Impact of navigation on knowledge and attitudes about clinical trials among Chinese patients undergoing treatment for breast and gynecologic cancers.

PubMed

Clair McClung, E; Davis, Sharon Watkins; Jeffrey, Stefanie S; Kuo, Mei-Chin; Lee, Marion M; Teng, Nelson N H

2015-06-01

Racial, ethnic and economic disparities in cancer rates, outcomes, and clinical trials participation persist despite significant research. We examined barriers to clinical trials enrollment among Chinese patients, and developed a navigation program for Chinese gynecologic and breast cancer patients. Six bilingual navigators were trained and a navigator assigned to each patient for at least 2 months. All patients received a clinical trials booklet in Chinese and English. Data collection included pre-and post-navigation surveys, intake forms, and documentation of navigation encounters. Between July 2010 and May 31, 2011, we recruited 28 breast and gynecologic cancer patients. Patients averaged 317 min of navigation (range 63-1,852) during 8 sessions (range 3-28). They improved in 4 of 10 true-false knowledge statements about clinical trials. A patient navigation program for Chinese-speaking cancer patients is feasible. It results in high patient satisfaction rates and modest improvements in clinical trials knowledge and participation.

Rationale and design of a randomised clinical trial comparing vascular closure device and manual compression to achieve haemostasis after diagnostic coronary angiography: the Instrumental Sealing of ARterial puncture site - CLOSURE device versus manual compression (ISAR-CLOSURE) trial.

PubMed

Xhepa, Erion; Byrne, Robert A; Schulz, Stefanie; Helde, Sandra; Gewalt, Senta; Cassese, Salvatore; Linhardt, Maryam; Ibrahim, Tareq; Mehilli, Julinda; Hoppe, Katharina; Grupp, Katharina; Kufner, Sebastian; Böttiger, Corinna; Hoppmann, Petra; Burgdorf, Christof; Fusaro, Massimiliano; Ott, Ilka; Schneider, Simon; Hengstenberg, Christian; Schunkert, Heribert; Laugwitz, Karl-Ludwig; Kastrati, Adnan

2014-06-01

Vascular closure devices (VCD) have been introduced into clinical practice with the aim of increasing the procedural efficiency and clinical safety of coronary angiography. However, clinical studies comparing VCD and manual compression have yielded mixed results, and large randomised clinical trials comparing the two strategies are missing. Moreover, comparative efficacy studies between different VCD in routine clinical use are lacking. The Instrumental Sealing of ARterial puncture site - CLOSURE device versus manual compression (ISAR-CLOSURE) trial is a prospective, randomised clinical trial designed to compare the outcomes associated with the use of VCD or manual compression to achieve femoral haemostasis. The test hypothesis is that femoral haemostasis after coronary angiography achieved using VCD is not inferior to manual compression in terms of access-site-related vascular complications. Patients undergoing coronary angiography via the common femoral artery will be randomised in a 1:1:1 fashion to receive FemoSeal VCD, EXOSEAL VCD or manual compression. The primary endpoint is the incidence of the composite of arterial access-related complications (haematoma ≥5 cm, pseudoaneurysm, arteriovenous fistula, access-site-related bleeding, acute ipsilateral leg ischaemia, the need for vascular surgical/interventional treatment or documented local infection) at 30 days after randomisation. According to power calculations based on non-inferiority hypothesis testing, enrolment of 4,500 patients is planned. The trial is registered at www.clinicaltrials.gov (study identifier: NCT01389375). The safety of VCD as compared to manual compression in patients undergoing transfemoral coronary angiography remains an issue of clinical equipoise. The aim of the ISAR-CLOSURE trial is to assess whether femoral haemostasis achieved through the use of VCD is non-inferior to manual compression in terms of access-site-related vascular complications.

Antibiotic prophylaxis for surgical site infection in people undergoing liver transplantation.

PubMed

Almeida, Ricardo A M B; Hasimoto, Claudia N; Kim, Anna; Hasimoto, Erica N; El Dib, Regina

2015-12-05

Surgical site infection is more frequent in liver transplantation than in other types of solid organ transplantation with different antibiotics. Studies have shown that the rate of surgical site infection varies from 8.8% to 37.5% after liver transplantation. Therefore, antimicrobial prophylaxis is likely an essential tool for reducing these infections. However, the literature lacks evidence indicating the best prophylactic antibiotic regimen that can be used for liver transplantation. To assess the benefits and harms of antibiotic prophylactic regimens for surgical site infection in people undergoing liver transplantation. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded and Latin American Caribbean Health Sciences Literature (LILACS). The most recent search was performed on 11 September 2015. All eligible randomised clinical trials comparing any antibiotic regimen versus placebo, versus no intervention or versus another antibiotic regimen for surgical site infection in liver transplant recipients, regardless of age, sex and reason for transplantation. Quasi-randomised studies and other observational studies were considered for data on harm if retrieved with search results for randomised clinical trials. Two review authors selected relevant trials, assessed risk of bias of studies and extracted data. The electronic search identified 786 publications after removal of duplicates. From this search, only one seemingly randomised clinical trial, published in abstract form, fulfilled the inclusion criteria of this review. This trial was conducted at Shiraz Transplant Centre, Shiraz, Iran, where investigators randomly assigned a total of 180 consecutive liver transplant recipients. We judged the overall risk of bias of the trial published in abstract form as high. Researchers reported no numerical data but mentioned that 163 participants met the inclusion criteria after randomisation, and hence were included in the analyses. Most probably, the 17 excluded participants were high-risk liver transplant recipients. Trial authors concluded that they could find no differences between the two antibiotic regimens - ceftriaxone plus metronidazole versus ampicillin-sulbactam plus ceftizoxime - when given to liver transplant recipients. Review authors could not reconfirm the analyses because, as it has been mentioned, trial authors provided no trial data for analyses. Benefits and harms of antibiotic prophylactic regimens for surgical site infection in liver transplantation remain unclear. Additional well-conducted randomised clinical trials adhering to SPIRIT (Spirit Protocol Items: Recommendations for Interventional Trials) and CONSORT (Consolidated Standards of Reporting Trials) guidelines are needed to determine the exact role of antibiotic prophylactic regimens in patients undergoing liver transplantation.

Interleukin-5 Inhibitors for Severe Asthma: Rationale and Future Outlook.

PubMed

Shrimanker, Rahul; Pavord, Ian D

2017-04-01

In this review, we outline the pathophysiology of severe asthma and discuss the role of anti-interleukin (IL)-5 inhibitors for the treatment of asthma. Anti-IL-5 treatments have shown efficacy in reducing the rate of severe asthma attacks in eosinophilic asthma. We review the history of the development of these agents, lessons learnt about severe asthma along the way and key clinical trials supporting efficacy of the three anti-IL-5 treatments that are clinically available or undergoing clinical trials in asthma.

Nanoparticle-Delivered Chemotherapy: Old Drugs in New Packages.

PubMed

Lee, Michael S; Dees, E Claire; Wang, Andrew Z

2017-03-15

Cytotoxic chemotherapies have a narrow therapeutic window, with high peaks and troughs of plasma concentration. Novel nanoparticle formulations of cytotoxic chemotherapy drugs can enhance pharmacokinetic characteristics and facilitate passive targeting of drugs to tumors via the enhanced permeability and retention effect, thus mitigating toxicity. Nanoparticle vehicles currently in clinical use or undergoing clinical investigation for anticancer therapies include liposomes, polymeric micelles, protein-drug nanoparticles, and dendrimers. Multiple nanoparticle formulations of existing cytotoxic chemotherapies are approved for use in several indications, with clinical data indeed showing optimization of pharmacokinetics and different toxicity profiles compared with their parent drugs. There are also many new nanoparticle drug formulations in development and undergoing early- and late-phase clinical trials, including several that utilize active targeting or triggered release based on environmental stimuli. Here, we review the rationale for nanoparticle formulations of existing or previously investigated cytotoxic drugs, describe currently approved nanoparticle formulations of drugs, and discuss some of the most promising clinical trials currently underway.

Rationale and design of the multicenter randomized trial investigating the effects of levosimendan pretreatment in patients with low ejection fraction (≤40 %) undergoing CABG with cardiopulmonary bypass (LICORN study).

PubMed

Caruba, Thibaut; Hourton, Delphine; Sabatier, Brigitte; Rousseau, Dominique; Tibi, Annick; Hoffart-Jourdain, Cécile; Souag, Akim; Freitas, Nelly; Yjjou, Mounia; Almeida, Carla; Gomes, Nathalie; Aucouturier, Pascaline; Djadi-Prat, Juliette; Menasché, Philippe; Chatellier, Gilles; Cholley, Bernard

2016-08-05

Patients with a left ventricular ejection fraction (LVEF) of less than 40 % are at high risk of developing postoperative low cardiac output syndrome (LCOS). Despite actual treatments (inotropic agents and/or mechanical assist devices), the mortality rate of such patients remains very high (13 to 24 %). The LICORN trial aims at assessing the efficacy of a preoperative infusion of levosimendan in reducing postoperative LCOS in patients with poor LVEF undergoing coronary artery bypass grafting (CABG). LICORN study is a multicenter, randomized double-blind, placebo-controlled trial in parallel groups. 340 patients with LVEF ≤40 %, undergoing CABG will be recruited from 13 French hospitals. The study drug will be started after anaesthesia induction and infused over 24 h (0.1 μg/kg/min). The primary outcome (postoperative LCOS) is evaluated using a composite criterion composed of: 1) need for inotropic agents beyond 24 h following discontinuation of the study drug; 2) need for post-operative mechanical assist devices or failure to wean from these techniques when inserted pre-operatively; 3) need for renal replacement therapy. Secondary outcomes include: 1) mortality at Day 28 and Day 180; 2) each item of the composite criterion of the primary outcome; 3) the number of "ventilator-free" days and "out of intensive care unit" days at Day 28. The usefulness of levosimendan in the perioperative period has not yet been documented with a high level of evidence. The LICORN study is the first randomized controlled trial evaluating the clinical value of preoperative levosimendan in high risk cardiac surgical patients undergoing CABG. NCT02184819 (ClinicalTrials.gov).

Screening for colorectal cancer with FOBT, virtual colonoscopy and optical colonoscopy: study protocol for a randomized controlled trial in the Florence district (SAVE study)

PubMed Central

2013-01-01

Background Colorectal cancer (CRC) is the most frequent cancer in Europe. Randomized clinical trials demonstrated that screening with fecal occult blood test (FOBT) reduces mortality from CRC. Accordingly, the European Community currently recommends population-based screening with FOBT. Other screening tests, such as computed tomography colonography (CTC) and optical colonoscopy (OC), are highly accurate for examining the entire colon for adenomas and CRC. Acceptability represents a critical determinant of the impact of a screening program. We designed a randomized controlled trial to compare participation rate and diagnostic yield of FOBT, CTC with computer-aided diagnosis, and OC as primary tests for population-based screening. Methods/Design A total of 14,000 subjects aged 55 to 64 years, living in the Florence district and never screened for CRC, will be randomized in three arms: group 1 (5,000 persons) invited to undergo CTC (divided into: subgroup 1A with reduced cathartic preparation and subgroup 1B with standard bowel preparation); group 2 (8,000 persons) invited to undergo a biannual FOBT for three rounds; and group 3 (1,000 persons) invited to undergo OC. Subjects of each group will be invited by mail to undergo the selected test. All subjects with a positive FOBT or CTC test (that is, mass or at least one polyp ≥6 mm) will be invited to undergo a second-level OC. Primary objectives of the study are to compare the participation rate to FOBT, CTC and OC; to compare the detection rate for cancer or advanced adenomas of CTC versus three rounds of biannual FOBT; to evaluate referral rate for OC induced by primary CTC versus three rounds of FOBT; and to estimate costs of the three screening strategies. A secondary objective of the study is to create a biological bank of blood and stool specimens from subjects undergoing CTC and OC. Discussion This study will provide information about participation/acceptability, diagnostic yield and costs of screening with CTC in comparison with the recommended test (FOBT) and OC. Trial registration ClinicalTrials.gov Identifier: NCT01651624. PMID:23497601

Clinically node negative breast cancer patients undergoing breast conserving therapy, sentinel lymph node procedure versus follow-up: a Dutch randomized controlled multicentre trial (BOOG 2013-08).

PubMed

van Roozendaal, L M; Vane, M L G; van Dalen, T; van der Hage, J A; Strobbe, L J A; Boersma, L J; Linn, S C; Lobbes, M B I; Poortmans, P M P; Tjan-Heijnen, V C G; Van de Vijver, K K B T; de Vries, J; Westenberg, A H; Kessels, A G H; de Wilt, J H W; Smidt, M L

2017-07-01

Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the outcome of the sentinel lymph node biopsy has no clinical consequence, the value of the procedure itself is being questioned. The aim of the BOOG 2013-08 trial is to investigate whether the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients treated with breast conserving therapy. The BOOG 2013-08 is a Dutch prospective non-inferiority randomized multicentre trial. Women with pathologically confirmed clinically node negative T1-2 invasive breast cancer undergoing breast conserving therapy will be randomized for sentinel lymph node biopsy versus no sentinel lymph node biopsy. Endpoints include regional recurrence after 5 (primary endpoint) and 10 years of follow-up, distant-disease free and overall survival, quality of life, morbidity and cost-effectiveness. Previous data indicate a 5-year regional recurrence free survival rate of 99% for the control arm and 96% for the study arm. In combination with a non-inferiority limit of 5% and probability of 0.8, this result in a sample size of 1.644 patients including a lost to follow-up rate of 10%. Primary and secondary endpoints will be reported after 5 and 10 years of follow-up. If the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients undergoing breast conserving therapy, this study will cost-effectively lead to a decreased axillary morbidity rate and thereby improved quality of life with non-inferior regional control, distant-disease free survival and overall survival. The BOOG 2013-08 study is registered in ClinicalTrials.gov since October 20, 2014, Identifier: NCT02271828. https://clinicaltrials.gov/ct2/show/NCT02271828.

Protection of xenon against postoperative oxygen impairment in adults undergoing Stanford Type-A acute aortic dissection surgery: Study protocol for a prospective, randomized controlled clinical trial.

PubMed

Jin, Mu; Cheng, Yi; Yang, Yanwei; Pan, Xudong; Lu, Jiakai; Cheng, Weiping

2017-08-01

The available evidence shows that hypoxemia after Stanford Type-A acute aortic dissection (AAD) surgery is a frequent cause of several adverse consequences. The pathogenesis of postoperative hypoxemia after AAD surgery is complex, and ischemia/reperfusion and inflammation are likely to be underlying risk factors. Xenon, recognized as an ideal anesthetic and anti-inflammatory treatment, might be a possible treatment for these adverse effects. The trial is a prospective, double-blind, 4-group, parallel, randomized controlled, a signal-center clinical trial. We will recruit 160 adult patients undergoing Stanford type-A AAD surgery. Patients will be allocated a study number and will be randomized on a 1:1:1:1 basis to receive 1 of the 3 treatment options (pulmonary inflated with 50% xenon, 75% xenon, or 100% xenon) or no treatment (control group, pulmonary inflated with 50% nitrogen). The aims of this study are to clarify the lung protection capability of xenon and its possible mechanisms in patients undergoing the Stanford type-A AAD surgery. This trial uses an innovative design to account for the xenon effects of postoperative oxygen impairment, and it also delineates the mechanism for any benefit from xenon. The investigational xenon group is considered a treatment intervention, as it includes 3 groups of pulmonary static inflation with 50%, 75%, and 100% xenon. It is suggested that future trials might define an appropriate concentration of xenon for the best practice intervention.

Protocol for a single-centre, randomised controlled study of a preoperative rehabilitation bundle in the frail and elderly undergoing abdominal surgery

PubMed Central

Lien, Victoria Peixin; Ong, Hwee Kuan; Er, Pei Ling; Hao, Ying; Khan, Shariq Ali; Liu, Christopher Weiyang

2017-01-01

Introduction Frail patients have decreased physiological reserves and consequently, they are unable to recover as quickly from surgery. Frailty, as an entity, is a risk factor of increased morbidity and mortality. It is also associated with a longer time to discharge. This trial is undertaken to determine if a novel prehabilitation protocol (10-day bundle of interventions—physiotherapy, nutritional supplementation and cognitive training) can reduce the postoperative length of stay of frail patients who are undergoing elective abdominal surgery, compared with standard care. Methods and analysis This is a prospective, single-centre, randomised controlled trial with two parallel arms. 62 patients who are frail and undergoing elective abdominal surgery will be recruited and randomised to receive either a novel prehabilitation protocol or standard care. Participants will receive telephone reminders preoperatively to encourage protocol compliance. Data will be collected for up to 30 days postoperatively. The primary outcome of the trial will be the postoperative length of stay and the secondary outcomes are the postoperative complications and functional recovery during the hospital admission. Ethics and dissemination This study has been approved by the Singapore General Hospital Institutional Review Board (CIRB Ref: 2016/2584). The study is also listed on ClinicalTrials.gov (Trial number: NCT02921932). All participants will sign an informed consent form before randomisation and translators will be made available to non-English speaking patients. The results of this study will be published in peer-reviewed journals as well as national and international conferences. The data collected will also be made available in a public data repository. Trial registration number NCT02921932 (ClinicalTrials.gov) PMID:28778994

Effects of testosterone supplementation on clinical and rehabilitative outcomes in older men undergoing on-pump CABG.

PubMed

Maggio, Marcello; Nicolini, Francesco; Cattabiani, Chiara; Beghi, Cesare; Gherli, Tiziano; Schwartz, Robert S; Valenti, Giorgio; Ceda, Gian Paolo

2012-07-01

Testosterone levels decrease with age. This decline is steeper during "critical illnesses". Cardiac surgery is a particular representative model of major clinical condition producing stress responses similar to those observed during severe nonsurgical illness. Cardiac revascularization with extracorporeal circulation is characterized by marked postoperative complications such as insulin resistance, a pro-inflammatory state, acute anemia and renal dysfunction. These phenomena are more evident in older subjects, who are particularly vulnerable in the post-operative state, a condition that has been recently termed as "acute postoperative frailty". We recently showed that in older men with low ejection fraction undergoing cardiac revascularization with extracorporeal circulation, there is a profound decline in anabolic hormones, including testosterone. After surgery testosterone concentration frequently declines to less than 200 ng/dl, a situation suggestive of overt hypogonadism. Since men with low testosterone levels have a high probability of developing mobility limitations, we considered this a rationale for the perioperative use of testosterone treatment in older men undergoing cardiac revasularization surgery. We hypothesized that testosterone supplementation at this time might attenuate the impressive post-surgical catabolic hormonal milieu. The aim of this manuscript is to elucidate an ongoing randomized clinical trial in older men (70+ years old) undergoing elective cardiovascular revascularization with extracorporeal circulation. This randomized clinical trial will evaluate the effects of intramuscular testosterone administration on clinical and functional outcomes in this population. The study will also address potential mechanisms underlying the expected beneficial effects of testosterone supplementation including improvement of insulin sensitivity, markers of inflammatory status and improved hemoglobin levels. Copyright © 2012 Elsevier Inc. All rights reserved.

Participation in clinical research: perspectives of adult patients and parents of pediatric patients undergoing hematopoietic stem cell transplantation.

PubMed

Keusch, Florian; Rao, Rohini; Chang, Lawrence; Lepkowski, James; Reddy, Pavan; Choi, Sung Won

2014-10-01

Despite major improvements over the past several decades, many patients undergoing hematopoietic stem cell transplantations (HSCT) continue to suffer from significant treatment-related morbidity and mortality. Clinical research studies (trials) have been integral to advancing the standard of care in HSCT. However, 1 of the biggest challenges with clinical trials is the low participation rate. Although barriers to participation in cancer clinical trials have been previously explored, studies specific to HSCT are lacking. The current study was undertaken to examine the knowledge, attitudes, and perceptions of HSCT patients regarding clinical trials. As members of focus groups, participants responded to open-ended questions that assessed factors influencing decision-making about HSCT clinical trials. Suggestions for improvements in the recruitment process were also solicited among participants. Seventeen adult HSCT patients and 6 parents of pediatric HSCT patients participated in the study. The median age was 56 years (range, 18 to 70) and 44 years (range, 28 to 54) for adult patients and parents, respectively. Participants universally indicated that too much information was provided within the informed consents and they were intimidated by the medical and legal language. Despite the large amount of information provided to them at the time of study enrollment, the participants had limited knowledge retention and recall of study details. Nevertheless, participants reported overall positive experiences with clinical trial participation and many would readily choose to participate again. A common concern among participants was the uncertainty of study outcome and general lack of feedback about results at the end of the study. Participants suggested that investigators provide more condensed and easier to understand informed consents and follow-up of study findings. These findings could be used to help guide the development of improved consent documents and enhanced participation in research studies, thereby affecting the future design of HSCT research protocols. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Persistent Atrial Fibrillation Ablation in Females: Insight from the MAGIC-AF Trial.

PubMed

Singh, Sheldon M; D'Avila, Andre; Aryana, Arash; Kim, Young-Hoon; Mangrum, J Michael; Michaud, Gregory F; Dukkipati, Srinivas R; Heist, E Kevin; Barrett, Conor D; Thorpe, Kevin E; Reddy, Vivek Y

2016-07-27

Atrial fibrillation (AF) ablation is less frequently performed in women when compared to men. There are conflicting data on the safety and efficacy of AF ablation in women. The objective of this study was to compare the clinical characteristics and outcomes in a contemporary cohort of men and women undergoing persistent AF ablation procedures. A total of 182 men and 53 women undergoing a first-ever persistent AF catheter ablation procedure in The Modified Ablation Guided by Ibutilide Use in Chronic Atrial Fibrillation (MAGIC-AF) trial were evaluated. Clinical and procedural characteristics were compared between each gender. The primary efficacy endpoint was the 1-year single procedure freedom from atrial arrhythmia off anti-arrhythmic drugs. Women undergoing catheter ablation procedures were older than men (P < 0.001). The duration of AF and associated co-morbidities were similar between both genders. Single procedure drug-free atrial arrhythmia recurrence occurred in 53% of the cohort with no difference based on gender (men = 54%, women = 53%; P = 1.0). Procedural (P = 0.04), fluoroscopic (P = 0.02), and ablation times (P = 0.003) were shorter in women compared to men. Periprocedural complications and postablation improvement in quality of life were similar between men and women. Women undergoing a first-ever persistent AF ablation procedure were older but had similar clinical outcomes and complications when compared with men. © 2016 Wiley Periodicals, Inc.

Preclinical Evidence for the Efficacy of Ischemic Postconditioning against Renal Ischemia-Reperfusion Injury, a Systematic Review and Meta-Analysis

PubMed Central

Jonker, Simone J.; Menting, Theo P.; Warlé, Michiel C.; Ritskes-Hoitinga, Merel; Wever, Kimberley E.

2016-01-01

Background Renal ischemia-reperfusion injury (IRI) is a major cause of kidney damage after e.g. renal surgery and transplantation. Ischemic postconditioning (IPoC) is a promising treatment strategy for renal IRI, but early clinical trials have not yet replicated the promising results found in animal studies. Method We present a systematic review, quality assessment and meta-analysis of the preclinical evidence for renal IPoC, and identify factors which modify its efficacy. Results We identified 39 publications studying >250 control animals undergoing renal IRI only and >290 animals undergoing renal IRI and IPoC. Healthy, male rats undergoing warm ischemia were used in the vast majority of studies. Four studies applied remote IPoC, all others used local IPoC. Meta-analysis showed that both local and remote IPoC ameliorated renal damage after IRI for the outcome measures serum creatinine, blood urea nitrogen and renal histology. Subgroup analysis indicated that IPoC efficacy increased with the duration of index ischemia. Measures to reduce bias were insufficiently reported. Conclusion High efficacy of IPoC is observed in animal models, but factors pertaining to the internal and external validity of these studies may hamper the translation of IPoC to the clinical setting. The external validity of future animal studies should be increased by including females, comorbid animals, and transplantation models, in order to better inform clinical trial design. The severity of renal damage should be taken into account in the design and analysis of future clinical trials. PMID:26963819

Intravenous iron isomaltoside 1000 (Monofer®) reduces postoperative anaemia in preoperatively non-anaemic patients undergoing elective or subacute coronary artery bypass graft, valve replacement or a combination thereof: a randomized double-blind placebo-controlled clinical trial (the PROTECT trial).

PubMed

Johansson, P I; Rasmussen, A S; Thomsen, L L

2015-10-01

This trial explores whether intravenous iron isomaltoside 1000 (Monofer®) results in a better regeneration of haemoglobin levels and prevents anaemia compared to placebo in preoperative non-anaemic patients undergoing cardiac surgery. The trial is a prospective, double-blind, comparative, placebo-controlled trial of 60 non-anaemic patients undergoing cardiac surgery. The patients were randomized 1:1 to either 1000 mg intravenous iron isomaltoside 1000 administered perioperatively by infusion or placebo. Mean preoperative haemoglobin in the active treatment group was 14·3 g/dl vs. 14·0 g/dl in the placebo group. At discharge 5 days after surgery, haemoglobin levels were reduced to 10·7 and 10·5 g/dl, respectively. One month after surgery, haemoglobin concentration had increased to an average of 12·6 g/dl vs. 11·8 g/dl (p = 0·012) and significantly more patients were non-anaemic in the intravenous iron isomaltoside 1000-treated group compared to the placebo group (38·5% vs. 8·0%; p = 0·019). There were no differences in side-effects between the groups. A single perioperative 1000 mg dose of intravenous iron isomaltoside 1000 significantly increased the haemoglobin level and prevented anaemia 4 weeks after surgery, with a short-term safety profile similar to placebo. Future trials on potential clinical benefits of preoperative treatment with intravenous iron in non-anaemic patients are needed. © 2015 The Authors ISBT Science Series published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.

Protocol for a single-centre, randomised controlled study of a preoperative rehabilitation bundle in the frail and elderly undergoing abdominal surgery.

PubMed

Abdullah, Hairil Rizal; Lien, Victoria Peixin; Ong, Hwee Kuan; Er, Pei Ling; Hao, Ying; Khan, Shariq Ali; Liu, Christopher Weiyang

2017-08-04

Frail patients have decreased physiological reserves and consequently, they are unable to recover as quickly from surgery. Frailty, as an entity, is a risk factor of increased morbidity and mortality. It is also associated with a longer time to discharge. This trial is undertaken to determine if a novel prehabilitation protocol (10-day bundle of interventions-physiotherapy, nutritional supplementation and cognitive training) can reduce the postoperative length of stay of frail patients who are undergoing elective abdominal surgery, compared with standard care. This is a prospective, single-centre, randomised controlled trial with two parallel arms. 62 patients who are frail and undergoing elective abdominal surgery will be recruited and randomised to receive either a novel prehabilitation protocol or standard care. Participants will receive telephone reminders preoperatively to encourage protocol compliance. Data will be collected for up to 30 days postoperatively. The primary outcome of the trial will be the postoperative length of stay and the secondary outcomes are the postoperative complications and functional recovery during the hospital admission. This study has been approved by the Singapore General Hospital Institutional Review Board (CIRB Ref: 2016/2584). The study is also listed on ClinicalTrials.gov (Trial number: NCT02921932). All participants will sign an informed consent form before randomisation and translators will be made available to non-English speaking patients. The results of this study will be published in peer-reviewed journals as well as national and international conferences. The data collected will also be made available in a public data repository. NCT02921932 (ClinicalTrials.gov). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Design and Evaluation of Micellar Nanocarriers for 17-allyamino-17-demethoxygeldanamycin (17-AAG)

EPA Science Inventory

17-Allyamino-17-demethoxygeldanamycin (17-AAG) is a potent anticancer agent currently undergoing phases I and II clinical trials. However, the clinical development of 17-AAG has been hindered by its poor aqueous solubility and hepatotoxicity. This study aimed to devise novel mice...

Medi-Port Pilot Randomized Controlled Trial

ClinicalTrials.gov

2017-12-29

Actively Undergoing Cancer Treatment; 4-9 Years of Age; At Least 1 Month From Diagnosis; Able to Speak and Understand English; Presenting to Clinic for at Least a 2nd Subcutaneous Port Needle Insertion

Preoperative versus postoperative ultrasound-guided rectus sheath block for improving pain, sleep quality and cytokine levels of patients with open midline incisions undergoing transabdominal gynaecological operation: study protocol for a randomised controlled trial.

PubMed

Jin, Feng; Li, Xiao-Qian; Tan, Wen-Fei; Ma, Hong; Lu, Huang-Wei

2015-12-10

Rectus sheath block (RSB) is used for postoperative pain relief in patients undergoing abdominal surgery with midline incision. Preoperative RSB has been shown to be effective, but it has not been compared with postoperative RSB. The aim of the present study is to evaluate postoperative pain, sleep quality and changes in the cytokine levels of patients undergoing gynaecological surgery with RSB performed preoperatively versus postoperatively. This study is a prospective, randomised, controlled (randomised, parallel group, concealed allocation), single-blinded trial. All patients undergoing transabdominal gynaecological surgery will be randomised 1:1 to the treatment intervention with general anaesthesia as an adjunct to preoperative or postoperative RSB. The objective of the trial is to evaluate postoperative pain, sleep quality and changes in the cytokine levels of patients undergoing gynaecological surgery with RSB performed preoperatively (n = 32) versus postoperatively (n = 32). All of the patients, irrespective of group allocation, will receive patient-controlled intravenous analgesia (PCIA) with oxycodone. The primary objective is to compare the interval between leaving the post-anaesthesia care unit and receiving the first PCIA bolus injection on the first postoperative night between patients who receive preoperative versus postoperative RSB. The secondary objectives will be to compare (1) cumulative oxycodone consumption at 24 hours after surgery; (2) postoperative sleep quality, as measured using a BIS-Vista monitor during the first night after surgery; and (3) cytokine levels (interleukin-1, interleukin-6, tumour necrosis factor-α and interferon-γ) during surgery and at 24 and 48 hours postoperatively. Clinical experience has suggested that RSB is a very effective postoperative analgesic technique, and we will answer the following questions with this trial. Do preoperative block and postoperative block have the same duration of analgesic effects? Can postoperative block extend the analgesic time? The results of this study could have actual clinical applications that could help to reduce postoperative pain and shorten hospital stays. Current Controlled Trials NCT02477098 15 June 2015.

Randomized trial of harp therapy during in vitro fertilization-embryo transfer.

PubMed

Murphy, Erin M; Nichols, Jennifer; Somkuti, Steve G; Sobel, Michael; Braverman, Andrea; Barmat, Larry I

2014-04-01

This study evaluated whether harp therapy reduces levels of stress and improves clinical outcomes in patients undergoing embryo transfer. This prospective randomized trial enrolled 181 women undergoing embryo transfer, who were randomized to harp therapy during embryo transfer or standard treatment. Patients underwent standardized psychological testing and physiologic assessment of stress. The study was conducted in a reproductive medicine practice. No statistically significant differences were found in the heart and respiratory rates, nor was there a significant difference in event-based anxiety at baseline. Harp therapy had a significantly larger decrease in state anxiety from pre- to post-embryo transfer. Clinical pregnancy was 53% versus 48% for the harp therapy and standard treatment groups, respectively. Harp therapy decreases state, or event-based, anxiety, significantly lowering state scores posttransfer and having a positive effect on acute levels of stress. There was an increased pregnancy rate, but larger sample sizes are needed to evaluate whether harp therapy has an effect on clinical outcomes.

Acupuncture to improve live birth rates for women undergoing in vitro fertilization: a protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background IVF is a costly treatment option for women, their partners, and the public. Therefore new therapies that improve reproductive and health outcomes are highly desirable. There is a growing body of research evaluating the effect of acupuncture administered during IVF, and specifically on the day of embryo transfer (ET). Many trials are heterogeneous and results inconsistent. There remains insufficient evidence to determine if acupuncture can enhance live birth rates when used as an adjunct to IVF treatment. The study will determine the clinical effectiveness of acupuncture with improving the proportion of women undergoing IVF having live births. Other objectives include: determination of the cost effectiveness of IVF with acupuncture; and examination of the personal and social context of acupuncture in IVF patients, and examining the reasons why the acupuncture may or may not have worked. Methods We will conduct a randomized controlled trial of acupuncture compared to placebo acupuncture. Inclusion criteria include: women aged less than 43 years; undergoing a fresh IVF or ICSI cycle; and restricted to women with the potential for a lower live birth rate defined as two or more previous unsuccessful ETs; and unsuccessful clinical pregnancies of quality embryos deemed by the embryologist to have been suitable for freezing by standard criteria. Women will be randomized to acupuncture or placebo acupuncture. Treatment is administered on days 6 to 8 of the stimulated cycle and two treatments on the day of ET. A non-randomized cohort of women not using acupuncture will be recruited to the study. The primary study outcome is the proportion of women reporting a live birth. Secondary outcomes include the proportion of women reporting a clinical pregnancy miscarriage prior to 12 weeks, quality of life, and self-efficacy. The sample size of the study is 1,168 women, with the aim of detecting a 7% difference in live births between groups (P = 0.05, 80% power). Discussion There remains a need for further research to add significant new knowledge to defining the exact role of certain acupuncture protocols in the management of infertility requiring IVF from a clinical and cost-effectiveness perspective. Clinical Trial Registration Australian and New Zealand Clinical Trial Registry ACTRN12611000226909 PMID:22607192

Treating Patients with High-Risk Smoldering Myeloma

Cancer.gov

In this phase III clinical trial, patients with smoldering myeloma classified as high risk for progression will be randomly assigned to undergo standard observation or six 4-week courses of treatment with the drug lenalidomide.

Technology evaluation: AVI-4126, AVI BioPharma.

PubMed

Stephens, Alick C

2004-10-01

AVI BioPharma is developing AVI-4126, an antisense oligonucleotide targeted to c-myc mRNA for the potential treatment of restenosis, cancer and polycystic kidney disease. AVI-4126 is currently undergoing phase II clinical trials.

Vaccine Therapy for Unresectable Chordoma

Cancer.gov

In this phase II clinical trial, adult patients with inoperable chordoma who are scheduled to undergo radiation therapy will be randomly assigned to receive a yeast-based vaccine that targets a protein called brachyury or a placebo injection.

Aspirin or Rivaroxaban for VTE Prophylaxis after Hip or Knee Arthroplasty.

PubMed

Anderson, David R; Dunbar, Michael; Murnaghan, John; Kahn, Susan R; Gross, Peter; Forsythe, Michael; Pelet, Stephane; Fisher, William; Belzile, Etienne; Dolan, Sean; Crowther, Mark; Bohm, Eric; MacDonald, Steven J; Gofton, Wade; Kim, Paul; Zukor, David; Pleasance, Susan; Andreou, Pantelis; Doucette, Steve; Theriault, Chris; Abianui, Abongnwen; Carrier, Marc; Kovacs, Michael J; Rodger, Marc A; Coyle, Doug; Wells, Philip S; Vendittoli, Pascal-Andre

2018-02-22

Clinical trials and meta-analyses have suggested that aspirin may be effective for the prevention of venous thromboembolism (proximal deep-vein thrombosis or pulmonary embolism) after total hip or total knee arthroplasty, but comparisons with direct oral anticoagulants are lacking for prophylaxis beyond hospital discharge. We performed a multicenter, double-blind, randomized, controlled trial involving patients who were undergoing total hip or knee arthroplasty. All the patients received once-daily oral rivaroxaban (10 mg) until postoperative day 5 and then were randomly assigned to continue rivaroxaban or switch to aspirin (81 mg daily) for an additional 9 days after total knee arthroplasty or for 30 days after total hip arthroplasty. Patients were followed for 90 days for symptomatic venous thromboembolism (the primary effectiveness outcome) and bleeding complications, including major or clinically relevant nonmajor bleeding (the primary safety outcome). A total of 3424 patients (1804 undergoing total hip arthroplasty and 1620 undergoing total knee arthroplasty) were enrolled in the trial. Venous thromboembolism occurred in 11 of 1707 patients (0.64%) in the aspirin group and in 12 of 1717 patients (0.70%) in the rivaroxaban group (difference, 0.06 percentage points; 95% confidence interval [CI], -0.55 to 0.66; P<0.001 for noninferiority and P=0.84 for superiority). Major bleeding complications occurred in 8 patients (0.47%) in the aspirin group and in 5 (0.29%) in the rivaroxaban group (difference, 0.18 percentage points; 95% CI, -0.65 to 0.29; P=0.42). Clinically important bleeding occurred in 22 patients (1.29%) in the aspirin group and in 17 (0.99%) in the rivaroxaban group (difference, 0.30 percentage points; 95% CI, -1.07 to 0.47; P=0.43). Among patients who received 5 days of rivaroxaban prophylaxis after total hip or total knee arthroplasty, extended prophylaxis with aspirin was not significantly different from rivaroxaban in the prevention of symptomatic venous thromboembolism. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT01720108 .).

Improving Awareness of Cancer Clinical Trials Among Hispanic Patients and Families: Audience Segmentation Decisions for a Media Intervention

PubMed Central

QUINN, GWENDOLYN P.; McINTYRE, JESSICA; GONZALEZ, LUIS E.; ANTONIA, TERESITA MUÑOZ; ANTOLINO, PRADO; WELLS, KRISTEN J.

2016-01-01

Clinical trials hold great promise for cancer treatment; yet, Hispanic cancer patients have low rates of clinical trial participation. Lack of awareness and knowledge of clinical trials and language barriers may account for low participation rates. Patient education through audiovisual materials can improve knowledge of and attitudes toward clinical trials among Hispanic populations. In this study, 36 Hispanic cancer patients/survivors and caregivers in Florida and Puerto Rico participated in focus groups to aid in developing a Spanish-language DVD and booklet intervention designed to increase knowledge about clinical trials. Focus group results showed (a) low levels of knowledge about clinical trials, (b) uncertainty about why a physician would expect a patient to make a choice about treatment, and (c) desire for family participation in decision making. Respondents expressed various preferences for aspects of the DVD such as showing extended family in the DVD and physician explanations about key terms. On the basis of these preferences, the authors developed a creative brief for a DVD. The content of the DVD was reviewed by Hispanic community leaders and key stakeholders. A final DVD was created, in Spanish, using Hispanic patients and physicians, which contained the information deemed important from the focus groups and stakeholder interviews. The DVD is complete with companion booklet and currently undergoing a randomized control trial. PMID:23639101

The use of a non-benzodiazepine hypnotic sleep-aid (Zolpidem) in patients undergoing ACL reconstruction: a randomized controlled clinical trial.

PubMed

Tompkins, Marc; Plante, Matthew; Monchik, Keith; Fleming, Braden; Fadale, Paul

2011-05-01

Previous studies have addressed post-operative pain management after ACL reconstruction by examining the use of intra-articular analgesia and/or modification of anesthesia techniques. To our knowledge, however, no previous studies have evaluated the effect of zolpidem on post-operative narcotic requirements, pain, and fatigue in patients undergoing outpatient arthroscopic ACL reconstruction. The purpose of this prospective, blinded, randomized, controlled clinical study was to evaluate the effect of zolpidem on post-operative narcotic requirements, pain, and fatigue in patients undergoing outpatient arthroscopic ACL reconstruction. Twenty-nine patients undergoing arthroscopic ACL reconstruction were randomized to a treatment group or placebo group. Both groups received post-operative hydrocodone/acetaminophen bitartrate (Vicodin ES). Patients in the treatment group received a single dose of zolpidem for the first seven post-operative nights. Patients in the placebo group received a gelatin capsule similar in appearance to zolpidem. The amount of Vicodin used in each group, the amount of post-operative pain, and the amount of post-operative fatigue were analyzed. Following ACL reconstruction, a 28% reduction was seen in the total amount of narcotic consumed with zolpidem (P = 0.047) when compared to placebo. There were no significant differences in post-operative pain or fatigue levels between zolpidem and placebo. Adding zolpidem to the post-operative medication regimen after arthroscopic ACL reconstruction helps to lower the amount of narcotic pain medication required for adequate analgesia. Randomized controlled clinical trial, Level I.

Ultrathin, bioresorbable polymer sirolimus-eluting stents versus thin, durable polymer everolimus-eluting stents in patients undergoing coronary revascularisation (BIOFLOW V): a randomised trial.

PubMed

Kandzari, David E; Mauri, Laura; Koolen, Jacques J; Massaro, Joseph M; Doros, Gheorghe; Garcia-Garcia, Hector M; Bennett, Johan; Roguin, Ariel; Gharib, Elie G; Cutlip, Donald E; Waksman, Ron

2017-10-21

The development of coronary drug-eluting stents has included use of new metal alloys, changes in stent architecture, and use of bioresorbable polymers. Whether these advancements improve clinical safety and efficacy has not been shown in previous randomised trials. We aimed to examine the clinical outcomes of a bioresorbable polymer sirolimus-eluting stent compared with a durable polymer everolimus-eluting stent in a broad patient population undergoing percutaneous coronary intervention. BIOFLOW V was an international, randomised trial done in patients undergoing elective and urgent percutaneous coronary intervention in 90 hospitals in 13 countries (Australia, Belgium, Canada, Denmark, Germany, Hungary, Israel, the Netherlands, New Zealand, South Korea, Spain, Switzerland, and the USA). Eligible patients were those aged 18 years or older with ischaemic heart disease undergoing planned stent implantation in de-novo, native coronary lesions. Patients were randomly assigned (2:1) to either an ultrathin strut (60 μm) bioresorbable polymer sirolimus-eluting stent or to a durable polymer everolimus-eluting stent. Randomisation was via a central web-based data capture system (mixed blocks of 3 and 6), and stratified by study site. The primary endpoint was 12-month target lesion failure. The primary non-inferiority comparison combined these data from two additional randomised trials of bioresorbable polymer sirolimus-eluting stent and durable polymer everolimus-eluting stent with Bayesian methods. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02389946. Between May 8, 2015, and March 31, 2016, 4772 patients were recruited into the study. 1334 patients met inclusion criteria and were randomly assigned to treatment with bioresorbable polymer sirolimus-eluting stents (n=884) or durable polymer everolimus-eluting stents (n=450). 52 (6%) of 883 patients in the bioresorbable polymer sirolimus-eluting stent group and 41 (10%) of 427 patients in the durable polymer everolimus-eluting stent group met the 12-month primary endpoint of target lesion failure (95% CI -6·84 to -0·29, p=0·0399), with differences in target vessel myocardial infarction (39 [5%] of 831 patients vs 35 [8%] of 424 patients, p=0·0155). The posterior probability that the bioresorbable polymer sirolimus-eluting stent is non-inferior to the durable polymer everolimus-eluting stent was 100% (Bayesian analysis, difference in target lesion failure frequency -2·6% [95% credible interval -5·5 to 0·1], non-inferiority margin 3·85%, n=2208). The outperformance of the ultrathin, bioresorbable polymer sirolimus-eluting stent over the durable polymer everolimus-eluting stent in a complex patient population undergoing percutaneous coronary intervention suggests a new direction in improving next generation drug-eluting stent technology. BIOTRONIK. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of remote ischaemic preconditioning on major clinical outcomes in patients undergoing cardiovascular surgery: A meta-analysis with trial sequential analysis of 32 randomised controlled trials.

PubMed

Wang, Shifei; Li, Hairui; He, Nvqin; Sun, Yili; Guo, Shengcun; Liao, Wangjun; Liao, Yulin; Chen, Yanmei; Bin, Jianping

2017-01-15

The impact of remote ischaemic preconditioning (RIPC) on major clinical outcomes in patients undergoing cardiovascular surgery remains controversial. We systematically reviewed the available evidence to evaluate the potential benefits of RIPC in such patients. PubMed, Embase, and Cochrane Library databases were searched for relevant randomised controlled trials (RCTs) conducted between January 2006 and March 2016. The pooled population of patients who underwent cardiovascular surgery was divided into the RIPC and control groups. Trial sequential analysis was applied to judge data reliability. The pooled relative risks (RRs) with 95% confidence intervals (CIs) between the groups were calculated for all-cause mortality, major adverse cardiovascular and cerebral events (MACCEs), myocardial infarction (MI), and renal failure. RIPC was not associated with improvement in all-cause mortality (RR, 1.04; 95%CI, 0.82-1.31; I 2 =26%; P>0.05) or MACCE incidence (RR, 0.90; 95%CI, 0.71-1.14; I 2 =40%; P>0.05) after cardiovascular surgery, and both results were assessed by trial sequential analysis as sufficient and conclusive. Nevertheless, RIPC was associated with a significantly lower incidence of MI (RR, 0.87; 95%CI, 0.76-1.00; I 2 =13%; P≤0.05). However, after excluding a study that had a high contribution to heterogeneity, RIPC was associated with increased rates of renal failure (RR, 1.53; 95%CI, 1.12-2.10; I 2 =5%; P≤0.05). In patients undergoing cardiovascular surgery, RIPC reduced the risk for postoperative MI, but not that for MACCEs or all-cause mortality, a discrepancy likely related to the higher rate of renal failure associated with RIPC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Meta-analysis of randomized trials of effect of milrinone on mortality in cardiac surgery: an update.

PubMed

Majure, David T; Greco, Teresa; Greco, Massimiliano; Ponschab, Martin; Biondi-Zoccai, Giuseppe; Zangrillo, Alberto; Landoni, Giovanni

2013-04-01

The long-term use of milrinone is associated with increased mortality in chronic heart failure. A recent meta-analysis suggested that it might increase mortality in patients undergoing cardiac surgery. The authors conducted an updated meta-analysis of randomized trials in patients undergoing cardiac surgery to determine if milrinone impacted survival. A meta-analysis. Hospitals. One thousand thirty-seven patients from 20 randomized trials. None. Biomed, Central, PubMed, EMBASE, the Cochrane central register of clinical trials, and conference proceedings were searched for randomized trials that compared milrinone versus placebo or any other control in adult and pediatric patients undergoing cardiac surgery. Authors of trials that did not include mortality data were contacted. Only trials for which mortality data were available were included. Overall analysis showed no difference in mortality between patients receiving milrinone versus control (12/554 [2.2%] in the milrinone group v 10/483 [2.1%] in the control arm; relative risk [RR] = 1.15; 95% confidence interval [CI], 0.55-2.43; p = 0.7) or in analysis restricted to adults (11/364 [3%] in the milrinone group v 9/371 [2.4%] in the control arm; RR = 1.17; 95% CI, 0.54-2.53; p = 0.7). Sensitivity analyses in trials with a low risk of bias showed a trend toward an increase in mortality with milrinone (8/153 [5.2%] in the milrinone arm v 2/152 [1.3%] in the control arm; RR = 2.71; 95% CI, 0.82-9; p for effect = 0.10). Despite theoretic concerns for increased mortality with intravenous milrinone in patients undergoing cardiac surgery, the authors were unable to confirm an adverse effect on survival. However, sensitivity analysis of high-quality trials showed a trend toward increased mortality with milrinone. Copyright © 2013 Elsevier Inc. All rights reserved.

Randomised controlled trial of exercise to prevent shoulder problems in women undergoing breast cancer treatment: study protocol for the prevention of shoulder problems trial (UK PROSPER)

PubMed Central

Williamson, Esther; Lait, Clare; Richmond, Helen; Betteley, Lauren; Lall, Ranjit; Petrou, Stavros; Rees, Sophie; Withers, Emma J; Lamb, Sarah E; Thompson, Alastair M

2018-01-01

Musculoskeletal shoulder problems are common after breast cancer treatment. Early postoperative exercises targeting the upper limb may improve shoulder function. This protocol describes a National Institute for Health Research-funded randomised controlled trial (RCT) to evaluate the clinical and cost-effectiveness of an early supervised structured exercise programme compared with usual care, for women at high risk of developing shoulder problems after breast cancer surgery. Methods This pragmatic two-armed, multicentre RCT is underway within secondary care in the UK. PRevention Of Shoulder ProblEms tRial (PROSPER) aims to recruit 350 women from approximately 15 UK centres with follow-up at 6 weeks, 6 and 12 months after randomisation. Recruitment processes and intervention development were optimised through qualitative research during a 6-month internal pilot phase. Participants are randomised to the PROSPER intervention or best practice usual care only. The PROSPER intervention is delivered by physiotherapists and incorporates three main components: shoulder-specific exercises targeting range of movement and strength; general physical activity and behavioural strategies to encourage adherence and support exercise behaviour. The primary outcome is upper arm function assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire at 12 months postrandomisation. Secondary outcomes include DASH subscales, acute and chronic pain, complications, health-related quality of life and healthcare resource use. We will interview a subsample of 20 participants to explore their experiences of the trial interventions. Discussion The PROSPER study is the first multicentre UK clinical trial to investigate the clinical and cost-effectiveness of supported exercise in the prevention of shoulder problems in high-risk women undergoing breast cancer surgery. The findings will inform future clinical practice and provide valuable insight into the role of physiotherapy-supported exercise in breast cancer rehabilitation. Protocol version Version 2.1; dated 11 January 2017 Trial registration number ISRCTN35358984; Pre-results. PMID:29574439

A randomized-controlled trial examining the effects of reflexology on anxiety of patients undergoing coronary angiography.

PubMed

Molavi Vardanjani, Mehdi; Masoudi Alavi, Negin; Razavi, Narges Sadat; Aghajani, Mohammad; Azizi-Fini, Esmail; Vaghefi, Seied Morteza

2013-09-01

The anxiety reduction before coronary angiography has clinical advantages and is one of the objectives of nursing. Reflexology is a non-invasive method that has been used in several clinical situations. Applying reflexology might have effect on the reduction of anxiety before coronary angiography. The aim of this randomized clinical trial was to investigate the effect of reflexology on anxiety among patients undergoing coronary angiography. This trial was conducted in Shahid Beheshti Hospital, in Kashan, Iran. One hundred male patients who were undergoing coronary angiography were randomly enrolled into intervention and placebo groups. The intervention protocol was included 30 minutes of general foot massage and the stimulation of three reflex points including solar plexus, pituitary gland, and heart. The placebo group only received the general foot massage. Spielbergers state trait anxiety inventory was used to assess the anxiety experienced by patients. Data was analyzed using Man-Witney, Wilcoxon and Chi-square tests. The stepwise multiple regressions used to analyze the variables that are involved in anxiety reduction. The mean range of anxiety decreased from 53.24 to 45.24 in reflexology group which represented 8 score reduction (P = 0.0001). The reduction in anxiety was 5.9 score in placebo group which was also significant (P = 0.0001). The anxiety reduction was significantly higher in reflexology group (P = 0.014). The stepwise multiple regression analysis showed that doing reflexology can explain the 7.5% of anxiety reduction which made a significant model. Reflexology can decrease the anxiety level before coronary angiography. Therefore, reflexology before coronary angiography is recommended.

International Technology Transfer of a GCLP-Compliant HIV-1 Neutralizing Antibody Assay for Human Clinical Trials

PubMed Central

Todd, Christopher A.; Greene, Kelli M.; Montefiori, David C.; Sarzotti-Kelsoe, Marcella

2012-01-01

The Collaboration for AIDS Vaccine Discovery/Comprehensive Antibody – Vaccine Immune Monitoring Consortium (CAVD/CA-VIMC) assisted an international network of laboratories in transferring a validated assay used to judge HIV-1 vaccine immunogenicity in compliance with Good Clinical Laboratory Practice (GCLP) with the goal of adding quality to the conduct of endpoint assays for Human Immunodeficiency Virus I (HIV-1) vaccine human clinical trials. Eight Regional Laboratories in the international setting (Regional Laboratories), many located in regions where the HIV-1 epidemic is most prominent, were selected to implement the standardized, GCLP-compliant Neutralizing Antibody Assay for HIV-1 in TZM-bl Cells (TZM-bl NAb Assay). Each laboratory was required to undergo initial training and implementation of the immunologic assay on-site and then perform partial assay re-validation, competency testing, and undergo formal external audits for GCLP compliance. Furthermore, using a newly established external proficiency testing program for the TZM-bl NAb Assay has allowed the Regional Laboratories to assess the comparability of assay results at their site with the results of neutralizing antibody assays performed around the world. As a result, several of the CAVD/CA-VIMC Regional Laboratories are now in the process of conducting or planning to conduct the GCLP-compliant TZM-bl NAb Assay as an indicator of vaccine immunogenicity for ongoing human clinical trials. PMID:22303476

International technology transfer of a GCLP-compliant HIV-1 neutralizing antibody assay for human clinical trials.

PubMed

Ozaki, Daniel A; Gao, Hongmei; Todd, Christopher A; Greene, Kelli M; Montefiori, David C; Sarzotti-Kelsoe, Marcella

2012-01-01

The Collaboration for AIDS Vaccine Discovery/Comprehensive Antibody-Vaccine Immune Monitoring Consortium (CAVD/CA-VIMC) assisted an international network of laboratories in transferring a validated assay used to judge HIV-1 vaccine immunogenicity in compliance with Good Clinical Laboratory Practice (GCLP) with the goal of adding quality to the conduct of endpoint assays for Human Immunodeficiency Virus I (HIV-1) vaccine human clinical trials. Eight Regional Laboratories in the international setting (Regional Laboratories), many located in regions where the HIV-1 epidemic is most prominent, were selected to implement the standardized, GCLP-compliant Neutralizing Antibody Assay for HIV-1 in TZM-bl Cells (TZM-bl NAb Assay). Each laboratory was required to undergo initial training and implementation of the immunologic assay on-site and then perform partial assay re-validation, competency testing, and undergo formal external audits for GCLP compliance. Furthermore, using a newly established external proficiency testing program for the TZM-bl NAb Assay has allowed the Regional Laboratories to assess the comparability of assay results at their site with the results of neutralizing antibody assays performed around the world. As a result, several of the CAVD/CA-VIMC Regional Laboratories are now in the process of conducting or planning to conduct the GCLP-compliant TZM-bl NAb Assay as an indicator of vaccine immunogenicity for ongoing human clinical trials.

Preconditioning Shields Against Vascular Events in Surgery (SAVES), a multicentre feasibility trial of preconditioning against adverse events in major vascular surgery: study protocol for a randomised control trial.

PubMed

Healy, Donagh; Clarke-Moloney, Mary; Gaughan, Brendan; O'Daly, Siobhan; Hausenloy, Derek; Sharif, Faisal; Newell, John; O'Donnell, Martin; Grace, Pierce; Forbes, John F; Cullen, Walter; Kavanagh, Eamon; Burke, Paul; Cross, Simon; Dowdall, Joseph; McMonagle, Morgan; Fulton, Greg; Manning, Brian J; Kheirelseid, Elrasheid A H; Leahy, Austin; Moneley, Daragh; Naughton, Peter; Boyle, Emily; McHugh, Seamus; Madhaven, Prakash; O'Neill, Sean; Martin, Zenia; Courtney, Donal; Tubassam, Muhammed; Sultan, Sherif; McCartan, Damian; Medani, Mekki; Walsh, Stewart

2015-04-23

Patients undergoing vascular surgery procedures constitute a 'high-risk' group. Fatal and disabling perioperative complications are common. Complications arise via multiple aetiological pathways. This mechanistic redundancy limits techniques to reduce complications that target individual mechanisms, for example, anti-platelet agents. Remote ischaemic preconditioning (RIPC) induces a protective phenotype in at-risk tissue, conferring protection against ischaemia-reperfusion injury regardless of the trigger. RIPC is induced by repeated periods of upper limb ischaemia-reperfusion produced using a blood pressure cuff. RIPC confers some protection against cardiac and renal injury during major vascular surgery in proof-of-concept trials. Similar trials suggest benefit during cardiac surgery. Several uncertainties remain in advance of a full-scale trial to evaluate clinical efficacy. We propose a feasibility trial to fully evaluate arm-induced RIPC's ability to confer protection in major vascular surgery, assess the incidence of a proposed composite primary efficacy endpoint and evaluate the intervention's acceptability to patients and staff. Four hundred major vascular surgery patients in five Irish vascular centres will be randomised (stratified for centre and procedure) to undergo RIPC or not immediately before surgery. RIPC will be induced using a blood pressure cuff with four cycles of 5 minutes of ischaemia followed by 5 minutes of reperfusion immediately before the start of operations. There is no sham intervention. Participants will undergo serum troponin measurements pre-operatively and 1, 2, and 3 days post-operatively. Participants will undergo 12-lead electrocardiograms pre-operatively and on the second post-operative day. Predefined complications within one year of surgery will be recorded. Patient and staff experiences will be explored using qualitative techniques. The primary outcome measure is the proportion of patients who develop elevated serum troponin levels in the first 3 days post-operatively. Secondary outcome measures include length of hospital and critical care stay, unplanned critical care admissions, death, myocardial infarction, stroke, mesenteric ischaemia and need for renal replacement therapy (within 30 days of surgery). RIPC is novel intervention with the potential to significantly improve perioperative outcomes. This trial will provide the first evaluation of RIPC's ability to reduce adverse clinical events following major vascular surgery. www.clinicaltrials.gov NCT02097186 Date Registered: 24 March 2014.

Timing luteal support in ART: a systematic review F & S 19112 revision non-highlighted

PubMed Central

Connell, Matthew T.; Szatkowski, Jennifer M.; Terry, Nancy; DeCherney, Alan H.; Propst, Anthony M.; Hill, Micah J.

2015-01-01

Objective To summarize the available published randomized controlled trial data regarding timing of progesterone supplementation during the luteal phase of patients undergoing ART. Design A systematic review. Setting Not applicable. Patient(s) Undergoing in vitro fertilization. Intervention(s) Different starting times of progesterone for luteal support. Main Outcome Measure(s) Clinical pregnancy and live birth. Results Five randomized controlled trials were identified that met inclusion criteria with a total of 872 patients. A planned meta-analysis was not performed due to a high degree of clinical heterogeneity in regards to the timing, dose, and route of progesterone. Two studies compared progesterone initiated before oocyte retrieval versus the day of oocyte retrieval and pregnancy rates were 5–12% higher when starting progesterone on the day of oocyte retrieval. One study compared starting progesterone on post retrieval day 6 versus day 3, reporting a 16% decrease in pregnancy in the day 6 group. Trials comparing progesterone start times on the day of oocyte retrieval versus two or three days post retrieval showed no significant differences in pregnancy. Conclusions There appears to be a window for progesterone start time between the evening of oocyte retrieval and day 3 after oocyte retrieval. While some studies have suggested a potential benefit in delaying vaginal progesterone start time to 2 days after oocyte retrieval, this review could not find randomized controlled trials to adequately assess this. Further randomized clinical trials are needed to better define progesterone start time for luteal support after ART. PMID:25638420

Infection, Alveolar Osteitis, and Adverse Effects Using Metronidazole in Healthy Patients Undergoing Third Molar Surgery: A Meta-analysis.

PubMed

Isiordia-Espinoza, Mario Alberto; Aragon-Martinez, Othoniel H; Bollogna-Molina, Ronell E; Alonso-Castro, Ángel J

2018-06-01

The aim of this systematic review and meta-analysis was to evaluate the risk of surgical infection, alveolar osteitis, and adverse effects using systemic metronidazole in comparison with placebo in healthy patients undergoing third molar surgery. The eligible reports were identified from diverse science sources. Clinical trials meeting the inclusion and exclusion criteria and an acceptable Oxford Quality Score were included in this study. The evaluation of risk was done using the Risk Reduction Calculator and Review Manager 5.3., from the Cochrane Library. A significant risk reduction was assumed when the upper limit of the 95% confidence intervals was <1 and the lower limit did not cross zero (negative number) alongside a p value of <0.05 for the overall test. Data of 667 patients from five clinical trials were used for the assessment of risk. Our analysis showed no reduction of the risk of infection or dry socket in patients receiving metronidazole compared to whom took placebo. Meanwhile, the adverse effects did not exhibit a difference between the studied groups. The routine use of systemic metronidazole to prevent surgical site infection and/or dry socket in healthy patients undergoing third molar surgery is not recommended.

Effects of recreational soccer in men with prostate cancer undergoing androgen deprivation therapy: study protocol for the ‘FC Prostate’ randomized controlled trial

PubMed Central

2013-01-01

Background Androgen deprivation therapy (ADT) is a cornerstone in the treatment of advanced prostate cancer. Adverse musculoskeletal and cardiovascular effects of ADT are widely reported and investigations into the potential of exercise to ameliorate the effects of treatment are warranted. The ‘Football Club (FC) Prostate’ study is a randomized trial comparing the effects of soccer training with standard treatment approaches on body composition, cardiovascular function, physical function parameters, glucose tolerance, bone health, and patient-reported outcomes in men undergoing ADT for prostate cancer. Methods/Design Using a single-center randomized controlled design, 80 men with histologically confirmed locally advanced or disseminated prostate cancer undergoing ADT for 6 months or more at The Copenhagen University Hospital will be enrolled on this trial. After baseline assessments eligible participants will be randomly assigned to a soccer training group or a control group receiving usual care. The soccer intervention will consist of 12 weeks of training 2–3 times/week for 45–60 min after which the assessment protocol will be repeated. Soccer training will then continue bi-weekly for an additional 20 weeks at the end of which all measures will be repeated to allow for additional analyses of long-term effects. The primary endpoint is changes in lean body mass from baseline to 12 weeks assessed by dual X-ray absorptiometry scan. Secondary endpoints include changes of cardiovascular, metabolic, and physical function parameters, as well as markers of bone metabolism and patient-reported outcomes. Discussion The FC Prostate trial will assess the safety and efficacy of a novel soccer-training approach to cancer rehabilitation on a number of clinically important health outcomes in men with advanced prostate cancer during ADT. The results may pave the way for innovative, community-based interventions in the approach to treating prostate cancer. Trial registration ClinicalTrials.gov: NCT01711892 PMID:24330570

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

PubMed

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

2016-04-01

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

Antibiotic prophylaxis for operative vaginal delivery.

PubMed

Liabsuetrakul, Tippawan; Choobun, Thanapan; Peeyananjarassri, Krantarat; Islam, Q Monir

2017-08-05

Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics may be prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum or forceps deliveries, or both. We searched Cochrane Pregnancy and Childbirth's Trials Register (12 July 2017), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (12 July 2017) and reference lists of retrieved studies. All randomised trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age undergoing vacuum or forceps delivery for any indications. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium) compared with either placebo or no treatment. Two review authors assessed trial eligibility and methodological quality. Two review authors extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all review authors. We assessed methodological quality of the one included trial using the GRADE approach. One trial, involving 393 women undergoing either vacuum or forceps deliveries, was included. The trial compared the antibiotic intravenous cefotetan after cord clamping compared with no treatment. This trial reported only two out of the nine outcomes specified in this review. Seven women in the group given no antibiotics had endomyometritis and none in prophylactic antibiotic group, the risk reduction was 93% (risk ratio (RR) 0.07; 95% confidence interval (CI) 0.00 to 1.21; low-quality evidence). There was no difference in the length of hospital stay between the two groups (mean difference (MD) 0.09 days; 95% CI -0.23 to 0.41; low-quality evidence). Overall, the risk of bias was judged to be unclear. The quality of the evidence using GRADE was low for both endometritis and maternal length of stay. One small trial was identified reporting only two outcomes. Evidence from this single trial suggests that antibiotic prophylaxis may lead to little or no difference in endometritis or maternal length of stay. There were no data on any other outcomes to evaluate the impact of antibiotic prophylaxis after operative vaginal delivery. Future research on antibiotic prophylaxis for operative vaginal delivery is needed to conclude whether it is useful for reducing postpartum morbidity.

Preoperative oral supplementation with carbohydrate and branched-chain amino acid-enriched nutrient improves insulin resistance in patients undergoing a hepatectomy: a randomized clinical trial using an artificial pancreas.

PubMed

Okabayashi, Takehiro; Nishimori, Isao; Yamashita, Koichi; Sugimoto, Takeki; Namikawa, Tsutomu; Maeda, Hiromichi; Yatabe, Tomoaki; Hanazaki, Kazuhiro

2010-03-01

Glucose metabolism is adversely affected in patients following major surgery. Patients may develop hyperglycemia due to a combination of surgical stress and postoperative insulin resistance. A randomized trial was conducted to elucidate the effect of preoperative supplementation with carbohydrates and branched-chain amino acids on postoperative insulin resistance in patients undergoing hepatic resection. A total of 26 patients undergoing a hepatectomy for the treatment of a hepatic neoplasm were randomly assigned to receive a preoperative supplement of carbohydrate and branched-chain amino acid-enriched nutrient mixture or not. The postoperative blood glucose level and the total insulin requirement for normoglycemic control during the 16 h following hepatic resection were determined using the artificial pancreas STG-22. Postoperative insulin requirements for normoglycemic control in the group with preoperative nutritional support was significantly lower than that in the control group (P = 0.039). There was no incidence of hypoglycemia (<40 mg/dL) observed in patients, including those with diabetes mellitus, when the STG-22 was used to control blood glucose levels. STG-22 is a safe and reliable tool to control postoperative glucose metabolism and evaluate insulin resistance. The preoperative oral administration of carbohydrate and branched-chain amino acid-enriched nutrient is of clinical benefit and reduces postoperative insulin resistance in patients undergoing hepatic resection.

The Healthy Heart-Mind trial: melatonin for prevention of delirium following cardiac surgery: study protocol for a randomized controlled trial.

