs 13 [10%]). There was one treatment-related adverse event leading to death in each group (radiation pneumonitis in the etoposide plus cisplatin group; brain infarction in the irinotecan plus cisplatin group). Four cycles of etoposide plus cisplatin and AHTRT should continue to be the standard of care for limited-stage SCLC. National Cancer Center and the Ministry of Health, Labour, and Welfare of Japan. Copyright © 2014 Elsevier Ltd. All rights reserved.

Foley catheter placement for induction of labor with or without stylette: a randomized clinical trial.

PubMed

Forgie, Marie M; Greer, Danielle M; Kram, Jessica J F; Vander Wyst, Kiley B; Salvo, Nicole P; Siddiqui, Danish S

2016-03-01

Foley catheters are used for cervical ripening during induction of labor. Previous studies suggest that use of a stylette (a thin, rigid wire) to guide catheter insertion decreases insertion failure. However, stylette effects on insertion outcomes have been sparsely studied. The purpose of this study was to compare catheter insertion times, patient-assessed pain levels, and insertion failure rates between women who received a digitally placed Foley catheter for cervical ripening with the aid of a stylette and women who received the catheter without a stylette. We conducted a randomized clinical trial of women aged ≥ 18 years who presented for induction of labor. Inclusion criteria were singletons with intact membranes and cephalic presentation. Women received a computer-generated random assignment of a Foley catheter insertion with a stylette (treatment group, n = 62) or without a stylette (control group, n = 61). For all women, a standard insertion technique protocol was used. Three primary outcomes were of interest, including the following: (1) insertion time (total minutes to successful catheter placement), (2) patient-assessed pain level (0-10), and (3) failure rate of the randomly assigned insertion method. Treatment control differences were first examined using the Pearson's test of independence and the Student t test. Per outcome, we also constructed 4 regression models, each including the random effect of physician and fixed effects of stylette use with patient nulliparity, a history of vaginal delivery, cervical dilation at presentation, or postgraduate year of the performing resident physician. Women who received the Foley catheter with the stylette vs without the stylette did not differ by age, race/ethnicity, body mass index, or any of several other characteristics. Regression models revealed that insertion time, patient pain, and insertion failure were unrelated to stylette use, nulliparity, and history of vaginal delivery. However, overall insertion time and failure were significantly influenced by cervical dilation, with insertion time decreasing by 21% (95% confidence interval [CI], 5-34%) and odds of failure decreasing by 71% (odds ratio, 0.29; 95% CI, 0.10-0.86) per 1 cm dilation. Resident postgraduate year also significantly influenced insertion time, with greater time required of physicians with less experience. Mean insertion time was 51% (95% CI, 23-69%) shorter for fourth-year than second-year residents. Statistically nonsignificant but prominent patterns in outcomes were also observed, suggesting stylette use may lengthen the overall insertion procedure but minimize variability in pain levels and decrease insertion failure. The randomized trial suggests that, even after accounting for nulliparity, history of vaginal delivery, cervical dilation, and physician experience, Foley catheter insertions with and without a stylette are equivalent in insertion times, patient pain levels, and failure of catheter placement. Copyright © 2016 Elsevier Inc. All rights reserved.

Tight control of mild-moderate pre-existing or non-proteinuric gestational hypertension.

PubMed

Nabhan, Ashraf F; Elsedawy, Maged M

2011-07-06

The question of the target blood pressure in pregnant women with mild-moderate hypertension continues to be an area of debate. To compare tight versus very tight control of mild-moderate pre-existing or non-proteinuric gestational hypertension for improving outcomes We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2011), CENTRAL (The Cochrane Library 2011, Issue 3), MEDLINE (January 1966 to March 2011), and the metaRegister of Controlled Trials (31 March 2011). We handsearched citation lists of relevant publications, review articles, and included studies. Randomized controlled trials of tight versus very tight control in pregnant women with mild or moderate pre-existing or non-proteinuric gestational hypertension. Two authors independently assessed trial quality and extracted data. We expressed results as risk ratio (RR) or mean differences, together with their 95% confidence intervals (CI). We included two studies (256 participants) with mild-moderate pre-existing or non-proteinuric gestational hypertension. There was no evidence of a difference between tight and very tight control groups regarding severe pre-eclampsia (risk ratio (RR) 1.28, 95% CI 0.97 to 1.70; two trials, 256 participants). More women in the tight group were hospitalized during their pregnancy (RR 2.53, 95% CI 1.14 to 5.63; one trial, 125 participants). There was no evidence of a difference in other outcome measures including fetal distress, IUGR, neonatal admission to a NICU, perinatal deaths, induction of labor and cesarean delivery between the tight and the very tight control groups. Gestational age at delivery had a non-significant mean difference (MD) of -0.15 weeks between the tight and very tight control groups (MD -0.15, 95% CI -1.52 to 1.21, random-effects, T² = 0.75, I² = 77%; two trials, 256 participants). The MD in birthweight between the tight and the very tight control group was not significant (MD -100.00 grams, 95% CI -363.69 to 163.69; one trial, 125 participants). For pregnant women with non-severe pre-existing or non-proteinuric gestational hypertension, there is insufficient evidence to determine how tight control of hypertension should be achieved to improve maternal and fetal-neonatal outcomes.

Induction of labor using prostaglandin E2 (PGE2) vaginal gel in triacetin base. An efficacy study comparing two dosage regimens.

PubMed

Seeras, R C; Olatunbosun, O A; Pierson, R A; Turnell, R W

1995-01-01

To compare two dosage regimens for the administration of vaginal prostaglandin gel in triacetin base for induction of labor. Seventy subjects planned for elective induction of labor at term were randomized to treatment with PGE2 vaginal gel every 6 or 12 hours. The 6-hourly group received an initial dose of 1 mg, followed by 2 mg at 6 hour intervals for a maximum of two additional doses if not in active labor. The 12-hourly group had an initial dose of 2 mg followed by two additional doses at 12 hour intervals if not in active labor. Successful induction rate was higher in the 12-hourly as compared to 6-hourly gel regimen (100% vs. 91%, P > 0.05). Twelve hours after the initial dose, delivery occurred in 34% delivery had occurred in 57% and 37% respectively (P < 0.01). We found no difference in the induction-active labor interval (P > 0.05), and the induction-delivery interval (P > 0.05) between the two groups. Active labor followed a single dose of gel in 66% of the 12-hourly group compared to 40% of the 6-hourly group (P < 0.01). Syntocinon augmentation was needed in 6% of subjects in the 12-hourly group as compared to 26% in the 6-hourly group (P < 0.01). The cesarean section rate was similar in both groups. Uterine hyperstimulation occurred less frequently in the 12-hourly group (P < 0.05). The perinatal outcome was similar in both groups. The 12-hourly regimen was more effective than the 6-hourly regimen in initiating labor. The majority of the subjects in the 12 hourly group achieved labor following a single dose of gel. Induction delivery interval, however, was similar in both groups.

Ipilimumab retreatment in patients with pretreated advanced melanoma: the expanded access programme in Italy

PubMed Central

Chiarion-Sileni, V; Pigozzo, J; Ascierto, P A; Simeone, E; Maio, M; Calabrò, L; Marchetti, P; De Galitiis, F; Testori, A; Ferrucci, P F; Queirolo, P; Spagnolo, F; Quaglino, P; Carnevale Schianca, F; Mandalà, M; Di Guardo, L; Del Vecchio, M

2014-01-01

Background: Retreatment with ipilimumab has been shown to re-establish disease control in some patients with disease progression. Here, we report the efficacy and safety of retreatment with ipilimumab 3 mg kg−1 among patients participating in an expanded access programme in Italy. Methods: Patients who achieved disease control during induction therapy were retreated with ipilimumab upon progression (3 mg kg−1 every 3 weeks for up to four doses), providing they had not experienced toxicity that precluded further dosing. Tumour assessments were conducted after retreatment, and patients were monitored throughout for adverse events. Results: Of 855 patients treated with ipilimumab, 51 were retreated upon disease progression. Of these, 28 (55%) regained disease control upon retreatment and 42% were alive 2 years after the first induction dose of ipilimumab; median overall survival was 21 months. Eleven patients (22%) had a treatment-related adverse event of any grade during retreatment. These were generally mild-to-moderate and resolved within a median of 4 days. No new types of toxicity were reported. Conclusions: For patients who meet predefined criteria, retreatment with ipilimumab is generally well tolerated and can translate into clinical benefit. This strategy should be compared with other therapeutic options in randomised controlled trials. PMID:24619072

Differentiating the Bishop ash bed and related tephra layers by elemental-based similarity coefficients of volcanic glass shards using solution inductively coupled plasma-mass spectrometry (S-ICP-MS)

USGS Publications Warehouse

Knott, J.R.; Sarna-Wojcicki, A. M.; Montanez, I.P.; Wan, E.

2007-01-01

Volcanic glass samples from the same volcanic center (intra-source) often have a similar major-element composition. Thus, it can be difficult to distinguish between individual tephra layers, particularly when using similarity coefficients calculated from electron microprobe major-element measurements. Minor/trace element concentrations in glass can be determined by solution inductively coupled plasma mass spectrometry (S-ICP-MS), but have not been shown as suitable for use in large tephrochronologic databases. Here, we present minor/trace-element concentrations measured by S-ICP-MS and compare these data by similarity coefficients, the method commonly used in large databases. Trial samples from the Bishop Tuff, the upper and lower tuffs of Glass Mountain and the tuffs of Mesquite Spring suites from eastern California, USA, which have an indistinguishable major-element composition, were analyzed using S-ICP-MS. The resulting minor/trace element similarity coefficients clearly separated the suites of tephra layers and, in most cases, individual tephra layers within each suite. Comparisons with previous instrumental neutron activation analysis (INAA) elemental measurements were marginally successful. This is important step toward quantitative correlation in large tephrochronologic databases to achieve definitive identification of volcanic glass samples and for high-resolution age determinations. ?? 2007 Elsevier Ltd and INQUA.

Delivery at Term: When, How, and Why.

PubMed

Walker, Kate F; Thornton, Jim G

2018-06-01

There is growing evidence from randomized trials that induction of labor at or near term does not increase cesarean delivery; observational data show that the optimal gestation for spontaneous delivery for the baby is 39 weeks. Elective cesarean at these gestations is also sometimes considered, but evaluating the associated risks is complex. For the baby, although cesarean obviates the risks of labor, it carries a risk of respiratory problems, which may be severe. For the mother, cesarean is more dangerous than vaginal and emergency cesarean is more dangerous than elective. The authors consider the evidence base for near-term induction of labor and cesarean for a range of scenarios. Copyright © 2018 Elsevier Inc. All rights reserved.

Design of a low parasitic inductance SiC power module with double-sided cooling

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

Yang, Fei; Liang, Zhenxian; Wang, Fei

In this paper, a low-parasitic inductance SiC power module with double-sided cooling is designed and compared with a baseline double-sided cooled module. With the unique 3D layout utilizing vertical interconnection, the power loop inductance is effectively reduced without sacrificing the thermal performance. Both simulations and experiments are carried out to validate the design. Q3D simulation results show a power loop inductance of 1.63 nH, verified by the experiment, indicating more than 60% reduction of power loop inductance compared with the baseline module. With 0Ω external gate resistance turn-off at 600V, the voltage overshoot is less than 9% of the busmore » voltage at a load of 44.6A.« less

The FOAM study: is Hysterosalpingo foam sonography (HyFoSy) a cost-effective alternative for hysterosalpingography (HSG) in assessing tubal patency in subfertile women? Study protocol for a randomized controlled trial.

PubMed

van Rijswijk, Joukje; van Welie, Nienke; Dreyer, Kim; van Hooff, Machiel H A; de Bruin, Jan Peter; Verhoeve, Harold R; Mol, Femke; Kleiman-Broeze, Kimiko A; Traas, Maaike A F; Muijsers, Guido J J M; Manger, Arentje P; Gianotten, Judith; de Koning, Cornelia H; Koning, Aafke M H; Bayram, Neriman; van der Ham, David P; Vrouenraets, Francisca P J M; Kalafusova, Michaela; van de Laar, Bob I G; Kaijser, Jeroen; van Oostwaard, Miriam F; Meijer, Wouter J; Broekmans, Frank J M; Valkenburg, Olivier; van der Voet, Lucy F; van Disseldorp, Jeroen; Lambers, Marieke J; Peters, Henrike E; Lier, Marit C I; Lambalk, Cornelis B; van Wely, Madelon; Bossuyt, Patrick M M; Stoker, Jaap; van der Veen, Fulco; Mol, Ben W J; Mijatovic, Velja

2018-05-09

Tubal pathology is a causative factor in 20% of subfertile couples. Traditionally, tubal testing during fertility work-up is performed by hysterosalpingography (HSG). Hysterosalpingo-foam sonography (HyFoSy) is a new technique that is thought to have comparable accuracy as HSG, while it is less expensive and more patient friendly. HyFoSy would be an acceptable alternative for HSG, provided it has similar effectiveness in terms of patient outcomes. We aim to compare the effectiveness and costs of management guided by HyFoSy or by HSG. Consenting women will undergo tubal testing by both HyFoSy and HSG in a randomized order during fertility work-up. The study group will consist of 1163 subfertile women between 18 and 41 years old who are scheduled for tubal patency testing during their fertility work-up. Women with anovulatory cycles not responding to ovulation induction, endometriosis, severe male subfertility or a known contrast (iodine) allergy will be excluded. We anticipate that 7 % (N = 82) of the participants will have discordant test results for HyFoSy and HSG. These participants will be randomly allocated to either a management strategy based on HyFoSy or a management strategy based on HSG, resulting in either a diagnostic laparoscopy with chromopertubation or a strategy that assumes tubal patency (intrauterine insemination or expectant management). The primary outcome is ongoing pregnancy leading to live birth within 12 months after randomization. Secondary outcomes are patient pain scores, time to pregnancy, clinical pregnancy, miscarriage rate, multiple pregnancy rate, preterm birth rate and number of additional treatments. Costs will be estimated by counting resource use and calculating unit prices. This trial will compare the effectiveness and costs of HyFoSy versus HSG in assessing tubal patency in subfertile women. Dutch Trial Register (NTR 4746, http://www.trialregister.nl ). Date of registration: 19 August 2014.

Prospective, randomized comparison between raloxifene and clomiphene citrate for ovulation induction in polycystic ovary syndrome.

PubMed

de Paula Guedes Neto, Ernesto; Savaris, Ricardo Francalacci; von Eye Corleta, Helena; de Moraes, Gisele Silva; do Amaral Cristovam, Rafael; Lessey, Bruce A

2011-09-01

To compare the ovulation rate between raloxifene and clomiphene citrate (CC) in patients with polycystic ovary syndrome (PCOS). Double-blind, randomized, superiority clinical trial. Tertiary university hospital. Women with ovulatory dysfunction and PCOS based on the Rotterdam criteria. One of two oral treatments: 5 days of 100 mg/day of CC or R. Ovulation, based on follicle collapse on serial ultrasound and midsecretory serum progesterone concentration (≥3 ng/dL). The women with PCOS (n = 82) were randomized to receive CC (n = 40) or raloxifene (n = 42). From these, 68 patients finished the trial according to the protocol (CC: n = 37; raloxifene: n = 31). There were no statistically significant differences between the groups in ovulation rates per an intention-to-treat analysis based on ultrasound alone (CC: 21 of 40 vs. raloxifene: 17 of 42) or on progesterone levels (CC: 16 of 40 vs. raloxifene: 11 of 42). No serious adverse events were observed in either group. No statistically significant difference in ovulation was observed between raloxifene and clomiphene citrate in patients with PCOS with ovulatory dysfunction. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

RESPIRATORY DYSFUNCTION IN UNSEDATED DOGS WITH GOLDEN RETRIEVER MUSCULAR DYSTROPHY

PubMed Central

DeVanna, Justin C.; Kornegay, Joe N.; Bogan, Daniel J.; Bogan, Janet R.; Dow, Jennifer L.; Hawkins, Eleanor C.

2013-01-01

Golden retriever muscular dystrophy (GRMD) is a well-established model of Duchenne muscular dystrophy. The value of this model would be greatly enhanced with practical tools to monitor progression of respiratory dysfunction during treatment trials. Arterial blood gas analysis, tidal breathing spirometry, and respiratory inductance plethysmography (RIP) were performed to determine if quantifiable abnormalities could be identified in unsedated, untrained, GRMD dogs. Results from 11 dogs with a mild phenotype of GRMD and 11 age-matched carriers were compared. Arterial blood gas analysis was successfully performed in all dogs, spirometry in 21 of 22 (95%) dogs, and RIP in 18 of 20 (90%) dogs. Partial pressure of carbon dioxide and bicarbonate concentration were higher in GRMD dogs. Tidal breathing peak expiratory flows were markedly higher in GRMD dogs. Abnormal abdominal motion was present in 7 of 10 (70%) GRMD dogs. Each technique provided objective, quantifiable measures that will be useful for monitoring respiratory function in GRMD dogs during clinical trials while avoiding the influence of sedation on results. Increased expiratory flows and the pattern of abdominal breathing are novel findings, not reported in people with Duchenne muscular dystrophy, and might be a consequence of hyperinflation. PMID:24295812

Experiment on a novel user input for computer interface utilizing tongue input for the severely disabled.

PubMed

Kencana, Andy Prima; Heng, John

2008-11-01

This paper introduces a novel passive tongue control and tracking device. The device is intended to be used by the severely disabled or quadriplegic person. The main focus of this device when compared to the other existing tongue tracking devices is that the sensor employed is passive which means it requires no powered electrical sensor to be inserted into the user's mouth and hence no trailing wires. This haptic interface device employs the use of inductive sensors to track the position of the user's tongue. The device is able perform two main PC functions that of the keyboard and mouse function. The results show that this device allows the severely disabled person to have some control in his environment, such as to turn on and off or control daily electrical devices or appliances; or to be used as a viable PC Human Computer Interface (HCI) by tongue control. The operating principle and set-up of such a novel passive tongue HCI has been established with successful laboratory trials and experiments. Further clinical trials will be required to test out the device on disabled persons before it is ready for future commercial development.

Polyclonal and monoclonal antibodies for induction therapy in kidney transplant recipients.

PubMed

Hill, Penny; Cross, Nicholas B; Barnett, A Nicholas R; Palmer, Suetonia C; Webster, Angela C

2017-01-11

Prolonging kidney transplant survival is an important clinical priority. Induction immunosuppression with antibody therapy is recommended at transplantation and non-depleting interleukin-2 receptor monoclonal antibodies (IL2Ra) are considered first line. It is suggested that recipients at high risk of rejection should receive lymphocyte-depleting antibodies but the relative benefits and harms of the available agents are uncertain. We aimed to: evaluate the relative and absolute effects of different antibody preparations (except IL2Ra) when used as induction therapy in kidney transplant recipients; determine how the benefits and adverse events vary for each antibody preparation; determine how the benefits and harms vary for different formulations of antibody preparation; and determine whether the benefits and harms vary in specific subgroups of recipients (e.g. children and sensitised recipients). Randomised controlled trials (RCTs) comparing monoclonal or polyclonal antibodies with placebo, no treatment, or other antibody therapy in adults and children who had received a kidney transplant. Randomised controlled trials (RCTs) comparing monoclonal or polyclonal antibodies with placebo, no treatment, or other antibody therapy in adults and children who had received a kidney transplant. Two authors independently extracted data and assessed risk of bias. Dichotomous outcomes are reported as relative risk (RR) and continuous outcomes as mean difference (MD) together with their 95% confidence intervals (CI). We included 99 studies (269 records; 8956 participants; 33 with contemporary agents). Methodology was incompletely reported in most studies leading to lower confidence in the treatment estimates.Antithymocyte globulin (ATG) prevented acute graft rejection (17 studies: RR 0.63, 95% CI 0.51 to 0.78). The benefits of ATG on graft rejection were similar when used with (12 studies: RR 0.61, 0.49 to 0.76) or without (5 studies: RR 0.65, 0.43 to 0.98) calcineurin inhibitor (CNI) treatment. ATG (with CNI therapy) had uncertain effects on death (3 to 6 months, 3 studies: RR 0.41, 0.13 to 1.22; 1 to 2 years, 5 studies: RR 0.75, 0.27 to 2.06; 5 years, 2 studies: RR 0.94, 0.11 to 7.81) and graft loss (3 to 6 months, 4 studies: RR 0.60, 0.34 to 1.05; 1 to 2 years, 3 studies: RR 0.65, 0.36 to 1.19). The effect of ATG on death-censored graft loss was uncertain at 1 to 2 years and 5 years. In non-CNI studies, ATG had uncertain effects on death but reduced death-censored graft loss (6 studies: RR 0.55, 0.38 to 0.78). When CNI and older non-CNI studies were combined, a benefit was seen with ATG at 1 to 2 years for both all-cause graft loss (7 studies: RR 0.71, 0.53 to 0.95) and death-censored graft loss (8 studies: RR 0.55, 0.39 to 0.77) but not sustained longer term. ATG increased cytomegalovirus (CMV) infection (6 studies: RR 1.55, 1.24 to 1.95), leucopenia (4 studies: RR 3.86, 2.79 to 5.34) and thrombocytopenia (4 studies: RR 2.41, 1.61 to 3.61) but had uncertain effects on delayed graft function, malignancy, post-transplant lymphoproliferative disorder (PTLD), and new onset diabetes after transplantation (NODAT).Alemtuzumab was compared to ATG in six studies (446 patients) with early steroid withdrawal (ESW) or steroid minimisation. Alemtuzumab plus steroid minimisation reduced acute rejection compared to ATG at one year (4 studies: RR 0.57, 0.35 to 0.93). In the two studies with ESW only in the alemtuzumab arm, the effect of alemtuzumab on acute rejection at 1 year was uncertain compared to ATG (RR 1.27, 0.50 to 3.19). Alemtuzumab had uncertain effects on death (1 year, 2 studies: RR 0.39, 0.06 to 2.42; 2 to 3 years, 3 studies: RR 0.67, 95% CI 0.15 to 2.95), graft loss (1 year, 2 studies: RR 0.39, 0.13 to 1.30; 2 to 3 years, 3 studies: RR 0.98, 95% CI 0.47 to 2.06), and death-censored graft loss (1 year, 2 studies: RR 0.38, 0.08 to 1.81; 2 to 3 years, 3 studies: RR 2.45, 95% CI 0.67 to 8.97) compared to ATG. Creatinine clearance was lower with alemtuzumab plus ESW at 6 months (2 studies: MD -13.35 mL/min, -23.91 to -2.80) and 2 years (2 studies: MD -12.86 mL/min, -23.73 to -2.00) compared to ATG plus triple maintenance. Across all 6 studies, the effect of alemtuzumab versus ATG was uncertain on all-cause infection, CMV infection, BK virus infection, malignancy, and PTLD. The effect of alemtuzumab with steroid minimisation on NODAT was uncertain, compared to ATG with steroid maintenance.Alemtuzumab plus ESW compared with triple maintenance without induction therapy had uncertain effects on death and all-cause graft loss at 1 year, acute rejection at 6 months and 1 year. CMV infection was increased (2 studies: RR 2.28, 1.18 to 4.40). Treatment effects were uncertain for NODAT, thrombocytopenia, and malignancy or PTLD.Rituximab had uncertain effects on death, graft loss, acute rejection and all other adverse outcomes compared to placebo. ATG reduces acute rejection but has uncertain effects on death, graft survival, malignancy and NODAT, and increases CMV infection, thrombocytopenia and leucopenia. Given a 45% acute rejection risk without ATG induction, seven patients would need treatment to prevent one having rejection, while incurring an additional patient experiencing CMV disease for every 12 treated. Excluding non-CNI studies, the risk of rejection was 37% without induction with six patients needing treatment to prevent one having rejection.In the context of steroid minimisation, alemtuzumab prevents acute rejection at 1 year compared to ATG. Eleven patients would require treatment with alemtuzumab to prevent 1 having rejection, assuming a 21% rejection risk with ATG.Triple maintenance without induction therapy compared to alemtuzumab combined with ESW had similar rates of acute rejection but adverse effects including NODAT were poorly documented. Alemtuzumab plus steroid withdrawal would cause one additional patient experiencing CMV disease for every six patients treated compared to no induction and triple maintenance, in the absence of any clinical benefit. Overall, ATG and alemtuzumab decrease acute rejection at a cost of increased CMV disease while patient-centred outcomes (reduced death or lower toxicity) do not appear to be improved.