PubMed

Ford, Andrew H; Flicker, Leon; Passage, Jurgen; Wibrow, Bradley; Anstey, Matthew; Edwards, Mark; Almeida, Osvaldo P

2016-01-28

Delirium is a common occurrence in patients undergoing major cardiac surgery and is associated with a number of adverse consequences for the individual, their family and the health system. Current approaches to the prevention of delirium include identifying those at risk together with various non-pharmacological and pharmacological strategies, although the efficacy of these is often modest. Emerging evidence suggests that melatonin may be biologically implicated in the development of delirium and that melatonin supplementation may be beneficial in reducing the incidence of delirium in medical and surgical patients. We designed this trial to determine whether melatonin reduces the incidence of delirium following cardiac surgery compared with placebo. The Healthy Heart-Mind trial is a randomized, double-blind, placebo-controlled clinical trial of 3 mg melatonin or matching placebo administered on seven consecutive days for the prevention of delirium following cardiac surgery. We will recruit 210 adult participants, aged 50 and older, undergoing elective or semi-elective cardiac surgery with the primary outcome of interest for this study being the difference in the incidence of delirium between the groups within 7 days of surgery. Secondary outcomes of interest include the difference between groups in the severity and duration of delirious episodes, hospital length of stay and referrals to mental health services during admission. In addition, we will assess differences in depressive and anxiety symptoms, as well as cognitive performance, at discharge and 3 months after surgery. The results of this trial will clarify whether melatonin reduces the incidence of delirium following cardiac surgery. The trial is registered with the Australian Clinical Trials Registry, trial number ACTRN12615000819527 (10 August 2015).

Knowledge and expectations of women undergoing cancer genetic risk assessment: a qualitative analysis of free-text questionnaire comments.

PubMed

Phelps, C; Wood, F; Bennett, P; Brain, K; Gray, J

2007-08-01

Individuals undergoing cancer genetic risk assessment have been found to have a poor understanding of the process, which may affect how well they cope with learning their risk. This paper reports free-text data from questionnaires completed by women undergoing a randomised controlled trial of a psychological intervention. Of the 268 women undergoing genetic assessment for familial breast/ovarian cancer risk who were invited to take part in the trial, 157 women returned research questionnaires. Of these, 97 women provided free-text comments upon referral to a cancer genetics clinic, 62 provided comments whilst waiting for risk information (average, moderate or high), and 36 women provided comments following notification of risk. This paper reports a thematic analysis of the free-text data. Themes reflected individuals' poor knowledge and uncertainty about genetic risk assessment. How well individuals responded to learning their risk depended upon whether expectations had been met. Regardless of risk, individuals undergoing cancer genetic risk assessment are likely to benefit from increased information about its process and timescales, and access to increased psychological support. Free-text comments can provide valuable data about individuals' expectations and knowledge of genetics services.

Intensive Home Hemodialysis: An Eye at the Past Looking for the Hemodialysis of the Future.

PubMed

Naso, Agostino; Scaparrotta, Giuseppe; Naso, Elena; Calò, Lorenzo A

2015-09-01

Multiple observational studies along with a limited number of randomized clinical trials suggest that intensive hemodialysis (IHD) not only improves outcomes for uremic patients undergoing chronic dialysis but does so with a more favorable cost/benefit ratio compared with conventional hemodialysis. As a result of this, there has been a rapid increase in the interest in home hemodialysis (HHD) as HHD represents the easiest means of implementing IHD. While HHD has generated increased interest given its association with better outcomes/reduced hospitalizations, there are very few randomized controlled trials comparing HHD with other hemodialysis methods. Reported HHD-associated increased survival benefits compared with in-center hemodialysis are from uncontrolled studies, which raise patient selection bias as underlying the differences found. Thus, while HHD draws increasing attention, studies that pay careful attention to the psychosocial, demographic, and clinical factors associated with patients selected to undergo HHD will be needed to ultimately demonstrate its benefits, clarify the clinical applications, and determine the limits of IHD use in dialysis patients. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Polyurethane on titanium unconstrained disc arthroplasty versus anterior discectomy and fusion for the treatment of cervical disc disease: a review of level I-II randomized clinical trials including clinical outcomes.

PubMed

Aragonés, María; Hevia, Eduardo; Barrios, Carlos

2015-12-01

To contrast the clinical and radiologic outcomes and adverse events of anterior cervical discectomy and fusion (ACDF) with a single cervical disc arthroplasty design, the polyurethane on titanium unconstrained cervical disc (PTUCD). This is a systematic review of randomized clinical trials (RCT) with evidence level I-II reporting clinical outcomes. After a search on different databases including PubMed, Cochrane Central Register of Controlled Trials, and Ovid MEDLINE, a total of 10 RCTs out of 51 studies found were entered in the study. RTCs were searched from the earliest available records in 2005 to November 2014. Out of a total of 1101 patients, 562 were randomly assigned into the PTUCD arthroplasty group and 539 into the ACDF group. The mean follow-up was 30.9 months. Patients undergoing arthroplasty had lower Neck Disability Index, and better SF-36 Physical component scores than ACDF patients. Patients with PTUCD arthroplasty had also less radiological degenerative changes at the upper adjacent level. Overall adverse events were twice more frequent in patients with ACDF. The rate of revision surgery including both adjacent and index level was slightly higher in patients with ACDF, showing no statistically significant difference. According to this review, PTUCD arthroplasty showed a global superiority to ACDF in clinical outcomes. The impact of both surgical techniques on the cervical spine (radiological spine deterioration and/or complications) was more severe in patients undergoing ACDF. However, the rate of revision surgeries at any cervical level was equivalent for ACDF and PTUCD arthroplasty.

Effects of reiki in clinical practice: a systematic review of randomised clinical trials.

PubMed

Lee, M S; Pittler, M H; Ernst, E

2008-06-01

The aim of this systematic review is to summarise and critically evaluate the evidence for the effectiveness of reiki. We searched the literature using 23 databases from their respective inceptions through to November 2007 (search again 23 January 2008) without language restrictions. Methodological quality was assessed using the Jadad score. The searches identified 205 potentially relevant studies. Nine randomised clinical trials (RCTs) met our inclusion criteria. Two RCTs suggested beneficial effects of reiki compared with sham control on depression, while one RCT did not report intergroup differences. For pain and anxiety, one RCT showed intergroup differences compared with sham control. For stress and hopelessness a further RCT reported effects of reiki and distant reiki compared with distant sham control. For functional recovery after ischaemic stroke there were no intergroup differences compared with sham. There was also no difference for anxiety between groups of pregnant women undergoing amniocentesis. For diabetic neuropathy there were no effects of reiki on pain. A further RCT failed to show the effects of reiki for anxiety and depression in women undergoing breast biopsy compared with conventional care. In total, the trial data for any one condition are scarce and independent replications are not available for each condition. Most trials suffered from methodological flaws such as small sample size, inadequate study design and poor reporting. In conclusion, the evidence is insufficient to suggest that reiki is an effective treatment for any condition. Therefore the value of reiki remains unproven.

Feasibility and safety of xenon compared with sevoflurane anaesthesia in coronary surgical patients: a randomized controlled pilot study.

PubMed

Stoppe, C; Fahlenkamp, A V; Rex, S; Veeck, N C; Gozdowsky, S C; Schälte, G; Autschbach, R; Rossaint, R; Coburn, M

2013-09-01

To date, only limited data exist about the use of xenon as an anaesthetic agent in patients undergoing cardiac surgery. The favourable cardio- and neuroprotective properties of xenon might attenuate postoperative complications, improve outcome, and reduce the incidence of delirium. Thus, the aims of this study were to investigate the feasibility and safety of balanced xenon anaesthesia in patients undergoing cardiac surgery and to gather pilot data for a future randomized multicentre study. Thirty patients undergoing elective coronary artery bypass grafting were enrolled in this randomized, single-blind controlled trial. They were randomized to receive balanced general anaesthesia with either xenon (45-50 vol%) or sevoflurane (1-1.4 vol%). The primary outcome was the occurrence of adverse events (AEs). Secondary outcome parameters were feasibility criteria (bispectral index, perioperative haemodynamic, and respiratory profile) and safety parameters (dosage of study treatments, renal function, intraoperative blood loss, need for inotropic support, regional cerebral tissue oxygenation). Furthermore, at predefined time points, systemic and pulmonary haemodynamics were assessed by the use of a pulmonary artery catheter. There were no patient characteristic differences between the groups. Patients undergoing xenon anaesthesia did not differ with respect to the incidence of AE (6 vs 8, P=0.464) compared with the sevoflurane group. No differences were detected regarding secondary feasibility and safety criteria. The haemodynamic and respiratory profile was comparable between the treatment groups. Balanced xenon anaesthesia is feasible and safe compared with sevoflurane anaesthesia in patients undergoing coronary artery bypass surgery. Acronym CARDIAX: A pre- and post-coronary artery bypass graft implantation disposed application of xenon. Clinical trial registration ClinicalTrials.gov: NCT01285271; EudraCT-number: 2010-023942-63. Approved by the ethics committee 'Ethik-Kommission an der Medizinischen Fakultät der Rheinisch-Westfälischen Technischen Hochschule Aachen (RWTH Aachen)': EK-218/10.

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

PubMed

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

2013-08-01

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

Methylprednisolone for prevention of ovarian hyperstimulation syndrome in patients with polycystic ovarian syndrome undergoing in-vitro fertilisation: a randomised controlled trial.

PubMed

Mohammadi Yeganeh, Ladan; Moini, Ashraf; Shiva, Marzieh; Mirghavam, Naimeh; Bagheri Lankarani, Narges

2018-02-01

This study aimed to evaluate the effect of methylprednisolone on prevention of ovarian hyperstimulation syndrome (OHSS) in polycystic ovarian syndrome (PCOS) patients undergoing in-vitro fertilisation (IVF). This randomised controlled trial was carried out between November 2009 and December 2013. A total of 219 eligible patients were randomly allocated for treatment (n = 108) or control groups (n = 111). The treatment group received oral methylprednisolone starting from the first day of stimulation. These patients also received an intravenous dose of methylprednisolone on the days of egg collection and embryo transfer. The control group received no glucocorticoid treatment to prevent OHSS. Nineteen percent of patients (18/93) who received methylprednisolone developed OHSS compared with 16.5% (15/91) in the control group and no significant difference was found (p = .61). There were no significant differences between treatment and control groups in the rates of implantation (10% versus 11%, p = .77) and clinical pregnancy (23.2% versus 17.7%, p = .46). Methylprednisolone did not reduce the incidence and severity of OHSS in PCOS patients undergoing IVF and no improvement in clinical outcomes was observed. Impact statement No significant differences were found in OHSS incidence and clinical outcomes between women who received methylprednisolone and control group. There seems to be no benefit for the routine use of glucocorticoids in IVF/ICSI treatments.

The Effect of Cognitive Behavior Therapy in Insomnia due to Methadone Maintenance Therapy: A Randomized Clinical Trial

PubMed Central

Soleimani, Robabeh; Modabbernia, Mohammad Jafar; Habibi, Sharareh; Roudsary, Maryam Habibi; Elahi, Masoumeh

2015-01-01

Background: Sleep disturbance is a common complaint of patients undergoing methadone maintenance therapy (MMT). There are limited studies about the effect of different treatments on insomnia due to MMT. In this study, we evaluated the effect of cognitive-behavioral treatment for insomnia (CBTI) on sleep disorders in patients undergoing MMT. Methods: Twenty-two patients with insomnia due to MMT (aged 18-60 years) participated in this randomized double-blind clinical trial. The intervention group received CBTI from a clinical psychologist for 8 weeks, whereas the control group received behavioral placebo therapy (BPT). The duration of individual sessions was 45 minutes, which was conducted once a week. The primary outcome was sleep disturbance assessed with Pittsburgh Sleep Quality Index (PSQI). Data were analyzed using SPSS software version 19. Results: Eleven patients were assigned to each group. Two groups were matched according to demographic characteristics (age, marital status, education, and daily methadone doses). Although PSQI score was significantly reduced during weeks 5 and 8 after both interventions, there was a significant difference in intervention versus time interaction (P<0.02). The effects of CBTI versus placebo were significantly different (P<0.001). The time course was also significant (P<0.001). Conclusion: This study showed that CBTI is more effective than BPT in overall sleep quality. We recommend further studies, with a larger sample, on CBTI in patients undergoing MMT. PMID:26379345

Transection Speed and Impact on Perioperative Inflammatory Response – A Randomized Controlled Trial Comparing Stapler Hepatectomy and CUSA Resection

PubMed Central

Schwarz, Christoph; Klaus, Daniel A.; Tudor, Bianca; Fleischmann, Edith; Wekerle, Thomas; Roth, Georg; Bodingbauer, Martin; Kaczirek, Klaus

2015-01-01

Background Parenchymal transection represents a crucial step during liver surgery and many different techniques have been described so far. Stapler resection is supposed to be faster than CUSA resection. However, whether speed impacts on the inflammatory response in patients undergoing liver resection (LR) remains unclear. Materials and Methods This is a randomized controlled trial including 40 patients undergoing anatomical LR. Primary endpoint was transection speed (cm2/min). Secondary endpoints included the perioperative change of pro- and anti-inflammatory cytokines, overall surgery duration, length of hospital stay, morbidity and mortality. Results Mean transection speed was significantly higher in patients undergoing stapler hepatectomy compared to CUSA resection (CUSA: 1 (0.4) cm2/min vs. Stapler: 10.8 (6.1) cm2/min; p<0.0001). Analyzing the impact of surgery duration on inflammatory response revealed a significant correlation between IL-6 levels measured at the end of surgery and the overall length of surgery (p<0.0001, r = 0.6188). Patients undergoing CUSA LR had significantly higher increase of interleukin-6 (IL-6) after parenchymal transection compared to patients with stapler hepatectomy in the portal and hepatic veins, respectively (p = 0.028; p = 0.044). C-reactive protein levels on the first post-operative day were significantly lower in the stapler cohort (p = 0.010). There was a trend towards a reduced overall surgery time in patients with stapler LR, especially in the subgroup of patients undergoing minor hepatectomies (p = 0.020). Conclusions Liver resection using staplers is fast, safe and suggests a diminished inflammatory response probably due to a decreased parenchymal transection time. Trial Registration ClinicalTrials.gov NCT01785212 PMID:26452162

Alternatives, and adjuncts, to prophylactic platelet transfusion for people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation

PubMed Central

Desborough, Michael; Estcourt, Lise J; Doree, Carolyn; Trivella, Marialena; Hopewell, Sally; Stanworth, Simon J; Murphy, Michael F

2016-01-01

Background Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people with thrombocytopenia. Although considerable advances have been made in platelet transfusion therapy since the mid-1970s, some areas continue to provoke debate especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. Objectives To determine whether agents that can be used as alternatives, or adjuncts, to platelet transfusions for people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation are safe and effective at preventing bleeding. Search methods We searched 11 bibliographic databases and four ongoing trials databases including the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 4), MEDLINE (OvidSP, 1946 to 19 May 2016), Embase (OvidSP, 1974 to 19 May 2016), PubMed (e-publications only: searched 19 May 2016), ClinicalTrials.gov, World Health Organization (WHO) ICTRP and the ISRCTN Register (searched 19 May 2016). Selection criteria We included randomised controlled trials in people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation who were allocated to either an alternative to platelet transfusion (artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, recombinant activated factor VII, desmopressin (DDAVP), or thrombopoietin (TPO) mimetics) or a comparator (placebo, standard care or platelet transfusion). We excluded studies of antifibrinolytic drugs, as they were the focus of another review. Data collection and analysis Two review authors screened all electronically derived citations and abstracts of papers identified by the review search strategy. Two review authors assessed risk of bias in the included studies and extracted data independently. Main results We identified 16 eligible trials. Four trials are ongoing and two have been completed but the results have not yet been published (trial completion dates: April 2012 to February 2017). Therefore, the review included 10 trials in eight references with 554 participants. Six trials (336 participants) only included participants with acute myeloid leukaemia undergoing intensive chemotherapy, two trials (38 participants) included participants with lymphoma undergoing intensive chemotherapy and two trials (180 participants) reported participants undergoing allogeneic stem cell transplantation. Men and women were equally well represented in the trials. The age range of participants included in the trials was from 16 years to 81 years. All trials took place in high-income countries. The manufacturers of the agent sponsored eight trials that were under investigation, and two trials did not report their source of funding. No trials assessed artificial platelet substitutes, fibrinogen concentrate, recombinant activated factor VII or desmopressin. Nine trials compared a TPO mimetic to placebo or standard care; seven of these used pegylated recombinant human megakaryocyte growth and differentiation factor (PEG-rHuMGDF) and two used recombinant human thrombopoietin (rhTPO). One trial compared platelet-poor plasma to platelet transfusion. We considered that all the trials included in this review were at high risk of bias and meta-analysis was not possible in seven trials due to problems with the way data were reported. We are very uncertain whether TPO mimetics reduce the number of participants with any bleeding episode (odds ratio (OR) 0.40, 95% confidence interval (CI) 0.10 to 1.62, one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce the risk of a life-threatening bleed after 30 days (OR 1.46, 95% CI 0.06 to 33.14, three trials, 209 participants, very low quality evidence); or after 90 days (OR 1.00, 95% CI 0.06 to 16.37, one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce platelet transfusion requirements after 30 days (mean difference -3.00 units, 95% CI -5.39 to -0.61, one trial, 120 participants, very low quality evidence). No deaths occurred in either group after 30 days (one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce all-cause mortality at 90 days (OR 1.00, 95% CI 0.24 to 4.20, one trial, 120 participants, very low quality evidence). No thromboembolic events occurred for participants treated with TPO mimetics or control at 30 days (two trials, 209 participants, very low quality evidence). We found no trials that looked at: number of days on which bleeding occurred, time from randomisation to first bleed or quality of life. One trial with 18 participants compared platelet-poor plasma transfusion with platelet transfusion. We are very uncertain whether platelet-poor plasma reduces the number of participants with any bleeding episode (OR 16.00, 95% CI 1.32 to 194.62, one trial, 18 participants, very low quality evidence). We are very uncertain whether platelet-poor plasma reduces the number of participants with severe or life-threatening bleeding (OR 4.00, 95% CI 0.56 to 28.40, one trial, 18 participants, very low quality evidence). We found no trials that looked at: number of days on which bleeding occurred, time from randomisation to first bleed, number of platelet transfusions, all-cause mortality, thromboembolic events or quality of life. Authors’ conclusions There is insufficient evidence to determine if platelet-poor plasma or TPO mimetics reduce bleeding for participants with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation. To detect a decrease in the proportion of participants with clinically significant bleeding from 12 in 100 to 6 in 100 would require a trial containing at least 708 participants (80% power, 5% significance). The six ongoing trials will provide additional information about the TPO mimetic comparison (424 participants) but this will still be underpowered to demonstrate this level of reduction in bleeding. None of the included or ongoing trials include children. There are no completed or ongoing trials assessing artificial platelet substitutes, fibrinogen concentrate, recombinant activated factor VII or desmopressin in people undergoing intensive chemotherapy or stem cell transplantation for haematological malignancies. PMID:27548292

[Differences between clinical trials according to the German law on pharmaceuticals (Arzneimittelgesetz) and trials according to the German law on medical products (Medizinproduktegesetz)].

PubMed

Krummenauer, F

2003-02-01

Similar to the registration process for pharmaceutical agents, medical devices have to undergo standardized clinical evaluation before being marketed and used in routine therapy or diagnostics. However, conduction, submission, and reporting of such clinical evaluations to authorities has to follow the German law on medical products(Medizinproduktegesetz,MPG), which in some central aspects differs remarkably from the German law on pharmaceuticals (Arzneimittelgesetz,AMG). Relevant deviations of MPG requirements from those of the AMG are reviewed with particular emphasis on submission, conduction, and reporting of trials to the authorities in charge. Whereas AMG-based trials focus on the proof of efficacy of pharmaceutical agents, the MPG demands instead proof of functionality of the medical devices; the MPG therefore concentrates more on technically satisfactory results in the context of function and patient safety. The aim of MPG trials is thus CE marking instead of AMG-based registration. However, this focus on functionality implies that medical devices need not necessarily be tested in a clinical trial--in some settings evidence-based evaluation alone will be sufficient. The decision on the necessity of a clinical trial is based mainly on the risk profile and invasive character of the device at hand. The early consideration of differences between AMG and MPG concerning the role and conduction of clinical trials will remarkably increase the (CE) certification process's outcome quality and juridical validity.

Reforming the community research program: from Community Clinical Oncology Program to the National Cancer Institute Community Oncology Research Program.

PubMed

Zon, Robin T

2014-01-01

Community research has been an integral and influential component of the National Research Program since the late 1970s. Institutionalization of community research in the Community Clinical Oncology Program (CCOP) has resulted in successful collaborations, meaningful accrual, achievement of quality standards, and translation of research into clinical practice. Although the national clinical trial system is undergoing modernization and improvement, the success of the CCOP and minority-based CCOP in cancer treatment, prevention, and control research is being extended to include cancer care delivery research in the newly created National Cancer Institute (NCI) Community Oncology Research Program. This article briefly presents a historic perspective of community involvement in federally sponsored clinical trials and introduces the continued involvement in the newly created NCI program.

A Randomized-Controlled Trial Examining the Effects of Reflexology on Anxiety of Patients Undergoing Coronary Angiography

PubMed Central

Molavi Vardanjani, Mehdi; Masoudi Alavi, Negin; Razavi, Narges Sadat; Aghajani, Mohammad; Azizi-Fini, Esmail; Vaghefi, Seied Morteza

2013-01-01

Background: The anxiety reduction before coronary angiography has clinical advantages and is one of the objectives of nursing. Reflexology is a non-invasive method that has been used in several clinical situations. Applying reflexology might have effect on the reduction of anxiety before coronary angiography. Objectives: The aim of this randomized clinical trial was to investigate the effect of reflexology on anxiety among patients undergoing coronary angiography. Patients and Methods: This trial was conducted in Shahid Beheshti Hospital, in Kashan, Iran. One hundred male patients who were undergoing coronary angiography were randomly enrolled into intervention and placebo groups. The intervention protocol was included 30 minutes of general foot massage and the stimulation of three reflex points including solar plexus, pituitary gland, and heart. The placebo group only received the general foot massage. Spielbergers state trait anxiety inventory was used to assess the anxiety experienced by patients. Data was analyzed using Man-Witney, Wilcoxon and Chi-square tests. The stepwise multiple regressions used to analyze the variables that are involved in anxiety reduction. Results: The mean range of anxiety decreased from 53.24 to 45.24 in reflexology group which represented 8 score reduction (P = 0.0001). The reduction in anxiety was 5.9 score in placebo group which was also significant (P = 0.0001). The anxiety reduction was significantly higher in reflexology group (P = 0.014). The stepwise multiple regression analysis showed that doing reflexology can explain the 7.5% of anxiety reduction which made a significant model. Conclusions: Reflexology can decrease the anxiety level before coronary angiography. Therefore, reflexology before coronary angiography is recommended. PMID:25414869

Magnesium Sulfate Reduced Opioid Consumption in Obese Patients Undergoing Sleeve Gastrectomy: a Prospective, Randomized Clinical Trial.

PubMed

Kizilcik, Nurcan; Koner, Ozge

2018-05-12

The purpose of the study was to investigate the effect of magnesium sulfate on pain management for pain after sleeve gastrectomy operation. A prospective, randomized, placebo-controlled clinical study. University hospital. Eighty patients undergoing sleeve gastrectomy. Visual analog scale for the evaluation of pain, sedation score, mean arterial pressure, heart rate, and total analgesic consumption was recorded. Serum magnesium levels were determined before the operation, at the end of the operation, and at 24 h. There were no significant differences between the groups with respect to demographics, and sedation scores. Cumulative morphine consumption and pain scores were found to be higher in the control group than the magnesium group. Perioperative use of magnesium sulfate reduced postoperative pain and opioid consumption in obese patients undergoing sleeve gastrectomy operations.

Immunosuppression by hypoxic cell radiosensitizers: a phenomenon of potential clinical importance

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

Rockwell, S.; Kapp, D.S.

1982-06-01

The nitroimidazoles metronidazole, misonidazol, and desmethyl misonidazole are currently undergoing clinical trials as possible adjuncts to radiotherapy. Ongoing clinical trials are evaluating the effectiveness of these agents and also documenting the pharmacokinetics and toxicities of radiosensitizing doses of these drugs in man. A variety of toxic effects have been noted in man, including anorexia, nausea and vomiting, peripheral neuropathy, central nervous system symptoms, ototoxicity, allergy, and fear. Laboratory studies have also suggested that these agents have potential to be mutagenic, carcinogenic, and teratogenic. In the editorial presented, the author attempts to draw attention to an additional toxic effect of nitroimidazolesmore » - the inhibition of cell-mediated immune responses. (JMT)« less

Exercise may reduce depression but not anxiety in self-referred cancer patients undergoing chemotherapy. Post-hoc analysis of data from the 'Body & Cancer' trial.

PubMed

Midtgaard, Julie; Stage, Maria; Møller, Tom; Andersen, Christina; Quist, Morten; Rørth, Mikael; Herrstedt, Jørn; Vistisen, Kirsten; Christiansen, Birgitte; Adamsen, Lis

2011-06-01

Abstract Background. The diagnosis and treatment of cancer may cause clinically significant and persistent psychological morbidity. The objective of this study was to determine the short-term effect of a six week exercise intervention on anxiety and depression in cancer patients undergoing chemotherapy (The 'Body & Cancer' trial). Methods. Two hundred and nine self-referred patients (52 males, 157 females, mean age 47 years) were randomised into an intervention group and a waiting-list control group. Anxiety and depression was measured by the Hospital Anxiety and Depression Scale. Results. At baseline, 23.5% and 11.5% of the population scored >8 on the HADS and were classified as suspicious or definite cases of anxiety and depression, respectively. Adjusted for baseline score, disease and demographic covariates the estimated intervention effect showed improvement at six weeks for depression of -0.7 points (95% confidence interval [CI] -1.27 to -0.14, p = 0.0153). No significant effect was seen on anxiety. Further subanalysis, including only suspicious or definite cases of depression, resulted in an estimated intervention effect of -2.53 points (95% CI, -0.64 to -0.42, p = 0.021). Conclusion. Anti-depressant effects could be caused by exercise in self-referred cancer patients undergoing chemotherapy. Dedicated trials and follow-up studies are needed to clarify the optimal duration and content of exercise interventions to meet the needs of clinically depressive or anxious patients.

Advances in Clinical Cardiology 2016: A Summary of the Key Clinical Trials.

PubMed

Gray, Alastair; McQuillan, Conor; Menown, Ian B A

2017-07-01

The findings of many new cardiology clinical trials over the last year have been published or presented at major international meetings. This paper aims to describe and place in context a summary of the key clinical trials in cardiology presented between January and December 2016. The authors reviewed clinical trials presented at major cardiology conferences during 2016 including the American College of Cardiology (ACC), European Association for Percutaneous Cardiovascular Interventions (EuroPCR), European Society of Cardiology (ESC), European Association for the Study of Diabetes (EASD), Transcatheter Cardiovascular Therapeutics (TCT), and the American Heart Association (AHA). Selection criteria were trials with a broad relevance to the cardiology community and those with potential to change current practice. A total of 57 key cardiology clinical trials were identified for inclusion. Here we describe and place in clinical context the key findings of new data relating to interventional and structural cardiology including delayed stenting following primary angioplasty, contrast-induced nephropathy, management of jailed wires, optimal duration of dual antiplatelet therapy (DAPT), stenting vs bypass for left main disease, new generation stents (BioFreedom, Orsiro, Absorb), transcatheter aortic valve implantation (Edwards Sapien XT, transcatheter embolic protection), and closure devices (Watchman, Amplatzer). New preventative cardiology data include trials of bariatric surgery, empagliflozin, liraglutide, semaglutide, PCSK9 inhibitors (evolocumab and alirocumab), and inclisiran. Antiplatelet therapy trials include platelet function monitoring and ticagrelor vs clopidogrel for peripheral vascular disease. New data are also presented in fields of heart failure (sacubitril/valsartan, aliskiren, spironolactone), atrial fibrillation (rivaroxaban in patients undergoing coronary intervention, edoxaban in DC cardioversion), cardiac devices (implantable cardioverter defibrillator in non-ischemic cardiomyopathy), and electrophysiology (cryoballoon vs radiofrequency ablation). This paper presents a summary of key clinical cardiology trials during the past year and should be of practical value to both clinicians and cardiology researchers.

Protocol, and practical challenges, for a randomised controlled trial comparing the impact of high intensity interval training against standard care before major abdominal surgery: study protocol for a randomised controlled trial.

PubMed

Woodfield, John; Zacharias, Matthew; Wilson, Genevieve; Munro, Fran; Thomas, Kate; Gray, Andrew; Baldi, James

2018-06-25

Risk factors, such as the number of pre-existing co-morbidities, the extent of the underlying pathology and the magnitude of the required operation, cannot be changed before surgery. It may, however, be possible to improve the cardiopulmonary fitness of the patient with an individualised exercise program. We are performing a randomised controlled trial (RCT) assessing the impact of High Intensity Interval Training (HIIT) on preoperative cardiopulmonary fitness and postoperative outcomes in patients undergoing major abdominal surgery. Consecutive eligible patients undergoing elective abdominal surgery are being randomised to HIIT or standard care in a 1:1 ratio. Participants allocated to HIIT will perform 14 exercise sessions on a stationary cycle ergometer, over a period of 4-6 weeks before surgery. The sessions, which are individualised, aim to start with ten repeated 1-min blocks of intense exercise with a target of reaching a heart rate exceeding 90% of the age predicted maximum, followed by 1 min of lower intensity cycling. As endurance improves, the duration of exercise is increased to achieve five 2-min intervals of high intensity exercise followed by 2 min of lower intensity cycling. Each training session lasts approximately 30 min. The primary endpoint, change in peak oxygen consumption (Peak VO 2 ) measured during cardiopulmonary exercise testing, is assessed at baseline and before surgery. Secondary endpoints include postoperative complications, length of hospital stay and three clinically validated scores: the surgical recovery scale; the postoperative morbidity survey; and the SF-36 quality of life score. The standard deviation for changes in Peak VO 2 will be assessed after the first 30 patients and will be used to calculate the required sample size. We want to assess if 14 sessions of HIIT is sufficient to improve Peak VO 2 by 2 mL/kg/min in patients undergoing major abdominal surgery and to explore the best clinical endpoint for a subsequent RCT designed to assess if improving Peak VO 2 will translate into improving clinical outcomes after surgery. Australian New Zealand Clinical Trials Registry, ACTRN12617000587303 . Registered on 26 April 2017.

Comparing multiple competing interventions in the absence of randomized trials using clinical risk-benefit analysis

PubMed Central

2012-01-01

Background To demonstrate the use of risk-benefit analysis for comparing multiple competing interventions in the absence of randomized trials, we applied this approach to the evaluation of five anticoagulants to prevent thrombosis in patients undergoing orthopedic surgery. Methods Using a cost-effectiveness approach from a clinical perspective (i.e. risk benefit analysis) we compared thromboprophylaxis with warfarin, low molecular weight heparin, unfractionated heparin, fondaparinux or ximelagatran in patients undergoing major orthopedic surgery, with sub-analyses according to surgery type. Proportions and variances of events defining risk (major bleeding) and benefit (thrombosis averted) were obtained through a meta-analysis and used to define beta distributions. Monte Carlo simulations were conducted and used to calculate incremental risks, benefits, and risk-benefit ratios. Finally, net clinical benefit was calculated for all replications across a range of risk-benefit acceptability thresholds, with a reference range obtained by estimating the case fatality rate - ratio of thrombosis to bleeding. Results The analysis showed that compared to placebo ximelagatran was superior to other options but final results were influenced by type of surgery, since ximelagatran was superior in total knee replacement but not in total hip replacement. Conclusions Using simulation and economic techniques we demonstrate a method that allows comparing multiple competing interventions in the absence of randomized trials with multiple arms by determining the option with the best risk-benefit profile. It can be helpful in clinical decision making since it incorporates risk, benefit, and personal risk acceptance. PMID:22233221

Formal education of patients about to undergo laparoscopic cholecystectomy.

PubMed

Gurusamy, Kurinchi Selvan; Vaughan, Jessica; Davidson, Brian R

2014-02-28

Generally, before being operated on, patients will be given informal information by the healthcare providers involved in the care of the patients (doctors, nurses, ward clerks, or healthcare assistants). This information can also be provided formally in different formats including written information, formal lectures, or audio-visual recorded information. To compare the benefits and harms of formal preoperative patient education for patients undergoing laparoscopic cholecystectomy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2013), MEDLINE, EMBASE, and Science Citation Index Expanded to March 2013. We included only randomised clinical trials irrespective of language and publication status. Two review authors independently extracted the data. We planned to calculate the risk ratio with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) or standardised mean difference (SMD) with 95% CI for continuous outcomes based on intention-to-treat analyses when data were available. A total of 431 participants undergoing elective laparoscopic cholecystectomy were randomised to formal patient education (215 participants) versus standard care (216 participants) in four trials. The patient education included verbal education, multimedia DVD programme, computer-based multimedia programme, and Power Point presentation in the four trials. All the trials were of high risk of bias. One trial including 212 patients reported mortality. There was no mortality in either group in this trial. None of the trials reported surgery-related morbidity, quality of life, proportion of patients discharged as day-procedure laparoscopic cholecystectomy, the length of hospital stay, return to work, or the number of unplanned visits to the doctor. There were insufficient details to calculate the mean difference and 95% CI for the difference in pain scores at 9 to 24 hours (1 trial; 93 patients); and we did not identify clear evidence of an effect on patient knowledge (3 trials; 338 participants; SMD 0.19; 95% CI -0.02 to 0.41; very low quality evidence), patient satisfaction (2 trials; 305 patients; SMD 0.48; 95% CI -0.42 to 1.37; very low quality evidence), or patient anxiety (1 trial; 76 participants; SMD -0.37; 95% CI -0.82 to 0.09; very low quality evidence) between the two groups.A total of 173 participants undergoing elective laparoscopic cholecystectomy were randomised to electronic consent with repeat-back (patients repeating back the information provided) (92 participants) versus electronic consent without repeat-back (81 participants) in one trial of high risk of bias. The only outcome reported in this trial was patient knowledge. The effect on patient knowledge between the patient education with repeat-back versus patient education without repeat-back groups was imprecise and based on 1 trial of 173 participants; SMD 0.07; 95% CI -0.22 to 0.37; very low quality evidence). Due to the very low quality of the current evidence, the effects of formal patient education provided in addition to the standard information provided by doctors to patients compared with standard care remain uncertain. Further well-designed randomised clinical trials of low risk of bias are necessary.

RECCAS - REmoval of Cytokines during CArdiac Surgery: study protocol for a randomised controlled trial.

PubMed

Baumann, Andreas; Buchwald, Dirk; Annecke, Thorsten; Hellmich, Martin; Zahn, Peter K; Hohn, Andreas

2016-03-12

On-pump cardiac surgery triggers a significant postoperative systemic inflammatory response, sometimes resulting in multiple-organ dysfunction associated with poor clinical outcome. Extracorporeal cytokine elimination with a novel haemoadsorption (HA) device (CytoSorb®) promises to attenuate inflammatory response. This study primarily assesses the efficacy of intraoperative HA during cardiopulmonary bypass (CPB) to reduce the proinflammatory cytokine burden during and after on-pump cardiac surgery, and secondarily, we aim to evaluate effects on postoperative organ dysfunction and outcomes in patients at high risk. This will be a single-centre randomised, two-arm, patient-blinded trial of intraoperative HA in patients undergoing on-pump cardiac surgery. Subjects will be allocated to receive either CPB with intraoperative HA or standard CPB without HA. The primary outcome is the difference in mean interleukin 6 (IL-6) serum levels between the two study groups on admission to the intensive care unit. A total number of 40 subjects was calculated as necessary to detect a clinically relevant 30 % reduction in postoperative IL-6 levels. Secondary objectives evaluate effects of HA on markers of inflammation up to 48 hours postoperatively, damage to the endothelial glycocalyx and effects on clinical scores and parameters of postoperative organ dysfunction and outcomes. In this pilot trial we try to assess whether intraoperative HA with CytoSorb® can relevantly reduce postoperative IL-6 levels in patients undergoing on-pump cardiac surgery. Differences in secondary outcome variables between the study groups may give rise to further studies and may lead to a better understanding of the mechanisms of haemoadsorption. German Clinical Trials Register number DRKS00007928 (Date of registration 3 Aug 2015).

Should the surgeon or the general practitioner (GP) follow up patients after surgery for colon cancer? A randomized controlled trial protocol focusing on quality of life, cost-effectiveness and serious clinical events.

PubMed

Augestad, Knut M; Vonen, Barthold; Aspevik, Ranveig; Nestvold, Torunn; Ringberg, Unni; Johnsen, Roar; Norum, Jan; Lindsetmo, Rolv-Ole

2008-06-25

All patients who undergo surgery for colon cancer are followed up according to the guidelines of the Norwegian Gastrointestinal Cancer Group (NGICG). These guidelines state that the aims of follow-up after surgery are to perform quality assessment, provide support and improve survival. In Norway, most of these patients are followed up in a hospital setting. We describe a multi-centre randomized controlled trial to test whether these patients can be followed up by their general practitioner (GP) without altering quality of life, cost effectiveness and/or the incidence of serious clinical events. Patients undergoing surgery for colon cancer with histological grade Dukes's Stage A, B or C and below 75 years of age are eligible for inclusion. They will be randomized after surgery to follow-up at the surgical outpatient clinic (control group) or follow-up by the district GP (intervention group). Both study arms comply with the national NGICG guidelines. The primary endpoints will be quality of life (QoL) (measured by the EORTC QLQ C-30 and the EQ-5D instruments), serious clinical events (SCEs), and costs. The follow-up period will be two years after surgery, and quality of life will be measured every three months. SCEs and costs will be estimated prospectively. The sample size was 170 patients. There is an ongoing debate on the best method of follow-up for patients with CRC. Due to a wide range of follow-up programmes and paucity of randomized trials, it is impossible to draw conclusions about the best combination and frequency of clinic (or family practice) visits, blood tests, endoscopic procedures and radiological examinations that maximize the clinical outcome, quality of life and costs. Most studies on follow-up of CRC patients have been performed in a hospital outpatient setting. We hypothesize that postoperative follow-up of colon cancer patients (according to national guidelines) by GPs will not have any impact on patients' quality of life. Furthermore, we hypothesize that there will be no increase in SCEs and that the incremental cost-effectiveness ratio will improve. This trial has been registered at ClinicalTrials.gov. The trial registration number is: NCT00572143.

Randomized controlled trial of tranexamic acid among parturients at increased risk for postpartum hemorrhage undergoing cesarean delivery.

PubMed

Sujata, Nambiath; Tobin, Raj; Kaur, Ranjeet; Aneja, Anjila; Khanna, Mona; Hanjoora, Vijay M

2016-06-01

To assess the effects of tranexamic acid among patients undergoing cesarean delivery who were at high risk of postpartum hemorrhage. Between August 1, 2012, and April 30, 2013, a randomized controlled trial was performed at a tertiary care center in India. Women undergoing an elective or emergency cesarean delivery who were at high risk for postpartum hemorrhage were enrolled. They were randomly assigned using sealed, opaque envelopes to receive 10mg/kg tranexamic acid or normal saline 10min before skin incision. Anesthesiologists were not masked to group assignment, but patients and obstetricians were. The primary outcome was need for additional uterotonic drugs within 24h after delivery. Analyses were by intention to treat. Thirty patients were assigned to each group. Additional uterotonic drugs were required in 7 (23%) patients assigned to tranexamic acid and 25 (83%) patients in the control group (P<0.001). Intravenous tranexamic acid, administered before skin incision, significantly reduced the requirement for additional uterotonics among women at increased risk for postpartum hemorrhage. Clinical Trials Registry India: CTRI/2015/05/005752. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Intraperitoneal local anaesthetic instillation versus no intraperitoneal local anaesthetic instillation for laparoscopic cholecystectomy.

PubMed

Gurusamy, Kurinchi Selvan; Nagendran, Myura; Guerrini, Gian Piero; Toon, Clare D; Zinnuroglu, Murat; Davidson, Brian R

2014-03-13

While laparoscopic cholecystectomy is generally considered less painful than open surgery, pain is one of the important reasons for delayed discharge after day surgery and overnight stay laparoscopic cholecystectomy. The safety and effectiveness of intraperitoneal local anaesthetic instillation in people undergoing laparoscopic cholecystectomy is unknown. To assess the benefits and harms of intraperitoneal instillation of local anaesthetic agents in people undergoing laparoscopic cholecystectomy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded to March 2013 to identify randomised clinical trials of relevance to this review. We considered only randomised clinical trials (irrespective of language, blinding, or publication status) comparing local anaesthetic intraperitoneal instillation versus placebo, no intervention, or inactive control during laparoscopic cholecystectomy for the review with regards to benefits while we considered quasi-randomised studies and non-randomised studies for treatment-related harms. Two review authors collected the data independently. We analysed the data with both fixed-effect and random-effects models using Review Manager 5 analysis. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). We included 58 trials, of which 48 trials with 2849 participants randomised to intraperitoneal local anaesthetic instillation (1558 participants) versus control (1291 participants) contributed data to one or more of the outcomes. All the trials except one trial with 30 participants were at high risk of bias. Most trials included only low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. Various intraperitoneal local anaesthetic agents were used but bupivacaine in the liquid form was the most common local anaesthetic used. There were considerable differences in the methods of local anaesthetic instillation including the location (subdiaphragmatic, gallbladder bed, or both locations) and timing (before or after the removal of gallbladder) between the trials. There was no mortality in either group in the eight trials that reported mortality (0/236 (0%) in local anaesthetic instillation versus 0/210 (0%) in control group; very low quality evidence). One participant experienced the outcome of serious morbidity (eight trials; 446 participants; 1/236 (0.4%) in local anaesthetic instillation group versus 0/210 (0%) in the control group; RR 3.00; 95% CI 0.13 to 67.06; very low quality evidence). Although the remaining trials did not report the overall morbidity, three trials (190 participants) reported that there were no intra-operative complications. Twenty trials reported that there were no serious adverse events in any of the 715 participants who received local anaesthetic instillation. None of the trials reported participant quality of life, return to normal activity, or return to work.The effect of local anaesthetic instillation on the proportion of participants discharged as day surgery between the two groups was imprecise and compatible with benefit and no difference of intervention (three trials; 242 participants; 89/160 (adjusted proportion 61.0%) in local anaesthetic instillation group versus 40/82 (48.8%) in control group; RR 1.25; 95% CI 0.99 to 1.58; very low quality evidence). The MD in length of hospital stay was 0.04 days (95% CI -0.23 to 0.32; five trials; 335 participants; low quality evidence). The pain scores as measured by the visual analogue scale (VAS) were significantly lower in the local anaesthetic instillation group than the control group at four to eight hours (32 trials; 2020 participants; MD -0.99 cm; 95% CI -1.10 to -0.88 on a VAS scale of 0 to 10 cm; very low quality evidence) and at nine to 24 hours (29 trials; 1787 participants; MD -0.53 cm; 95% CI -0.62 to -0.44; very low quality evidence). Various subgroup analyses and meta-regressions to investigate the influence of the different local anaesthetic agents, different methods of local anaesthetic instillation, and different controls on the effectiveness of local anaesthetic intraperitoneal instillation were inconsistent. Serious adverse events were rare in studies evaluating local anaesthetic intraperitoneal instillation (very low quality evidence). There is very low quality evidence that it reduces pain in low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. However, the clinical importance of this reduction in pain is unknown and likely to be small. Further randomised clinical trials of low risk of systematic and random errors are necessary. Such trials should include important clinical outcomes such as quality of life and time to return to work in their assessment.

Randomised controlled trial of exercise to prevent shoulder problems in women undergoing breast cancer treatment: study protocol for the prevention of shoulder problems trial (UK PROSPER).

PubMed

Bruce, Julie; Williamson, Esther; Lait, Clare; Richmond, Helen; Betteley, Lauren; Lall, Ranjit; Petrou, Stavros; Rees, Sophie; Withers, Emma J; Lamb, Sarah E; Thompson, Alastair M

2018-03-23

Musculoskeletal shoulder problems are common after breast cancer treatment. Early postoperative exercises targeting the upper limb may improve shoulder function. This protocol describes a National Institute for Health Research-funded randomised controlled trial (RCT) to evaluate the clinical and cost-effectiveness of an early supervised structured exercise programme compared with usual care, for women at high risk of developing shoulder problems after breast cancer surgery. This pragmatic two-armed, multicentre RCT is underway within secondary care in the UK. PRevention Of Shoulder ProblEms tRial (PROSPER) aims to recruit 350 women from approximately 15 UK centres with follow-up at 6 weeks, 6 and 12 months after randomisation. Recruitment processes and intervention development were optimised through qualitative research during a 6-month internal pilot phase. Participants are randomised to the PROSPER intervention or best practice usual care only. The PROSPER intervention is delivered by physiotherapists and incorporates three main components: shoulder-specific exercises targeting range of movement and strength; general physical activity and behavioural strategies to encourage adherence and support exercise behaviour. The primary outcome is upper arm function assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire at 12 months postrandomisation. Secondary outcomes include DASH subscales, acute and chronic pain, complications, health-related quality of life and healthcare resource use. We will interview a subsample of 20 participants to explore their experiences of the trial interventions. The PROSPER study is the first multicentre UK clinical trial to investigate the clinical and cost-effectiveness of supported exercise in the prevention of shoulder problems in high-risk women undergoing breast cancer surgery. The findings will inform future clinical practice and provide valuable insight into the role of physiotherapy-supported exercise in breast cancer rehabilitation. Version 2.1; dated 11 January 2017 TRIAL REGISTRATION NUMBER: ISRCTN35358984; Pre-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.

Cannabinoid Regulation of Acute and Anticipatory Nausea

PubMed Central

Rock, Erin M.; Sticht, Martin A.; Limebeer, Cheryl L.; Parker, Linda A.

2016-01-01

Abstract Chemotherapy-induced nausea is one of the most distressing symptoms reported by patients undergoing treatment, and even with the introduction of newer antiemetics such as ondansetron and aprepitant, nausea remains problematic in the clinic. Indeed, when acute nausea is not properly managed, the cues of the clinic can become associated with this distressing symptom resulting in anticipatory nausea for which no effective treatments are available. Clinical trials exploring the potential of exogenous or endogenous cannabinoids to reduce chemotherapy-induced nausea are sparse; therefore, we must rely on the data from pre-clinical rat models of nausea. In this review, we explore the human and pre-clinical animal literature examining the potential for exogenous and endogenous cannabinoid treatments to regulate chemotherapy-induced nausea. The pre-clinical evidence points to a compelling need to evaluate the antinausea potential of cannabidiol, cannabidiolic acid, and treatments that boost the functioning of the endocannabinoid system in human clinical trials. PMID:28861486

A comparison of three induction regimens using succinylcholine, vecuronium, or no muscle relaxant: impact on the intraoperative monitoring of the lateral spread response in hemifacial spasm surgery: study protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Surgical microvascular decompression (MVD) is the curative treatment for hemifacial spasm (HFS). Monitoring MVD by recording the lateral spread response (LSR) intraoperatively can predict a successful clinical outcome. However, the rate of the LSR varies between trials, and the reason for this variation is unclear. The aim of our trial is to evaluate the rate of the LSR after intubation following treatment with succinylcholine, vecuronium, or no muscle relaxant. Methods and design This trial is a prospective randomised controlled trial of 96 patients with HFS (ASA status I or II) undergoing MVD under general anaesthesia. Patients are randomised to receive succinylcholine, vecuronium, or no muscle relaxant before intubation. Intraoperative LSR will be recorded until dural opening. The primary outcome of this study is the rate of the LSR, and the secondary outcomes are post-intubation pharyngolaryngeal symptoms, the rate of difficult intubations, the rate of adverse haemodynamic events and the relationship between the measurement of LSR or not, and clinical success rates at 30 days after surgery. Discussion This study aims to evaluate the impact of muscle relaxants on the rate of the LSR, and the study may provide evidence supporting the use of muscle relaxants before intubation in patients with HFS undergoing MVD surgery. Trials registration http://www.chictr.org/ ChiCTR-TRC-11001504 Date of registration: 24 June, 2011. The date the first patient was randomised: 30 September, 2011. PMID:22958580

Acupuncture to improve live birth rates for women undergoing in vitro fertilization: a protocol for a randomized controlled trial.

PubMed

Smith, Caroline A; de Lacey, Sheryl; Chapman, Michael; Ratcliffe, Julie; Norman, Robert J; Johnson, Neil; Sacks, Gavin; Lyttleton, Jane; Boothroyd, Clare

2012-05-18

IVF is a costly treatment option for women, their partners, and the public. Therefore new therapies that improve reproductive and health outcomes are highly desirable. There is a growing body of research evaluating the effect of acupuncture administered during IVF, and specifically on the day of embryo transfer (ET). Many trials are heterogeneous and results inconsistent. There remains insufficient evidence to determine if acupuncture can enhance live birth rates when used as an adjunct to IVF treatment.The study will determine the clinical effectiveness of acupuncture with improving the proportion of women undergoing IVF having live births. Other objectives include: determination of the cost effectiveness of IVF with acupuncture; and examination of the personal and social context of acupuncture in IVF patients, and examining the reasons why the acupuncture may or may not have worked. We will conduct a randomized controlled trial of acupuncture compared to placebo acupuncture.Inclusion criteria include: women aged less than 43 years; undergoing a fresh IVF or ICSI cycle; and restricted to women with the potential for a lower live birth rate defined as two or more previous unsuccessful ETs; and unsuccessful clinical pregnancies of quality embryos deemed by the embryologist to have been suitable for freezing by standard criteria. Women will be randomized to acupuncture or placebo acupuncture. Treatment is administered on days 6 to 8 of the stimulated cycle and two treatments on the day of ET. A non-randomized cohort of women not using acupuncture will be recruited to the study. The primary study outcome is the proportion of women reporting a live birth. Secondary outcomes include the proportion of women reporting a clinical pregnancy miscarriage prior to 12 weeks, quality of life, and self-efficacy. The sample size of the study is 1,168 women, with the aim of detecting a 7% difference in live births between groups (P = 0.05, 80% power). There remains a need for further research to add significant new knowledge to defining the exact role of certain acupuncture protocols in the management of infertility requiring IVF from a clinical and cost-effectiveness perspective. Australian and New Zealand Clinical Trial Registry ACTRN12611000226909.

Effect of steroids on inflammatory markers and clinical parameters in congenital open heart surgery: a randomised controlled trial.

PubMed

Amanullah, Muhammad M; Hamid, Mohammad; Hanif, Hashim M; Muzaffar, Marium; Siddiqui, Maria T; Adhi, Fatima; Ahmad, Khabir; Khan, Shahjahan; Hasan, Zahra

2016-03-01

Cardiopulmonary bypass is associated with systemic inflammatory response. Steroids suppress this response, although the therapeutic evidence remains controversial. We hypothesised that intravenous steroids in children undergoing open-heart surgery would decrease inflammation leading to better early post-operative outcomes. We conducted a randomised controlled trial to evaluate the trends in the levels of immunomodulators and their effects on clinical parameters. To assess the effects of intravenous steroids on early post-operative inflammatory markers and clinical parameters in children undergoing open-heart surgery. A randomised controlled trial involving 152 patients, from one month up to 18 years of age, who underwent open-heart surgery for congenital heart disease from April 2010-2012 was carried out. Patients were randomised and administered either three scheduled intravenous pulse doses of dexamethasone (1 mg/kg) or placebo. Blood samples were drawn at four time intervals and serum levels of inflammatory cytokines - Interleukin-6, 8, 10, 18, and tumour necrosis factor-alpha - were measured. Clinical parameters were also assessed. Blood cytokine levels were compared between the dexamethasone (n=65) and placebo (n=64) groups. Interleukin-6 levels were lower at 6 and 24 hours post-operatively (p<0.001), and Interleukin-10 levels were higher 6 hours post-operatively (p<0.001) in the steroid group. Interleukin-8, 18, and tumour necrosis factor-alpha levels did not differ between the groups at any time intervals. The clinical parameters were similar in both the groups. Dexamethasone caused quantitative suppression of Interleukin-6 and increased Interleukin-10 activation, contributing to reduced immunopathology, but it did not translate into clinical benefit in the short term.

Ethics of Mandatory Research Biopsy for Correlative End Points Within Clinical Trials in Oncology

PubMed Central

Peppercorn, Jeffrey; Shapira, Iuliana; Collyar, Deborah; Deshields, Teresa; Lin, Nancy; Krop, Ian; Grunwald, Hans; Friedman, Paula; Partridge, Ann H.; Schilsky, Richard L.; Bertagnolli, Monica M.

2010-01-01

Clinical investigators in oncology are increasingly interested in using molecular analysis of cancer tissue to understand the biologic bases of response or resistance to novel interventions and to develop prognostic and predictive biomarkers that will guide clinical decision making. Some scientific questions of this nature can only be addressed, or may best be addressed, through the conduct of a clinical trial in which research biopsies are obtained from all participants. However, trial designs with mandatory research biopsies have raised ethical concerns related to the risk of harm to participants, the adequacy of voluntary informed consent, and the potential for misunderstanding among research participants when access to an experimental intervention is linked to the requirement to undergo a research biopsy. In consideration of the ethical and scientific issues at stake in this debate, the Cancer and Leukemia Group B Ethics Committee proposes guidelines for clinical trials involving mandatory research biopsies. Any cancer clinical trial that requires research biopsies of participants must be well designed to address the scientific question, obtain the biopsy in a way that minimizes risk, and ensure that research participants are fully informed of the risks, rationale, and requirements of the study, as well as of treatment alternatives. Further guidelines and discussions of this issue are specified in this position paper. We feel that if these principles are respected, an informed adult with cancer can both understand and voluntarily consent to participation in a clinical trial involving mandatory research biopsy for scientific end points. PMID:20406927

Early mobilization reduces the atelectasis and pleural effusion in patients undergoing coronary artery bypass graft surgery: A randomized clinical trial.

PubMed

Moradian, Seyed Tayeb; Najafloo, Mohammad; Mahmoudi, Hosein; Ghiasi, Mohammad Saeid

2017-09-01

Atelectasis and pleural effusion are common after coronary artery bypass graft surgery (CABG). Longer stay in the bed is one of the most important contributing factors in pulmonary complications. Some studies confirm the benefits of early mobilization (EM) in critically ill patients, but the efficacy of EM on pulmonary complications after CABG is not clear. This study was designed to examine the effect of EM on the incidence of atelectasis and pleural effusion in patients undergoing CABG. In a single-blinded randomized clinical trial, 100 patients who were undergoing coronary artery bypass graft surgery were randomly assigned into two groups each consisted of 50 patients. Patients in the experimental group were enrolled in a mobilization protocol consisting of the mobilization from the bed in the first 3 days after surgery in the morning and evening. Patients in the control group were mobilized from bed in third postoperation day, according to the hospital routine. Arterial blood gases, pleural effusion, and atelectasis were compared between groups. Atelectasis and pleural effusion was reduced in experimental group. The partial pressure of oxygen in arterial blood in third postoperative day and the percentage of arterial oxygen saturation in the fourth postoperative day were higher in the intervention group (P value < .05). EM from bed could be an effective intervention in reducing atelectasis and pleural effusion in patients undergoing CABG. Copyright © 2017 Society for Vascular Nursing, Inc. Published by Elsevier Inc. All rights reserved.

Patient characteristics associated with response to NSAID monotherapy in children with systemic juvenile idiopathic arthritis.

PubMed

Sura, Anjali; Failing, Christopher; Sturza, Julie; Stannard, Jasmine; Riebschleger, Meredith

2018-01-05

Systemic juvenile idiopathic arthritis (sJIA) is an auto-inflammatory disease characterized by fever, arthritis, and ≥1 of rash, generalized lymphadenopathy, hepato/splenomegaly, and serositis. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the initial treatments of sJIA, but there is currently no evidence indicating which children should undergo a trial of NSAID monotherapy and which should not. Our objective is to identify presentation characteristics which are associated with response and lack of response to a trial of NSAID monotherapy. This is a retrospective single-center cohort study of children diagnosed with sJIA from 2000 to 2014. Patient demographics and disease characteristics were investigated to identify predictors of response to NSAID monotherapy. Eighty-seven children were newly diagnosed with sJIA 2000-2014. Thirteen of the 51 children who received NSAID monotherapy achieved clinically inactive disease (CID) without other medications. Age at presentation (≤8 years old), initial joint count (≤5), and C-reactive protein (CRP) (≤13 mg/dL) at diagnosis were associated with achievement of CID on NSAIDs alone. Physicians were less likely to trial NSAID monotherapy if the patient had either serositis or macrophage activation syndrome (MAS) at diagnosis. Ultimate achievement of CID and time to CID were not significantly affected by whether the patient received a trial of NSAID monotherapy. While a subset of children with sJIA can achieve CID with NSAID monotherapy, we recommend against a trial in patients who are >8 years old, with >5 joints involved, or with CRP > 13 mg/dL. Patients who undergo a trial of NSAID monotherapy should follow up within 2-4 weeks to evaluate for possible need for drug escalation. Clinical trials are necessary to confirm these findings.

Protocol for the PREHAB study—Pre-operative Rehabilitation for reduction of Hospitalization After coronary Bypass and valvular surgery: a randomised controlled trial

PubMed Central

Stammers, Andrew N; Kehler, D Scott; Afilalo, Jonathan; Avery, Lorraine J; Bagshaw, Sean M; Grocott, Hilary P; Légaré, Jean-Francois; Logsetty, Sarvesh; Metge, Colleen; Nguyen, Thang; Rockwood, Kenneth; Sareen, Jitender; Sawatzky, Jo-Ann; Tangri, Navdeep; Giacomantonio, Nicholas; Hassan, Ansar; Duhamel, Todd A; Arora, Rakesh C

2015-01-01

Introduction Frailty is a geriatric syndrome characterised by reductions in muscle mass, strength, endurance and activity level. The frailty syndrome, prevalent in 25–50% of patients undergoing cardiac surgery, is associated with increased rates of mortality and major morbidity as well as function decline postoperatively. This trial will compare a preoperative, interdisciplinary exercise and health promotion intervention to current standard of care (StanC) for elective coronary artery bypass and valvular surgery patients for the purpose of determining if the intervention improves 3-month and 12-month clinical outcomes among a population of frail patients waiting for elective cardiac surgery. Methods and analysis This is a multicentre, randomised, open end point, controlled trial using assessor blinding and intent-to-treat analysis. Two-hundred and forty-four elective cardiac surgical patients will be recruited and randomised to receive either StanC or StanC plus an 8-week exercise and education intervention at a certified medical fitness facility. Patients will attend two weekly sessions and aerobic exercise will be prescribed at 40–60% of heart rate reserve. Data collection will occur at baseline, 1–2 weeks preoperatively, and at 3 and 12 months postoperatively. The primary outcome of the trial will be the proportion of patients requiring a hospital length of stay greater than 7 days. Potential impact of study The healthcare team is faced with an increasingly complex older adult patient population. As such, this trial aims to provide novel evidence supporting a health intervention to ensure that frail, older adult patients thrive after undergoing cardiac surgery. Ethics and dissemination Trial results will be published in peer-reviewed journals, and presented at national and international scientific meetings. The University of Manitoba Health Research Ethics Board has approved the study protocol V.1.3, dated 11 August 2014 (H2014:208). Trial registration number The trial has been registered on ClinicalTrials.gov, a registry and results database of privately and publicly funded clinical studies (NCT02219815). PMID:25753362

Patient navigation for American Indians undergoing cancer treatment: utilization and impact on care delivery in a regional healthcare center.

PubMed

Guadagnolo, B Ashleigh; Boylan, Amy; Sargent, Michele; Koop, David; Brunette, Deb; Kanekar, Shalini; Shortbull, Vanessa; Molloy, Kevin; Petereit, Daniel G

2011-06-15

A study was undertaken to assess patient navigation utilization and its impact on treatment interruptions and clinical trial enrollment among American Indian cancer patients. Between February 2004 and September 2009, 332 American Indian cancer patients received patient navigation services throughout cancer treatment. The patient navigation program provided culturally competent navigators to assist patients with navigating cancer therapy, obtaining medications, insurance issues, communicating with medical providers, and travel and lodging logistics. Data on utilization and trial enrollment were prospectively collected. Data for a historical control group of 70 American Indian patients who did not receive patient navigation services were used to compare treatment interruptions among those undergoing patient navigation during curative radiation therapy (subgroup of 123 patients). The median number of contacts with a navigator was 12 (range, 1-119). The median time spent with the navigator at first contact was 40 minutes (range, 10-250 minutes), and it was 15 minutes for subsequent contacts. Patients treated with radiation therapy with curative intent who underwent patient navigation had fewer days of treatment interruption (mean, 1.7 days; 95% confidence interval [CI], 1.1-2.2 days) than historical controls who did not receive patient navigation services (mean, 4.9 days; 95% CI, 2.9-6.9 days). Of the 332 patients, 72 (22%; 95% CI, 17%-26%) were enrolled on a clinical treatment trial or cancer control protocol. Patient navigation was associated with fewer treatment interruptions and relatively high rates of clinical trial enrollment among American Indian cancer patients compared with national reports. Copyright © 2010 American Cancer Society.

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

Drug evaluation: TAK-475--an oral inhibitor of squalene synthase for hyperlipidemia.

PubMed

Burnett, John R

2006-09-01

Takeda Pharmaceutical Co Ltd is developing TAK-475, a squalene synthetase inhibitor from a series of 4,1-benzoxazepine-3-acetic acid derivatives, for the potential oral treatment of hyperlipidemia. By March 2005, TAK-475 was undergoing phase III clinical trials in the US and Europe.

Mechanism and early intervention research on ALI during emergence surgery of Stanford type-A AAD: Study protocol for a prospective, double-blind, clinical trial.

PubMed

Cheng, Yi; Jin, Mu; Dong, Xiuhua; Sun, Lizhong; Liu, Jing; Wang, Rong; Yang, Yanwei; Lin, Peirong; Hou, Siyu; Ma, Yuehua; Wang, Yuefeng; Pan, Xudong; Lu, Jiakai; Cheng, Weiping

2016-10-01

Stanford type-A acute aortic dissection (AAD) is a severe cardiovascular disease demonstrating the characteristics of acute onset and rapid development, with high morbidity and mortality. The available evidence shows that preoperative acute lung injury (ALI) induced by Stanford type-A AAD is a frequent and important cause for a number of untoward consequences. However, there is no study assessing the incidence of preoperative ALI and its independent determinants before Standford type-A AAD surgery in Chinese adult patients. This is a prospective, double-blind, signal-center clinical trial. We will recruit 130 adult patients undergoing Stanford type-A AAD surgery. The incidence of preoperative ALI will be evaluated. Perioperative clinical baselines and serum variables including coagulation, fibrinolysis, inflammatory, reactive oxygen species, and endothelial cell function will be assayed. The independent factors affecting the occurrence of preoperative ALI will be identified by multiple logistic regression analysis. ClinicalTrials.gov (https://register.clinicaltrials.gov/), Registration number NCT01894334.

Prasugrel compared to clopidogrel in patients with acute coronary syndrome undergoing percutenaous coronary intervention: a Spanish model-based cost effectiveness analysis.

PubMed

Davies, A; Sculpher, M; Barrett, A; Huete, T; Sacristán, J A; Dilla, T

2013-01-01

To assess the long-term cost-effectiveness of 12 months treatment of prasugrel compared to clopidogrel in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in the Spanish health care system. A Markov state transition model was developed to estimate health outcomes, quality adjusted life years (QALYs), life years (LY), and costs over patients' lifetimes. Clinical inputs were based on an analysis of the TRITON-TIMI 38 clinical trial. Hospital readmissions captured during the trial in a sub-study of patients from eight countries (and subsequent re-hospitalisations modelled to accrue beyond the time horizon of the trial), were assigned to Spanish diagnosis-related group payment schedules to estimate hospitalisation costs. Mean total treatment costs were ?11,427 and ?10,910 for prasugrel and clopidogrel respectively. The mean cost of the study drug was ?538 higher for prasugrel vs. clopidogrel, but rehospitalisation costs at 12 months were ?79 lower for prasugrel due to reduced rates of revascularisation. Hospitalisation costs beyond 12 months were higher with prasugrel by ?55, due to longer life expectancy (+0.071 LY and +0.054 QALYs) associated with the decreased nonfatal myocardial infarction rate in the prasugrel group. The incremental cost per life year and QALY gained with prasugrel was ?7,198, and ?9,489, respectively. Considering a willingness-to-pay threshold of ?30,000/QALY gained in the Spanish setting, prasugrel represents a cost-effective option in comparison with clopidogrel among patients with ACS undergoing PCI. Copyright © 2013 SEFH. Published by AULA MEDICA. All rights reserved.