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial.

PubMed

Jerkeman, Mats; Eskelund, Christian Winther; Hutchings, Martin; Räty, Riikka; Wader, Karin Fahl; Laurell, Anna; Toldbod, Helle; Pedersen, Lone Bredo; Niemann, Carsten Utoft; Dahl, Christina; Kuitunen, Hanne; Geisler, Christian H; Grønbæk, Kirsten; Kolstad, Arne

2018-03-01

Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data on either regimen alone. In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients aged 18 years or older with relapsed or refractory mantle cell lymphoma who had previously been treated with at least one rituximab-containing regimen, an Eastern Cooperative Oncology Group performance status score of 0-3, and at least one site of measurable disease, and who met criteria for several laboratory-assessed parameters. Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only (cycle duration 56 days), given until disease progression or unacceptable toxicity. In the induction phase, patients received intravenous (375 mg/m 2 ) or subcutaneous (1400 mg) rituximab once a week during cycle 1 and then once every 8 weeks. Oral ibrutinib (560 mg once a day) was given to patients every day in the cycle, whereas oral lenalidomide (15 mg once a day) was given on days 1-21. The primary endpoint was overall response assessed in the intention-to-treat population according to Lugano criteria. Safety analysis included all patients who received the treatment, irrespective of eligibility or duration of treatment. The trial is ongoing, but is no longer accruing patients, and is registered with ClinicalTrials.gov, number NCT02460276. Between April 30, 2015, and June 1, 2016, we enrolled 50 patients with relapsed or refractory mantle cell lymphoma at ten centres in Sweden, Finland, Norway, and Denmark. At a median follow-up of 17·8 months (IQR 14·7-20·9), 38 (76%, 95% CI 63-86) patients had an overall response, including 28 (56%, 42-69) patients who had a complete response and ten (20%, 11-33) who had a partial response. The most common grade 3-4 adverse events were neutropenia (in 19 [38%] of 50 patients), infections (in 11 [22%] patients), and cutaneous toxicity (in seven [14%] patients). There were three treatment-related deaths during the study, two due to sepsis and one due to embolic stroke. Our results provide preliminary evidence that the triplet combination of ibrutinib, lenalidomide, and rituximab is an active regimen in patients with relapsed or refractory mantle cell lymphoma, and should be evaluated in a prospective randomised controlled trial. Janssen and Celgene. Copyright © 2018 Elsevier Ltd. All rights reserved.

The effect of St John’s wort extracts on CYP3A: a systematic review of prospective clinical trials

PubMed Central

Whitten, D L; Myers, S P; Hawrelak, J A; Wohlmuth, H

2006-01-01

Aim The aim of this systematic review was to assess the quality and outcomes of clinical trials investigating the effect of St John’s wort extracts on the metabolism of drugs by CYP3A. Methods Prospective clinical trials assessing the effect of St John’s wort (SJW) extracts on metabolism by CYP3A were identified through computer-based searches (from their inception to May 2005) of Medline, Cinahl, PsycINFO, AMED, Current Contents and Embase, hand-searches of bibliographies of relevant papers and consultation with manufacturers and researchers in the field. Two reviewers selected trials for inclusion, independently extracted data and recorded details on study design. Results Thirty-one studies met the eligibility criteria. More than two-thirds of the studies employed a before-and-after design, less than one-third of the studies used a crossover design, and only three studies were double-blind and placebo controlled. In 12 studies the SJW extract had been assayed, and 14 studies stated the specific SJW extract used. Results from 26 studies, including all of the 19 studies that used high-dose hyperforin extracts (>10 mg day−1), had outcomes consistent with CYP3A induction. The three studies using low-dose hyperforin extracts (<4 mg day−1) demonstrated no significant effect on CYP3A. Conclusion There is reasonable evidence to suggest that high-dose hyperforin SJW extracts induce CYP3A. More studies are required to determine whether decreased CYP3A induction occurs after low-dose hyperforin extracts. Future studies should adopt study designs with a control phase or control group, identify the specific SJW extract employed and provide quantitative analyses of key constituents. PMID:17010103

A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma

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

Hiniker, Susan M., E-mail: shiniker@stanford.edu; Reddy, Sunil A.; Maecker, Holden T.

Purpose: Local radiation therapy (RT) combined with systemic anti-cytotoxic T-lymphocyte–associated protein-4 immunotherapy may enhance induction of systemic antimelanoma immune responses. The primary objective of the present trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. The secondary objectives included laboratory assessment of induction of antimelanoma immune responses. Methods and Materials: In our prospective clinical trial, 22 patients with stage IV melanoma were treated with palliative RT and ipilimumab for 4 cycles. RT to 1 to 2 disease sites was initiated within 5 days after starting ipilimumab. Patients had ≥1 nonirradiated metastasismore » measuring ≥1.5 cm available for response assessment. Tumor imaging studies were obtained at baseline, 2 to 4 weeks after cycle 4 of ipilimumab, and every 3 months until progression. Laboratory immune response parameters were measured before and during treatment. Results: Combination therapy was well-tolerated without unexpected toxicities. Eleven patients (50.0%) experienced clinical benefit from therapy, including complete and partial responses and stable disease at median follow-up of 55 weeks. Three patients (27.3%) achieved an ongoing systemic complete response at a median follow-up of 55 weeks (range 32-65), and 3 (27.3%) had an initial partial response for a median of 40 weeks. Analysis of immune response data suggested a relationship between elevated CD8-activated T-cells and response. Conclusion: This is the second prospective clinical trial of treatment of metastatic melanoma using the combination of RT and systemic immunotherapy and the first using this sequence of therapy. The results from the present trial demonstrate that a subset of patients may benefit from combination therapy, arguing for continued clinical investigation of the use of RT combined with immunotherapy, including programmed cell death 1 inhibitors, which might have the potential to be even more effective in combination with RT.« less

Interferon-alpha in the treatment of multiple myeloma.

PubMed

Khoo, Teh Liane; Vangsted, Annette Juul; Joshua, Douglas; Gibson, John

2011-03-01

Interferons are soluble proteins produced naturally by cells in response to viruses. It has both anti-proliferative and immunomodulating properties and is one of the first examples of a biological response modifier use to treat the haematological malignancy multiple myeloma. Interferon has been used in this clinical practice for over thirty years. However, despite considerable efforts, numerous clinical trials and two large meta-analysis, its exact role in the management of multiple myeloma still remains unclear. Its role in the treatment of multiple myeloma has been as a single induction agent, a co-induction agent with other chemotherapy regimens, and as maintenance therapy after conventional chemotherapy or complete remission after autologous or allogeneic transplantation. Interferon as a single induction agent or co-induction agent with other chemotherapy agents appears only to have minimal benefit in myeloma. Its role as maintenance therapy in the plateau phase of myeloma also remains uncertain. More recently, the use of interferon must now compete with the "new drugs"--thalidomide, lenalidomide and bortezomib in myeloma treatment. Will there be a future role of interferon in the treatment of multiple myeloma or will interferon be resigned to the history books remains to be seen.

Causal knowledge and the development of inductive reasoning.

PubMed

Bright, Aimée K; Feeney, Aidan

2014-06-01

We explored the development of sensitivity to causal relations in children's inductive reasoning. Children (5-, 8-, and 12-year-olds) and adults were given trials in which they decided whether a property known to be possessed by members of one category was also possessed by members of (a) a taxonomically related category or (b) a causally related category. The direction of the causal link was either predictive (prey→predator) or diagnostic (predator→prey), and the property that participants reasoned about established either a taxonomic or causal context. There was a causal asymmetry effect across all age groups, with more causal choices when the causal link was predictive than when it was diagnostic. Furthermore, context-sensitive causal reasoning showed a curvilinear development, with causal choices being most frequent for 8-year-olds regardless of context. Causal inductions decreased thereafter because 12-year-olds and adults made more taxonomic choices when reasoning in the taxonomic context. These findings suggest that simple causal relations may often be the default knowledge structure in young children's inductive reasoning, that sensitivity to causal direction is present early on, and that children over-generalize their causal knowledge when reasoning. Copyright © 2013 Elsevier Inc. All rights reserved.

Aromatase inhibitors for subfertile women with polycystic ovary syndrome.

PubMed

Franik, Sebastian; Kremer, Jan A M; Nelen, Willianne L D M; Farquhar, Cindy

2014-02-24

Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 4% to 8% of women worldwide and often leads to anovulatory subfertility. Aromatase inhibitors (AIs) are a novel class of drugs that were introduced for ovulation induction in 2001. Over the last ten years clinical trials have reached differing conclusions as to whether the AI letrozole is at least as effective as the first-line treatment clomiphene citrate (CC). To evaluate the effectiveness and safety of aromatase inhibitors for subfertile women with anovulatory PCOS. We searched the following sources from inception to 24/10/2013 to identify relevant randomised controlled trials (RCTs): the Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO, Pubmed, LILACS, Web of Knowledge, the World Health Organisation (WHO) clinical trials register and Clinicaltrials.gov. Furthermore, we manually searched the references of relevant articles.The search was not restricted by language or publication status. We included all RCTs of aromatase inhibitors used alone or with other medical therapies for ovulation induction in women of reproductive age with anovulatory PCOS. Two review authors independently selected trials, extracted the data and assessed trial quality. Studies were pooled where appropriate using a fixed effect model to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs) for most outcomes and risk differences (RDs) for ovarian hyperstimulation syndrome (OHSS). The primary outcomes were live birth and OHSS. Secondary outcomes were pregnancy, miscarriage and multiple pregnancy. The quality of the evidence for each comparison was assessed using GRADE methods. We included 26 RCTs (5560 women). In all studies the aromatase inhibitor was letrozole. Live birth (12 RCTs) One RCT compared letrozole with placebo in women who were clomiphene resistant and the results were inconclusive (OR 3.17, 95% CI 0.12 to 83.17, n=36)Nine RCTs compared letrozole with clomiphene citrate (with or without adjuncts) followed by timed intercourse. The birth rate was higher in the letrozole group (OR 1.63, 95% CI 1.31 to 2.03, n=1783, I²=3%)Two RCTs compared letrozole with laparoscopic ovarian drilling. There was no evidence of a difference between the groups in live birth rate (OR 1.19, 95% CI 0.76 to 1.86, n=407, I²=0%) OHSS (16 RCTs) There was no evidence of a difference in OHSS rates when letrozole was compared with placebo (one RCT, n=36), clomiphene citrate (with or without adjuncts) followed by timed intercourse (nine RCTs, n=2179), clomiphene citrate (with or without adjuncts) followed by intrauterine insemination (IUI) (two RCTs, n=1494), laparoscopic ovarian drilling (one RCT, n=260) or anastrozole (one RCT, n=220). Events were absent or very rare, and no study had more than 2 cases of OHSS. Clinical pregnancy (25 RCTs) One RCT compared letrozole versus placebo in women who were clomiphene resistant and the results were inconclusive (OR 3.17, 95% CI 0.12 to 83.17, n=36)Fourteen RCTs compared letrozole versus clomiphene citrate (with or without adjuncts) followed by timed intercourse. The pregnancy rate was higher in the letrozole group (OR 1.32, 95% CI 1.09 to 1.60, n=2066, I²=25%)Three RCTs compared letrozole versus clomiphene citrate (with or without adjuncts) followed by IUI. The pregnancy rate was higher in the letrozole group (OR 1.71, 95% CI 1.30 to 2.25, n=1597)Three RCTs compared letrozole versus laparoscopic ovarian drilling. There was no evidence of a difference in the clinical pregnancy rate (OR 1.14, 95% CI 0.80 to 1.65, n=553, I²=0%)Two RCTs compared letrozole versus anastrozole, one RCT compared a five day versus a 10 day administration protocol for letrozole and another RCT compared 5 mg of letrozole versus 7.5 mg of letrozole. There was no evidence of a difference in the clinical pregnancy rate in these comparisons.The quality of the evidence was rated as low for live birth and pregnancy outcomes. The reasons for downgrading the evidence were poor reporting of study methods, possible publication bias and the tendency for studies that reported live birth to report higher clinical pregnancy rates in the letrozole group than studies that failed to report live birth (suggesting that results might be somewhat less favourable to letrozole if all studies reported live birth). Letrozole appears to improve live birth and pregnancy rates in subfertile women with anovulatory PCOS, compared to clomiphene citrate. The quality of this evidence is low and findings should be regarded with some caution. There appears to be no difference in effectiveness between letrozole and laparoscopic ovarian drilling, though there were few relevant studies. OHSS was a very rare event, with no occurrences in most studies.

High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: results of the EORTC-GIMEMA AML-12 trial.

PubMed

Willemze, Roelof; Suciu, Stefan; Meloni, Giovanna; Labar, Boris; Marie, Jean-Pierre; Halkes, Constantijn J M; Muus, Petra; Mistrik, Martin; Amadori, Sergio; Specchia, Giorgina; Fabbiano, Francesco; Nobile, Francesco; Sborgia, Marco; Camera, Andrea; Selleslag, Dominik L D; Lefrère, Francois; Magro, Domenico; Sica, Simona; Cantore, Nicola; Beksac, Meral; Berneman, Zwi; Thomas, Xavier; Melillo, Lorella; Guimaraes, Jose E; Leoni, Pietro; Luppi, Mario; Mitra, Maria E; Bron, Dominique; Fillet, Georges; Marijt, Erik W A; Venditti, Adriano; Hagemeijer, Anne; Mancini, Marco; Jansen, Joop; Cilloni, Daniela; Meert, Liv; Fazi, Paola; Vignetti, Marco; Trisolini, Silvia M; Mandelli, Franco; de Witte, Theo

2014-01-20

Cytarabine plays a pivotal role in the treatment of patients with acute myeloid leukemia (AML). Most centers use 7 to 10 days of cytarabine at a daily dose of 100 to 200 mg/m(2) for remission induction. Consensus has not been reached on the benefit of higher dosages of cytarabine. The European Organisation for Research and Treatment of Cancer (EORTC) and Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) Leukemia Groups conducted a randomized trial (AML-12; Combination Chemotherapy, Stem Cell Transplant and Interleukin-2 in Treating Patients With Acute Myeloid Leukemia) in 1,942 newly diagnosed patients with AML, age 15 to 60 years, comparing remission induction treatment containing daunorubicin, etoposide, and either standard-dose (SD) cytarabine (100 mg/m(2) per day by continuous infusion for 10 days) or high-dose (HD) cytarabine (3,000 mg/m(2) every 12 hours by 3-hour infusion on days 1, 3, 5, and 7). Patients in complete remission (CR) received a single consolidation cycle containing daunorubicin and intermediate-dose cytarabine (500 mg/m(2) every 12 hours for 6 days). Subsequently, a stem-cell transplantation was planned. The primary end point was survival. At a median follow-up of 6 years, overall survival was 38.7% for patients randomly assigned to SD cytarabine and 42.5% for those randomly assigned to HD cytarabine (log-rank test P = .06; multivariable analysis P = .009). For patients younger than age 46 years, survival was 43.3% and 51.9%, respectively (P = .009; multivariable analysis P = .003), and for patients age 46 to 60 years, survival was 33.9% and 32.9%, respectively (P = .91). CR rates were 72.0% and 78.7%, respectively (P < .001) and were 75.6% and 82.4% for patients younger than age 46 years (P = .01) and 68.3% and 74.8% for patients age 46 years and older (P = .03). Patients of all ages with very-bad-risk cytogenetic abnormalities and/or FLT3-ITD (internal tandem duplication) mutation, or with secondary AML benefitted from HD cytarabine. HD cytarabine produces higher remission and survival rates than SD cytarabine, especially in patients younger than age 46 years.

Flavored Anesthetic Masks for Inhalational Induction in Children.

PubMed

Gupta, Aakriti; Mathew, Preethy Joseph; Bhardwaj, Neerja

2017-10-01

To evaluate the clinical efficacy of masking the odor of inhalational agents using fruit flavors on the anxiety behavior and compliance of children for inhalational induction. A prospective randomized double blind, placebo controlled study was conducted on 60 unpremedicated children in the age group of 4-12 y. Thirty children received anesthetic masks smeared with a flavor of child's choice while the other 30 children were induced using masks without flavor. Anxiety was assessed using modified Yale Pre-operative Anxiety Scale (mYPAS) in the pre-op room and during inhalational induction. Mask acceptance was graded by Induction Compliance Checklist (ICC). The cost-effectiveness of flavored anesthetic masks was compared to that of commercially available pre-scented masks. The baseline anxiety in the two groups was comparable. The number of children demonstrating high levels of anxiety at anesthetic induction was similar in flavored and non-flavored mask groups (p 0.45). The compliance to mask induction was also equally good (p 0.99). The authors found significant difference in the cost of flavored mask (INR 56.45 per mask) as compared to commercially available pre-scented masks (INR 660 per mask). The authors observed a placebo effect that reduced the pre-op anxiety in the control group which probably made the quality of induction equivalent with flavored and non-flavored masks. Therefore, using a flavored anesthetic mask is cost-effective than using a commercially available pre-scented mask.

Rapacuronium and the risk of bronchospasm in pediatric patients.

PubMed

Rajchert, Donna M; Pasquariello, Caroline A; Watcha, Mehernoor F; Schreiner, Mark S

2002-03-01

We conducted this study to determine the risk factors for the development of bronchospasm after the administration of rapacuronium and to determine if children with bronchospasm on induction of anesthesia were more likely to have received rapacuronium compared with other muscle relaxants. In a retrospective cohort study, all anesthetic records in which rapacuronium was administered were reviewed to determine which patients developed bronchospasm during induction of anesthesia. Two-hundred-eighty-seven patients were identified, of whom 12 (4.2%; 95% confidence interval [CI], 2.2%--7.2%) developed bronchospasm during induction of anesthesia. Significant risk factors for the development of bronchospasm with administration of rapacuronium included rapid sequence induction (relative risk [RR], 17.9; 95% CI, 2.9--infinity) and prior history of reactive airways disease (RR, 4.6; 95% CI, 1.5--14.3). In a case-control study, all cases of bronchospasm during induction of anesthesia in the 5-mo time period that rapacuronium was available for clinical use were identified. Aside from the 12 cases of bronchospasm with rapacuronium, 11 additional cases of bronchospasm were associated with the use of other muscle relaxants. Four controls were randomly selected for each of the 23 cases of bronchospasm. Children with bronchospasm during induction of anesthesia were several times more likely (odds ratio, 10.1; 95% CI, 3.5--28.8) for having received rapacuronium compared with other muscle relaxants. In a retrospective cohort study, significant risk factors for the development of bronchospasm with the administration of rapacuronium on induction of anesthesia included rapid sequence induction and prior history of reactive airways disease. In a case-control study, children with bronchospasm during induction of anesthesia were several times more likely to have received rapacuronium compared with other muscle relaxants.

A comparison of ketamine + midazolam to propofol for procedural sedation for lumbar puncture in pediatric oncology by nonanesthesiologists-a randomized comparative trial.

PubMed

Chayapathi, Varsha; Kalra, Manas; Bakshi, Anita S; Mahajan, Amita

2018-05-04

Both ketamine-midazolam and propofol are frequently used in pediatric oncology units for procedural sedation. However, there are no prospective, randomized comparative trials (RCT) comparing the two groups when the procedure is performed by nonanesthesiologists. To compare ketamine + midazolam (group A) and propofol (group B) as sedative agents for intrathecal chemotherapy with regard to efficacy, side effects, time to induction, time to recovery, and smoothness of recovery. A partially-blinded RCT was conducted between August 2015 and March 2017 after gaining institutional ethics committee approval. Children aged 1-12 years requiring intravenous sedation for intrathecal chemotherapy were included. Patients were allocated to two treatment arms using computer-generated randomization tables, after obtaining written consent. The initial doses used were: ketamine 2 mg/kg, midazolam 0.2 mg/kg, and propofol 2.5 mg/kg, as per standard recommendations. The patient, parents, and person analyzing the data were blinded. Time to sedation, dose required, depth of sedation, vital parameters, time and smoothness of recovery, and emergence phenomena were documented. We enrolled 152 patients (76 each in group A and B). Nine patients had a failure of sedation (all in group B). Mean time to sedation and recovery was shorter in group B (P < 0.001). Transient drop in saturation was more frequent in group B, without statistical significance (P = 0.174). Mean depth of sedation was greater in group A (P < 0.001). Emergence symptoms were more frequently experienced in group A (P < 0.001). Ketamine-midazolam combination is safer and more effective. Propofol is faster in onset and recovery, and has smoother emergence with poor efficacy at recommended initial doses. © 2018 Wiley Periodicals, Inc.