Review of Yoga Therapy During Cancer Treatment

PubMed Central

Danhauer, Suzanne C.; Addington, Elizabeth L.; Sohl, Stephanie J.; Chaoul, Alejandro; Cohen, Lorenzo

2017-01-01

Purpose Reviews of yoga research that distinguish results of trials conducted during (versus after) cancer treatment are needed to guide future research and clinical practice. We therefore conducted a review of non-randomized studies and randomized controlled trials of yoga interventions for children and adults undergoing treatment for any cancer type. Methods Studies were identified via research databases and reference lists. Inclusion criteria: (1) children or adults undergoing cancer treatment; (2) intervention stated as yoga or component of yoga; and (3) publication in English in peer-reviewed journals through October 2015. Exclusion criteria: (1) samples receiving hormone therapy only; (2) interventions involving only meditation; and (3) yoga delivered within broader cancer recovery or mindfulness-based stress reduction programs. Results Results of non-randomized (adult: n=8, pediatric: n=4) and randomized controlled trials (adult: n=13, pediatric: n=0) conducted during cancer treatment are summarized separately by age group. Findings most consistently support improvement in psychological outcomes (e.g., depression, distress, anxiety). Several studies also found that yoga enhanced quality of life, though further investigation is needed to clarify domain-specific efficacy (e.g., physical, social, cancer-specific). Regarding physical and biomedical outcomes, evidence increasingly suggests that yoga ameliorates sleep and fatigue; additional research is needed to advance preliminary findings for other treatment sequelae and stress/immunity biomarkers. Conclusions Among adults undergoing cancer treatment, evidence supports recommending yoga for improving psychological outcomes, with potential for also improving physical symptoms. Evidence is insufficient to evaluate the efficacy of yoga in pediatric oncology. We describe suggestions for strengthening yoga research methodology to inform clinical practice guidelines. PMID:28064385

Cost-effectiveness analysis of a postoperative clinical care pathway in head and neck surgery with microvascular reconstruction.

PubMed

Dautremont, Jonathan F; Rudmik, Luke R; Yeung, Justin; Asante, Tiffany; Nakoneshny, Steve C; Hoy, Monica; Lui, Amanda; Chandarana, Shamir P; Matthews, Thomas W; Schrag, Christiaan; Dort, Joseph C

2013-12-19

The objective of this study is to evaluate the cost-effectiveness of a postoperative clinical care pathway for patients undergoing major head and neck oncologic surgery with microvascular reconstruction. This is a comparative trial of a prospective treatment group managed on a postoperative clinical care pathway and a historical group managed prior to pathway implementation. Effectiveness outcomes evaluated were total hospital days, return to OR, readmission to ICU and rate of pulmonary complications. Costing perspective was from the government payer. 118 patients were included in the study. All outcomes demonstrated that the postoperative pathway group was both more effective and less costly, and is therefore a dominant clinical intervention. The overall mean pre- and post-pathway costs are $22,733 and $16,564 per patient, respectively. The incremental cost reduction associated with the postoperative pathway was $6,169 per patient. Implementing the postoperative clinical care pathway in patients undergoing head and neck oncologic surgery with reconstruction resulted in improved clinical outcomes and reduced costs.

Treatment for preventing bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgery.

PubMed

Coppola, Antonio; Windyga, Jerzy; Tufano, Antonella; Yeung, Cindy; Di Minno, Matteo Nicola Dario

2015-02-09

In people with haemophilia or other congenital bleeding disorders undergoing surgical interventions, haemostatic treatment is needed in order to correct the underlying coagulation abnormalities and minimise the bleeding risk. This treatment varies according to the specific haemostatic defect, its severity and the type of surgical procedure. The aim of treatment is to ensure adequate haemostatic coverage for as long as the bleeding risk persists and until wound healing is complete. To assess the effectiveness and safety of different haemostatic regimens (type, dose and duration, modality of administration and target haemostatic levels) administered in people with haemophilia or other congenital bleeding disorders for preventing bleeding complications during and after surgical procedures. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of the last search: 20 November 2014. Randomised and quasi-randomised controlled trials comparing any hemostatic treatment regimen to no treatment or to another active regimen in children and adults with haemophilia or other congenital bleeding disorders undergoing any surgical intervention. Two authors independently assessed trials (eligibility and risks of bias) and extracted data. Meta-analyses were performed on available and relevant data. Of the 16 identified trials, four (112 participants) were eligible for inclusion.Two trials evaluated 59 people with haemophilia A and B undergoing 63 dental extractions. Trials compared the use of a different type (tranexamic acid or epsilon-aminocaproic acid) and regimen of antifibrinolytic agents as haemostatic support to the initial replacement treatment. Neither trial specifically addressed mortality (one of this review's primary outcomes); however, in the frame of safety assessments, no fatal adverse events were reported. The second primary outcome of blood loss was assessed after surgery and these trials showed the reduction of blood loss and requirement of post-operative replacement treatment in people receiving antifibrinolytic agents compared with placebo. The remaining primary outcome of need for re-intervention was not reported by either trial.Two trials reported on 53 people with haemophilia A and B with inhibitors treated with different regimens of recombinant activated factor VII (rFVIIa) for haemostatic coverage of 33 major and 20 minor surgical interventions. Neither of the included trials specifically addressed any of the review's primary outcomes (mortality, blood loss and need for re-intervention). In one trial a high-dose rFVIIa regimen (90 μg/kg) was compared with a low-dose regimen (35 μg/kg); the higher dose showed increased haemostatic efficacy, in particular in major surgery, with shorter duration of treatment, similar total dose of rFVIIa administered and similar safety levels. In the second trial, bolus infusion and continuous infusion of rFVIIa were compared, showing similar haemostatic efficacy, duration of treatment and safety. There is insufficient evidence from randomised controlled trials to assess the most effective and safe haemostatic treatment to prevent bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgical procedures. Ideally large, adequately powered, and well-designed randomised controlled trials would be needed, in particular to address the cost-effectiveness of such demanding treatments in the light of the increasing present economic constraints, and to explore the new challenge of ageing patients with haemophilia or other congenital bleeding disorders. However, performing such trials is always a complex task in this setting and presently does not appear to be a clinical and research priority. Indeed, major and minor surgeries are effectively and safely performed in these individuals in clinical practice, with the numerous national and international recommendations and guidelines providing regimens for treatment in this setting mainly based on data from observational, uncontrolled studies.

A randomized trial of microdose leuprolide acetate protocol versus luteal phase ganirelix protocol in predicted poor responders.

PubMed

DiLuigi, Andrea J; Engmann, Lawrence; Schmidt, David W; Benadiva, Claudio A; Nulsen, John C

2011-06-30

We performed a randomized trial to compare IVF outcomes in 54 poor responder patients undergoing a microdose leuprolide acetate (LA) protocol or a GnRH antagonist protocol incorporating a luteal phase E(2) patch and GnRH antagonist in the preceding menstrual cycle. Cancellation rates, number of oocytes retrieved, clinical pregnancy rates (PR), and ongoing PRs were similar between the two groups. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Biotechnology stock prices before public announcements: evidence of insider trading?

PubMed

Overgaard, C B; van den Broek, R A; Kim, J H; Detsky, A S

2000-03-01

Unique financial challenges faced by biotechnology companies developing therapeutics have contributed to the creation of a highly sensitive market, where stock prices are capable of great fluctuation. The potential for significant financial reward and the nature of the scientific review process make this industry susceptible to illegal share trading on nonpublic information. We examined stock prices of biotechnology products before and after announcement of Phase III clinical trial and Food and Drug Administration (FDA) Advisory Panel results for indirect evidence of insider trading. Biotechnology stock prices were recorded for 98 products undergoing Phase III clinical trials and 49 products undergoing FDA Advisory Panel review between 1990 and 1998. Prices were recorded for 120 consecutive trading days before and after public announcement of these two events. We compared the average change in stock price of successful products ('winners') with unsuccessful products ('losers') before the public announcement of results for both critical events. The difference between average stock price change from 120 to 3 days before public announcement of results of Phase III clinical trial winners (+27%) and losers (-4%) was highly significant (P = 0.0007). A similar but non-significant difference was observed between the average stock price of winning (+27%) and losing products (+13%) before FDA Advisory Panel review announcements (P = 0.25). Our results provide indirect evidence that insider trading may be common in the biotechnology industry. Clinical investigators may wish to consider this issue before participating in any equity position in the biotechnology industry, especially if they are going to perform research for those companies.

Recent developments of cyclotron produced radionuclides for nuclear cardiology

NASA Astrophysics Data System (ADS)

Kulkarni, P. V.; Jansen, D. E.; Corbett, J. R.

1987-04-01

For over a decade myocardial perfusion imaging with thallium-201, a cyclotron product, has been routinely used in clinical medicine. Recent advances have allowed the efficient production of very high purity (> 99.8%) iodine-123. New metabolically active 123I labeled radiopharmaceuticals, including alkyl and phenyl fatty acids, and norepinephrine analogs, have been developed and are undergoing clinical trials. Fab' fragments of monoclonal antibodies to cardiac myosin have been labeled with indium-111 ( 111In) and are undergoing clinical evaluation for imaging myocardial infarcts. Monoclonal antibodies to platelets, fibrin, and the thrombolytic agent, tissue plasminogen activator (TPA), have recently been labeled with 111In. Together these developments in radiotracers and instrumentation should have a significant impact on the future of cardiovascular nuclear medicine. This manuscript will discuss developments in single photon emitting radiotracers for myocardial imaging.

SheppHeartCABG trial—comprehensive early rehabilitation after coronary artery bypass grafting: a protocol for a randomised clinical trial

PubMed Central

Moons, Philip; Hansen, Niels Viggo; La Cour, Søren; Olsen, Peter Skov; Gluud, Christian; Winkel, Per; Lindschou, Jane; Thygesen, Lau Caspar; Egerod, Ingrid; Berg, Selina Kikkenborg

2017-01-01

Introduction Patients undergoing coronary artery bypass graft surgery often experience a range of symptoms. Studies indicate that non-pharmacological interventions such as exercise training and psychoeducation have a positive physiological and psychological effect in early outpatient rehabilitation. The SheppHeartCABG trial will investigate the effect of early comprehensive rehabilitation in early phase rehabilitation versus usual care. The aim of this paper is to present the protocol for the SheppHeartCABG trial. Methods/analysis SheppHeartCABG is an investigator-initiated randomised clinical superiority trial with blinded outcome assessment, employing 1:1 central randomisation to rehabilitation plus usual care versus usual care alone. On the basis of a sample size calculation, 326 patients undergoing coronary artery bypass grafting will be included from two clinical sites. All patients receive usual care and patients allocated to the experimental intervention follow 4 weeks rehabilitation consisting of an exercise programme, psycho-educative consultations and a compact mindfulness programme. The primary outcome is physical function measured by the 6-min walk test. The secondary outcomes are mental health and physical activity measured by the Medical Outcome Study Short Form (SF-12), anxiety and depression measured by the Hospital Anxiety and Depression Scale questionnaire, physical, emotional and global scores by the HeartQoL questionnaire, sleep measured by the Pittsburgh Sleep Quality Index, pain measured by the Örebro Musculoskeletal Screening Questionnaire and muscle endurance measured by the sit-to-stand test. A number of explorative analyses will also be conducted. Ethics and dissemination SheppHeartCABG is approved by the regional ethics committee (no. H-4-2014-109) and the Danish Data Protection Agency (no. 30-1309) and is performed in accordance with good clinical practice and the Declaration of Helsinki in its latest form. Positive, neutral and negative results of the trial will be submitted to international peer-reviewed journals. Furthermore, results will be presented at national and international conferences relevant to the subject fields. Trial registration number NCT02290262; pre-results. PMID:28096255

Design and rationale for the Influenza vaccination After Myocardial Infarction (IAMI) trial. A registry-based randomized clinical trial.

PubMed

Fröbert, Ole; Götberg, Matthias; Angerås, Oskar; Jonasson, Lena; Erlinge, David; Engstrøm, Thomas; Persson, Jonas; Jensen, Svend E; Omerovic, Elmir; James, Stefan K; Lagerqvist, Bo; Nilsson, Johan; Kåregren, Amra; Moer, Rasmus; Yang, Cao; Agus, David B; Erglis, Andrejs; Jensen, Lisette O; Jakobsen, Lars; Christiansen, Evald H; Pernow, John

2017-07-01

Registry studies and case-control studies have demonstrated that the risk of acute myocardial infarction (AMI) is increased following influenza infection. Small randomized trials, underpowered for clinical end points, indicate that future cardiovascular events can be reduced following influenza vaccination in patients with established cardiovascular disease. Influenza vaccination is recommended by international guidelines for patients with cardiovascular disease, but uptake is varying and vaccination is rarely prioritized during hospitalization for AMI. The Influenza vaccination After Myocardial Infarction (IAMI) trial is a double-blind, multicenter, prospective, registry-based, randomized, placebo-controlled, clinical trial. A total of 4,400 patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing coronary angiography will randomly be assigned either to in-hospital influenza vaccination or to placebo. Baseline information is collected from national heart disease registries, and follow-up will be performed using both registries and a structured telephone interview. The primary end point is a composite of time to all-cause death, a new AMI, or stent thrombosis at 1 year. The IAMI trial is the largest randomized trial to date to evaluate the effect of in-hospital influenza vaccination on death and cardiovascular outcomes in patients with STEMI or non-STEMI. The trial is expected to provide highly relevant clinical data on the efficacy of influenza vaccine as secondary prevention after AMI. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Vaccines for Drug Abuse

PubMed Central

Shen, Xiaoyun; Orson, Frank M.; Kosten, Thomas R.

2012-01-01

Current medications for drug abuse have had only limited success. Anti-addiction vaccines to elicit antibodies that block the pharmacological effects of drugs have great potential for treating drug abuse. We review the status for two vaccines that are undergoing clinical trials (cocaine and nicotine) and two that are still in pre-clinical development (methamphetamine and heroin). We also outline the challenges and ethical concerns for anti-addiction vaccine development and their use as future therapeutics. PMID:22130115

Stemless shoulder arthroplasty: current status.

PubMed

Churchill, R Sean

2014-09-01

Since the original Neer humeral replacement in the 1950s, the standard primary anatomic total shoulder arthroplasty design has slowly evolved. Most recently, the humeral stem has become progressively shorter to help combat stem-related complications. Currently, there are several companies who have developed and marketed a stemless humeral arthroplasty component. Manufacturers' data for 5 stemless shoulder arthroplasty components currently on the market were analyzed and reviewed. A literature review of short-term results for stemless shoulder arthroplasty was completed. Of the stemless shoulder arthroplasty systems available on the market, 3 are currently undergoing clinical trials in the United States. The Tornier Simpliciti (Tornier, Edina, MN, USA) clinical trial began in 2011. The study with 2-year minimum follow-up results is scheduled for completion in November 2014. The Arthrex Eclipse (Arthrex, Naples, FL, USA) clinical trial was started in January 2013. The tentative study completion date is 2017. The Biomet Nano (Biomet, Warsaw, IN, USA) clinical trial began in October 2013 and also has a tentative completion date of 2017. No other clinical trial is currently under way in the United States. Early results for stemless shoulder arthroplasty indicate clinical results similar to standard stemmed shoulder arthroplasty. Radiographic analysis indicates implant stability without migration or subsidence at 2- to 3-year minimum follow-up.. Several stemless shoulder arthroplasty implants are available outside the United States. Early clinical and radiographic results are promising, but well-designed clinical studies and midterm results are lacking. Three clinical trials are currently under way in the United States with initial availability for use anticipated in 2015. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions.

PubMed

van Galen, Karin P M; Engelen, Eveline T; Mauser-Bunschoten, Evelien P; van Es, Robert J J; Schutgens, Roger E G

2015-12-24

Minor oral surgery or dental extractions (oral or dental procedures) are widely performed and can be complicated by hazardous oral bleeding, especially in people with an inherited bleeding disorder such as haemophilia or Von Willebrand disease. The amount and severity of singular bleedings depend on disease-related factors, such as the severity of the haemophilia, both local and systemic patient factors (such as periodontal inflammation, vasculopathy or platelet dysfunction) and intervention-related factors (such as the type and number of teeth extracted or the dimension of the wound surface). Similar to local haemostatic measures and suturing, antifibrinolytic therapy is a cheap, safe and potentially effective treatment to prevent bleeding complications in individuals with bleeding disorders undergoing oral or dental procedures. However, a systematic review of trials reporting outcomes after oral surgery or a dental procedure in people with an inherited bleeding disorder, with or without, the use of antifibrinolytic agents has not been performed to date. The primary objective was to assess the efficacy of local or systemic use of antifibrinolytic agents to prevent bleeding complications in people with haemophilia or Von Willebrand disease undergoing oral or dental procedures. Secondary objectives were to assess if antifibrinolytic agents can replace or reduce the need for clotting factor concentrate therapy in people with haemophilia or Von Willebrand disease and to further establish the effects of these agents on bleeding in oral or dental procedures for each of these populations. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches of the Cochrane Central Register of Controlled Trials (CENTRAL), of MEDLINE and from handsearching of journals and conference abstract books. We additionally searched the reference lists of relevant articles and reviews. We searched PubMed, Embase and The Cochrane Library. Additional searches were performed in ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP).Date of last search of the Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 14 December 2015. Randomised and quasi-randomised controlled trials in people with haemophilia or Von Willebrand disease undergoing oral or dental procedures using antifibrinolytic agents (tranexamic acid or epsilon aminocaproic acid) to prevent perioperative bleeding compared to no intervention or usual care with or without placebo. Two authors independently screened the titles and abstracts of all identified articles. Full texts were obtained for potentially relevant abstracts and two authors independently assessed these for inclusion based on the selection criteria. A third author verified trial eligibility. Two authors independently performed data extraction and risk of bias assessments using standardized forms. While there were no eligible trials in people with Von Willebrand disease identified, two randomised, double-blind, placebo-controlled trials (total of 59 participants) in people with haemophilia undergoing dental extraction were included. One trial of tranexamic acid published in 1972 included 28 participants with mild, moderate or severe haemophilia A and B and one of epsilon aminocaproic acid published in 1971 included 31 people with haemophilia with factor VIII or factor IX levels less than 15%. Overall, the two included trials showed a beneficial effect of tranexamic acid and EACA, administered systemically, in reducing the number of bleedings, the amount of blood loss and the need for therapeutic clotting factor concentrates. Regarding postoperative bleeding, the tranexamic acid trial showed a risk difference of -0.64 (95% confidence interval -0.93 to - 0.36) and the EACA trial a risk difference of -0.50 (95% confidence interval 0.77 to -0.22). The combined risk difference of both trials was -0.57 (95% confidence interval -0.76 to -0.37), with the quality of the evidence (GRADE) for this outcome is rated as moderate. Side effects occurred once and required stopping epsilon aminocaproic acid (combined risk difference of -0.03 (95% CI -0.08 to 0.13). There was heterogeneity between the two trials regarding the proportion of people with severe haemophilia included, the concomitant standard therapy and fibrinolytic agent treatment regimens used. We cannot exclude that a selection bias has occurred in the epsilon aminocaproic acid trial, but overall the risk of bias appeared to be low for both trials. Despite the discovery of a beneficial effect of systemically administered tranexamic acid and epsilon aminocaproic acid in preventing postoperative bleeding in people with haemophilia undergoing dental extraction, the limited number of randomised controlled trials identified, in combination with the small sample sizes and heterogeneity regarding standard therapy and treatment regimens between the two trials, do not allow us to conclude definite efficacy of antifibrinolytic therapy in oral or dental procedures in people with haemophilia. No trials were identified in people with Von Willebrand disease.

High-volume forced diuresis with matched hydration using the RenalGuard System to prevent contrast-induced nephropathy: A meta-analysis of randomized trials.

PubMed

Shah, Rahman; Wood, Sarah J; Khan, Sajjad A; Chaudhry, Amina; Rehan Khan, M; Morsy, Mohamed S

2017-12-01

Contrast-induced nephropathy (CIN) is a well-recognized complication of coronary angiography that is associated with poor outcomes. Several small randomized controlled trials (RCTs) have recently shown that in patients with chronic kidney disease (CKD), furosemide-induced forced diuresis with matched hydration using the RenalGuard system can prevent its occurrence. However, individual studies have been underpowered and thus cannot show significant differences in major clinical endpoints. Forced diuresis with matched hydration using the RenalGuard system improves clinical outcomes in patients undergoing coronary angiography. Scientific databases and websites were searched for relevant RCTs. The pooled risk ratios were calculated using random-effects models. The primary endpoint was CIN, and the secondary endpoints were major adverse clinical events (MACEs) and the need for renal replacement therapy. Data from 3 trials including 586 patients were analyzed. High-volume forced diuresis with matched hydration using the RenalGuard system decreased risk of CIN by 60% (risk ratio: 0.40, 95% confidence interval: 0.25 to 0.65, P < 0.001), MACE rate by 59%, and the need for renal replacement therapy by 78%, compared with the standard of care. In patients with CKD undergoing coronary angiography, high-volume forced diuresis with matched hydration using the RenalGuard system significantly reduces the risk of CIN, MACE rate, and the need for renal replacement therapy. Larger RCTs with sufficient power are needed to confirm these findings. © 2017 Wiley Periodicals, Inc.

Embedding a randomized clinical trial into an ongoing registry infrastructure: unique opportunities for efficiency in design of the Study of Access site For Enhancement of Percutaneous Coronary Intervention for Women (SAFE-PCI for Women).

PubMed

Hess, Connie N; Rao, Sunil V; Kong, David F; Aberle, Laura H; Anstrom, Kevin J; Gibson, C Michael; Gilchrist, Ian C; Jacobs, Alice K; Jolly, Sanjit S; Mehran, Roxana; Messenger, John C; Newby, L Kristin; Waksman, Ron; Krucoff, Mitchell W

2013-09-01

Women are at higher risk than men for bleeding and vascular complications after percutaneous coronary intervention (PCI). Compared with femoral access, radial access reduces these complications but may be more challenging in women because of higher rates of radial artery spasm, tortuosity, and occlusion as well as lower rates of procedure success. Whether the safety advantages of radial versus femoral access in women undergoing PCI are outweighed by reduced effectiveness has not been studied. The Study of Access site For Enhancement of PCI for Women is a prospective, randomized clinical trial comparing radial with femoral arterial access in women undergoing PCI. In conjunction with the US Food and Drug Administration's Critical Path Cardiac Safety Research Consortium, this study embeds the randomized clinical trial into the existing infrastructure of the National Cardiovascular Data Registry CathPCI Registry through the National Institute of Health's National Cardiovascular Research Infrastructure. The primary efficacy end point is a composite of bleeding (Bleeding Academic Research Consortium types 2, 3, or 5) or vascular complication requiring intervention occurring at 72 hours after PCI or by hospital discharge. The primary feasibility end point is procedure success. Secondary end points include procedure duration, contrast volume, radiation dose, quality of life, and a composite of 30-day death, vascular complication, or unplanned revascularization. © 2013.

Statistical Literacy: Data Tell a Story

ERIC Educational Resources Information Center

Sole, Marla A.

2016-01-01

Every day, students collect, organize, and analyze data to make decisions. In this data-driven world, people need to assess how much trust they can place in summary statistics. The results of every survey and the safety of every drug that undergoes a clinical trial depend on the correct application of appropriate statistics. Recognizing the…

ARDS following oesophagectomy: a comparison of two trials.

PubMed

Howells, Phillip A; Aldridge, Kerrie A; Parekh, Dhruv; Park, Daniel; Tucker, Olga; Dancer, Rachel C A; Gao, Fang; Perkins, Gavin D; Thickett, David R

2017-01-01

The Beta Agonist Lung Injury Trial-Prevention (BALTI-P) translational substudy and Vitamin D to Prevent Acute Lung Injury Following Oesophagectomy (VINDALOO) trials recruited patients undergoing oesophagectomy, 4 years apart. The acute respiratory distress syndrome (ARDS) rates were lower in the VINDALOO trial. We sought to identify changes between these two trials and identify risk factors for ARDS in oesophagectomy. There were data available from 61 patients in the BALTI-P substudy and 68 from VINDALOO. Databases were available for both trials; additional data were collected. Multivariate logistic regression was used to analyse risk factors for ARDS and postoperative complications in the cohorts combined. Logistic regression analysis showed active smoking was associated with an increase in ARDS (OR 3.91; 95% CI 1.33 to 11.5) and dihydropyridine use (OR 5.34;95% CI 1.56 to 18.3). Hospital length of stay was longer for those who took dihydropyridines (median 29 days (IQR 17-42) vs 13 days (IQR 10-18), P=0.0007) or were diabetic (median 25 days (IQR 14-39) vs 13 (IQR 10-19), P=0.023) but not for current smokers (median in never/ex-smokers 13 (IQR 10-23) vs current smokers 15 (IQR 11-20), P=0.73). Smoking cessation trials should be promoted. Dihydropyridine effects perioperatively require further clinical and mechanistic evaluation. Patients undergoing oesophagectomy are a useful model for studying perioperative ARDS.

Clinical and economic effectiveness of percutaneous ventricular assist devices for high-risk patients undergoing percutaneous coronary intervention.

PubMed

Shah, Atman P; Retzer, Elizabeth M; Nathan, Sandeep; Paul, Jonathan D; Friant, Janet; Dill, Karin E; Thomas, Joseph L

2015-03-01

Comparative effectiveness research (CER) is taking a more prominent role in formalizing hospital treatment protocols and health-care coverage policies by having health-care providers consider the impact of new devices on costs and outcomes. CER balances the need for innovation with fiscal responsibility and evidence-based care. This study compared the clinical and economic impact of percutaneous ventricular assist devices (pVAD) with intraaortic balloon pumps for high-risk patients undergoing percutaneous coronary intervention (PCI). This study conducted a review of all comparative randomized control trials of the pVADS (Impella and TandemHeart) vs IABP for patients undergoing high-risk percutaneous coronary intervention (PCI). A retrospective analysis of the 2010 and 2011 Medicare MEDPAR data files was also performed to compare procedural costs and hospital length of stay (LOS). Readmission rates between the devices were also studied. Based on available trials, there is no significant clinical benefit with pVAD compared to IABP. Use of pVADs is associated with increased length of Intensive Care Unit stay and a total longer LOS. The incremental budget impact for pVADs was $33,957,839 for the United States hospital system (2010-2011). pVADs are not associated with improved clinical outcomes, reduced hospital length of stay, or reduced readmission rates. Management of high-risk PCI and cardiogenic shock patients with IABP is more cost effective than a routine use of pVADS. Use of IABP as initial therapy in high-risk PCI and cardiogenic shock patients may result in savings of up to $2.5 billion annually of incremental costs to the hospital system.

Perceptions of Cancer Care and Clinical Trials in the Black Community: Implications for Care Coordination Between Oncology and Primary Care Teams.

PubMed

Sprague Martinez, Linda; Freeman, Elmer R; Winkfield, Karen M

2017-09-01

Despite efforts to ameliorate disparities in cancer care and clinical trials, barriers persist. As part of a multiphase community-engaged assessment, an exploratory community-engaged research partnership, forged between an academic hospital and a community-based organization, set out to explore perceptions of cancer care and cancer clinical trials by black Bostonians. Key informant interviews with health care providers and patient advocates in community health centers (CHCs), organizers from grassroots coalitions focused on cancer, informed the development of a focus group protocol. Six focus groups were conducted with black residents in Boston, including groups of cancer survivors and family members. Transcripts were coded thematically and a code-based report was generated and analyzed by community and academic stakeholders. While some participants identified clinical trials as beneficial, overall perceptions conjured feelings of fear and exploitation. Participants describe barriers to clinical trial participation in the context of cancer care experiences, which included negative interactions with providers and mistrust. Primary care physicians (PCPs) reported being levied as a trusted resource for patients undergoing care, but lamented the absence of a mechanism by which to gain information about cancer care and clinical trials. Confusion about cancer care and clinical trials persists, even among individuals who have undergone treatment for cancer. Greater coordination between PCPs and CHC care teams and oncology care teams may improve patient experiences with cancer care, while also serving as a mechanism to disseminate information about treatment options and clinical trials. Inequities in cancer care and clinical trial participation persist. The findings of this study indicate that greater coordination with primary care physicians (PCPs) and community health center (CHC) providers may be an important step for both improving the quality of cancer care in communities and increasing awareness of clinical trials. However, PCPs and CHCs are often stretched to capacity with caring for their communities. This leaves the oncology community well positioned to create programs to bridge the communication gaps and provide resources necessary to support oncologic care along the cancer continuum, from prevention through survivorship. © AlphaMed Press 2017.

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.

Transection Speed and Impact on Perioperative Inflammatory Response - A Randomized Controlled Trial Comparing Stapler Hepatectomy and CUSA Resection.

PubMed

Schwarz, Christoph; Klaus, Daniel A; Tudor, Bianca; Fleischmann, Edith; Wekerle, Thomas; Roth, Georg; Bodingbauer, Martin; Kaczirek, Klaus

2015-01-01

Parenchymal transection represents a crucial step during liver surgery and many different techniques have been described so far. Stapler resection is supposed to be faster than CUSA resection. However, whether speed impacts on the inflammatory response in patients undergoing liver resection (LR) remains unclear. This is a randomized controlled trial including 40 patients undergoing anatomical LR. Primary endpoint was transection speed (cm2/min). Secondary endpoints included the perioperative change of pro- and anti-inflammatory cytokines, overall surgery duration, length of hospital stay, morbidity and mortality. Mean transection speed was significantly higher in patients undergoing stapler hepatectomy compared to CUSA resection (CUSA: 1 (0.4) cm2/min vs. Stapler: 10.8 (6.1) cm2/min; p<0.0001). Analyzing the impact of surgery duration on inflammatory response revealed a significant correlation between IL-6 levels measured at the end of surgery and the overall length of surgery (p<0.0001, r = 0.6188). Patients undergoing CUSA LR had significantly higher increase of interleukin-6 (IL-6) after parenchymal transection compared to patients with stapler hepatectomy in the portal and hepatic veins, respectively (p = 0.028; p = 0.044). C-reactive protein levels on the first post-operative day were significantly lower in the stapler cohort (p = 0.010). There was a trend towards a reduced overall surgery time in patients with stapler LR, especially in the subgroup of patients undergoing minor hepatectomies (p = 0.020). Liver resection using staplers is fast, safe and suggests a diminished inflammatory response probably due to a decreased parenchymal transection time. ClinicalTrials.gov NCT01785212.

Oral anticoagulant use in cardiovascular disorders: a perspective on present and potential indications for rivaroxaban.

PubMed

Camm, A John; Fox, Keith A A

2018-05-21

Four non-vitamin-K-antagonist oral anticoagulants (NOACs) have been approved for use in various cardiovascular indications. The direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban and rivaroxaban are now increasingly used in clinical practice. For some of these agents, available data from real-world studies support the efficacy and safety data in phase III clinical trials. This review aims to summarize the current status of trials and observational studies of oral anticoagulant use over the spectrum of cardiovascular disorders (excluding venous thrombosis), provide a reference source beyond stroke prevention for atrial fibrillation (AF) and examine the potential for novel applications in the cardiovascular field. We searched the recent literature for data on completed and upcoming trials of oral anticoagulants with a particular focus on rivaroxaban. Recent data in specific patient subgroups, such as patients with AF undergoing catheter ablation or cardioversion, have led to an extended approval for rivaroxaban, whereas the other NOACs have ongoing or recently completed trials in this setting. However, there are unmet medical needs for several arterial thromboembolic-related conditions, including patients with: AF and acute coronary syndrome, AF and coronary artery disease undergoing elective percutaneous coronary intervention, coronary artery disease and peripheral artery disease, implanted cardiac devices, and embolic stroke of unknown source. NOACs may provide alternative treatment options in areas of unmet need, and numerous studies are underway to assess their benefit-risk profiles in these settings.

Role of genetic testing in patients undergoing percutaneous coronary intervention.

PubMed

Moon, Jae Youn; Franchi, Francesco; Rollini, Fabiana; Rivas Rios, Jose R; Kureti, Megha; Cavallari, Larisa H; Angiolillo, Dominick J

2018-02-01

Variability in individual response profiles to antiplatelet therapy, in particular clopidogrel, is a well-established phenomenon. Genetic variations of the cytochrome P450 (CYP) 2C19 enzyme, a key determinant in clopidogrel metabolism, have been associated with clopidogrel response profiles. Moreover, the presence of a CYP2C19 loss-of-function allele is associated with an increased risk of atherothrombotic events among clopidogrel-treated patients undergoing percutaneous coronary interventions (PCI), prompting studies evaluating the use of genetic tests to identify patients who may be potential candidates for alternative platelet P2Y 12 receptor inhibiting therapies (prasugrel or ticagrelor). Areas covered: The present manuscript provides an overview of genetic factors associated with response profiles to platelet P2Y 12 receptor inhibitors and their clinical implications, as well as the most recent developments and future considerations on the role of genetic testing in patients undergoing PCI. Expert commentary: The availability of more user-friendly genetic tests has contributed towards the development of many ongoing clinical trials and personalized medicine programs for patients undergoing PCI. Results of pilot investigations have shown promising results, which however need to be confirmed in larger-scale studies to support the routine use of genetic testing as a strategy to personalize antiplatelet therapy and improve clinical outcomes.

Role of Genetic Testing in Patients undergoing Percutaneous Coronary Intervention

PubMed Central

Moon, Jae Youn; Franchi, Francesco; Rollini, Fabiana; Rios, Jose R. Rivas; Kureti, Megha; Cavallari, Larisa H.; Angiolillo, Dominick J.

2017-01-01

Introduction Variability in individual response profiles to antiplatelet therapy, in particular clopidogrel, is a well-established phenomenon. Genetic variations of the cytochrome P450 (CYP) 2C19 enzyme, a key determinant in clopidogrel metabolism, have been associated with clopidogrel response profiles. Moreover, the presence of a CYP2C19 loss-of-function allele is associated with an increased risk of atherothrombotic events among clopidogrel-treated patients undergoing percutaneous coronary interventions (PCI), prompting studies evaluating the use of genetic tests to identify patients who may be potential candidates for alternative platelet P2Y12 receptor inhibiting therapies (prasugrel or ticagrelor). Areas covered The present manuscript provides an overview of genetic factors associated with response profiles to platelet P2Y12 receptor inhibitors and their clinical implications, as well as the most recent developments and future considerations on the role of genetic testing in patients undergoing PCI. Expert Commentary The availability of more user-friendly genetic tests has contributed towards the development of many ongoing clinical trials and personalized medicine programs for patients undergoing PCI. Results of pilot investigations have shown promising results, which however need to be confirmed in larger-scale studies to support the routine use of genetic testing as a strategy to personalize antiplatelet therapy and improve clinical outcomes. PMID:28689434

Non-small cell lung cancer clinical trials requiring biopsies with biomarker-specific results for enrollment provide unique challenges.

PubMed

Spiegel, Marshall L; Goldman, Jonathan W; Wolf, Brian R; Nameth, Danielle J; Grogan, Tristan R; Lisberg, Aaron E; Wong, Deborah J L; Ledezma, Blanca A; Mendenhall, Melody A; Genshaft, Scott J; Gutierrez, Antonio J; Abtin, Fereidoun; Wallace, W Dean; Adame, Carlos R; McKenzie, Jordan R; Abarca, Phillip A; Li, Alice J; Strunck, Jennifer L; Famenini, Sina; Carroll, James M; Tucker, D Andrew; Sauer, Lauren M; Moghadam, Nima M; Elashoff, David A; Abaya, Christina D; Brennan, Meghan B; Garon, Edward B

2017-12-15

Clinical trials in lung cancer increasingly require patients to provide fresh tumor tissue as a prerequisite to enrollment. The effects of this requirement on enrollment rates, enrollment durations, and patient selection have not been fully elucidated. The authors retrospectively reviewed data generated by patients who consented to 1 or more interventional lung cancer clinical trials at the University of California-Los Angeles Jonsson Comprehensive Cancer Center between January 2013 and December 2014. Trials were considered to require a biopsy when enrollment was conditional on the procurement of tissue without intervening therapy between procurement and enrollment. In total, 311 patients underwent 368 screening incidents for 1 or more of 19 trials. Trials that required a new biopsy had a longer median screening duration (34 vs 14 days) than trials that did not require a biopsy (P < .001). Trials that required a biopsy had a greater screen failure rate (49.1% vs 26.5%; P < .001), which was largely driven by patients who did not undergo the required biopsy or lacked the required biomarker. Worsening performance status led to the majority of screen failures (56.5%) among biomarker-eligible patients. Although the scientific benefits of obtaining a new biopsy and requiring specific results for trial enrollment are clear, these requirements lead to a lengthening of the screening period, which, in some patients, is associated with clinical decline before enrollment. Implications for the interpretation of data from studies of this design should be explored. Cancer 2017;123:4800-7. © 2017 American Cancer Society. © 2017 American Cancer Society.

Comparison of high glucose concentration blood and crystalloid cardioplegia in paediatric cardiac surgery: a randomized clinical trial

PubMed Central

Mimic, Branko; Ilic, Slobodan; Vulicevic, Irena; Milovanovic, Vladimir; Tomic, Danijela; Mimic, Ana; Stankovic, Sanja; Zecevic, Tatjana; Davies, Ben; Djordjevic, Miroslav

2016-01-01

OBJECTIVES This study investigates the effects of high glucose content on patients undergoing cold crystalloid versus cold blood cardioplegia in terms of early clinical results, functional myocardial recovery and ischaemia–reperfusion injury in patients undergoing repair of acyanotic cardiac lesions. METHODS Patients were randomly assigned to receive either crystalloid (n = 31) or blood cardioplegia (n = 31). Early clinical results were assessed. Changes in left ventricular fractional shortening, arterial blood lactate levels, central venous saturation, cardiac Troponin I release and blood glucose concentration were measured during the first 24 h after ischaemia. RESULTS There was no significant difference in clinical outcomes and postoperative complication rates between groups. The postoperative changes in left ventricular function, lactate levels, central venous saturation and Troponin I were not significantly different between groups. The use of crystalloid cardioplegia was associated with significant increases in serum glucose compared with blood cardioplegia. CONCLUSIONS A high glucose content blood cardioplegia does not show any advantage compared with crystalloid cardioplegia in terms of clinical outcomes, functional recovery and the degree of ischaemic injury in infants and children undergoing repair of acyanotic heart lesions. High glucose concentration of the cardioplegic solution might potentiate ischaemia–reperfusion injury and diminish the beneficial effects of blood cardioplegia. PMID:26831677

Extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing intrauterine insemination: A randomized controlled trial

PubMed Central

2011-01-01

Background The aim of this randomized controlled trial was to compare the efficacy of extended letrozole regimen with clomiphene citrate in women with unexplained infertility undergoing superovulation and intrauterine insemination (IUI). Methods Two hundred and fourteen patients with unexplained infertility were randomized into two equal groups using computer generated list and were treated by either letrozole 2.5 mg/day from cycle day 1 to 9 (extended letrozole group, 211 cycles) or clomiphene citrate 100 mg/day from cycle day 3 to 7 (clomiphene citrate group,210 cycles). Intrauterine insemination was performed 36 to 40 hours after HCG administration. Results Both groups were comparable with regard to number of mature follicles (2.24 +/- 0.80 Vs 2.13 +/- 0.76) and the day of HCG administration. Serum estradiol was significantly greater in clomiphene citrate group (356 +/- 151 Vs 822 +/- 302 pg/ml, P = < 0.001) and the endometrial thickness was significantly greater in extended letrozole group (9.10 +/- 1.84 Vs 8.18 +/- 1.93 mm, P = < 0.001).The pregnancy rate per cycle and cumulative pregnancy rate were significantly greater in extended letrozole group (18.96% Vs 11.43% and 37.73% Vs 22.86%, respectively). Conclusion The extended letrozole regimen had a superior efficacy as compared with clomiphene citrate in patients of unexplained infertility undergoing superovulation and IUI. Trial registration ClinicalTrials.gov, NCT01232075 PMID:21693030

Protection of xenon against postoperative oxygen impairment in adults undergoing Stanford Type-A acute aortic dissection surgery

PubMed Central

Jin, Mu; Cheng, Yi; Yang, Yanwei; Pan, Xudong; Lu, Jiakai; Cheng, Weiping

2017-01-01

Abstract Objectives: The available evidence shows that hypoxemia after Stanford Type-A acute aortic dissection (AAD) surgery is a frequent cause of several adverse consequences. The pathogenesis of postoperative hypoxemia after AAD surgery is complex, and ischemia/reperfusion and inflammation are likely to be underlying risk factors. Xenon, recognized as an ideal anesthetic and anti-inflammatory treatment, might be a possible treatment for these adverse effects. Methods/Design: The trial is a prospective, double-blind, 4-group, parallel, randomized controlled, a signal-center clinical trial. We will recruit 160 adult patients undergoing Stanford type-A AAD surgery. Patients will be allocated a study number and will be randomized on a 1:1:1:1 basis to receive 1 of the 3 treatment options (pulmonary inflated with 50% xenon, 75% xenon, or 100% xenon) or no treatment (control group, pulmonary inflated with 50% nitrogen). The aims of this study are to clarify the lung protection capability of xenon and its possible mechanisms in patients undergoing the Stanford type-A AAD surgery. Discussion: This trial uses an innovative design to account for the xenon effects of postoperative oxygen impairment, and it also delineates the mechanism for any benefit from xenon. The investigational xenon group is considered a treatment intervention, as it includes 3 groups of pulmonary static inflation with 50%, 75%, and 100% xenon. It is suggested that future trials might define an appropriate concentration of xenon for the best practice intervention. PMID:28834897

The Effects of Preoperative Volume Replacement in Diabetic Patients Undergoing Coronary Artery Bypass Grafting Surgery: Protocol for a Randomized Controlled Trial (VeRDiCT Trial)

PubMed Central

Clout, Madeleine; Harris, Tracy; Rogers, Chris; Culliford, Lucy; Taylor, Jodi; Angelini, Gianni; Narayan, Pradeep; Reeves, Barnaby; Hillier, James; Ashton, Kate; Sarkar, Kunal

2017-01-01

Background Diabetes mellitus is a major risk factor for prolonged hospital stays, renal failure, and mortality in patients having coronary artery bypass grafting (CABG). Complications pose a serious threat to patients and prolong intensive care and hospital stays. Low glomerular filtration rate (GFR) due to existing renal impairment or volume depletion may exacerbate acute renal impairment/failure in these patients. Preoperative volume replacement therapy (VRT) is reported to increase the GFR and we hypothesize that VRT will reduce renal impairment and related complications in diabetic patients. Objective The objective of this study is to establish the efficacy of preoperative VRT in reducing postoperative complications in diabetic patients undergoing CABG surgery. Time to “fit for discharge”, incidence of postoperative renal failure, cardiac injury, inflammation, and other health outcomes will be investigated. Methods In this open parallel group randomized controlled trial, 170 diabetic patients undergoing elective or urgent CABG surgery received 1 mL/kg/hour of Hartmann’s solution for 12 consecutive hours prior to surgery, versus routine care. The primary outcome was time until participants were “fit for discharge”, which is defined as presence of: normal temperature, pulse, and respiration; normal oxygen saturation on air; normal bowel function; and physical mobility. Secondary outcomes included: incidence of renal failure; markers of renal function, inflammation, and cardiac damage; operative morbidity; intensive care stay; patient-assessed outcome, including the Coronary Revascularization Outcome Questionnaire; and use of hospital resources. Results Recruitment started in July 2010. Enrolment for the study was completed in July 2014. Data analysis commenced in December 2016. Study results will be submitted for publication in the summer of 2017. Conclusions VRT is a relatively easy treatment to administer in patients undergoing surgical procedures who are at risk of renal failure. This experimental protocol will increase scientific and clinical knowledge of VRT in diabetic patients undergoing elective or urgent CABG surgery. Findings supporting the efficacy of this intervention could easily be implemented in the health care system. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 02159606; http://www.controlled-trials.com/ISRCTN02159606 (Archived by WebCite at http://www.webcitation.org/6rDkSSkkK) PMID:28630035

Thromboprophylaxis With Apixaban in Patients Undergoing Major Orthopedic Surgery: Meta-Analysis and Trial-Sequential Analysis.

PubMed

Caldeira, Daniel; Rodrigues, Filipe B; Pinto, Fausto J; Ferreira, Joaquim J; Costa, João

2017-01-01

Venous thromboembolism (VTE) is a potentially fatal complication of orthopedic surgery, and until recently, few antithrombotic compounds were available for postoperative thromboprophylaxis. The introduction of the non-vitamin K antagonists oral anticoagulants (NOAC), including apixaban, has extended the therapeutic armamentarium in this field. Therefore, estimation of NOAC net clinical benefit in comparison with the established treatment is needed to inform clinical decision making. Systematic review to assess the efficacy and safety of apixaban 2.5 mg twice a day versus low-molecular-weight heparins (LMWH) for thromboprophylaxis in patients undergoing knee or hip replacement. MEDLINE, Embase, and CENTRAL were searched from inception to September 2016, other systematic reviews, reference lists, and experts were consulted. All major orthopedic surgery randomized controlled trials comparing apixaban 2.5 mg twice daily with LMWH, reporting thrombotic and bleeding events. Two independent reviewers, using a predetermined form. The Cochrane tool to assess risk bias was used by two independent authors. RevMan software was used to estimate pooled risk ratio (RR) and 95% confidence intervals (95% CI) using random-effects meta-analysis. Trial sequential analysis (TSA) was performed in statistical significant results to evaluate whether cumulative sample size was powered for the obtained effect. Overall confidence in cumulative evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group methodology. Four studies comparing apixaban 2.5 mg twice daily with LMWH were included, with a total of 11.828 patients (55% undergoing knee and 45% hip replacement). The overall risk of bias across studies was low. In comparison with LMWH (all regimens), apixaban showed a significantly lower risk of VTE events and overall mortality combined (RR: 0.63, 95% CI: 0.42-0.95, I 2 = 84%, n = 8346), but not of major VTE events (RR: 0.62, 95% CI: 0.32-1.19, I 2 = 63%, n = 9493), or of symptomatic VTE events and VTE-related mortality combined (RR: 1.14, 95% CI: 0.68-1.90, I 2 = 0%, n = 11 879). Trial sequential analysis showed that the risk reduction obtained for VTE and mortality was based on underpowered cumulative sample size and effect dimension. Subgroup analysis according to LMWH regimens showed that apixaban reduced the risk of VTE events and overall mortality, and major VTE events, when compared with LMWH once daily, without differences between apixaban and LMWH twice daily. There is low to moderate evidence that in patients undergoing knee or hip replacement, apixaban seems equally effective and safe to LMWH twice a day. When compared with LMWH once a day, apixaban seems a superior thromboprophylaxis option. However, the results are underpowered which precludes definite answers regarding the true net clinical benefit of apixaban versus LMWH in this clinical context.

Arthroscopic Surgery or Physical Therapy for Patients With Femoroacetabular Impingement Syndrome: A Randomized Controlled Trial With 2-Year Follow-up.

PubMed

Mansell, Nancy S; Rhon, Daniel I; Meyer, John; Slevin, John M; Marchant, Bryant G

2018-05-01

Arthroscopic hip surgery has risen 18-fold in the past decade; however, there is a dearth of clinical trials comparing surgery with nonoperative management. To determine the comparative effectiveness of surgery and physical therapy for femoroacetabular impingement syndrome. Randomized controlled trial; Level of evidence, 1. Patients were recruited from a large military hospital after referral to the orthopaedic surgery clinic and were eligible for surgery. Of 104 eligible patients, 80 elected to participate, and the majority were active-duty service members (91.3%). No patients withdrew because of adverse events. The authors randomly selected patients to undergo either arthroscopic hip surgery (surgery group) or physical therapy (rehabilitation group). Patients in the rehabilitation group began a 12-session supervised clinic program within 3 weeks, and patients in the surgery group were scheduled for the next available surgery at a mean of 4 months after enrollment. Patient-reported outcomes of pain, disability, and perception of improvement over a 2-year period were collected. The primary outcome was the Hip Outcome Score (HOS; range, 0-100 [lower scores indicating greater disability]; 2 subscales: activities of daily living and sport). Secondary measures included the International Hip Outcome Tool (iHOT-33), Global Rating of Change (GRC), and return to work at 2 years. The primary analysis was on patients within their original randomization group. Statistically significant improvements were seen in both groups on the HOS and iHOT-33, but the mean difference was not significant between the groups at 2 years (HOS activities of daily living, 3.8 [95% CI, -6.0 to 13.6]; HOS sport, 1.8 [95% CI, -11.2 to 14.7]; iHOT-33, 6.3 [95% CI, -6.1 to 18.7]). The median GRC across all patients was that they "felt about the same" (GRC = 0). Two patients assigned to the surgery group did not undergo surgery, and 28 patients in the rehabilitation group ended up undergoing surgery. A sensitivity analysis of "actual surgery" to "no surgery" did not change the outcome. Twenty (33.3%) patients who underwent surgery and 4 (33.3%) who did not undergo surgery were medically separated from military service at 2 years. There was no significant difference between the groups at 2 years. Most patients perceived little to no change in status at 2 years, and one-third of military patients were not medically fit for duty at 2 years. Limitations include a single hospital, a single surgeon, and a high rate of crossover. Registration: NCT01993615 ( ClinicalTrials.gov identifier).

Grating visual acuity results in the early treatment for retinopathy of prematurity study.

PubMed

Dobson, Velma; Quinn, Graham E; Summers, C Gail; Hardy, Robert J; Tung, Betty; Good, William V

2011-07-01

To compare grating (resolution) visual acuity at 6 years of age in eyes that received early treatment (ET) for high-risk prethreshold retinopathy of prematurity (ROP) with that in eyes that underwent conventional management (CM). In a randomized clinical trial, infants with bilateral, high-risk prethreshold ROP (n = 317) had one eye undergo ET and the other eye undergo CM, with treatment only if ROP progressed to threshold severity. For asymmetric cases (n = 84), the high-risk prethreshold eye was randomized to ET or CM. Grating visual acuity measured at 6 years of age by masked testers using Teller acuity cards. Monocular grating acuity results were obtained from 317 of 370 surviving children (85.6%). Analysis of grating acuity results for all study participants with high-risk prethreshold ROP showed no statistically significant overall benefit of ET (18.1% vs 22.8% unfavorable outcomes; P = .08). When the 6-year grating acuity results were analyzed according to a clinical algorithm (high-risk types 1 and 2 prethreshold ROP), a benefit was seen in type 1 eyes (16.4% vs 25.2%; P = .004) undergoing ET, but not in type 2 eyes (21.3% vs 15.9%; P = .29). Early treatment of eyes with type 1 ROP improves grating acuity outcomes, but ET for eyes with type 2 ROP does not. APPLICATION TO CLINICAL MEDICINE: Type 1 eyes should be treated early; however, based on acuity results at 6 years of age, type 2 eyes should be cautiously monitored for progression to type 1 ROP. Trial Registration clinicaltrials.gov Identifier: NCT00027222.

Use of Dual Antiplatelet Therapy and Patient Outcomes in Those Undergoing Percutaneous Coronary Intervention: The ROCKET AF Trial.

PubMed

Sherwood, Matthew W; Cyr, Derek D; Jones, W Schuyler; Becker, Richard C; Berkowitz, Scott D; Washam, Jeffrey B; Breithardt, Günter; Fox, Keith A A; Halperin, Jonathan L; Hankey, Graeme J; Singer, Daniel E; Piccini, Jonathan P; Nessel, Christopher C; Mahaffey, Kenneth W; Patel, Manesh R

2016-08-22

The authors assessed the use of dual antiplatelet therapy (DAPT) and outcomes in patients undergoing percutaneous coronary intervention (PCI) during the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation). The frequency, patterns, and outcomes when adding DAPT to non-vitamin K antagonist oral anticoagulants in the setting of PCI in patients with AF are largely unknown. The study population included all patients in the treatment group of the ROCKET AF trial divided by the receipt of PCI during follow-up. Clinical characteristics, PCI frequency, and rates of DAPT were reported. Clinical outcomes were adjudicated independently as part of the trial. Among 14,171 patients, 153 (1.1%) underwent PCI during a median 806 days of follow-up. Patients treated with rivaroxaban were significantly less likely to undergo PCI compared with warfarin-treated patients (61 vs. 92; p = 0.01). Study drug was continued during PCI in 81% of patients. Long-term DAPT (≥30 days) was used in 37% and single antiplatelet therapy in 34%. A small number switched from DAPT to monotherapy within 30 days of PCI (n = 19 [12.3%]) and 15% of patients received no antiplatelet therapy after PCI. Rates of stroke/systemic embolism and major bleeding events were high in post-PCI patients (4.5/100 patient-years and 10.2/100 patient-years) in both treatment groups. In patients with AF at moderate to high risk for stroke, PCI occurred in <1% per year. DAPT was used in a variable manner, with the majority of patients remaining on study drug after PCI. Rates of both thrombotic and bleeding events were high after PCI, highlighting the need for studies to determine the optimal antithrombotic therapy. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The importance of intraoperative selenium blood levels on organ dysfunction in patients undergoing off-pump cardiac surgery: a randomised controlled trial.

PubMed

Stevanovic, Ana; Coburn, Mark; Menon, Ares; Rossaint, Rolf; Heyland, Daren; Schälte, Gereon; Werker, Thilo; Wonisch, Willibald; Kiehntopf, Michael; Goetzenich, Andreas; Rex, Steffen; Stoppe, Christian

2014-01-01

Cardiac surgery is accompanied by an increase of oxidative stress, a significantly reduced antioxidant (AOX) capacity, postoperative inflammation, all of which may promote the development of organ dysfunction and an increase in mortality. Selenium is an essential co-factor of various antioxidant enzymes. We hypothesized a less pronounced decrease of circulating selenium levels in patients undergoing off-pump coronary artery bypass (OPCAB) surgery due to less intraoperative oxidative stress. In this prospective randomised, interventional trial, 40 patients scheduled for elective coronary artery bypass grafting were randomly assigned to undergo either on-pump or OPCAB-surgery, if both techniques were feasible for the single patient. Clinical data, myocardial damage assessed by myocard specific creatine kinase isoenzyme (CK-MB), circulating whole blood levels of selenium, oxidative stress assessed by asymmetric dimethylarginine (ADMA) levels, antioxidant capacity determined by glutathionperoxidase (GPx) levels and perioperative inflammation represented by interleukin-6 (IL-6) levels were measured at predefined perioperative time points. At end of surgery, both groups showed a comparable decrease of circulating selenium concentrations. Likewise, levels of oxidative stress and IL-6 were comparable in both groups. Selenium levels correlated with antioxidant capacity (GPx: r = 0.720; p<0.001) and showed a negative correlation to myocardial damage (CK-MB: r =  -0.571, p<0.001). Low postoperative selenium levels had a high predictive value for the occurrence of any postoperative complication. OPCAB surgery is not associated with less oxidative stress and a better preservation of the circulating selenium pool than on-pump surgery. Low postoperative selenium levels are predictive for the development of complications. ClinicalTrials.gov NCT01409057.

Does Age Influence Cardiac Resynchronization Therapy Use and Outcome?

PubMed

Heidenreich, Paul A; Tsai, Vivian; Bao, Haikun; Curtis, Jeptha; Goldstein, Mary; Curtis, Lesley; Hernandez, Adrian; Peterson, Pamela; Turakhia, Mintu P; Masoudi, Frederick A

2015-06-01

This study sought to describe the use of CRT-D and its association with survival for older patients. Many patients who receive cardiac resynchronization therapy with defibrillator (CRT-D) in practice are older than those included in clinical trials. We identified patients undergoing ICD implantation in the National Cardiovascular Disease Registry (NCDR) ICD registry from 2006 to 2009, who also met clinical trial criteria for CRT, including left ventricular ejection fraction (LVEF) ≤35%, QRS ≥120 ms, and New York Heart Association (NYHA) functional class III or IV. NCDR registry data were linked to the social security death index to determine the primary outcome of time to death from any cause. We identified 70,854 patients from 1,187 facilities who met prior trial criteria for CRT-D. The mean age of the 58,147 patients receiving CRT-D was 69.4 years with 6.4% of patients age 85 or older. CRT use was 80% or higher among candidates in all age groups. Follow-up was available for 42,285 patients age ≥65 years at 12 months. Receipt of CRT-D was associated with better survival at 1 year (82.1% vs. 77.1%, respectively) and 4 years (54.0% vs. 46.2% , respectively) than in those receiving only an ICD (p < 0.001). The CRT association with improved survival was not different for different age groups (p = 0.86 for interaction). More than 80% of older patients undergoing ICD implantation who were candidates for a CRT-D received the combined device. Mortality in older patients undergoing ICD implantation was high but was lower for those receiving CRT-D. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Review of yoga therapy during cancer treatment.

PubMed

Danhauer, Suzanne C; Addington, Elizabeth L; Sohl, Stephanie J; Chaoul, Alejandro; Cohen, Lorenzo

2017-04-01

Reviews of yoga research that distinguish results of trials conducted during (versus after) cancer treatment are needed to guide future research and clinical practice. We therefore conducted a review of non-randomized studies and randomized controlled trials of yoga interventions for children and adults undergoing treatment for any cancer type. Studies were identified via research databases and reference lists. Inclusion criteria were the following: (1) children or adults undergoing cancer treatment, (2) intervention stated as yoga or component of yoga, and (3) publication in English in peer-reviewed journals through October 2015. Exclusion criteria were the following: (1) samples receiving hormone therapy only, (2) interventions involving meditation only, and (3) yoga delivered within broader cancer recovery or mindfulness-based stress reduction programs. Results of non-randomized (adult n = 8, pediatric n = 4) and randomized controlled trials (adult n = 13, pediatric n = 0) conducted during cancer treatment are summarized separately by age group. Findings most consistently support improvement in psychological outcomes (e.g., depression, distress, anxiety). Several studies also found that yoga enhanced quality of life, though further investigation is needed to clarify domain-specific efficacy (e.g., physical, social, cancer-specific). Regarding physical and biomedical outcomes, evidence increasingly suggests that yoga ameliorates sleep and fatigue; additional research is needed to advance preliminary findings for other treatment sequelae and stress/immunity biomarkers. Among adults undergoing cancer treatment, evidence supports recommending yoga for improving psychological outcomes, with potential for also improving physical symptoms. Evidence is insufficient to evaluate the efficacy of yoga in pediatric oncology. We describe suggestions for strengthening yoga research methodology to inform clinical practice guidelines.

The effect of simethicone on postoperative ileus in patients undergoing colorectal surgery (SPOT), a randomized controlled trial.

PubMed

Springer, Jeremy E; Elkheir, Shiraz; Eskicioglu, Cagla; Doumouras, Aristithes G; Kelly, Stephen; Yang, Ilun; Forbes, Shawn

2018-06-12

Postoperative ileus is a poorly understood multifactorial outcome following colorectal surgery that presents significant clinical challenges and contributes to increased morbidity, length of stay, and healthcare cost. To date, there are few pharmacological interventions that shorten the duration of postoperative ileus. This study is the first to evaluate the efficacy of simethicone in treating postoperative ileus symptoms in patients undergoing colorectal surgery. A multicenter, double-blinded, placebo controlled randomized controlled trial. This trial was conducted at two academic tertiary care centres in Ontario, Canada. 118 patients undergoing colorectal surgery. Patients were randomized to receive either a five-day course of oral simethicone (n = 58) or a placebo (n = 60). The primary outcome was time to first passage of flatus. Secondary outcomes included time to first bowel movement, postoperative length of stay, and postoperative pain. Statistical analyses were performed on an intention-to-treat basis. Statistical significance set at p = 0.05. The median time to first passage of flatus in simethicone arm was 25.2 h and 26.7 h in controls (P = 0.98). There were no significant differences in the median time to first bowel movement (simethicone = 41.1 h vs. control = 42.9 h, P = 0.91) or median length of hospital stay (simethicone = 4.5 days vs. control = 4.0 days, P = 0.63). This study failed to show a difference in return of gastrointestinal motility in patients receiving simethicone following colorectal surgery. Postoperative ileus remains a significant clinical and economic burden to the healthcare system and further research is needed to identify a reliable and effective method of treatment. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

[Glycaemic management in type 1 and 2 diabetes patients undergoing interventional cardiology procedures. Heart and Diabetes Working Group. Sociedad Espan˜ola de Cardiologı´a. Sociedad Espan˜ola de Diabetes].

PubMed

Alonso-García, Angeles; Moreno Gómez, Raúl; Miranda Guardiola, Faustino; Artola-Menéndez, Sara; Lisbona-Gil, Arturo

2012-03-03

Despite the growing number of therapeutic alternatives available as well as general reviews and treatment guidelines for the treatment of diabetes, physicians are often left without a clear pathway of therapy to follow in specific clinical contexts such as interventional cardiology. The present document proposes a consensus treatment algorithm, based both on a critical appraisal of evidence from recent clinical trials and on value judgements supported by the authors' collective clinical knowledge and experience, in an attempt to guide practitioners when choosing the most appropriate alternatives in the context of glycemic management in type 1 and 2 diabetic patients scheduled to undergo interventional cardiology procedures in a haemodynamic laboratory. Copyright © 2011 Elsevier España, S.L. All rights reserved.

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

Bookman, M.A.; Bast, R.C. Jr.

Small volume residual peritoneal disease in patients undergoing therapy for ovarian carcinoma remains an attractive, but elusive, target for immunobiological therapy. Hypothetical advantages and disadvantages of regional peritoneal therapy are being better defined through increased clinical experience and more sophisticated animal models. Developments in cytokine biology, adoptive cellular therapy, monoclonal antibody conjugation, and molecular biology continue to provide an exciting, and nearly overwhelming, array of reagents for clinical evaluation. Ongoing and anticipated investigational trials should provide intriguing data in years to follow.198 references.

Human antitransforming growth factor beta(2) monoclonal antibody--a new modulator of wound healing in trabeculectomy: a randomized placebo controlled clinical study.

PubMed

Siriwardena, Dilani; Khaw, Peng T; King, Anthony J; Donaldson, Mark L; Overton, Barry M; Migdal, Clive; Cordeiro, M Francesca

2002-03-01

The human monoclonal antibody that neutralizes the growth factor TGFbeta(2) (CAT-152) safely and effectively inhibits in vitro and in vivo models of conjunctival scarring. This phase I/IIa clinical trial was designed to assess the safety and tolerability of CAT-152 in patients undergoing trabeculectomy. Prospective randomized placebo-controlled clinical trial. Twenty-four patients who were due to undergo primary trabeculectomy at Moorfields or Western Eye Hospitals in London, England, were recruited for this study and randomly assigned to treatment with either CAT-152 (100 microg in 100 microl) (n = 16) or placebo (n = 8). The treatment regimen was a series of four 100-microl subconjunctival injections, given immediately before and after surgery, and at 1 day and 1 week postoperatively. Assessment consisted of a full ophthalmic examination with recordings of the logarithm of the minimum angle of resolution visual acuities performed at baseline and at set intervals after surgery. Any adverse events were recorded. Logarithm of the minimum angle of resolution visual acuity, intraocular pressure, complications, and adverse events. The results of 12 month's follow-up on all patients are documented. There were no statistically significant differences in the incidence of complications between the two groups, and no serious adverse events related to the study drug occurred. Blebs after CAT-152 antibody treatment were diffuse, noncystic, and nonavascular, unlike blebs associated with antimetabolites. The fall in intraocular pressure was greater in the CAT-152 group at 3 and 6 months (P < 0.05) and approached statistical significance at 12 months. There was a trend toward less intervention in those patients treated with CAT-152. The small number of patients included limited the power of the study (34%) to detect a difference between groups. Sixteen patients in each arm of the study would be required to obtain a power of 90% with a 5% significance level. This is the first clinical study of CAT-152 in patients undergoing glaucoma filtration surgery. CAT-152 seems to be well tolerated, and based on these results further multicenter trials are underway.

Left atrial concomitant surgical ablation for treatment of atrial fibrillation in cardiac surgery: A meta-analysis of randomized controlled trials

PubMed Central

Wang, Chunguo; Ye, Minhua; Lin, Jiang; Jin, Jiang; Hu, Quanteng; Zhu, Chengchu; Chen, Baofu

2018-01-01

Introduction Surgical ablation is a generally established treatment for patients with atrial fibrillation undergoing concomitant cardiac surgery. Left atrial (LA) lesion set for ablation is a simplified procedure suggested to reduce the surgery time and morbidity after procedure. The present meta-analysis aims to explore the outcomes of left atrial lesion set versus no ablative treatment in patients with AF undergoing cardiac surgery. Methods A literature research was performed in six database from their inception to July 2017, identifying all relevant randomized controlled trials (RCTs) comparing left atrial lesion set versus no ablative treatment in AF patient undergoing cardiac surgery. Data were extracted and analyzed according to predefined clinical endpoints. Results Eleven relevant RCTs were included for analysis in the present study. The prevalence of sinus rhythm in ablation group was significantly higher at discharge, 6-month and 1-year follow-up period. The morbidity including 30 day mortality, late all-cause mortality, reoperation for bleeding, permanent pacemaker implantation and neurological events were of no significant difference between two groups. Conclusions The result of our meta-analysis demonstrates that left atrial lesion set is an effective and safe surgical ablation strategy for AF patients undergoing concomitant cardiac surgery. PMID:29360851

Early and late benefits of prasugrel in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis.