Phenobarbitone versus phenytoin for treatment of neonatal seizures: an open-label randomized controlled trial.

PubMed

Pathak, Garima; Upadhyay, Amit; Pathak, Umesh; Chawla, Deepak; Goel, Sneh P

2013-08-01

To compare the efficacy of phenobarbitone and phenytoin for treatment of neonatal seizures in term and near-term neonates. Open labeled randomized controlled trial. Neonatal intensive care unit of a level II unit from India, from November 2008 to September 2009. All term and late pre-term neonates admitted with clinically apparent seizures and not having any transient metabolic disorders (hypoglycemia or hypocalcemia) were randomly assigned. Phenobarbitone (n=54) or phenytoin (n=55) intravenously 20 mg/kg/dose over 20-30 min. Neonates whose seizures were not controlled by the assigned drug were then crossed over to be treated with other drug in same dose. Clinical control of seizures (seizure free period of 24 hours after giving anticonvulsant). Baseline characteristics including mean birthweight, gestation age and sex were comparable in both groups. Seizures were controlled in 8 of the 55 (14.5%) neonates who received phenytoin, as compared to 39 of 54 (72.2%) neonates who received phenobarbitone (P <0.001). In babies not responding to assigned drugs, after cross-over to the other drug, seizure control was achieved in 44/55 (80%) of the neonates assigned to receive phenytoin first as compared to 49/54 (91%) of those assigned to receive phenobarbitone first (P=0.014). After maximum dose of phenobarbitone seizures were controlled in 49/55(89%) in phenytoin group and 52/54 (96%) in phenobarbitone group (P<0.05). Phenobarbitone is more efficacious than phenytoin in control of clinical seizures in term or near-term neonates, irrespective of etiology. To evaluate serum vascular endothelial growth factor (VEGF) levels in children with acute lymphoblastic leukemia (ALL) during the induction phase of chemotherapy.

Routine interim disease assessment in patients undergoing induction chemotherapy for acute myeloid leukemia: Can we do better?

PubMed

Campuzano-Zuluaga, Germán; Deutsch, Yehuda; Salzberg, Matthew; Gomez, Alexandra; Vargas, Fernando; Elias, Roy; Kwon, Deukwoo; Goodman, Mark; Ikpatt, Offiong F; Chapman, Jennifer R; Watts, Justin; Vega, Francisco; Swords, Ronan

2016-03-01

The presence of >5% blasts at "day 14" (D14), in patients undergoing induction chemotherapy for acute myeloid leukemia (AML) is problematic. It is unclear if a second course of chemotherapy for early persistent disease will alter outcome in these patients. We conducted a retrospective study of AML patients undergoing induction chemotherapy where diagnostic, interim (around day 14), and recovery (days 21-42) bone marrow (BM) evaluations were available for review. Of the 113 patients included in the final analysis, 99 (87.6%) achieved CR at hematologic recovery. At D14, 90 patients (79.6%) had <5% blasts and of these, 87 (96.7%) ultimately achieved CR. At D14, Twenty-three (20.4%) patients had residual leukemia (>5% blasts). Of these, 11 (47.8%) received a second course of chemotherapy (double induction [DI]) and 12 (52.2%) were observed until count recovery (single induction [SI]). No significant difference in CR rates was observed between these two groups (58.3% DI group vs. 45.5% SI group, P value = 0.684). In our analysis, D14 BM evaluation did not uniformly identify patients with primary induction failure. To unequivocally determine the value of a D14 marrow assessment in AML, prospective studies in the context of large cooperative group trials are required. Considering our findings and similar reports from others, we propose that D14 marrow assessment should be individualized, and that other factors, such as cytogenetics and early peripheral blood blast clearance should be considered, to identify patients most likely to benefit from interim disease assessment during AML induction therapy. © 2015 Wiley Periodicals, Inc.

Efficacy and toxicity of a paediatric protocol in teenagers and young adults with Philadelphia chromosome negative acute lymphoblastic leukaemia: results from UKALL 2003.

PubMed

Hough, Rachael; Rowntree, Clare; Goulden, Nick; Mitchell, Chris; Moorman, Anthony; Wade, Rachel; Vora, Ajay

2016-02-01

Despite the substantial outcome improvements achieved in paediatric acute lymphoblastic leukaemia (ALL), survival in teenage and young adult (TYA) patients has remained inferior. We report the treatment outcomes and toxicity profiles observed in TYA patients treated on the UK paediatric ALL trial, UKALL2003. UKALL2003 was a multi-centre, prospective, randomized phase III trial, investigating treatment intensification or de-escalation according to minimal residual disease (MRD) kinetics at the end of induction. Of 3126 patients recruited to UKALL2003, 229 (7·3%) were aged 16-24 years. These patients were significantly more likely to have high risk MRD compared to 10-15 year olds (47·9% vs. 36·6%, P = 0·004). Nonetheless, 5-year event-free survival for the TYA cohort (aged 16-24 years) was 72·3% [95% confidence interval (CI): 66·2-78·4] overall and 92·6% (95% CI: 85·5-99·7) for MRD low risk patients. The risk of serious adverse events was higher in patients aged ≥10 years compared to those aged 9 or younger (P < 0·0001) and novel age-specific patterns of treatment-related toxicity were observed. TYA patients obtain excellent outcomes with a risk- and response-adapted paediatric chemotherapy protocol. Whilst those aged 10 years and older have excess toxicity compared with younger patients, the age association is specific to individual toxicities. © 2015 John Wiley & Sons Ltd.

Patient representatives' views on patient information in clinical cancer trials.

PubMed

Dellson, Pia; Nilbert, Mef; Carlsson, Christina

2016-02-01

Patient enrolment into clinical trials is based on oral information and informed consent, which includes an information sheet and a consent certificate. The written information should be complete, but at the same time risks being so complex that it may be questioned if a fully informed consent is possible to provide. We explored patient representatives' views and perceptions on the written trial information used in clinical cancer trials. Written patient information leaflets used in four clinical trials for colorectal cancer were used for the study. The trials included phase I-III trials, randomized and non-randomized trials that evaluated chemotherapy/targeted therapy in the neoadjuvant, adjuvant and palliative settings. Data were collected through focus groups and were analysed using inductive content analysis. Two major themes emerged: emotional responses and cognitive responses. Subthemes related to the former included individual preferences and perceptions of effect, while subthemes related to the latter were comprehensibility and layout. Based on these observations the patient representatives provided suggestions for improvement, which largely included development of future simplified and more attractive informed consent forms. The emotional and cognitive responses to written patient information reported by patient representatives provides a basis for revised formats in future trials and add to the body of information that support use of plain language, structured text and illustrations to improve the informed consent process and thereby patient enrolment into clinical trials.

The administration sequence of propofol and remifentanil does not affect the ED50 and ED95 of rocuronium in rapid sequence induction of anesthesia: a double-blind randomized controlled trial.

PubMed

Ozcelik, M; Guclu, C; Bermede, O; Baytas, V; Altay, N; Karahan, M A; Erdogan, B; Can, O

2016-04-01

The topic of drug administration sequence in rapid sequence induction (RSI) is still an object of interest in terms of rocuronium effectiveness. The aim of this prospective, randomized trial was to evaluate the effect of administration sequence of propofol and remifentanil on ED50 and ED95 of rocuronium in a RSI model. Eighty-four patients were randomized into Group Remifentanil (Group R, n = 43), where induction of general anesthesia started with remifentanil (2 µg/kg) and followed by propofol (2 mg/kg) and rocuronium administrations; and Group Propofol (Group P, n = 41), where induction of general anesthesia started with propofol and followed by remifentanil and rocuronium. First patients in each group were paralyzed by 0.8 mg/kg rocuronium. In case of acceptable intubation as evaluated according to the criteria described by Viby-Mogensen et al, rocuronium dose was decreased by 0.1 mg/kg for the next patient; otherwise, rocuronium dose was increased by 0.1 mg/kg. After three crossover points, increments or decrements in rocuronium dosage were set to 0.05 mg/kg. The process was repeated until a total of ten crossover points were obtained. The ED50 and ED95 doses of rocuronium were similar in Group R (0.182 mg/kg, and 0.244 mg/kg, respectively) and Group P (0.121 mg/kg, and 0.243 mg/kg, respectively) according to 95% CI of the estimates. There was no statistically significant difference in terms of clinically acceptable intubation conditions between the two groups (56.1% in Group R vs. 59% in Group P, p = 0.795). The choice of administration sequence of propofol and remifentanil does not have an impact on estimated ED50 and ED95 of rocuronium in providing acceptable intubation conditions in the RSI technique.

Reactive oxygen species-mediated synergistic and preferential induction of cell death and reduction of clonogenic resistance in breast cancer cells by combined cisplatin and FK228.

PubMed

Pluchino, Lenora Ann; Choudhary, Shambhunath; Wang, Hwa-Chain Robert

2016-10-10

Safe and effective combination chemotherapy regimens against breast cancer are lacking. We used our cellular system, consisting of the non-cancerous human breast epithelial MCF10A cell line and its derived tumorigenic, oncogenic H-Ras-expressing, MCF10A-Ras cell line, to investigate the effectiveness of a combination chemotherapy regimen in treating breast cancer cells using two FDA-approved agents, cisplatin and FK228. Cisplatin and FK228 significantly, synergistically, and preferentially induced death and reduced drug resistance of MCF10A-Ras versus MCF10A cells. The ERK-Nox-ROS pathway played a major role in both synergistic cell death induction and GSH-level reduction, which contributed to the synergistic suppression of drug resistance in cells. Enhancement of the Ras-ERK-Nox pathway by combined cisplatin and FK228 significantly increased ROS levels, leading to induction of death, reduction of drug resistance, and induction of DNA damage and oxidation in cancerous MCF10A-Ras cells. Furthermore, synergistic induction of cell death and reduction of drug resistance by combined cisplatin and FK228 in breast cells is independent of their estrogen receptor status. Our study suggests that combined cisplatin and FK228 should be considered in clinical trials as a new regimen for therapeutic control of breast cancers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Single-dose rATG induction at renal transplantation: superior renal function and glucoregulation with less hypomagnesemia.

PubMed

Stevens, R Brian; Lane, James T; Boerner, Brian P; Miles, Clifford D; Rigley, Theodore H; Sandoz, John P; Nielsen, Kathleen J; Skorupa, Jill Y; Skorupa, Anna J; Kaplan, Bruce; Wrenshall, Lucile E

2012-01-01

Rabbit anti-thymocyte globulin (rATG) induction reduces reperfusion injury and improves renal function in kidney recipients by means of properties unrelated to T-cell lysis. Here, we analyze intensive rATG induction (single dose, rATG(S) , vs. divided dose, rATG(D) ) for improved renal function and protection against hyperglycemia. Patients without diabetes (n = 98 of 180) in a prospective randomized trial of intensive rATG induction were followed for six months for the major secondary composite end point of impaired glucose regulation (hyperglycemia and new-onset diabetes after transplantation, NODAT). Prospectively collected data included fasting blood glucose and HbA(1c). Serum Mg(++) was routinely collected and retrospectively analyzed. Induction with rATG(S) produced less impaired glucose regulation (p = 0.05), delayed NODAT development (p = 0.02), less hyperglycemia (p = 0.02), better renal function (p = 0.04), and less hypomagnesemia (p = 0.02), a factor associated with a lower incidence of NODAT. Generalized linear modeling confirmed that rATG(S) protects against a synergistic interaction between tacrolimus and sirolimus that otherwise increased hypomagnesemia (p = 0.008) and hyperglycemia (p = 0.03). rATG(S) initiated before renal reperfusion improved early renal function and reduced impaired glucose regulation, an injury by diabetogenic maintenance agents (tacrolimus and sirolimus). © 2011 John Wiley & Sons A/S.

Induction of labor in a contemporary obstetric cohort.

PubMed

Laughon, S Katherine; Zhang, Jun; Grewal, Jagteshwar; Sundaram, Rajeshwari; Beaver, Julie; Reddy, Uma M

2012-06-01

We sought to describe details of labor induction, including precursors and methods, and associated vaginal delivery rates. This was a retrospective cohort study of 208,695 electronic medical records from 19 hospitals across the United States, 2002 through 2008. Induction occurred in 42.9% of nulliparas and 31.8% of multiparas and elective or no recorded indication for induction at term occurred in 35.5% and 44.1%, respectively. Elective induction at term in multiparas was highly successful (vaginal delivery 97%) compared to nulliparas (76.2%). For all precursors, cesarean delivery was more common in nulliparas in the latent compared to active phase of labor. Regardless of method, vaginal delivery rates were higher with a ripe vs unripe cervix, particularly for multiparas (86.6-100%). Induction of labor was a common obstetric intervention. Selecting appropriate candidates and waiting longer for labor to progress into the active phase would make an impact on decreasing the national cesarean delivery rate. Published by Mosby, Inc.

Induction of Labor in a Contemporary Obstetric Cohort

PubMed Central

Laughon, S. Katherine; Zhang, Jun; Grewal, Jagteshwar; Sundaram, Rajeshwari; Beaver, Julie; Reddy, Uma M.

2012-01-01

Objective To describe details of labor induction, including precursors and methods, and associated vaginal delivery rates. Study Design A retrospective cohort study of 208,695 electronic medical records from 19 hospitals across the United States, 2002–2008. Results Induction occurred in 42.9% of nulliparas and 31.8% of multiparas and elective or no recorded indication for induction at term occurred in 35.5% and 44.1%, respectively. Elective induction at term in multiparas was highly successful (vaginal delivery 97%) compared to nulliparas (76.2%). For all precursors, cesarean delivery was more common in nulliparas in the latent compared to active phase of labor. Regardless of method, vaginal delivery rates were higher with a ripe versus unripe cervix, particularly for multiparas (86.6 – 100%). Conclusions Induction of labor was a common obstetric intervention. Selecting appropriate candidates and waiting longer for labor to progress into the active phase would make an impact on decreasing the national cesarean delivery rate. PMID:22520652

Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis.

PubMed

Feagan, Brian G; Macdonald, John K

2012-10-17

Oral 5-aminosalicylic acid (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. Previously, it was found that 5-ASA drugs in doses of at least 2 g/day, were more effective than placebo but no more effective than SASP for inducing remission in ulcerative colitis. This updated review includes more recent studies and evaluates the efficacy and safety of 5-ASA preparations used for the treatment of mild to moderately active ulcerative colitis. The primary objectives were to assess the efficacy, dose-responsiveness and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators for induction of remission in active ulcerative colitis. A secondary objective of this systematic review was to compare the efficacy and safety of once daily dosing of oral 5-ASA with conventional (two or three times daily) dosing regimens. A computer-assisted literature search for relevant studies (inception to January 20, 2012) was performed using MEDLINE, EMBASE and the Cochrane Library. Review articles and conference proceedings were also searched to identify additional studies. Studies were accepted for analysis if they were randomized controlled clinical trials of parallel design, with a minimum treatment duration of four weeks. Studies of oral 5-ASA therapy for treatment of patients with active ulcerative colitis compared with placebo, SASP or other formulations of 5-ASA were considered for inclusion. Studies that compared once daily 5-ASA treatment with conventional dosing of 5-ASA (two or three times daily) and 5-ASA dose ranging studies were also considered for inclusion. The outcomes of interest were the failure to induce global/clinical remission, global/clinical improvement, endoscopic remission, endoscopic improvement, adherence, adverse events, withdrawals due to adverse events, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus sulfasalazine, once daily dosing versus conventional dosing, 5-ASA versus comparator 5-ASA, and 5-ASA dose-ranging. Placebo-controlled trials were subgrouped by dosage. SASP-controlled trials were subgrouped by 5-ASA/SASP mass ratios. Once daily versus conventional dosing studies were subgrouped by formulation. 5-ASA-controlled trials were subgrouped by common 5-ASA comparators (e.g. Asacol, Claversal, Salofalk and Pentasa). Dose-ranging studies were subgrouped by 5-ASA formulation. We calculated the relative risk (RR) and 95% confidence intervals (95% CI) for each outcome. Data were analyzed on an intention to treat basis. Forty-eight studies (7776 patients) were included. The majority of included studies were rated as low risk of bias. 5-ASA was significantly superior to placebo with regard to all measured outcome variables. Seventy-two per cent of 5-ASA patients failed to enter clinical remission compared to 85% of placebo patients (RR 0.86, 95% CI 0.81 to 0.91). A dose-response trend for 5-ASA was also observed. No statistically significant differences in efficacy were found between 5-ASA and SASP. Fifty-four per cent of 5-ASA patients failed to enter remission compared to 58% of SASP patients (RR 0.90, 95% CI 0.77 to 1.04). No statistically significant differences in efficacy or adherence were found between once daily and conventionally dosed 5-ASA. Forty-two per cent of once daily patients failed to enter clinical remission compared to 44% of conventionally dosed patients (RR 0.95, 95% CI 0.82 to 1.10). Eight per cent of patients dosed once daily failed to adhere to their medication regimen compared to 6% of conventionally dosed patients (RR 1.36, 95% CI 0.64 to 2.86). There does not appear to be any difference in efficacy among the various 5-ASA formulations. Forty-eight per cent of patients in the 5-ASA group failed to enter remission compared to 50% of patients in the 5-ASA comparator group (RR 0.94, 95% CI 0.86 to 1.03). A pooled analysis of the ASCEND (I, II and III, n = 1459 patients) studies found no statistically significant difference in clinical improvement between Asacol 4.8 g/day and 2.4 g/day used for the treatment of moderately active ulcerative colitis. Thirty-seven per cent of patients in the 4.8 g/day group failed to improve clinically compared to 41% of patients in the 2.4 g/day group (RR 0.89; 95% CI 0.78 to 1.01). Subgroup analysis indicated that patients with moderate disease may benefit from the higher dose of 4.8 g/day. One study compared (n = 123 patients) Pentasa 4 g/day to 2.25 g/day in patients with moderate disease. Twenty-five per cent of patients in the 4 g/day group failed to improve clinically compared to 57% of patients in the 2.25 g/day group (RR 0.44; 95% CI 0.27 to 0.71). A pooled analysis of two studies comparing MMX mesalamine 4.8 g/day to 2.4 g/day found no statistically significant difference in efficacy (RR 1.03, 95% CI 0.82 to 1.29). 5-ASA was generally safe and common adverse events included flatulence, abdominal pain, nausea, diarrhea, headache and worsening ulcerative colitis. There were no statistically significant differences in the incidence of adverse events between 5-ASA and placebo, once daily and conventionally dosed 5-ASA, 5-ASA and comparator 5-ASA formulation and 5-ASA dose ranging (high dose versus low dose) studies. SASP was not as well tolerated as 5-ASA. Twenty-nine percent of SASP patients experienced an adverse event compared to 15% of 5-ASA patients (RR 0.48, 95% CI 0.37 to 0.63). 5-ASA was superior to placebo and no more effective than SASP. Considering their relative costs, a clinical advantage to using oral 5-ASA in place of SASP appears unlikely. 5-ASA dosed once daily appears to be as efficacious and safe as conventionally dosed 5-ASA. Adherence does not appear to be enhanced by once daily dosing in the clinical trial setting. It is unknown if once daily dosing of 5-ASA improves adherence in a community-based setting. There do not appear to be any differences in efficacy or safety among the various 5-ASA formulations. A daily dosage of 2.4 g appears to be a safe and effective induction therapy for patients with mild to moderately active ulcerative colitis. Patients with moderate disease may benefit from an initial dose of 4.8 g/day.

Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis.