PubMed

Antman, Elliott M; Wiviott, Stephen D; Murphy, Sabina A; Voitk, Juri; Hasin, Yonathan; Widimsky, Petr; Chandna, Harish; Macias, William; McCabe, Carolyn H; Braunwald, Eugene

2008-05-27

We evaluated the relative contributions of the loading and maintenance doses of prasugrel on events in a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis. Prasugrel is superior to clopidogrel in preventing ischemic events in patients with an acute coronary syndrome who are undergoing percutaneous coronary intervention, but it is associated with an increased risk of major bleeding. Landmark analyses for efficacy, safety, and net clinical benefit were performed from randomization to day 3 and from day 3 to the end of the trial. Significant reductions in ischemic events, including myocardial infarction, stent thrombosis, and urgent target vessel revascularization, were observed with the use of prasugrel both during the first 3 days and from 3 days to the end of the trial. Thrombolysis In Myocardial Infarction major non-coronary artery bypass graft bleeding was similar to clopidogrel during the first 3 days but was significantly greater with the use of prasugrel from 3 days to the end of the study. Net clinical benefit significantly favored prasugrel both early and late in the trial. Both the loading dose and maintenance dose of prasugrel were superior to clopidogrel for the reduction of ischemic events. This result emphasizes the importance of maintaining high levels of inhibition of platelet aggregation via P2Y(12) receptor inhibition, not only for the prevention of periprocedural ischemic events but also during long-term follow-up. The excess major bleeding observed with the use of prasugrel occurred predominantly during the maintenance phase. Approaches to reduce the relative excess of bleeding with prasugrel should focus on the maintenance dose (e.g., reduction in maintenance dose in previously reported high-risk subgroups, such as the elderly and those patients with low body weight). (A Comparison of CS-747 and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention; NCT00097591).

The Emergence of Suicidal Ideation during the Post-Hospital Treatment of Depressed Patients

ERIC Educational Resources Information Center

Gaudiano, Brandon A.; Andover, Margaret S.; Miller, Ivan W.

2008-01-01

There is a paucity of research on the emergence of suicidal ideation in recently hospitalized patients undergoing treatment for depression. As part of a larger clinical trial, patients (N = 103) with major depression without suicidal ideation at hospital discharge were followed for up to 6 months while receiving study-related outpatient…

New clinical trial opens to determine safety and efficacy of PROSTVAC, nivolumab and ipilimumab in men with localized prostate cancer | Center for Cancer Research

Cancer.gov

A new study is now open to evaluate the safety and effectiveness of a treatment regimen that combines PROSTVAC with ipilimumab and/or nivolumab in men with localized prostate cancer who have elected to undergo surgical resection (prostatectomy).  Learn more...

Aspirin for in vitro fertilisation.

PubMed

Siristatidis, Charalampos S; Basios, George; Pergialiotis, Vasilios; Vogiatzi, Paraskevi

2016-11-03

Aspirin is used with the aim of optimising the chance of live birth in women undergoing assisted reproductive technology (ART), despite inconsistent evidence of its efficacy and safety (in terms of intraoperative bleeding during oocyte retrieval and risk of miscarriage). The most appropriate time to commence aspirin therapy and the length of treatment required are also still to be determined. This is the second update of the review first published in 2007. To evaluate the effectiveness and safety of aspirin in women undergoing ART. We searched the Cochrane Gynaecology and Fertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 4) in the Cochrane Library (searched 9 May 2016); the databases MEDLINE (1946 to 9 May 2016) and Embase (1974 to 9 May 2016); and trial registers (ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform search portal). We also examined the reference lists of all known primary studies and review articles, citation lists of relevant publications and abstracts of major scientific meetings, combined with the Cochrane Gynaecology and Fertility Group's search strategy. Randomised controlled trials on aspirin for women undergoing ART. Two review authors independently assessed trial eligibility and risk of bias and extracted the data. The primary review outcome was live birth. Secondary outcomes included clinical pregnancy, ongoing pregnancy, multiple pregnancy, miscarriage, and other complications associated with IVF/ICSI or with pregnancy and birth. We combined data to calculate risk ratios (RRs) (for dichotomous data) and mean differences (MDs) (for continuous data) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I² statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods. The search identified 13 trials as eligible for inclusion in the review, including a total of 2653 participants with a mean age of 35 years. Ten studies used a dose of 100 mg and three used 80 mg of aspirin per day. In most of them, aspirin was commenced immediately at the start of down-regulation, while the duration of treatment varied widely. Eight studies provided a placebo for the control group.There was no evidence of a difference between the aspirin group and the group receiving no treatment or placebo in rates of live birth (RR 0.91, 95% CI 0.72 to 1.15, 3 RCTs, n = 1053, I² = 15%, moderate-quality evidence). In addition, clinical pregnancy rates were also similar for the two groups (RR 1.03, 95% CI 0.91 to 1.17, 10 RCTs, n = 2142, I² = 27%, moderate-quality evidence); sensitivity analysis, excluding studies at high risk of bias, did not change the effect estimate. There was no evidence of a difference between groups in terms of multiple pregnancy as confirmed by ultrasound (RR 0.67, 95% CI 0.37 to 1.25, 2 RCTs, n = 656, I² = 0%, low-quality evidence), miscarriage (RR 1.10, 95% CI 0.68 to 1.77, 5 RCTs, n = 1497, I² = 0%, low-quality evidence), ectopic pregnancy (RR 1.86, 95% CI 0.75 to 4.63, 3 RCTs, n = 1135, I² = 0%, very low quality evidence) or vaginal bleeding (RR 1.01, 95% CI 0.14 to 7.13, 1 RCT, n = 487, very low quality evidence). Data were lacking on other adverse effects.The overall quality of the evidence ranged from very low to moderate; limitations were poor reporting of study methods and suspected publication bias. Currently there is no evidence in favour of routine use of aspirin in order to improve pregnancy rates for a general IVF population. This is based on available data from randomised controlled trials, where there is currently no evidence of an effect of aspirin on women undergoing ART, as there is no single outcome measure demonstrating a benefit with its use. Furthermore, current evidence does not exclude the possibility of adverse effects.

Collagen Augmentation Improves the Quality of Cartilage Repair After Microfracture in Patients Undergoing High Tibial Osteotomy: A Randomized Controlled Trial.

PubMed

Kim, Man Soo; Koh, In Jun; Choi, Young Jun; Pak, Kyu Hyung; In, Yong

2017-07-01

The quality of cartilage repair after marrow stimulation is unpredictable. To overcome the shortcomings of the microfracture technique, various augmentation techniques have been developed. However, their efficacies remain unclear. The quality of cartilage repair and clinical outcomes would be superior in patients undergoing high tibial osteotomy (HTO) with microfracture and collagen augmentation compared to those undergoing HTO with microfracture alone without collagen augmentation for the treatment of medial compartment osteoarthritis (OA) of the knee. Randomized controlled trial; Level of evidence, 2. Twenty-eight patients undergoing HTO were randomized into 2 groups: microfracture alone (group 1, n = 14) or microfracture with collagen augmentation (group 2, n = 14). At 1 year postoperatively, second-look arthroscopic surgery and biopsy of repaired cartilage were performed at the time of HTO plate removal. Biopsy specimens were graded using the International Cartilage Repair Society Visual Assessment Scale II (ICRS II). In addition, imaging outcomes in terms of the magnetic resonance observation of cartilage repair tissue (MOCART) score were assessed based on magnetic resonance imaging (MRI). Finally, clinical outcomes in terms of the visual analog scale (VAS) for pain score, Knee Injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) score, and Tegner activity scale score were evaluated. The mean ICRS II score in group 2 was significantly higher than that in group 1 (1053.2 vs 885.4, respectively; P = .002). Group 2 showed greater improvement in tissue morphology, cell morphology, surface architecture, middle/deep zone assessment, and overall assessment compared with group 1 ( P < .050 for all comparisons). Imaging outcomes based on the MOCART score were superior in group 2 compared to those in group 1 on MRI at 1 year postoperatively (64.6 vs 45.4, respectively; P = .001). The degree of defect repair was better in group 2 than in group 1 ( P = .040). Clinical outcomes in terms of the VAS for pain score, KOOS, IKDC score, and Tegner activity scale score were improved in both groups without between-group differences ( P > .100 for all comparisons). The quality of cartilage repair after microfracture with collagen augmentation was superior to that after microfracture alone in patients undergoing HTO. Clinical results after 1 year did not reflect this difference in tissue repair. Therefore, a longer follow-up of the cohort is needed to answer this question.

Effects of clopidogrel, prasugrel and ticagrelor on endothelial function, inflammatory and oxidative stress parameters and platelet function in patients undergoing coronary artery stenting for an acute coronary syndrome. A randomised, prospective, controlled study

PubMed Central

Schnorbus, Boris; Daiber, Andreas; Jurk, Kerstin; Warnke, Silke; König, Jochem; Krahn, Ulrike; Lackner, Karl; Munzel, Thomas; Gori, Tommaso

2014-01-01

Introduction Particularly in the setting of acute coronary syndromes, the interplay between vascular and platelet function has been postulated to have direct clinical implications. The present trial is designed to test the effect of clopidogrel, prasugrel and ticagrelor on multiple parameters of vascular function, platelet aggregation, oxidative and inflammatory stress before and up to 4 weeks after coronary artery stenting. Methods and analysis The study is designed as a three-arm, parallel design, randomised, investigator-blinded study. Patients with unstable angina or non-ST elevation myocardial infarction undergoing coronary intervention with a drug-eluting stent will be randomised to receive 600 mg clopidogrel, 60 mg prasugrel or 180 mg ticagrelor followed by oral therapy with the same drug. The primary endpoint of the trial is the impact of antiplatelet treatments on endothelial function as assessed by flow-mediated dilation at 1 day, 1 week and 1 month in patients who have undergone stenting. Secondary endpoints include the impact of study medications on parameters of macrovascular and microvascular function, platelet reactivity, oxidative and inflammatory stress. The study recruitment is currently ongoing and, after an interim analysis which was performed at 50% of the initially planned population, it is planned to continue until July 2015. Ethics and dissemination The protocol was approved by the local ethics committee. The trial will provide important pathophysiological insight on the relationship between platelet aggregation and endothelial function, two parameters that have been shown to influence patients’ prognosis. Trial registration number ClinicalTrials.gov Identifier: NCT01700322; EudraCT-Nr.: 2011-005305-73. Current V.1.3, from 24 February 2014. PMID:24801283

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.

Effect of milrinone on cardiac functions in patients undergoing coronary artery bypass graft: a meta-analysis of randomized clinical trials

PubMed Central

You, Zhigang; Huang, Lin; Cheng, Xiaoshu; Wu, Qinghua; Jiang, Xinghua; Wu, Yanqing

2016-01-01

Background and aim Inotropes are commonly used to treat myocardial dysfunction, which is the major complication after coronary artery bypass graft (CABG). Milrinone, a phosphodiesterase 3 inhibitor, is one of these inotropes. Recently, a number of clinical studies have been carried out to evaluate the effects of milrinone on cardiac function in patients with low ventricular ejection fraction undergoing CABG. However, it has been inconclusive because of the inconsistent results. In addition, some studies found that milrinone increased the incidence of postoperative atrial arrhythmias and did not show any long-term beneficial effects on survival. Therefore, it is very important to perform a meta-analysis to summarize the results so as to determine the clinical efficacy and safety of milrinone. Method Several databases and websites for clinical trials were searched until October 2015 for prospective clinical studies comparing milrinone versus placebo on cardiac functions in patients undergoing CAGB. Results Four articles were identified by our search strategy. 1) Milrinone decreased incidence of myocardial ischemia and myocardial infarction (15.6% versus 44.4%; 4.7% versus 18% in milrinone and control group, respectively). 2) Milrinone decreased duration of inotropic support (95% confidence interval [CI]: −6.52 to −1.68; P=0.0009) and mechanical ventilation (h) support (95% CI −5.00 to −0.69; P=0.010), but did not decrease the requirement for intra-aortic balloon pump or inotropic support (P>0.05). 3) Milrinone did not decrease the overall mortality or morbidity, intensive care unit stay (P>0.05). Conclusion Perioperative continuous infusion of milrinone is effective to lower incidence of myocardial ischemia and myocardial infarction in patients post-CABG, but it was unable to improve the overall morbidity and mortality or decreased duration of intensive care unit stay. The available sample size is small; therefore, future studies should be directed toward a better understanding of the benefit of milrinone to CABG patients. PMID:26766900

Effect of milrinone on cardiac functions in patients undergoing coronary artery bypass graft: a meta-analysis of randomized clinical trials.

PubMed

You, Zhigang; Huang, Lin; Cheng, Xiaoshu; Wu, Qinghua; Jiang, Xinghua; Wu, Yanqing

2016-01-01

Inotropes are commonly used to treat myocardial dysfunction, which is the major complication after coronary artery bypass graft (CABG). Milrinone, a phosphodiesterase 3 inhibitor, is one of these inotropes. Recently, a number of clinical studies have been carried out to evaluate the effects of milrinone on cardiac function in patients with low ventricular ejection fraction undergoing CABG. However, it has been inconclusive because of the inconsistent results. In addition, some studies found that milrinone increased the incidence of postoperative atrial arrhythmias and did not show any long-term beneficial effects on survival. Therefore, it is very important to perform a meta-analysis to summarize the results so as to determine the clinical efficacy and safety of milrinone. Several databases and websites for clinical trials were searched until October 2015 for prospective clinical studies comparing milrinone versus placebo on cardiac functions in patients undergoing CAGB. Four articles were identified by our search strategy. 1) Milrinone decreased incidence of myocardial ischemia and myocardial infarction (15.6% versus 44.4%; 4.7% versus 18% in milrinone and control group, respectively). 2) Milrinone decreased duration of inotropic support (95% confidence interval [CI]: -6.52 to -1.68; P=0.0009) and mechanical ventilation (h) support (95% CI -5.00 to -0.69; P=0.010), but did not decrease the requirement for intra-aortic balloon pump or inotropic support (P>0.05). 3) Milrinone did not decrease the overall mortality or morbidity, intensive care unit stay (P>0.05). Perioperative continuous infusion of milrinone is effective to lower incidence of myocardial ischemia and myocardial infarction in patients post-CABG, but it was unable to improve the overall morbidity and mortality or decreased duration of intensive care unit stay. The available sample size is small; therefore, future studies should be directed toward a better understanding of the benefit of milrinone to CABG patients.

A conceptual framework and ethics analysis for prevention trials of Alzheimer Disease.

PubMed

Peters, Kevin R; Lynn Beattie, B; Feldman, Howard H; Illes, Judy

2013-11-01

As our understanding of the neurobiology of Alzheimer Disease deepens, it has become evident that early intervention is critical to achieving successful therapeutic impact. The availability of diagnostic criteria for preclinical Alzheimer Disease adds momentum to research directed at this goal and even to prevention. The landscape of therapeutic research is thus poised to undergo a dramatic shift in the next 5-10 years, with clinical trials involving subjects at risk for Alzheimer Disease who have few or no symptoms. These trials will also likely rely heavily on genetics, biomarkers, and or risk factor stratification to identify individuals at risk for Alzheimer Disease. Here, we propose a conceptual framework to guide this next generation of pharmacological and non-pharmacological clinical pursuit, and discuss some of the foreseeable ethical considerations that may accompany them. Copyright © 2013 Elsevier Ltd. All rights reserved.

Low molecular weight heparins in the prevention of deep-vein thrombosis in general surgery.

PubMed

Breddin, H K

1999-01-01

Unfractionated heparin (UFH) was the established treatment in the early 1980s for the prophylaxis of venous thromboembolic disease (VTED) in patients undergoing general surgery. This was one of the earliest indications in which low molecular weight heparins (LMWHs) were tested, and about 40 trials have revealed that these agents are at least as effective and safe as UFH with a tendency of superiority when higher dosages are used. In most trials, the fibrinogen uptake test has been used to assess the frequency of deep vein thrombosis. LMWHs exhibit a number of improved features over UFH, including ease of administration and convenient once daily dosing, facilitating outpatient management. A still open question is the ideal time and dose of the first one or two injections of a LMWH. To determine the clinical relevance of product differentiation further, clinical trials, directly comparing different LMWHs, are required.

The Individualized Diet and Exercise Adherence Pilot Trial (IDEA-P) in prostate cancer patients undergoing androgen deprivation therapy: study protocol for a randomized controlled trial.

PubMed

Focht, Brian C; Lucas, Alexander R; Grainger, Elizabeth; Simpson, Christina; Thomas-Ahner, Jennifer M; Clinton, Steven K

2014-09-09

Androgen deprivation therapy (ADT) is the foundation of treatment for men with metastatic prostate cancer and is now frequently incorporated into multimodality strategies for the curative treatment of locally advanced prostate cancer. Nevertheless, the catabolic effects of ADT result in meaningful adverse effects on physiological and quality of life outcomes, which may, in turn, increase the risk of functional decline, frailty, cardiovascular disease, and metabolic syndrome. Recent evidence demonstrates that lifestyle intervention promoting change in exercise and dietary behaviors is a promising approach, and may offset, or even reverse, the adverse effects accompanying ADT. Unfortunately, the limited existing studies of the effects of exercise and dietary interventions targeting patients with prostate cancer on ADT are characterized by high attrition rates and poor postintervention maintenance of treatment effects. Consequently, the Individualized Diet and Exercise Adherence Pilot Trial (IDEA-P) is designed to contrast the effects of a lifestyle intervention designed to promote independent self-management of exercise and dietary behavior with those of standard care disease management approach in the treatment of prostate cancer. A total of 40 patients with prostate cancer undergoing ADT will be randomly assigned to lifestyle intervention or standard care. Outcomes of interest in IDEA-P include changes in self-reported and objectively assessed physical function and physical activity, dietary behavior, body composition, muscular strength, and quality of life. Outcomes will be obtained at baseline, 2-month, and 3-month assessments by trial personnel blinded to participants' randomization assignment. Findings from this study will establish the feasibility and preliminary efficacy of an innovative lifestyle intervention designed to promote progressively independent self-regulated exercise and dietary behavior change in the treatment of patients with prostate cancer undergoing ADT. ClinicalTrials.gov NCT02050906.

Optimization of the decision-making process for the selection of therapeutics to undergo clinical testing for spinal cord injury in the North American Clinical Trials Network.

PubMed

Guest, James; Harrop, James S; Aarabi, Bizhan; Grossman, Robert G; Fawcett, James W; Fehlings, Michael G; Tator, Charles H

2012-09-01

The North American Clinical Trials Network (NACTN) includes 9 clinical centers funded by the US Department of Defense and the Christopher Reeve Paralysis Foundation. Its purpose is to accelerate clinical testing of promising therapeutics in spinal cord injury (SCI) through the development of a robust interactive infrastructure. This structure includes key committees that serve to provide longitudinal guidance to the Network. These committees include the Executive, Data Management, and Neurological Outcome Assessments Committees, and the Therapeutic Selection Committee (TSC), which is the subject of this manuscript. The NACTN brings unique elements to the SCI field. The Network's stability is not restricted to a single clinical trial. Network members have diverse expertise and include experts in clinical care, clinical trial design and methodology, pharmacology, preclinical and clinical research, and advanced rehabilitation techniques. Frequent systematic communication is assigned a high value, as is democratic process, fairness and efficiency of decision making, and resource allocation. This article focuses on how decision making occurs within the TSC to rank alternative therapeutics according to 2 main variables: quality of the preclinical data set, and fit with the Network's aims and capabilities. This selection process is important because if the Network's resources are committed to a therapeutic, alternatives cannot be pursued. A proposed methodology includes a multicriteria decision analysis that uses a Multi-Attribute Global Inference of Quality matrix to quantify the process. To rank therapeutics, the TSC uses a series of consensus steps designed to reduce individual and group bias and limit subjectivity. Given the difficulties encountered by industry in completing clinical trials in SCI, stable collaborative not-for-profit consortia, such as the NACTN, may be essential to clinical progress in SCI. The evolution of the NACTN also offers substantial opportunity to refine decision making and group dynamics. Making the best possible decisions concerning therapeutics selection for trial testing is a cornerstone of the Network's function.

Low pressure versus standard pressure pneumoperitoneum in laparoscopic cholecystectomy.

PubMed

Gurusamy, Kurinchi Selvan; Vaughan, Jessica; Davidson, Brian R

2014-03-18

A pneumoperitoneum of 12 to 16 mm Hg is used for laparoscopic cholecystectomy. Lower pressures are claimed to be safe and effective in decreasing cardiopulmonary complications and pain. To assess the benefits and harms of low pressure pneumoperitoneum compared with standard pressure pneumoperitoneum in people undergoing laparoscopic cholecystectomy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until February 2013 to identify randomised trials,using search strategies. We considered only randomised clinical trials, irrespective of language, blinding, or publication status for inclusion in the review. Two review authors independently identified trials and independently extracted data. We calculated the risk ratio (RR), mean difference (MD), or standardised mean difference (SMD) with 95% confidence intervals (CI) using both fixed-effect and random-effects models with RevMan 5 based on available case analysis. A total of 1092 participants randomly assigned to the low pressure group (509 participants) and the standard pressure group (583 participants) in 21 trials provided information for this review on one or more outcomes. Three additional trials comparing low pressure pneumoperitoneum with standard pressure pneumoperitoneum (including 179 participants) provided no information for this review. Most of the trials included low anaesthetic risk participants undergoing elective laparoscopic cholecystectomy. One trial including 140 participants was at low risk of bias. The remaining 20 trials were at high risk of bias. The overall quality of evidence was low or very low. No mortality was reported in either the low pressure group (0/199; 0%) or the standard pressure group (0/235; 0%) in eight trials that reported mortality. One participant experienced the outcome of serious adverse events (low pressure group 1/179, 0.6%; standard pressure group 0/215, 0%; seven trials; 394 participants; RR 3.00; 95% CI 0.14 to 65.90; very low quality evidence). Quality of life, return to normal activity, and return to work were not reported in any of the trials. The difference between groups in the conversion to open cholecystectomy was imprecise (low pressure group 2/269, adjusted proportion 0.8%; standard pressure group 2/287, 0.7%; 10 trials; 556 participants; RR 1.18; 95% CI 0.29 to 4.72; very low quality evidence) and was compatible with an increase, a decrease, or no difference in the proportion of conversion to open cholecystectomy due to low pressure pneumoperitoneum. No difference in the length of hospital stay was reported between the groups (five trials; 415 participants; MD -0.30 days; 95% CI -0.63 to 0.02; low quality evidence). Operating time was about two minutes longer in the low pressure group than in the standard pressure group (19 trials; 990 participants; MD 1.51 minutes; 95% CI 0.07 to 2.94; very low quality evidence). Laparoscopic cholecystectomy can be completed successfully using low pressure in approximately 90% of people undergoing laparoscopic cholecystectomy. However, no evidence is currently available to support the use of low pressure pneumoperitoneum in low anaesthetic risk patients undergoing elective laparoscopic cholecystectomy. The safety of low pressure pneumoperitoneum has to be established. Further well-designed trials are necessary, particularly in people with cardiopulmonary disorders who undergo laparoscopic cholecystectomy.

Patent Foramen Ovale Closure in the Setting of Cryptogenic Stroke: A Meta-Analysis of Five Randomized Trials.

PubMed

Garg, Lohit; Haleem, Affan; Varade, Shweta; Sivakumar, Keithan; Shah, Mahek; Patel, Brijesh; Agarwal, Manyoo; Agrawal, Sahil; Leary, Megan; Kluck, Bryan

2018-05-24

The clinical benefit of patent foramen ovale (PFO) closure after cryptogenic stroke has been a topic of debate for decades. Recently, 3 randomized controlled trials of PFO closure in patients with cryptogenic stroke demonstrated a significantly reduced risk of recurrent stroke compared with standard medical therapy alone. This meta-analysis was performed to clarify the efficacy of PFO closure for future stroke prevention in this population. A systematic literature search was undertaken. Published pooled data from 5 large randomized clinical trials (CLOSE, RESPECT, Gore REDUCE, CLOSURE I, and PC) were combined and then subsequently analyzed. Enrolled patients with cryptogenic stroke were assigned to receive standard medical care or to undergo endovascular PFO closure, with a primary outcome of reduction in stroke recurrence rate. Secondary outcomes included rates of transient ischemic attack (TIA), composite outcome of stroke, TIA, and death from all causes, and rates of atrial fibrillation events. We analyzed data for 3412 patients. Transcatheter PFO closure resulted in a statistically significant reduced rate of recurrent stroke, compared with medication alone. Patients undergoing closure were 58% less likely to have another stroke. The number needed to treat with PFO closure to reduce recurrent stroke for 1 patient was 40. Endovascular PFO closure was associated with a reduced risk of recurrent stroke in patients with a prior cryptogenic cerebral infarct. Although the absolute stroke reduction was small, these findings are clinically significant, given the young age of this patient population and the patients' lifetime risk of recurrent stroke. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Safety and feasibility of xenon as an adjuvant to sevoflurane anaesthesia in children undergoing interventional or diagnostic cardiac catheterization: study protocol for a randomised controlled trial.

PubMed

Devroe, Sarah; Lemiere, Jurgen; Van de Velde, Marc; Gewillig, Marc; Boshoff, Derize; Rex, Steffen

2015-03-04

Xenon has minimal haemodynamic side effects when compared to volatile or intravenous anaesthetics. Moreover, in in vitro and in animal experiments, xenon has been demonstrated to convey cardio- and neuroprotective effects. Neuroprotection could be advantageous in paediatric anaesthesia as there is growing concern, based on both laboratory studies and retrospective human clinical studies, that anaesthetics may trigger an injury in the developing brain, resulting in long-lasting neurodevelopmental consequences. Furthermore, xenon-mediated neuroprotection could help to prevent emergence delirium/agitation. Altogether, the beneficial haemodynamic profile combined with its putative organ-protective properties could render xenon an attractive option for anaesthesia of children undergoing cardiac catheterization. In a phase-II, mono-centre, prospective, single-blind, randomised, controlled study, we will test the hypothesis that the administration of 50% xenon as an adjuvant to general anaesthesia with sevoflurane in children undergoing elective cardiac catheterization is safe and feasible. Secondary aims include the evaluation of haemodynamic parameters during and after the procedure, emergence characteristics, and the analysis of peri-operative neuro-cognitive function. A total of 40 children ages 4 to 12 years will be recruited and randomised into two study groups, receiving either a combination of sevoflurane and xenon or sevoflurane alone. Children undergoing diagnostic or interventional cardiac catheterization are a vulnerable patient population, one particularly at risk for intra-procedural haemodynamic instability. Xenon provides remarkable haemodynamic stability and potentially has cardio- and neuroprotective properties. Unfortunately, evidence is scarce on the use of xenon in the paediatric population. Our pilot study will therefore deliver important data required for prospective future clinical trials. EudraCT: 2014-002510-23 (5 September 2014).

Efficacy and safety of recombinant activated factor vii in major surgical procedures: systematic review and meta-analysis of randomized clinical trials.

PubMed

Ranucci, Marco; Isgrò, Giuseppe; Soro, Giorgio; Conti, Daniela; De Toffol, Barbara

2008-03-01

To investigate the efficacy and safety of recombinant activated factor VII (rFVIIa) treatment in patients undergoing major surgical procedures. Relevant studies were searched in BioMedCentral, CENTRAL, PubMed, and PubMed Central. Only randomized controlled trials on humans undergoing major surgery were included. Efficacy was determined as the rate of patients receiving allogeneic packed red blood cells; safety was assessed in terms of thromboembolic complications and mortality rate. We followed the Cochrane Collaboration method for data extraction and internal validity procedures, as well as the Quality of Reporting of Meta-analyses statement. Seven randomized controlled trials met the inclusion criteria. Treatment with rFVIIa is associated with a reduced risk of receiving allogeneic packed red blood cells (odds ratio, 0.29; 95% confidence interval, 0.10-0.80). In a subgroup analysis, only patients receiving at least 50 mug/kg of rFVIIa had a significant benefit (odds ratio, 0.43; 95% confidence interval, 0.23-0.78). No differences in thromboembolic complications and mortality rates were observed. Treatment with rFVIIa is effective in reducing the rate of patients undergoing transfusion with allogeneic packed red blood cells. However, the cost-benefit ratio is favorable only in patients who need a huge number of packed red blood cell units. No safety concerns arise from the present study.

Analgesic Effects of Intra-Articular Bupivacaine/Intravenous Parecoxib Combination Therapy versus Intravenous Parecoxib Monotherapy in Patients Receiving Total Knee Arthroplasty: A Randomized, Double-Blind Trial

PubMed Central

Shen, Shih-Jyun; Peng, Pei-Yu; Chen, Hsiu-Pin; Lin, Jr-Rung; Lee, Mel S.; Yu, Huang-Ping

2015-01-01

Objectives. The purpose of this double-blind, randomized study was to investigate whether the addition of intra-articular bupivacaine to intravenous parecoxib could improve pain relief in patients undergoing total knee arthroplasty. Methods. A total of 36 patients undergoing total knee arthroplasty were enrolled into our study. These patients were randomly allocated either to a placebo-controlled group or study group. Postoperative pain scores and analgesic consumption were evaluated. Results. Numeric rating scale (NRS) data of bupivacaine group in postoperative room were significantly lower than that of control group (control group versus bupivacaine group, 7.9 (6.7–9.1) (mean and 95% confidence interval) versus 4.5 (3.2–5.8) (mean and 95% confidence interval), p = 0.001). NRS data of bupivacaine group in ward were also significantly lower than that of control group. A significantly lower dose of meperidine was used in the study group postoperatively during the first 24 hours (control group versus bupivacaine group, 3.08 ± 0.80 mg/Kg versus 2.34 ± 0.42 mg/Kg, p = 0.001). Conclusion. Intra-articular bupivacaine in combination with intravenous parecoxib may improve pain relief and reduce the demand for rescue analgesics in patients undergoing total knee arthroplasty. The trial is registered with Australian New Zealand Clinical Trials Registry (ACTRN12615000463572). PMID:26171392

Analgesic Effects of Intra-Articular Bupivacaine/Intravenous Parecoxib Combination Therapy versus Intravenous Parecoxib Monotherapy in Patients Receiving Total Knee Arthroplasty: A Randomized, Double-Blind Trial.

PubMed

Shen, Shih-Jyun; Peng, Pei-Yu; Chen, Hsiu-Pin; Lin, Jr-Rung; Lee, Mel S; Yu, Huang-Ping

2015-01-01

The purpose of this double-blind, randomized study was to investigate whether the addition of intra-articular bupivacaine to intravenous parecoxib could improve pain relief in patients undergoing total knee arthroplasty. A total of 36 patients undergoing total knee arthroplasty were enrolled into our study. These patients were randomly allocated either to a placebo-controlled group or study group. Postoperative pain cores and analgesic consumption were evaluated. Numeric rating scale (NRS) data of bupivacaine group in postoperative room were significantly lower than that of control group (control group versus bupivacaine group, 7.9 (6.7-9.1) (mean and 95% confidence interval) versus 4.5 (3.2-5.8) (mean and 95% confidence interval), p = 0.001). NRS data of bupivacaine group in ward were also significantly lower than that of control group. A significantly lower dose of meperidine was used in the study group postoperatively during the first 24 hours (control group versus bupivacaine group, 3.08 ± 0.80 mg/Kg versus 2.34 ± 0.42 mg/Kg, p = 0.001). Intra-articular bupivacaine in combination with intravenous parecoxib may improve pain relief and reduce the demand for rescue analgesics in patients undergoing total knee arthroplasty. The trial is registered with Australian New Zealand Clinical Trials Registry (ACTRN12615000463572).

Improving outcomes in adults with epilepsy and intellectual disability (EpAID) using a nurse-led intervention: study protocol for a cluster randomised controlled trial.

PubMed

Ring, Howard; Gilbert, Nakita; Hook, Roxanne; Platt, Adam; Smith, Christopher; Irvine, Fiona; Donaldson, Cam; Jones, Elizabeth; Kelly, Joanna; Mander, Adrian; Murphy, Caroline; Pennington, Mark; Pullen, Angela; Redley, Marcus; Rowe, Simon; Wason, James

2016-06-24

In adults with intellectual disability (ID) and epilepsy there are suggestions that improvements in management may follow introduction of epilepsy nurse-led care. However, this has not been tested in a definitive clinical trial and results cannot be generalised from general population studies as epilepsy tends to be more severe and to involve additional clinical comorbidities in adults with ID. This trial investigates whether nurses with expertise in epilepsy and ID, working proactively to a clinically defined role, can improve clinical and quality of life outcomes in the management of epilepsy within this population, compared to treatment as usual. The trial also aims to establish whether any perceived benefits represent good value for money. The EpAID clinical trial is a two-arm cluster randomised controlled trial of nurse-led epilepsy management versus treatment as usual. This trial aims to obtain follow-up data from 320 participants with ID and drug-resistant epilepsy. Participants are randomly assigned either to a 'treatment as usual' control or a 'defined epilepsy nurse role' active arm, according to the cluster site at which they are treated. The active intervention utilises the recently developed Learning Disability Epilepsy Specialist Nurse Competency Framework for adults with ID. Participants undergo 4 weeks of baseline data collection, followed by a minimum of 20 weeks intervention (novel treatment or treatment as usual), followed by 4 weeks of follow-up data collection. The primary outcome is seizure severity, including associated injuries and the level of distress manifest by the patient in the preceding 4 weeks. Secondary outcomes include cost-utility analysis, carer strain, seizure frequency and side effects. Descriptive measures include demographic and clinical descriptors of participants and clinical services in which they receive their epilepsy management. Qualitative study of clinical interactions and semi-structured interviews with clinicians and participants' carers are also undertaken. The EpAID clinical trial is the first cluster randomised controlled trial to test possible benefits of a nurse-led intervention in adults with epilepsy and ID. This research will have important implications for ID and epilepsy services. The challenges of undertaking such a trial in this population, and the approaches to meeting these are discussed. International Standard Randomised Controlled Trial Number: ISRCTN96895428 version 1.1. Registered on 26 March 2013.

Use of Levosimendan in Cardiac Surgery: An Update After the LEVO-CTS, CHEETAH, and LICORN Trials in the Light of Clinical Practice.

PubMed

Guarracino, Fabio; Heringlake, Matthias; Cholley, Bernard; Bettex, Dominique; Bouchez, Stefaan; Lomivorotov, Vladimir V; Rajek, Angela; Kivikko, Matti; Pollesello, Piero

2018-01-01

Levosimendan is a calcium sensitizer and adenosine triphosphate-dependent potassium channel opener, which exerts sustained hemodynamic, symptomatic, and organ-protective effects. It is registered for the treatment of acute heart failure, and when inotropic support is considered appropriate. In the past 15 years, levosimendan has been widely used in clinical practice and has also been tested in clinical trials to stabilize at-risk patients undergoing cardiac surgery. Recently, 3 randomized, placebo-controlled, multicenter studies (LICORN, CHEETAH, and LEVO-CTS) have been published reporting on the perioperative use of levosimendan in patients with compromised cardiac ventricular function. Taken together, many smaller trials conducted in the past suggested beneficial outcomes with levosimendan in perioperative settings. By contrast, the latest 3 studies were neutral or inconclusive. To understand the reasons for such dissimilarity, a group of experts from Austria, Belgium, Finland, France, Germany, Italy, Switzerland, and Russia, including investigators from the 3 most recent studies, met to discuss the study results in the light of both the previous literature and current clinical practice. Despite the fact that the null hypothesis could not be ruled out in the recent multicenter trials, we conclude that levosimendan can still be viewed as a safe and effective inodilator in cardiac surgery.

Effect of Acupuncture vs Sham Acupuncture on Live Births Among Women Undergoing In Vitro Fertilization: A Randomized Clinical Trial.

PubMed

Smith, Caroline A; de Lacey, Sheryl; Chapman, Michael; Ratcliffe, Julie; Norman, Robert J; Johnson, Neil P; Boothroyd, Clare; Fahey, Paul

2018-05-15

Acupuncture is widely used by women undergoing in vitro fertilization (IVF), although the evidence for efficacy is conflicting. To determine the efficacy of acupuncture compared with a sham acupuncture control performed during IVF on live births. A single-blind, parallel-group randomized clinical trial including 848 women undergoing a fresh IVF cycle was conducted at 16 IVF centers in Australia and New Zealand between June 29, 2011, and October 23, 2015, with 10 months of pregnancy follow-up until August 2016. Women received either acupuncture (n = 424) or a sham acupuncture control (n = 424). The first treatment was administered between days 6 to 8 of follicle stimulation, and 2 treatments were administered prior to and following embryo transfer. The sham control used a noninvasive needle placed away from the true acupuncture points. The primary outcome was live birth, defined as the delivery of 1 or more living infants at greater than 20 weeks' gestation or birth weight of at least 400 g. Among 848 randomized women, 24 withdrew consent, 824 were included in the study (mean [SD] age, 35.4 [4.3] years); 371 [45.0%] had undergone more than 2 previous IVF cycles), 607 proceeded to an embryo transfer, and 809 (98.2%) had data available on live birth outcomes. Live births occurred among 74 of 405 women (18.3%) receiving acupuncture compared with 72 of 404 women (17.8%) receiving sham control (risk difference, 0.5% [95% CI, -4.9% to 5.8%]; relative risk, 1.02 [95% CI, 0.76 to 1.38]). Among women undergoing IVF, administration of acupuncture vs sham acupuncture at the time of ovarian stimulation and embryo transfer resulted in no significant difference in live birth rates. These findings do not support the use of acupuncture to improve the rate of live births among women undergoing IVF. anzctr.org.au Identifier: ACTRN12611000226909.

Company stock prices before and after public announcements related to oncology drugs.

PubMed

Rothenstein, Jeffrey M; Tomlinson, George; Tannock, Ian F; Detsky, Allan S

2011-10-19

Phase III clinical trials and Food and Drug Administration (FDA) regulatory decisions are critical for success of new drugs and can influence a company's market valuation. Knowledge of trial results before they are made public (ie, "inside information") can affect the price of a drug company's stock. We examined the stock prices of companies before and after public announcements regarding experimental anticancer drugs owned by the companies. We identified drugs that were undergoing evaluation in phase III trials or for regulatory approval by the US FDA from January 2000 to January 2009. Stock prices of companies that owned such drugs were analyzed for 120 trading days before and after the first public announcement of 1) results of clinical trials with positive and negative outcomes and 2) positive and negative regulatory decisions. All statistical tests were two-sided. We identified public announcements from 23 positive trials and 36 negative trials and from 41 positive and nine negative FDA regulatory decisions. The mean stock price for the 120 trading days before a phase III clinical trial announcement increased by 13.7% (95% confidence interval = -2.2% to 29.6%) for companies that reported positive trials and decreased by 0.7% (95% confidence interval = -13.8% to 12.3%) for companies that reported negative trials (P = .09). In a post hoc analysis comparing the stock price averaged over 60 trading days before and after day -60 relative to the clinical trial announcement, the mean stock price increased by 9.4% for companies that reported positive trials and decreased by 4.5% for companies that reported negative trials (P = .03). Changes in company stock prices before FDA regulatory decisions did not differ statistically between companies with positive decision and companies with negative decisions. Trends in company stock prices before the first public announcement differ for companies that report positive vs negative trials. This finding has important legal and ethical implications for investigators, drug companies, and the investment industry.

Effects of a Delphi consensus acupuncture treatment protocol on the levels of stress and vascular tone in women undergoing in-vitro fertilization: a randomized clinical trial protocol.

PubMed

Zhang, Yan; Phy, Jennifer; Scott-Johnson, Chris; Garos, Sheila; Orlando, Jennie; Prien, Samuel; Huang, Jaou-Chen

2017-04-04

The variability of published acupuncture protocols for patients undergoing In-Vitro Fertilization (IVF) complicates the interpretation of data and hinders our understanding of acupuncture's impact. In 2012, an acupuncture treatment protocol developed by a Delphi consensus process was published to describe the parameters of best practice acupuncture for Assisted Reproductive Technology and future research. However, there has been no clinical trial utilizing this protocol to assess the effects of acupuncture. This study aims to assess the implementation of Dephi consensus acupuncture protocol and to examine the impact of acupuncture on stress and uterine and ovarian blood flow among women between ages 21-42 years seeking IVF. This study is a one site prospective, two-arm randomized controlled non-blind clinical trial conducted in a medical school-affiliated fertility center . Participants will be randomized 1:1 into either the acupuncture group or the standard of care (no acupuncture) group using computer generated tables. Both groups will have 3 regular clinical visits as their standard IVF care during an approximately 2 to 3 weeks window. Women who are randomized into the acupuncture group would receive three sessions based on the Delphi consensus acupuncture protocol in addition to the standard care. The first treatment will be administered between days 6 to 8 of the stimulated IVF cycle. The second session will be performed on the day of embryo transfer at least 1 h prior to the transfer. The third session will be performed within 48 h post-embryo transfer. Participants will be followed for their pregnancy test and pregnancy outcome when applicable. The outcomes stress and blood flow will be measured by a validated perceived stress scale and vasoactive molecules, respectively. Although recruitment and scheduling could be challenging at times, the Delphi consensus acupuncture protocol was implemented as planned and well-accepted by the patients. Because of the time-specified sessions around patients' IVF cycle, it is highly recommended to have on-site study acupuncturist(s) to accommodate the schedule. ClinicalTrials NCT02591186 registered on October 7, 2015.

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

PubMed Central

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

2017-01-01

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

The effect of cyclosporin-A on peri-operative myocardial injury in adult patients undergoing coronary artery bypass graft surgery: a randomised controlled clinical trial

PubMed Central

Hausenloy, DJ; Kunst, G; Boston-Griffiths, E; Kolvekar, S; Chaubey, S; John, L; Desai, J; Yellon, DM

2014-01-01

Objective Cyclosporin-A (CsA) has been reported to reduce myocardial infarct size in both the experimental and clinical settings. This protective effect is dependent on its ability to prevent the opening of the mitochondrial permeability transition pore, a critical determinant of cell death in the setting of acute ischaemia-reperfusion injury. Whether CsA can reduce the extent of peri-operative myocardial injury (PMI) in patients undergoing coronary artery bypass graft (CABG) surgery is unknown, and is investigated in this randomised controlled clinical trial. Methods 78 adult patients undergoing elective CABG surgery were randomised to receive either an intravenous bolus of CsA (2.5 mg/kg) or placebo administered after induction of anaesthesia and prior to sternotomy. PMI was assessed by measuring serum cardiac enzymes, troponin T (cTnT) and CK-MB at 0, 6, 12, 24, 48 and 72 h after surgery. Results There was no significant difference in mean peak cTnT levels between control (n=43) and CsA treatment (n=40) patients (0.56±0.06 ng/mL with control vs 0.35±0.05 ng/mL with CsA; p=0.07). However, in higher-risk patients with longer cardiopulmonary bypass times, there was a significant reduction in PMI with CsA therapy (p=0.049), with a reduced postoperative cTnT rise by 0.03 ng/mL for every 10 min, when compared with control. Conclusions In patients with longer cardiopulmonary bypass times, a single intravenous bolus of CsA administered prior to CABG surgery reduced the extent of PMI. PMID:24488610

Randomized trial comparing 600- with 300-mg loading dose of clopidogrel in patients with non-ST elevation acute coronary syndrome undergoing percutaneous coronary intervention: results of the Platelet Responsiveness to Aspirin and Clopidogrel and Troponin Increment after Coronary intervention in Acute coronary Lesions (PRACTICAL) Trial.

PubMed

Yong, Gerald; Rankin, Jamie; Ferguson, Louise; Thom, Jim; French, John; Brieger, David; Chew, Derek P; Dick, Ron; Eccleston, David; Hockings, Bernard; Walters, Darren; Whelan, Alan; Eikelboom, John W

2009-01-01

There is uncertainty about the benefit of a higher loading dose (LD) of clopidogrel in patients with non-ST elevation acute coronary syndrome (NSTEACS) undergoing early percutaneous coronary intervention (PCI). We compared the effects of a 600- versus a 300-mg LD of clopidogrel on inhibition of platelet aggregation, myonecrosis, and clinical outcomes in patients with NSTEACS undergoing an early invasive management strategy. Patients with NSTEACS (n = 256, mean age 63 years, 81.6% elevated troponin) without thienopyridine for at least 7 days were randomized to receive 600- or 300-mg LD of clopidogrel. Percutaneous coronary intervention was performed in 140 patients, with glycoprotein IIb/IIIa inhibitor use in 68.6%. Adenosine diphosphate (ADP)-induced platelet aggregation was measured by optical platelet aggregometry immediately before coronary angiography. Post-PCI myonecrosis was defined as a next-day troponin I greater than 5 times the upper limit of reference range and greater than baseline levels. Clopidogrel 600-mg LD compared with 300-mg LD was associated with significantly reduced ADP-induced platelet aggregation (49.7% vs 55.7% with ADP 20 micromol/L) but did not reduce post-PCI myonecrosis or adverse clinical outcomes to 6 months. There was no association between preprocedural platelet aggregation and outcome. These data confirm a modest incremental antiplatelet effect of a 600-mg clopidogrel LD compared with 300-mg LD but provide no support for a clinical benefit in patients with NSTEACS managed with an early invasive strategy including a high rate (69%) of glycoprotein IIb/IIIa inhibitor use during PCI.

Firefighter willingness to participate in a stem cell clinical trial for burns: A mixed methods study.

PubMed

Horch, Jenny D; Carr, Eloise C J; Harasym, Patricia; Burnett, Lindsay; Biernaskie, Jeff; Gabriel, Vincent

2016-12-01

Adult stem cells represent a potentially renewable and autologous source of cells to regenerate skin and improve wound healing. Firefighters are at risk of sustaining a burn and potentially benefiting from a split thickness skin graft (STSG). This mixed methods study examined firefighter willingness to participate in a future stem cell clinical trial, outcome priorities and factors associated with this decision. A sequential explanatory mixed methods design was used. The quantitative phase (online questionnaire) was followed by the qualitative phase (semi-structured interviews). A sample of 149 firefighters completed the online survey, and a purposeful sample of 15 firefighters was interviewed. A majority (74%) reported they would participate in a future stem cell clinical trial if they experienced burn benefiting from STSG. Hypothetical concerns related to receiving a STSG were pain, itch, scarring/redness and skin durability. Participants indicated willingness to undergo stem cell therapy if the risk of no improvement was 43% or less. Risk tolerance was predicted by perceived social support and having children. Interviews revealed four main themes: a desire to help others, improving clinical outcomes, trusting relationships, and a belief in scientific investigation. Many participants admitted lacking sufficient knowledge to make an informed decision regarding stem cell therapies. Firefighters indicated they were largely willing to participate in a stem cell clinical trial but also indicated a lack of knowledge upon which to make a decision. Public education of the role of stem cells in STSG will be increasingly important as clinical trials are developed. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Treatment of Anxiety in Patients with Coronary Heart Disease: Rationale and Design of the UNWIND Randomized Clinical Trial

PubMed Central

Blumenthal, James A.; Feger, Bryan J.; Smith, Patrick J.; Watkins, Lana L.; Jiang, Wei; Davidson, Jonathan; Hoffman, Benson M.; Ashworth, Megan; Mabe, Stephanie K.; Babyak, Michael A.; Kraus, William E.; Hinderliter, Alan; Sherwood, Andrew

2016-01-01

Background Anxiety is highly prevalent among patients with coronary heart disease (CHD), and there is growing evidence that high levels of anxiety are associated with worse prognosis. However, few studies have evaluated the efficacy of treating anxiety in CHD patients for reducing symptoms and improving clinical outcomes. Exercise and selective serotonin reuptake inhibitors have been shown to be effective in treating patients with depression, but have not been studied in cardiac patients with high anxiety. Methods The UNWIND trial is a randomized clinical trial of patients with CHD who are at increased risk for adverse events because of comorbid anxiety. One hundred fifty participants with CHD and elevated anxiety symptoms and/or with a diagnosed anxiety disorder will be randomly assigned to 12 weeks of aerobic exercise (3×/wk, 35 min, 70–85% VO2peak), escitalopram (5–20 mg qd), or placebo. Before and after 12 weeks of treatment, participants will undergo assessments of anxiety symptoms and CHD biomarkers of risk, including measures of inflammation, lipids, hemoglobin A1c, heart rate variability, and vascular endothelial function. Primary outcomes include post-intervention effects on symptoms of anxiety and CHD biomarkers. Secondary outcomes include clinical outcomes (cardiovascular hospitalizations and all-cause death) and measures of quality of life. Conclusions The UNWIND trial (ClinicalTrials.gov NCT02516332) will evaluate the efficacy of aerobic exercise and escitalopram for improving anxiety symptoms and reducing risk for adverse clinical events in anxious CHD patients. PMID:27264220

Edoxaban versus enoxaparin-warfarin in patients undergoing cardioversion of atrial fibrillation (ENSURE-AF): a randomised, open-label, phase 3b trial.

PubMed

Goette, Andreas; Merino, Jose L; Ezekowitz, Michael D; Zamoryakhin, Dmitry; Melino, Michael; Jin, James; Mercuri, Michele F; Grosso, Michael A; Fernandez, Victor; Al-Saady, Naab; Pelekh, Natalya; Merkely, Bela; Zenin, Sergey; Kushnir, Mykola; Spinar, Jindrich; Batushkin, Valeriy; de Groot, Joris R; Lip, Gregory Y H

2016-10-22

Edoxaban, an oral factor Xa inhibitor, is non-inferior for prevention of stroke and systemic embolism in patients with atrial fibrillation and is associated with less bleeding than well controlled warfarin therapy. Few safety data about edoxaban in patients undergoing electrical cardioversion are available. We did a multicentre, prospective, randomised, open-label, blinded-endpoint evaluation trial in 19 countries with 239 sites comparing edoxaban 60 mg per day with enoxaparin-warfarin in patients undergoing electrical cardioversion of non-valvular atrial fibrillation. The dose of edoxaban was reduced to 30 mg per day if one or more factors (creatinine clearance 15-50 mL/min, low bodyweight [≤60 kg], or concomitant use of P-glycoprotein inhibitors) were present. Block randomisation (block size four)-stratified by cardioversion approach (transoesophageal echocardiography [TEE] or not), anticoagulant experience, selected edoxaban dose, and region-was done through a voice-web system. The primary efficacy endpoint was a composite of stroke, systemic embolic event, myocardial infarction, and cardiovascular mortality, analysed by intention to treat. The primary safety endpoint was major and clinically relevant non-major (CRNM) bleeding in patients who received at least one dose of study drug. Follow-up was 28 days on study drug after cardioversion plus 30 days to assess safety. This trial is registered with ClinicalTrials.gov, number NCT02072434. Between March 25, 2014, and Oct 28, 2015, 2199 patients were enrolled and randomly assigned to receive edoxaban (n=1095) or enoxaparin-warfarin (n=1104). The mean age was 64 years (SD 10·54) and mean CHA 2 DS 2 -VASc score was 2·6 (SD 1·4). Mean time in therapeutic range on warfarin was 70·8% (SD 27·4). The primary efficacy endpoint occurred in five (<1%) patients in the edoxaban group versus 11 (1%) in the enoxaparin-warfarin group (odds ratio [OR] 0·46, 95% CI 0·12-1·43). The primary safety endpoint occurred in 16 (1%) of 1067 patients given edoxaban versus 11 (1%) of 1082 patients given enoxaparin-warfarin (OR 1·48, 95% CI 0·64-3·55). The results were independent of the TEE-guided strategy and anticoagulation status. ENSURE-AF is the largest prospective randomised clinical trial of anticoagulation for cardioversion of patients with non-valvular atrial fibrillation. Rates of major and CRNM bleeding and thromboembolism were low in the two treatment groups. Daiichi Sankyo provided financial support for the study. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Changing surgical therapy because of clinical studies?].

PubMed

Schwenk, W; Haase, O; Müller, J M

2002-04-01

The randomised controlled clinical trial (RCT) is a powerful instrument to evaluate different therapeutic regimens. In a survey among 115 physicians visiting the 25th annual meeting of the Surgical Society of Berlin and Brandenburg, the RCT was judged to be very important when changes of therapeutic strategies are discussed. 90 % of all participants claimed to use data from RCTs in the clinical routine and 89 % would participate in such a trial. In official (e. g. discussions during coffee breaks at scientific meetings) or non-medical (e. g. non-scientific press or media) sources of information were assessed as irrelevant for decisions regarding therapeutic strategies. However, in contrast to this view laparoscopic cholecystectomy was introduced into clinical practice rapidly because patients informed by external (non-medical) sources preferred to be operated on with the "modern" technique. Clinical trials with a high level of evidence had no relevant influence on the rapid distribution of laparoscopic cholecystectomy. Controversial discussions concerning the extent of lymphadenectomy with gastric resection for carcinoma demonstrate that the value of excellent clinical RCTs is low if their results challenge a stable paradigma of the surgical scientific society. To allow a rational judgement, new surgical technologies should undergo a scientific gradual evaluation in agreement with the principles of evidence based medicine.

Evaluation of a multi-center randomised clinical trial on prophylactic transfusion of fresh frozen plasma: implications for future trials.

PubMed

Müller, M C A; de Haan, R J; Vroom, M B; Juffermans, N P

2014-10-01

Prophylactic use of fresh frozen plasma (FFP) in critically ill patients with a coagulopathy is common. However, a lack of evidence of efficacy has resulted in a call for trials on the benefit of FFP in these patients. To date, conducting a trial on this subject has not been successful. Recently, a multi-center randomised trial was stopped prematurely due to slow inclusion. To assess clinicians' opinions regarding a trial on prophylactic administration of FFP in coagulopathic critically ill patients who need to undergo an intervention. A survey among 55 intensivists who all participated in a randomised trial on the risks and benefits of FFP in critically ill patients. Response rate was 84%. Majority of respondents indicated that international normalised ratio (INR) should be assessed before insertion of a central venous catheter (CVC) (61%), chest tube (89%) or tracheostomy (91%). Reasons to withhold transfusion of FFP to non-bleeding critically ill patients are risk of transfusion-related acute lung injury (TRALI) (46%), fluid overload (39%) and allergic reaction (24%). Although, the majority of respondents expressed the opinion that the trial was clinically relevant, 56% indicated that ≥1 patient subgroups should have been excluded from participation. Intensivists express the need for more evidence on the prophylactic use of FFP in coagulopathic critically ill patients. However, lack of knowledge about FFP and personal beliefs about the preferable transfusion strategy among clinicians, resulted in premature termination of a clinical trial on this topic. © 2014 British Blood Transfusion Society.

MitoQ--a mitochondria-targeted antioxidant.

PubMed

Tauskela, Joseph S

2007-06-01

MitoQ is an orally active antioxidant that has the ability to target mitochondrial dysfunction. The agent is currently under development by Antipodean Pharmaceuticals Inc in phase II clinical trials for Parkinson's disease and liver damage associated with HCV infection. MitoQ has demonstrated encouraging preclinical results in numerous studies in isolated mitochondria, cells and tissues undergoing oxidative stress and apoptotic death. MitoQ aims to not only mimic the role of the endogenous mitochondrial antioxidant coenzyme Q10 (CoQ10), but also to augment substantially the antioxidant capacity of CoQ to supraphysiological levels in a mitochondrial membrane potential-dependent manner. MitoQ represents the first foray into the clinic in an attempt to deliver an antioxidant to an intracellular region that is responsible for the formation of increased levels of potentially deleterious reactive oxygen species. Results from the clinical trials with MitoQ will have important repercussions on the relevance of a mitochondrial-targeted approach.

Hypertonic saline for brain relaxation and intracranial pressure in patients undergoing neurosurgical procedures: a meta-analysis of randomized controlled trials.

PubMed

Shao, Liujiazi; Hong, Fangxiao; Zou, Yi; Hao, Xiaofang; Hou, Haijun; Tian, Ming

2015-01-01

A wealth of evidence from randomized controlled trials (RCTs) has indicated that hypertonic saline (HS) is at least as effective as, if not better than, mannitol in the treatment of increased intracranial pressure(ICP). However, there is little known about the effects of HS in patients during neurosurgery. Thus, this meta-analysis was performed to compare the intraoperative effects of HS with mannitol in patients undergoing craniotomy. According to the research strategy, we searched PUBMED, EMBASE and Cochrane Central Register of Controlled Trials. Other sources such as the internet-based clinical trial registries and conference proceedings were also searched. After literature searching, two investigators independently performed literature screening, quality assessment of the included trials and data extraction. The outcomes included intraoperative brain relaxation, intraoperative ICP, total volume of fluid required, diuresis, hemodynamic parameters, electrolyte level, mortality or dependence and adverse events. Seven RCTs with 468 participants were included. The quality of the included trials was acceptable. HS could significantly increase the odds of satisfactory intraoperative brain relaxation (OR: 2.25, 95% CI: 1.32-3.81; P = 0.003) and decrease the mean difference (MD) of maximal ICP (MD: -2.51 mmHg, 95% CI: -3.39--1.93 mmHg; P<0.00001) in comparison with mannitol with no significant heterogeneity among the study results. Compared with HS, mannitol had a more prominent diuretic effect. And patients treated with HS had significantly higher serum sodium than mannitol-treated patients. Considering that robust outcome measures are absent because brain relaxation and ICP can be influenced by several factors except for the hyperosmotic agents, the results of present meta-analysis should be interpreted with cautions. Well-designed RCTs in the future are needed to further test the present results, identify the impact of HS on the clinically relevant outcomes and explore the potential mechanisms of HS.

Does Preoperative Radio(chemo)therapy Increase Anastomotic Leakage in Rectal Cancer Surgery? A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Qin, Changjiang; Ren, Xuequn; Xu, Kaiwu; Chen, Zhihui; He, Yulong; Song, Xinming

2014-01-01

Objective. Preoperative radio(chemo)therapy (pR(C)T) appears to increase postoperative complications of rectal cancer resection, but clinical trials have reported conflicting results. The objective of this meta-analysis was performed to assess the effects of pR(C)T on anastomotic leak after rectal cancer resection. Methods. PubMed, Embase, and the Cochrane Library were searched from January 1980 to January 2014. Randomized controlled trials included all original articles reporting anastomotic leak in patients with rectal cancer, among whom some received preoperative radiotherapy or chemoradiotherapy while others did not. The analysed end-points were the anastomotic leak. Result. Seven randomized controlled trials with 3375 patients were included in the meta-analysis. 1660 forming the group undergoing preoperative radiotherapy or chemoradiotherapy versus 1715 patients undergoing without preoperative radiotherapy or chemoradiotherapy. The meta-analyses found that pR(C)T was not an independent risk factor for anastomotic leakage (OR 1.02, 95% CI 0.80–1.30; P = 0.88). Subgroups analysis was performed and the result was not altered. Conclusions. Current evidence demonstrates that pR(C)T did not increase the risk of postoperative anastomotic leak after rectal cancer resection in patients. PMID:25477955

Designing Comparative Effectiveness Trials of Surgical Ablation for Atrial Fibrillation: Experience of the Cardiothoracic Surgical Trials Network

PubMed Central

Gillinov, A. Marc; Argenziano, Michael; Blackstone, Eugene H.; Iribarne, Alexander; DeRose, Joseph J.; Ailawadi, Gorav; Russo, Mark J.; Ascheim, Deborah D.; Parides, Michael K.; Rodriguez, Evelio; Bouchard, Denis; Taddei-Peters, Wendy C.; Geller, Nancy L.; Acker, Michael A.; Gelijns, Annetine C.

2013-01-01

Background Since the introduction of the cut-and-sew Cox-Maze procedure for atrial fibrillation (AF) there has been substantial innovation in techniques for ablation. Use of alternate energy sources for ablation simplified the procedure and has resulted in dramatic increase in the number of AF patients treated by surgical ablation. Despite its increasingly widespread adoption, there is lack of rigorous clinical evidence to establish this as an effective clinical therapy. Methods and Results This paper describes a comparative effectiveness randomized trial, supported by the Cardiothoracic Surgical Trials Network, of surgical ablation with left atrial appendage (LAA) closure versus LAA closure alone in patients with persistent and longstanding persistent AF undergoing mitral valve surgery. Nested within this trial, is a further randomized comparison of 2 different lesions sets: pulmonary vein isolation and full Maze lesion set. This paper addresses trial design challenges, including how to best characterize the target population, operationalize freedom from AF as a primary endpoint, account for the impact of anti-arrhythmic drugs, and measure and analyze secondary endpoints, such as post-operative AF load. Conclusions This paper concludes by discussing how insights that emerge from this trial may affect surgical practice and guide future research in this area. PMID:21616507

Sinusitis in patients undergoing allogeneic bone marrow transplantation - a review.

PubMed

Drozd-Sokolowska, Joanna Ewa; Sokolowski, Jacek; Wiktor-Jedrzejczak, Wieslaw; Niemczyk, Kazimierz

Sinusitis is a common morbidity in general population, however little is known about its occurrence in severely immunocompromised patients undergoing allogeneic hematopoietic stem cell transplantation. The aim of the study was to analyze the literature concerning sinusitis in patients undergoing allogeneic bone marrow transplantation. An electronic database search was performed with the objective of identifying all original trials examining sinusitis in allogeneic hematopoietic stem cell transplant recipients. The search was limited to English-language publications. Twenty five studies, published between 1985 and 2015 were identified, none of them being a randomized clinical trial. They reported on 31-955 patients, discussing different issues i.e. value of pretransplant sinonasal evaluation and its impact on post-transplant morbidity and mortality, treatment, risk factors analysis. Results from analyzed studies yielded inconsistent results. Nevertheless, some recommendations for good practice could be made. First, it seems advisable to screen all patients undergoing allogeneic hematopoietic stem cell transplantation with Computed Tomography (CT) prior to procedure. Second, patients with symptoms of sinusitis should be treated before hematopoietic stem cell transplantation (HSCT), preferably with conservative medical approach. Third, patients who have undergone hematopoietic stem cell transplantation should be monitored closely for sinusitis, especially in the early period after transplantation. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

A pilot randomized trial of pentoxifylline for the reduction of periprocedural myocardial injury in patients undergoing elective percutaneous coronary intervention.

PubMed

Aslanabadi, Naser; Shirzadi, Hamid Reza; Asghari-Soufi, Hossein; Dousti, Samaneh; Ghaffari, Samad; Sohrabi, Bahram; Mashayekhi, Simin Ozar; Hamishehkar, Hadi; Entezari-Maleki, Taher

2015-02-01

Periprocedural myocardial injury (PMI) following percutaneous coronary intervention (PCI) has received great attention due to its significant association with mortality and morbidity. Accordingly, cardioprotection during PCI is one of the important therapeutic concerns. Regarding the potential cardiovascular benefits of pentoxifylline this study was performed to evaluate whether the pretreatment pentoxifylline could reduce PMI in patients who are undergoing elective PCI. A randomized clinical trial on 85 patients undergoing elective PCI was performed. The intervention group (n = 41) received 1200 mg pentoxifylline in divided doses plus the standard treatment before PCI, while the control group (n = 44) received the standard treatment. For assessing myocardial damage during PCI, the levels of CK-MB and troponin-I were measured at baseline, 8, and 24 h after the procedure. Then, patients were followed up for a 1-month period regarding the major adverse cardiac effect. Comparing with the control group, no significant change of CK-MB at 8 (p = 0.315) and 24 h (p = 0.896) after PCI was documented in pentoxifylline group. Similarly, no significant change was found in troponin-I at 8 (p = 0.141) and 24 h (p = 0.256) after PCI. This study could not support the pretreatment with pentoxifylline in the prevention of PMI in patients undergoing elective PCI. However, the trend was toward the potential benefit of pentoxifylline.

Efficacy of a dual-ring wound protector for prevention of incisional surgical site infection after Whipple's procedure (pancreaticoduodenectomy) with preoperatively-placed intrabiliary stents: protocol for a randomised controlled trial.

PubMed

Bressan, Alexsander K; Roberts, Derek J; Edwards, Janet P; Bhatti, Sana U; Dixon, Elijah; Sutherland, Francis R; Bathe, Oliver; Ball, Chad G

2014-08-21

Among surgical oncology patients, incisional surgical site infection is associated with substantially increased morbidity, mortality and healthcare costs. Moreover, while adults undergoing pancreaticoduodenectomy with preoperative placement of an intrabiliary stent have a high risk of this type of infection, and wound protectors may significantly reduce its risk, no relevant studies of wound protectors yet exist involving this patient population. This study will evaluate the efficacy of a dual-ring wound protector for prevention of incisional surgical site infection among adults undergoing pancreaticoduodenectomy with preoperatively-placed intrabiliary stents. This study will be a parallel, dual-arm, randomised controlled trial that will utilise a more explanatory than pragmatic attitude. All adults (≥18 years) undergoing a pancreaticoduodenectomy at the Foothills Medical Centre in Calgary, Alberta, Canada with preoperative placement of an intrabiliary stent will be considered eligible. Exclusion criteria will include patient age <18 years and those receiving long-term glucocorticoids. The trial will employ block randomisation to allocate patients to a commercial dual-ring wound protector (the Alexis Wound Protector) or no wound protector and the current standard of care. The main outcome measure will be the rate of surgical site infection as defined by the Centers for Disease Control and Prevention criteria within 30 days of the index operation date as determined by a research assistant blinded to treatment allocation. Outcomes will be analysed by a statistician blinded to allocation status by calculating risk ratios and 95% CIs and compared using Fisher's exact test. This will be the first randomised trial to evaluate the efficacy of a dual-ring wound protector for prevention of incisional surgical site infection among patients undergoing pancreaticoduodenectomy. Results of this study are expected to be available in 2016/2017 and will be disseminated using an integrated and end-of-grant knowledge translation strategy. ClinicalTrials.gov identifier NCT01836237. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A Meta-Analysis Comparing Liposomal Bupivacaine and Traditional Periarticular Injection for Pain Control after Total Knee Arthroplasty.