PubMed

Wang, Yongjun; Parker, Claire E; Bhanji, Tania; Feagan, Brian G; MacDonald, John K

2016-04-21

Oral 5-aminosalicylic acid (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. Previously, it was found that 5-ASA drugs in doses of at least 2 g/day, were more effective than placebo but no more effective than SASP for inducing remission in ulcerative colitis. This updated review includes more recent studies and evaluates the efficacy and safety of 5-ASA preparations used for the treatment of mild to moderately active ulcerative colitis. The primary objectives were to assess the efficacy, dose-responsiveness and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators for induction of remission in active ulcerative colitis. A secondary objective of this systematic review was to compare the efficacy and safety of once daily dosing of oral 5-ASA with conventional (two or three times daily) dosing regimens. A computer-assisted literature search for relevant studies (inception to July 9, 2015) was performed using MEDLINE, EMBASE and the Cochrane Library. Review articles and conference proceedings were also searched to identify additional studies. Studies were accepted for analysis if they were randomized controlled clinical trials of parallel design, with a minimum treatment duration of four weeks. Studies of oral 5-ASA therapy for treatment of patients with active ulcerative colitis compared with placebo, SASP or other formulations of 5-ASA were considered for inclusion. Studies that compared once daily 5-ASA treatment with conventional dosing of 5-ASA (two or three times daily) and 5-ASA dose ranging studies were also considered for inclusion. The outcomes of interest were the failure to induce global/clinical remission, global/clinical improvement, endoscopic remission, endoscopic improvement, adherence, adverse events, withdrawals due to adverse events, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus sulfasalazine, once daily dosing versus conventional dosing, 5-ASA versus comparator 5-ASA, and 5-ASA dose-ranging. Placebo-controlled trials were subgrouped by dosage. SASP-controlled trials were subgrouped by 5-ASA/SASP mass ratios. Once daily versus conventional dosing studies were subgrouped by formulation. 5-ASA-controlled trials were subgrouped by common 5-ASA comparators (e.g. Asacol, Claversal, Salofalk and Pentasa). Dose-ranging studies were subgrouped by 5-ASA formulation. We calculated the relative risk (RR) and 95% confidence intervals (95% CI) for each outcome. Data were analyzed on an intention-to-treat basis. Fifty-three studies (8548 patients) were included. The majority of included studies were rated as low risk of bias. 5-ASA was significantly superior to placebo with regard to all measured outcome variables. Seventy-one per cent of 5-ASA patients failed to enter clinical remission compared to 83% of placebo patients (RR 0.86, 95% CI 0.82 to 0.89). A dose-response trend for 5-ASA was also observed. No statistically significant differences in efficacy were found between 5-ASA and SASP. Fifty-four per cent of 5-ASA patients failed to enter remission compared to 58% of SASP patients (RR 0.90, 95% CI 0.77 to 1.04). No statistically significant differences in efficacy or adherence were found between once daily and conventionally dosed 5-ASA. Forty-five per cent of once daily patients failed to enter clinical remission compared to 48% of conventionally dosed patients (RR 0.94, 95% CI 0.83 to 1.07). Eight per cent of patients dosed once daily failed to adhere to their medication regimen compared to 6% of conventionally dosed patients (RR 1.36, 95% CI 0.64 to 2.86). There does not appear to be any difference in efficacy among the various 5-ASA formulations. Fifty per cent of patients in the 5-ASA group failed to enter remission compared to 52% of patients in the 5-ASA comparator group (RR 0.94, 95% CI 0.86 to 1.02). A pooled analysis of 3 studies (n = 1459 patients) studies found no statistically significant difference in clinical improvement between Asacol 4.8 g/day and 2.4 g/day used for the treatment of moderately active ulcerative colitis. Thirty-seven per cent of patients in the 4.8 g/day group failed to improve clinically compared to 41% of patients in the 2.4 g/day group (RR 0.89; 95% CI 0.78 to 1.01). Subgroup analysis indicated that patients with moderate disease may benefit from the higher dose of 4.8 g/day. One study compared (n = 123 patients) Pentasa 4 g/day to 2.25 g/day in patients with moderate disease. Twenty-five per cent of patients in the 4 g/day group failed to improve clinically compared to 57% of patients in the 2.25 g/day group (RR 0.44; 95% CI 0.27 to 0.71). A pooled analysis of two studies comparing MMX mesalamine 4.8 g/day to 2.4 g/day found no statistically significant difference in efficacy (RR 1.03, 95% CI 0.82 to 1.29). There were no statistically significant differences in the incidence of adverse events between 5-ASA and placebo, once daily and conventionally dosed 5-ASA, 5-ASA and comparator 5-ASA formulation and 5-ASA dose ranging (high dose versus low dose) studies. Common adverse events included flatulence, abdominal pain, nausea, diarrhea, headache and worsening ulcerative colitis. SASP was not as well tolerated as 5-ASA. Twenty-nine percent of SASP patients experienced an adverse event compared to 15% of 5-ASA patients (RR 0.48, 95% CI 0.37 to 0.63). 5-ASA was superior to placebo and no more effective than SASP. Considering their relative costs, a clinical advantage to using oral 5-ASA in place of SASP appears unlikely. 5-ASA dosed once daily appears to be as efficacious and safe as conventionally dosed 5-ASA. Adherence does not appear to be enhanced by once daily dosing in the clinical trial setting. It is unknown if once daily dosing of 5-ASA improves adherence in a community-based setting. There do not appear to be any differences in efficacy or safety among the various 5-ASA formulations. A daily dosage of 2.4 g appears to be a safe and effective induction therapy for patients with mild to moderately active ulcerative colitis. Patients with moderate disease may benefit from an initial dose of 4.8 g/day.

Efficacy of intravenous fluid warming during goal-directed fluid therapy in patients undergoing laparoscopic colorectal surgery: a randomized controlled trial.

PubMed

Choi, Ji-Won; Kim, Duk-Kyung; Lee, Seung-Won; Park, Jung-Bo; Lee, Gyu-Hong

2016-06-01

To evaluate the clinical efficacy of intravenous (IV) fluid warming in patients undergoing laparoscopic colorectal surgery. Adult patients undergoing laparoscopic colorectal surgery were randomly assigned to receive either IV fluids at room temperature (control group) or warmed IV fluids (warm fluids group). Each patient received a standardized goal-directed fluid regimen based on stroke volume variances. Oesophageal temperature was measured at 15 min intervals for 2 h after induction of anaesthesia. A total of 52 patients were enrolled in the study. The drop in core temperature in the warm fluids group was significantly less than in the control group 2 h after the induction of anaesthesia. This significant difference was seen from 30 min after induction. IV fluid warming was associated with a smaller drop in core temperature than room temperature IV fluids in laparoscopic colorectal surgery incorporating goal-directed fluid therapy. © The Author(s) 2016.

Medical therapeutics: from induction to scientific evolution.

PubMed

Nunes, José Pedro Lopes

2013-01-01

The field of medical therapeutics may be characterized as having suffered major scientific evolution in the last decades. The publication of landmark studies has been important enough to produce shifts in patient care. However, the scientific evolution in this field does not necessarily imply a progressively greater degree of certitude. In fact, it is not uncommon for new knowledge, when reflected in clinical practice, to weaken previous knowledge. In medical therapeutics, strict inductive reasoning implies the existence of empirical intervention data, typically clinical trial data. In many instances, however, such data does not exist-leaving room for a mixture of inductive and "pseudo-deductive" reasoning. It is often necessary to establish treatment on the basis of incomplete and inconclusive information, more so when the clinical situation is grave, but when no valid information exists, no treatment may be an option. In many instances, the rule "I wish not to impose on others" has superseded the concept "Do not impose on others what you yourself do not desire."

Modeling induction heater temperature distribution in polymeric material

NASA Astrophysics Data System (ADS)

Sorokin, A. G.; Filimonova, O. V.

2017-10-01

An induction heating system has a number of inherent benefits compared to traditional heating systems due to a non-contact heating process. The main interesting area of the induction heating process is the efficiency of the usage of energy, choice of the plate material and different coil configurations based on application. Correctly designed, manufactured and maintained induction coils are critical to the overall efficiency of induction heating solutions. The paper describes how the induction heating system in plastic injection molding is designed. The use of numerical simulation in order to get the optimum design of the induction coil is shown. The purpose of this work is to consider various coil configurations used in the induction heating process, which is widely used in plastic molding. Correctly designed, manufactured and maintained induction coils are critical to the overall efficiency of induction heating solutions. The results of calculation are in the numerical model.

Daily low-dose hCG stimulation during the luteal phase combined with GnRHa triggered IVF cycles without exogenous progesterone: a proof of concept trial.

PubMed

Andersen, Claus Yding; Elbaek, Helle Olesen; Alsbjerg, Birgit; Laursen, Rita Jakubcionyte; Povlsen, Betina Boel; Thomsen, Lise; Humaidan, Peter

2015-10-01

Can the luteal phase support be improved in terms of efficacy, hormonal profiles and convenience as compared with today's standard care? Daily low-dose rhCG supplementation in GnRHa triggered IVF cycles can replace the traditional used luteal phase support with exogenous progesterone. A bolus of hCG for final maturation of follicles in connection with COS may induce the risk of OHSS and the luteal phase progesterone levels rise very abruptly in the early luteal phase. This is a proof-of-concept study conducted as a three arm RCT with a total of 93 patients. First patient enrolled in January 2012 and the study finished in January 2014. Normal responder women undergoing IVF/ICSI treatment in a university hospital. One arm served as control, where women followed a standard antagonist protocol. Two study arms were included both having 125 IU hCG daily for luteal phase support without exogenous progesterone after using a GnRHa trigger for ovulation induction. In both study arms exogenous FSH was stopped on stimulation day 6 and replaced by exogenous hCG that was initiated on either stimulation day 2 or day 6. Blood samples were obtained on the day of ovulation induction, on the day of oocyte pickup (OPU) and day OPU + 7. The mean serum levels of hCG did not exceeded the normal physiological range of LH activity in any samples. Mid-luteal progesterone levels were significantly higher in the two study groups receiving daily low-dose hCG for luteal phase support as compared with the control group (control group: 177 ± 27 nmol/l; study group 1: 334 ± 42 nmol/l; study group 2: 277 ± 27 nmol/l; (mean ± SEM). No differences in reproductive outcome were seen between groups. The number of patients included is limited and conclusions need to be verified in a larger RCT. Endogenous production of progesterone may become more attractive as the luteal phase support with levels of LH-like activity only in the physiological range and may, from the patients' point of view, replace inconvenient exogenous progesterone preparation. Further hCG may reduce the cost of stimulation and may collectively be used for stimulation of the follicular phase, ovulation induction and for luteal phase support. An unrestricted grant from ARTS Biologics made this study possible. None of the authors has any competing interests to declare. ClinicalTrial.gov number: NCT01504139. 28 December 2011. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia.

PubMed

Burnett, A K; Russell, N H; Hills, R K; Kell, J; Nielsen, O J; Dennis, M; Cahalin, P; Pocock, C; Ali, S; Burns, S; Freeman, S; Milligan, D; Clark, R E

2017-02-01

The study was designed to compare clofarabine plus daunorubicin vs daunorubicin/ara-C in older patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS). Eight hundred and six untreated patients in the UK NCRI AML16 trial with AML/high-risk MDS (median age, 67 years; range 56-84) and normal serum creatinine were randomised to two courses of induction chemotherapy with either daunorubicin/ara-C (DA) or daunorubicin/clofarabine (DClo). Patients were also included in additional randomisations; ± one dose of gemtuzumab ozogamicin in course 1; 2v3 courses and ± azacitidine maintenance. The primary end point was overall survival. The overall response rate was 69% (complete remission (CR) 60%; CRi 9%), with no difference between DA (71%) and DClo (66%). There was no difference in 30-/60-day mortality or toxicity: significantly more supportive care was required in the DA arm even though platelet and neutrophil recovery was significantly slower with DClo. There were no differences in cumulative incidence of relapse (74% vs 68%; hazard ratio (HR) 0.93 (0.77-1.14), P=0.5); survival from relapse (7% vs 9%; HR 0.96 (0.77-1.19), P=0.7); relapse-free (31% vs 32%; HR 1.02 (0.83-1.24), P=0.9) or overall survival (23% vs 22%; HR 1.08 (0.93-1.26), P=0.3). Clofarabine 20 mg/m 2 given for 5 days with daunorubicin is not superior to ara-C+daunorubicin as induction for older patients with AML/high-risk MDS.

Prognostic significance of FLT3 internal tandem repeat in patients with de novo acute myeloid leukemia treated with reinforced courses of chemotherapy.

PubMed

Boissel, N; Cayuela, J M; Preudhomme, C; Thomas, X; Grardel, N; Fund, X; Tigaud, I; Raffoux, E; Rousselot, P; Sigaux, F; Degos, L; Castaigne, S; Fenaux, P; Dombret, H

2002-09-01

FLT3 internal tandem duplications (FLT3-ITDs) are present in nearly 25% of patients with AML and have been associated with poor response to conventional therapy and poor outcome. We retrospectively evaluated the effect of reinforced courses of chemotherapy on the prognostic value of FLT3-ITDs in 159 AML patients prospectively enrolled in the ALFA-9000 trial, which randomly compared three reinforced induction regimens (standard 3+7 including high-dose daunorubicin, double induction, and timed-sequential therapy). FLT3-ITD was present in 40/159 (25%) blast samples and associated with high WBC (P = 0.002) and cytogenetics (P < 0.001) with a higher incidence (35%) in patients with a normal karyotype. There was no difference in CR rate between FLT3-wt and FLT3-ITD patients (80% vs 78%). Relapse-free survival (RFS) was similar in both groups (5-year RFS, 33% vs 32%; P = 0.41), even after adjustment for age, sex, WBC, cytogenetics, and treatment arm. A trend to a worse survival was observed in the FLT3-ITD group (estimated 5-year OS, 23% vs 37%; P = 0.09), mainly in patients with a normal karyotype. This was associated with a dramatic outcome in relapsing FLT3-ITD patients (estimated 3-year post-relapse survival, 0% vs 27%; P = 0.04). These results suggest that the bad prognosis associated with FLT3-ITDs in AML might be partly overcome using reinforced chemotherapy. Early detection of FLT3 mutations might thus be useful to intensify induction as well as post-remission therapy in FLT3-ITD patients.

A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia

PubMed Central

Burnett, A K; Russell, N H; Hills, R K; Kell, J; Nielsen, O J; Dennis, M; Cahalin, P; Pocock, C; Ali, S; Burns, S; Freeman, S; Milligan, D; Clark, R E

2017-01-01

The study was designed to compare clofarabine plus daunorubicin vs daunorubicin/ara-C in older patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS). Eight hundred and six untreated patients in the UK NCRI AML16 trial with AML/high-risk MDS (median age, 67 years; range 56–84) and normal serum creatinine were randomised to two courses of induction chemotherapy with either daunorubicin/ara-C (DA) or daunorubicin/clofarabine (DClo). Patients were also included in additional randomisations; ± one dose of gemtuzumab ozogamicin in course 1; 2v3 courses and ± azacitidine maintenance. The primary end point was overall survival. The overall response rate was 69% (complete remission (CR) 60% CRi 9%), with no difference between DA (71%) and DClo (66%). There was no difference in 30-/60-day mortality or toxicity: significantly more supportive care was required in the DA arm even though platelet and neutrophil recovery was significantly slower with DClo. There were no differences in cumulative incidence of relapse (74% vs 68% hazard ratio (HR) 0.93 (0.77–1.14), P=0.5); survival from relapse (7% vs 9% HR 0.96 (0.77–1.19), P=0.7); relapse-free (31% vs 32% HR 1.02 (0.83–1.24), P=0.9) or overall survival (23% vs 22% HR 1.08 (0.93–1.26), P=0.3). Clofarabine 20 mg/m2 given for 5 days with daunorubicin is not superior to ara-C+daunorubicin as induction for older patients with AML/high-risk MDS. PMID:27624670

Preliminary Evaluation of Three-Dimensional Primary Human Hepatocyte Culture System for Assay of Drug-Metabolizing Enzyme-Inducing Potential.

PubMed

Arakawa, Hiroshi; Kamioka, Hiroki; Jomura, Tomoko; Koyama, Satoshi; Idota, Yoko; Yano, Kentaro; Kojima, Hajime; Ogihara, Takuo

2017-01-01

Drug-induced liver injury (DILI) is a common reason for withdrawal of candidate drugs from clinical trials, or of approved drugs from the market. DILI may be induced not only by intact parental drugs, but also by metabolites or intermediates, and therefore should be evaluated in the enzyme-induced state. Here, we present a protocol for assay of drug-metabolizing enzyme-inducing potential using three-dimensional (3D) primary cultures of human hepatocytes (hepatocyte spheroids). Hepatocyte spheroids could be used up to 21 d after seeding (pre-culture for 7 d and exposure to inducer for up to 14 d), based on preliminary evaluation of basal activities of CYP subtypes and mRNA expression of the corresponding transcription factor and xenobiotic receptors (aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR) and pregnane X receptor (PXR)). After 2 d exposure of hepatocyte spheroids to omeprazole, phenobarbital and rifampicin (typical inducers of CYP1A2, 2B6 and 3A4, respectively), CYP1A2, 2B6 and 3A4 mRNA expression levels were significantly increased. The mRNA induction of CYP2B6 remained reasonably stable between days 2 and 14 of exposure to inducers, while induction of both CYP1A2 and 3A4 continued to increase up to day 14. These enzyme activities were all significantly increased compared with the control until day 14. Our findings indicate that our 3D hepatocyte spheroids system would be especially suitable for long-term testing of enzyme activity induction by drugs, either to predict or to verify clinical events.

Transplanting Sensitized Kidney Transplant Patients With Equivalent Outcomes Utilizing Stringent HLA Crossmatching.

PubMed

Rohan, Vinayak S; Taber, David J; Moussa, Omar; Pilch, Nicole A; Denmark, Signe; Meadows, Holly B; McGillicuddy, John W; Chavin, Kenneth D; Baliga, Prabhakar K; Bratton, Charles F

2017-02-01

Elevated panel reactive antibody levels have been traditionally associated with increased acute rejection rate and decreased long-term graft survival after kidney transplant. In this study, our objective was to determine patient and allograft outcomes in sensitized kidney transplant recipients with advanced HLA antibody detection and stringent protein sequence epitope analyses. This was a subanalysis of a prospective, risk-stratified randomized controlled trial that compared interleukin 2 receptor antagonist to rabbit antithymocyte globulin induction in 200 kidney transplant recipients, examining outcomes based on panel reactive antibody levels of < 20% (low) versus ≥ 20% (high, sensitized). The study was conducted between February 2009 and July 2011. All patients underwent solid-phase single antigen bead assays to detect HLA antibodies and stringent HLA epitope analyses with protein sequence alignment for virtual crossmatching. Delayed graft function, acute rejection rates, and graft loss were the main outcomes measured. Both the low (134 patients) and high (66 patients) panel reactive antibody level cohorts had equivalent induction and maintenance immunosuppression. Patients in the high-level group were more likely to be female (P < .001), African American (P < .001), and received a kidney from a deceased donor (P = .004). Acute rejection rates were similar between the low (rate of 8%) and high (rate of 9%) panel reactive antibody groups (P = .783). Delayed graft function, borderline rejection, graft loss, and death were not different between groups. Multivariate analyses demonstrated delayed graft function to be the strongest predictor of acute rejection (odds ratio, 5.7; P = .005); panel reactive antibody level, as a continuous variable, had no significant correlation with acute rejection (C statistic, 0.48; P = .771). Appropriate biologic matching with single antigen bead assays and stringent epitope analyses provided excellent outcomes in sensitized patients regardless of the induction therapy choice.

Feasibility, safety, and preliminary efficacy of Low Amplitude Seizure Therapy (LAP-ST): A proof of concept clinical trial in man.

PubMed

Youssef, Nagy A; Sidhom, Emad

2017-11-01

Current pulse amplitude used in clinical ECT may be higher than needed. Reducing pulse amplitude may improve focality of the electric field and thus cognitive adverse effects. Here we examine the feasibility, safety, and whether Low Pulse Amplitude Seizure Therapy (LAP-ST, 0.5-0.6A) minimizes cognitive adverse effects while retaining efficacy. Patients with treatment-resistant primary mood (depressive episodes) or psychotic disorders who were clinically indicated to undergo ECT were offered to be enrolled in an open-label study. The study consisted of a full acute course of LAP-ST under standard anesthesia and muscle relaxation. The primary outcome was feasibility of seizure induction. Clinical outcome measures were: time to reorientation (TRO), Mini Mental State Examination, Montgomery Aberg Depression Scale, and Brief Psychiatric Rating Scale, and Clinical Global Impression Scale. Twenty-two patients consented for enrollment in the study. LAP-ST was feasible, and all patients had seizures in the first session. Participants had a quick orientation with median TRO of 4.5min. Treatment was efficacious for both depressive and psychotic symptoms. Relatively small sample size, non-blinded, and no randomization was performed in this initial proof of concept study. This first human preliminary data of a full course of focal LAP-ST demonstrates that seizure induction is feasible. These results, although preliminary, suggest that the LAP-ST compared to the standard ECT techniques may result in less cognitive side effects, but comparable efficacy. Larger studies are needed to replicate these findings. Copyright © 2017 Elsevier B.V. All rights reserved.

Feeling sad makes us feel older: Effects of a sad-mood induction on subjective age.

PubMed

Dutt, Anne J; Wahl, Hans-Werner

2017-08-01

A mood-induction paradigm was implemented in a sample of 144 adults covering midlife and old age (40-80 years) to investigate associations between mood and subjective age. Sad or neutral mood was induced by texts and music pieces. Subjective age was operationalized as felt age relative to chronological age. Participants receiving the sad-mood induction reported changes toward older felt ages from pre- to postinduction. Participants receiving the neutral-mood induction reported comparable levels of subjective age at pre- and postinduction. Effects were comparable across middle- and older aged participants. Results suggest that sad affective states might dampen subjective age. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Induction immunosuppressive therapies in renal transplantation.

PubMed

Gabardi, Steven; Martin, Spencer T; Roberts, Keri L; Grafals, Monica

2011-02-01

Induction immunosuppressive therapies for patients undergoing renal transplantation are reviewed. The goal of induction therapy is to prevent acute rejection during the early posttransplantation period by providing a high degree of immunosuppression at the time of transplantation. Induction therapy is often considered essential to optimize outcomes, particularly in patients at high risk for poor short-term outcomes. All of the induction immunosuppressive agents currently used are biological agents and are either monoclonal (muromonab-CD3, daclizumab, basiliximab, alemtuzumab) or polyclonal (antithymocyte globulin [equine] or antithymocyte globulin [rabbit]) antibodies. Although antithymocyte globulin (rabbit) is not labeled for induction therapy, it is used for this purpose more than any other agent. Basiliximab is not considered as potent an immunosuppressive agent but has a much more favorable adverse-effect profile compared with antithymocyte globulin (rabbit) and is most commonly used in patients at low risk for acute rejection. Rituximab is being studied for use as induction therapy but to date has not demonstrated any significant benefits over placebo. While head-to-head data are available comparing most induction agents, the final decision on the most appropriate induction therapy for a transplant recipient is highly dependent on preexisting medical conditions, donor characteristics, and the maintenance immunosuppressive regimen to be used. No standard induction immunosuppressive regimen exists for patients undergoing renal transplantation. Antithymocyte globulin (rabbit) is the most commonly used agent, whereas basiliximab appears safer. The choice of regimen depends on the preferences of clinicians and institutions.

A cost-effectiveness analysis of first-line induction and maintenance treatment sequences in patients with advanced nonsquamous non-small-cell lung cancer in France

PubMed Central

Taipale, Kaisa; Winfree, Katherine B; Boye, Mark; Basson, Mickael; Sleilaty, Ghassan; Eaton, James; Evans, Rachel; Chouaid, Christos

2017-01-01

Background Comparative effectiveness and cost-effectiveness data for induction–maintenance (I–M) sequences for the treatment of patients with nonsquamous non-small-cell lung cancer (nsqNSCLC) are limited because of a lack of direct evidence. This analysis aimed to compare the cost-effectiveness of I–M pemetrexed with those of other I–M regimens used for the treatment of patients with advanced nsqNSCLC in the French health-care setting. Materials and methods A previously developed global partitioned survival model was adapted to the France-only setting by restricting treatment sequences to include 12 I–M regimens most relevant to France, and incorporating French costs and resource-use data. Following a systematic literature review, network meta-analyses were performed to obtain hazard ratios for progression-free survival (PFS) and overall survival (OS) relative to gemcitabine + cisplatin (induction sequences) or best supportive care (BSC) (maintenance sequences). Modeled health-care benefits were expressed as life-years (LYs) and quality-adjusted LYs (QALYs) (estimated using French EuroQol five-dimension questionnaire tariffs). The study was conducted from the payer perspective (National Health Insurance). Cost- and benefit-model inputs were discounted at an annual rate of 4%. Results Base-case results showed pemetrexed + cisplatin induction followed by (→) pemetrexed maintenance had the longest mean OS and PFS and highest LYs and QALYs. Costs ranged from €12,762 for paclitaxel + carboplatin → BSC to €35,617 for pemetrexed + cisplatin → pemetrexed (2015 values). Gemcitabine + cisplatin → BSC, pemetrexed + cisplatin → BSC, and pemetrexed + cisplatin → pemetrexed were associated with fully incremental cost-effectiveness ratios (ICERs) of €16,593, €80,656, and €102,179, respectively, per QALY gained versus paclitaxel + carboplatin → BSC. All other treatment sequences were either dominated (ie, another sequence had lower costs and better/equivalent outcomes) or extendedly dominated (ie, the comparator had a higher ICER than a more effective comparator) in the model. Sensitivity analyses showed the model to be relatively insensitive to plausible changes in the main assumptions, with none increasing or decreasing the ICER by more than ~€20,000 per QALY gained. Conclusion In the absence of direct comparative trial evidence, this cost-effectiveness analysis indicated that of a large number of I–M sequences used for the treatment of patients with nsqNSCLC in France, pemetrexed + cisplatin → pemetrexed achieved the best clinical outcomes (0.28 incremental QALYs gained) versus paclitaxel + carboplatin → BSC. PMID:28860832

Design and physical features of inductive coaxial copper vapor lasers

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

Batenin, V. M.; Kazaryan, M. A.; Karpukhin, V. T.