PubMed

Sun, Hao; Huang, Zhiyu; Zhang, Zhiqi; Liao, Weiming

2018-04-04

Liposomal bupivacaine is a novel method for pain control after total knee arthroplasty (TKA), but recent studies showed no advantage for patients undergoing TKA compared with traditional periarticular injection (PAI). The purpose of this analysis was to compare the clinical outcomes between liposomal bupivacaine treatment and traditional PAI. We retrospectively reviewed data from 16 clinical trials in published databases from their inception to June 2017. The primary outcome was postoperative Visual Analogue Scale (VAS) score and secondary outcomes included opiate usage, narcotic consumption, range of motion, and length of stay. Nine randomized controlled trials and seven nonrandomized controlled trials involving 924 liposomal bupivacaine cases and 1,293 traditional PAI cases were eligible for inclusion in the meta-analysis. No differences were detected in most of the clinical outcomes, except for postoperative VAS within 12 hours and length of stay. This analysis showed that liposomal bupivacaine is not associated with significant improvement in postoperative pain control or other outcomes in TKA compared with PAI. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Music and 25% glucose pain relief for the premature infant: a randomized clinical trial.

PubMed

Cardoso, Maria Vera Lúcia Moreira Leitão; Farias, Leiliane Martins; de Melo, Gleicia Martins

2014-10-01

To analyze the total Premature Infant Pain Profile scores of premature infants undergoing arterial puncture during music and 25% glucose interventions, and to assess their association with neonatal and therapeutic variables. A randomized clinical trial with 80 premature infants; 24 in the Experimental Group 1 (music), 33 in the Experimental Group 2 (music and 25% glucose), 23 in the Positive Control Group (25% glucose). All premature infants were videotaped and a lullaby was played for ten minutes before puncture in Experimental Groups 1 and 2; 25% glucose administered in Experimental Group 2 and the Positive Control Group two minutes before puncture. 60.0% of premature infants had moderate or maximum pain; pain scores and intervention groups were not statistically significant. Statistically significant variables: Experimental Group 1: head and chest circumference, Apgar scores, corrected gestational age; Experimental Group 2: chest circumference, Apgar scores, oxygen therapy; Positive Control group: birth weight, head circumference. Neonatal variables are associated with pain in premature infants. Brazilian Registry of Clinical Trials: UTN: U1111-1123-4821.

Design and Rationale for the Endothelin-1 Receptor Antagonism in the Prevention of Microvascular Injury in Patients with non-ST Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention (ENDORA-PCI) Trial.

PubMed

Liou, Kevin; Jepson, Nigel; Buckley, Nicolas; Chen, Vivien; Thomas, Shane; Russell, Elizabeth Anne; Ooi, Sze-Yuan

2016-04-01

Peri-procedural myocardial infarction (PMI) occurs in a small but significant portion of patients undergoing percutaneous intervention (PCI). The underlying mechanisms are complex and may include neurohormonal activation and release of vasoactive substances resulting in disruption of the coronary microcirculation. Endothelin in particular has been found in abundance in atherosclerotic plaques and in systemic circulation following PCI, and may be a potential culprit for PMI through its action on microvascular vasoconstriction, and platelet and neutrophil activation. In this study we aim to characterize the behavior of the coronary microcirculation during a PCI with the index of microvascular resistance (IMR) and the effect of peri-procedural endothelin antagonism. The ENDORA-PCI trial is a randomized, double-blind, placebo-controlled, single-center clinical trial designed to evaluate the efficacy of endothelin antagonism in attenuating the peri-procedural rise in IMR as a surrogate marker for PMI. The patients of interest are those with non-ST elevation acute coronary syndrome (NSTEACS) undergoing PCI, and we aim to recruit 52 patients overall to give the study a power of 80 % at an α level of 5 %. Patients will be randomized in a 1:1 fashion to either Ambrisentan, an endothelin antagonist, or placebo, prior to their PCI. IMR will be measured before and after PCI. The primary endpoint is the difference in peri-procedural changes in patients' IMR between the two groups. The ENDORA-PCI study will investigate whether endothelin antagonism with Ambrisentan attenuates the peri-procedural rise in IMR in patients with NSTEACS undergoing PCI, and thus potentially the risk of PMI.

Should TAVR be Performed in Nonagenarians? Insights from the STS/ACC TVT Registry

PubMed Central

Arsalan, Mani; Szerlip, Molly; Vemulapalli, Sreekanth; Holper, Elizabeth M.; Arnold, Suzanne V.; Li, Zhuokai; DiMaio, Michael J.; Rumsfeld, John S.; Brown, David L.; Mack, Michael J.

2017-01-01

Background Despite clinical trial evidence and clinical experience supporting the efficacy of transcatheter aortic valve replacement (TAVR), data demonstrating the benefit of TAVR specifically in the very elderly patients are limited, as they often represent only a small proportion of the clinical trial populations. Objectives To compare the outcomes of nonagenarians to younger patients undergoing TAVR in current clinical practice. Methods National U.S. data from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) Registry were analyzed. Outcomes at 30-days and 1-year were compared between patients ≥90 vs <90 years of age using cumulative incidence curves. Quality of life was assessed with the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Results Between November 2011 and September 2014, 24,025 patients underwent TAVR in 329 participating hospitals, of which 3,773 (15.7%) were age ≥90. The 30-day and 1-year mortality was significantly higher among nonagenarians (≥90 vs. <90: 30-day: 8.8% vs. 5.9%, p<0.001; 1-year: 24.8% vs. 22.0%, p<0.001, absolute risk 2.8%, relative risk 12.7%). However, nonagenarians had a higher mean STS PROM score(10.9% vs. 8.1%; p<0.001) and therefore had similar ratios of observed to expected rates of 30-day death (≥90 vs. <90: 0.81, 95% CI 0.70–0.92 vs. 0.72, 95% CI 0.67–0.78). There were no differences in the rates of stroke, aortic valve reintervention or myocardial infarction at 30-days or 1-year. Nonagenarians had lower (worse) median KCCQ-12 scores at 30-days; however, there was no significant difference at 1-year. Conclusions In current U.S. clinical practice, approximately 16% of patients undergoing TAVR are ≥90 years of age. Although 30-day and 1-year mortality was statistically higher compared with younger patients undergoing TAVR, the absolute and relative differences were clinically modest. TAVR also improves quality of life to the same degree in nonagenarians as in younger patients. These data support safety and efficacy of TAVR in select very elderly patients. PMID:27012397

Protocol for a multi-centre randomised controlled trial comparing arthroscopic hip surgery to physiotherapy-led care for femoroacetabular impingement (FAI): the Australian FASHIoN trial.

PubMed

Murphy, Nicholas J; Eyles, Jillian; Bennell, Kim L; Bohensky, Megan; Burns, Alexander; Callaghan, Fraser M; Dickenson, Edward; Fary, Camdon; Grieve, Stuart M; Griffin, Damian R; Hall, Michelle; Hobson, Rachel; Kim, Young Jo; Linklater, James M; Lloyd, David G; Molnar, Robert; O'Connell, Rachel L; O'Donnell, John; O'Sullivan, Michael; Randhawa, Sunny; Reichenbach, Stephan; Saxby, David J; Singh, Parminder; Spiers, Libby; Tran, Phong; Wrigley, Tim V; Hunter, David J

2017-09-26

Femoroacetabular impingement syndrome (FAI), a hip disorder affecting active young adults, is believed to be a leading cause of hip osteoarthritis (OA). Current management approaches for FAI include arthroscopic hip surgery and physiotherapy-led non-surgical care; however, there is a paucity of clinical trial evidence comparing these approaches. In particular, it is unknown whether these management approaches modify the future risk of developing hip OA. The primary objective of this randomised controlled trial is to determine if participants with FAI who undergo hip arthroscopy have greater improvements in hip cartilage health, as demonstrated by changes in delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) index between baseline and 12 months, compared to those who undergo physiotherapy-led non-surgical management. This is a pragmatic, multi-centre, two-arm superiority randomised controlled trial comparing hip arthroscopy to physiotherapy-led management for FAI. A total of 140 participants with FAI will be recruited from the clinics of participating orthopaedic surgeons, and randomly allocated to receive either surgery or physiotherapy-led non-surgical care. The surgical intervention involves arthroscopic FAI surgery from one of eight orthopaedic surgeons specialising in this field, located in three different Australian cities. The physiotherapy-led non-surgical management is an individualised physiotherapy program, named Personalised Hip Therapy (PHT), developed by a panel to represent the best non-operative care for FAI. It entails at least six individual physiotherapy sessions over 12 weeks, and up to ten sessions over six months, provided by experienced musculoskeletal physiotherapists trained to deliver the PHT program. The primary outcome measure is the change in dGEMRIC score of a ROI containing both acetabular and femoral head cartilages at the chondrolabral transitional zone of the mid-sagittal plane between baseline and 12 months. Secondary outcomes include patient-reported outcomes and several structural and biomechanical measures relevant to the pathogenesis of FAI and development of hip OA. Interventions will be compared by intention-to-treat analysis. The findings will help determine whether hip arthroscopy or an individualised physiotherapy program is superior for the management of FAI, including for the prevention of hip OA. Australia New Zealand Clinical Trials Registry reference: ACTRN12615001177549 . Trial registered 2/11/2015 (retrospectively registered).

Preemptive carprofen for peri-operative analgesia in dogs undergoing Tibial Plateau Leveling Osteotomy (TPLO): a prospective, randomized, blinded, placebo controlled clinical trial.

PubMed

Bufalari, A; Maggio, C; Cerasoli, I; Morath, U; Adami, C

2012-03-01

Eighteen client-owned dogs undergoing Tibial Plateau Leveling Osteotomy (TPLO) were included in this blinded clinical study and randomly assigned to one of two treatment groups. Group C (carprofen) received intravenous (IV) carprofen, 4 mg/kg, prior to anesthesia, whereas group P (placebo) received IV saline. General anesthesia was maintained with isoflurane in oxygen and a constant rate infusion (CRI) of sufentanyl IV. Intra-operatively, assessment of nociception was based on changes in physiological parameters and on the analgesics requirement, whereas in the post-operative period evaluation of pain was performed by using a Hellyer and Gaynor pain score and by comparing the doses of rescue buprenorphine required by the two treatment groups. Although no statistically significant differences in intra-operative sufentanyl doses were found between treatment groups, group C had superior cardiovascular stability, and lower post-operative pain scores and rescue buprenorphine doses than group P. Our results indicate that administration of carprofen prior to surgery was effective in improving peri-operative analgesia in dogs undergoing TPLO.

Tranexamic acid for reducing mortality in emergency and urgent surgery.

PubMed

Perel, Pablo; Ker, Katharine; Morales Uribe, Carlos Hernando; Roberts, Ian

2013-01-31

Emergency or urgent surgery, which can be defined as surgery which must be done promptly to save life, limb, or functional capacity, is associated with a high risk of bleeding and death. Antifibrinolytic agents, such as tranexamic acid, inhibit blood clot breakdown (fibrinolysis) and can reduce perioperative bleeding. Tranexamic acid has been shown to reduce the need for a blood transfusion in adult patients undergoing elective surgery but its effects in patients undergoing emergency or urgent surgery is unclear.   To assess the effects of tranexamic acid on mortality, blood transfusion and thromboembolic events in adults undergoing emergency or urgent surgery. We searched the following electronic databases: the Cochrane Injuries Group's Specialised Register (22 August 2012); Cochrane Central Register of Controlled Trials (2012, issue 8 of 12); MEDLINE (Ovid SP) 1950 to August Week 2, 2012; PubMed 1 June 2012 to 22 August 2012; EMBASE (Ovid SP) 1980 to 2012 Week 33; ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) 1990 to 22 August 2012; ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) 1970 to 22 August 2012. We also searched online trial registers on 22 August 2012 to identify unpublished studies. Randomised controlled trials comparing tranexamic acid with no tranexamic acid or placebo in adults undergoing emergency or urgent surgery. Two authors examined titles, abstracts and keywords of citations from the electronic databases for eligibility and extracted data for analysis and risk of bias assessment. Outcome measures of interest were mortality, receipt of a blood transfusion, units of blood transfused, reoperation, seizures and thromboembolic events (myocardial infarction, stroke, deep vein thrombosis and pulmonary embolism). We identified five trials involving 372 people that met the inclusion criteria. Three trials (260 patients) contributed data to the analyses. The effect of tranexamic acid on mortality (RR 1.01; 95% CI 0.14 to 7.3) is uncertain. However, tranexamic acid reduces the probability of receiving a blood transfusion by 30% although the estimate is imprecise (RR 0.70; 95% CI 0.52 to 0.94). The effect on deep venous thrombosis (RR 2.29; 95% CI 0.68 to 7.66), and stroke (RR 2.79; 95% CI 0.12 to 67.10) is uncertain. There were no events of pulmonary embolism or myocardial infarction. None of the trials reported units of blood transfused, reoperation, or seizure outcomes. There is evidence that tranexamic acid reduces blood transfusion in patients undergoing emergency or urgent surgery. There is a need for a large pragmatic clinical trial to assess the effects of routine use of tranexamic acid on mortality in a heterogeneous group of urgent and emergency surgical patients.

[Leber hereditary optic neuropathy].

PubMed

Mazunin, I O; Volodko, N V

2018-01-01

Leber hereditary optic neuropathy is characterized by bilateral, painless loss of vision in children and young adults (generally up to 25 years old). Since its first description in 1871, the understanding of its etiology and pathogenesis has improved considerably. The article considers Leber neuropathy from the points of view of ophthalmology, neurology and molecular genetics, and presents data on experimental treatment methods, one of which is undergoing clinical trial.

Transversus Abdominis Plane Block versus Ilioinguinal/Iliohypogastric Nerve Block with Wound Infiltration for Postoperative Analgesia in Inguinal Hernia Surgery: A Randomized Clinical Trial.

PubMed

Sujatha, Chinthavali; Zachariah, Mamie; Ranjan, R V; George, Sagiev Koshy; Ramachandran, T R; Pillai, Anil Radhakrishna

2017-01-01

Various analgesic modalities have been used for postoperative analgesia in patients undergoing inguinal hernia surgery. In this randomized clinical trial, we have compared the analgesic efficacy of transversus abdominis plane (TAP) block with that of ilioinguinal/iliohypogastric (IIIH) nerve block with wound infiltration in patients undergoing unilateral open inguinal hernia repair. The primary objective of this study was to compare the efficacy of postoperative analgesia of ultrasound-guided TAP block and IIIH block with wound infiltration (WI) in patients undergoing open inguinal hernia surgery. This was a randomized clinical trial performed in a tertiary care hospital. Sixty patients scheduled for hernia repair were randomized into two groups, Group T and Group I. Postoperatively, under ultrasound guidance, Group T received 20 ml of 0.25% ropivacaine - TAP block and Group I received 10 ml of 0.25% ropivacaine - IIIH block + WI with 10 ml of 0.25% ropivacaine. The primary outcome measure was the time to rescue analgesia in the first 24 h postoperatively. Fentanyl along with diclofenac was given as first rescue analgesic when the patient complained of pain. Statistical comparisons were performed using Student's t -test and Chi-square test. Mean time to rescue analgesia was 5.900 ± 1.881 h and 3.766 ± 1.754 h ( P < 0.001) and the mean pain scores were 5.73 ± 0.784 and 6.03 ± 0.850 for Group TAP and IIIH + WI, respectively. Hemodynamics were stable in both the groups. One-third of the patients received one dose of paracetamol in addition to the rescue analgesic in the first 24 h. There were no complications attributed to the block. As a multimodal analgesic regimen, definitely both TAP block and IIIH block with wound infiltration have a supporting role in providing analgesia in the postoperative period for adult inguinal hernia repair. In this study, ultrasound-guided TAP block provided longer pain control postoperatively than IIIH block with WI after inguinal hernia repair. There were no complications attributed to the blocks in either of the group.

Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery.

PubMed

Hausenloy, Derek J; Candilio, Luciano; Evans, Richard; Ariti, Cono; Jenkins, David P; Kolvekar, Shyam; Knight, Rosemary; Kunst, Gudrun; Laing, Christopher; Nicholas, Jennifer; Pepper, John; Robertson, Steven; Xenou, Maria; Clayton, Tim; Yellon, Derek M

2015-10-08

Whether remote ischemic preconditioning (transient ischemia and reperfusion of the arm) can improve clinical outcomes in patients undergoing coronary-artery bypass graft (CABG) surgery is not known. We investigated this question in a randomized trial. We conducted a multicenter, sham-controlled trial involving adults at increased surgical risk who were undergoing on-pump CABG (with or without valve surgery) with blood cardioplegia. After anesthesia induction and before surgical incision, patients were randomly assigned to remote ischemic preconditioning (four 5-minute inflations and deflations of a standard blood-pressure cuff on the upper arm) or sham conditioning (control group). Anesthetic management and perioperative care were not standardized. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, coronary revascularization, or stroke, assessed 12 months after randomization. We enrolled a total of 1612 patients (811 in the control group and 801 in the ischemic-preconditioning group) at 30 cardiac surgery centers in the United Kingdom. There was no significant difference in the cumulative incidence of the primary end point at 12 months between the patients in the remote ischemic preconditioning group and those in the control group (212 patients [26.5%] and 225 patients [27.7%], respectively; hazard ratio with ischemic preconditioning, 0.95; 95% confidence interval, 0.79 to 1.15; P=0.58). Furthermore, there were no significant between-group differences in either adverse events or the secondary end points of perioperative myocardial injury (assessed on the basis of the area under the curve for the high-sensitivity assay of serum troponin T at 72 hours), inotrope score (calculated from the maximum dose of the individual inotropic agents administered in the first 3 days after surgery), acute kidney injury, duration of stay in the intensive care unit and hospital, distance on the 6-minute walk test, and quality of life. Remote ischemic preconditioning did not improve clinical outcomes in patients undergoing elective on-pump CABG with or without valve surgery. (Funded by the Efficacy and Mechanism Evaluation Program [a Medical Research Council and National Institute of Health Research partnership] and the British Heart Foundation; ERICCA ClinicalTrials.gov number, NCT01247545.).

Targeted rehabilitation to improve outcome after total knee replacement (TRIO): study protocol for a randomised controlled trial.

PubMed

Simpson, A Hamish R W; Hamilton, David F; Beard, David J; Barker, Karen L; Wilton, Timothy; Hutchison, James D; Tuck, Chris; Stoddard, Andrew; Macfarlane, Gary J; Murray, Gordon D

2014-02-01

Approximately 20% of patients are not satisfied with the outcome of total knee replacement, great volumes of which are carried out yearly. Physiotherapy is often provided by the NHS to address dysfunction following knee replacement; however the efficacy of this is unknown. Although clinically it is accepted that therapy is useful, provision of physiotherapy to all patients post-operatively does not enhance outcomes at one year. No study has previously assessed the effect of targeting therapy to individuals struggling to recover in the early post-operative phase.The aim of the TRIO study is to determine whether stratifying care by targeting physiotherapy to those individuals performing poorly following knee replacement is effective in improving the one year outcomes. We are also investigating whether the structure of the physiotherapy provision itself influences outcomes. The study is a multi-centre prospective randomised controlled trial (RCT) of patients undergoing primary total knee replacement, with treatment targeted at those deemed most susceptible to gain from it. Use of the national PROMS programme for pre-operative data collection allows us to screen all patients at initial post-operative clinical review, and recruit only those deemed to be recovering slowly.We aim to recruit 440 patients through various NHS orthopaedic centres who will undergo six weeks of physiotherapy. The intervention will be either 'intensive' involving both hospital and home-based functional exercise rehabilitation, or 'standard of care' consisting of home exercises. Patients will be randomised to either group using a web-based system. Both groups will receive pre and post-intervention physiotherapy review. Patients will be followed-up to one year post-operation. The primary outcome measure is the Oxford Knee Score. Secondary outcomes are patient satisfaction, functional ability, pain scores and cost-effectiveness. Current Controlled Trials ISRCTN23357609. ClinicalTrials.gov NCT01849445.

Childhood Ataxia: Clinical Features, Pathogenesis, Key Unanswered Questions, and Future Directions

PubMed Central

Ashley, Claire N.; Hoang, Kelly D.; Lynch, David R.; Perlman, Susan L.; Maria, Bernard L.

2013-01-01

Childhood ataxia is characterized by impaired balance and coordination primarily due to cerebellar dysfunction. Friedreich ataxia, a form of childhood ataxia, is the most common multisystem autosomal recessive disease. Most of these patients are homozygous for the GAA repeat expansion located on the first intron of the frataxin gene on chromosome 9. Mutations in the frataxin gene impair mitochondrial function, increase reactive oxygen species, and trigger redistribution of iron in the mitochondria and cytosol. Targeted therapies for Friedreich ataxia are undergoing testing. In addition, a centralized database, patient registry, and natural history study have been launched to support clinical trials in Friedreich ataxia. The 2011 Neurobiology of Disease in Children symposium, held in conjunction with the 40th annual Child Neurology Society meeting, aimed to (1) describe clinical features surrounding Friedreich ataxia, including cardiomyopathy and genetics; (2) discuss recent advances in the understanding of the pathogenesis of Friedreich ataxia and developments of clinical trials; (3) review new investigations of characteristic symptoms; (4) establish clinical and biochemical overlaps in neurodegenerative diseases and possible directions for future basic, translational, and clinical studies. PMID:22859693

Colorectal Liver Metastases: Does the Future of Precision Medicine Lie in Genetic Testing?

PubMed

Barbon, Carlotta; Margonis, Georgios Antonios; Andreatos, Nikolaos; Rezaee, Neda; Sasaki, Kazunari; Buettner, Stefan; Damaskos, Christos; Pawlik, Timothy M; He, Jin; Wolfgang, Christopher L; Weiss, Matthew J

2018-04-11

Colorectal liver metastases (CRLM) present an important clinical challenge in both surgical and medical oncology. Despite improvements in management, survival among patients undergoing resection of CRLM is still very variable and there is a paucity of clinical trial data and reliable biomarkers that could guide prognostic forecasts, treatment selection, and follow-up. Fortunately, recent advances in molecular biology and tumor sequencing have identified a number of critical genetic loci and proliferation markers that may hold the key to understanding the biologic behavior of CRLM; specifically, mutations of KRAS, BRAF, TP53, PIK3CA, APC, expression of Ki-67, and the presence of microsatellite instability appear to have a decisive impact on prognosis and response to treatment in patients with CRLM. While the applicability of genetic biomarkers in everyday clinical practice remains conditional on the development of inexpensive bedside sequencing, targeted therapies, and the conduct of appropriate clinical trials, the promise of personalized treatment may be closer to realization than ever before.

Triiodothyronine Supplementation in Infants and Children Undergoing Cardiopulmonary Bypass (TRICC) A Multicenter Placebo-Controlled Randomized Trial: Age Analysis

PubMed Central

Portman, Michael A.; Slee, April; Olson, Aaron K.; Cohen, Gordon; Karl, Tom; Tong, Elizabeth; Hastings, Laura; Patel, Hitendra; Reinhartz, Olaf; Mott, Antonio R.; Mainwaring, Richard; Linam, Justin; Danzi, Sara

2011-01-01

Background Triiodothyronine levels decrease in infants and children after cardiopulmonary bypass. We tested the primary hypothesis that triiodothyronine (T3) repletion is safe in this population and produces improvements in postoperative clinical outcome. Methods and Results The TRICC study was a prospective, multicenter, double-blind, randomized, placebo-controlled trial in children younger than 2 years old undergoing heart surgery with cardiopulmonary bypass. Enrollment was stratified by surgical diagnosis. Time to extubation (TTE) was the primary outcome. Patients received intravenous T3 as Triostat (n=98) or placebo (n=95), and data were analyzed using Cox proportional hazards. Overall, TTE was similar between groups. There were no differences in adverse event rates, including arrhythmia. Prespecified analyses showed a significant interaction between age and treatment (P=0.0012). For patients younger than 5 months, the hazard ratio (chance of extubation) for Triostat was 1.72. (P=0.0216). Placebo median TTE was 98 hours with 95% confidence interval (CI) of 71 to 142 compared to Triostat TTE at 55 hours with CI of 44 to 92. TTE shortening corresponded to a reduction in inotropic agent use and improvement in cardiac function. For children 5 months of age, or older, Triostat produced a significant delay in median TTE: 16 hours (CI, 7–22) for placebo and 20 hours (CI, 16–45) for Triostat and (hazard ratio, 0.60; P=0.0220). Conclusions T3 supplementation is safe. Analyses using age stratification indicate that T3 supplementation provides clinical advantages in patients younger than 5 months and no benefit for those older than 5 months. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00027417. PMID:20837917

Evaluating efficacy and feasibility of transcutaneous electrical nerve stimulation for postoperative pain after video-assisted thoracoscopic surgery: A randomized pilot trial.

PubMed

Engen, Deborah J; Carns, Paul E; Allen, Mark S; Bauer, Brent A; Loehrer, Laura L; Cha, Stephen S; Chartrand, Christine M; Eggler, Eric J; Cutshall, Susanne M; Wahner-Roedler, Dietlind L

2016-05-01

Transcutaneous electrical nerve stimulation (TENS) has been applied for pain relief after surgical procedures. This study evaluated whether TENS after video-assisted thoracoscopic surgery (VATS), in addition to opioid administration, decreased postoperative pain and pain medication use. In a controlled trial, 56 patients scheduled to undergo VATS were randomly assigned to TENS plus opioids (Group 1) or opioids alone (Group 2) for 48 h. Forty patients completed the study. Pain scores and use of oral morphine equivalents (OMEs) were not significantly different between the groups during the first and second 24 h. A decreased use of OMEs between the first and second 24 h was significant for Group 1 (P = .005) but not for Group 2 (P = .11); a decreased use of OMEs between groups was not significant (P = .35). A larger, well-powered clinical trial is indicated to evaluate the effects of TENS for pain control after a VATS procedure. Clinical Trial No.: NCT01046695. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

The Risk of Oxygen during Cardiac Surgery (ROCS) trial: study protocol for a randomized clinical trial.

PubMed

Lopez, Marcos G; Pretorius, Mias; Shotwell, Matthew S; Deegan, Robert; Eagle, Susan S; Bennett, Jeremy M; Sileshi, Bantayehu; Liang, Yafen; Gelfand, Brian J; Kingeter, Adam J; Siegrist, Kara K; Lombard, Frederick W; Richburg, Tiffany M; Fornero, Dane A; Shaw, Andrew D; Hernandez, Antonio; Billings, Frederic T

2017-06-26

Anesthesiologists administer excess supplemental oxygen (hyper-oxygenation) to patients during surgery to avoid hypoxia. Hyper-oxygenation, however, may increase the generation of reactive oxygen species and cause oxidative damage. In cardiac surgery, increased oxidative damage has been associated with postoperative kidney and brain injury. We hypothesize that maintenance of normoxia during cardiac surgery (physiologic oxygenation) decreases kidney injury and oxidative damage compared to hyper-oxygenation. The Risk of Oxygen during Cardiac Surgery (ROCS) trial will randomly assign 200 cardiac surgery patients to receive physiologic oxygenation, defined as the lowest fraction of inspired oxygen (FIO 2 ) necessary to maintain an arterial hemoglobin saturation of 95 to 97%, or hyper-oxygenation (FIO 2  = 1.0) during surgery. The primary clinical endpoint is serum creatinine change from baseline to postoperative day 2, and the primary mechanism endpoint is change in plasma concentrations of F 2 -isoprostanes and isofurans. Secondary endpoints include superoxide production, clinical delirium, myocardial injury, and length of stay. An endothelial function substudy will examine the effects of oxygen treatment and oxidative stress on endothelial function, measured using flow mediated dilation, peripheral arterial tonometry, and wire tension myography of epicardial fat arterioles. The ROCS trial will test the hypothesis that intraoperative physiologic oxygenation decreases oxidative damage and organ injury compared to hyper-oxygenation in patients undergoing cardiac surgery. ClinicalTrials.gov, ID: NCT02361944 . Registered on the 30th of January 2015.

Progress in the development of animal models of acute kidney injury and its impact on drug discovery.

PubMed

Sanz, Ana B; Sanchez-Niño, María Dolores; Martín-Cleary, Catalina; Ortiz, Alberto; Ramos, Adrián M

2013-07-01

Acute kidney injury (AKI) is a clinical syndrome characterized by the acute loss of kidney function. AKI is increasingly frequent and is associated with impaired survival and chronic kidney disease progression. Experimental AKI models have contributed to a better understanding of pathophysiological mechanisms but they have not yet resulted in routine clinical application of novel therapeutic approaches. The authors present the advances in experimental AKI models over the last decade. Furthermore, the authors review their current and expected impact on novel drug discovery. New AKI models have been developed in rodents and non-rodents. Non-rodents allow the evaluation of specific aspects of AKI in both bigger animals and simpler organisms such as drosophila and zebrafish. New rodent models have recently reproduced described clinical entities, such as aristolochic and warfarin nephropathies, and have also provided better models for old entities such as thrombotic microangiopathy-induced AKI. Several therapies identified in animal models are now undergoing clinical trials in human AKI, including p53 RNAi and bone-marrow derived mesenchymal stem cells. It is conceivable that further refinement of animal models in combination with ongoing trials and novel trials based on already identified potential targets will eventually yield effective therapies for clinical AKI.

Impact of Tight Glycemic Control on Neurodevelopmental Outcomes at 1 Year of Age for Children with Congenital Heart Disease: A Randomized Controlled Trial.

PubMed

Sadhwani, Anjali; Asaro, Lisa A; Goldberg, Caren; Ware, Janice; Butcher, Jennifer; Gaies, Michael; Smith, Cynthia; Alexander, Jamin L; Wypij, David; Agus, Michael S D

2016-07-01

To assess the association of postoperative tight glycemic control and hypoglycemia in children undergoing cardiac surgery with neurodevelopmental outcomes at 1 year of age. A 2-center, prospective, randomized trial of postoperative tight glycemic control vs standard care was conducted in 980 children undergoing cardiac surgery. Neurodevelopmental outcomes were assessed at nine to 18 months using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), the Adaptive Behavior Assessment System, Second Edition, the Ages and Stages Questionnaire, Third Edition, and the Brief Infant Toddler Social-Emotional Assessment. Neurodevelopmental follow-up was performed on 237 patients with a mean age of 13 months. No significant treatment group differences were found in the Bayley-III and Adaptive Behavior Assessment System, Second Edition composite scores or percentage at risk based on the Ages and Stages Questionnaire, Third Edition and the Brief Infant Toddler Social-Emotional Assessment. Patients who experienced moderate to severe hypoglycemia (n = 8) had lower Bayley-III composite scores compared with patients with no to mild hypoglycemia, even after controlling for factors known to be associated with poorer neurodevelopmental outcomes. For infants undergoing cardiac surgery, tight glycemic control did not impact neurodevelopmental outcomes compared with standard care. These data suggest a possible association between moderate to severe hypoglycemia and poorer neurodevelopmental outcomes at 1 year of age. ClinicalTrials.gov: NCT00443599. Copyright © 2016 Elsevier Inc. All rights reserved.

Oral supplementation with carbohydrate- and branched-chain amino acid-enriched nutrients improves postoperative quality of life in patients undergoing hepatic resection.

PubMed

Okabayashi, Takehiro; Iyoki, Miho; Sugimoto, Takeki; Kobayashi, Michiya; Hanazaki, Kazuhiro

2011-04-01

The long-term outcomes of branched-chain amino acid (BCAA) administration in patients undergoing hepatic resection remain unclear. The aim of this study is to assess the impact of oral supplementation with BCAA-enriched nutrients on postoperative quality of life (QOL) in patients undergoing liver resection. A prospective randomized clinical trial was conducted in 96 patients undergoing hepatic resection. Patients were randomly assigned to receive BCAA supplementation (AEN group, n = 48) or a conventional diet (control group, n = 48). Postoperative QOL and short-term outcomes were regularly and continuously evaluated in all patients using a short-form 36 (SF-36) health questionnaire and by measuring various clinical parameters. This study demonstrated a significant improvement in QOL after hepatectomy for liver neoplasm in the AEN group based on the same patients' preoperative SF-36 scores (P < 0.05). Perioperative BCAA supplementation preserved liver function and general patient health in the short term for AEN group patients compared to those not receiving the nutritional supplement. BCAA supplementation improved postoperative QOL after hepatic resection over the long term by restoring and maintaining nutritional status and whole-body kinetics. This study was registered at http://www.clinicaltrials.gov (registration number: NCT00945568).

Cost-effectiveness and clinical efficacy of biliary stents in patients undergoing neoadjuvant therapy for pancreatic adenocarcinoma in a randomized controlled trial.

PubMed

Gardner, Timothy B; Spangler, Chad C; Byanova, Katerina L; Ripple, Gregory H; Rockacy, Matthew J; Levenick, John M; Smith, Kerrington D; Colacchio, Thomas A; Barth, Richard J; Zaki, Bassem I; Tsapakos, Michael J; Gordon, Stuart R

2016-09-01

The optimal type of stent for the palliation of malignant biliary obstruction in patients with pancreatic adenocarcinoma undergoing neoadjuvant chemoradiotherapy with curative intent is unknown. We performed a prospective trial comparing 3 types of biliary stents-fully covered self-expandable metal (fcSEMS), uncovered self-expandable metal (uSEMS), and plastic-to determine which best optimized cost-effectiveness and important clinical outcomes. In this prospective randomized trial, consecutive patients with malignant biliary obstruction from newly diagnosed pancreatic adenocarcinoma who were to start neoadjuvant chemoradiotherapy were randomized to receive fcSEMSs, uSEMSs, or plastic stents during the index ERCP. The primary outcomes were time to stent occlusion, attempted surgical resection, or death after the initiation of neoadjuvant therapy, and the secondary outcomes were total patient costs associated with the stent, including the index ERCP cost, downstream hospitalization cost due to stent occlusion, and the cost associated with procedural adverse event. Fifty-four patients were randomized and reached the primary end point: 16 in the fcSEMS group, 17 in the uSEMS group, and 21 in the plastic stent group. No baseline demographic or tumor characteristic differences were noted among the groups. The fcSEMSs had a longer time to stent occlusion compared with uSEMSs and plastic stents (220 vs 74 and 76 days, P < .01), although the groups had equivalent rates of stent occlusion, attempted surgical resection, and death. Although SEMS placement cost more during the index ERCP (uSEMS = $24,874 and fcSEMS = $22,729 vs plastic = $18,701; P < .01), they resulted in higher procedural AE costs per patient (uSEMS = $5522 and fcSEMS = $12,701 vs plastic = $0; P < .01). Conversely, plastic stents resulted in an $11,458 hospitalization cost per patient due to stent occlusion compared with $2301 for uSEMSs and $0 for fcSEMSs (P < .01). In a prospective trial comparing fcSEMSs, uSEMSs, and plastic stents for malignant biliary obstruction in patients undergoing neoadjuvant therapy with curative intent for pancreatic adenocarcinoma, no stent type was superior in optimizing cost-effectiveness, although fcSEMSs resulted in fewer days of neoadjuvant treatment delay and a longer time to stent occlusion. (Clincial trial registration number: NCT01038713.). Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

The Effects of Intra-Aortic Balloon Pumps on Mortality in Patients Undergoing High-Risk Coronary Revascularization: A Meta-Analysis of Randomized Controlled Trials of Coronary Artery Bypass Grafting and Stenting Era

PubMed Central

Wan, You-Dong; Sun, Tong-Wen; Kan, Quan-Cheng; Guan, Fang-Xia; Liu, Zi-Qi; Zhang, Shu-Guang

2016-01-01

Background Intra-aortic balloon pumps (IABP) have generally been used for patients undergoing high-risk mechanical coronary revascularization. However, there is still insufficient evidence to determine whether they can improve outcomes in reperfusion therapy patients, mainly by percutaneous coronary intervention (PCI) with stenting or coronary artery bypass graft (CABG). This study was designed to determine the difference between high-risk mechanical coronary revascularization with and without IABPs on mortality, by performing a meta-analysis on randomized controlled trials of the current era. Methods Pubmed and Embase databases were searched from inception to May 2015. Unpublished data were obtained from the investigators. Randomized clinical trials of IABP and non-IABP in high-risk coronary revascularization procedures (PCI or CABG) were included. In the case of PCI procedures, stents should be used in more than 80% of patients. Numbers of events at the short-term and long-term follow-up were extracted. Results A total of 12 randomized trials enrolling 2155 patients were included. IABPs did not significantly decrease short-term mortality (relative risk (RR) 0.66; 95% CI, 0.42–1.01), or long-term mortality (RR 0.79; 95% CI, 0.47–1.35), with low heterogeneity across the studies. The findings remained stable in patients with acute myocardial infarction with or without cardiogenic shock. But in high-risk CABG patients, IABP was associated with reduced mortality (71 events in 846 patients; RR 0.40; 95%CI 0.25–0.67). Conclusion In patients undergoing high-risk coronary revascularization, IABP did not significantly decrease mortality. But high-risk CABG patients may be benefit from IABP. Rigorous criteria should be applied to the use of IABPs. PMID:26784578

Treatment of anxiety in patients with coronary heart disease: Rationale and design of the UNderstanding the benefits of exercise and escitalopram in anxious patients WIth coroNary heart Disease (UNWIND) randomized clinical trial.

PubMed

Blumenthal, James A; Feger, Bryan J; Smith, Patrick J; Watkins, Lana L; Jiang, Wei; Davidson, Jonathan; Hoffman, Benson M; Ashworth, Megan; Mabe, Stephanie K; Babyak, Michael A; Kraus, William E; Hinderliter, Alan; Sherwood, Andrew

2016-06-01

Anxiety is highly prevalent among patients with coronary heart disease (CHD), and there is growing evidence that high levels of anxiety are associated with worse prognosis. However, few studies have evaluated the efficacy of treating anxiety in CHD patients for reducing symptoms and improving clinical outcomes. Exercise and selective serotonin reuptake inhibitors have been shown to be effective in treating patients with depression, but have not been studied in cardiac patients with high anxiety. The UNWIND trial is a randomized clinical trial of patients with CHD who are at increased risk for adverse events because of comorbid anxiety. One hundred fifty participants with CHD and elevated anxiety symptoms and/or with a diagnosed anxiety disorder will be randomly assigned to 12 weeks of aerobic exercise (3×/wk, 35 min, 70%-85% VO2peak), escitalopram (5-20 mg qd), or placebo. Before and after 12 weeks of treatment, participants will undergo assessments of anxiety symptoms and CHD biomarkers of risk, including measures of inflammation, lipids, hemoglobin A1c, heart rate variability, and vascular endothelial function. Primary outcomes include post-intervention effects on symptoms of anxiety and CHD biomarkers. Secondary outcomes include clinical outcomes (cardiovascular hospitalizations and all-cause death) and measures of quality of life. The UNWIND trial (ClinicalTrials.gov NCT02516332) will evaluate the efficacy of aerobic exercise and escitalopram for improving anxiety symptoms and reducing risk for adverse clinical events in anxious CHD patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Randomized controlled trial of multidisciplinary team stress and performance in immersive simulation for management of infant in shock: study protocol.

PubMed

Ghazali, Daniel Aiham; Ragot, Stéphanie; Breque, Cyril; Guechi, Youcef; Boureau-Voultoury, Amélie; Petitpas, Franck; Oriot, Denis

2016-03-25

Human error and system failures continue to play a substantial role in adverse outcomes in healthcare. Simulation improves management of patients in critical condition, especially if it is undertaken by a multidisciplinary team. It covers technical skills (technical and therapeutic procedures) and non-technical skills, known as Crisis Resource Management. The relationship between stress and performance is theoretically described by the Yerkes-Dodson law as an inverted U-shaped curve. Performance is very low for a low level of stress and increases with an increased level of stress, up to a point, after which performance decreases and becomes severely impaired. The objectives of this randomized trial are to study the effect of stress on performance and the effect of repeated simulation sessions on performance and stress. This study is a single-center, investigator-initiated randomized controlled trial including 48 participants distributed in 12 multidisciplinary teams. Each team is made up of 4 persons: an emergency physician, a resident, a nurse, and an ambulance driver who usually constitute a French Emergency Medical Service team. Six multidisciplinary teams are planning to undergo 9 simulation sessions over 1 year (experimental group), and 6 multidisciplinary teams are planning to undergo 3 simulation sessions over 1 year (control group). Evidence of the existence of stress will be assessed according to 3 criteria: biological, electrophysiological, and psychological stress. The impact of stress on overall team performance, technical procedure and teamwork will be evaluated. Participant self-assessment of the perceived impact of simulations on clinical practice will be collected. Detection of post-traumatic stress disorder will be performed by self-assessment questionnaire on the 7(th) day and after 1 month. We will concomitantly evaluate technical and non-technical performance, and the impact of stress on both. This is the first randomized trial studying repetition of simulation sessions and its impact on both clinical performance and stress, which is explored by objective and subjective assessments. We expect that stress decreases team performance and that repeated simulation will increase it. We expect no variation of stress parameters regardless of the level of performance. ClinicalTrials.gov registration number NCT02424890.

Effects of foot reflexology on anxiety and physiological parameters in patients undergoing coronary artery bypass graft surgery: A clinical trial.

PubMed

Abbaszadeh, Yaser; Allahbakhshian, Atefeh; Seyyedrasooli, Alehe; Sarbakhsh, Parvin; Goljarian, Sakineh; Safaei, Naser

2018-05-01

This study aimed to investigate the effect of foot reflexology on anxiety and physiological parameters in patients after CABG surgery. This was a single-blind, three-arm, parallel-group, randomized controlled trial with three groups of 40 male patients undergoing CABG. Participants were placed in three groups, named intervention, placebo, and control. Physiological parameters were measured including systolic and diastolic blood pressure, mean arterial pressure, heart rate, respiratory rate, percutaneous oxygen saturation, and anxiety of participants. Results showed a statistically significant difference between intervention and control groups in terms of the level of anxiety (p < 0.05). Also, results showed a statistically significant effect on all physiological parameters except heart rate (p < 0.05). This study indicated that foot reflexology may be used by nurses as an adjunct to standard ICU care to reduce anxiety and stabilize physiological parameters such as systolic, diastolic, mean arterial pressure, and heart rate. Copyright © 2018 Elsevier Ltd. All rights reserved.

The effect of foot reflexology on physiologic parameters and mechanical ventilation weaning time in patients undergoing open-heart surgery: A clinical trial study.

PubMed

Ebadi, Abbas; Kavei, Parastoo; Moradian, Seyyed Tayyeb; Saeid, Yaser

2015-08-01

The aim of this study was to investigate the efficacy of foot reflexology on physiological parameters and mechanical ventilation weaning time in patients undergoing open-heart surgery. This was a double blind three-group randomized controlled trial. Totally, 96 patients were recruited and randomly allocated to the experimental, placebo, and the control groups. Study groups respectively received foot reflexology, simple surface touching, and the routine care of the study setting. Physiological parameters (pulse rate, respiratory rate, systolic and diastolic blood pressures, mean arterial pressure, percutaneous oxygen saturation) and weaning time were measured. The study groups did not differ significantly in terms of physiological parameters (P value > 0.05). However, the length of weaning time in the experimental group was significantly shorter than the placebo and the control groups (P value < 0.05). The study findings demonstrated the efficiency of foot reflexology in shortening the length of weaning time. Copyright © 2015 Elsevier Ltd. All rights reserved.

ABSORB II randomized controlled trial: a clinical evaluation to compare the safety, efficacy, and performance of the Absorb everolimus-eluting bioresorbable vascular scaffold system against the XIENCE everolimus-eluting coronary stent system in the treatment of subjects with ischemic heart disease caused by de novo native coronary artery lesions: rationale and study design.

PubMed

Diletti, Roberto; Serruys, Patrick W; Farooq, Vasim; Sudhir, Krishnankutty; Dorange, Cecile; Miquel-Hebert, Karine; Veldhof, Susan; Rapoza, Richard; Onuma, Yoshinobu; Garcia-Garcia, Hector M; Chevalier, Bernard

2012-11-01

Currently, no data are available on the direct comparison between the Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) and conventional metallic drug-eluting stents. The ABSORB II study is a randomized, active-controlled, single-blinded, multicenter clinical trial aiming to compare the second-generation Absorb BVS with the XIENCE everolimus-eluting metallic stent. Approximately 501 subjects will be enrolled on a 2:1 randomization basis (Absorb BVS/XIENCE stent) in approximately 40 investigational sites across Europe and New Zealand. Treated lesions will be up to 2 de novo native coronary artery lesions, each located in different major epicardial vessels, all with an angiographic maximal luminal diameter between 2.25 and 3.8 mm as estimated by online quantitative coronary angiography (QCA) and a lesion length of ≤48 mm. Clinical follow-up is planned at 30 and 180 days and at 1, 2, and 3 years. All subjects will undergo coronary angiography, intravascular ultrasound (IVUS) and IVUS-virtual histology at baseline (pre-device and post-device implantation) and at 2-year angiographic follow-up. The primary end point is superiority of the Absorb BVS vs XIENCE stent in terms of vasomotor reactivity of the treated segment at 2 years, defined as the QCA quantified change in the mean lumen diameter prenitrate and postnitrate administration. The coprimary end point is the noninferiority (reflex to superiority) of the QCA-derived minimum lumen diameter at 2 years postnitrate minus minimum lumen diameter postprocedure postnitrate by QCA. In addition, all subjects allocated to the Absorb BVS group will undergo multislice computed tomography imaging at 3 years. The ABSORB II randomized controlled trial (ClinicalTrials.gov NCT01425281) is designed to compare the safety, efficacy, and performance of Absorb BVS against the XIENCE everolimus-eluting stent in the treatment of de novo native coronary artery lesions. Copyright © 2012 Mosby, Inc. All rights reserved.

Clinical hypnosis versus cognitive behavioral training for pain management with pediatric cancer patients undergoing bone marrow aspirations.

PubMed

Liossi, C; Hatira, P

1999-04-01

A randomized controlled trial was conducted to compare the efficacy of clinical hypnosis versus cognitive behavioral (CB) coping skills training in alleviating the pain and distress of 30 pediatric cancer patients (age 5 to 15 years) undergoing bone marrow aspirations. Patients were randomized to one of three groups: hypnosis, a package of CB coping skills, and no intervention. Patients who received either hypnosis or CB reported less pain and pain-related anxiety than did control patients and less pain and anxiety than at their own baseline. Hypnosis and CB were similarly effective in the relief of pain. Results also indicated that children reported more anxiety and exhibited more behavioral distress in the CB group than in the hypnosis group. It is concluded that hypnosis and CB coping skills are effective in preparing pediatric oncology patients for bone marrow aspiration.

Clinical effectiveness of late maxillary protraction in cleft lip and palate: a methods paper

PubMed Central

Lee, MK; Lane, C; Azeredo, F; Landsberger, M; Kapadia, H; Sheller, B; Yen, SL

2017-01-01

Objectives A prospective parallel cohort trial was conducted to compare outcomes of patients treated with maxillary protraction vs. LeFort 1 maxillary advancement surgery. Setting and Sample Population The primary site for the clinical trial is Children’s Hospital Los Angeles; the satellite test site is Seattle Children’s Hospital. All patients have isolated cleft lip and palate and a skeletal Class III malocclusion. Material & Methods A total of 50 patients, ages 11–14 will be recruited for the maxillary protraction cohort. The maxillary surgery cohort consists of 50 patients, ages 16–21, who will undergo LeFort 1 maxillary advancement surgery. Patients with additional medical or cognitive handicaps were excluded from the study. Results Current recruitment of patients is on track to complete the study within the proposed recruitment period. Conclusion This observational trial is collecting information that will examine dental, skeletal, financial, and quality of life issues from both research cohorts. PMID:28643931

Ethical clinical translation of stem cell interventions for neurologic disease.

PubMed

Cote, David J; Bredenoord, Annelien L; Smith, Timothy R; Ammirati, Mario; Brennum, Jannick; Mendez, Ivar; Ammar, Ahmed S; Balak, Naci; Bolles, Gene; Esene, Ignatius Ngene; Mathiesen, Tiit; Broekman, Marike L

2017-01-17

The application of stem cell transplants in clinical practice has increased in frequency in recent years. Many of the stem cell transplants in neurologic diseases, including stroke, Parkinson disease, spinal cord injury, and demyelinating diseases, are unproven-they have not been tested in prospective, controlled clinical trials and have not become accepted therapies. Stem cell transplant procedures currently being carried out have therapeutic aims, but are frequently experimental and unregulated, and could potentially put patients at risk. In some cases, patients undergoing such operations are not included in a clinical trial, and do not provide genuinely informed consent. For these reasons and others, some current stem cell interventions for neurologic diseases are ethically dubious and could jeopardize progress in the field. We provide discussion points for the evaluation of new stem cell interventions for neurologic disease, based primarily on the new Guidelines for Stem Cell Research and Clinical Translation released by the International Society for Stem Cell Research in May 2016. Important considerations in the ethical translation of stem cells to clinical practice include regulatory oversight, conflicts of interest, data sharing, the nature of investigation (e.g., within vs outside of a clinical trial), informed consent, risk-benefit ratios, the therapeutic misconception, and patient vulnerability. To help guide the translation of stem cells from the laboratory into the neurosurgical clinic in an ethically sound manner, we present an ethical discussion of these major issues at stake in the field of stem cell clinical research for neurologic disease. © 2016 American Academy of Neurology.

Reduced anaesthetic requirements and postoperative analgesics in patients undergoing laparoscopic cholecystectomy: premedication with intravenous paracetamol versus ketorolac, a double blind and randomised clinical trial.

PubMed

Medina-Vera, A J; Novoa, L M

2017-02-01

To compare the effects of premedication with intravenous paracetamol versus ketorolac, in decreasing intraoperative anaesthetic and postoperative opioid analgesics requirements in patients undergoing laparoscopic cholecystectomy. An experimental, prospective, comparative, double blind, and randomised clinical trial was conducted to determine intraoperative opioid requirements, and pain and analgesic requirements in the postoperative period in 100 healthy patients undergoing laparoscopic cholecystectomy. They were randomised into 2 groups: Group 1: pre-medicated with paracetamol 1g, and Group 2: with ketorolac 30mg (both administered intravenously 30minutes prior to surgery). There were no statistically significant differences between groups as regards intraoperative remifentanil use (Group 1: 0.0739±0.016μg/kg/min, Group 2: 0.0741±0.018μg/kg/min). The number of patients in Group 2 that had values of VAS>4 points (22.4%) was lower than in Group 1 (28.6%), but with no statistically significant difference. Of the patients who needed postoperative opioid rescue, most required a single rescue and application of analgesics during hospitalisation, that prevailed between 3 and 12hours, without any significant differences between groups. No adverse effects were observed in the study sample. Paracetamol 1g IV given preoperatively decreased anaesthetic requirements and the need for postoperative analgesics similar to the preoperative administration of ketorolac 30mg IV. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Effect of Agaricus sylvaticus supplementation on nutritional status and adverse events of chemotherapy of breast cancer: a randomized, placebo-controlled, double-blind clinical trial.

PubMed

Valadares, Fabiana; Garbi Novaes, Maria Rita Carvalho; Cañete, Roberto

2013-01-01

Breast cancer (BC) represents the highest incidence of malignancy in women throughout the world. Medicinal fungi can stimulate the body, reduce side-effects associated with chemotherapy and improve the quality of life in patients with cancer. To evaluate the effects of dietary supplementation of Agaricus sylvaticus on clinical and nutritional parameters in BC patients undergoing chemotherapy. A randomized, placebo-controlled, double-blind, clinical trial was carried out at the Oncology Clinic, Hospital of the Federal District-Brazil from September 2007 to July 2009. Forty six patients with BC, Stage II and III, were randomly assigned to receive either nutritional supplement with A. sylvaticus (2.1 g/day) or placebo. Patients were evaluated during treatment period. Patient supplemented with A. sylvaticus improved in clinical parameters and gastrointestinal functions. Poor appetite decreased by 20% with no changes in bowel functions (92.8%), nausea and vomiting (80%). Dietary supplementation with A. sylvaticus improved nutritional status and reduced abnormal bowel functions, nausea, vomiting, and anorexia in patients with BC receiving chemotherapy.

Randomised clinical trial: prucalopride, a colonic pro-motility agent, reduces the duration of post-operative ileus after elective gastrointestinal surgery.

PubMed

Gong, J; Xie, Z; Zhang, T; Gu, L; Yao, W; Guo, Z; Li, Y; Lu, N; Zhu, W; Li, N; Li, J

2016-04-01

Previous studies have shown that recovery of colonic transit is a major determinant of post-operative ileus and clinical recovery after gastrointestinal surgery. Prucalopride is a highly selective 5-hydroxytryptamine receptor-4 agonist with colonic pro-motility effects. To evaluate the effect and safety of prucalopride on post-operative ileus and surgical outcomes after elective gastrointestinal surgery. In this phase II randomised clinical trial, 110 patients undergoing elective gastrointestinal surgery were randomised to either oral prucalopride (2 mg/day) (n = 55) or placebo (n = 55). Intervention was started 24 h after surgery and stopped after defecation or maximally at 7 days. The primary outcome was time to defecation. Secondary outcomes included time to first passage of flatus, tolerance of solid food, nasogastric tube reinsertion, post-operative length of stay, hospital readmission, overall cost, time to walk independently, surgical complications and inflammatory parameters. Patients who received prucalopride had a shorter time to defecation (65.0 vs. 94.5 h, P = 0.001), passage of flatus (53.0 vs. 73.0 h, P < 0.001), and post-operative length of stay (7.0 vs. 8.0 days, P = 0.001) than controls. The number of patients with prolonged ileus (>5 days) (16.4% vs. 34.5%, P = 0.026) and the C-reactive protein level on post-operative day 5 (35.67 vs. 59.07 mg/L, P = 0.040) were lower in the prucalopride group. There was no significant difference in post-operative Clavien-Dindo grade III and IV complications (P = 0.606) between the groups. Prucalopride is a safe and effective treatment to reduce post-operative ileus and systemic inflammation without affecting post-operative complications in patients undergoing elective gastrointestinal surgery. ClinicalTrials.gov: NCT02004652. © 2016 John Wiley & Sons Ltd.

Can virtual reality exposure therapy gains be generalized to real-life? A meta-analysis of studies applying behavioral assessments.

PubMed

Morina, Nexhmedin; Ijntema, Hiske; Meyerbröker, Katharina; Emmelkamp, Paul M G

2015-11-01

In virtual reality exposure therapy (VRET), patients are exposed to virtual environments that resemble feared real-life situations. The aim of the current study was to assess the extent to which VRET gains can be observed in real-life situations. We conducted a meta-analysis of clinical trials applying VRET to specific phobias and measuring treatment outcome by means of behavioral laboratory tests or recordings of behavioral activities in real-life. Data sources were searches of databases (Medline, PsycInfo, and Cochrane). We included in total 14 clinical trials on specific phobias. Results revealed that patients undergoing VRET did significantly better on behavioral assessments following treatment than before treatment, with an aggregated uncontrolled effect size of g = 1.23. Furthermore, patients undergoing VRET performed better on behavioral assessments at post-treatment than patients on wait-list (g = 1.41). Additionally, results of behavioral assessment at post-treatment and at follow-up revealed no significant differences between VRET and exposure in vivo (g = -0.09 and 0.53, respectively). Finally, behavioral measurement effect sizes were similar to those calculated from self-report measures. The findings demonstrate that VRET can produce significant behavior change in real-life situations and support its application in treating specific phobias. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of Low-Intensity Extracorporeal Shockwave Therapy on Erectile Dysfunction: A Systematic Review and Meta-Analysis.

PubMed

Clavijo, Raul I; Kohn, Taylor P; Kohn, Jaden R; Ramasamy, Ranjith

2017-01-01

Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been proposed as an effective non-invasive treatment option for erectile dysfunction (ED). To use systematic review and meta-analysis to assess the efficacy of Li-ESWT by comparing change in erectile function as assessed by the erectile function domain of the International Index of Erectile Function (IIEF-EF) in men undergoing Li-ESWT vs sham therapy for the treatment of ED. Systematic search was conducted of MEDLINE, EMBASE, and ClinicalTrials.gov for randomized controlled trials that were published in peer-reviewed journals or presented in abstract form of Li-ESWT used for the treatment of ED from January 2010 through March 2016. Randomized controlled trials were eligible for inclusion if they were published in the peer-reviewed literature and assessed erectile function outcomes using the IIEF-EF score. Estimates were pooled using random-effects meta-analysis. Change in IIEF-EF score after treatment with Li-ESWT in patients treated with active treatment vs sham Li-ESWT probes. Data were extracted from seven trials involving 602 participants. The average age was 60.7 years and the average follow-up was 19.8 weeks. There was a statistically significant improvement in pooled change in IIEF-EF score from baseline to follow-up in men undergoing Li-ESWT vs those undergoing sham therapy (6.40 points; 95% CI = 1.78-11.02; I 2  = 98.7%; P < .0001 vs 1.65 points; 95% CI = 0.92-2.39; I 2  = 64.6%; P < .0001; between-group difference, P = .047). Significant between-group differences were found for total treatment shocks received by patients (P < .0001). In this meta-analysis of seven randomized controlled trials, treatment of ED with Li-ESWT resulted in a significant increase in IIEF-EF scores. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Effects of a Group-Mediated Exercise and Dietary Intervention in the Treatment of Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: Results From the IDEA-P Trial.

PubMed

Focht, Brian C; Lucas, Alexander R; Grainger, Elizabeth; Simpson, Christina; Fairman, Ciaran M; Thomas-Ahner, Jennifer M; Buell, Jackie; Monk, J Paul; Mortazavi, Amir; Clinton, Steven K

2018-04-19

Although androgen-deprivation therapy (ADT) is the foundation of treatment for prostate cancer, the physiological impacts of ADT result in functional decline and enhanced risk of chronic disease and metabolic syndrome. The Individualized Diet and Exercise Adherence Pilot Trial (IDEA-P) is a single-blind, randomized, pilot trial comparing the effects of a group-mediated, cognitive-behavioral (GMCB) exercise and dietary intervention (EX+D) with those of a standard-of-care (SC) control during the treatment of prostate cancer patients undergoing ADT. A total of 32 prostate cancer patients (M age = 66.28, SD = 7.79) undergoing ADT were randomly assigned to the 12-week EX+D intervention (n = 16) or control (n = 16). The primary outcome in IDEA-P was change in mobility performance with secondary outcomes including body composition and muscular strength. Blinded assessment of outcomes were obtained at baseline and at 2- and 3-month follow-ups. Favorable adherence and retention rates were observed, and no serious intervention-related adverse events were documented. Intent-to-treat ANCOVA controlling for baseline value and ADT duration demonstrated that EX+D resulted in significantly greater improvements in mobility performance (p < .02), muscular strength (p < .01), body fat percentage (p < .05), and fat mass (p < .03) at 3-month follow-up, relative to control. Findings from the IDEA-P trial suggest that a GMCB-based EX+D intervention resulted in significant, clinically meaningful improvements in mobility performance, muscular strength, and body composition, relative to controls. Collectively, these results suggest that the EX+D was a safe and well-tolerated intervention for prostate cancer patients on ADT. The utility of implementing this approach in the treatment of prostate cancer patients on ADT should be evaluated in future large-scale efficacy trials. NCT02050906.

Induction of labor versus expectant management for women with a prior cesarean delivery.

PubMed

Palatnik, Anna; Grobman, William A

2015-03-01

Previous studies of induction of labor in the setting of trial of labor after cesarean have compared women undergoing trial of labor after cesarean to those undergoing spontaneous labor. However, the clinically relevant comparison is to those undergoing expectant management. The objective of this study was to compare obstetric outcomes between women undergoing induction of labor and those undergoing expectant management ≥39 weeks of gestation. This was a secondary analysis of data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network Cesarean Registry that included women with singleton gestations at a gestational age of ≥39 weeks and a history of 1 low transverse cesarean delivery. Outcomes of induction at 39, 40, and 41 weeks were compared to expectant management beyond each gestational age period using univariable and multivariable analyses. Women with scheduled repeat cesarean deliveries done for the indication of prior cesarean delivery were excluded from the analysis. In all, 12,676 women were eligible for analysis. The rate of vaginal birth after cesarean (VBAC) was higher among women undergoing induction of labor at 39 weeks compared to expectant management (73.8% vs 61.3%, P < .001). The risk of uterine rupture also was higher among women undergoing induction of labor at 39 weeks compared to expectant management (1.4% vs 0.5%, P = .006, respectively). In multivariable analysis, induction of labor at 39 weeks remained associated with a significantly higher chance of VBAC and uterine rupture (odds ratio, 1.31; 95% confidence interval, 1.03-1.67; and odds ratio, 2.73; 95% confidence interval, 1.22-6.12, respectively). Induction of labor at 39 weeks, when compared to expectant management, was associated with a higher chance of VBAC but also of uterine rupture. Copyright © 2015 Elsevier Inc. All rights reserved.

A randomized trial comparing primary angioplasty versus stent placement for symptomatic intracranial stenosis

PubMed Central

Qureshi, Adnan I; Chaudhry, Saqib A; Siddiq, Farhan; Majidi, Shahram; Rodriguez, Gustavo J; Suri, M Fareed K

2013-01-01

Background: Both primary angioplasty alone and angioplasty with a self-expanding stent have been compared in non-randomized concurrent clinical studies that suggest equivalent results. However, there is no randomized trial that has compared the two procedures in patients with symptomatic high grade intracranial stenosis. Objective: The primary aim of the randomized trial was to compare the clinical and angiographic efficacy of primary angioplasty and angioplasty followed by stent placement in preventing restenosis, stroke, requirement for second treatment, and death in patients with symptomatic intracranial stenosis. Methods: The study prospectively evaluated efficacy and safety of the two existing neurointerventional techniques for treatment of moderate intracranial stenosis (stenosis ≥ 50%) with documented failure of medical treatment or severe stenosis (≥70%) with or without failure of medical treatment. Results: A total of 18 patients were recruited in the study (mean age [±SD] was 64.7 ± 15.1 years); out of these, 12 were men. Of these 18, 10 were treated with primary angioplasty and 8 were treated with angioplasty followed by self-expanding stent. The technical success rates of intracranial angioplasty and stent placements defined as ability to achieve <30% residual stenosis when assessed by immediate post-procedure angiography was 5 of 10 and 5 of 8 patients, respectively. The total fluoroscopic time (mean [±SD]) was lower in patients undergoing primary angioplasty 37 [±11] min versus those undergoing angioplasty followed by self-expanding stent 42 [±15] min, P = 0.4321. The stroke and death rate within 1 month was very low in both patient groups (1 of 10 versus 0 of 8 patients). One patient randomized to stent placement continued to have recurrent ischemic symptoms requiring another angioplasty in the vertebral artery on post-procedure Day 2. Conclusions: The trial suggests that a randomized trial comparing primary angioplasty to angioplasty followed by stent placement is feasible. The immediate procedural outcomes with primary angioplasty are comparable to stent placement and warrant further studies. PMID:24358415

Outcomes in Elderly Patients With Severely Calcified Coronary Lesions Undergoing Orbital Atherectomy.

PubMed

Lee, Michael S; Shlofmitz, Evan; Lluri, Gentian; Shlofmitz, Richard A

2017-04-01

We evaluated the clinical outcomes of elderly patients who underwent orbital atherectomy for the treatment of severe coronary artery calcification (CAC) prior to stenting. Percutaneous coronary intervention (PCI) of severe CAC is associated with worse clinical outcomes including death, myocardial infarction (MI), and target vessel revascularization (TVR). The elderly represents a high-risk group of patients, often have more comorbid conditions, and have worse outcomes after PCI compared to younger patients. Clinical trials and a large multicenter registry have demonstrated the safety and efficacy of orbital atherectomy for the treatment of severe CAC. Clinical outcomes of elderly patients who undergo orbital atherectomy are unknown. Of the 458 patients, 229 were ≥75 years old (elderly) and 229 were <75 years old (younger). The primary endpoint was rate of 30-day major adverse cardiac and cerebrovascular events (MACCE), comprised of cardiac death, MI, TVR, and stroke. The primary endpoint was similar in the elderly and younger groups (2.2% vs. 2.2%, P = 1), as were the individual endpoints of death (2.2% vs. 0.4%, P = 0.1), MI (0.9% vs. 1.3%, P = 0.65), TVR (0% vs. 0%, P = 1), and stroke (0% vs. 0.4%, P = 0.32). The rates of angiographic complications and stent thrombosis were similarly low in both groups. The elderly represented a sizeable number of patients who underwent orbital atherectomy. It is a safe and effective treatment strategy for elderly patients with severe CAC as the clinical outcomes were similar to their younger counterparts. A randomized trial should further clarify the role of orbital atherectomy in these patients. © 2017, Wiley Periodicals, Inc.

Kinetics of salivary pH after acidic beverage intake by patients undergoing orthodontic treatment.

PubMed

Turssi, Cecilia P; Silva, Carolina S; Bridi, Enrico C; Amaral, Flavia Lb; Franca, Fabiana Mg; Basting, Roberta T

2015-01-01

The saliva of patients undergoing orthodontic treatment with fixed appliances can potentially present a delay in the diluting, clearing, and buffering of dietary acids due to an increased number of retention areas. The aim of this clinical trial was to compare salivary pH kinetics of patients with and without orthodontic treatment, following the intake of an acidic beverage. Twenty participants undergoing orthodontic treatment and 20 control counterparts had their saliva assessed for flow rate, pH, and buffering capacity. There was no significant difference between salivary parameters in participants with or without an orthodontic appliance. Salivary pH recovery following acidic beverage intake was slower in the orthodontic subjects compared to controls. Patients with fixed orthodontic appliances, therefore, seem to be at higher risk of dental erosion, suggesting that dietary advice and preventive care need to be implemented during orthodontic treatment.

The Effects of Preoperative Volume Replacement in Diabetic Patients Undergoing Coronary Artery Bypass Grafting Surgery: Protocol for a Randomized Controlled Trial (VeRDiCT Trial).

PubMed

Clout, Madeleine; Harris, Tracy; Rogers, Chris; Culliford, Lucy; Taylor, Jodi; Angelini, Gianni; Narayan, Pradeep; Reeves, Barnaby; Hillier, James; Ashton, Kate; Sarkar, Kunal; Ascione, Raimondo

2017-06-19

Diabetes mellitus is a major risk factor for prolonged hospital stays, renal failure, and mortality in patients having coronary artery bypass grafting (CABG). Complications pose a serious threat to patients and prolong intensive care and hospital stays. Low glomerular filtration rate (GFR) due to existing renal impairment or volume depletion may exacerbate acute renal impairment/failure in these patients. Preoperative volume replacement therapy (VRT) is reported to increase the GFR and we hypothesize that VRT will reduce renal impairment and related complications in diabetic patients. The objective of this study is to establish the efficacy of preoperative VRT in reducing postoperative complications in diabetic patients undergoing CABG surgery. Time to "fit for discharge", incidence of postoperative renal failure, cardiac injury, inflammation, and other health outcomes will be investigated. In this open parallel group randomized controlled trial, 170 diabetic patients undergoing elective or urgent CABG surgery received 1 mL/kg/hour of Hartmann's solution for 12 consecutive hours prior to surgery, versus routine care. The primary outcome was time until participants were "fit for discharge", which is defined as presence of: normal temperature, pulse, and respiration; normal oxygen saturation on air; normal bowel function; and physical mobility. Secondary outcomes included: incidence of renal failure; markers of renal function, inflammation, and cardiac damage; operative morbidity; intensive care stay; patient-assessed outcome, including the Coronary Revascularization Outcome Questionnaire; and use of hospital resources. Recruitment started in July 2010. Enrolment for the study was completed in July 2014. Data analysis commenced in December 2016. Study results will be submitted for publication in the summer of 2017. VRT is a relatively easy treatment to administer in patients undergoing surgical procedures who are at risk of renal failure. This experimental protocol will increase scientific and clinical knowledge of VRT in diabetic patients undergoing elective or urgent CABG surgery. Findings supporting the efficacy of this intervention could easily be implemented in the health care system. International Standard Randomized Controlled Trial Number (ISRCTN): 02159606; http://www.controlled-trials.com/ISRCTN02159606 (Archived by WebCite at http://www.webcitation.org/6rDkSSkkK). ©Madeleine Clout, Tracy Harris, Chris Rogers, Lucy Culliford, Jodi Taylor, Gianni Angelini, Pradeep Narayan, Barnaby Reeves, James Hillier, Kate Ashton, Kunal Sarkar, Raimondo Ascione. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 19.06.2017.

Coagulation management in patients undergoing neurosurgical procedures.

PubMed

Robba, Chiara; Bertuetti, Rita; Rasulo, Frank; Bertuccio, Alessando; Matta, Basil

2017-10-01

Management of coagulation in neurosurgical procedures is challenging. In this contest, it is imperative to avoid further intracranial bleeding. Perioperative bleeding can be associated with a number of factors, including anticoagulant drugs and coagulation status but is also linked to the characteristic and the site of the intracranial disorder. The aim of this review will be to focus primarily on the new evidence regarding the management of coagulation in patients undergoing craniotomy for neurosurgical procedures. Antihemostatic and anticoagulant drugs have shown to be associated with perioperative bleeding. On the other hand, an increased risk of venous thromboembolism and hypercoagulative state after elective and emergency neurosurgery, in particular after brain tumor surgery, has been described in several patients. To balance the risk between thrombosis and bleeding, it is important to be familiar with the perioperative changes in coagulation and with the recent management guidelines for anticoagulated patients undergoing neurosurgical procedures, in particular for those taking new direct anticoagulants. We have considered the current clinical trials and literature regarding both safety and efficacy of deep venous thrombosis prophylaxis in the neurosurgical population. These were mainly trials concerning both elective surgical and intensive care patients with a poor grade intracranial bleed or multiple traumas with an associated severe traumatic brain injury (TBI). Coagulation management remains a major issue in patients undergoing neurosurgical procedures. However, in this field of research, literature quality is poor and further studies are necessary to identify the best strategies to minimize risks in this group of patients.

The Ontario Uterine Fibroid Embolization Trial. Part 1. Baseline patient characteristics, fibroid burden, and impact on life.

PubMed

Pron, Gaylene; Cohen, Marsha; Soucie, Jennifer; Garvin, Greg; Vanderburgh, Leslie; Bell, Stuart

2003-01-01

To determine baseline characteristics of women undergoing uterine artery embolization (UAE) for symptomatic fibroids. Multicenter, prospective, single-arm clinical treatment trial. Eight Ontario university and community hospitals. Five hundred fifty-five women undergoing UAE for fibroids. Baseline questionnaires completed before UAE. Questionnaires were analyzed for demographic, medical, and gynecologic histories. Fibroid symptoms, impact of symptoms, previous consultations, and treatments were also analyzed. The Ontario cohort (66% white, 23% black, 11% other races) had an average age of 43. Thirty-one percent were under age 40. Most women were university educated (68%) and working outside the home (85%). Women reported heavy menstrual bleeding (80%), urinary urgency/frequency (73%), pain during intercourse (41%), and work absences (40%). They experienced fibroid-related symptoms for an average of 5 years and consulted with on average of three gynecologists before UAE. High fibroid life-impact scores were reported by 58%. Black women were significantly younger (40.7 vs. 44.0 years), more likely to experience symptoms longer (7 vs. 5 years), and more likely to undergo myomectomy before UAE (24% vs. 9%) than white women. Our study illustrates that large numbers of women with highly symptomatic fibroid disease are averse to surgery despite their burden of suffering and are actively seeking alternatives to hysterectomy.

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

PubMed

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

2017-08-18

The transfusion-related respiratory complications, transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO), are leading causes of transfusion-related morbidity and mortality. At present, there are no effective preventive strategies with red blood cell (RBC) transfusion. Although mechanisms remain incompletely defined, soluble biological response modifiers (BRMs) within the RBC storage solution may play an important role. Point-of-care (POC) washing of allogeneic RBCs may remove these BRMs, thereby mitigating their impact on post-transfusion respiratory complications. This is a multicenter randomised clinical trial of standard allogeneic versus washed allogeneic RBC transfusion for adult patients undergoing cardiac surgery testing the hypothesis that POC RBC washing is feasible, safe, and efficacious and will reduce recipient immune and physiologic responses associated with transfusion-related respiratory complications. Relevant clinical outcomes will also be assessed. This investigation will enrol 170 patients at two hospitals in the USA. Simon's two-stage design will be used to assess the feasibility of POC RBC washing. The primary safety outcomes will be assessed using Wilcoxon Rank-Sum tests for continuous variables and Pearson chi-square test for categorical variables. Standard mixed modelling practices will be employed to test for changes in biomarkers of lung injury following transfusion. Linear regression will assess relationships between randomised group and post-transfusion physiologic measures. Safety oversight will be conducted under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained by the DSMB as well as the institutional review boards at each institution prior to enrolling the first study participant. This study aims to provide important information regarding the feasibility of POC washing of allogeneic RBCs and its potential impact on ameliorating post-transfusion respiratory complications. Additionally, it will inform the feasibility and scientific merit of pursuing a more definitive phase II/III clinical trial. ClinicalTrials.gov registration number is NCT02094118 (Pre-results). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Wound infiltration with local anaesthetic agents for laparoscopic cholecystectomy.

PubMed

Loizides, Sofronis; Gurusamy, Kurinchi Selvan; Nagendran, Myura; Rossi, Michele; Guerrini, Gian Piero; Davidson, Brian R

2014-03-12

While laparoscopic cholecystectomy is generally considered to be less painful than open surgery, pain is one of the important reasons for delayed discharge after day surgery resulting in overnight stay following laparoscopic cholecystectomy. The safety and effectiveness of local anaesthetic wound infiltration in people undergoing laparoscopic cholecystectomy is not known. To assess the benefits and harms of local anaesthetic wound infiltration in patients undergoing laparoscopic cholecystectomy and to identify the best method of local anaesthetic wound infiltration with regards to the type of local anaesthetic, dosage, and time of administration of the local anaesthetic. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded until February 2013 to identify studies of relevance to this review. We included randomised clinical trials for benefit and quasi-randomised and comparative non-randomised studies for treatment-related harms. Only randomised clinical trials (irrespective of language, blinding, or publication status) comparing local anaesthetic wound infiltration versus placebo, no intervention, or inactive control during laparoscopic cholecystectomy, trials comparing different local anaesthetic agents for local anaesthetic wound infiltration, and trials comparing the different times of local anaesthetic wound infiltration were considered for the review. Two review authors collected the data independently. We analysed the data with both fixed-effect and random-effects meta-analysis models using RevMan. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). Twenty-six trials fulfilled the inclusion criteria of the review. All the 26 trials except one trial of 30 participants were at high risk of bias. Nineteen of the trials with 1263 randomised participants provided data for this review. Ten of the 19 trials compared local anaesthetic wound infiltration versus inactive control. One of the 19 trials compared local anaesthetic wound infiltration with two inactive controls, normal saline and no intervention. Two of the 19 trials had four arms comparing local anaesthetic wound infiltration with inactive controls in the presence and absence of co-interventions to decrease pain after laparoscopic cholecystectomy. Four of the 19 trials had three or more arms that could be included for the comparison of local anaesthetic wound infiltration versus inactive control and different methods of local anaesthetic wound infiltration. The remaining two trials compared different methods of local anaesthetic wound infiltration.Most trials included only low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. Seventeen trials randomised a total of 1095 participants to local anaesthetic wound infiltration (587 participants) versus no local anaesthetic wound infiltration (508 participants). Various anaesthetic agents were used but bupivacaine was the commonest local anaesthetic used. There was no mortality in either group in the seven trials that reported mortality (0/280 (0%) in local anaesthetic infiltration group versus 0/259 (0%) in control group). The effect of local anaesthetic on the proportion of people who developed serious adverse events was imprecise and compatible with increase or no difference in serious adverse events (seven trials; 539 participants; 2/280 (0.8%) in local anaesthetic group versus 1/259 (0.4%) in control; RR 2.00; 95% CI 0.19 to 21.59; very low quality evidence). None of the serious adverse events were related to local anaesthetic wound infiltration. None of the trials reported patient quality of life. The proportion of participants who were discharged as day surgery patients was higher in the local anaesthetic infiltration group than in the no local anaesthetic infiltration group (one trial; 97 participants; 33/50 (66.0%) in the local anaesthetic group versus 20/47 (42.6%) in the control group; RR 1.55; 95% CI 1.05 to 2.28; very low quality evidence). The effect of local anaesthetic on the length of hospital stay was compatible with a decrease, increase, or no difference in the length of hospital stay between the two groups (four trials; 327 participants; MD -0.26 days; 95% CI -0.67 to 0.16; very low quality evidence). The pain scores as measured by the visual analogue scale (0 to 10 cm) were lower in the local anaesthetic infiltration group than the control group at 4 to 8 hours (13 trials; 806 participants; MD -1.33 cm on the VAS; 95% CI -1.54 to -1.12; very low quality evidence) and 9 to 24 hours (12 trials; 756 participants; MD -0.36 cm on the VAS; 95% CI -0.53 to -0.20; very low quality evidence). The effect of local anaesthetic on the time taken to return to normal activity between the two groups was imprecise and compatible with a decrease, increase, or no difference in the time taken to return to normal activity (two trials; 195 participants; MD 0.14 days; 95% CI -0.59 to 0.87; very low quality evidence). None of the trials reported on return to work.Four trials randomised a total of 149 participants to local anaesthetic wound infiltration prior to skin incision (74 participants) versus local anaesthetic wound infiltration at the end of surgery (75 participants). Two trials randomised a total of 176 participants to four different local anaesthetics (bupivacaine, levobupivacaine, ropivacaine, neosaxitoxin). Although there were differences between the groups in some outcomes the changes were not consistent. There was no evidence to support the preference of one local anaesthetic over another or to prefer administration of local anaesthetic at a specific time compared with another. Serious adverse events were rare in studies evaluating local anaesthetic wound infiltration (very low quality evidence). There is very low quality evidence that infiltration reduces pain in low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. However, the clinical importance of this reduction in pain is likely to be small. Further randomised clinical trials at low risk of systematic and random errors are necessary. Such trials should include important clinical outcomes such as quality of life and time to return to work in their assessment.

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.

The effects of low-intensity pulsed ultrasound and pulsed electromagnetic fields bone growth stimulation in acute fractures: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Hannemann, P F W; Mommers, E H H; Schots, J P M; Brink, P R G; Poeze, M

2014-08-01

The aim of this systematic review and meta-analysis was to evaluate the best currently available evidence from randomized controlled trials comparing pulsed electromagnetic fields (PEMF) or low-intensity pulsed ultrasound (LIPUS) bone growth stimulation with placebo for acute fractures. We performed a systematic literature search of the medical literature from 1980 to 2013 for randomized clinical trials concerning acute fractures in adults treated with PEMF or LIPUS. Two reviewers independently determined the strength of the included studies by assessing the risk of bias according to the criteria in the Cochrane Handbook for Systematic Reviews of Interventions. Seven hundred and thirty-seven patients from 13 trials were included. Pooled results from 13 trials reporting proportion of nonunion showed no significant difference between PEMF or LIPUS and control. With regard to time to radiological union, we found heterogeneous results that significantly favoured PEMF or LIPUS bone growth stimulation only in non-operatively treated fractures or fractures of the upper limb. Furthermore, we found significant results that suggest that the use of PEMF or LIPUS in acute diaphyseal fractures may accelerate the time to clinical union. Current evidence from randomized trials is insufficient to conclude a benefit of PEMF or LIPUS bone growth stimulation in reducing the incidence of nonunions when used for treatment in acute fractures. However, our systematic review and meta-analysis suggest that PEMF or LIPUS can be beneficial in the treatment of acute fractures regarding time to radiological and clinical union. PEMF and LIPUS significantly shorten time to radiological union for acute fractures undergoing non-operative treatment and acute fractures of the upper limb. Furthermore, PEMF or LIPUS bone growth stimulation accelerates the time to clinical union for acute diaphyseal fractures.

Cushing’s Disease

PubMed Central

ElShafie, Omayma; Osman, Anjum; Aamer, Fatima; Al-Mamari, Ali; Woodhouse, NJY

2012-01-01

We report five cases of Cushing’s disease where the patients were given a therapeutic trial of cabergoline. Morning serum cortisol, adrenocorticotrophic hormone (ACTH), and sleeping cortisol concentrations were significantly raised. Magnetic resonance imaging (MRI) scans revealed pituitary microadenomas in 3 patients but were normal in the others. Ectopic ACTH production was excluded in the 2 patients with normal MRI scans. All were given a therapeutic trial of cabergoline (1 mg daily). Four patients responded with a prompt fall in serum cortisol levels and had a sustained clinical and biochemical remission for 378, 44, 28 and 14 days, respectively. One patient failed to respond. In conclusion, we suggest that all patients with Cushing’s disease should undergo a therapeutic trial of cabergoline. Responders can then be prepared for surgery or, if needed, treated medically in the long term. PMID:23275847

Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI).

PubMed

Kwan, I; Bhattacharya, S; McNeil, A; van Rumste, M M E

2008-04-16

Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation (IVF) treatment has included ultrasonography plus serum estradiol concentration to ensure safe practice by reducing the incidence and severity of ovarian hyperstimulation syndrome (OHSS). The need for intensive monitoring during ovarian stimulation in IVF is controversial. It has been suggested that close monitoring is time consuming, expensive and inconvenient for the woman and simplification of IVF therapy by using ultrasound only should be considered. This systematic review assessed the effects of ovarian monitoring by ultrasound only versus ultrasound plus serum estradiol measurement on IVF outcomes and the occurrence of OHSS in women undergoing stimulated cycles in IVF and intra-cytoplasmic sperm injection (ICSI) treatment. To quantify the effect of monitoring controlled ovarian stimulation in IVF and ICSI cycles with ultrasound plus serum estradiol concentration versus ultrasound only in terms of live birth rates, pregnancy rates and the incidence of OHSS. We searched the Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL) on the latest issue of The Cochrane Library, MEDLINE (1966 to May 2007), EMBASE (1980 to May 2007), CINAHL (1982 to May 2007), the National Research Register, and web-based trial databases such as Current Controlled Trials. There was no language restriction. Additionally all references in the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data. Only randomised controlled trials that compared monitoring with ultrasound plus serum estradiol concentration versus ultrasound only in women undergoing ovarian hyperstimulation for IVF and ICSI treatment were included. Two review authors independently examined the electronic search results for relevant trials, extracted data and assessed trial quality. They resolved disagreements by discussion with two other authors. Outcomes data were pooled when appropriate and summary statistics presented when limited data did not allow meta-analysis. Our search strategy identified 1119 potentially eligible reports, of which two met our inclusion criteria. These involved 411 women who underwent controlled ovarian stimulation monitoring. Our primary outcome of live birth rate was not reported in either study. One trial reported clinical pregnancy rate per woman (33% versus 31%; RR 1.07, 95% CI 0.77 to 1.49), the second trial reported clinical pregnancy rate per oocyte retrieval (22% versus 25%). There was no significant difference between the ultrasound plus estradiol group and the ultrasound alone group in the mean number of oocytes retrieved (WMD -0.55, 95% CI -1.79 to 0.69) and the incidence of ovarian hyperstimulation (RR 0.73, 95% CI 0.30 to 1.78) for the two studies. There is no evidence from randomised trials to support cycle monitoring by ultrasound plus serum estradiol as more efficacious than cycle monitoring by ultrasound only on outcomes of live birth and pregnancy rates. A large well-designed randomised controlled trial is needed that reports on live birth rates and pregnancy, with economic evaluation of the costs involved and the views of the women undergoing cycle monitoring. A randomised trial with sufficiently large sample size to test the effects of different monitoring protocols on OHSS, a rare outcome, will pose a great challenge. Until such a trial is considered feasible, cycle monitoring by transvaginal ultrasound plus serum estradiol may need to be retained as a precautionary good practice point.

A Markov chain model for reliability growth and decay

NASA Technical Reports Server (NTRS)

Siegrist, K.

1982-01-01

A mathematical model is developed to describe a complex system undergoing a sequence of trials in which there is interaction between the internal states of the system and the outcomes of the trials. For example, the model might describe a system undergoing testing that is redesigned after each failure. The basic assumptions for the model are that the state of the system after a trial depends probabilistically only on the state before the trial and on the outcome of the trial and that the outcome of a trial depends probabilistically only on the state of the system before the trial. It is shown that under these basic assumptions, the successive states form a Markov chain and the successive states and outcomes jointly form a Markov chain. General results are obtained for the transition probabilities, steady-state distributions, etc. A special case studied in detail describes a system that has two possible state ('repaired' and 'unrepaired') undergoing trials that have three possible outcomes ('inherent failure', 'assignable-cause' 'failure' and 'success'). For this model, the reliability function is computed explicitly and an optimal repair policy is obtained.

The Recombinant Bacille Calmette-Guérin Vaccine VPM1002: Ready for Clinical Efficacy Testing.

PubMed

Nieuwenhuizen, Natalie E; Kulkarni, Prasad S; Shaligram, Umesh; Cotton, Mark F; Rentsch, Cyrill A; Eisele, Bernd; Grode, Leander; Kaufmann, Stefan H E

2017-01-01

The only licensed vaccine against tuberculosis (TB), bacille Calmette-Guérin (BCG), protects against severe extrapulmonary forms of TB but is virtually ineffective against the most prevalent form of the disease, pulmonary TB. BCG was genetically modified at the Max Planck Institute for Infection Biology to improve its immunogenicity by replacing the urease C encoding gene with the listeriolysin encoding gene from Listeria monocytogenes . Listeriolysin perturbates the phagosomal membrane at acidic pH. Urease C is involved in neutralization of the phagosome harboring BCG. Its depletion allows for rapid phagosome acidification and promotes phagolysosome fusion. As a result, BCGΔ ureC :: hly (VPM1002) promotes apoptosis and autophagy and facilitates release of mycobacterial antigens into the cytosol. In preclinical studies, VPM1002 has been far more efficacious and safer than BCG. The vaccine was licensed to Vakzine Projekt Management and later sublicensed to the Serum Institute of India Pvt. Ltd., the largest vaccine producer in the world. The vaccine has passed phase I clinical trials in Germany and South Africa, demonstrating its safety and immunogenicity in young adults. It was also successfully tested in a phase IIa randomized clinical trial in healthy South African newborns and is currently undergoing a phase IIb study in HIV exposed and unexposed newborns. A phase II/III clinical trial will commence in India in 2017 to assess efficacy against recurrence of TB. The target indications for VPM1002 are newborn immunization to prevent TB as well as post-exposure immunization in adults to prevent TB recurrence. In addition, a Phase I trial in non-muscle invasive bladder cancer patients has been completed, and phase II trials are ongoing. This review describes the development of VPM1002 from the drawing board to its clinical assessment.

Effectiveness of N-acetylcysteine for preserving residual renal function in patients undergoing maintenance hemodialysis: multicenter randomized clinical trial.

PubMed

Ahmadi, Farrokhlaga; Abbaszadeh, Mahsa; Razeghi, Effat; Maziar, Sima; Khoidaki, Simin Dashti; Najafi, Mohammad Taghi; Lessan-Pezeshki, Mahboob

2017-04-01

To investigate the efficacy and safety of oral N-acetylcysteine (NAC) for preserving residual renal function in patients undergoing hemodialysis. Randomized, multi-center, parallel-group, open-label clinical trial (Registration No. IRCT 2014071418482N1). 54 patients who have been undergoing hemodialysis for at least 3 months and had residual urine volume >100 ml/24 h were randomly allocated to NAC or no medication. Residual renal function evaluated by (1) estimated glomerular filtration rate (GFR), (2) 24 h urine volume, and (3) renal Kt/V. GFR and Kt/V was determined at baseline and after 3 months. 24 h urine volume was measured at baseline, after 1, 2, and 3 months. Intention-to-treat analysis was performed on 47 patients (NAC = 26, control = 21). GFR in patients receiving NAC improved, whereas in the control arm a decline of 1.0 ml/min/1.73 m 2 was recorded (3.59 vs. 2.11 ml/min/1.73 m 2 , effect size = 17.0 %, p = 0.004). For 24 h urine volume, the between-group difference after 1 month was significant (669 vs. 533 ml/24 h, effect size = 15.4 %, p = 0.004). After 3 months, 24 h urine volume in the NAC arm was on average 137 ml higher than in the control group, and the difference reached near significance (673 vs. 536 ml/24 h, p = 0.072). In the follow-up visit, Kt/V was higher in the NAC arm but the difference did not reach statistical significance (0.81 vs. 0.54, p = 0.152). Three months treatment with NAC appears to be effective in preserving renal function in patients undergoing hemodialysis and the medication is generally well-tolerated.

Population pharmacokinetics of ϵ-aminocaproic acid in adolescents undergoing posterior spinal fusion surgery

PubMed Central

Stricker, P. A.; Gastonguay, M. R.; Singh, D.; Fiadjoe, J. E.; Sussman, E. M.; Pruitt, E. Y.; Goebel, T. K.; Zuppa, A. F.

2015-01-01

Background Despite demonstrated efficacy of ϵ-aminocaproic acid (EACA) in reducing blood loss in adolescents undergoing spinal fusion, there are no population-specific pharmacokinetic data to guide dosing. The aim of this study was to determine the pharmacokinetics of EACA in adolescents undergoing spinal fusion surgery and make dosing recommendations. Methods Twenty children ages 12–17 years were enrolled, with 10 children in each of two groups based on diagnosis (idiopathic scoliosis or non-idiopathic scoliosis). Previously reported data from infants undergoing craniofacial surgery were included in the model to enable dosing recommendations over a wide range of weights, ages, and diagnoses. A population non-linear mixed effects modelling approach was used to characterize EACA pharmacokinetics. Results Population pharmacokinetic parameters were estimated using a two-compartment disposition model with allometrically scaled weight and an age effect on clearance. Pharmacokinetic parameters for the typical patient were a plasma clearance of 153 ml min−1 70 kg−1 (6.32 ml min−1 kg−0.75), intercompartmental clearance of 200 ml min−1 70 kg−1 (8.26 ml min−1 kg−0.75), central volume of distribution of 8.78 litre 70 kg−1 (0.13 litre kg−1), and peripheral volume of distribution of 15.8 litre 70 kg−1 (0.23 litre kg−1). Scoliosis aetiology did not have a clinically significant effect on drug pharmacokinetics. Conclusions The following dosing schemes are recommended according to patient weight: weight <25 kg, 100 mg kg−1 loading dose and 40 mg kg−1 h−1 infusion; weight ≤25 kg–<50 kg, 100 mg kg−1 loading dose and 35 mg kg−1 h−1 infusion; and weight ≥50 kg, 100 mg kg−1 loading dose and 30 mg kg−1 h−1 infusion. An efficacy trial employing this dosing strategy is warranted. Clinical trial registration NCT01408823. PMID:25586726

The Novel Antipsychotic Cariprazine (RGH-188): State-of-the-Art in the Treatment of Psychiatric Disorders.

PubMed

De Berardis, Domenico; Orsolini, Laura; Iasevoli, Felice; Prinzivalli, Emiliano; de Bartolomeis, Andrea; Serroni, Nicola; Mazza, Monica; Valchera, Alessandro; Fornaro, Michele; Vecchiotti, Roberta; Carano, Alessandro; Sepede, Gianna; Vellante, Federica; Matarazzo, Ilaria; Pompili, Maurizio; Perna, Giampaolo; Conti, Chiara; Segura-García, Cristina; Martinotti, Giovanni; Di Giannantonio, Massimo

2016-01-01

Cariprazine (RGH-188) is a novel antipsychotic drug that exerts partial agonism of dopamine D2/D3 receptors with preferential binding to D3 receptor, antagonism of 5HT2B receptors and partial agonism of 5HT1A. Currently, cariprazine is in late-stage clinical development (phase III clinical trials) in patients with schizophrenia (S) and in patients with bipolar disorder (BD), as well as an adjunctive treatment in patients with Major Depressive Disorder (MDD) and drug-resistant MDD. Cariprazine has completed phase III trials for the acute treatment of schizophrenia and bipolar mania, phase II trials for the bipolar depression and MDD whilst it is undergoing phase III trials as an adjunct to antidepressants. The present review aims at proving a comprehensive summary of the current evidence on the safety, tolerability and efficacy of cariprazine in the treatment of schizophrenia, BD (manic/mixed/ depressive episode) and MDD. A systematic search was conducted on PubMed/Medline/ Scopus and the database on Clinical Trials from inception until April 2015 by typing a set of specified keywords. Available evidence seems to support cariprazine efficacy in the treatment of cognitive and negative symptoms of schizophrenia. Preliminary findings suggest its antimanic activity whilst it is still under investigation its efficacy in the treatment of bipolar depression and MDD. Furthermore, the available data seems not to allow judgements about its antipsychotic potential in comparison with currently prescribed antipsychotics. Further studies should be carried out to better investigate its pharmacodynamic and clinical potential, particularly as alternative to current antipsychotic drugs.

Tuberculosis vaccine development at a divide.

PubMed

Kaufmann, Stefan H E

2014-05-01

Tuberculosis (TB) remains a major health threat that will only be defeated by a combination of better drugs, diagnostics and vaccines. The only licensed TB vaccine, bacille Calmette-Guérin (BCG), protects against extrapulmonary TB in infants. Novel vaccine candidates that could protect against pulmonary TB either in TB naïve or in latent TB-infected healthy individuals have been developed and are currently being assessed in clinical trials. Subunit booster vaccines are either based on viral vectors expressing TB-specific antigens or on TB-protein antigens in adjuvants. Subunit vaccines are administered on top of BCG. Replacement vaccines for BCG are recombinant viable BCG or Mycobacterium tuberculosis. Several candidates are undergoing, or will soon start, phase IIb assessment for efficacy. The first vaccine candidate, MVA85A, to complete a phase IIb trial, unfortunately failed to show protection against TB in infants. Therapeutic vaccines composed of killed mycobacterial preparations target patients with complicated TB in adjunct to drug treatment. With increasing numbers of TB vaccine candidates in clinical trials, financial, regulatory and infrastructural issues arise, which would be best tackled by a global strategy. In addition, selection of the most promising vaccine candidates for further clinical development gains increasing importance.

Cardioprotection by remote ischaemic preconditioning.

PubMed

Walsh, S R; Tang, T; Sadat, U; Dutka, D P; Gaunt, M E

2007-11-01

Perioperative myocardial infarction is a leading cause of morbidity and mortality after major non-cardiac surgery. Pharmacological agents such as beta-blockers may reduce the risk but are associated with side-effects and may be contra-indicated in some patients. Basic scientific experiments and preliminary clinical trials in humans suggest that remote ischaemic preconditioning (RIPC), where brief ischaemia in one tissue confers resistance to subsequent sustained ischaemic insults in another tissue, may provide a simple, cost-effective means of reducing the risk of perioperative myocardial ischaemia. The Medline and Pubmed databases were searched for articles concerning RIPC. The mechanism may be humoral, neural, or a combination of both, and involves adenosine, opioids, bradykinins, protein kinase C, and K-ATP channels, although the precise end-effector remains unclear. Small randomized trials in humans undergoing major surgery suggest that RIPC induced by brief lower limb ischaemia significantly reduces myocardial injury. It may also reduce other ischaemic complications of surgery and anaesthesia. Small studies provide some evidence that RIPC could reduce myocardial injury and other ischaemic complications of surgery. However, large-scale clinical trials to assess the effect of RIPC on mortality and morbidity are required before RIPC can be recommended for routine clinical use.

Outcomes in elderly and young patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with bivalirudin versus heparin: Pooled analysis from the EUROMAX and HORIZONS-AMI trials.

PubMed

Qaderdan, Khalid; Vos, Gerrit-Jan A; McAndrew, Thomas; Steg, Philippe Gabriel; Hamm, Christian W; Van't Hof, Arnoud; Mehran, Roxana; Deliargyris, Efthymios N; Bernstein, Debra; Stone, Gregg W; Ten Berg, Jurriën M

2017-12-01

Since older age is a strong predictor of not only bleeding but also of ischemic events, understanding the risk:benefit profile of bivalirudin in the elderly undergoing primary percutaneous coronary intervention (pPCI) for ST-segment elevation (STEMI) is important. For this, we aim to compare elderly with young patients, who all underwent pPCI for STEMI and randomly received either bivalirudin or heparin. We performed a patient-level pooled analysis (n=5800) of two large randomized trials. A total of 2149 (37.1%) elderly patients (>65 years of age) with STEMI were enrolled and randomly assigned to either bivalirudin or heparin with or without a GPI (control group) before pPCI. Clinical outcomes at 30 days were analyzed. In elderly patients, bivalirudin significantly reduced non-CABG major bleeding (7.1% vs 10.4%; P<.01), subacute ST (0.4% vs 1.5%; P<.01), and net adverse clinical events (NACE; composite of all-cause mortality, reinfarction, IDR, stroke or protocol-defined non-CABG major bleeding [13.7% vs 17.2%; P=.03]) with comparable rates of stroke, MI, acute ST, or all-cause death, when compared with heparin with or without GPI. In a large group of elderly patients enrolled in the EUROMAX and HORIZONS-AMI trials, bivalirudin was associated with lower 30-day rates of non-CABG major bleeding, subacute ST and NACE, with similar 30-day rates of acute ST and mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

Randomized controlled trial of supplemental augmentative and alternative communication versus voice rest alone after phonomicrosurgery.

PubMed

Rousseau, Bernard; Gutmann, Michelle L; Mau, Theodore; Francis, David O; Johnson, Jeffrey P; Novaleski, Carolyn K; Vinson, Kimberly N; Garrett, C Gaelyn

2015-03-01

This randomized trial investigated voice rest and supplemental text-to-speech communication versus voice rest alone on visual analog scale measures of communication effectiveness and magnitude of voice use. Randomized clinical trial. Multicenter outpatient voice clinics. Thirty-seven patients undergoing phonomicrosurgery. Patients undergoing phonomicrosurgery were randomized to voice rest and supplemental text-to-speech communication or voice rest alone. The primary outcome measure was the impact of voice rest on ability to communicate effectively over a 7-day period. Pre- and postoperative magnitude of voice use was also measured as an observational outcome. Patients randomized to voice rest and supplemental text-to-speech communication reported higher median communication effectiveness on each postoperative day compared to those randomized to voice rest alone, with significantly higher median communication effectiveness on postoperative days 3 (P=.03) and 5 (P=.01). Magnitude of voice use did not differ on any preoperative (P>.05) or postoperative day (P>.05), nor did patients significantly decrease voice use as the surgery date approached (P>.05). However, there was a significant reduction in median voice use pre- to postoperatively across patients (P<.001) with median voice use ranging from 0 to 3 throughout the postoperative week. Supplemental text-to-speech communication increased patient-perceived communication effectiveness on postoperative days 3 and 5 over voice rest alone. With the prevalence of smartphones and the widespread use of text messaging, supplemental text-to-speech communication may provide an accessible and cost-effective communication option for patients on vocal restrictions. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Aspirin for in vitro fertilisation.

PubMed

Siristatidis, Charalambos S; Dodd, Susanna R; Drakeley, Andrew J

2011-08-10

Aspirin is used to improve the outcome in women undergoing in vitro fertilisation despite inconsistent evidence of its efficacy. The most appropriate time to commence aspirin therapy and the length of treatment required are also still to be determined. This is an update of the review first published in 2007. To determine the effectiveness and safety of aspirin for improving the outcome of in vitro fertilisation and intracytoplasmic sperm injection treatment cycles. We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library January 2011), MEDLINE (1966 to January 2011) and EMBASE (1980 to January 2011) databases. We used the research terms: "(aspirin OR acetylsalicylic acid) AND (in-vitro fertilisation OR intracytoplasmic sperm injection)", combined with the Cochrane Menstrual Disorders and Subfertility Group's search strategy, in order to identify randomised controlled trials on aspirin for women undergoing in vitro fertilisation. Randomised controlled trials. Two authors independently selected studies to include in the review, extracted data and assessed trial quality. The searches identified 13 trials which were eligible for inclusion in the review, including a total of 2653 participants. No significant differences were found between the treatment and control groups for any of the outcomes assessed. No significant differences were found in the meta-analysis of studies investigating the effect of aspirin compared with control on live birth rate (RR 0.91, 95% CI 0.72 to 1.15; three studies and 1053 participants), clinical pregnancy rate (RR 1.03, 95% CI 0.91 to 1.17; 10 studies and 2142 participants), ectopic and miscarriage rates (RR 1.86, 95% CI 0.75 to 4.63; RR 1.10, 95% CI 0.68 to 1.77) respectively (three and five studies involving 1135 and 1497 participants). Use of aspirin for women undergoing in vitro fertilisation cannot be recommended due to lack of evidence from the current trial data. Adequately powered trials are needed. It was proposed in the initial version of this review that a sample size of 350 women in each group would be required in order to demonstrate a 10% improvement from the use of aspirin, with 80% power at the 5% significance level. Until such evidence is available, this treatment can not be recommended.

Follistatin Gene Therapy Improves Ambulation in Becker Muscular Dystrophy

PubMed Central

Al-Zaidy, Samiah A.; Sahenk, Zarife; Rodino-Klapac, Louise R.; Kaspar, Brian; Mendell, Jerry R.

2015-01-01

Abstract Follistatin is a ubiquitous secretory propeptide that functions as a potent inhibitor of the myostatin pathway, resulting in an increase in skeletal muscle mass. Its ability to interact with the pituitary activin-inhibin axis and suppress the secretion of follicle-stimulating hormone (FSH) called for caution in its clinical applicability. This limitation was circumvented by the use of one of the alternatively spliced follistatin variants, FS344, undergoing post-translational modification to FS315. This follistatin isoform is serum-based, and has a 10-fold lower affinity to activin compared to FS288. Preclinical studies of intramuscular delivery of the follistatin gene demonstrated safety and efficacy in enhancing muscle mass. We herein review the evidence supporting the utility of follistatin as a genetic enhancer to improve cellular performance. In addition, we shed light on the results of the first clinical gene transfer trial using the FS344 isoform of follistatin in subjects with Becker muscular dystrophy as well as the future directions for clinical gene therapy trials using follistatin. PMID:27858738

Follistatin Gene Therapy Improves Ambulation in Becker Muscular Dystrophy.

PubMed

Al-Zaidy, Samiah A; Sahenk, Zarife; Rodino-Klapac, Louise R; Kaspar, Brian; Mendell, Jerry R

2015-09-02

Follistatin is a ubiquitous secretory propeptide that functions as a potent inhibitor of the myostatin pathway, resulting in an increase in skeletal muscle mass. Its ability to interact with the pituitary activin-inhibin axis and suppress the secretion of follicle-stimulating hormone (FSH) called for caution in its clinical applicability. This limitation was circumvented by the use of one of the alternatively spliced follistatin variants, FS344, undergoing post-translational modification to FS315. This follistatin isoform is serum-based, and has a 10-fold lower affinity to activin compared to FS288. Preclinical studies of intramuscular delivery of the follistatin gene demonstrated safety and efficacy in enhancing muscle mass. We herein review the evidence supporting the utility of follistatin as a genetic enhancer to improve cellular performance. In addition, we shed light on the results of the first clinical gene transfer trial using the FS344 isoform of follistatin in subjects with Becker muscular dystrophy as well as the future directions for clinical gene therapy trials using follistatin.

External beam radiation therapy for clinically localized prostate cancer: when and how we optimize with concurrent hormonal deprivation.

PubMed

Koontz, Bridget F; Lee, W Robert

2011-10-01

Androgen deprivation plays a major role in the treatment of prostate cancer.Preclinical studies have shown that androgen deprivation provides both an independent cytotoxic effect and radiosensitization on prostate tumors. For men with non-metastatic prostate cancer, the addition of androgen deprivation to radiotherapy has been shown to improve survival for intermediate and high risk disease compared to radiation alone.This review discusses the clinical trial data regarding combination of androgen deprivation and radiation and provides recommendations for its use in men undergoing radiotherapy for localized prostate cancer.

Benzydamine hydrochloride in prevention and management of pain in oral mucositis associated with radiation therapy

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

Epstein, J.B.; Stevenson-Moore, P.

1986-08-01

Benzydamine hydrochloride rinse reduced pain associated with radiation mucositis when it was used during the course of radiation therapy. Fewer patients using benzydamine rinse required systemic analgesics. All patients using benzydamine tolerated the rinse well and continued with regular rinsing throughout the course of radiation therapy. Benzydamine hydrochloride is currently undergoing clinical trials in the United States for application for approval from the Food and Drug Administration.

The effects of acupuncture on rates of clinical pregnancy among women undergoing in vitro fertilization: a systematic review and meta-analysis

PubMed Central

Manheimer, Eric; van der Windt, Daniëlle; Cheng, Ke; Stafford, Kristen; Liu, Jianping; Tierney, Jayne; Lao, Lixing; Berman, Brian M.; Langenberg, Patricia; Bouter, Lex M.

2013-01-01

BACKGROUND Recent systematic reviews of adjuvant acupuncture for IVF have pooled heterogeneous trials, without examining variables that might explain the heterogeneity. The aims of our meta-analysis were to quantify the overall pooled effects of adjuvant acupuncture on IVF clinical pregnancy success rates, and evaluate whether study design-, treatment- and population-related factors influence effect estimates. METHODS We included randomized controlled trials that compared needle acupuncture administered within 1 day of embryo transfer, versus sham acupuncture or no adjuvant treatment. Our primary outcome was clinical pregnancy rates. We obtained from all investigators additional methodological details and outcome data not included in their original publications. We analysed sham-controlled and no adjuvant treatment-controlled trials separately, but since there were no large or significant differences between these two subsets, we pooled all trials for subgroup analyses. We prespecified 11 subgroup variables (5 clinical and 6 methodological) to investigate sources of heterogeneity, using single covariate meta-regressions. RESULTS Sixteen trials (4021 participants) were included in the meta-analyses. There was no statistically significant difference between acupuncture and controls when combining all trials [risk ratio (RR) 1.12, 95% confidence interval (CI), 0.96–1.31; I2 = 68%; 16 trials; 4021 participants], or when restricting to sham-controlled (RR 1.02, 0.83–1.26; I2 = 66%; 7 trials; 2044 participants) or no adjuvant treatment-controlled trials (RR 1.22, 0.97–1.52; I2 = 67%; 9 trials; 1977 participants). The type of control used did not significantly explain the statistical heterogeneity (interaction P = 0.27). Baseline pregnancy rate, measured as the observed rate of clinical pregnancy in the control group of each trial, was a statistically significant effect modifier (interaction P < 0.001), and this covariate explained most of the heterogeneity of the effects of adjuvant acupuncture across all trials (adjusted R2 = 93%; I2 residual = 9%). Trials with lower control group rates of clinical pregnancy showed larger effects of adjuvant acupuncture (RR 1.53, 1.28–1.84; 7 trials; 1732 participants) than trials with higher control group rates of clinical pregnancy (RR 0.90, 0.80–1.01; 9 trials; 2289 participants). The asymmetric funnel plot showed a tendency for the intervention effects to be more beneficial in smaller trials. CONCLUSIONS We found no pooled benefit of adjuvant acupuncture for IVF. The subgroup finding of a benefit in trials with lower, but not higher, baseline pregnancy rates (the only statistically significant subgroup finding in our earlier review) has been confirmed in this update, and was not explained by any confounding variables evaluated. However, this baseline pregnancy rate subgroup finding among published trials requires further confirmation and exploration in additional studies because of the multiple subgroup tests conducted, the risk of unidentified confounders, the multiple different factors that determine baseline rates, and the possibility of publication bias. PMID:23814102

A registry-based randomized trial comparing radial and femoral approaches in women undergoing percutaneous coronary intervention: the SAFE-PCI for Women (Study of Access Site for Enhancement of PCI for Women) trial.

PubMed

Rao, Sunil V; Hess, Connie N; Barham, Britt; Aberle, Laura H; Anstrom, Kevin J; Patel, Tejan B; Jorgensen, Jesse P; Mazzaferri, Ernest L; Jolly, Sanjit S; Jacobs, Alice; Newby, L Kristin; Gibson, C Michael; Kong, David F; Mehran, Roxana; Waksman, Ron; Gilchrist, Ian C; McCourt, Brian J; Messenger, John C; Peterson, Eric D; Harrington, Robert A; Krucoff, Mitchell W

2014-08-01

This study sought to determine the effect of radial access on outcomes in women undergoing percutaneous coronary intervention (PCI) using a registry-based randomized trial. Women are at increased risk of bleeding and vascular complications after PCI. The role of radial access in women is unclear. Women undergoing cardiac catheterization or PCI were randomized to radial or femoral arterial access. Data from the CathPCI Registry and trial-specific data were merged into a final study database. The primary efficacy endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding or vascular complications requiring intervention. The primary feasibility endpoint was access site crossover. The primary analysis cohort was the subgroup undergoing PCI; sensitivity analyses were conducted in the total randomized population. The trial was stopped early for a lower than expected event rate. A total of 1,787 women (691 undergoing PCI) were randomized at 60 sites. There was no significant difference in the primary efficacy endpoint between radial or femoral access among women undergoing PCI (radial 1.2% vs. 2.9% femoral, odds ratio [OR]: 0.39; 95% confidence interval [CI]: 0.12 to 1.27); among women undergoing cardiac catheterization or PCI, radial access significantly reduced bleeding and vascular complications (0.6% vs. 1.7%; OR: 0.32; 95% CI: 0.12 to 0.90). Access site crossover was significantly higher among women assigned to radial access (PCI cohort: 6.1% vs. 1.7%; OR: 3.65; 95% CI: 1.45 to 9.17); total randomized cohort: (6.7% vs. 1.9%; OR: 3.70; 95% CI: 2.14 to 6.40). More women preferred radial access. In this pragmatic trial, which was terminated early, the radial approach did not significantly reduce bleeding or vascular complications in women undergoing PCI. Access site crossover occurred more often in women assigned to radial access. (SAFE-PCI for Women; NCT01406236). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Outcomes after coronary computed tomography angiography in the emergency department: a systematic review and meta-analysis of randomized, controlled trials.

PubMed

Hulten, Edward; Pickett, Christopher; Bittencourt, Marcio Sommer; Villines, Todd C; Petrillo, Sara; Di Carli, Marcelo F; Blankstein, Ron

2013-02-26

The aim of the study was to systematically review and perform a meta-analysis of randomized, controlled trials of coronary computed tomography angiography (CCTA) versus usual care (UC) triage of acute chest pain in the emergency department (ED). CCTA allows rapid evaluation of patients presenting to the ED with acute chest pain syndromes; however, the impact of such testing on patient management and downstream testing has emerged as a concern. We systematically searched for randomized, controlled trials of CCTA in the ED and performed a meta-analysis of clinical outcomes. Four randomized, controlled trials were included, with 1,869 patients undergoing CCTA and 1,397 undergoing UC. There were no deaths and no difference in the incidence of myocardial infarction, post-discharge ED visits, or rehospitalizations. Four studies reported decreased length of stay with CCTA and 3 reported cost savings; 8.4% of patients undergoing CCTA versus 6.3% of those receiving UC underwent invasive coronary angiography (ICA), whereas 4.6% of patients undergoing CCTA versus 2.6% of those receiving UC underwent coronary revascularization. The odds ratio of ICA for CCTA patients versus UC patients was 1.36 (95% confidence interval [CI]: 1.03 to 1.80, p = 0.030), and for revascularization, it was 1.81 (95% CI: 1.20 to 2.72, p = 0.004). The absolute increase in ICA after CCTA was 21 per 1,000 CCTA patients (95% CI: 1.8 to 44.9), and the number needed to scan was 48. The absolute increase in revascularization after CCTA was 20 per 1,000 patients (95% CI: 5.0 to 41.4); the number needed to scan was 50. Both percutaneous coronary intervention and coronary artery bypass graft surgery independently contributed to the significant increase in revascularization. Compared with UC, the use of CCTA in the ED is associated with decreased ED cost and length of stay but increased ICA and revascularization. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Impact of aspirin resistance on outcomes among patients following coronary artery bypass grafting: exploratory analysis from randomized controlled trial (NCT01159639).

PubMed

Petricevic, Mate; Kopjar, Tomislav; Gasparovic, Hrvoje; Milicic, Davor; Svetina, Lucija; Zdilar, Boris; Boban, Marko; Mihaljevic, Martina Zrno; Biocina, Bojan

2015-05-01

Individual variability in the response to aspirin, has been established by various platelet function assays, however, the clinical relevance of aspirin resistance (AR) in patients undergoing coronary artery bypass grafting (CABG) has to be evaluated. Our working group conducted a randomized controlled trial (NCT01159639) with the aim to assess impact of dual antiplatelet therapy (APT) on outcomes among patients with AR following CABG. Patients that were aspirin resistant on fourth postoperative day (POD 4) were randomly assigned to receive either dual APT with clopidogrel (75 mg) plus aspirin (300 mg)-intervention arm or monotherapy with aspirin (300 mg)-control arm. This exploratory analysis compares clinical outcomes between aspirin resistant patients allocated to control arm and patients that have had adequate platelet inhibitory response to aspirin at POD 4. Both groups were treated with 300 mg of aspirin per day following surgery. We sought to evaluate the impact of early postoperative AR on outcomes among patients following CABG. Exploratory analysis included a total number of 325 patients. Of those, 215 patients with adequate response to aspirin and 110 patients with AR allocated to aspirin monotherapy following randomization protocol. The primary efficacy end point (MACCEs-major adverse cardiac and cardiovascular events) occurred in 10 and 6 % of patients with AR and with adequate aspirin response, respectively (p = 0.27). Non-significant differences were observed in bleeding events occurrence. Subgroup analysis of the primary end point revealed that aspirin resistant patients with BMI > 30 kg/m(2) tend to have a higher occurrence of MACCEs 18 versus 5 % (relative risk 0.44 [95 % CI 0.16-1.16]; p = 0.05). This exploratory analysis did not reveal significant impact of aspirin resistance on outcomes among patients undergoing CABG. Further, sufficiently powered studies are needed in order to evaluate clinical relevance of AR in patients undergoing CABG.

Outcomes of patients with chronic lung disease and severe aortic stenosis treated with transcatheter versus surgical aortic valve replacement or standard therapy: insights from the PARTNER trial (placement of AoRTic TraNscathetER Valve).

PubMed

Dvir, Danny; Waksman, Ron; Barbash, Israel M; Kodali, Susheel K; Svensson, Lars G; Tuzcu, E Murat; Xu, Ke; Minha, Sa'ar; Alu, Maria C; Szeto, Wilson Y; Thourani, Vinod H; Makkar, Raj; Kapadia, Samir; Satler, Lowell F; Webb, John G; Leon, Martin B; Pichard, Augusto D

2014-01-28

The study aimed to evaluate the impact of chronic lung disease (CLD) on outcomes of severe aortic stenosis patients across all treatment modalities. Outcomes of patients with CLD undergoing transcatheter aortic valve replacement (TAVR) have not been systematically examined. All patients who underwent TAVR in the PARTNER (Placement of AoRTic TraNscathetER Valve) trial, including the continued access registry (n = 2,553; 1,108 with CLD), were evaluated according to CLD clinical severity. Additionally, outcomes of CLD patients included in the randomization arms of the PARTNER trial were compared: Cohort A patients (high-risk operable) treated by either TAVR (n = 149) or surgical aortic valve replacement (SAVR); (n = 138); and Cohort B patients (inoperable) treated by either TAVR (n = 72) or standard therapy only (n = 95). Among all TAVR-treated patients, at 1-year follow-up, patients with CLD had higher mortality than those without it (23.4% vs. 19.6%, p = 0.02). Baseline characteristics of CLD patients who underwent TAVR were similar to respective controls. In Cohort A, 2-year all-cause death rates were similar (TAVR 35.2% and SAVR 33.6%, p = 0.92), whereas in Cohort B, the death rate was lower after TAVR (52.0% vs. 69.6% after standard therapy only, p = 0.04). Independent predictors for mortality in CLD patients undergoing TAVR included poor mobility (6-min walk test <50 m; hazard ratio: 1.67, p = 0.0009) and oxygen-dependency (hazard ratio: 1.44, p = 0.02). Although CLD patients undergoing TAVR have worse outcomes than patients without CLD, TAVR is better in these patients than standard therapy and is similar to SAVR. Although patients with CLD undergoing TAVR had worse outcomes than patients without CLD, TAVR performed better in these patients than standard therapy and was similar to SAVR. However, CLD patients who were either poorly mobile or oxygen-dependent had poor outcomes. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Global regulatory developments for clinical stem cell research: diversification and challenges to collaborations.

PubMed

Rosemann, Achim; Bortz, Gabriela; Vasen, Federico; Sleeboom-Faulkner, Margaret

2016-10-01

In this article, we explore regulatory developments in stem cell medicine in seven jurisdictions: Japan, China, India, Argentina, Brazil, the USA and the EU. We will show that the research methods, ethical standards and approval procedures for the market use of clinical stem cell interventions are undergoing an important process of global diversification. We will discuss the implications of this process for international harmonization and the conduct of multicountry clinical research collaborations. It will become clear that the increasing heterogeneity of research standards and regulations in the stem cell field presents a significant challenge to international clinical trial partnerships, especially with countries that diverge from the regulatory models that have been developed in the USA and the EU.

Pre-Operative Lugol's Iodine Treatment in the Management of Patients Undergoing Thyroidectomy for Graves' Disease: A Review of the Literature.

PubMed

Hope, Nicholas; Kelly, Andrew

2017-02-01

To undertake a review of the relevant English literature published on the pre-operative use of Lugol's iodine in the management of patients undergoing thyroidectomy for Graves' disease. We reviewed all relevant papers found through Ovid Medline, PubMed, EMBASE and the American Thyroid Association website. Searches were limited to the English language only. The critical appraisal tool CASP was used to help analyse the papers. Following this, the evidence was ranked using the Harbour and Miller classification of hierarchy. Four papers were deemed appropriate for analysis. The evidence contained within the review is considered weak. The literature available in the public domain regarding the use of iodinated solutions in the pre-operative period for those patients about to undergo thyroidectomy for Graves' disease is scant. Having undertaken an extensive literature review, we are of the opinion that the evidence on which the American Thyroid Association's guidance on the use of preoperative Lugol's iodine is based is tenuous. There appears to be little in the way of sound clinical evidence that post-operative outcomes are any different following a course of Lugol's iodine. Given the lack of robust clinical evidence regarding the clinical need for iodine solution in the pre-operative period, it appears clear that a larger, prospective, randomised controlled trial of all relevant outcomes - clinical and scientific - is required to answer whether or not patient preparation with Lugol's iodine is in fact necessary prior to operative intervention for Graves' disease.

Is hydrokinesitherapy effective on gait and balance in patients with stroke? A clinical and baropodometric investigation.

PubMed

Furnari, Anna; Calabrò, Rocco Salvatore; Gervasi, Giuseppe; La Fauci-Belponer, Francesca; Marzo, Antonio; Berbiglia, Fabio; Paladina, Giuseppe; De Cola, Maria Cristina; Bramanti, Placido

2014-01-01

Patients with stroke present an asymmetric posture, severe balance dysfunction with delayed and disrupted equilibrium reactions, exaggerated postural sway and abnormal gait with an increased risk of falling. The aim of this study is to evaluate the efficacy of hydrokinesytherapy on stance, balance and gait in individuals after stroke. In this single-blinded randomized controlled trial, patients with stroke were divided into two groups: an experimental one (G1), performing hydrokinesytherapy (3 times/week) in addition to a conventional physical therapy (3 times/week) and a control one (G2), performing only a conventional physical therapy (6 times/week). All of the participants underwent a proper clinical and baropodometric evaluation before and after 8 weeks of treatment. The two groups presented similar clinical and instrumental features at enrolment (mean modified Rankin Scale of 3, and a disease duration of 6.3 ± 1.4 months). After treatment, the patients undergoing hydrokinesytherapy showed a significantly greater improvement than those undergoing traditional training. Hydrokinesytherapy may be considered a promising treatment in improving gait and balance in individuals following stroke.

A non-randomized confirmatory trial of segmentectomy for clinical T1N0 lung cancer with dominant ground glass opacity based on thin-section computed tomography (JCOG1211).

PubMed

Aokage, Keiju; Saji, Hisashi; Suzuki, Kenji; Mizutani, Tomonori; Katayama, Hiroshi; Shibata, Taro; Watanabe, Syunichi; Asamura, Hisao

2017-05-01

Lobectomy has been the standard surgery for even stage I lung cancer since the validity of limited resection for stage I lung cancer was denied by the randomized study reported in 1995. The aim of this non-randomized confirmatory going on since September 2013 is to confirm the efficacy of a segmentectomy for clinical T1N0 lung cancer with dominant ground glass opacity based on thin-slice computed tomography. A total of 390 patients from 42 Japanese institutions are recruited within 4 years. The primary endpoint of this study is a 5-year relapse-free survival in all of the patients who undergo a segmentectomy for a lung nodule. The secondary endpoints are overall survival, annual relapse-free survival, disease-free survival, proportion of local relapse, postoperative pulmonary function, proportion of segmentectomy completion, proportion of R0 resection completion by segmentectomy, adverse events, and serious adverse events. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000011819 ( http://www.umin.ac.jp/ctr/ ). Patient's accrual has been already finished in November, 2015 and the primary analysis will be performed in 2021. This study is one of the pivotal trial of lung segmentectomy for early lung cancer. The result will provide a clear evidence for our daily clinics and will be possible contribution to preserving pulmonary function for lung cancer patients.

Protocol biopsy of the stable renal transplant: a multicenter study of methods and complication rates.

PubMed

Furness, Peter N; Philpott, Carl M; Chorbadjian, Mary T; Nicholson, Michael L; Bosmans, Jean-Louis; Corthouts, Bob L; Bogers, Johannes J P M; Schwarz, Anke; Gwinner, Wilfried; Haller, Hermann; Mengel, Michael; Seron, Daniel; Moreso, Francesc; Cañas, Conception

2003-09-27

Clinical trials in renal transplantation must use surrogate markers of long-term graft survival if conclusions are to be drawn at acceptable speed and cost. Morphologic changes in transplant biopsies provide the earliest available evidence of damage, and "protocol" biopsies from stable grafts can be used to reduce the number of patients needed in clinical trials. This approach has been inhibited by concerns over safety, but the risk of biopsy of a stable kidney, with no active inflammation or acute functional impairment, has never been formally estimated. In accordance with a predefined set of questions, a retrospective audit of a sequential series of protocol biopsies was performed in four major transplant centers. A total of 2,127 biopsy events were assessed for major complications, and 1,486 were assessed for minor ones. There were no deaths. One graft was lost, under circumstances indicating that the loss should have been prevented. Three episodes of hemorrhage required direct intervention. Three further patients required transfusion. There were two episodes of peritonitis, but one was arguably an unrelated event. All serious complications presented within 4 hr of biopsy. The incidence of clinically significant complications after protocol biopsy of a stable renal transplant is low. Direct benefits to the patients concerned (irrespective of the benefit that may accrue in clinical trials) were not formally assessed but seem likely to outweigh the risk of the procedure. We believe that it is ethically justifiable to ask renal transplant recipients to undergo protocol biopsies in clinical trials and routine care.

Regulation (EC) No 1901/2006 on medicinal products for paediatric use & clinical research in vulnerable populations.

PubMed

Lehmann, Birka

2008-12-08

Before any medicinal product is authorised for use in adults, it must undergo extensive pharmaceutical consistency and stability tests, toxicological tests and clinical trials to ensure that it is of high quality, safe and effective.The same approach may not always be applied to medicinal products used to treat children.Studies showed that over 50% of the medicinal products used in children may not have been tested for use in this age group. The absence of suitable authorised medicinal products to treat conditions in children results from the fact that pharmaceutical companies do not adapt medicinal products to the needs of the paediatric population. This leaves health care professionals with no alternative other than to use medicinal products "off-label" and to use unauthorised products with the associated risks of inefficacy and/or adverse reactions.The Regulation (EC) No 1901/2006 sets up a system of requirements, rewards and incentives, together with horizontal measures, to ensure that medicinal products are researched, developed and authorised to meet the therapeutic needs of children.The Regulation is addressed to: 1. The pharmaceutical industry by setting out the legal framework for receiving rewards and incentives by conducting clinical trials in the paediatric population. 2. The Member States to set out to support research into, and the development and availability of, medicinal products for paediatric use. 3. The Community as funds for research into medicinal products for the paediatric population shall be provided for in the Community budget in order to support studies relating to medicinal products or active substances not covered by a patent or a supplementary protection certificate. The legal framework for conducting clinical trials, including children/minors, is set up in Directive 2001/20/EC, the Clinical Trials Directive (CTD), for the European Union (EU). The CTD establishes specific provisions regarding conduct of clinical trials, including multi-centre trials, on human subjects involving medicinal products and in particular relating to the implementation of good clinical practice. Compliance with this good practice provides assurance that the rights, safety and well-being of trial subjects are protected, and that the results of the clinical trials are credible. The CTD is addressed to all investigators conducting clinical trials including clinical trials in the paediatric population and had to be applied accordingly.In the framework of the authorisation of medicinal products regulated by the Regulation (EC) No 726/2004 and Directive 2001/83/EC as amended and the CTD, and additional implementing Directives and guidelines, the new Regulation (EC) No 1901/2006 is an important new piece of legislation focusing on the requirements to improve the situation for the paediatric population. All Regulations/Directives to be found: http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol1_en.htm.

Regulation (EC) No 1901/2006 on medicinal products for paediatric use & clinical research in vulnerable populations

PubMed Central

Lehmann, Birka

2008-01-01

Before any medicinal product is authorised for use in adults, it must undergo extensive pharmaceutical consistency and stability tests, toxicological tests and clinical trials to ensure that it is of high quality, safe and effective. The same approach may not always be applied to medicinal products used to treat children. Studies showed that over 50% of the medicinal products used in children may not have been tested for use in this age group. The absence of suitable authorised medicinal products to treat conditions in children results from the fact that pharmaceutical companies do not adapt medicinal products to the needs of the paediatric population. This leaves health care professionals with no alternative other than to use medicinal products "off-label" and to use unauthorised products with the associated risks of inefficacy and/or adverse reactions. The Regulation (EC) No 1901/2006 sets up a system of requirements, rewards and incentives, together with horizontal measures, to ensure that medicinal products are researched, developed and authorised to meet the therapeutic needs of children. The Regulation is addressed to: 1. The pharmaceutical industry by setting out the legal framework for receiving rewards and incentives by conducting clinical trials in the paediatric population. 2. The Member States to set out to support research into, and the development and availability of, medicinal products for paediatric use. 3. The Community as funds for research into medicinal products for the paediatric population shall be provided for in the Community budget in order to support studies relating to medicinal products or active substances not covered by a patent or a supplementary protection certificate. The legal framework for conducting clinical trials, including children/minors, is set up in Directive 2001/20/EC, the Clinical Trials Directive (CTD), for the European Union (EU). The CTD establishes specific provisions regarding conduct of clinical trials, including multi-centre trials, on human subjects involving medicinal products and in particular relating to the implementation of good clinical practice. Compliance with this good practice provides assurance that the rights, safety and well-being of trial subjects are protected, and that the results of the clinical trials are credible. The CTD is addressed to all investigators conducting clinical trials including clinical trials in the paediatric population and had to be applied accordingly. In the framework of the authorisation of medicinal products regulated by the Regulation (EC) No 726/2004 and Directive 2001/83/EC as amended and the CTD, and additional implementing Directives and guidelines, the new Regulation (EC) No 1901/2006 is an important new piece of legislation focusing on the requirements to improve the situation for the paediatric population. All Regulations/Directives to be found: PMID:19063722

A randomized clinical trial of continuous aspiration of subglottic secretions in cardiac surgery patients.

PubMed

Kollef, M H; Skubas, N J; Sundt, T M

1999-11-01

To determine whether the application of continuous aspiration of subglottic secretions (CASS) is associated with a decreased incidence of ventilator-associated pneumonia (VAP). Prospective clinical trial. Cardiothoracic ICU (CTICU) of Barnes-Jewish Hospital, St. Louis, a university-affiliated teaching hospital. Three hundred forty-three patients undergoing cardiac surgery and requiring mechanical ventilation in the CTICU. Patients were assigned to receive either CASS, using a specially designed endotracheal tube (Hi-Lo Evac; Mallinckrodt Inc; Athlone, Ireland), or routine postoperative medical care without CASS. One hundred sixty patients were assigned to receive CASS, and 183 were assigned to receive routine postoperative medical care without CASS. The two groups were similar at the time of randomization with regard to demographic characteristics, surgical procedures performed, and severity of illness. Risk factors for the development of VAP were also similar during the study period for both treatment groups. VAP was seen in 8 patients (5.0%) receiving CASS and in 15 patients (8. 2%) receiving routine postoperative medical care without CASS (relative risk, 0.61%; 95% confidence interval, 0.27 to 1.40; p = 0. 238). Episodes of VAP occurred statistically later among patients receiving CASS ([mean +/- SD] 5.6 +/- 2.3 days) than among patients who did not receive CASS (2.9 +/- 1.2 days); (p = 0.006). No statistically significant differences for hospital mortality, overall duration of mechanical ventilation, lengths of stay in the hospital or CTICU, or acquired organ system derangements were found between the two treatment groups. No complications related to CASS were observed in the intervention group. Our findings suggest that CASS can be safely administered to patients undergoing cardiac surgery. The occurrence of VAP can be significantly delayed among patients undergoing cardiac surgery using this simple-to-apply technique.

Effects of an alveolar recruitment maneuver on subdural pressure, brain swelling, and mean arterial pressure in patients undergoing supratentorial tumour resection: a randomized crossover study.

PubMed

Flexman, Alana M; Gooderham, Peter A; Griesdale, Donald E; Argue, Ruth; Toyota, Brian

2017-06-01

Although recruitment maneuvers have been advocated as part of a lung protective ventilation strategy, their effects on cerebral physiology during elective neurosurgery are unknown. Our objectives were to determine the effects of an alveolar recruitment maneuver on subdural pressure (SDP), brain relaxation score (BRS), and cerebral perfusion pressure among patients undergoing supratentorial tumour resection. In this prospective crossover study, patients scheduled for resection of a supratentorial brain tumour were randomized to undergo either a recruitment maneuver (30 cm of water for 30 sec) or a "sham" maneuver (5 cm of water for 30 sec), followed by the alternative intervention after a 90-sec equilibration period. Subdural pressure was measured through a dural perforation following opening of the cranium. Subdural pressure and mean arterial pressure (MAP) were recorded continuously. The blinded neurosurgeon provided a BRS at baseline and at the end of each intervention. During each treatment, the changes in SDP, BRS, and MAP were compared. Twenty-one patients underwent the study procedure. The increase in SDP was higher during the recruitment maneuver than during the sham maneuver (difference, 3.9 mmHg; 95% confidence interval [CI], 2.2 to 5.6; P < 0.001). Mean arterial pressure decreased further in the recruitment maneuver than in the sham maneuver (difference, -9.0 mmHg; 95% CI, -12.5 to -5.6; P < 0.001). Cerebral perfusion pressure decreased 14 mmHg (95% CI, 4 to 24) during the recruitment maneuver. The BRS did not change with either maneuver. Our results suggest that recruitment maneuvers increase subdural pressure and reduce cerebral perfusion pressure, although the clinical importance of these findings is thus far unknown. This trial was registered with ClinicalTrials.gov, NCT02093117.