A physical model of a copper vapor laser pumped by a pulse-periodic inductive (electrodeless) discharge is considered. The feasibility of efficient laser pumping by an inductive discharge and reaching high output parameters comparable to those of conventional copper vapor lasers pumped by a longitudinal electrode discharge is demonstrated. The design and physical features of an inductive copper vapor laser with an annular working volume are discussed.

Diet and exercise interventions for preventing gestational diabetes mellitus.

PubMed

Bain, Emily; Crane, Morven; Tieu, Joanna; Han, Shanshan; Crowther, Caroline A; Middleton, Philippa

2015-04-12

Gestational diabetes mellitus (GDM) is associated with a wide range of adverse health consequences for women and their babies in the short and long term. With an increasing prevalence of GDM worldwide, there is an urgent need to assess strategies for GDM prevention, such as combined diet and exercise interventions. To assess the effects of combined diet and exercise interventions for preventing GDM and associated adverse health consequences for women and their babies. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (11 February 2014) and reference lists of retrieved studies. We updated the search in February 2015 but these results have not yet been incorporated and are awaiting classification. Randomised controlled trials (RCTs) and cluster-RCTs assessing the effects of interventions that included diet and exercise components. We included studies where combined diet and exercise interventions were compared with no intervention (i.e. standard care).We planned to also compare diet and exercise interventions with alternative diet and/or exercise interventions but no trials were identified for this comparison. Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of the included studies. Data were checked for accuracy. We included 13 randomised controlled trials (involving 4983 women and their babies). We assessed the included trials as being of moderate risk of bias overall.When comparing women receiving a diet and exercise intervention with those receiving no intervention, there was no clear difference in the risk of developing GDM (average risk ratio (RR) 0.92, 95% confidence interval (CI) 0.68 to 1.23; 11 trials, 3744 women), caesarean section (RR 0.92, 95% CI 0.83 to 1.01; seven trials, 3246 women), or large-for-gestational age (RR 0.90, 95% CI 0.77 to 1.05; 2950 infants). Only one trial reported on perinatal mortality, and found no clear difference in the risk of stillbirth (RR 0.99, 95% CI 0.29 to 3.42; 2202 fetuses) or neonatal death (RR 0.99, 95% CI 0.06 to 15.85; 2202 neonates).Very few differences were shown between groups for the review's secondary outcomes, including for induction of labour, perineal trauma, pre-eclampsia, postpartum haemorrhage and infection, macrosomia, birthweight, small-for-gestational age, ponderal index, neonatal hypoglycaemia requiring treatment, hyperbilirubinaemia requiring treatment, shoulder dystocia, bone fracture or nerve palsy. Women receiving a combined diet and exercise intervention were, however, found to have a reduced risk of preterm birth compared with women receiving no intervention (RR 0.71, 95% CI 0.55 to 0.93; five trials, 2713 women).A trend towards reduced weight gain during pregnancy was shown for women receiving the combined diet and exercise intervention (mean difference (MD) -0.76 kg, 95% CI -1.55 to 0.03; eight trials, 2707 women; P = 0.06, random-effects); but no clear difference in postnatal weight retention was observed overall.In relation to adherence to the interventions, a number of trials that reported on behaviour modifications showed benefits in diet- (5/8 trials) and physical activity- (4/8 trials) related behaviours for women receiving the combined diet and exercise intervention, compared with women receiving no intervention; however there was notable variation across trials in outcomes measured and results observed. Only two trials reported on well-being and quality of life of women, and did not observe differences between groups for these outcomes.Very few trials reported on outcomes relating to the use of health services, although one trial suggested a reduced length of antenatal hospital stay for women receiving a combined diet and exercise intervention (MD -0.27 days, 95% CI -0.49 to -0.05; 2153 women).No information was available on outcomes for the infant as a child or adult, or for most longer-term outcomes for the mother. There are limitations associated with the available RCT evidence on the effects of combined diet and exercise interventions during pregnancy for preventing GDM. Results from 13 RCTs (of moderate quality) suggest no clear difference in the risk of developing GDM for women receiving a combined diet and exercise intervention compared with women receiving no intervention. However, the ability to draw firm conclusions was limited by variations in the quality of trials, characteristics of the interventions and populations assessed, and outcome definitions between trials.Based on the data currently available, conclusive evidence is not available to guide practice. Further large, well-designed RCTs, addressing the limitations of previous studies, are needed to assess the effects of combined interventions on preventing GDM and other relevant pregnancy outcomes including caesarean birth, large-for-gestational age and perinatal mortality. Health service utilisation and costs, and longer-term outcomes for mothers and their babies should be included. We identified another 16 trials which are ongoing and we will consider these for inclusion in the next update of this review.

EFFICACY OF TACROLIMUS FOR INDUCTION OF REMISSION IN PATIENTS WITH MODERATE-TO-SEVERE ULCERATIVE COLITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

PubMed

Lasa, Juan; Olivera, Pablo

2017-01-01

There is evidence that shows that calcineurin inhibitors may be useful for the treatment of severe ulcerative colitis. However, evidence regarding the efficacy of tacrolimus for remission induction in this setting is scarce. To develop a systematic review on the existing evidence regarding the clinical efficacy of tacrolimus for the induction of remission in patients with moderate-to-severe ulcerative colitis. A literature search was undertaken from 1966 to August 2016 using MEDLINE, Embase, LILACS and the Cochrane Library. The following MeSH terms were used: "Inflammatory Bowel Diseases" or "Ulcerative Colitis" and "Calcineurin Inhibitors" or "Tacrolimus" or "FK506". Studies performed in adult ulcerative colitis patients that evaluated the clinical efficacy of tacrolimus for the induction of remission were considered for revision. A meta-analysis was performed with those included studies that were also placebo-controlled and randomized. Clinical response as well as clinical remission and mucosal healing were evaluated. Overall, 755 references were identified, from which 22 studies were finally included. Only two of them were randomized, placebo-controlled trials. A total of 172 patients were evaluated. A significantly lower risk of failure in clinical response was found for tacrolimus versus placebo [RR 0.58 (0.45-0.73)]; moreover, a lower risk of failure in the induction of remission was also found versus placebo [RR 0.91 (0.82-1)]. Tacrolimus seems to be a valid therapeutic alternative for the induction of remission in patients with moderate-to-severe ulcerative colitis.

Efficacy of Creative Clay Work for Reducing Negative Mood: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Kimport, Elizabeth R.; Robbins, Steven J.

2012-01-01

Clay work has long been used in art therapy to achieve therapeutic goals. However, little empirical evidence exists to document the efficacy of such work. The present study randomly assigned 102 adult participants to one of four conditions following induction of a negative mood: (a) handling clay with instructions to create a pinch pot, (b)…

Specific apoptosis induction by the dual PI3K/mTor inhibitor NVP-BEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells

PubMed Central

Brachmann, Saskia M.; Hofmann, Irmgard; Schnell, Christian; Fritsch, Christine; Wee, Susan; Lane, Heidi; Wang, Shaowen; Garcia-Echeverria, Carlos; Maira, Sauveur-Michel

2009-01-01

NVP-BEZ235 is a dual PI3K/mTOR inhibitor currently in phase I clinical trials. We profiled this compound against a panel of breast tumor cell lines to identify the patient populations that would benefit from such treatment. In this setting, NVP-BEZ235 selectively induced cell death in cell lines presenting either HER2 amplification and/or PIK3CA mutation, but not in cell lines with PTEN loss of function or KRAS mutations, for which resistance could be attributed, in part to ERK pathway activity. An in depth analysis of death markers revealed that the cell death observed upon NVP-BEZ235 treatment could be recapitulated with other PI3K inhibitors and that this event is linked to active PARP cleavage indicative of an apoptotic process. Moreover, the effect seemed to be partly independent of the caspase-9 executioner and mitochondrial activated caspases, suggesting an alternate route for apoptosis induction by PI3K inhibitors. Overall, this study will provide guidance for patient stratification for forthcoming breast cancer phase II trials for NVP-BEZ235. PMID:20007781

IL6 blockade potentiates the anti-tumor effects of γ-secretase inhibitors in Notch3-expressing breast cancer.

PubMed

Wang, Dong; Xu, Jiahui; Liu, Bingjie; He, Xueyan; Zhou, Lei; Hu, Xin; Qiao, Feng; Zhang, Anli; Xu, Xiaojun; Zhang, Huafeng; Wicha, Max S; Zhang, Lixing; Shao, Zhi-Ming; Liu, Suling

2018-02-01

Notch pathways have important roles in carcinogenesis including pathways involving the Notch1 and Notch2 oncogenes. Pan-Notch inhibitors, such as gamma secretase inhibitors (GSIs), have been used in the clinical trials, but the outcomes of these trials have been insufficient and have yielded unclear. In the present study, we demonstrated that GSIs, such as MK-0752 and RO4929097, inhibit breast tumor growth, but increase the breast cancer stem cell (BCSC) population in Notch3-expressing breast cancer cells, in a process that is coupled with IL6 induction and is blocked by the IL6R antagonist Tocilizumab (TCZ). IL6 induction results from inhibition of Notch3-Hey2 signaling through MK-0752. Furthermore, HIF1α upregulates Notch3 expression via direct binding to the Notch3 promoter and subsequently downregulates BCSCs by decreasing the IL6 levels in Notch3-expressing breast cancer cells. Utilizing both breast cancer cell line xenografts and patient-derived xenografts (PDX), we showed that the combination of MK-0752 and Tocilizumab significantly decreases BCSCs and inhibits tumor growth and thus might serve as a novel therapeutic strategy for treating women with Notch3-expressing breast cancers.

An effective modestly intensive re-induction regimen with bortezomib in relapsed or refractory paediatric acute lymphoblastic leukaemia.

PubMed

Kaspers, Gertjan J L; Niewerth, Denise; Wilhelm, Bram A J; Scholte-van Houtem, Peggy; Lopez-Yurda, Marta; Berkhof, Johannes; Cloos, Jacqueline; de Haas, Valerie; Mathôt, Ron A; Attarbaschi, Andishe; Baruchel, André; de Bont, Eveline S; Fagioli, Franca; Rössig, Claudia; Klingebiel, Thomas; De Moerloose, Barbara; Nelken, Brigitte; Palumbo, Giuseppe; Reinhardt, Dirk; Rohrlich, Pierre-Simon; Simon, Pauline; von Stackelberg, Arend; Zwaan, Christian Michel

2018-05-01

This trial explored the efficacy of re-induction chemotherapy including bortezomib in paediatric relapsed/refractory acute lymphoblastic leukaemia. Patients were randomized 1:1 to bortezomib (1.3 mg/m 2 /dose) administered early or late to a dexamethasone and vincristine backbone. Both groups did not differ regarding peripheral blast count on day 8, the primary endpoint. After cycle 1, 8 of 25 (32%) patients achieved complete remission with incomplete blood count recovery, 7 (28%) a partial remission and 10 had treatment failure. Most common grade 3-4 toxicities were febrile neutropenia (31%) and pain (17%). Bortezomib was safely combined with vincristine. Bortezomib rarely penetrated the cerebrospinal fluid. © 2018 John Wiley & Sons Ltd.

Use of mixed-function oxygenases to monitor contaminant exposure in wildlife

USGS Publications Warehouse

Rattner, B.A.; Hoffman, D.J.; Marn, C.M.

1989-01-01

This overview examines the utility of mixed-function oxygenase (MFO) enzymes as a bioeffects monitor for wildlife (amphibians, reptiles, birds and mammals) in view of their widespread use as indicators of contaminant exposure in aquatic invertebrates and fish. Phylogenetic trends in MFO activity, toxicological implications of induction and the relationship between contaminant exposure and MFO activity are discussed. Field studies using avian embryos and hatchlings suggest that MFO induction has utility for documenting contaminant exposure; however, findings in adult birds and mammals are equivocal. Age, sex and season are sources of variation that require consideration when undertaking field trials. Further understanding of MFO inducibility among species and application of recently developed analytical techniques including quantification of specific cytochrome P-450 isozymes are warranted.

Standardized Uptake Decrease on [18F]-Fluorodeoxyglucose Positron Emission Tomography After Neoadjuvant Chemotherapy Is a Prognostic Classifier for Long-Term Outcome After Multimodality Treatment: Secondary Analysis of a Randomized Trial for Resectable Stage IIIA/B Non-Small-Cell Lung Cancer.

PubMed

Pöttgen, Christoph; Gauler, Thomas; Bellendorf, Alexander; Guberina, Maja; Bockisch, Andreas; Schwenzer, Nina; Heinzelmann, Frank; Cordes, Sebastian; Schuler, Martin H; Welter, Stefan; Stamatis, Georgios; Friedel, Godehard; Darwiche, Kaid; Jöckel, Karl-Heinz; Eberhardt, Wilfried; Stuschke, Martin

2016-07-20

A confirmatory analysis was performed to determine the prognostic value of metabolic response during induction chemotherapy followed by bimodality/trimodality treatment of patients with operable locally advanced non-small-cell lung cancer. Patients with potentially operable stage IIIA(N2) or selected stage IIIB non-small-cell lung cancer received three cycles of cisplatin/paclitaxel (induction chemotherapy) followed by neoadjuvant radiochemotherapy (RCT) to 45 Gy (1.5 Gy twice per day concurrent cisplatin/vinorelbine) within the ESPATUE (Phase III Study of Surgery Versus Definitive Concurrent Chemoradiotherapy Boost in Patients With Resectable Stage IIIA[N2] and Selected IIIB Non-Small-Cell Lung Cancer After Induction Chemotherapy and Concurrent Chemoradiotherapy) trial. Positron emission tomography scans were recommended before (t0) and after (t2) induction chemotherapy. Patients who were eligible for surgery after neoadjuvant RCT were randomly assigned to definitive RCT or surgery. The prognostic value of percentage of maximum standardized uptake value (%SUVmax) remaining in the primary tumor after induction chemotherapy-%SUVremaining = SUVmax(t2)/SUVmax(t0)-was assessed by proportional hazard analysis and receiver operating characteristic analysis. Overall, 161 patients were randomly assigned (155 from the Essen and Tübingen centers), and 124 of these received positron emission tomography scans at t0 and t2. %SUVremaining as a continuous variable was prognostic for the three end points of overall survival, progression-free survival, and freedom from extracerebral progression in univariable and multivariable analysis (P < .016). The respective hazard ratios per 50% increase in %SUVremaining from multivariable analysis were 2.3 (95% CI, 1.5 to 3.4; P < .001), 1.8 (95% CI, 1.3 to 2.5; P < .001), and 1.8 (95% CI, 1.2 to 2.7; P = .006) for the three end points. %SUVremaining dichotomized at a cut point of maximum sum of sensitivity and specificity from receiver operating characteristic analysis at 36 months was also prognostic. Exploratory analysis revealed that %SUVremaining was likewise prognostic for overall survival in both treatment arms and was more closely associated with extracerebral distant metastases (P = .016) than with isolated locoregional relapses (P = .97). %SUVremaining is a predictor for survival and other end points after multimodality treatment and can serve as a parameter for treatment stratification after induction chemotherapy or for evaluation of adjuvant new systemic treatment options for high-risk patients. © 2016 by American Society of Clinical Oncology.

A Student Teamwork Induction Protocol

ERIC Educational Resources Information Center

Kamau, Caroline; Spong, Abigail

2015-01-01

Faulty group processes have harmful effects on performance but there is little research about intervention protocols to pre-empt them in higher education. This naturalistic experiment compared a control cohort with an inducted cohort. The inducted cohort attended a workshop, consultations, elected a leader and used tools (a group log and group…

Test and evaluation of Japanese GPR-EMI dual sensor systems at Benkovac test site in Croatia

NASA Astrophysics Data System (ADS)

Ishikawa, J.; Furuta, K.; Pavković, Nikola

2007-04-01

This paper presents an experimental design and the evaluation result of a trial that were carried out from 1 February to 9 March 2006 using real PMA-1A and PMA-2 landmines at the Benkovac test site in Croatia. The objective of the Croatia- Japan joint trial is to evaluate dual sensor systems, which use both ground penetrating radar (GPR) and electromagnetic inductive (EMI) sensors. A comparative trial was also carried out by Croatian deminers using an existing EMI sensor, i.e., a metal detector (MD). The trial aims at evaluating differences in performance between dual sensors and MDs, especially in terms of discrimination of landmines from metal fragments and extension of detectable range in the depth direction. Devices evaluated here are 4 prototypes of anti-personnel landmine detection systems developed under a project of the Japan Science and Technology Agency (JST), the supervising authority of which is the Ministry of Education, Culture, Sports, Science and Technology (MEXT). The prototypes provide operators with subsurface images, and final decision whether a shadow in the image is a real landmine or not is left to the operator. This is similar to the way that medical doctors find cancer by reading CT images. Since operators' pre-knowledge of locations of buried targets significantly influences the test result, three test lanes, which have 3 different kinds of soils, have been designed to be suitable for blind tests. The result showed that the dual sensor systems have a potential to discriminate landmines from metal fragments and that probability of detection for small targets in mineralized soils can be improved by using GPR.

Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen.

PubMed

Andersen, Rikke; Donia, Marco; Ellebaek, Eva; Borch, Troels Holz; Kongsted, Per; Iversen, Trine Zeeberg; Hölmich, Lisbet Rosenkrantz; Hendel, Helle Westergren; Met, Özcan; Andersen, Mads Hald; Thor Straten, Per; Svane, Inge Marie

2016-08-01

Adoptive cell transfer therapy (ACT) based on autologous tumor-infiltrating lymphocytes (TIL) has achieved impressive clinical results in several phase I and II trials performed outside of Europe. Although transient, the toxicities associated with high-dose (HD) bolus IL2 classically administered together with TILs are severe. To further scrutinize whether similar results can be achieved with lower doses of IL2, we have carried out a phase I/II trial of TIL transfer after classical lymphodepleting chemotherapy followed by an attenuated IL2 regimen. Twenty-five patients with progressive treatment-refractory metastatic melanoma, good clinical performance, age < 70 years, and at least one resectable metastasis were eligible. TIL infusion was preceded by standard lymphodepleting chemotherapy and followed by attenuated doses of IL2 administered in an intravenous, continuous decrescendo regimen (ClinicalTrials.gov Identifier: NCT00937625). Classical IL2-related toxicities were observed but patients were manageable in a general oncology ward without the need for intervention from the intensive care unit. RECIST 1.0 evaluation displayed three complete responses and seven partial responses (ORR 42%). Median overall survival was 21.8 months. Tumor regression was associated with a higher absolute number of infused tumor-reactive T cells. Moreover, induction and persistence of antimelanoma T-cell responses in the peripheral blood was strongly correlated to clinical response to treatment. TIL-ACT with a reduced IL2 decrescendo regimen results in long-lasting complete responses in patients with treatment-refractory melanoma. Larger randomized trials are needed to elucidate whether clinical efficacy is comparable with TIL-ACT followed by HD bolus IL2. Clin Cancer Res; 22(15); 3734-45. ©2016 AACR. ©2016 American Association for Cancer Research.

Effect of a Perioperative Intra-Aortic Balloon Pump in High-Risk Cardiac Surgery Patients: A Randomized Clinical Trial.

PubMed

Rocha Ferreira, Graziela Santos; de Almeida, Juliano Pinheiro; Landoni, Giovanni; Vincent, Jean Louis; Fominskiy, Evgeny; Gomes Galas, Filomena Regina Barbosa; Gaiotto, Fabio A; Dallan, Luís Oliveira; Franco, Rafael Alves; Lisboa, Luiz Augusto; Palma Dallan, Luis Roberto; Fukushima, Julia Tizue; Rizk, Stephanie Itala; Park, Clarice Lee; Strabelli, Tânia Mara; Gelas Lage, Silvia Helena; Camara, Ligia; Zeferino, Suely; Jardim, Jaquelline; Calvo Arita, Elisandra Cristina Trevisan; Caldas Ribeiro, Juliana; Ayub-Ferreira, Silvia Moreira; Costa Auler, Jose Otavio; Filho, Roberto Kalil; Jatene, Fabio Biscegli; Hajjar, Ludhmila Abrahao

2018-04-30

The aim of this study was to evaluate the efficacy of perioperative intra-aortic balloon pump use in high-risk cardiac surgery patients. A single-center randomized controlled trial and a meta-analysis of randomized controlled trials. Heart Institute of São Paulo University. High-risk patients undergoing elective coronary artery bypass surgery. Patients were randomized to receive preskin incision intra-aortic balloon pump insertion after anesthesia induction versus no intra-aortic balloon pump use. The primary outcome was a composite endpoint of 30-day mortality and major morbidity (cardiogenic shock, stroke, acute renal failure, mediastinitis, prolonged mechanical ventilation, and a need for reoperation). A total of 181 patients (mean [SD] age 65.4 [9.4] yr; 32% female) were randomized. The primary outcome was observed in 43 patients (47.8%) in the intra-aortic balloon pump group and 42 patients (46.2%) in the control group (p = 0.46). The median duration of inotrope use (51 hr [interquartile range, 32-94 hr] vs 39 hr [interquartile range, 25-66 hr]; p = 0.007) and the ICU length of stay (5 d [interquartile range, 3-8 d] vs 4 d [interquartile range, 3-6 d]; p = 0.035) were longer in the intra-aortic balloon pump group than in the control group. A meta-analysis of 11 randomized controlled trials confirmed a lack of survival improvement in high-risk cardiac surgery patients with perioperative intra-aortic balloon pump use. In high-risk patients undergoing cardiac surgery, the perioperative use of an intra-aortic balloon pump did not reduce the occurrence of a composite outcome of 30-day mortality and major complications compared with usual care alone.

Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial.

PubMed

Vora, Ajay; Goulden, Nick; Wade, Rachel; Mitchell, Chris; Hancock, Jeremy; Hough, Rachael; Rowntree, Clare; Richards, Sue

2013-03-01

Minimal residual disease (MRD) is the most sensitive and specific predictor of relapse risk in children with acute lymphoblastic leukaemia (ALL) during remission. We assessed whether treatment intensity could be adjusted for children and young adults according to MRD risk stratification. Between Oct 1, 2003 and June 30, 2011, consecutive children and young adults (aged 1-25 years) with ALL from the UK and Ireland were recruited. Eligible patients were categorised into clinical standard, intermediate, and high risk groups on the basis of a combination of National Cancer Institute (NCI) criteria, cytogenetics, and early response to induction therapy, which was assessed by bone marrow blast counts taken at days 8 (NCI high-risk patients) and 15 (NCI standard-risk patients) after induction began. Clinical standard-risk and intermediate-risk patients were assessed for MRD. Those classified as MRD low risk (undetectable MRD at the end of induction [day 29] or detectable MRD at day 29 that became undetectable by week 11) were randomly assigned to receive one or two delayed intensification courses. Patients had received induction, consolidation, and interim maintenance therapy before they began delayed intensification. Delayed intensification consisted of pegylated asparaginase on day 4; vincristine, dexamethasone (alternate weeks), and doxorubicin for 3 weeks; and 4 weeks of cyclophosphamide and cytarabine. Computer randomisation was done with stratification by MRD result and balancing for sex, age, and white blood cell count at diagnosis by method of minimisation. Patients, clinicians, and data analysts were not masked to treatment allocation. The primary outcome was event-free survival (EFS), which was defined as time to relapse, secondary tumour, or death. Our aim was to rule out a 7% reduction in EFS in the group given one delayed intensification course relative to that given two delayed intensification courses. Analyses were by intention to treat. This trial is registered, number ISRCTN07355119. Of 3207 patients registered in the trial overall, 521 MRD low-risk patients were randomly assigned to receive one (n=260) or two (n=261) delayed intensification courses. Median follow-up of these patients was 57 months (IQR 42-72). We recorded no significant difference in EFS between the group given one delayed intensification (94·4% at 5 years, 95% CI 91·1-97·7) and that given two delayed intensifications (95·5%, 92·8-98·2; unadjusted odds ratio 1·00, 95% CI 0·43-2·31; two-sided p=0·99). The difference in 5-year EFS between the two groups was 1·1% (95% CI -5·6 to 2·5). 11 patients (actuarial relapse at 5 years 5·6%, 95% CI 2·3-8·9) given one delayed intensification and six (2·4%, 0·2-4·6) given two delayed intensifications relapsed (p=0·23). Three patients (1·2%, 0-2·6) given two delayed intensifications died of treatment-related causes compared with none in the group given one delayed intensification (p=0·08). We recorded no significant difference between groups for serious adverse events and grade 3 or 4 toxic effects; however, the second delayed intensification course was associated with one (<1%) treatment-related death, and 74 episodes of grade 3 or 4 toxic effects in 45 patients (17%). Treatment reduction is feasible for children and young adults with ALL who are predicted to have a low risk of relapse on the basis of rapid clearance of MRD by the end of induction therapy. Medical Research Council and Leukaemia and Lymphoma Research. Copyright © 2013 Elsevier Ltd. All rights reserved.

High-dose rapid and standard induction chemotherapy for patients aged over 1 year with stage 4 neuroblastoma: a randomised trial.

PubMed

Pearson, Andrew D J; Pinkerton, C Ross; Lewis, Ian J; Imeson, John; Ellershaw, Caroline; Machin, David

2008-03-01

The current standard treatment for patients with high-risk neuroblastoma includes initial induction chemotherapy with a 21-day interval between induction treatments. We aimed to assess whether an intensive chemotherapy protocol that had a 10-day interval between treatments would improve event-free survival (EFS) in patients aged 1 year or over with high-risk neuroblastoma. Between Oct 30, 1990, and March 18, 1999, patients with stage 4 neuroblastoma who had not received previous chemotherapy were enrolled from 29 centres in Europe. Patients were randomly assigned to rapid treatment (cisplatin [C], vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C], known as COJEC) or standard treatment (vincristine [O], cisplatin [P], etoposide [E], and cyclophosphamide [C], ie, OPEC, alternated with vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C], ie, OJEC). Both regimens used the same total cumulative doses of each drug (except vincristine), but the dose intensity of the rapid regimen was 1.8-times higher than that of the standard regimen. The standard regimen was given every 21 days if patients showed haematological recovery, whereas the rapid regimen was given every 10 days irrespective of haematological recovery. Response to chemotherapy was assessed according to the conventional International Neuroblastoma Response Criteria (INRC). In responders, surgical excision of the primary tumour was attempted, followed by myeloablation (with 200 mg/m2 of melphalan) and haemopoietic stem-cell rescue. Primary endpoints were 3-year, 5-year, and 10-year EFS. Data were analysed by intention to treat. This trial is registered on the clinical trials site of the US National Cancer Institute website, number NCT00365755, and also as EU-20592 and CCLG-NB-1990-11. 262 patients, of median age 2.95 years (range 1.03-20.97), were randomly assigned-132 patients to standard and 130 patients to rapid treatment. 111 patients in the standard group and 109 patients in the rapid group completed chemotherapy. Chemotherapy doses were recorded for 123 patients in the standard group and 126 patients in the rapid group. 97 of 123 (79%) patients in the standard group and 84 of 126 (67%) patients in the rapid group received at least 90% of the scheduled chemotherapy, and the relative dose intensity was 1.94 compared with the standard regimen. 3-year EFS was 24.2% for patients in the standard group and 31.0% for those in the rapid group (hazard ratio [HR] 0.86 [95% CI 0.66-1.14], p=0.30. 5-year EFS was 18.2% in the standard group and 30.2% in the rapid group, representing a difference of 12.0% (1.8 to 22.3), p=0.022. 10-year EFS was 18.2% in the standard group and 27.1% in the rapid group, representing a difference of 8.9% (-1.2 to 19.0), p=0.085. Myeloablation was given a median of 55 days earlier in patients assigned rapid treatment than those assigned standard treatment. Infective complications (numbers of patients with febrile neutropenia and septicaemia, and if given, time on antibiotic and antifungal treatment) and time in hospital were greater with rapid treatment. Occurrence of fungal infection was the same in both regimens. Dose intensity can be increased with a rapid induction regimen in patients with high-risk neuroblastoma. There was no significant difference in OS between the rapid and standard regimens at 5 years and 10 years. However, an increasing difference in EFS after 3 years suggests that the efficacy of the rapid regimen is better than the standard regimen. A rapid induction regimen enables myeloablation to be given much earlier, which might contribute to a better outcome.

Co-Administration of Metformin and N-Acetyl Cysteine Fails to Improve Clinical Manifestations in PCOS Individual Undergoing ICSI

PubMed Central

Cheraghi, Ebrahim; Soleimani Mehranjani, Malek; Shariatzadeh, Mohammad Ali; Nasr Esfahani, Mohammad Hossein; Ebrahimi, Zahra

2014-01-01

Background Studies have demonstrated the efficacy of metformin (MTF ) in reducing insulin resistance and N-acetyl cysteine (NAC) in inhibiting oxidative stress which are involved in the pathogenesis of polycystic ovarian syndrome (PCOS). We aimed to compare the effects of MTF and NAC combination on serum metabolite and hormonal levels during the course of ovulation induction in PCOS individual candidates of intracytoplasmic sperm injection (ICSI). Materials and Methods In this prospective randomized clinical trial, placebo con- trolled pilot study, 80 patients of polycystic ovarian syndrome at the age of 25-35 years were divided into 4 groups (n=20): i. NAC=treated with N-acetyl cysteine (600 mg three times daily), ii. MTF=treated with metformin (500 mg three times daily), iii. MTF+NAC=treated with N-acetyl cysteine plus metformin (the offered doses) and iv. placebo (PLA). A total number of 20 patients (6 from MTF group, 4 from NAC group, 6 from MTF+NAC group and 4 from PLA group) were dropped of the study. The drugs were administrated from day 3 of menses of previous cycle until ovum pick-up. Results Serum levels of luteinizing hormone (LH), total testosterone, cholester- ol and triglyceride, insulin and leptin significantly reduced in the MTF and NAC groups compared to the placebo (p<0.01). But levels of LH, total testosterone, cholesterol and triglyceride had no significant reduction in the MTF+NAC groups compared to the placebo. The serum levels of malonyldialdehyde (MDA), insulin and leptin reduced significantly after treatment in the MTF+NAC group compared to the placebo (p<0.05). Conclusion Considering the adverse effect of combination therapy, we proposed the conadministration might have no beneficial effect for PCOS patient during course of ovulation induction of ICSI (Registration Number: IRCT201204159476N1). PMID:25083175

B-cell-targeted therapies in systemic lupus erythematosus and ANCA-associated vasculitis: current progress.

PubMed

Md Yusof, Md Yuzaiful; Vital, Edward M J; Emery, Paul

2013-08-01

B cells play a central role in the pathogenesis of systemic lupus erythematosus and anti-neutrophil cytoplasmic antibody-associated vasculitis. There are various strategies for targeting B cells including depletion, inhibition of survival factors, activation and inhibition of co-stimulatory molecules. Controlled trials in systemic lupus erythematosus have shown positive results for belimumab, promising results for epratuzumab and negative results for rituximab. The failure of rituximab in controlled trials has been attributed to trial design, sample size and outcome measures rather than true inefficacy. In anti-neutrophil cytoplasmic antibody-associated vasculitis, rituximab is effective for remission induction and in relapsing disease. However, the optimal long-term re-treatment strategy remains to be determined. Over the next 5 years, evidence will be available regarding the clinical efficacy of these novel therapies, biomarkers and their long-term safety.

CLL2-BXX Phase II trials: sequential, targeted treatment for eradication of minimal residual disease in chronic lymphocytic leukemia.

PubMed

Cramer, Paula; von Tresckow, Julia; Bahlo, Jasmin; Engelke, Anja; Langerbeins, Petra; Fink, Anna-Maria; Fischer, Kirsten; Wendtner, Clemens-Martin; Kreuzer, Karl-Anton; Stilgenbauer, Stephan; Böttcher, Sebastian; Eichhorst, Barbara; Hallek, Michael

2018-03-01

Four Phase II trials (clinical trials numbers: NCT02345863, NCT02401503, NCT02445131 and NCT02689141) evaluate a different combination of targeted agents in an all-comer population of approximately 60 patients with chronic lymphocytic leukemia irrespective of prior treatment, physical fitness and genetic risk factors. Patients with a higher tumor load start with a debulking treatment with bendamustine. The subsequent induction and maintenance treatment with an anti-CD20 antibody (obinutuzumab or ofatumumab) and a targeted oral agent (ibrutinib, idelalisib or venetoclax) are continued until achievement of a complete response and minimal residual disease negativity. This strategy represents a new era of chronic lymphocytic leukemia therapy where chemotherapy is increasingly replaced by targeted agents and treatment duration is tailored to the patient's individual tumor load and response.

Histone deacetylase inhibitors: current status and overview of recent clinical trials.

PubMed

Ma, Xujun; Ezzeldin, Hany H; Diasio, Robert B

2009-10-01

Histone deacetylase (HDAC) inhibitors are a new group of anticancer agents that have a potential role in the regulation of gene expression, induction of cell death, apoptosis and cell cycle arrest of cancer cells by altering the acetylation status of chromatin and other non-histone proteins. In clinical trials, HDAC inhibitors have demonstrated promising antitumour activity as monotherapy in cutaneous T-cell lymphoma and other haematological malignancies. In solid tumours, several HDAC inhibitors have been shown to be efficacious as single agents; however, results of most clinical trials were in favour of using HDAC inhibitors either prior to the initiation of chemotherapy or in combination with other treatments. Currently, the molecular basis of response to HDAC inhibitors in patients is not fully understood. In this review, we summarize the current status of HDAC inhibitors, as single agents or in combination with other agents in different phases of clinical trials. In most of the clinical trials, HDAC inhibitors were tolerable and exerted biological or antitumor activity. HDAC inhibitors have been studied in phase I, II and III clinical trials with variable efficacy. The combination of HDAC inhibitors with other anticancer agents including epigenetic or chemotherapeutic agents demonstrated favourable clinical outcome.

Augmented post-remission therapy for a minimal residual disease-defined high-risk subgroup of children and young people with clinical standard-risk and intermediate-risk acute lymphoblastic leukaemia (UKALL 2003): a randomised controlled trial.

PubMed

Vora, Ajay; Goulden, Nick; Mitchell, Chris; Hancock, Jeremy; Hough, Rachael; Rowntree, Clare; Moorman, Anthony V; Wade, Rachel

2014-07-01

No randomised study has shown whether stratification of treatment by minimal residual disease (MRD) response improves outcome in children and young people with acute lymphoblastic leukaemia (ALL). We assessed whether children and young people with clinical standard and intermediate-risk ALL who have persistent MRD at the end of induction therapy benefit from augmented post-remission therapy. Between Oct 1, 2003, and June 30, 2011, we enrolled eligible patients aged 1-24 years and initially categorised them into clinical standard-risk, intermediate-risk, and high-risk groups on the basis of a combination of National Cancer Institute criteria, cytogenetics, and early morphological response to induction therapy. Clinical standard-risk and intermediate-risk patients with MRD of 0·01% or higher at day 29 of induction (MRD high risk) were randomly assigned (1:1) to standard therapy (treatment regimens A and B) or augmented post-remission therapy (regimen C). Compared with standard therapy, the augmented treatment regimen (regimen C) included an additional eight doses of pegylated asparaginase, 18 doses of vincristine, and escalated-dose intravenous methotrexate without folinic acid rescue during interim maintenance courses. Computer randomisation was used for treatment allocation and was balanced for sex, age (<10 years vs ≥10 years), and white blood cell count at diagnosis (<50 × 10(9)/L vs ≥50 × 10(9)/L) by minimisation. Patients, clinicians, and data analysts were not masked to treatment allocation. The primary outcomes were event-free survival and overall survival. Analyses were by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN07355119. 533 MRD high-risk patients were randomly assigned to receive standard (n=266) or augmented (n=267) post-remission therapy. After a median follow-up of 70 months (IQR 52-91), 5-year event-free survival was better in the augmented treatment group (89·6% [95% CI 85·9-93·3]) than in the standard group (82·8% [78·1-87·5]; odds ratio [OR] 0·61 [95% CI 0·39-0·98], p=0·04). Overall survival at 5 years was numerically, but not significantly, higher in the augmented treatment group (92·9% [95% CI 89·8-96·0]) than in the standard therapy group (88·9% [85·0-92·8]; OR 0·67 [95% CI 0·38-1·17], p=0·16). More adverse events occurred in the augmented treatment group than in the standard group (asparaginase-related hypersensitivity in 18 [6·7%] in the augmented group vs two [0·8%] in the standard group and asparaginase-related pancreatitis in eight [3·0%] vs one [0·4%]; intravenous methotrexate-related mucositis in 11 [4·1%] vs three [1·1%] and methotrexate-related stomatitis in 48 [18·0%] vs 12 [4·5%]). Our findings suggest that children and young people with acute lymphoblastic leukaemia and 0·01% or more MRD at the end of remission induction therapy could benefit from augmented post-remission therapy. However, the asparaginase and intravenous methotrexate used in the augmented treatment regimen is associated with more adverse events than is the standard post-remission treatment regimen. Medical Research Council and Leukaemia and Lymphoma Research. Copyright © 2014 Elsevier Ltd. All rights reserved.

Creativity and Memory: Effects of an Episodic Specificity Induction on Divergent Thinking

PubMed Central

Madore, Kevin P.; Addis, Donna Rose; Schacter, Daniel L.

2015-01-01

After receiving an episodic specificity induction - brief training in recollecting details of a recent event - people produce more episodic details when imagining future events and solving means-end problems than after receiving a control induction not focused on episodic retrieval. Here we show for the first time that an episodic specificity induction also enhances divergent creative thinking. In Experiment 1, participants exhibited a selective boost on a divergent thinking task that involves generating unusual uses of common objects after a specificity induction compared with a control induction; by contrast, performance was similar on an object association task thought to involve little divergent thinking. In Experiment 2, we replicated the specificity induction effect on divergent thinking using a different control induction, and also found that participants performed similarly on a convergent thinking task following both inductions. These experiments provide novel evidence that episodic memory is involved in divergent creative thinking. PMID:26205963

Ultrasound cervical length measurement in prediction of labor induction outcome.

PubMed

Kehila, M; Abouda, H S; Sahbi, K; Cheour, H; Chanoufi, M Badis

2016-05-17

Induction of labor is one of the most common procedures in modern obstetrics, with an incidence of approximately 20% of all deliveries. Not all of these inductions result in vaginal delivery; some lead to cesarean sections, either for emergency reasons or for failed induction. That's why, It seems necessary to outline strategies for the improvement of the success rate of induced deliveries. Traditionally, the identification of women in whom labor induction is more likely to be successful is based on the Bishop score. However, several studies have shown it to be subjective, with high variation and a poor predictor of the outcome of labor induction. Transvaginal sonography for cervical measurement can be a more objective criterion in assessing the success of labor induction. Many studies have been done recently to compare cervical measurement and Bishop Score in labor induction.This paper reviewed the literature that evaluated sonographic cervical length measurement to predict induction of labor outcome.

Compare and Contrast Inductive and Deductive Research Approaches

ERIC Educational Resources Information Center

Soiferman, L. Karen

2010-01-01

This discussion paper compares and contrasts "inductive" and "deductive" research approaches as described by Trochim (2006) and Plano Clark and Creswell (2007). It also examines the "exploratory" and "confirmatory" approaches by Onwueghuzie and Leech (2005) with respect to the assumption each holds about the nature of knowledge. The paper starts…

Randomized controlled trial of FTY720 versus MMF in de novo renal transplantation.

PubMed

Tedesco-Silva, Helio; Pescovitz, Mark D; Cibrik, Diane; Rees, Michael A; Mulgaonkar, Shamkant; Kahan, Barry D; Gugliuzza, Kristene K; Rajagopalan, P R; Esmeraldo, Ronaldo de M; Lord, Hélène; Salvadori, Maurizio; Slade, Jennifer M

2006-12-27

Phase II trials of FTY720, a novel immunomodulator, have shown promise in preventing rejection with both standard and reduced cyclosporine exposure. This study was designed to confirm those findings. This one-year, multicenter, randomized, phase III study in 696 de novo renal transplant patients compared FTY720 5 mg plus reduced-dose cyclosporine (RDC) or FTY720 2.5 mg plus full-dose cyclosporine (FDC) with mycophenolate mofetil (MMF) plus FDC. All patients received concomitant corticosteroid therapy without antibody induction. The primary efficacy composite endpoint was the incidence of first treated biopsy-proven acute rejection (treated BPAR), graft loss, death or premature study discontinuation at month 12. FTY720 2.5 mg plus FDC was demonstrated to be non-inferior to MMF plus FDC as the primary efficacy endpoint (30.8% and 30.6%) was comparable. The FTY720 5 mg plus RDC treatment regimen was discontinued due to an increased incidence of acute rejection episodes (primary endpoint 43.3%). FTY720 was associated with significantly lower creatinine clearance with a mean difference at 12 months between FTY720 2.5 mg plus FDC and MMF plus FDC of 8 ml/min. While FTY720 2.5 mg plus FDC yielded similar efficacy to MMF plus FDC, the FTY720 5 mg plus RDC did not allow a 50% reduction in cyclosporine exposure. The associated lower creatinine clearance indicated that FTY720 combined with cyclosporine provided no benefit over standard care.

Physical symptoms and emotional responses among women undergoing induced abortion protocols during the second trimester.

PubMed

Freeman, Martine D; Porat, Nurit; Rojansky, Nathan; Elami-Suzin, Matan; Winograd, Orit; Ben-Meir, Assaf

2016-11-01

To compare the physical and emotional effects of two medical protocols for induced abortion during the second trimester. The present study was part of a prospective randomized controlled trial comparing mifepristone followed by oxytocin or misoprostol that was conducted at the Hadassah Hebrew University Medical Center, Jerusalem, Israel, from January 10, 2009, to February 22, 2012. Inclusion criteria were pregnancy (14-24weeks), epidural analgesia, and medical induction of abortion (either elective or following missed abortion). A structured questionnaire was used to assess the participants' physical symptoms and emotional responses. The primary outcome for the present analysis was the degree of physical symptoms reported. Overall, 68 women in the oxytocin group and 67 in the misoprostol group received epidural analgesia and completed the questionnaire. As assessed using a five-point Likert scale, women in the misoprostol group were more likely than those in the oxytocin group to experience diarrhea (1.34±0.84 vs 1.10±0.55; P=0.05) and shivers (3.03±1.75 vs 1.75±1.21; P<0.001). No other between-group differences were detected for the physical or emotional variables evaluated. Differences in physical symptoms experienced by the two treatment groups did not influence the participants' subsequent emotional response. ClinicalTrials.gov: NCT00784797. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Post-prandial effects of hazelnut-enriched high fat meal on LDL oxidative status, oxidative and inflammatory gene expression of healthy subjects: a randomized trial.