Rescue Sedation With Intranasal Dexmedetomidine for Pediatric Ophthalmic Examination After Chloral Hydrate Failure: A Randomized, Controlled Trial.

PubMed

Gan, Xiaoliang; Lin, Haotian; Chen, Jingjing; Lin, Zhuoling; Lin, Yiquan; Chen, Weirong

2016-06-01

It is a challenge to rescue ophthalmology examinations performed in children in the sedation room after initial chloral hydrate failure. Intranasal dexmedetomidine can be used in rescue sedation in children undergoing computed tomography. The present study aimed to assess the efficacy and tolerability of intranasal dexmedetomidine use in children undergoing ophthalmic examination after chloral hydrate failure. Sixty uncooperative pediatric patients with cataract (aged 5-36 months; weight, 7-15 kg) presented for follow-up ophthalmic examination. Patients who experienced chloral hydrate failure were randomized to 1 of 2 groups to receive intranasal dexmedetomidine 1 or 2 μg/kg for rescue sedation. Each group contained 30 patients. The primary outcome was the rate of a successful ophthalmic examination. Secondary outcomes included sedation onset time, recovery time, duration of examination, discharge time, and adverse events, including percentage of heart rate reduction, respiratory depression, vomiting, and postsedative agitation. A successful ophthalmic examination was achieved in 93.3% (28/30) of patients in the 2-μg/kg dose group and in 66.7% (20/30) of patients in the 1-μg/kg dose group (P = 0.021). The onset time, recovery time, and discharge time did not significantly differ between the 2 groups. None of the patients required clinical intervention due to heart rate reduction, and none of the patients in either group experienced vomiting, respiratory depression, or agitation after the administration of dexmedetomidine. In children undergoing ophthalmic examination, intranasal dexmedetomidine can be administered in the sedation room for rescue sedation after chloral hydrate failure, with the 2-μg/kg dose being more efficacious than the 1-μg/kg dose, as measured by success rate. ClinicalTrials.gov identifier: NCT02077712. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis.

PubMed

Chertow, Glenn M; Block, Geoffrey A; Correa-Rotter, Ricardo; Drüeke, Tilman B; Floege, Jürgen; Goodman, William G; Herzog, Charles A; Kubo, Yumi; London, Gerard M; Mahaffey, Kenneth W; Mix, T Christian H; Moe, Sharon M; Trotman, Marie-Louise; Wheeler, David C; Parfrey, Patrick S

2012-12-27

Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients. In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle. The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02; P=0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet. In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis. (Funded by Amgen; EVOLVE ClinicalTrials.gov number, NCT00345839.).

The effect of intrauterine HCG injection on IVF outcome: a systematic review and meta-analysis.

PubMed

Osman, A; Pundir, J; Elsherbini, M; Dave, S; El-Toukhy, T; Khalaf, Y

2016-09-01

In this systematic review and meta-analysis, the effect of intrauterine HCG infusion before embryo transfer on IVF outcomes (live birth rate, clinical pregnancy rate and spontaneous aboretion rate) was investigated. Searches were conducted on MEDLINE, EMBASE and The Cochrane Library. Randomized studies in women undergoing IVF and intracytoplasmic sperm injection comparing intrauterine HCG administration at embryo transfer compared with no intrauterine HCG were eligible for inclusion. Eight randomized controlled trials were eligible for inclusion in the meta-analysis. A total of 3087 women undergoing IVF and intracytoplasmic sperm injection cycles were enrolled (intrauterine HCG group: n = 1614; control group: n = 1473). No significant difference was found in the live birth rate (RR 1.13; 95% CI 0.84 to 1.53) and spontaneous abortion rate (RR 1.00, 95% CI 0.74 to 1.34) between women who received intrauterine HCG and those who did not receive HCG. Although this review was extensive and included randomized controlled trials, no significant heterogeneity was found, and the overall included numbers are relatively small. In conclusion the current evidence does not support the use of intrauterine HCG administration before embryo transfer. Well-designed multicentre trials are needed to provide robust evidence. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Antibiotic prophylaxis in transarterial therapy of hepatocellular carcinoma: A meta-analysis

PubMed Central

Wang, Jun; He, Xiao Dong; Zhang, You Cheng

2012-01-01

BACKGROUND: The use of prophylactic antibiotics against postprocedure infection in patients undergoing transarterial therapy for hepatocellular carcinoma is controversial. AIM: To compare the effects of prophylactic antibiotic treatment and no prophylactic antibiotic treatment on infectious complications following transarterial procedures. METHODS: Clinical trials fulfilling predefined selection criteria were identified by searching several bibliographic databases; a meta-analysis was performed where appropriate. RESULTS: Four trials of inadequate quality consisting of 210 patients were included in the analysis. Only one case of possible postprocedure infection in each group was reported. The rate of patients developing fever (RR 0.91 [95% CI 0.61 to 1.35]), changes in peripheral white blood cell count or serum C-reactive protein levels, and the mean length of hospital stay (mean difference 0.20 [95% CI 0.75 to 1.14]) showed no significant intergroup differences between antibiotic and no antibiotic treatment. Furthermore, the results of the present study indicated that the incidence of bacteremia, septicemia, sepsis or hepatic abscess after transarterial therapy was rare. CONCLUSION: Antibiotic prophylaxis in patients undergoing transarterial therapy for hepatocellular carcinoma may not be routinely necessary. However, a more judicious use of antibiotics is recommended for patients who are at an increased risk of infection. Nevertheless, prospective trials on a larger scale are clearly needed. PMID:22312607

Antibiotic prophylaxis in transarterial therapy of hepatocellular carcinoma: a meta-analysis.

PubMed

Wang, Jun; He, Xiao Dong; Zhang, You Cheng

2012-02-01

The use of prophylactic antibiotics against postprocedure infection in patients undergoing transarterial therapy for hepatocellular carcinoma is controversial. To compare the effects of prophylactic antibiotic treatment and no prophylactic antibiotic treatment on infectious complications following transarterial procedures. Clinical trials fulfilling predefined selection criteria were identified by searching several bibliographic databases; a meta-analysis was performed where appropriate. Four trials of inadequate quality consisting of 210 patients were included in the analysis. Only one case of possible postprocedure infection in each group was reported. The rate of patients developing fever (RR 0.91 [95% CI 0.61 to 1.35]), changes in peripheral white blood cell count or serum C-reactive protein levels, and the mean length of hospital stay (mean difference 0.20 [95% CI 0.75 to 1.14]) showed no significant intergroup differences between antibiotic and no antibiotic treatment. Furthermore, the results of the present study indicated that the incidence of bacteremia, septicemia, sepsis or hepatic abscess after transarterial therapy was rare. Antibiotic prophylaxis in patients undergoing transarterial therapy for hepatocellular carcinoma may not be routinely necessary. However, a more judicious use of antibiotics is recommended for patients who are at an increased risk of infection. Nevertheless, prospective trials on a larger scale are clearly needed.

Randomised clinical trial of chest drainage systems.

PubMed Central

Graham, A N; Cosgrove, A P; Gibbons, J R; McGuigan, J A

1992-01-01

BACKGROUND: Problems in the management of thoracic trauma have stimulated the search for an alternative to underwater seals for drainage of the pleural cavity. A chest drainage bag incorporating a one way flutter valve has been compared with underwater seal drains in a randomised clinical trial. METHODS: During June-December 1989 119 patients undergoing elective thoracotomy were randomised to receive postoperative chest drainage by drainage bags (56 patients, 87 drains) or by underwater seal drains (63 patients, 98 drains). Daily drainage volumes, the requirement for pleural suction, mobility, and complications were recorded prospectively. RESULTS: There was no significant difference between the two groups in the mean volume drained, the requirements for pleural suction, or the occurrence of complications. Patients with drainage bags were fully mobile 23 hours (95% confidence interval 0-47 hours) earlier than the others. CONCLUSIONS: When used after elective thoracotomy drainage bags are safe and effective and permit earlier mobility than underwater seal drains. PMID:1496507

Principles and strategies for monitoring data collection integrity in a multi-site randomized clinical trial of a behavioral intervention.

PubMed

Phillips-Salimi, Celeste R; Donovan Stickler, Molly A; Stegenga, Kristin; Lee, Melissa; Haase, Joan E

2011-08-01

Although treatment fidelity strategies for enhancing the integrity of behavioral interventions have been well described, little has been written about monitoring data collection integrity. This article describes the principles and strategies developed to monitor data collection integrity of the "Stories and Music for Adolescent/Young Adult Resilience During Transplant" study (R01NR008583, U10CA098543, and U10CA095861)-a multi-site Children's Oncology Group randomized clinical trial of a music therapy intervention for adolescents and young adults undergoing stem cell transplant. The principles and strategies outlined in this article provide one model for development and evaluation of a data collection integrity monitoring plan for behavioral interventions that may be adapted by investigators and may be useful to funding agencies and grant application reviewers in evaluating proposals. Copyright © 2011 Wiley Periodicals, Inc.

Endometrial Injury May Increase the Pregnancy Rate in Patients Undergoing Intrauterine Insemination: An Interventional Randomized Clinical Trial.

PubMed

Bahaa Eldin, Ahmed M; Abdelmaabud, Karim H; Laban, Mohamed; Hassanin, Alaa S; Tharwat, Ahmed A; Aly, Tarek R; Elbohoty, Ahmed E; Elsayed, Helmy M; Ibrahim, Ahmed M; Ibrahim, Mohammed E; Sabaa, Haitham M; Abdelrazik, Azza A; Abdelhady, Ibrahim

2016-10-01

This study aimed to investigate the effect of endometrial injury using Pipelle catheter in the follicular phase (cycle day 5, 6, or 7) of the stimulation cycle on pregnancy rates in patients undergoing intrauterine insemination. This prospective randomized controlled study was carried out in the Assisted Reproductive Technology Unit of Ain Shams University Maternity Hospital, Cairo, Egypt, from July 1, 2013 to August 31, 2015. Three hundred sixty women, 20 to 35 years of age, with patent fallopian tubes, mild male factor infertility, or unexplained infertility were recruited. Participants were allocated randomly into 2 groups: experimental arm and control arm. Women in the experimental arm underwent endometrial biopsy using a Pipelle catheter on day 5, 6, or 7 of the stimulation cycle combined with intrauterine insemination. Women in the control group underwent intrauterine insemination with no endometrial biopsy done. The primary outcomes were the clinical and chemical pregnancy rates. Data of 344 participants were statistically analyzed. The chemical pregnancy rate was 23.66% in the experimental arm and 10.85% in the control arm (P = .002). The clinical pregnancy rate was 18.93% in the experimental arm and 7.42% in the control arm (P = .003). Endometrial injury using a Pipelle catheter in the stimulation cycle may improve pregnancy rates in women undergoing intrauterine insemination. © The Author(s) 2016.

Baduanjin Exercise Prevents post-Myocardial Infarction Left Ventricular Remodeling (BE-PREMIER trial): Design and Rationale of a Pragmatic Randomized Controlled Trial.

PubMed

Mao, Shuai; Zhang, Xiaoxuan; Shao, Biying; Hu, Xiyan; Hu, Yanan; Li, Winny; Guo, Liheng; Zhang, Minzhou

2016-06-01

Left ventricular (LV) remodeling following myocardial infarction (MI) is an established prognostic factor for adverse cardiovascular events and the leading cause of heart failure. Empirical observations have suggested that Baduanjin exercise, an important component of traditional Chinese Qigong, may exert potential benefits on cardiopulmonary function. However, the impact of a Baduanjin exercise-based cardiac rehabilitation program for patients recovering from a recent MI has yet to be assessed. The aim of this trial is to evaluate the potential role of Baduanjin exercise in preventing the maladaptive progression to adverse LV remodeling in patients post-MI. A total of 110 clinically stable patients following an MI after undergoing successful infarct-related artery reperfusion will be randomly assigned to the Baduanjin exercise group or usual exercise control group. In addition to usual physical activity, participants in the Baduanjin exercise group will participate in a 45 min Baduanjin exercise training session twice a week, for a total of 12 weeks. The primary endpoint will be the percentage change in LV end-diastolic volume index (LVEDVi) assessed using echocardiography from baseline to 6 months. The results of this study may provide novel evidence on the efficacy of Baduanjin exercise therapy in post-MI patients in reversing adverse LV remodeling and improving clinical outcome. Clinical Trials.gov: NCT02693795.

Current role of cryotherapy in retinopathy of prematurity: a report by the American Academy of Ophthalmology.

PubMed

Simpson, Jennifer L; Melia, Michele; Yang, Michael B; Buffenn, Angela N; Chiang, Michael F; Lambert, Scott R

2012-04-01

To evaluate the role of cryotherapy in the current treatment of retinopathy of prematurity (ROP). Literature searches of PubMed and the Cochrane Library were conducted on December 2, 2009, for articles published after 1984. The searches included all languages and retrieved 187 relevant citations. Thirteen articles were deemed relevant to the assessment question and were rated according to the strength of evidence. Four articles reported results from 2 large multicenter randomized clinical trials, and the remaining 9 articles reported results of 3 small randomized trials that directly compared cryotherapy and laser. Neither of the multicenter randomized clinical trials was a direct comparison of cryotherapy with laser. These studies were used to evaluate the comparative trials based on treatment criteria, study populations, and clinical results. Higher percentages of poor structural and functional outcomes generally were seen in eyes treated with cryotherapy compared with eyes undergoing laser treatment. Higher rates of systemic complications and myopia also were identified after treatment with cryotherapy. Despite a relative paucity of level I evidence directly comparing cryotherapy and laser treatment for threshold ROP, the literature suggests that neonatal facilities should gain access to laser technology and laser-trained ophthalmic staff to achieve better outcomes for treatment of the disease. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Safety and efficacy of autologous cell therapy in critical limb ischemia: a systematic review.

PubMed

Benoit, Eric; O'Donnell, Thomas F; Patel, Amit N

2013-01-01

Researchers have accumulated a decade of experience with autologous cell therapy in the treatment of critical limb ischemia (CLI). We conducted a systematic review of clinical trials in the literature to determine the safety and efficacy of cell therapy in CLI. We searched the literature for clinical trials of autologous cell therapy in CLI, including observational series of five or more patients to accrue a large pool of patients for safety analysis. Safety analysis included evaluation of death, cancer, unregulated angiogenesis, and procedural adverse events such as bleeding. Efficacy analysis included the clinical endpoints amputation and death as well as functional and surrogate endpoints. We identified 45 clinical trials, including seven RCTs, and 1,272 patients who received cell therapy. The overall adverse event rate was low (4.2%). Cell therapy patients did not have a higher mortality rate than control patients and demonstrated no increase in cancer incidence when analyzed against population rates. With regard to efficacy, cell therapy patients had a significantly lower amputation rate than control patients (OR 0.36, p = 0.0004). Cell therapy also demonstrated efficacy in a variety of functional and surrogate outcomes. Clinical trials differed in the proportion of patients with risk factors for clinical outcomes, and these influenced rates of amputation and death. Cell therapy presents a favorable safety profile with a low adverse event rate and no increase in severe events such as mortality and cancer and treatment with cell therapy decreases the risk of amputation. Cell therapy has a positive benefit-to-risk ratio in CLI and may be a valuable treatment option, particularly for those challenging patients who cannot undergo arterial reconstruction.

Effectiveness of acupuncture in women with polycystic ovarian syndrome undergoing in vitro fertilisation or intracytoplasmic sperm injection: a systematic review and meta-analysis.

PubMed

Jo, Junyoung; Lee, Yoon Jae

2017-06-01

The aim of this systematic review was to assess the evidence from randomised controlled trials (RCTs) on the efficacy, effectiveness and safety of acupuncture in women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). We searched a total of 15 databases through October 2015. The participants were women with PCOS (diagnosed using the Rotterdam criteria) undergoing IVF or ICSI. Eligible trials were those with intervention groups receiving manual acupuncture (MA) or electroacupuncture (EA), and control groups receiving sham acupuncture, no treatment or other treatments. Outcomes included the clinical pregnancy rate (CPR), live birth rate (LBR), ongoing pregnancy rate (OPR) and incidence of ovarian hyperstimulation syndrome (OHSS) and adverse events (AEs). For statistical pooling, the risk ratio (RR) and its 95% (confidence interval) CI was calculated using a random effects model. Four RCTs including 430 participants were selected. All trials compared acupuncture (MA/EA) against no treatment. Acupuncture significantly increased the CPR (RR 1.33, 95% CI 1.03 to 1.71) and OPR (RR 2.03, 95% CI 1.08 to 3.81) and decreased the risk of OHSS (RR 0.63, 95% CI 0.42 to 0.94); however, there was no significant difference in the LBR (RR 1.61, 95% CI 0.73 to 3.58). None of the RCTs reported on AEs. Acupuncture may increase the CPR and OPR and decrease the risk of OHSS in women with PCOS undergoing IVF or ICSI. Further studies are needed to confirm the efficacy and safety of acupuncture as an adjunct to assisted reproductive technology in this particular population. 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/.

Same versus next day discharge after elective transradial PCI: The RAdial SAme Day DischArge after PCI trial. (The RASADDA-PCI trial).

PubMed

Rodriguez-Araujo, Gerardo; Cilingiroglu, Mehmet; Mego, David; Hakeem, Abdul; Lendel, Vasili; Cawich, Ian; Paixao, Andre; Marmagkiolis, Konstantinos; Flaherty, Patrick; Rollefson, William

2018-06-02

Transradial percutaneous coronary intervention (TR-PCI) has been increasingly popular over the last decade in the US. Previous studies have shown that same-day (SD) discharge after elective PCI is as safe as overnight (ON) observation. Our study was performed to assess the clinical and financial impact of early discharge in patients undergoing TR-PCI. This is a single center registry of patients undergoing elective TR-PCI. Timing of discharge was determined by the treating physician. (Groups: Same Day Discharge -SD-; Overnight Stay -ON-). Demographic data, procedural characteristics and adverse outcomes were recorded. Outcomes included 30 day-MACE and procedure- related complications, as well as total operative costs in patients from both groups. Propensity score matching for patient demographics, coronary symptoms and procedure indicators was used to compare both groups. The entire cohort included 852 patients (429 in SD group and 423 in ON group) and the propensity score matched groups of 245 patients in the SD group and 245 patients in the ON group. The two groups had no significant baseline clinical differences, and had similar clinical outcomes. Specifically, no significant difference was noted in procedural complications (3.7% vs 2.5%, p = 0.43), re-hospitalization (4.1% vs 4.1%, p = 0.92), re-intervention (2.5% vs 2.1%, p = 0.77), myocardial infarction (0% vs 0.08%, p = 0.15), stroke (0% vs 0%, p = 1.0) and all-cause mortality (0% vs 0%, p = 1.0). SD Group patients had a significant lower procedure-related cost compared to overnight stay patients ($3,346.45 vs $4,681.99, p < 0.0001) and lower 30-day post procedure-associated cumulative costs/total operating costs ($4,493.22 vs $7,112.21, p < 0.0001). In elective patients undergoing low risk TR-PCI, same-day discharge seems to be a safe and feasible clinical practice, with significant potential savings to the US healthcare system. Copyright © 2018 Elsevier Inc. All rights reserved.

Does oral health promotion influence the oral hygiene and gingival health of patients undergoing fixed appliance orthodontic treatment? A systematic literature review.

PubMed

Gray, Darren; McIntyre, Grant

2008-12-01

To determine the effectiveness of orthodontic oral health promotion (OHP) upon gingival health. The Cochrane Central Register of Controlled Trials [CENTRAL (January 2005)], MEDLINE [OVID and PubMed platforms (1966 to May 2005)] and EMBASE (1966 to May 2005) were searched. A grey literature search was also conducted. Of the 218 studies identified, 37 were retrieved for detailed examination. Methodological quality was determined using a checklist and inter-rater reliability was calculated using the unweighted kappa statistic. Six randomised (RCT) and quasi-randomised controlled clinical trails (CCT) met the inclusion criteria. Categorical data about the effect of oral health promotion on dental plaque levels and/or gingival bleeding were independently collected from the four RCTs and two CCTs by two reviewers using a data extraction proforma. Positive effects on plaque and/or gingival health were produced in only four of the included trials. OHP resulted in no difference being detected in two of the included trials. None of the trials that were included produced a negative effect of orthodontic oral health promotion on oral hygiene and gingival health. Direct comparison between the trials was difficult due to the heterogeneity in the outcome measures between the included studies. An OHP programme for patients undergoing fixed appliance orthodontic treatment produces a short-term reduction (up to 5 months) in plaque and improvement in gingival health No particular OHP method produces a greater short term benefit to periodontal health during fixed appliance orthodontic treatment Further studies using appropriate methods and in particular longer follow up periods are required.

Audiovisual biofeedback breathing guidance for lung cancer patients receiving radiotherapy: a multi-institutional phase II randomised clinical trial.

PubMed

Pollock, Sean; O'Brien, Ricky; Makhija, Kuldeep; Hegi-Johnson, Fiona; Ludbrook, Jane; Rezo, Angela; Tse, Regina; Eade, Thomas; Yeghiaian-Alvandi, Roland; Gebski, Val; Keall, Paul J

2015-07-18

There is a clear link between irregular breathing and errors in medical imaging and radiation treatment. The audiovisual biofeedback system is an advanced form of respiratory guidance that has previously demonstrated to facilitate regular patient breathing. The clinical benefits of audiovisual biofeedback will be investigated in an upcoming multi-institutional, randomised, and stratified clinical trial recruiting a total of 75 lung cancer patients undergoing radiation therapy. To comprehensively perform a clinical evaluation of the audiovisual biofeedback system, a multi-institutional study will be performed. Our methodological framework will be based on the widely used Technology Acceptance Model, which gives qualitative scales for two specific variables, perceived usefulness and perceived ease of use, which are fundamental determinants for user acceptance. A total of 75 lung cancer patients will be recruited across seven radiation oncology departments across Australia. Patients will be randomised in a 2:1 ratio, with 2/3 of the patients being recruited into the intervention arm and 1/3 in the control arm. 2:1 randomisation is appropriate as within the interventional arm there is a screening procedure where only patients whose breathing is more regular with audiovisual biofeedback will continue to use this system for their imaging and treatment procedures. Patients within the intervention arm whose free breathing is more regular than audiovisual biofeedback in the screen procedure will remain in the intervention arm of the study but their imaging and treatment procedures will be performed without audiovisual biofeedback. Patients will also be stratified by treating institution and for treatment intent (palliative vs. radical) to ensure similar balance in the arms across the sites. Patients and hospital staff operating the audiovisual biofeedback system will complete questionnaires to assess their experience with audiovisual biofeedback. The objectives of this clinical trial is to assess the impact of audiovisual biofeedback on breathing motion, the patient experience and clinical confidence in the system, clinical workflow, treatment margins, and toxicity outcomes. This clinical trial marks an important milestone in breathing guidance studies as it will be the first randomised, controlled trial providing the most comprehensive evaluation of the clinical impact of breathing guidance on cancer radiation therapy to date. This study is powered to determine the impact of AV biofeedback on breathing regularity and medical image quality. Objectives such as determining the indications and contra-indications for the use of AV biofeedback, evaluation of patient experience, radiation toxicity occurrence and severity, and clinician confidence will shed light on the design of future phase III clinical trials. This trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), its trial ID is ACTRN12613001177741 .

Cardiac surgery-associated acute kidney injury.

PubMed

Vives, Marc; Wijeysundera, Duminda; Marczin, Nandor; Monedero, Pablo; Rao, Vivek

2014-05-01

Acute kidney injury develops in up to 30% of patients who undergo cardiac surgery, with up to 3% of patients requiring dialysis. The requirement for dialysis after cardiac surgery is associated with an increased risk of infection, prolonged stay in critical care units and long-term need for dialysis. The development of acute kidney injury is independently associated with substantial short- and long-term morbidity and mortality. Its pathogenesis involves multiple pathways. Haemodynamic, inflammatory, metabolic and nephrotoxic factors are involved and overlap each other leading to kidney injury. Clinical studies have identified predictors for cardiac surgery-associated acute kidney injury that can be used effectively to determine the risk for acute kidney injury in patients undergoing cardiac surgery. High-risk patients can be targeted for renal protective strategies. Nonetheless, there is little compelling evidence from randomized trials supporting specific interventions to protect or prevent acute kidney injury in cardiac surgery patients. Several strategies have shown some promise, including less invasive procedures in those at greatest risk, natriuretic peptide, fenoldopam, preoperative hydration, preoperative optimization of anaemia and postoperative early use of renal replacement therapy. The efficacy of larger-scale trials remains to be confirmed.

A comparison of regional and general anaesthesia for total replacement of the hip or knee: a meta-analysis.

PubMed

Hu, S; Zhang, Z-Y; Hua, Y-Q; Li, J; Cai, Z-D

2009-07-01

We performed a meta-analysis to evaluate the relative efficacy of regional and general anaesthesia in patients undergoing total hip or knee replacement. A comprehensive search for relevant studies was performed in PubMed (1966 to April 2008), EMBASE (1969 to April 2008) and the Cochrane Library. Only randomised studies comparing regional and general anaesthesia for total hip or knee replacement were included. We identified 21 independent, randomised clinical trials. A random-effects model was used to calculate all effect sizes. Pooled results from these trials showed that regional anaesthesia reduces the operating time (odds ratio (OR) -0.19; 95% confidence interval (CI) -0.33 to -0.05), the need for transfusion (OR 0.45; 95% CI 0.22 to 0.94) and the incidence of thromboembolic disease (deep-vein thrombosis OR 0.45, 95% CI 0.24 to 0.84; pulmonary embolism OR 0.46, 95% CI 0.29 to 0.80). Regional anaesthesia therefore seems to improve the outcome of patients undergoing total hip or knee replacement.

The effect of on-demand vs deep neuromuscular relaxation on rating of surgical and anaesthesiologic conditions in patients undergoing thoracolaparoscopic esophagectomy (DEPTH trial): study protocol for a randomized controlled trial.

PubMed

Veelo, Denise P; Gisbertz, Suzanne S; Hannivoort, Rebekka A; van Dieren, Susan; Geerts, Bart F; van Berge Henegouwen, Mark I; Hollmann, Markus W

2015-08-05

Deep muscle relaxation has been shown to facilitate operating conditions during laparoscopic surgery. Minimally invasive esophageal surgery is a high-risk procedure in which the use of deep neuromuscular block (NMB) may improve conditions in the thoracic phase as well. Neuromuscular antagonists can be given on demand or by continuous infusion (deep NMB). However, the positioning of the patient often hampers train-of-four (TOF) monitoring. A continuous infusion thus may result in a deep NMB at the end of surgery. The use of neostigmine not only is insufficient for reversing deep NMB but also may be contraindicated for this procedure because of its cholinergic effects. Sugammadex is an effective alternative but is rather expensive. This study aims to evaluate the use of deep versus on-demand NMB on operating, anaesthesiologic conditions, and costs in patients undergoing a two- or three-phase thoracolaparoscopic esophageal resection. We will conduct a single-center randomized controlled double-blinded intervention study. Sixty-six patients undergoing a thoracolaparoscopic esophageal resection will be included. Patients will receive either continuous infusion of rocuronium 0.6 mg/kg per hour (group 1) or continuous infusion of NaCl 0.9 % 0.06 ml/kg per hour (group 2). In both groups, on-demand boluses of rocuronium can be given (open-label design). The primary aim of this study is to compare the surgical rating scale (SRS) during the abdominal phase. Main secondary aims are to evaluate SRS during the thoracic phase, to evaluate anesthesiologic conditions, and to compare costs (in euros) associated with use of rocuronium, sugammadex, and duration of surgery. This study is the first to evaluate the benefits of deep neuromuscular relaxation on surgical and anaesthesiologic conditions during thoracolaparoscopic esophageal surgery. This surgical procedure is unique because it consists of both an abdominal phase and a thoracic phase taking place in different order depending on the subtype of surgery (a two- or three-stage transthoracic esophagectomy). In addition, possible benefits associated with deep NMB, such as decrease in operating time, will be weighed against costs. European Clinical Trials Database (EudraCT) number: 2014-002147-18 (obtained 19 May 2014) ClinicalTrials.gov: NCT02320734 (obtained 18 Dec. 2014).

The potential cost-effectiveness of the Diamondback 360® Coronary Orbital Atherectomy System for treating de novo, severely calcified coronary lesions: an economic modeling approach

PubMed Central

Chambers, Jeffrey; Généreux, Philippe; Lee, Arthur; Lewin, Jack; Young, Christopher; Crittendon, Janna; Mann, Marita; Garrison, Louis P.

2015-01-01

Background: Patients who undergo percutaneous coronary intervention (PCI) for severely calcified coronary lesions have long been known to have worse clinical and economic outcomes than patients with no or mildly calcified lesions. We sought to assess the likely cost-effectiveness of using the Diamondback 360® Orbital Atherectomy System (OAS) in the treatment of de novo, severely calcified lesions from a health-system perspective. Methods and results: In the absence of a head-to-head trial and long-term follow up, cost-effectiveness was based on a modeled synthesis of clinical and economic data. A cost-effectiveness model was used to project the likely economic impact. To estimate the net cost impact, the cost of using the OAS technology in elderly (⩾ 65 years) Medicare patients with de novo severely calcified lesions was compared with cost offsets. Elderly OAS patients from the ORBIT II trial (Evaluate the Safety and Efficacy of OAS in Treating Severely Calcified Coronary Lesions) [ClinicalTrials.gov identifier: NCT01092426] were indirectly compared with similar patients using observational data. For the index procedure, the comparison was with Medicare data, and for both revascularization and cardiac death in the following year, the comparison was with a pooled analysis of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI)/Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trials. After adjusting for differences in age, gender, and comorbidities, the ORBIT II mean index procedure costs were 17% (p < 0.001) lower, approximately US$2700. Estimated mean revascularization costs were lower by US$1240 in the base case. These cost offsets in the first year, on average, fully cover the cost of the device with an additional 1.2% cost savings. Even in the low-value scenario, the use of the OAS is cost-effective with a cost per life-year gained of US$11,895. Conclusions: Based on economic modeling, the recently approved coronary OAS device is projected to be highly cost-effective for patients who undergo PCI for severely calcified lesions. PMID:26702147

Impact of preoperative Vitamin D3 administration on postoperative hypocalcaemia in patients undergoing total thyroidectomy (HypoCalViD): study protocol for a randomized controlled trial.

PubMed

Wolak, Stefanie; Scheunchen, Mandy; Holzer, Katharina; Busch, Mirjam; Trumpf, Esra; Zielke, Andreas

2016-02-20

Total thyroidectomy is increasingly used as a surgical approach for many thyroid conditions. Subsequently, postoperative hypocalcaemia is observed with increasing frequency, often resulting in prolonged hospital stay, increased use of resources, reduced quality of life and delayed return to work. The administration of vitamin D is essential in the therapy of postoperative hypocalcaemia; calcitriol is most commonly used. What has not been examined so far is whether and how routine preoperative vitamin D prophylaxis using calcitriol can help to prevent postoperative hypocalcaemia. This study evaluates routine preoperative calcitriol prophylaxis for all patients who are to undergo a total thyroidectomy, compared with the current standard of post-treatment, i.e., selective vitamin D treatment for patients with postoperative hypocalcaemia. This clinical observational (minimal interventional clinical trial) trial is a multicentre, prospective, randomized superiority trial with an adaptive design. Datasets will be pseudonymized for analysis. Patients will be randomly allocated (1:1) to the intervention and the control groups. The only intervention is 0.5 μg calcitriol orally twice a day for 3 days prior to surgery. For the primary endpoint measure (number of patients with hypocalcaemia), hypocalcaemia is defined as serum calcium of less than 2.1 mmol/l on any day during the postoperative course; this measure will be analyzed using a Chi-square test comparing the two groups. Secondary endpoint measures, such as number of days to discharge, quality of life, and economic parameters will also be analyzed. By virtue of the direct comparison of clinically and economically relevant endpoints, the efficacy as well as efficiency of preoperative calcitriol prophylaxis of hypocalcaemia will be clarified. These results should be available 24 months after the first patient has been enrolled. The results will be used to inform a revised practice parameter guideline of whether or not to recommend preoperative calcitriol for all patients in whom total thyroidectomy is planned. Deutsches Register Klinischer Studien, DRKS00005615 (Feb.12.2016).

Cardiovascular risk and mortality in end-stage renal disease patients undergoing dialysis: sleep study, pulmonary function, respiratory mechanics, upper airway collapsibility, autonomic nervous activity, depression, anxiety, stress and quality of life: a prospective, double blind, randomized controlled clinical trial.

PubMed

dos Reis Santos, Israel; Danaga, Aline Roberta; de Carvalho Aguiar, Isabella; Oliveira, Ezequiel Fernandes; Dias, Ismael Souza; Urbano, Jessica Julioti; Martins, Aline Almeida; Ferraz, Leonardo Macario; Fonsêca, Nina Teixeira; Fernandes, Virgilio; Fernandes, Vinicius Alves Thomaz; Lopes, Viviane Cristina Delgado; Leitão Filho, Fernando Sérgio Studart; Nacif, Sérgio Roberto; de Carvalho, Paulo de Tarso Camillo; Sampaio, Luciana Maria Malosá; Giannasi, Lílian Christiane; Romano, Salvatore; Insalaco, Giuseppe; Araujo, Ana Karina Fachini; Dellê, Humberto; Souza, Nadia Karina Guimarães; Giannella-Neto, Daniel; Oliveira, Luis Vicente Franco

2013-10-08

Chronic kidney disease (CKD) is one of the most serious public health problems. The increasing prevalence of CKD in developed and developing countries has led to a global epidemic. The hypothesis proposed is that patients undergoing dialysis would experience a marked negative influence on physiological variables of sleep and autonomic nervous system activity, compromising quality of life. A prospective, consecutive, double blind, randomized controlled clinical trial is proposed to address the effect of dialysis on sleep, pulmonary function, respiratory mechanics, upper airway collapsibility, autonomic nervous activity, depression, anxiety, stress and quality of life in patients with CKD. The measurement protocol will include body weight (kg); height (cm); body mass index calculated as weight/height(2); circumferences (cm) of the neck, waist, and hip; heart and respiratory rates; blood pressures; Mallampati index; tonsil index; heart rate variability; maximum ventilatory pressures; negative expiratory pressure test, and polysomnography (sleep study), as well as the administration of specific questionnaires addressing sleep apnea, excessive daytime sleepiness, depression, anxiety, stress, and quality of life. CKD is a major public health problem worldwide, and its incidence has increased in part by the increased life expectancy and increasing number of cases of diabetes mellitus and hypertension. Sleep disorders are common in patients with renal insufficiency. Our hypothesis is that the weather weight gain due to volume overload observed during interdialytic period will influence the degree of collapsibility of the upper airway due to narrowing and predispose to upper airway occlusion during sleep, and to investigate the negative influences of haemodialysis in the physiological variables of sleep, and autonomic nervous system, and respiratory mechanics and thereby compromise the quality of life of patients. The protocol for this study is registered with the Brazilian Registry of Clinical Trials (ReBEC RBR-7yhr4w and World Health Organization under Universal Trial Number UTN: U1111-1127-9390 [http://www.ensaiosclinicos.gov.br/rg/RBR-7yhr4w/]).

The potential cost-effectiveness of the Diamondback 360® Coronary Orbital Atherectomy System for treating de novo, severely calcified coronary lesions: an economic modeling approach.

PubMed

Chambers, Jeffrey; Généreux, Philippe; Lee, Arthur; Lewin, Jack; Young, Christopher; Crittendon, Janna; Mann, Marita; Garrison, Louis P

2016-04-01

Patients who undergo percutaneous coronary intervention (PCI) for severely calcified coronary lesions have long been known to have worse clinical and economic outcomes than patients with no or mildly calcified lesions. We sought to assess the likely cost-effectiveness of using the Diamondback 360(®) Orbital Atherectomy System (OAS) in the treatment of de novo, severely calcified lesions from a health-system perspective. In the absence of a head-to-head trial and long-term follow up, cost-effectiveness was based on a modeled synthesis of clinical and economic data. A cost-effectiveness model was used to project the likely economic impact. To estimate the net cost impact, the cost of using the OAS technology in elderly (⩾ 65 years) Medicare patients with de novo severely calcified lesions was compared with cost offsets. Elderly OAS patients from the ORBIT II trial (Evaluate the Safety and Efficacy of OAS in Treating Severely Calcified Coronary Lesions) [ClinicalTrials.gov identifier: NCT01092426] were indirectly compared with similar patients using observational data. For the index procedure, the comparison was with Medicare data, and for both revascularization and cardiac death in the following year, the comparison was with a pooled analysis of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI)/Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trials. After adjusting for differences in age, gender, and comorbidities, the ORBIT II mean index procedure costs were 17% (p < 0.001) lower, approximately US$2700. Estimated mean revascularization costs were lower by US$1240 in the base case. These cost offsets in the first year, on average, fully cover the cost of the device with an additional 1.2% cost savings. Even in the low-value scenario, the use of the OAS is cost-effective with a cost per life-year gained of US$11,895. Based on economic modeling, the recently approved coronary OAS device is projected to be highly cost-effective for patients who undergo PCI for severely calcified lesions. © The Author(s), 2015.

Accelerated partial breast irradiation: Past, present, and future

PubMed Central

Tann, Anne W; Hatch, Sandra S; Joyner, Melissa M; Wiederhold, Lee R; Swanson, Todd A

2016-01-01

Accelerated partial breast irradiation (APBI) focuses higher doses of radiation during a shorter interval to the lumpectomy cavity, in the setting of breast conserving therapy for early stage breast cancer. The utilization of APBI has increased in the past decade because of the shorter treatment schedule and a growing body of outcome data showing positive cosmetic outcomes and high local control rates in selected patients undergoing breast conserving therapy. Technological advances in various APBI modalities, including intracavitary and interstitial brachytherapy, intraoperative radiation therapy, and external beam radiation therapy, have made APBI more accessible in the community. Results of early APBI trials served as the basis for the current consensus guidelines, and multiple prospective randomized clinical trials are currently ongoing. The pending long term results of these trials will help us identify optimal candidates that can benefit from ABPI. Here we provide an overview of the clinical and cosmetic outcomes of various APBI techniques and review the current guidelines for selecting suitable breast cancer patients. We also discuss the impact of APBI on the economics of cancer care and patient reported quality of life. PMID:27777879

Trial watch

PubMed Central

Vacchelli, Erika; Galluzzi, Lorenzo; Fridman, Wolf Hervé; Galon, Jerome; Sautès-Fridman, Catherine; Tartour, Eric; Kroemer, Guido

2012-01-01

The long-established notion that apoptosis would be immunologically silent, and hence it would go unnoticed by the immune system, if not tolerogenic, and hence it would actively suppress immune responses, has recently been revisited. In some instances, indeed, cancer cells undergo apoptosis while emitting a spatiotemporally-defined combination of signals that renders them capable of eliciting a long-term protective antitumor immune response. Importantly, only a few anticancer agents can stimulate such an immunogenic cell death. These include cyclophosphamide, doxorubicin and oxaliplatin, which are currently approved by FDA for the treatment of multiple hematologic and solid malignancies, as well as mitoxantrone, which is being used in cancer therapy and against multiple sclerosis. In this Trial Watch, we will review and discuss the progress of recent (initiated after January 2008) clinical trials evaluating the off-label use of cyclophosphamide, doxorubicin, oxaliplatin and mitoxantrone. PMID:22720239

Importance of tissue perfusion in ST segment elevation myocardial infarction patients undergoing reperfusion strategies: role of adenosine.

PubMed

Forman, Mervyn B; Jackson, Edwin K

2007-11-01

High risk ST segment elevation myocardial infarction (STEMI) patients undergoing reperfusion therapy continue to exhibit significant morbidity and mortality due in part to myocardial reperfusion injury. Importantly, preclinical studies demonstrate that progressive microcirculatory failure (the "no-reflow" phenomenon) contributes significantly to myocardial reperfusion injury. Diagnostic techniques to measure tissue perfusion have validated this concept in humans, and it is now clear that abnormal tissue perfusion occurs frequently in STEMI patients undergoing reperfusion therapy. Moreover, because tissue perfusion correlates poorly with epicardial blood flow (TIMI flow grade), clinical studies show that tissue perfusion is an independent predictor of early and late mortality in STEMI patients and is associated with infarct size, ventricular function, CHF and ventricular arrhythmias. The mechanisms responsible for abnormal tissue perfusion are multifactorial and include both mechanical obstruction and vasoconstrictor humoral factors. Adenosine, an endogenous nucleoside, maintains microcirculatory flow following reperfusion by activating four well-characterized extracellular receptors. Because activation of adenosine receptors attenuates the mechanical and functional mechanisms leading to the "no reflow" phenomenon and activates other cardioprotective pathways as well, it is not surprising that both experimental and clinical studies show striking myocardial salvage with intravenous infusions of adenosine administered in the peri-reperfusion period. For example, a post hoc analysis of the AMISTAD II trial indicates a significant reduction in 1 and 6-month mortality in STEMI patients undergoing reperfusion therapy who are treated with adenosine within 3 hours of symptoms. In conclusion, adenosine's numerous cardioprotective effects, including attenuation of the "no-reflow" phenomenon, support its use in high risk STEMI undergoing reperfusion.

External cephalic version in premature rupture of membranes: a systematic review.

PubMed

Quist-Nelson, Johanna; Landers, Kathryn; McCurdy, Rebekah; Berghella, Vincenzo

2017-09-01

External cephalic version (ECV) increases the likelihood of a vaginal delivery in patients with breech presentation. Our objective was to determine the rate of cephalic vaginal delivery in women undergoing ECV after PROM. We performed a systematic review of all case reports, case series and clinical trials of patients undergoing an ECV after PROM ≥ 24 weeks. Maternal demographics and outcome data were obtained. The primary outcome was rate of cephalic vaginal delivery. Statistical analysis was performed for continuous outcomes by calculating mean and standard deviations for appropriate variables. The systematic review yielded six papers with 13 case reports and no clinical trials of ECV after PROM. The rate of success to cephalic presentation was 46.1% (six of 13 cases), with a subsequent vaginal delivery rate of 23.1% (three of 13 cases). The rate of umbilical cord prolapse was 33.3% (two of six cases). ECV after PROM has been reported in 13 cases in the literature. For the cases reported, 46.1% of ECV were successful in turning to cephalic position, but only 23.1% resulted in a vaginal delivery. There was a 33.3% incidence of umbilical cord prolapse. Given the high rate of umbilical cord prolapse, it would be imperative to offer an ECV in the setting of PROM only at an institution that has the ability to perform the indicated emergent cesarean delivery and only after appropriate counseling.

[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.

Preoperative oral carbohydrate therapy.

PubMed

Nygren, Jonas; Thorell, Anders; Ljungqvist, Olle

2015-06-01

Management of the postoperative response to surgical stress is an important issue in major surgery. Avoiding preoperative fasting using preoperative oral carbohydrates (POC) has been suggested as a measure to prevent and reduce the extent to which such derangements occur. This review summarizes the current evidence and rationale for this treatment. A recent review from the Cochrane Collaboration reports enhanced gastrointestinal recovery and shorter hospital stay with the use of POC with no effect on postoperative complication rates. Multiple randomized controlled trials demonstrate improved postoperative metabolic response after POC administration, including reduced insulin resistance, protein sparing, improved muscle function and preserved immune response. Cohort studies in patients undergoing major abdominal surgery have shown that the use of POC as part of an enhanced recovery after surgery protocol is a significant predictor for improved clinical outcomes. Avoiding preoperative fasting with POC is associated with attenuated postoperative insulin resistance, improved metabolic response, enhanced perioperative well-being, and better clinical outcomes. The impact is greatest for patients undergoing major surgeries.

Optimal pharmacological therapy in ST-elevation myocardial infarction-a review : A review of antithrombotic therapies in STEMI.

PubMed

Hermanides, R S; Kilic, S; van 't Hof, A W J

2018-04-23

Antithrombotic therapy is an essential component in the optimisation of clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. There are currently several intravenous anticoagulant drugs available for primary percutaneous coronary intervention. Dual antiplatelet therapy comprising aspirin and P2Y12 inhibitor represents the cornerstone treatment for STEMI. However, these effective treatment strategies may be associated with bleeding complications. Compared with clopidogrel, prasugrel and ticagrelor are more potent and predictable, which translates into better clinical outcomes. Therefore, these agents are the first-line treatment in primary percutaneous coronary intervention. However, patients can still experience adverse ischaemic events, which might be in part attributed to alternative pathways triggering thrombosis. In this review, we provide a critical and updated review of currently available antithrombotic therapies used in patients with STEMI undergoing primary PCI. Finding a balance that minimises both thrombotic and bleeding risk is difficult, but crucial. Further randomised trials for this optimal balance are needed.

Brachytherapy with an improved MammoSite Radiation Therapy System

NASA Astrophysics Data System (ADS)

Karthik, Nanda; Keppel, Cynthia; Nazaryan, Vahagn

2007-03-01

Accelerated partial breast irradiation treatment utilizing the MammoSite Radiation Therapy System (MRTS) is becoming increasingly popular. Clinical studies show excellent results for disease control and localization, as well as for cosmesis. Several Phase I, II, and III clinical trials have found significant association between skin spacing and cosmetic results after treatment with MRTS. As a result, patients with skin spacing less then 7 mm are not recommended to undergo this treatment. We have developed a practical innovation to the MammoSite brachytherapy methodology that is directed to overcome the skin spacing problem. The idea is to partially shield the radiation dose to the skin where the skin spacing is less then 7 mm, thereby protecting the skin from radiation damage. Our innovation to the MRTS will allow better cosmetic outcome in breast conserving therapy (BCT), and will furthermore allow more women to take advantage of BCT. Reduction in skin radiation exposure is particularly important for patients also undergoing adjuvant chemotherapy. We will present the method and preliminary laboratory and Monte Carlo simulation results.

Effects of Peer-Facilitated, Video-Based and Combined Peer-and-Video Education on Anxiety Among Patients Undergoing Coronary Angiography: Randomised controlled trial.

PubMed

Habibzadeh, Hosein; Milan, Zahra D; Radfar, Moloud; Alilu, Leyla; Cund, Audrey

2018-02-01

Coronary angiography can be stressful for patients and anxiety-caused physiological responses during the procedure increase the risk of dysrhythmia, coronary artery spasms and rupture. This study therefore aimed to investigate the effects of peer, video and combined peer-and-video training on anxiety among patients undergoing coronary angiography. This single-blinded randomised controlled clinical trial was conducted at two large educational hospitals in Iran between April and July 2016. A total of 120 adult patients undergoing coronary angiography were recruited. Using a block randomisation method, participants were assigned to one of four groups, with those in the control group receiving no training and those in the three intervention groups receiving either peer-facilitated training, video-based training or a combination of both. A Persian-language validated version of the State-Trait Anxiety Inventory was used to measure pre- and post-intervention anxiety. There were no statistically significant differences in mean pre-intervention anxiety scores between the four groups (F = 0.31; P = 0.81). In contrast, there was a significant reduction in post-intervention anxiety among all three intervention groups compared to the control group (F = 27.71; P <0.01); however, there was no significant difference in anxiety level in terms of the type of intervention used. Peer, video and combined peer-and-video education were equally effective in reducing angiography-related patient anxiety. Such techniques are recommended to reduce anxiety amongst patients undergoing coronary angiography in hospitals in Iran.

Computer tablet distraction reduces pain and anxiety in pediatric burn patients undergoing hydrotherapy: A randomized trial.

PubMed

Burns-Nader, Sherwood; Joe, Lindsay; Pinion, Kelly

2017-09-01

Distraction is often used in conjunction with analgesics to minimize pain in pediatric burn patients during treatment procedures. Computer tablets provide many options for distraction items in one tool and are often used during medical procedures. Few studies have examined the effectiveness of tablet distraction in improving the care of pediatric burn patients. This study examines the effectiveness of tablet distraction provided by a child life specialist to minimize pain and anxiety in pediatric burn patients undergoing hydrotherapy. Thirty pediatric patients (4-12) undergoing hydrotherapy for the treatment of burns participated in this randomized clinical trial. The tablet distraction group received tablet distraction provided by a child life specialist while those in the control group received standard care. Pain was assessed through self-reports and observation reports. Anxiety was assessed through behavioral observations. Length of procedure was also recorded. Nurses reported significantly less pain for the tablet distraction group compared to the control group. There was no significant difference between groups on self-reported pain. The tablet distraction group displayed significantly less anxiety during the procedure compared to the control group. Also, the tablet distraction group returned to baseline after the procedure while those in the control group displayed higher anxiety post-procedure. There was no difference in the length of the procedure between groups. These findings suggest tablet distraction provided by a child life specialist may be an effective method for improving pain and anxiety in children undergoing hydrotherapy treatment for burns. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

Therapeutic efficacy of traditional Chinese medicine, Shen-Mai San, in cancer patients undergoing chemotherapy or radiotherapy: study protocol for a randomized, double-blind, placebo-controlled trial

PubMed Central

2012-01-01

Background Cancer is one of the major health issues worldwide. An increasing number of cancer patients are offered treatment with surgery, chemotherapy and radiotherapy. Traditional Chinese medicine (TCM) is one of the most common complementary therapies offered to cancer patients in Taiwan. We designed a randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy of TCM in patients with cancer. Methods/design In this study, inclusion criteria are postoperative patients with histologically confirmed cancer within 3 years who are undergoing chemotherapy or radiotherapy, more than 18 years old, have given signed informed consent, have the ability to read Chinese, and the ability for oral intake. Exclusion criteria include being pregnant, breast feeding, having completed chemotherapy or radiotherapy, brain metastasis with Eastern Cooperative Oncology Group (ECOG) performance status of two to four, delusion or hallucinations, acute infection, and have received medications under other clinical trials. The patients were separated into an intervention group (Shen-Mai-San, SMS) and a placebo group for four weeks using a randomized, double-blind procedure. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (QOL-C30) was used to evaluate the quality of life. General data, hemoglobin (Hb), hematocrit (Hct), glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine, carcinoembryonic antigen (CEA), TCM diagnosis data and heart rate variability (HRV) were also recorded. These data were collected at baseline, two weeks and four weeks after receiving medication. The patients were prescribed granules which contained therapeutic medicines or placebo. Paired-T test was used for statistical analysis. Discussion Shen-Mai-San is composed of processed Ginseng radis, Liriope spicata, and Schizandrae fructus. It was found to be effective for treating cancer-related fatigue and had anti-fatigue activity. In TCM theory, SMS has a synergistic effect for qi and yin deficiency and has the ability to prevent fatigue. The symptoms of qi and yin deficiency are similar to chemotherapy- or radiotherapy-induced side effects. In order to evaluate the efficacy of SMS on cancer treatment, we designed a randomized, double-blind, placebo-controlled trial. Trial registration This study is registered to Clinical Trails.gov NCT01580358 PMID:23206440

[Attractiveness of France for international clinical research: 8th survey conducted by Leem (French association for pharmaceutical companies)].

PubMed

Galaup, Ariane; Barthélémy, Philippe; Pouletty-Lefebvre, Brigitte; Béhier, Jehan-Michel; Zetlaoui, Jean; Borel, Thomas

2018-04-18

The Leem (French association of pharmaceutical companies) has conducted the eighth survey on attractiveness of France for clinical research. It serves to measure France's global competitiveness for international clinical trials and assess its strengths and areas of excellence. It also highlights the potential for progress and emerging trends at a time when the regulatory environment in France and Europe is undergoing change. This survey has been updated every two years since 2002 using the same methodology. It assesses the current status of research undertaken in France by the pharmaceutical industry between January 1st 2014 and December 31st 2015. Thirty companies (62% of the French market) have participated in this 8th survey which involved 3474 centers (versus 2860 in 2014) and 16,622 patients (versus 14,634 in 2014) enrolled in France across 586 clinical trials (versus 613 in 2014). This survey shows a reduction in the number of phase I and phase II trials. It also confirms that the studies conducted in France are primarily concerned with oncology (45%). Despite improvements across hospital contracts times (due to the adoption of the sole agreement) and performance indicators in trials (such as the number of patients enrolled by center), trial setup times in France are still overly lengthy (with stable times by French authorities). Ensuring that clinical research remains a priority issue for country is crucial for patients because of rapid access to innovation but also for the vitality of the French economy. Constructive dialogue with stakeholders on the subject of clinical research is essential to enhance the attractiveness of France and to improve the continuum between research, innovation and care. Copyright © 2018 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

The cost-effectiveness of a treatment-based classification system for low back pain: design of a randomised controlled trial and economic evaluation

PubMed Central

2010-01-01

Background Systematic reviews have shown that exercise therapy and spinal manipulation are both more effective for low back pain (LBP) than no treatment at all. However, the effects are at best modest. To enhance the clinical outcomes, recommendations are to improve the patient selection process, and to identify relevant subgroups to guide clinical decision-making. One of the systems that has potentials to improve clinical decision-making is a treatment-based classification system that is intended to identify those patients who are most likely to respond to direction-specific exercises, manipulation, or stabilisation exercises. Methods/Design The primary aim of this randomised controlled trial will be to assess the effectiveness of a classification-based system. A sample of 150 patients with subacute and chronic LBP who attend a private physical therapy clinic for treatment will be recruited. At baseline, all participants will undergo a standard evaluation by trained research physical therapists and will be classified into one of the following subgroups: direction-specific exercises, manipulation, or stabilisation. The patient will not be informed about the results of the examination. Patients will be randomly assigned to classification-based treatment or usual care according to the Dutch LBP guidelines, and will complete questionnaires at baseline, and 8, 26, and 52 weeks after the start of the treatment. The primary outcomes will be general perceived recovery, functional status, and pain intensity. Alongside this trial, an economic evaluation of cost-effectiveness and cost-utility will be conducted from a societal perspective. Discussion The present study will contribute to our knowledge about the effectiveness and cost-effectiveness of classification-based treatment in patients with LBP. Trial registration Trial registration number: NTR1176 PMID:20346133

A randomized controlled trial of levosimendan to reduce mortality in high-risk cardiac surgery patients (CHEETAH): Rationale and design.

PubMed

Zangrillo, Alberto; Alvaro, Gabriele; Pisano, Antonio; Guarracino, Fabio; Lobreglio, Rosetta; Bradic, Nikola; Lembo, Rosalba; Gianni, Stefano; Calabrò, Maria Grazia; Likhvantsev, Valery; Grigoryev, Evgeny; Buscaglia, Giuseppe; Pala, Giovanni; Auci, Elisabetta; Amantea, Bruno; Monaco, Fabrizio; De Vuono, Giovanni; Corcione, Antonio; Galdieri, Nicola; Cariello, Claudia; Bove, Tiziana; Fominskiy, Evgeny; Auriemma, Stefano; Baiocchi, Massimo; Bianchi, Alessandro; Frontini, Mario; Paternoster, Gianluca; Sangalli, Fabio; Wang, Chew-Yin; Zucchetti, Maria Chiara; Biondi-Zoccai, Giuseppe; Gemma, Marco; Lipinski, Michael J; Lomivorotov, Vladimir V; Landoni, Giovanni

2016-07-01

Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with 3 beneficial cardiovascular effects (inotropic, vasodilatory, and anti-inflammatory), which appears effective in improving clinically relevant outcomes. Double-blind, placebo-controlled, multicenter randomized trial. Tertiary care hospitals. Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 μg/[kg min]) or placebo for 24-48 hours. The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction. This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of levosimendan on mortality in patients undergoing cardiac surgery: A systematic review and meta-analysis.

PubMed

Chen, Peili; Wu, Xiaoqiang; Wang, Zhiwei; Li, Zhenya; Tian, Xiangyong; Wang, Junpeng; Yan, Tianzhong

2018-06-01

We sought to determine the impact of levosimendan on mortality following cardiac surgery based on large-scale randomized controlled trials (RCTs). We searched PubMed, Web of Science, Cochrane databases, and ClinicalTrials.gov for RCTs published up to December 2017, on levosimendan for patients undergoing cardiac surgery. A total of 25 RCTs enrolling 2960 patients met the inclusion criteria; data from 15 placebo-controlled randomized trials were included for meta-analysis. Pooled analysis showed that the all-cause mortality rate was 6.4% (71 of 1106) in the levosimendan group and 8.4% (93 of 1108) in the placebo group (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.55-1.04; P = 0.09). There were no significant differences between the two groups in the rates of myocardial infarction (OR: 0.91; 95% CI, 0.68-1.21; P = 0.52), serious adverse events (OR: 0.84; 95% CI, 0.66-1.07; P = 0.17), hypotension (OR: 1.69; 95% CI, 0.94-3.03; P = 0.08), and low cardiac output syndrome (OR: 0.47; 95% CI, 0.22-1.02; P = 0.05). Levosimendan did not result in a reduction in mortality in adult cardiac surgery patients. Well designed, adequately powered, multicenter trials are necessary to determine the role of levosimendan in adult cardiac surgery. © 2018 The Authors. Journal of Cardiac Surgery Published by Wiley Periodicals Inc.

Reminder systems to improve patient adherence to tuberculosis clinic appointments for diagnosis and treatment

PubMed Central

Liu, Qin; Abba, Katharine; Alejandria, Marissa M; Sinclair, David; Balanag, Vincent M; Lansang, Mary Ann D

2014-01-01

Background People with active tuberculosis (TB) require six months of treatment. Some people find it difficult to complete treatment, and there are several approaches to help ensure completion. One such system relies on reminders, where the health system prompts patients to attend for appointments on time, or re-engages people who have missed or defaulted on a scheduled appointment. Objectives To assess the effects of reminder systems on improving attendance at TB diagnosis, prophylaxis, and treatment clinic appointments, and their effects on TB treatment outcomes. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, Cochrane Effective Practice andOrganization of Care Group Specialized Register, CENTRAL,MEDLINE, EMBASE, LILACS, CINAHL, SCI-EXPANDED, SSCI, m RCT, and the Indian Journal of Tuberculosis without language restriction up to 29 August 2014. We also checked reference lists and contacted researchers working in the field. Selection criteria Randomized controlled trials (RCTs), including cluster RCTs and quasi-RCTs, and controlled before-and-after studies comparing reminder systems with no reminders or an alternative reminder system for people with scheduled appointments for TB diagnosis, prophylaxis, or treatment. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias in the included trials. We compared the effects of interventions by using risk ratios (RR) and presented RRs with 95% confidence intervals (CIs). Also we assessed the quality of evidence using the GRADE approach. Main results Nine trials, including 4654 participants, met our inclusion criteria. Five trials evaluated appointment reminders for people on treatment for active TB, two for people on prophylaxis for latent TB, and four for people undergoing TB screening using skin tests.We classified the interventions into 'pre-appointment' reminders (telephone calls or letters prior to a scheduled appointment) or'default' reminders (telephone calls, letters, or home visits to people who had missed an appointment). For people being treated for active TB, clinic attendance and TB treatment completion were higher in people receiving pre-appointment reminder phone-calls (clinic attendance: 66% versus 50%; RR 1.32, 95% CI 1.10 to 1.59, one trial (USA), 615 participants, low quality evidence; TB treatment completion: 100% versus 88%; RR 1.14, 95% CI 1.02 to 1.27, one trial (Thailand), 92 participants, low quality evidence). Clinic attendance and TB treatment completion were also higher with default reminders (letters or home visits) (clinic attendance: 52% versus 10%; RR 5.04, 95% CI 1.61 to 15.78, one trial (India), 52 participants, low quality evidence; treatment completion: RR 1.17, 95% CI 1.11 to 1.24, two trials (Iraq and India), 680 participants, moderate quality evidence). For people on TB prophylaxis, clinic attendance was higher with a policy of pre-appointment phone-calls (63% versus 48%; RR 1.30, 95% CI 1.07 to 1.59, one trial (USA), 536 participants); and attendance at the final clinic was higher with regular three-monthly phone-calls or nurse visits (93% versus 65%, one trial (Spain), 318 participants). For people undergoing screening for TB, three trials of pre-appointment phone-calls found little or no effect on the proportion of people returning to clinic for the result of their skin test (three trials, 1189 participants, low quality evidence), and two trials found little or no effect with take home reminder cards (two trials, 711 participants). All four trials were conducted among healthy volunteers in the USA. Authors' conclusions Policies of sending reminders to people pre-appointment, and contacting people who miss appointments, seem sensible additions to any TB programme, and the limited evidence available suggests they have small but potentially important benefits. Future studies of modern technologies such as short message service (SMS) reminders would be useful, particularly in low-resource settings. Plain Language Summary Reminder systems to improve patient attendance at tuberculosis clinics This Cochrane Review summarizes trials evaluating the effects of reminder systems on attendance at tuberculosis (TB) clinics and completion of TB treatment. After searching for relevant trials up to 29 August 2014, we included nine trials, including 4654 people. What are reminder systems and how might they help? Effective treatment for TB requires people to take multiple drugs daily for at least six months. Consequently, once they start to feel well again, some patients stop attending clinics and stop taking theirmedication which can lead to the illness returning and the development of drug resistance. One strategy theWorldHealthOrganization recommends is that an appointed person (a health worker or volunteer) watches the person take their medication everyday (called direct observation). Other strategies include reminder systems to prompt patients to attend for appointments on time, or to re-engage people who have missed or defaulted on a scheduled appointment. These prompts may be in the form of telephone calls or letters before the next scheduled appointment (“pre-appointment reminders”), or phone calls, letters, or home visits after a missed appointment (“default reminders”). What the research says: For people being treated for active TB: - More people attended the clinic and completed TB treatment with pre-appointment reminder phone-calls (low quality evidence). - More people attended the clinic and completed TB treatment with a policy of default reminders (low and moderate quality evidence respectively). For people on TB prophylaxis: - More people attended the clinic with pre-appointment phone-calls, and the number attending the final clinic was higher with threemonthly phone-calls or nurse home visits. For people being treated for active TB: - Similar numbers of people attended clinic for skin test reading with and without pre-appointment phone-calls (low quality evidence). - Similar numbers of people attended clinic for skin test reading with and without take home reminder cards. PMID:25403701

Cervical auscultation in the diagnosis of oropharyngeal aspiration in children: a study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background Oropharyngeal aspiration (OPA) can lead to recurrent respiratory illnesses and chronic lung disease in children. Current clinical feeding evaluations performed by speech pathologists have poor reliability in detecting OPA when compared to radiological procedures such as the modified barium swallow (MBS). Improved ability to diagnose OPA accurately via clinical evaluation potentially reduces reliance on expensive, less readily available radiological procedures. Our study investigates the utility of adding cervical auscultation (CA), a technique of listening to swallowing sounds, in improving the diagnostic accuracy of a clinical evaluation for the detection of OPA. Methods We plan an open, unblinded, randomised controlled trial at a paediatric tertiary teaching hospital. Two hundred and sixteen children fulfilling the inclusion criteria will be randomised to one of the two clinical assessment techniques for the clinical detection of OPA: (1) clinical feeding evaluation only (CFE) group or (2) clinical feeding evaluation with cervical auscultation (CFE + CA) group. All children will then undergo an MBS to determine radiologically assessed OPA. The primary outcome is the presence or absence of OPA, as determined on MBS using the Penetration-Aspiration Scale. Our main objective is to determine the sensitivity, specificity, negative and positive predictive values of ‘CFE + CA’ versus ‘CFE’ only compared to MBS-identified OPA. Discussion Early detection and appropriate management of OPA is important to prevent chronic pulmonary disease and poor growth in children. As the reliability of CFE to detect OPA is low, a technique that can improve the diagnostic accuracy of the CFE will help minimise consequences to the paediatric respiratory system. Cervical auscultation is a technique that has previously been documented as a clinical adjunct to the CFE; however, no published RCTs addressing the reliability of this technique in children exist. Our study will be the first to establish the utility of CA in assessing and diagnosing OPA risk in young children. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12613000589785. PMID:24199872

The role of remote ischemic preconditioning in organ protection after cardiac surgery: a meta-analysis.