PubMed

Di Renzo, L; Merra, G; Botta, R; Gualtieri, P; Manzo, A; Perrone, M A; Mazza, M; Cascapera, S; De Lorenzo, A

2017-04-01

Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. Micronutrients modulate the immune system and exert a protective action by reducing low-density lipoproteins oxidation (ox-LDL) via induction of antioxidant enzymes. The clinical study was a randomized and cross-over trial, conducted through the CONSORT flowchart. We evaluated the gene expression of 103 genes related to oxidative stress (HOSp) and human inflammasome pathways (HIp), and ox-LDL level at fasting and after 40 g raw "Tonda Gentile delle Langhe" hazelnut consumption, in association with a McDonald's® Meal (McDM) in 22 healthy human volunteers. Ox-LDL levels significantly increased comparing no dietary treatment (NDT) vs. McDM, and decreased comparing McDM vs. McDM + H (p<0.05). Percentage of significant genes expressed after each dietary treatment were the follows: (A) NDT vs. McDM: 3.88% HIp and 17.48% HOSp; (B) NDT vs. McDM + H: 17.48% HIp and 23.30% HOSp; (C) McDM vs. McDM + H: 17.48% HIp and 33.98% HOSp. Hazelnut consumption reduced post prandial risk factors of atherosclerosis, such as ox-LDL, and the expression of inflammation and oxidative stress related genes. Chronic studies on larger population are necessary before definitive conclusions.

The effect of pain on task switching: pain reduces accuracy and increases reaction times across multiple switching paradigms.

PubMed

Attridge, Nina; Keogh, Edmund; Eccleston, Christopher

2016-10-01

Pain disrupts attention, which may have negative consequences for daily life for people with acute or chronic pain. It has been suggested that switching between tasks may leave us particularly susceptible to pain-related attentional disruption, because we need to disengage our attention from one task before shifting it onto another. Switching tasks typically elicit lower accuracies and/or longer reaction times when participants switch to a new task compared with repeating the same task, and pain may exacerbate this effect. We present 3 studies to test this hypothesis. In study 1, participants completed 2 versions of an alternating runs switching task under pain-free and thermal pain-induction conditions. Pain did not affect performance on either task. In studies 2 and 3, we examined 7 versions of the switching task using large general population samples, experiencing a variety of naturally occurring pain conditions, recruited and tested on the internet. On all tasks, participants with pain had longer reaction times on both switch and repeat trials compared with participants without pain, but pain did not increase switch costs. In studies 2 and 3, we also investigated the effects of type of pain, duration of pain, and analgesics on task performance. We conclude that pain has a small dampening effect on performance overall on switching tasks. This suggests that pain interrupts attention even when participants are engaged in a trial, not only when attention has been disengaged for shifting to a new task set.

Oral tetra-arsenic tetra-sulfide formula versus intravenous arsenic trioxide as first-line treatment of acute promyelocytic leukemia: a multicenter randomized controlled trial.

PubMed

Zhu, Hong-Hu; Wu, De-Pei; Jin, Jie; Li, Jian-Yong; Ma, Jun; Wang, Jian-Xiang; Jiang, Hao; Chen, Sai-Juan; Huang, Xiao-Jun

2013-11-20

This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of an oral tetra-arsenic tetra-sulfide (As4S4) -containing formula named the Realgar-Indigo naturalis formula (RIF) compared with intravenous arsenic trioxide (ATO) as both induction and maintenance therapies for newly diagnosed acute promyelocytic leukemia (APL). In all, 242 patients with APL were randomly assigned (1:1) to oral RIF (60 mg/kg) or ATO (0.16 mg/kg) combined with all-trans retinoic acid (ATRA; 25 mg/m(2)) during induction therapy. After achieving complete remission (CR), all patients received three courses of consolidation chemotherapy and maintenance treatment with sequential ATRA followed by either RIF or ATO for 2 years. The primary end point was the rate of disease-free survival (DFS) at 2 years, which was assessed for noninferiority with a 10% noninferiority margin. The median follow-up time was 39 months. DFS at 2 years was 98.1% (106 of 108) in the RIF group and 95.5% (107 of 112) in the ATO group. The DFS difference was 2.6% (95% CI, -3.0% to 8.0%). The lower limit of the 95% CI of DFS difference was greater than the -10% noninferiority margin, confirming noninferiority (P < .001). No significant differences were noted between the RIF and ATO groups with regard to the CR rate (99.1% v 97.2%; P = .62) or the overall survival at 3 years (99.1% v 96.6%; P = .18). The rates of adverse events were similar in the two groups. Oral RIF plus ATRA is not inferior to intravenous ATO plus ATRA as first-line treatment of APL and may be considered as a routine treatment option for appropriate patients.

Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2).

PubMed

Charles, Pierre; Terrier, Benjamin; Perrodeau, Élodie; Cohen, Pascal; Faguer, Stanislas; Huart, Antoine; Hamidou, Mohamed; Agard, Christian; Bonnotte, Bernard; Samson, Maxime; Karras, Alexandre; Jourde-Chiche, Noémie; Lifermann, François; Gobert, Pierre; Hanrotel-Saliou, Catherine; Godmer, Pascal; Martin-Silva, Nicolas; Pugnet, Grégory; Matignon, Marie; Aumaitre, Olivier; Viallard, Jean-François; Maurier, François; Meaux-Ruault, Nadine; Rivière, Sophie; Sibilia, Jean; Puéchal, Xavier; Ravaud, Philippe; Mouthon, Luc; Guillevin, Loïc

2018-04-25

To compare individually tailored, based on trimestrial biological parameter monitoring, to fixed-schedule rituximab reinfusion for remission maintenance of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAVs). Patients with newly diagnosed or relapsing granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in complete remission after induction therapy were included in an open-label, multicentre, randomised controlled trial. All tailored-arm patients received a 500 mg rituximab infusion at randomisation, with rituximab reinfusion only when CD19+B lymphocytes or ANCA had reappeared or ANCA titre rose markedly based on trimestrial testing until month 18. Controls received a fixed 500 mg rituximab infusion on days 0 and 14 postrandomisation, then 6, 12 and 18 months after the first infusion. The primary endpoint was the number of relapses (new or reappearing symptom(s) or worsening disease with Birmingham Vasculitis Activity Score (BVAS)>0) at month 28 evaluated by an independent Adjudication Committee blinded to treatment group. Among the 162 patients (mean age: 60 years; 42% women) included, 117 (72.2%) had GPA and 45 (27.8%) had MPA. Preinclusion induction therapy included cyclophosphamide for 100 (61.7%), rituximab for 61 (37.6%) and methotrexate for 1 (0.6%). At month 28, 21 patients had suffered 22 relapses: 14/81 (17.3%) in 13 tailored-infusion recipients and 8/81 (9.9%) in 8 fixed-schedule patients (p=0.22). The tailored-infusion versus fixed-schedule group, respectively, received 248 vs 381 infusions, with medians (IQR) of 3 (2-4) vs 5 (5-5) administrations. AAV relapse rates did not differ significantly between individually tailored and fixed-schedule rituximab regimens. Individually tailored-arm patients received fewer rituximab infusions. NCT01731561; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Clomiphene citrate or anastrozole for ovulation induction in women with polycystic ovary syndrome? A prospective controlled trial.

PubMed

Badawy, Ahmed; Abdel Aal, Ibrahim; Abulatta, Mohamed

2009-09-01

To compare the effects of anastrozole (1 mg) and clomiphene citrate (CC; 100 mg) used for ovulation induction in women with polycystic ovary syndrome. Prospective controlled trial. University teaching hospital and private-practice setting. The study comprised a total of 216 infertile women (469 cycles) with polycystic ovary syndrome. Patients received anastrozole (1 mg/d; 115 patients, 243 cycles) for 5 days, starting on day 3 of menses. A matched historical group of patients with polycystic ovary syndrome who were treated with CC (100 mg/d; 101 patients, 226 cycles) was used as a control group. Timed intercourse was advised 24-36 hours after hCG injection. Number of follicles, serum E(2), serum P, endometrial thickness, and pregnancy and miscarriage rates. The mean age, parity, and duration of infertility in both groups were similar, but statistically significantly more polycystic ovaries were found in the anastrozole group (odds ratio = 2.44; 95% confidence interval = 1.19-5.02). The total numbers of follicles were significantly higher in the CC group (3.8 +/- 0.6 vs. 3.4 +/- 0.5). Endometrial thickness at the time of hCG administration was significantly greater in the anastrozole group (10.1 +/- 0.22 mm vs. 8.2 +/- 0.69 mm). The duration of stimulation was similar in the two groups. Ovulation occurred in 165 (67.9%) of 243 cycles in the anastrozole group and in 150 (68.6%) of 226 cycles in the CC group without significant difference. Serum P was significantly higher in the CC group (7.1 +/- 1.11 vs. 8.1 +/- 0.88 ng/mL). The pregnancy and miscarriage rates were similar in the two groups. Anastrozole was associated with significantly fewer mature and growing follicles, thicker endometrium, and slightly higher pregnancy rate. Anastrozole may be helpful in situations in which multiple pregnancy is not desirable or the risk of ovarian hyperstimulation syndrome is high.

[Phase II clinical trial of two different modes of administration of the induction chemotherapy for locally advanced nasopharyngeal carcinoma].

PubMed

Bi, Ting; Jin, Feng; Wu, Weili; Long, Jinhua; Li, Yuanyuan; Gong, Xiuyun; Luo, Xiuling; Li, Zhuoling; He, Qianyong; Qu, Bo

2015-09-01

To compare the therapeutic effects, toxic side effects and influence on the immune function in patients treated with TPF [docetaxel (DOC) + cisplatin (DDP) + 5-fluorouracil (5-Fu)] induction chronochemotherapy and conventional chemotherapy for locally advanced nasopharyngeal (NPC). Seventy patients with locally advanced nasopharyngeal carcinoma were treated in our department at their first visit from April 2013 to December 2013. They were divided randomly into two groups: the chronochemotherapy group (38 patients) and conventional chemotherapy group (32 patients). All of the patients were treated with TPF regimen with 2 cycles of induction chemotherapy in a 21-28-days/cycle. The chronochemotherapy group: DOC: 75 mg/m2, i. v. gtt, d1 (03: 30-04: 30); DDP: 75 mg/m2, 10 am-10 pm, c.i.v, d1-d5; 5-Fu: 750 mg·m(-2)·d(-1), 10 pm-10 am, c. i.v., d1-d5, both chemotherapies were administered by intravenous infusion using an automatic electric pump. The conventional chemotherapy group: Both DOC and DDP were administered intravenously at a dose of 75 mg/m2 on d1. 5-Fu was given at a dose of 750 mg/m2 for 24 hours from d1-d5 with continuous infusion in a total of 120 hours. In this procedure, prescribing the conventional intravenous infusion, intensity modulated radiation therapy was used after the induction chemotherapy. The prescribed nasopharyngeal lesion dose (GTVnx) was 69.96 Gy/33 fractions for the T1-T2 nasopharygeal cancer, while 73.92 Gy/33 fractions nasopharynx lesion dose (GTVnx) for the T3-T4 nasopharyngeal cancer. The planning target volume (PTV) of positive lymph node (PTVnd) dose was 69.96 Gy/33 fractions. Concurrent chemoradiotherapy: cisplatin 100 mg/m2, i. v. gtt. d1-d2, and there were two cycles in total and 21 days each cycle. Sixty-six patients were evaluable for the response assessment. There were 36 patients in the chronochemotherapy group and 30 patients in the conventional chemotherapy group. After the induction chemotherapy, no CR case was found in both of the two groups. The PR was 80.6% in the chronochemotherapy group and 50.0% in the conventional chemotherapy group (P=0.009). After concurrent chemoradiotherapy, the CR rate in the chronocheotherapy group was 45.5%, significantly higher than 20.7% in the conventional chemotherapy group (P=0.040). Secondly, the incidence rates of adverse reactions including bone marrow suppression, nausea, vomiting, diarrhea, constipation, oral mucositis, fatigue, anorexia in the chrono-chemotherapy group were significantly lower than that in the conventional group (P<0.05 for all). Finally, compared the two groups, the CD4+ /CD8+ ratio was significantly lower in the chronochemotherapy group than that in the conventional chemotherapy group (P<0.05). The lymphocytes CD19+ and CD4+/CD8+ were decreased and CD3+, CD4+, CD8+, CD16++CD56+ were increased in the chronochemotherapy group, while only CD3+ and CD8+ were increased in the conventional chemotherapy group. Compared with the conventional chemotherapy, the chronochemotherapy may be more favorable in the treatment of NPC, with a better therapeutic effects and effectiveness than that of conventional chemotherapy after induction chemotherapy, with less side effects, and can improve the immune function in the patients.

Episodic specificity induction impacts activity in a core brain network during construction of imagined future experiences

PubMed Central

Madore, Kevin P.; Szpunar, Karl K.; Addis, Donna Rose; Schacter, Daniel L.

2016-01-01

Recent behavioral work suggests that an episodic specificity induction—brief training in recollecting the details of a past experience—enhances performance on subsequent tasks that rely on episodic retrieval, including imagining future experiences, solving open-ended problems, and thinking creatively. Despite these far-reaching behavioral effects, nothing is known about the neural processes impacted by an episodic specificity induction. Related neuroimaging work has linked episodic retrieval with a core network of brain regions that supports imagining future experiences. We tested the hypothesis that key structures in this network are influenced by the specificity induction. Participants received the specificity induction or one of two control inductions and then generated future events and semantic object comparisons during fMRI scanning. After receiving the specificity induction compared with the control, participants exhibited significantly more activity in several core network regions during the construction of imagined events over object comparisons, including the left anterior hippocampus, right inferior parietal lobule, right posterior cingulate cortex, and right ventral precuneus. Induction-related differences in the episodic detail of imagined events significantly modulated induction-related differences in the construction of imagined events in the left anterior hippocampus and right inferior parietal lobule. Resting-state functional connectivity analyses with hippocampal and inferior parietal lobule seed regions and the rest of the brain also revealed significantly stronger core network coupling following the specificity induction compared with the control. These findings provide evidence that an episodic specificity induction selectively targets episodic processes that are commonly linked to key core network regions, including the hippocampus. PMID:27601666

Creativity and Memory: Effects of an Episodic-Specificity Induction on Divergent Thinking.

PubMed

Madore, Kevin P; Addis, Donna Rose; Schacter, Daniel L

2015-09-01

People produce more episodic details when imagining future events and solving means-end problems after receiving an episodic-specificity induction-brief training in recollecting details of a recent event-than after receiving a control induction not focused on episodic retrieval. Here we show for the first time that an episodic-specificity induction also enhances divergent creative thinking. In Experiment 1, participants exhibited a selective boost on a divergent-thinking task (generating unusual uses of common objects) after a specificity induction compared with a control induction; by contrast, performance following the two inductions was similar on an object association task thought to involve little divergent thinking. In Experiment 2, we replicated the specificity-induction effect on divergent thinking using a different control induction, and also found that participants performed similarly on a convergent-thinking task following the two inductions. These experiments provide novel evidence that episodic memory is involved in divergent creative thinking. © The Author(s) 2015.

Vedolizumab for Treating Moderately to Severely Active Crohn's Disease After Prior Therapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

PubMed

Rafia, Rachid; Scope, Alison; Harnan, Sue; Stevens, John W; Stevenson, Matt; Lobo, Alan

2016-12-01

As part of its single technology appraisal process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of vedolizumab (Takeda UK) to submit evidence of the clinical effectiveness and cost effectiveness of vedolizumab for the treatment of patients with moderate-to-severe, active Crohn's disease. The School of Health and Related Research (ScHARR) at the University of Sheffield was commissioned as the Evidence Review Group (ERG) and produced a critical review of the evidence of the clinical effectiveness and cost effectiveness of the technology, based upon the company's submission to NICE. The GEMINI II and III trials formed the main supporting evidence for the intervention. Both studies were phase III, randomised, double-blind, placebo-controlled, multicentre trials designed to evaluate the efficacy and safety of vedolizumab. They included patients who were naïve to tumour necrosis factor alpha antagonist (anti-TNF-α) therapy and patients who had an inadequate response to, loss of response to or intolerance of immunomodulators or anti-TNF-α agents. GEMINI II was designed to evaluate the efficacy and safety of vedolizumab as an induction treatment (dosing at weeks 0 and 2, with assessment at week 6) and maintenance treatment (during weeks 6-52). In contrast, GEMINI III was designed to evaluate the efficacy and safety of vedolizumab as an induction treatment only, with doses at weeks 0, 2 and 6, and assessment at weeks 6 and 10. In the absence of any direct head-to-head, randomised, controlled trials comparing vedolizumab with other relevant biologic therapies (adalimumab and infliximab) for the treatment of moderate-to-severe Crohn's disease, the company conducted a network meta-analysis, which compared vedolizumab, adalimumab, infliximab and placebo for the outcomes of clinical response, enhanced clinical response, clinical remission and discontinuation due to adverse events. The company model estimated the incremental cost-effectiveness ratio (ICER) for vedolizumab compared with the standard of care (consisting of 5-aminosalicylic acids, corticosteroids and immunosuppressants) to be £21,620 per quality-adjusted life-year (QALY) gained within the anti-TNF-α-failure population (which included a confidential patient access scheme for vedolizumab). The ICERs were above £30,000 per QALY gained for the mixed intention-to-treat population (including both anti-TNF-α-naïve and anti-TNF-α-failure populations) and in patients who were anti-TNF-α naïve only. The ERG identified a number of limitations that were believed to limit the robustness of the results presented by the company. These limitations could not be addressed by the ERG without major restructuring of the economic model. Therefore, the ERG concluded that the results from the company's model needed to be interpreted with caution and that it was unclear whether the ICERs would increase or decrease following amendment of the identified structural issues.

Application of adaptive design and decision making to a phase II trial of a phosphodiesterase inhibitor for the treatment of intermittent claudication.

PubMed

Lewis, Roger J; Connor, Jason T; Teerlink, John R; Murphy, James R; Cooper, Leslie T; Hiatt, William R; Brass, Eric P

2011-05-25

Claudication secondary to peripheral artery disease (PAD) is associated with substantial functional impairment. Phosphodiesterase (PDE) inhibitors have been shown to increase walking performance in these patients. K-134 is a selective PDE 3 inhibitor being developed as a potential treatment for claudication. The use of K-134, as with other PDE 3 inhibitors, in patients with PAD raises important safety and tolerability concerns, including the induction of cardiac ischemia, tachycardia, and hypotension. We describe the design, oversight, and implementation of an adaptive, phase II, dose-finding trial evaluating K-134 for the treatment of stable, intermittent claudication. The study design was a double-blind, multi-dose (25 mg, 50 mg, and 100 mg of K-134), randomized trial with both placebo and active comparator arms conducted in the United States and Russia. The primary objective of the study was to compare the highest tolerable dose of K-134 versus placebo using peak walking time after 26 weeks of therapy as the primary outcome. Study visits with intensive safety assessments were included early in the study period to provide data for adaptive decision making. The trial used an adaptive, dose-finding strategy to efficiently identify the highest dose(s) most likely to be safe and well tolerated, based on the side effect profiles observed within the trial, so that less promising doses could be abandoned. Protocol specified criteria for safety and tolerability endpoints were used and modeled prior to the adaptive decision making. The maximum target sample size was 85 subjects in each of the retained treatment arms. When 199 subjects had been randomized and 28-day data were available from 143, the Data Monitoring Committee (DMC) recommended termination of the lowest dose (25 mg) treatment arm. Safety evaluations performed during 14- and 28-day visits which included in-clinic dosing and assessments at peak drug concentrations provided core data for the DMC review. At the time of review, no subject in any of the five treatment arms (placebo, three K-134-containing arms, and cilostazol) had met pre-specified definitions for resting tachycardia or ischemic changes on exercise ECG. If, instead of dropping the 25-mg K-134 treatment arm, all arms had been continued to full enrollment, then approximately 43 additional research subjects would have been required to complete the trial. In this phase II, dose-finding trial of K-134 in the treatment of stable intermittent claudication, no concerning safety signals were seen at interim analysis, allowing the discontinuation of the lowest-dose-containing arm and the retention of the two highest-dose-containing arms. The adaptive design facilitated safe and efficient evaluation of K-134 in this high-risk cardiovascular population. ClinicalTrials.gov: NCT00783081.

Development of Specialization Scales for the MSPI: A Comparison of Empirical and Inductive Strategies

ERIC Educational Resources Information Center

Porfeli, Erik J.; Richard, George V.; Savickas, Mark L.

2010-01-01

An empirical measurement model for interest inventory construction uses internal criteria whereas an inductive measurement model uses external criteria. The empirical and inductive measurement models are compared and contrasted and then two models are assessed through tests of the effectiveness and economy of scales for the Medical Specialty…

The effect of farrowing induction on colostrum and piglet serum immunocrits is dependent on parity

USDA-ARS?s Scientific Manuscript database

Farrowing induction is a common practice among swine producers to manage timing of farrowing and the labor associated with farrowing. In this experiment, the effect of induction of labor using cloprostenol on day 114 of gestation (n = 88) was compared to our standard farrowing protocol at USMARC (na...

Systematic approach to optimal design of induction heating installations for aluminum extrusion process

NASA Astrophysics Data System (ADS)

Zimin, L. S.; Sorokin, A. G.; Egiazaryan, A. S.; Filimonova, O. V.

2018-03-01

An induction heating system has a number of inherent benefits compared to traditional heating systems due to a non-contact heating process. It is widely used in vehicle manufacture, cast-rolling, forging, preheating before rolling, heat treatment, galvanizing and so on. Compared to other heating technologies, induction heating has the advantages of high efficiency, fast heating rate and easy control. The paper presents a new systematic approach to the design and operation of induction heating installations (IHI) in aluminum alloys production. The heating temperature in industrial complexes “induction heating - deformation” is not fixed in advance, but is determined in accordance with the maximization or minimization of the total economic performance during the process of metal heating and deformation. It is indicated that the energy efficient technological complex “IHI – Metal Forming (MF)” can be designed only with regard to its power supply system (PSS). So the task of designing systems of induction heating is to provide, together with the power supply system and forming equipment, the minimum energy costs for the metal retreating.

Systematic Review with Network Meta-Analysis: Comparative Efficacy of Biologics in the Treatment of Moderately to Severely Active Ulcerative Colitis.

PubMed

Vickers, Adrian D; Ainsworth, Claire; Mody, Reema; Bergman, Annika; Ling, Caroline S; Medjedovic, Jasmina; Smyth, Michael

2016-01-01

Biological therapies are increasingly used to treat ulcerative colitis (UC). To compare the efficacy of biologics in adults with moderately-to-severely active UC, stratified by prior exposure to anti-tumour necrosis factor (anti-TNF) therapy. A systematic literature review was undertaken to identify studies of biologics approved for UC. Network meta-analysis was conducted for endpoints at induction and maintenance. Seven studies were included in the meta-analysis of induction treatment for anti-TNF therapy-naïve patients. All biologics were more effective than placebo in inducing clinical response, clinical remission, and mucosal healing. Infliximab demonstrated a statistically significant improvement over adalimumab in clinical response (odds ratio [OR] [95% credible interval (CrI)]: 2.19 [1.35-3.55]), clinical remission (OR [95% CrI]: 2.81 [1.49-5.49]), and mucosal healing (OR [95% CrI]: 2.23 [1.21-4.14]); there were no other significant differences between biologics for induction efficacy. Five studies were included in the meta-analysis of maintenance treatment, two studies rerandomised responder patients at end of induction, and three followed the same patients 'straight through'. To account for design differences, the number of responders at end of induction was assumed to be equivalent to the number rerandomised. Vedolizumab showed significantly different durable clinical response from comparators (OR [95% CrI] infliximab 3.18 [1.14-9.20], golimumab 2.33 [1.04-5.41], and adalimumab 3.96 [1.67-9.84]). In anti-TNF therapy-experienced patients, only vedolizumab and adalimumab could be compared. At induction, no significant differences in efficacy were seen. During maintenance, vedolizumab showed significantly improved rates of mucosal healing versus adalimumab (OR [95% CrI]: 6.72 [1.36-41.0]). This study expands the understanding of comparative efficacies of biologic treatments for UC, encompassing outcomes and populations not previously studied. All biologic treatments were effective for UC during induction. Vedolizumab demonstrated possible clinical benefits in the maintenance setting versus all comparators, irrespective of prior anti-TNF exposure and after adjusting for differences in study design.

Improving recruitment to pharmacological trials for illicit opioid use: findings from a qualitative focus group study

PubMed Central

Tompkins, Charlotte N. E.; McDonald, Rebecca; Strang, John

2018-01-01

Abstract Aim To explore potential study participants’ views on willingness to join clinical trials of pharmacological interventions for illicit opioid use to inform and improve future recruitment strategies. Design Qualitative focus group study [six groups: oral methadone (two groups); buprenorphine tablets (two groups); injectable opioid agonist treatment (one group); and former opioid agonist treatment (one group)]. Settings Drug and alcohol services and a peer support recovery service (London, UK). Participants Forty people with experience of opioid agonist treatment for heroin dependence (26 males, 14 females; aged 33–66 years). Measurements Data collection was facilitated by a topic guide that explored willingness to enrol in clinical pharmacological trials. Groups were audio‐recorded and transcribed. Transcribed data were analysed inductively via Iterative Categorization. Findings Participants’ willingness to join pharmacological trials of medications for opioid dependence was affected by factors relating to study burden, study drug, study design, study population and study relationships. Participants worried that the trial drug might be worse than, or interfere with, their current treatment. They also misunderstood aspects of trial design despite the researchers’ explanations. Conclusions Recruitment of participants for clinical trials of pharmacological interventions for illicit opioid use could be improved if researchers became better at explaining clinical trials to potential participants, dispelling misconceptions about trials and increasing trust in the research process and research establishment. A checklist of issues to consider when designing pharmacological trials for illicit opioid use is proposed. PMID:29356208

Comparative evaluation of power factor impovement techniques for squirrel cage induction motors

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

Spee, R.; Wallace, A.K.

1992-04-01

This paper describes the results obtained from a series of tests of relatively simple methods of improving the power factor of squirrel-cage induction motors. The methods, which are evaluated under controlled laboratory conditions for a 10-hp, high-efficiency motor, include terminal voltage reduction; terminal static capacitors; and a floating'' winding with static capacitors. The test results are compared with equivalent circuit model predictions that are then used to identify optimum conditions for each of the power factor improvement techniques compared with the basic induction motor. Finally, the relative economic value, and the implications of component failures, of the three methods aremore » discussed.« less

Post-remission treatment with allogeneic stem cell transplantation in patients aged 60 years and older with acute myeloid leukaemia: a time-dependent analysis.

PubMed

Versluis, Jurjen; Hazenberg, Carin L E; Passweg, Jakob R; van Putten, Wim L J; Maertens, Johan; Biemond, Bart J; Theobald, Matthias; Graux, Carlos; Kuball, Jurgen; Schouten, Harry C; Pabst, Thomas; Löwenberg, Bob; Ossenkoppele, Gert; Vellenga, Edo; Cornelissen, Jan J

2015-10-01

Acute myeloid leukaemia mainly affects elderly people, with a median age at diagnosis of around 70 years. Although about 50-60% of patients enter first complete remission upon intensive induction chemotherapy, relapse remains high and overall outcomes are disappointing. Therefore, effective post-remission therapy is urgently needed. Although often no post-remission therapy is given to elderly patients, it might include chemotherapy or allogeneic haemopoietic stem cell transplantation (HSCT) following reduced-intensity conditioning. We aimed to assess the comparative value of allogeneic HSCT with other approaches, including no post-remission therapy, in patients with acute myeloid leukaemia aged 60 years and older. For this time-dependent analysis, we used the results from four successive prospective HOVON-SAKK acute myeloid leukaemia trials. Between May 3, 2001, and Feb 5, 2010, a total of 1155 patients aged 60 years and older were entered into these trials, of whom 640 obtained a first complete remission after induction chemotherapy and were included in the analysis. Post-remission therapy consisted of allogeneic HSCT following reduced-intensity conditioning (n=97), gemtuzumab ozogamicin (n=110), chemotherapy (n=44), autologous HSCT (n=23), or no further treatment (n=366). Reduced-intensity conditioning regimens consisted of fludarabine combined with 2 Gy of total body irradiation (n=71), fludarabine with busulfan (n=10), or other regimens (n=16). A time-dependent analysis was done, in which allogeneic HSCT was compared with other types of post-remission therapy. The primary endpoint of the study was 5-year overall survival for all treatment groups, analysed by a time-dependent analysis. 5-year overall survival was 35% (95% CI 25-44) for patients who received an allogeneic HSCT, 21% (17-26) for those who received no additional post-remission therapy, and 26% (19-33) for patients who received either additional chemotherapy or autologous HSCT. Overall survival at 5 years was strongly affected by the European LeukemiaNET acute myeloid leukaemia risk score, with patients in the favourable risk group (n=65) having better 5-year overall survival (56% [95% CI 43-67]) than those with intermediate-risk (n=131; 23% [19-27]) or adverse-risk (n=444; 13% [8-20]) acute myeloid leukaemia. Multivariable analysis with allogeneic HSCT as a time-dependent variable showed that allogeneic HSCT was associated with better 5-year overall survival (HR 0·71 [95% CI 0·53-0·95], p=0·017) compared with non-allogeneic HSCT post-remission therapies or no post-remission therapy, especially in patients with intermediate-risk (0·82 [0·58-1·15]) or adverse-risk (0.39 [0·21-0·73]) acute myeloid leukaemia. Collectively, the results from these four trials suggest that allogeneic HSCT might be the preferred treatment approach in patients 60 years of age and older with intermediate-risk and adverse-risk acute myeloid leukaemia in first complete remission, but the comparative value should ideally be shown in a prospective randomised study. None. Copyright © 2015 Elsevier Ltd. All rights reserved.

A PRIM approach to predictive-signature development for patient stratification

PubMed Central

Chen, Gong; Zhong, Hua; Belousov, Anton; Devanarayan, Viswanath

2015-01-01

Patients often respond differently to a treatment because of individual heterogeneity. Failures of clinical trials can be substantially reduced if, prior to an investigational treatment, patients are stratified into responders and nonresponders based on biological or demographic characteristics. These characteristics are captured by a predictive signature. In this paper, we propose a procedure to search for predictive signatures based on the approach of patient rule induction method. Specifically, we discuss selection of a proper objective function for the search, present its algorithm, and describe a resampling scheme that can enhance search performance. Through simulations, we characterize conditions under which the procedure works well. To demonstrate practical uses of the procedure, we apply it to two real-world data sets. We also compare the results with those obtained from a recent regression-based approach, Adaptive Index Models, and discuss their respective advantages. In this study, we focus on oncology applications with survival responses. PMID:25345685

High-dose melphalan and autologous stem cell transplantation for AL amyloidosis: recent trends in treatment-related mortality and 1-year survival at a single institution

PubMed Central

Seldin, D. C.; Andrea, N.; Berenbaum, I.; Berk, J. L.; Connors, L.; Dember, L. M.; Doros, G.; Fennessey, S.; Finn, K.; Girnius, S.; Lerner, A.; Libbey, C.; Meier-Ewert, H. K.; O’Connell, R.; O’Hara, C.; Quillen, K.; Ruberg, F. L.; Sam, F.; Segal, A.; Shelton, A.; Skinner, M.; Sloan, J. M.; Wiesman, J. F.; Sanchorawala, V.

2017-01-01

Treatment with high-dose melphalan chemotherapy supported by hematopoietic rescue with autologous stem cells produces high rates of hematologic responses and improvement in survival and organ function for patients with AL amyloidosis. Ongoing clinical trials explore pre-transplant induction regimens, post-transplant consolidation or maintenance approaches, and compare transplant to non-transplant regimens. To put these studies into context, we reviewed our recent experience with transplant for AL amyloidosis in the Amyloid Treatment and Research Program at Boston Medical Center and Boston University School of Medicine. Over the past 10 years, there was a steady reduction in rates of treatment-related mortality and improvement in 1-year survival, now approximately 5% and 90%, respectively, based upon an intention-to-treat analysis. Median overall survival of patients treated with this approach at our center exceeds 7.5 years. PMID:21838459

The role of ovarian surgery in polycystic ovary syndrome.

PubMed

Farquhar, Cynthia M

2004-10-01

Problems in inducing ovulation in women with polycystic ovary syndrome (PCOS) and anovulation are well recognized. In 1935, Stein and Leventhal first described surgical treatment by ovarian wedge resection at laparotomy for women with anovulation and PCOS. Ovarian wedge resection was eventually abandoned because of the significant risk of postsurgical adhesion formation, which resulted in tubal adhesions, and because of the advent of medical ovulation induction with clomiphene and gonadotrophins. However, since the arrival of minimally invasive surgical techniques, laparoscopic ovarian surgery has become feasible. The potential advantages of laparoscopic ovarian surgery include repeated single ovulations and less adhesion formation. Lowered costs make ovarian surgery an attractive alternative to gonadotrophins. However, although many case series have suggested that ovarian surgery is an effective strategy, few randomized, controlled trials have been undertaken comparing the success rates of surgery with gonadotrophins. The long-term concerns with surgery include adhesion formation and premature ovarian failure.

Induced pluripotent stem cells for the treatment of stroke: the potential and the pitfalls.

PubMed

Yu, Fenggang; Li, Yingying; Morshead, Cindi M

2013-09-01

The extraordinary discovery of induced pluripotent stem cells (iPSCs) has led to the very real possibility that patient-specific cell therapy can be realized. The potential to develop cell replacement therapies outside the ethical and legal limitations, has initiated a new era of hope for regenerative strategies to treat human neurological disease including stroke. In this article, we will review and compare the current approaches to derive iPSCs from different somatic cells, and the induction into neuronal phenotypes, considering the advantages and disadvantages to the methodologies of derivation. We will highlight the work relating to the use of iPSC-based therapies in models of stroke and their potential use in clinical trials. Finally, we will consider future directions and areas of exploration which may promote the realization of iPSC-based cell replacement strategies for the treatment of stroke.

[Clinical views from the forefront of immunosuppressive drugs].

PubMed

Kobayashi, Eiji

2005-11-01

Recently, many immunosuppressants have been developed and some of them have already been introduced in clinical organ transplantation. With a new concept of immunoregulation, which focuses on prevention of rejection and over-immunosuppression, the latest protocol has been conducted. Chimeric or humanized antibodies targeting the lymphocyte surface molecule such as CD19, 20, 25, 40, and 52 are administrated in the induction phase, and calcineurin inhibitors (cyclosporin and tacrolimus) are used as key drugs. For tapering the doses of them, the combined application of anti-metabolic agents of azathioprine, mizoribine, or mycophenolate mofetil (MMF) has been proved effective. Lymphocyte forming drugs induce unique immunoregulation, targeting at sphingosine 1-phosphate (SlP) receptors. FTY720 is now in the procedure of clinical trial to compare with MMF. KRP203 is also a candidate for more specific SIP receptor agonist. In this issue, I reviewed the recent immunosuppressive strategy and focused on the advance of novel immunosuppressive drugs.

Treatment of Opioid Dependent Pregnant Women: Clinical and Research Issues

PubMed Central

Jones, H.E.; Martin, P.R.; Heil, S.H.; Stine, S.M.; Kaltenbach, K.; Selby, P.; Coyle, M.G.; O’Grady, K.E.; Arria, A.M.; Fischer, G.

2008-01-01

This paper addresses common questions that clinicians face when treating pregnant women with opioid dependence. Guidance is provided to aid clinical decision-making, based on both research evidence and the collective clinical experience of the authors which include investigators in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) project. MOTHER is a double-blind, double-dummy, flexible–dosing, parallel-group clinical trial examining the comparative safety and efficacy of methadone and buprenorphine for the opioid dependence treatment among pregnant women and their neonates. The paper begins with a discussion of appropriate assessment during pregnancy, and then addresses clinical management stages, including maintenance medication selection, induction and stabilization, opioid agonist medication management before, during and after delivery, pain management, breast-feeding, and transfer to aftercare. Lastly, other important clinical issues including managing co-occurring psychiatric disorders and medication interactions are discussed. PMID:18248941

Comparison of pregnancy rates between patients with and without local endometrial scratching before intrauterine insemination.

PubMed

Senocak, G C; Yapca, O E; Borekci, B

2017-11-01

To determine the implantation success of local endometrial injury in patients undergoing intrauterine insemination following ovulation induction with gonadotropins as an infertility treatment. In this prospective randomized controlled trial, ovulation induction was performed with gonadotropins in 80 patients following intrauterine insemination. In 40 patients, local endometrial injury (scratch) was performed in the midluteal phase of the cycle preceding ovarian stimulation with a Novak curette to the posterior side of the endometrial cavity. Fifteen pregnancies (37.5%) and 11 clinical pregnancies (27.5%) occurred in the intervention group, whereas eight pregnancies (20%) and five clinical pregnancies (12.5%) occurred in the control group. Although the pregnancy rates and clinical pregnancy rates were increased in the intervention group, no statistically significant difference was found between the intervention and control groups (pregnancy rates: P=0.084; clinical pregnancy rates: P=0.094). Performing local endometrial injury (scratch) in the cycle preceding ovulation induction in patients with a diagnosis of infertility and indication for intrauterine insemination increased the pregnancy and clinical pregnancy rates. This increase was not, however, statistically significant. More randomized, controlled, prospective studies with larger patient numbers are required before the use of iatrogenic induction of local endometrial injury can be recommended in routine clinical practice. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Adalimumab for Moderately to Severely Active Ulcerative Colitis: A Systematic Review and Meta-Analysis.

PubMed

Chen, Xinlin; Hou, Jiangtao; Yuan, Yujie; Huang, Chaoyuan; Liu, Tianwen; Mo, Chuanwei; Li, Haiwen; Chen, Bin; Xu, Qian; Hou, Zhengkun; He, Weiling; Liu, Fengbin

2016-06-01

Evidence-based studies are increasingly being focused on evaluating the efficacy and safety of adalimumab (ADA) for moderately to severely active ulcerative colitis (UC). However, the dosage pattern of ADA for UC management is still not clear. A meta-analysis was conducted to evaluate the efficacy and safety of different ADA dosage regimens for moderately to severely active UC. The Medline, EMBASE, ISI Web of Knowledge, and Cochrane databases were searched from their inception to January 2015. Randomized controlled trials (RCTs) comparing ADA with placebo were eligible for initial inclusion. The efficacy and side effects were evaluated for ADA 160/80 (ADA 160/80 mg at weeks 0/2 and then 40 mg at weeks 4 and 6), and ADA 80/40 (ADA 80/40 mg at weeks 0/2 and then 40 mg at weeks 4 and 6) induction therapy, with ADA 40 mg every other week (EOW) for maintenance therapy of 52 weeks. The pooled risk ratio (RR) and its 95 % confidence interval (CI) were calculated. Three RCTs were included. All of the studies were considered to have a low risk of bias. ADA 160/80 was more effective than placebo for induction of clinical remission (RR 1.62, 95 % CI 1.15-2.29), clinical response (RR 1.37, 95 % CI 1.19-1.59), mucosal healing (RR 1.27, 95 % CI 1.08-1.50), and inflammatory bowel disease questionnaire (IBDQ) response (RR 1.22, 95 % CI 1.05-1.43) and did not increase adverse events (RR 1.10, 95 % CI 0.95-1.27). Compared with placebo, ADA 80/40 did not show significant differences for induction of clinical remission and clinical response and did not increase adverse events. ADA 40 mg EOW was superior to placebo in maintaining clinical remission (RR 2.38, 95 % CI 1.57-3.59), clinical response (RR 1.69, 95 % CI 1.29-2.21), mucosal healing (RR 1.69, 95 % CI 1.26-2.28), and IBDQ response (RR 1.73, 95 % CI 1.28-2.34). Compared with placebo, ADA 40 mg EOW increased adverse events (RR 1.28, 95 % CI 1.06-1.54). ADA 160/80 was a safe and effective treatment for induction management of moderately to severely active UC, but the benefits of ADA 80/40 application were limited. ADA 40 mg EOW was effective for maintenance management of UC. Additional well designed RCTs are needed to confirm these results.

Induced resistance to infection of lobsters Homarus americanus by Aerococcus viridans (var.) homari, the bacterium causing gaffkemia.

PubMed

Stewart, James E; Arie, B; Marks, L J

2004-12-13

A vaccine composed of steam sterilized (autoclaved) cells of a virulent strain of Aerococcus viridans (var.) homari was effective in protecting lobsters Homarus americanus against gaffkemia. At 15 degrees C the heat-killed vaccines (HKV) at concentrations between 1 and 5 x 10(7) particles kg(-1) lobster body wt induced maximal protection in induction periods ranging from 7 to 11 d. Protection was substantial over the course of a 30 d post-induction trial period. Spring-caught lobsters (i.e. those more fully rehabilitated following ecdysis) gained more protection (LD50 = 1.9 x 10(4)) from the vaccination than did those caught in the late fall-early winter period (lobsters that were not yet fully recovered from ecdysis) (LD50 = 3.2 x 10(3)). The protection offered by the HK vaccine was comparable to that induced by a vaccine produced by incubating the pathogen with low concentrations (2 pg ml(-1)) of the antibiotic vancomycin. The bacterins produced by both methods exhibited similar new properties: (1) agglutination at low titres by lobster hemolymph serum, suggesting an impaired capsule layer, and (2) increased permeability to the large Alcian Blue molecule. With both vaccines, the protection may be a direct result of increased exposure to intact bacterial cell structures by the lobster defences, an exposure which otherwise would be prevented by an intact capsule.

Pancreas Transplantation: Lessons Learned From a Decade of Experience at Wake Forest Baptist Medical Center

PubMed Central

Rogers, Jeffrey; Farney, Alan C.; Al-Geizawi, Samer; Iskandar, Samy S.; Doares, William; Gautreaux, Michael D.; Hart, Lois; Kaczmorski, Scott; Reeves-Daniel, Amber; Winfrey, Stephanie; Ghanta, Mythili; Adams, Patricia L.; Stratta, Robert J.

2011-01-01

This article reviews the outcome of pancreas transplantations in diabetic recipients according to risk factors, surgical techniques, and immunosuppression management that evolved over the course of a decade at Wake Forest Baptist Medical Center. A randomized trial of alemtuzumab versus rabbit anti-thymocyte globulin (rATG) induction in simultaneous kidney-pancreas transplantation (SKPT) at our institution demonstrated lower rates of acute rejection and infection in the alemtuzumab group. Consequently, alemtuzumab induction has been used exclusively in all pancreas transplantations since February 2009. Early steroid elimination has been feasible in the majority of patients. Extensive experience with surveillance pancreas biopsies in solitary pancreas transplantation (SPT) is described. Surveillance pancreas biopsy-directed immunosuppression has contributed to equivalent long-term pancreas graft survival rates in SKPT and SPT recipients at our center, in contrast to recent registry reports of persistently higher rates of immunologic pancreas graft loss in SPT. Furthermore, the impact of donor and recipient selection on outcomes is explored. Excellent results have been achieved with older (extended) donors and recipients, in recipients of organs from donation after cardiac death donors managed with extracorporeal support, and in African-American patients. Type 2 diabetics with detectable C-peptide levels have been transplanted successfully with outcomes comparable to those of insulinopenic diabetics. Our experiences are discussed in the light of findings reported in the literature. PMID:21720669

Pancreas transplantation: lessons learned from a decade of experience at Wake Forest Baptist Medical Center.

PubMed

Rogers, Jeffrey; Farney, Alan C; Al-Geizawi, Samer; Iskandar, Samy S; Doares, William; Gautreaux, Michael D; Hart, Lois; Kaczmorski, Scott; Reeves-Daniel, Amber; Winfrey, Stephanie; Ghanta, Mythili; Adams, Patricia L; Stratta, Robert J

2011-01-01

This article reviews the outcome of pancreas transplantations in diabetic recipients according to risk factors, surgical techniques, and immunosuppression management that evolved over the course of a decade at Wake Forest Baptist Medical Center. A randomized trial of alemtuzumab versus rabbit anti-thymocyte globulin (rATG) induction in simultaneous kidney-pancreas transplantation (SKPT) at our institution demonstrated lower rates of acute rejection and infection in the alemtuzumab group. Consequently, alemtuzumab induction has been used exclusively in all pancreas transplantations since February 2009. Early steroid elimination has been feasible in the majority of patients. Extensive experience with surveillance pancreas biopsies in solitary pancreas transplantation (SPT) is described. Surveillance pancreas biopsy-directed immunosuppression has contributed to equivalent long-term pancreas graft survival rates in SKPT and SPT recipients at our center, in contrast to recent registry reports of persistently higher rates of immunologic pancreas graft loss in SPT. Furthermore, the impact of donor and recipient selection on outcomes is explored. Excellent results have been achieved with older (extended) donors and recipients, in recipients of organs from donation after cardiac death donors managed with extracorporeal support, and in African-American patients. Type 2 diabetics with detectable C-peptide levels have been transplanted successfully with outcomes comparable to those of insulinopenic diabetics. Our experiences are discussed in the light of findings reported in the literature.