PubMed

Haji Mohd Yasin, Nur A B; Herbison, Peter; Saxena, Pankaj; Praporski, Slavica; Konstantinov, Igor E

2014-01-01

Remote ischemic preconditioning (RIPC) appears to protect distant organs from ischemia-reperfusion injury. We undertook meta-analysis of clinical studies to evaluate the effects of RIPC on organ protection and clinical outcomes in patients undergoing cardiac surgery. A review of evidence for cardiac, renal, and pulmonary protection after RIPC was performed. We also did meta-regressions on RIPC variables, such as duration of ischemia, cuff pressure, and timing of application of preconditioning. Secondary outcomes included length of hospital and intensive care unit stay, duration of mechanical ventilation, and mortality at 30 days. Randomized control trials (n = 25) were included in the study for quantitative analysis of cardiac (n = 16), renal (n = 6), and pulmonary (n = 3) protection. RIPC provided statistically significant cardiac protection (standardized mean difference [SMD], -0.77; 95% confidence interval [CI], -1.15, -0.39; Z = 3.98; P < 0.0001) and on subgroup analysis, the protective effect remained consistent for all types of cardiac surgical procedures. However, there was no evidence of renal protection (SMD, 0.74; 95% CI, 0.53, 1.02; Z = 1.81; P = 0.07) or pulmonary protection (SMD, -0.03; 95% CI, -0.56, 0.50; Z = 0.12; P = 0.91). There was no statistical difference in the short-term clinical outcomes between the RIPC and control groups. RIPC provides cardiac protection, but there is no evidence of renal or pulmonary protection in patients undergoing cardiac surgery using cardiopulmonary bypass. Larger multicenter trials are required to define the role of RIPC in surgical practice. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Effects of propranolol on fear of dental extraction: study protocol for a randomized controlled trial.

PubMed

Steenen, Serge A; van Wijk, Arjen J; van Westrhenen, Roos; de Lange, Jan; de Jongh, Ad

2015-11-25

Undergoing an extraction has been shown to pose a significantly increased risk for the development of chronic apprehension for dental surgical procedures, disproportionate forms of dental anxiety (that is, dental phobia), and symptoms of post-traumatic stress. Evidence suggests that intrusive emotional memories of these events both induce and maintain these forms of anxiety. Addressing these problems effectively requires an intervention that durably reduces both the intrusiveness of key fear-related memories and state anxiety during surgery. Moreover, evidence suggests that propranolol is capable of inhibiting "memory reconsolidation" (that is, it blocks the process of storing a recently retrieved fear memory). Hence, the purpose of this trial is to determine the anxiolytic and fear memory reconsolidation inhibiting effects of the ß-adrenoreceptor antagonist propranolol on patients with high levels of fear in anticipation of a dental extraction. This trial is designed as a multicenter, randomized, placebo-controlled, two-group, parallel, double-blind trial of 34 participants. Consecutive patients who have been referred by their dentist to the departments of oral and maxillofacial surgery of a University hospital or a secondary referral hospital in the Netherlands for at least two tooth and/or molar removals and with self-reported high to extreme fear in anticipation of a dental extraction will be recruited. The intervention is the administration of two 40 mg propranolol capsules 1 hour prior to a dental extraction, followed by one 40 mg capsule directly postoperatively. Placebo capsules will be used as a comparator. The primary outcome will be dental trait anxiety score reduction from baseline to 4-weeks follow-up. The secondary outcomes will be self-reported anxiety during surgery, physiological parameters (heart rate and blood pressure) during recall of the crucial fear-related memory, self-reported vividness, and emotional charge of the crucial fear-related memory. This randomized trial is the first to test the efficacy of 120 mg of perioperative propranolol versus placebo in reducing short-term ("state") anxiety during dental extraction, fear memory reconsolidation, and lasting dental ("trait") anxiety in a clinical population. If the results show a reduction in anxiety, this would offer support for routinely prescribing propranolol in patients who are fearful of undergoing dental extractions. ClinicalTrials.gov identifier: NCT02268357 , registered on 7 October 2014. The Netherlands National Trial Register identifier: NTR5364 , registered on 16 August 2015.

A pragmatic multi-centre randomised controlled trial of fluid loading in high-risk surgical patients undergoing major elective surgery - the FOCCUS study

PubMed Central

2011-01-01

Introduction Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery. Methods This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome. Results A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective. Conclusions Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care. Trial registration Prospective Clinical Trials, ISRCTN32188676 PMID:22177541

[Multimodal distraction to relieve pain in children undergoing acute medical procedures].

PubMed

Miller, Kate; Rodger, Sylvia; Bucolo, Sam; Wang, Xue-Qing; Kimble, Roy M

2009-10-01

Non-pharmacological approaches to pain management have been used by therapists for decades to reduce the anxiety and pain experienced by children during burn care procedures. With a greater understanding of pain and the principles behind what causes a child to be distracted, combined with access to state of the art technology, we have developed an easy to use, hand held multimodal distraction device (MMD). MMD is an interactive device that prepares the child for a procedure and uses developmentally appropriate distraction stories and games during the procedures to alleviate anxiety and pain. This paper summarizes the results of three randomized control trials. The trials aimed to understand the effectiveness of MMD as a distraction and preparation tool in reducing anxiety and pain in children undergoing burns and non-burns medical procedures compared to pure pharmacological approaches Standard Distraction (SD) and off the shelf video games (VG). Three separate prospective randomized control trials involving 182 children having 354 dressing changes were conducted in the burns and orthopedic departments at Royal Children's Hospital, Brisbane, Australia, to address the above aims. Pain and anxiety scores were completed for the child, caregiver and nursing staff according to the Modified Faces, Legs, Activity, Cry and Consolability Scale, Faces Pain Scale-Revised, Visual Analogue Scale and Wong-Baker Faces Pain Rating Scale. Procedural length was recorded. MMD as a preparation and distraction tool were shown to have a significant impact on child, parent and nursing staff reported anxiety and pain during procedures compared to standard care and video games (P < 0.01). The MMD had a positive effect on clinical time and was shown to sustain its impact on pain and time with further dressing changes. MMD is more effective in reducing the pain and anxiety experienced by children in acute medical procedures as compared with SD and VG. MMD is continuing to be trialed and is continuing to show positive clinical outcomes.

The EQ-5D-5L is a valid approach to measure health related quality of life in patients undergoing bariatric surgery.

PubMed

Fermont, Jilles M; Blazeby, Jane M; Rogers, Chris A; Wordsworth, Sarah

2017-01-01

Bariatric surgery is considered an effective treatment for individuals with severe and complex obesity. Besides reducing weight and improving obesity related comorbidities such as diabetes, bariatric surgery could improve patients' health-related quality of life. However, the frequently used instrument to measure quality of life, the EQ-5D has not been validated for use in bariatric surgery, which is a major limitation to its use in this clinical context. Our study undertook a psychometric validation of the 5 level EQ-5D (EQ-5D-5L) using clinical trial data to measure health-related quality of life in patients with severe and complex obesity undergoing bariatric surgery. Health-related quality of life was assessed at baseline (before randomisation) and six months later in 189 patients in a randomised controlled trial of bariatric surgery. Patients completed two generic health-related quality of life instruments, the EQ-5D-5L and SF-12, which were used together for the validation using data from all patients in the trial as the trial is ongoing. Psychometric analyses included construct and criterion validity and responsiveness to change. Of the 189 validation patients, 141 (75%) were female, the median age was 49 years old (range 23-70 years) and body mass index ranged from 33-70 kg/m2. For construct validity, there were significant improvements in the distribution of responses in all EQ-5D dimensions between baseline and 6 months after randomisation. For criterion validity, the highest degree of correlation was between the EQ-5D pain/discomfort and SF-12 bodily pain domain. For responsiveness the EQ-5D and SF-12 showed statistically significant improvements in health-related quality of life between baseline and 6 months after randomisation. The EQ-5D-5L is a valid generic measure for measuring health-related quality of life in bariatric surgery patients.

Randomized trial of primary PCI with or without routine manual thrombectomy.

PubMed

Jolly, Sanjit S; Cairns, John A; Yusuf, Salim; Meeks, Brandi; Pogue, Janice; Rokoss, Michael J; Kedev, Sasko; Thabane, Lehana; Stankovic, Goran; Moreno, Raul; Gershlick, Anthony; Chowdhary, Saqib; Lavi, Shahar; Niemelä, Kari; Steg, Philippe Gabriel; Bernat, Ivo; Xu, Yawei; Cantor, Warren J; Overgaard, Christopher B; Naber, Christoph K; Cheema, Asim N; Welsh, Robert C; Bertrand, Olivier F; Avezum, Alvaro; Bhindi, Ravinay; Pancholy, Samir; Rao, Sunil V; Natarajan, Madhu K; ten Berg, Jurriën M; Shestakovska, Olga; Gao, Peggy; Widimsky, Petr; Džavík, Vladimír

2015-04-09

During primary percutaneous coronary intervention (PCI), manual thrombectomy may reduce distal embolization and thus improve microvascular perfusion. Small trials have suggested that thrombectomy improves surrogate and clinical outcomes, but a larger trial has reported conflicting results. We randomly assigned 10,732 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI to a strategy of routine upfront manual thrombectomy versus PCI alone. The primary outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within 180 days. The key safety outcome was stroke within 30 days. The primary outcome occurred in 347 of 5033 patients (6.9%) in the thrombectomy group versus 351 of 5030 patients (7.0%) in the PCI-alone group (hazard ratio in the thrombectomy group, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P=0.86). The rates of cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone; hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P=0.34) and the primary outcome plus stent thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio, 1.00; 95% CI, 0.89 to 1.14; P=0.95) were also similar. Stroke within 30 days occurred in 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%) in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P=0.02). In patients with STEMI who were undergoing primary PCI, routine manual thrombectomy, as compared with PCI alone, did not reduce the risk of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heart failure within 180 days but was associated with an increased rate of stroke within 30 days. (Funded by Medtronic and the Canadian Institutes of Health Research; TOTAL ClinicalTrials.gov number, NCT01149044.).

Temporal Trends in Quality of Life Outcomes after Transapical TAVR: A PARTNER Trial Substudy

PubMed Central

Gada, Hemal; Kirtane, Ajay J; Wang, Kaijun; Lei, Yang; Magnuson, Elizabeth; Reynolds, Matthew R; Williams, Mathew R; Kodali, Susheel; Vahl, Torsten P; Arnold, Suzanne V; Leon, Martin B; Thourani, Vinod; Szeto, Wilson Y; Cohen, David J

2016-01-01

Background In the PARTNER randomized controlled trial (RCT), which represented the first exposure to transapical transcatheter aortic valve replacement (TA-TAVR) for many clinical sites, high risk patients undergoing TA-TAVR derived similar health-related quality-of-life (HRQoL) outcomes when compared with surgical AVR (SAVR). With increasing experience, it is possible that HRQoL outcomes of TA-TAVR may have improved. Methods and Results We evaluated HRQoL outcomes at 1-, 6-, and 12-month follow-up among 875 patients undergoing TA-TAVR in the PARTNER non-randomized continued access (NRCA) registry, and compared these outcomes with those of the TA-TAVR and SAVR patients in the PARTNER RCT. HRQoL was assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Medical Outcomes Study Short Form-12, and the EuroQoL-5D, with the KCCQ overall summary score serving as the primary endpoint. The NRCA TA-TAVR and RCT TA-TAVR and SAVR groups were generally similar. The primary outcome, the KCCQ summary score, did not differ between the NRCA TA-TAVR and the RCT TA-TAVR group at any follow-up timepoints, although there were small differences in favor of the NRCA cohort on several KCCQ subscales at 1 month. There were no significant differences in follow-up HRQOL between the NRCA-TAVR and the RCT SAVR cohorts on the KCCQ overall summary scale or any of the disease-specific or generic subscales. Conclusions Despite greater experience with TA-TAVR in the NRCA registry, HRQoL outcomes remained similar to those of TA-TAVR in the original RCT cohort and no better than those with SAVR. These findings have important implications for patient selection for TAVR when transfemoral access is not an option. Clinical Trial Registration Placement of AoRTic TraNscathetER Valve [PARTNER] trial; NCT00530894; http://clinicaltrials.gov/show/NCT00530894 PMID:26058718

Early Use of N-acetylcysteine With Nitrate Therapy in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction Reduces Myocardial Infarct Size (the NACIAM Trial [N-acetylcysteine in Acute Myocardial Infarction]).

PubMed

Pasupathy, Sivabaskari; Tavella, Rosanna; Grover, Suchi; Raman, Betty; Procter, Nathan E K; Du, Yang Timothy; Mahadavan, Gnanadevan; Stafford, Irene; Heresztyn, Tamila; Holmes, Andrew; Zeitz, Christopher; Arstall, Margaret; Selvanayagam, Joseph; Horowitz, John D; Beltrame, John F

2017-09-05

Contemporary ST-segment-elevation myocardial infarction management involves primary percutaneous coronary intervention, with ongoing studies focusing on infarct size reduction using ancillary therapies. N-acetylcysteine (NAC) is an antioxidant with reactive oxygen species scavenging properties that also potentiates the effects of nitroglycerin and thus represents a potentially beneficial ancillary therapy in primary percutaneous coronary intervention. The NACIAM trial (N-acetylcysteine in Acute Myocardial Infarction) examined the effects of NAC on infarct size in patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention. This randomized, double-blind, placebo-controlled, multicenter study evaluated the effects of intravenous high-dose NAC (29 g over 2 days) with background low-dose nitroglycerin (7.2 mg over 2 days) on early cardiac magnetic resonance imaging-assessed infarct size. Secondary end points included cardiac magnetic resonance-determined myocardial salvage and creatine kinase kinetics. Of 112 randomized patients with ST-segment-elevation myocardial infarction, 75 (37 in NAC group, 38 in placebo group) underwent early cardiac magnetic resonance imaging. Median duration of ischemia pretreatment was 2.4 hours. With background nitroglycerin infusion administered to all patients, those randomized to NAC exhibited an absolute 5.5% reduction in cardiac magnetic resonance-assessed infarct size relative to placebo (median, 11.0%; [interquartile range 4.1, 16.3] versus 16.5%; [interquartile range 10.7, 24.2]; P =0.02). Myocardial salvage was approximately doubled in the NAC group (60%; interquartile range, 37-79) compared with placebo (27%; interquartile range, 14-42; P <0.01) and median creatine kinase areas under the curve were 22 000 and 38 000 IU·h in the NAC and placebo groups, respectively ( P =0.08). High-dose intravenous NAC administered with low-dose intravenous nitroglycerin is associated with reduced infarct size in patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention. A larger study is required to assess the impact of this therapy on clinical cardiac outcomes. Australian New Zealand Clinical Trials Registry. URL: http://www.anzctr.org.au/. Unique identifier: 12610000280000. © 2017 American Heart Association, Inc.

Does rectal indomethacin eliminate the need for prophylactic pancreatic stent placement in patients undergoing high-risk ERCP? Post hoc efficacy and cost-benefit analyses using prospective clinical trial data.

PubMed

Elmunzer, B Joseph; Higgins, Peter D R; Saini, Sameer D; Scheiman, James M; Parker, Robert A; Chak, Amitabh; Romagnuolo, Joseph; Mosler, Patrick; Hayward, Rodney A; Elta, Grace H; Korsnes, Sheryl J; Schmidt, Suzette E; Sherman, Stuart; Lehman, Glen A; Fogel, Evan L

2013-03-01

A recent large-scale randomized controlled trial (RCT) demonstrated that rectal indomethacin administration is effective in addition to pancreatic stent placement (PSP) for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. We performed a post hoc analysis of this RCT to explore whether rectal indomethacin can replace PSP in the prevention of PEP and to estimate the potential cost savings of such an approach. We retrospectively classified RCT subjects into four prevention groups: (1) no prophylaxis, (2) PSP alone, (3) rectal indomethacin alone, and (4) the combination of PSP and indomethacin. Multivariable logistic regression was used to adjust for imbalances in the prevalence of risk factors for PEP between the groups. Based on these adjusted PEP rates, we conducted an economic analysis comparing the costs associated with PEP prevention strategies employing rectal indomethacin alone, PSP alone, or the combination of both. After adjusting for risk using two different logistic regression models, rectal indomethacin alone appeared to be more effective for preventing PEP than no prophylaxis, PSP alone, and the combination of indomethacin and PSP. Economic analysis revealed that indomethacin alone was a cost-saving strategy in 96% of Monte Carlo trials. A prevention strategy employing rectal indomethacin alone could save approximately $150 million annually in the United States compared with a strategy of PSP alone, and $85 million compared with a strategy of indomethacin and PSP. This hypothesis-generating study suggests that prophylactic rectal indomethacin could replace PSP in patients undergoing high-risk ERCP, potentially improving clinical outcomes and reducing healthcare costs. A RCT comparing rectal indomethacin alone vs. indomethacin plus PSP is needed.

Effect of erythropoietin on the incidence of acute kidney injury following complex valvular heart surgery: a double blind, randomized clinical trial of efficacy and safety

PubMed Central

2013-01-01

Introduction Recombinant human erythropoietin (EPO) is known to provide organ protection against ischemia-reperfusion injury through its pleiotropic properties. The aim of this single-site, randomized, case-controlled, and double-blind study was to investigate the effect of pre-emptive EPO administration on the incidence of postoperative acute kidney injury (AKI) in patients with risk factors for AKI undergoing complex valvular heart surgery. Methods We studied ninety-eight patients with preoperative risk factors for AKI. The patients were randomly allocated to either the EPO group (n = 49) or the control group (n = 49). The EPO group received 300 IU/kg of EPO intravenously after anesthetic induction. The control group received an equivalent volume of normal saline. AKI was defined as an increase in serum creatinine >0.3 mg/dl or >50% from baseline. Biomarkers of renal injury were serially measured until five days postoperatively. Results Patient characteristics and operative data, including the duration of cardiopulmonary bypass, were similar between the two groups. Incidence of postoperative AKI (32.7% versus 34.7%, P = 0.831) and biomarkers of renal injury including cystatin C and neutrophil gelatinase-associated lipocalin showed no significant differences between the groups. The postoperative increase in interleukin-6 and myeloperoxidase was similar between the groups. None of the patients developed adverse complications related to EPO administration, including thromboembolic events, throughout the study period. Conclusions Intravenous administration of 300 IU/kg of EPO did not provide renal protection in patients who are at increased risk of developing AKI after undergoing complex valvular heart surgery. Trial registration Clinical Trial.gov, NCT01758861 PMID:24156702

Randomized Controlled Trial of Supplemental Augmentative and Alternative Communication versus Voice Rest Alone after Phonomicrosurgery

PubMed Central

Rousseau, Bernard; Gutmann, Michelle L.; Mau, I-fan Theodore; Francis, David O.; Johnson, Jeffrey P.; Novaleski, Carolyn K.; Vinson, Kimberly N.; Garrett, C. Gaelyn

2015-01-01

Objective This randomized trial investigated voice rest and supplemental text-to-speech communication versus voice rest alone on visual analog scale measures of communication effectiveness and magnitude of voice use. Study Design Randomized clinical trial. Setting Multicenter outpatient voice clinics. Subjects Thirty-seven patients undergoing phonomicrosurgery. Methods Patients undergoing phonomicrosurgery were randomized to voice rest and supplemental text-to-speech communication or voice rest alone. The primary outcome measure was the impact of voice rest on ability to communicate effectively over a seven-day period. Pre- and post-operative magnitude of voice use was also measured as an observational outcome. Results Patients randomized to voice rest and supplemental text-to-speech communication reported higher median communication effectiveness on each post-operative day compared to those randomized to voice rest alone, with significantly higher median communication effectiveness on post-operative day 3 (p = 0.03) and 5 (p = 0.01). Magnitude of voice use did not differ on any pre-operative (p > 0.05) or post-operative day (p > 0.05), nor did patients significantly decrease voice use as the surgery date approached (p > 0.05). However, there was a significant reduction in median voice use pre- to post-operatively across patients (p < 0.001) with median voice use ranging from 0–3 throughout the post-operative week. Conclusion Supplemental text-to-speech communication increased patient perceived communication effectiveness on post-operative days 3 and 5 over voice rest alone. With the prevalence of smartphones and the widespread use of text messaging, supplemental text-to-speech communication may provide an accessible and cost-effective communication option for patients on vocal restrictions. PMID:25605690

Systematic review and meta-analysis of studies of the timing of tracheostomy in adult patients undergoing artificial ventilation

PubMed Central

Griffiths, John; Barber, Vicki S; Morgan, Lesley; Young, J Duncan

2005-01-01

Objective To compare outcomes in critically ill patients undergoing artificial ventilation who received a tracheostomy early or late in their treatment. Data sources The Cochrane Central Register of Clinical Trials, Medline, Embase, CINAHL, the National Research Register, the NHS Trusts Clinical Trials Register, the Medical Research Council UK database, the NHS Research and Development Health Technology Assessment Programme, the British Heart Foundation database, citation review of relevant primary and review articles, and expert informants. Study selection Randomised and quasi-randomised controlled studies that compared early tracheostomy with either late tracheostomy or prolonged endotracheal intubation. From 15 950 articles screened, 12 were identified as “randomised or quasi-randomised” controlled trials, and five were included for data extraction. Data extraction Five studies with 406 participants were analysed. Descriptive and outcome data were extracted. The main outcome measure was mortality in hospital. The incidence of hospital acquired pneumonia, length of stay in a critical care unit, and duration of artificial ventilation were also recorded. Random effects meta-analyses were performed. Results Early tracheostomy did not significantly alter mortality (relative risk 0.79, 95% confidence interval 0.45 to 1.39). The risk of pneumonia was also unaltered by the timing of tracheostomy (0.90, 0.66 to 1.21). Early tracheostomy significantly reduced duration of artificial ventilation (weighted mean difference –8.5 days, 95% confidence interval –15.3 to –1.7) and length of stay in intensive care (–15.3 days, –24.6 to –6.1). Conclusions In critically ill adult patients who require prolonged mechanical ventilation, performing a tracheostomy at an earlier stage than is currently practised may shorten the duration of artificial ventilation and length of stay in intensive care. PMID:15901643

Pituitary block with gonadotrophin-releasing hormone antagonist during intrauterine insemination cycles: a systematic review and meta-analysis of randomised controlled trials.

PubMed

Vitagliano, A; Saccone, G; Noventa, M; Borini, A; Coccia, M E; Nardelli, G B; Saccardi, C; Bifulco, G; Litta, P S; Andrisani, A

2018-06-03

Several randomised controlled trials (RCTs) have investigated the usefulness of pituitary block with gonadotrophin-releasing hormone (GnRH) antagonists during intrauterine insemination (IUI) cycles, with conflicting results. The aim of the present systematic review and meta-analysis of RCTs was to evaluate the effectiveness of GnRH antagonist administration as an intervention to improve the success of IUI cycles. Electronic databases (MEDLINE, Scopus, EMBASE, Sciencedirect) and clinical registers were searched from their inception until October 2017. Randomised controlled trials of infertile women undergoing one or more IUI stimulated cycles with GnRH antagonists compared with a control group. The primary outcomes were ongoing pregnancy/live birth rate (OPR/LBR) and clinical pregnancy rate (CPR). Pooled results were expressed as odds ratio (OR) or mean differences with 95% confidence interval (95% CI). Sources of heterogeneity were investigated through sensitivity and subgroups analysis. The body of evidence was rated using GRADE methodology. Publication bias was assessed with funnel plot, Begg's and Egger's tests. Fifteen RCTs were included (3253 IUI cycles, 2345 participants). No differences in OPR/LBR (OR 1.14, 95% CI 0.82-1.57, P = 0.44) and CPR (OR 1.28, 95% CI 0.97-1.69, P = 0.08) were found. Sensitivity and subgroup analyses did not provide statistical changes in pooled results. The body of evidence was rated as low (GRADE 2/4). No publication bias was detected. Pituitary block with GnRH antagonists does not improve OPR/LBR and CPR in women undergoing IUI cycles. Pituitary block with GnRH antagonists does not improve the success of IUI cycles. © 2018 Royal College of Obstetricians and Gynaecologists.

Intracranial drug delivery for subarachnoid hemorrhage.

PubMed

Macdonald, Robert Loch; Leung, Ming; Tice, Tom

2012-01-01

Tice and colleagues pioneered site-specific, sustained-release drug delivery to the brain almost 30 years ago. Currently there is one drug approved for use in this manner. Clinical trials in subarachnoid hemorrhage have led to approval of nimodipine for oral and intravenous use, but other drugs, such as clazosentan, hydroxymethylglutaryl CoA reductase inhibitors (statins) and magnesium, have not shown consistent clinical efficacy. We propose that intracranial delivery of drugs such as nimodipine, formulated in sustained-release preparations, are good candidates for improving outcome after subarachnoid hemorrhage because they can be administered to patients that are already undergoing surgery and who have a self-limited condition from which full recovery is possible.

No association between intraoperative hypothermia or supplemental protective drug and neurologic outcomes in patients undergoing temporary clipping during cerebral aneurysm surgery: findings from the Intraoperative Hypothermia for Aneurysm Surgery Trial.

PubMed

Hindman, Bradley J; Bayman, Emine O; Pfisterer, Wolfgang K; Torner, James C; Todd, Michael M

2010-01-01

Although hypothermia and barbiturates improve neurologic outcomes in animal temporary focal ischemia models, the clinical efficacy of these interventions during temporary occlusion of the cerebral vasculature during intracranial aneurysm surgery (temporary clipping) is not established. A post hoc analysis of patients from the Intraoperative Hypothermia for Aneurysm Surgery Trial who underwent temporary clipping was performed. Univariate and multivariate logistic regression methods were used to test for associations between hypothermia, supplemental protective drug, and short- (24-h) and long-term (3-month) neurologic outcomes. An odds ratio more than 1 denotes better outcome. Patients undergoing temporary clipping (n = 441) were assigned to intraoperative hypothermia (33.3 degrees +/- 0.8 degrees C, n = 208) or normothermia (36.7 degrees +/- 0.5 degrees C, n = 233), with 178 patients also receiving supplemental protective drug (thiopental or etomidate) during temporary clipping. Three months after surgery, 278 patients (63%) had good outcome (Glasgow Outcome Score = 1). Neither hypothermia (P = 0.847; odds ratio = 1.043, 95% CI = 0.678-1.606) nor supplemental protective drug (P = 0.835; odds ratio = 1.048, 95% CI = 0.674-1.631) were associated with 3-month Glasgow Outcome Score. The effect of supplemental protective drug did not significantly vary with temperature. The effects of hypothermia and protective drug did not significantly vary with temporary clip duration. Similar findings were made for 24-h neurologic status and 3-month Neuropsychological Composite Score. In the Intraoperative Hypothermia for Aneurysm Surgery Trial, neither systemic hypothermia nor supplemental protective drug affected short- or long-term neurologic outcomes of patients undergoing temporary clipping.

A randomised controlled pilot trial to evaluate and optimize the use of anti-platelet agents in the perioperative management in patients undergoing general and abdominal surgery--the APAP trial (ISRCTN45810007).

PubMed

Antolovic, D; Rakow, A; Contin, P; Ulrich, A; Rahbari, N N; Büchler, M W; Weitz, J; Koch, M

2012-02-01

Surgeons are increasingly confronted by patients on long-term low-dose acetylsalicylic acid (ASA). However, owing to a lack of evidence-based data, a widely accepted consensus on the perioperative management of these patients in the setting of non-cardiac surgery has not yet been reached. Primary objective was to evaluate the safety of continuous versus discontinuous use of ASA in the perioperative period in elective general or abdominal surgery. Fifty-two patients undergoing elective cholecystectomy, inguinal hernia repair or colonic/colorectal surgery were recruited to this pilot study. According to cardiological evaluation, non-high-risk patients who were on long-term treatment with low-dose ASA were eligible for inclusion. Patients were allocated randomly to continuous use of ASA or discontinuation of ASA intake for 5 days before until 5 days after surgery. The primary outcome was the incidence of major haemorrhagic and thromboembolic complications within 30 days after surgery. A total of 26 patients were allocated to each study group. One patient (3.8%) in the ASA continuation group required re-operation due to post-operative haemorrhage. In neither study group, further bleeding complications occurred. No clinically apparent thromboembolic events were reported in the ASA continuation and the ASA discontinuation group. Furthermore, there were no significant differences between both study groups in the secondary endpoints. Perioperative intake of ASA does not seem to influence the incidence of severe bleeding in non-high-risk patients undergoing elective general or abdominal surgery. Further, adequately powered trials are required to confirm the findings of this study.

Therapeutic clowns in pediatrics: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Sridharan, Kannan; Sivaramakrishnan, Gowri

2016-10-01

Children and/or their parents are in fear and anxiety when admitted to hospitals or undergo invasive surgeries or investigations. Clown therapy has been shown as an effective measure in reducing this hospital fear and anxiety. Hence, we carried out a systematic compilation of the existing evidence on the clinical utility of hospital clowns in pediatric population. Electronic databases were searched with an appropriate search strategy, and only randomized controlled trials comparing the effect of clown therapy with standard care in children were included. The key outcome measures were as follows: extent of anxiety and pain felt by children and extent of state and trait parental anxiety. Random effect model was applied when moderate to severe heterogeneity was observed. Forest plot, I(2) statistics and risk of bias were evaluated using RevMan 5.3 software. A total of 19 studies were found eligible to be included in the systematic review and 16 for meta-analysis. The pooled SMD [95 % CI] for child anxiety score was -0.83 [-1.16, -0.51] favoring clown therapy. Similarly, a statistically significant reduction {SMD [95 % CI] -0.46 [-0.7, -0.21]} in the state anxiety was observed amongst parents. We found that hospital clowns play a significant role in reducing stress and anxiety levels in children admitted to hospitals as well as their parents. • Trials with clown doctors in pediatric population have shown conflicting results in allaying anxiety amongst children undergoing either hospitalization or invasive procedures What is new: • This is the first systematic review and meta-analysis on hospital clowns • We found out that hospital clowns reduce anxiety amongst children before undergoing either hospitalization or invasive procedures.

Effect of lung-protective ventilation with lower tidal volumes on clinical outcomes among patients undergoing surgery: a meta-analysis of randomized controlled trials.

PubMed

Gu, Wan-Jie; Wang, Fei; Liu, Jing-Chen

2015-02-17

In anesthetized patients undergoing surgery, the role of lung-protective ventilation with lower tidal volumes is unclear. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of this ventilation strategy on postoperative outcomes. We searched electronic databases from inception through September 2014. We included RCTs that compared protective ventilation with lower tidal volumes and conventional ventilation with higher tidal volumes in anesthetized adults undergoing surgery. We pooled outcomes using a random-effects model. The primary outcome measures were lung injury and pulmonary infection. We included 19 trials (n=1348). Compared with patients in the control group, those who received lung-protective ventilation had a decreased risk of lung injury (risk ratio [RR] 0.36, 95% confidence interval [CI] 0.17 to 0.78; I2=0%) and pulmonary infection (RR 0.46, 95% CI 0.26 to 0.83; I2=8%), and higher levels of arterial partial pressure of carbon dioxide (standardized mean difference 0.47, 95% CI 0.18 to 0.75; I2=65%). No significant differences were observed between the patient groups in atelectasis, mortality, length of hospital stay, length of stay in the intensive care unit or the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen. Anesthetized patients who received ventilation with lower tidal volumes during surgery had a lower risk of lung injury and pulmonary infection than those given conventional ventilation with higher tidal volumes. Implementation of a lung-protective ventilation strategy with lower tidal volumes may lower the incidence of these outcomes. © 2015 Canadian Medical Association or its licensors.

Effect of intravenous ascorbic acid infusion on blood loss during laparoscopic myomectomy: a randomized, double-blind, placebo-controlled trial.

PubMed

Lee, Banghyun; Kim, Kidong; Cho, Hye Yon; Yang, Eun Joo; Suh, Dong Hoon; No, Jae Hong; Lee, Jung Ryeol; Hwang, Jung Won; Do, Sang Hwan; Kim, Yong Beom

2016-04-01

Most interventions aimed at reducing bleeding during myomectomy lack sufficient evidence regarding their effectiveness. Recently, it was reported that intraoperative ascorbic acid administration effectively reduced blood loss during abdominal myomectomy. Therefore, this study aimed to investigate whether intravenous ascorbic acid infusion would affect intraoperative blood loss in women undergoing laparoscopic myomectomy. A randomized, double-blind, parallel-group, placebo-controlled trial including 50 women undergoing laparoscopic myomectomy was conducted. Women with ≤4 myomas, ≤9cm in maximum diameter were eligible. The study:control group ratio was 1:1. Starting 30minutes before anesthesia, 2g of ascorbic acid or a placebo were administered for 2hours intraoperatively. Intraoperative blood loss, the primary endpoint, was calculated as the difference between the volume of fluids acquired from suction and that used for irrigation of the abdominal cavity during surgery using constant values. Among the 50 randomized women, 1 and 3 in the study and control groups, respectively, were excluded due to withdrawal of consent, cancelation of surgery, or non-measurement of the primary endpoint. The baseline and operative characteristics were similar between the study and control groups, as was the intraoperative blood loss (193±204mL vs. 159±193mL, P=0.52). In addition, the operating time (95±29min vs. 110±52min; P=0.50) and decrease in hemoglobin level after surgery (1.9±1.31g/dL vs. 1.4±1.4g/dL; P=0.24) were similar between the study and control groups. Intravenous ascorbic acid infusion did not reduce intraoperative blood loss in women undergoing laparoscopic myomectomy. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01715597. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Stopping vs. Continuing Aspirin before Coronary Artery Surgery.

PubMed

Myles, Paul S; Smith, Julian A; Forbes, Andrew; Silbert, Brendan; Jayarajah, Mohandas; Painter, Thomas; Cooper, D James; Marasco, Silvana; McNeil, John; Bussières, Jean S; Wallace, Sophie

2016-02-25

Most patients with coronary artery disease receive aspirin for primary or secondary prevention of myocardial infarction, stroke, and death. Aspirin poses a risk of bleeding in patients undergoing surgery, but it is unclear whether aspirin should be stopped before coronary artery surgery. We used a 2-by-2 factorial trial design to randomly assign patients who were scheduled to undergo coronary artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the aspirin trial are reported here. Patients were randomly assigned to receive 100 mg of aspirin or matched placebo preoperatively. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. Among 5784 eligible patients, 2100 were enrolled; 1047 were randomly assigned to receive aspirin and 1053 to receive placebo. A primary outcome event occurred in 202 patients in the aspirin group (19.3%) and in 215 patients in the placebo group (20.4%) (relative risk, 0.94; 95% confidence interval, 0.80 to 1.12; P=0.55). Major hemorrhage leading to reoperation occurred in 1.8% of patients in the aspirin group and in 2.1% of patients in the placebo group (P=0.75), and cardiac tamponade occurred at rates of 1.1% and 0.4%, respectively (P=0.08). Among patients undergoing coronary artery surgery, the administration of preoperative aspirin resulted in neither a lower risk of death or thrombotic complications nor a higher risk of bleeding than that with placebo. (Funded by the Australian National Health and Medical Research Council and others; Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639.).

Comparing parecoxib and ketorolac as preemptive analgesia in patients undergoing posterior lumbar spinal fusion: a prospective randomized double-blinded placebo-controlled trial.

PubMed

Siribumrungwong, Koopong; Cheewakidakarn, Julin; Tangtrakulwanich, Boonsin; Nimmaanrat, Sasikaan

2015-03-18

Poor postoperative pain control is frequently associated with complications and delayed discharge from a hospital. Preemptive analgesia is one of the methods suggested for reducing postoperative pain. Opioids are effective for pain control, but there known addictive properties make physicians cautious about using them. Parecoxib and ketorolac are potent non-opioid NSAIDs that are attractive alternative drugs to opioids to avoid opioid-related side effects. However, there are no good head-to-head comparisons between these two drugs in the aspect of preemptive analgesic effects in lumbar spinal fusion surgery. This study aimed to compare the efficacy in terms of postoperative pain control and safety of parecoxib with ketorolac as preemptive analgesia in posterior lumbar spinal fusion patients. A prospective, double-blinded randomized controlled trial was carried out in patients undergoing posterior lumbar spinal fusion, who were randomized into 3 groups (n = 32). Parecoxib, ketorolac or a placebo was given to each patient via injection around 30 minutes prior to incision. The efficacy of postoperative pain control was assessed by a verbal numerical rating score (0-10). And various postoperative things were monitored for analysis, such as total opioid consumption, complications, and estimated blood loss. Both the ketorolac and parecoxib groups showed significantly better early postoperative pain reduction at the postanesthesia care unit (PACU) than the control group (p < 0.05). There were no differences between the pain scores of ketorolac and parecoxib at any time points. Complications and bleeding were not significantly different between all three groups. Preemptive analgesia using both ketorolac and parecoxib showed a significantly better early postoperative pain control in the PACU than the control group in patients undergoing lumbar spinal fusion. ClinicalTrials.gov NCT01859585. Registered 15 May 2013.

Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial.

PubMed

Noordman, Bo Jan; Wijnhoven, Bas P L; Lagarde, Sjoerd M; Boonstra, Jurjen J; Coene, Peter Paul L O; Dekker, Jan Willem T; Doukas, Michael; van der Gaast, Ate; Heisterkamp, Joos; Kouwenhoven, Ewout A; Nieuwenhuijzen, Grard A P; Pierie, Jean-Pierre E N; Rosman, Camiel; van Sandick, Johanna W; van der Sangen, Maurice J C; Sosef, Meindert N; Spaander, Manon C W; Valkema, Roelf; van der Zaag, Edwin S; Steyerberg, Ewout W; van Lanschot, J Jan B

2018-02-06

Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4-6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6-8 weeks after CRE-I. CRE-II will include 18F-FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care.

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.

Comparison among the efficacy of interventions for the return rate to receive the pap test report: randomized controlled clinical trial 1

PubMed Central

Vasconcelos, Camila Teixeira Moreira; Pinheiro, Ana Karina Bezerra; Nicolau, Ana Izabel Oliveira; Lima, Thaís Marques; Barbosa, Denise de Fátima Fernandes

2017-01-01

ABSTRACT Objective: to test the effects of a behavioral, an educative and a comparative intervention on women's adherence to the return appointment to receive the pap test report. Methods: randomized controlled clinical trial at a Primary Health Care Service, involving three groups: EG (educative session and test demonstration), BG (recall ribbon) and standard intervention (card containing the return appointment - graphical reminder), called comparative group here (CG). To select the sample, the following was established: having started sexual activity and undergoing the pap smear during the study, resulting in 775 women. Results: among the 775 women, 585 (75.5%) returned to receive the test result within 65 days. The educative group presented the highest return rate (EG=82%/CG=77%/BG=66%), statistically significant only when compared to the behavioral group (p=0.000). The educative group obtained the smallest interval (p<0.05) concerning the mean number of days of return to receive the test result (EG:M=43days/BG:M=47.5days/CG:M=44.8 days). Conclusion: the educative group reached higher return rates and the women returned earlier, but the behavioral intervention showed to be the least effective. Brazilian Clinical Trial Register: RBR-93ykhs. PMID:28301035

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy.

PubMed

Gurusamy, Kurinchi Selvan; Vaughan, Jessica; Rossi, Michele; Davidson, Brian R

2014-02-20

Traditionally, laparoscopic cholecystectomy is performed using two 10-mm ports and two 5-mm ports. Recently, a reduction in the number of ports has been suggested as a modification of the standard technique with a view to decreasing pain and improving cosmesis. The safety and effectiveness of using fewer-than-four ports has not yet been established. To assess the benefits (such as improvement in cosmesis and earlier return to activity) and harms (such as increased complications) of using fewer-than-four ports (fewer-than-four-ports laparoscopic cholecystectomy) versus four ports in people undergoing laparoscopic cholecystectomy for any reason (symptomatic gallstones, acalculous cholecystitis, gallbladder polyp, or any other condition). We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 8, 2013), MEDLINE, EMBASE, Science Citation Index Expanded, and the World Health Organization International Clinical Trials Registry Platform portal to September 2013. We included all randomised clinical trials comparing fewer-than-four ports versus four ports, that is, with standard laparoscopic cholecystectomy that is performed with two ports of at least 10-mm incision and two ports of at least 5-mm incision. Two review authors independently identified the trials and extracted the data. We analysed the data using both the fixed-effect and the random-effects models. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) based on intention-to-treat analysis, whenever possible. We found nine trials with 855 participants that randomised participants to fewer-than-four-ports laparoscopic cholecystectomy (n = 427) versus four-port laparoscopic cholecystectomy (n = 428). Most trials included low anaesthetic risk participants undergoing elective laparoscopic cholecystectomy. Seven of the nine trials used a single port laparoscopic cholecystectomy and the remaining two trials used three-port laparoscopic cholecystectomy as the experimental intervention. Only one trial including 70 participants had low risk of bias. Fewer-than-four-ports laparoscopic cholecystectomy could be completed successfully in more than 90% of participants in most trials. The remaining participants were mostly converted to four-port laparoscopic cholecystectomy but some participants had to undergo open cholecystectomy.There was no mortality in either group in the seven trials that reported mortality (318 participants in fewer-than-four-ports laparoscopic cholecystectomy group and 316 participants in four-port laparoscopic cholecystectomy group). The proportion of participants with serious adverse events was low in both treatment groups and the estimated RR was compatible with a reduction and substantial increased risk with the fewer-than-four-ports group (6/318 (1.9%)) and four-port laparoscopic cholecystectomy group (0/316 (0%)) (RR 3.93; 95% CI 0.86 to 18.04; 7 trials; 634 participants; very low quality evidence). The estimated difference in the quality of life (measured between 10 and 30 days) was imprecise (standardised mean difference (SMD) 0.18; 95% CI -0.05 to 0.42; 4 trials; 510 participants; very low quality evidence), as was the proportion of participants in whom the laparoscopic cholecystectomy had to be converted to open cholecystectomy between the groups (fewer-than-four ports 3/289 (adjusted proportion 1.2%) versus four port: 5/292 (1.7%); RR 0.68; 95% CI 0.19 to 2.35; 5 trials; 581 participants; very low quality evidence). The fewer-than-four-ports laparoscopic cholecystectomy took 14 minutes longer to complete (MD 14.44 minutes; 95% CI 5.95 to 22.93; 9 trials; 855 participants; very low quality evidence). There was no clear difference in hospital stay between the groups (MD -0.01 days; 95% CI -0.28 to 0.26; 6 trials; 731 participants) or in the proportion of participants discharged as day surgery (RR 0.92; 95% CI 0.70 to 1.22; 1 trial; 50 participants; very low quality evidence) between the two groups. The times taken to return to normal activity and work were shorter by two days in the fewer-than-four-ports group compared with four-port laparoscopic cholecystectomy (return to normal activity: MD -1.20 days; 95% CI -1.58 to -0.81; 2 trials; 325 participants; very low quality evidence; return to work: MD -2.00 days; 95% CI -3.31 to -0.69; 1 trial; 150 participants; very low quality evidence). There was no significant difference in cosmesis scores at 6 to 12 months between the two groups (SMD 0.37; 95% CI -0.10 to 0.84; 2 trials; 317 participants; very low quality evidence). There is very low quality evidence that is insufficient to determine whether there is any significant clinical benefit in using fewer-than-four-ports laparoscopic cholecystectomy compared with four-port laparoscopic cholecystectomy. The safety profile of using fewer-than-four ports is yet to be established and fewer-than-four-ports laparoscopic cholecystectomy should be reserved for well-designed randomised clinical trials.

Oncosurgical Management of Liver Limited Stage IV Colorectal Cancer: Preliminary Data and Protocol for a Randomized Controlled Trial.

PubMed

Sutton, Paul; Vimalachandran, Dale; Poston, Graeme; Fenwick, Stephen; Malik, Hassan

2018-05-09

Colorectal cancer is the fourth commonest cancer and second commonest cause of cancer-related death in the United Kingdom. Almost 15% of patients have metastases on presentation. An increasing number of surgical strategies and better neoadjuvant treatment options are responsible for more patients undergoing resection of liver metastases, with prolonged survival in a select group of patients who present with synchronous disease. It is clear that the optimal strategy for the management of these patients remains unclear, and there is certainly a complete absence of Level 1 evidence in the literature. The objective of this study is to undertake preliminary work and devise an outline trial protocol to inform the future development of clinical studies to investigate the management of patients with liver limited stage IV colorectal cancer. We have undertaken some preliminary work and begun the process of designing a randomized controlled trial and present a draft trial protocol here. This study is at the protocol development stage only, and as such no results are available. There is no funding in place for this study, and no anticipated start date. We have presented preliminary work and an outline trial protocol which we anticipate will inform the future development of clinical studies to investigate the management of patients with liver limited stage IV colorectal cancer. We do not believe that the trial we have designed will answer the most significant clinical questions, nor that it is feasible to be delivered within the United Kingdom's National Health Service at this current time. ©Paul Sutton, Dale Vimalachandran, Graeme Poston, Stephen Fenwick, Hassan Malik. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 09.05.2018.

Rationale and design of the Patient Related OuTcomes with Endeavor versus Cypher stenting Trial (PROTECT): randomized controlled trial comparing the incidence of stent thrombosis and clinical events after sirolimus or zotarolimus drug-eluting stent implantation.

PubMed

Camenzind, Edoardo; Wijns, William; Mauri, Laura; Boersma, Eric; Parikh, Keyur; Kurowski, Volkhard; Gao, Runlin; Bode, Christoph; Greenwood, John P; Gershlick, Anthony; O'Neill, William; Serruys, Patrick W; Jorissen, Brenda; Steg, P Gabriel

2009-12-01

Drug-eluting stents (DES) reduce restenosis rates compared to bare-metal stents. Most trials using DES enrolled selected patient and lesion subtypes, and primary endpoint focused on angiographic metrics or relatively short-term outcomes. When DES are used in broader types of lesions and patients, important differences may emerge in long-term outcomes between stent types, particularly the incidence of late stent thrombosis. PROTECT is a randomized, open-label trial comparing the long-term safety of the zotarolimus-eluting stent and the sirolimus-eluting stent. The trial has enrolled 8,800 patients representative of those seen in routine clinical practice, undergoing elective, unplanned, or emergency procedures in native coronary arteries in 196 centers in 36 countries. Indications for the procedure and selection of target vessel and lesion characteristics were at the operator's discretion. Procedures could be staged, but no more than 4 target lesions could be treated per patient. Duration of dual antiplatelet therapy was prespecified to achieve similar lengths of treatment in both study arms. The shortest predefined duration was 3 months, as per the manufacturer's instructions. The primary outcome measure is the composite rate of definite and probable stent thrombosis at 3 years, centrally adjudicated using Academic Research Consortium definitions. The main secondary end points are 3-year all-cause mortality, cardiac death, large nonfatal myocardial infarction, and all myocardial infarctions. This large, international, randomized, controlled trial will provide important information on comparative rates of stent thrombosis between 2 different DES systems and safety as assessed by patient-relevant long-term clinical outcomes.

The Hand Eczema Trial (HET): Design of a randomised clinical trial of the effect of classification and individual counselling versus no intervention among health-care workers with hand eczema.

PubMed

Ibler, Kristina Sophie; Agner, Tove; Hansen, Jane Lindschou; Gluud, Christian

2010-08-31

Hand eczema is the most frequently recognized occupational disease in Denmark with an incidence of approximately 0.32 per 1000 person-years. Consequences of hand eczema include chronic severe eczema, prolonged sick leave, unemployment, and impaired quality of life. New preventive strategies are needed to reduce occupational hand eczema. We describe the design of a randomised clinical trial to investigate the effects of classification of hand eczema plus individual counselling versus no intervention. The trial includes health-care workers with hand eczema identified from a self-administered questionnaire delivered to 3181 health-care workers in three Danish hospitals. The questionnaire identifies the prevalence of hand eczema, knowledge of skin-protection, and exposures that can lead to hand eczema. At entry, all participants are assessed regarding: disease severity (Hand Eczema Severity Index); self-evaluated disease severity; number of eruptions; quality of life; skin protective behaviour, and knowledge of skin protection. The patients are centrally randomised to intervention versus no intervention 1:1 stratified for hospital, profession, and severity score. The experimental group undergoes patch and prick testing; classification of the hand eczema; demonstration of hand washing and appliance of emollients; individual counselling, and a skin-care programme. The control group receives no intervention. All participants are reassessed after six months. The primary outcome is observer-blinded assessment of disease severity and the secondary outcomes are unblinded assessments of disease severity; number of eruptions; knowledge of skin protection; skin-protective behaviour, and quality of life. The trial is registered in ClinicalTrials.Gov, NCT01012453.

Safety and efficacy of defibrotide for the treatment of severe hepatic veno-occlusive disease.

PubMed

Richardson, Paul G; Ho, Vincent T; Giralt, Sergio; Arai, Sally; Mineishi, Shin; Cutler, Corey; Antin, Joseph H; Stavitzski, Nicole; Niederwieser, Dietger; Holler, Ernst; Carreras, Enric; Soiffer, Robert

2012-08-01

Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome, is a potentially life-threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem-cell transplantation (SCT). VOD may occur in up to 62% of patients undergoing SCT, with onset generally within the first month after SCT. In severe cases, 100-day mortality is in excess of 80%. Current management consists of best supportive care, with no agents to date approved for treatment in the USA or the EU. Defibrotide, a polydisperse oligonucleotide, has been shown in phase II and III trials to improve complete response and survival in patients undergoing SCT with severe VOD. This article reviews our current understanding of VOD, and examines recent clinical findings on defibrotide for the treatment and prophylaxis of VOD.

Increased Patient Enrollment to a Randomized Surgical Trial Through Equipoise Polling of an Expert Surgeon Panel.

PubMed

Ghogawala, Zoher; Schwartz, J Sanford; Benzel, Edward C; Magge, Subu N; Coumans, Jean Valery; Harrington, J Fred; Gelbs, Jared C; Whitmore, Robert G; Butler, William E; Barker, Fred G

2016-07-01

To determine whether patients who learned the views of an expert surgeons' panel's assessment of equipoise between 2 alternative operative treatments had increased likelihood of consenting to randomization. Difficulty obtaining patient consent to randomization is an important barrier to conducting surgical randomized clinical trials, the gold standard for generating clinical evidence. Observational study of the rate of patient acceptance of randomization within a 5-center randomized clinical trial comparing lumbar spinal decompression versus lumbar spinal decompression plus instrumented fusion for patients with symptomatic grade I degenerative lumbar spondylolisthesis with spinal stenosis. Eligible patients were enrolled in the trial and then asked to accept randomization. A panel of 10 expert spine surgeons was formed to review clinical information and images for individual patients to provide an assessment of suitability for randomization. The expert panel vote was disclosed to the patient by the patient's surgeon before the patient decided whether to accept randomization or not. Randomization acceptance among eligible patients without expert panel review was 40% (19/48) compared with 81% (47/58) among patients undergoing expert panel review (P < 0.001). Among expert-reviewed patients, randomization acceptance was 95% when all experts or all except 1 voted for randomization, 75% when 2 experts voted against randomization, and 20% with 3 or 4 votes against (P < 0.001 for trend). Patients provided with an expert panel's assessment of their own suitability for randomization were twice as likely to agree to randomization compared with patients receiving only their own surgeon's recommendation.

Assessing renal changes after remote ischemic preconditioning (RIPC) of the upper extremity using BOLD imaging at 3T.

PubMed

Siedek, Florian; Persigehl, Thorsten; Mueller, Roman-Ulrich; Burst, Volker; Benzing, Thomas; Maintz, David; Haneder, Stefan

2018-06-01

Acute kidney injury (AKI) is an important risk factor for a number of adverse outcomes including end-stage renal disease and cardiovascular morbidity and mortality. Whilst many clinical situations that can induce AKI are known-e.g. drug toxicity, contrast agent exposure or ischemia during surgery-targeted preventive or therapeutic measures are still lacking. As to renoprotective strategies, remote ischemic preconditioning (RIPC) is one of the most promising novel approaches and has been examined by a number of clinical trials. The aim of this study was to use blood oxygenation level-dependent (BOLD) MRI as a surrogate parameter to assess the effect of RIPC in healthy volunteers. In this IRB-approved, prospective study, 40 healthy volunteers were stratified with 20 undergoing an RIPC procedure (i.e. RIPC group) with a transient ischemia of the right arm, and 20 undergoing a sham procedure. Before and after the procedure, both kidneys of all participants were scanned using a 12-echo mGRE sequence for functional BOLD imaging at 3T. For each volunteer, 180 ROIs were placed in the cortex and the medulla of the kidneys. Ultimately, R2* values, which have an inverse correlation with the oxygenation level of tissue, were averaged for the RIPC and control groups. Following intervention, mean R2* values significantly decreased in the RIPC group in both the cortex (18.6 ± 2.3 vs. 17.5 ± 1.7 Hz; p = 0.0047) and medulla (34 ± 5.2 vs. 32.2 ± 4.2 Hz; p = 0.0001). However, no significant differences were observed in the control group. RIPC can be non-invasively assessed in healthy volunteers using BOLD MRI at 3T, demonstrating a higher oxygen content in kidney tissue. This study presents a first-in-man trial establishing a quantifiable readout of RIPC and its effects on kidney physiology. BOLD measurements may advance clinical trials in further evaluating RIPC for future clinical care.

Evaluation of efficacy of a new hybrid fusion device: a randomized, two-centre controlled trial.

PubMed

Siewe, Jan; Bredow, Jan; Oppermann, Johannes; Koy, Timmo; Delank, Stefan; Knoell, Peter; Eysel, Peer; Sobottke, Rolf; Zarghooni, Kourosh; Röllinghoff, Marc

2014-09-05

The 360° fusion of lumbar segments is a common and well-researched therapy to treat various diseases of the spine. But it changes the biomechanics of the spine and may cause adjacent segment disease (ASD). Among the many techniques developed to avoid this complication, one appears promising. It combines a rigid fusion with a flexible pedicle screw system (hybrid instrumentation, "topping off"). However, its clinical significance is still uncertain due to the lack of conclusive data. The study is a randomized, therapy-controlled, two-centre trial conducted in a clinical setting at two university hospitals. If they meet the criteria, outpatients presenting with degenerative disc disease, facet joint arthrosis or spondylolisthesis will be included in the study and randomized into two groups: a control group undergoing conventional fusion surgery (PLIF - posterior lumbar intervertebral fusion), and an intervention group undergoing fusion surgery using a new flexible pedicle screw system (PLIF + "topping off"), which was brought on the market in 2013. Follow-up examination will take place immediately after surgery, after 6 weeks and after 6, 12, 24 and 36 months. An ongoing assessment will be performed every year.Outcome measurements will include quality of life and pain assessments using validated questionnaires (ODI - Ostwestry Disability Index, SF-36™ - Short Form Health Survey 36, COMI - Core Outcome Measure Index). In addition, clinical and radiologic ASD, sagittal balance parameters and duration of work disability will be assessed. Inpatient and 6-month mortality, surgery-related data (e.g., intraoperative complications, blood loss, length of incision, surgical duration), postoperative complications (e.g. implant failure), adverse events, and serious adverse events will be monitored and documented throughout the study. New hybrid "topping off" systems might improve the outcome of lumbar spine fusion. But to date, there is a serious lack of and a great need of convincing data on safety or efficacy, including benefits and harms to the patients, of these systems. Health care providers are particularly interested in such data as these implants are much more expensive than conventional implants. In such a case, randomized clinical trials are the best way to evaluate benefits and risks. NCT01852526.

Effect of postoperative goal-directed therapy in cancer patients undergoing high-risk surgery: a randomized clinical trial and meta-analysis.

PubMed

Gerent, Aline Rejane Muller; Almeida, Juliano Pinheiro; Fominskiy, Evgeny; Landoni, Giovanni; de Oliveira, Gisele Queiroz; Rizk, Stephanie Itala; Fukushima, Julia Tizue; Simoes, Claudia Marques; Ribeiro, Ulysses; Park, Clarice Lee; Nakamura, Rosana Ely; Franco, Rafael Alves; Cândido, Patricia Inês; Tavares, Cintia Rosa; Camara, Ligia; Dos Santos Rocha Ferreira, Graziela; de Almeida, Elisangela Pinto Marinho; Filho, Roberto Kalil; Galas, Filomena Regina Barbosa Gomes; Hajjar, Ludhmila Abrahão

2018-05-23

Perioperative goal-directed hemodynamic therapy (GDHT) has been advocated in high-risk patients undergoing noncardiac surgery to reduce postoperative morbidity and mortality. We hypothesized that using cardiac index (CI)-guided GDHT in the postoperative period for patients undergoing high-risk surgery for cancer treatment would reduce 30-day mortality and postoperative complications. A randomized, parallel-group, superiority trial was performed in a tertiary oncology hospital. All adult patients undergoing high-risk cancer surgery who required intensive care unit admission were randomly allocated to a CI-guided GDHT group or to a usual care group. In the GDHT group, postoperative therapy aimed at CI ≥ 2.5 L/min/m 2 using fluids, inotropes and red blood cells during the first 8 postoperative hours. The primary outcome was a composite endpoint of 30-day all-cause mortality and severe postoperative complications during the hospital stay. A meta-analysis was also conducted including all randomized trials of postoperative GDHT published from 1966 to May 2017. A total of 128 patients (64 in each group) were randomized. The primary outcome occurred in 34 patients of the GDHT group and in 28 patients of the usual care group (53.1% vs 43.8%, absolute difference 9.4 (95% CI, - 7.8 to 25.8); p = 0.3). During the 8-h intervention period more patients in the GDHT group received dobutamine when compared to the usual care group (55% vs 16%, p < 0.001). A meta-analysis of nine randomized trials showed no differences in postoperative mortality (risk ratio 0.85, 95% CI 0.59-1.23; p = 0.4; p for heterogeneity = 0.7; I 2  = 0%) and in the overall complications rate (risk ratio 0.88, 95% CI 0.71-1.08; p = 0.2; p for heterogeneity = 0.07; I 2  = 48%), but a reduced hospital length of stay in the GDHT group (mean difference (MD) - 1.6; 95% CI - 2.75 to - 0.46; p = 0.006; p for heterogeneity = 0.002; I 2  = 74%). CI-guided hemodynamic therapy in the first 8 postoperative hours does not reduce 30-day mortality and severe complications during hospital stay when compared to usual care in cancer patients undergoing high-risk surgery. www.clinicaltrials.gov , NCT01946269 . Registered on 16 September 2013.

Feasibility and Efficacy of the Nintendo Wii Gaming System to Improve Balance Performance Post-Stroke: Protocol of a Phase II Randomized Controlled Trial in an Inpatient Rehabilitation Setting.

PubMed

Bower, Kelly J; Clark, Ross A; McGinley, Jennifer L; Martin, Clarissa L; Miller, Kimberly J

2013-04-01

Balance deficits following stroke are common and debilitating. Commercially available gaming systems, such as the Nintendo(®) (Kyoto, Japan) Wii™, have been widely adopted clinically; however, there is limited evidence supporting their feasibility and efficacy for improving balance performance following stroke. The aim of this trial is to investigate the clinical feasibility and efficacy of using the Nintendo Wii gaming system as an adjunct to standard care to improve balance performance following stroke in an inpatient rehabilitation setting. Thirty participants undergoing inpatient stroke rehabilitation will be recruited into this Phase II, single-blind, randomized controlled trial. Participants will be allocated into a Balance or Upper Limb Group, and both groups will perform activities using the Nintendo Wii in addition to their standard care. Participants will attend three 45-minute sessions per week, for a minimum of 2 and a maximum of 4 weeks. The main focus of the study is to investigate the feasibility of the intervention protocol. This will be evaluated through recruitment, retention, adherence, acceptability, and safety. The Step Test and Functional Reach Test will be the primary efficacy outcomes. Secondary outcomes will include force platform, mobility, and upper limb measures. Assessments will occur at baseline, 2 weeks, and 4 weeks after study entry. To the authors' knowledge, this will be the largest randomized clinical trial to investigate the feasibility and efficacy of the Nintendo Wii gaming system for improving balance performance in a stroke population. The results will inform the design of a Phase III multicenter trial.

Extended lymphadenectomy in bladder cancer.

PubMed

Dorin, Ryan P; Skinner, Eila C

2010-09-01

Radical cystectomy with pelvic lymph node dissection (PLND) is the preferred treatment for invasive bladder cancer. It not only results in the best disease-free term survival rates, but also provides the most accurate disease staging and most effective local symptom control. Recent investigations have demonstrated a clinical benefit to performance of an extended PLND, including all lymphatic tissue to the level of the aortic bifurcation. This review will summarize recent findings regarding the clinical benefits of radical cystectomy with extended lymphadenectomy, and will also examine the latest surgical techniques for optimizing the performance of this technically demanding procedure. Recent studies have demonstrated increased recurrence-free survival and overall survival rates in patients undergoing radical cystectomy with extended PLND, even in cases of pathologically lymph node negative disease. The growing use of minimally invasive techniques has prompted interest in robotic radical cystectomy and extended PLND, and recent reports have demonstrated the feasibility of this technique. The standardization of extended PLND templates has also been a focus of contemporary research. Contemporary research strongly suggests that all patients undergoing radical cystectomy for bladder cancer should undergo concomitant extended PLND. Randomized trials are still needed to confirm the benefits of extended over 'standard' PLND, and to clarify which patients may receive the greatest benefit from this procedure.

AN-2728, a PDE4 inhibitor for the potential topical treatment of psoriasis and atopic dermatitis.

PubMed

Nazarian, Rachel; Weinberg, Jeffrey M

2009-11-01

Cytokines are signaling molecules that are believed to be key factors in perpetuating the inflammatory process in psoriasis and atopic dermatitis. AN-2728, being developed by Anacor Pharmaceuticals Inc, is a topically administered, boron-containing, anti-inflammatory compound that inhibits PDE4 activity and thereby suppresses the release of TNFalpha, IL-12, IL-23 and other cytokines. At the time of publication, three phase Ib clinical trials, a IIa trial and a IIb trial of AN-2728 in patients with psoriasis had been completed; the compound was also undergoing phase II development for atopic dermatitis, but no data were available for this indication. AN-2728 was reported to be well tolerated and to demonstrate significant effects on markers of efficacy, with results that were comparable to positive controls. AN-2728 appears to have good therapeutic potential, although further and larger trials are required to assess the long-term safety and characterize the broad utility of this drug.

Piezoelectric Versus Conventional Rotary Techniques for Impacted Third Molar Extraction: A Meta-analysis of Randomized Controlled Trials.

PubMed

Jiang, Qian; Qiu, Yating; Yang, Chi; Yang, Jingyun; Chen, Minjie; Zhang, Zhiyuan

2015-10-01

Impacted third molars are frequently encountered in clinical work. Surgical removal of impacted third molars is often required to prevent clinical symptoms. Traditional rotary cutting instruments are potentially injurious, and piezosurgery, as a new osteotomy technique, has been introduced in oral and maxillofacial surgery. No consistent conclusion has been reached regarding whether this new technique is associated with fewer or less severe postoperative sequelae after third molar extraction.The aim of this study was to compare piezosurgery with rotary osteotomy techniques, with regard to surgery time and the severity of postoperative sequelae, including pain, swelling, and trismus.We conducted a systematic literature search in the Cochrane Library, PubMed, Embase, and Google Scholar.The eligibility criteria of this study included the following: the patients were clearly diagnosed as having impacted mandibular third molars; the patients underwent piezosurgery osteotomy, and in the control group rotary osteotomy techniques, for removing impacted third molars; the outcomes of interest include surgery time, trismus, swelling or pain; the studies are randomized controlled trials.We used random-effects models to calculate the difference in the outcomes, and the corresponding 95% confidence interval. We calculated the weighted mean difference if the trials used the same measurement, and a standardized mean difference if otherwise.A total of seven studies met the eligibility criteria and were included in our analysis. Compared with rotary osteotomy, patients undergoing piezosurgery experienced longer surgery time (mean difference 4.13 minutes, 95% confidence interval 2.75-5.52, P < 0.0001). Patients receiving the piezoelectric technique had less swelling at postoperative days 1, 3, 5, and 7 (all Ps ≤0.023). Additionally, there was a trend of less postoperative pain and trismus in the piezosurgery groups.The number of included randomized controlled trials and the sample size of each trial were relatively small, double blinding was not possible, and cost analysis was unavailable due to a lack of data.Our meta-analysis indicates that although patients undergoing piezosurgery experienced longer surgery time, they had less postoperative swelling, indicating that piezosurgery is a promising alternative technique for extraction of impacted third molars.

Study design and rationale of the 'Balloon-Expandable Cobalt Chromium SCUBA Stent versus Self-Expandable COMPLETE-SE Nitinol Stent for the Atherosclerotic ILIAC Arterial Disease (SENS-ILIAC Trial) Trial': study protocol for a randomized controlled trial.

PubMed

Choi, Woong Gil; Rha, Seung Woon; Choi, Cheol Ung; Kim, Eung Ju; Oh, Dong Joo; Cho, Yoon Hyung; Park, Sang Ho; Lee, Seung Jin; Hur, Ae Yong; Ko, Young Guk; Park, Sang Min; Kim, Ki Chang; Kim, Joo Han; Kim, Min Woong; Kim, Sang Min; Bae, Jang Ho; Bong, Jung Min; Kang, Won Yu; Seo, Jae Bin; Jung, Woo Yong; Cho, Jang Hyun; Kim, Do Hoi; Ahn, Ji Hoon; Kim, Soo Hyun; Jang, Ji Yong

2016-06-25

The self-expandable COMPLETE™ stent (Medtronic) has greater elasticity, allowing it to regain its shape after the compression force reduces, and has higher trackability, thus is easier to maneuver through tortuous vessels, whereas the balloon-expandable SCUBA™ stent (Medtronic) has higher radial stiffness and can afford more accurate placement without geographic miss, which is important in aortoiliac bifurcation lesions. To date, there have been no randomized control trials comparing efficacy and safety between the self-expanding stent and balloon-expandable stent in advanced atherosclerotic iliac artery disease. The purpose of our study is to examine primary patency (efficacy) and incidence of stent fracture and geographic miss (safety) between two different major representative stents, the self-expanding nitinol stent (COMPLETE-SE™) and the balloon-expanding cobalt-chromium stent (SCUBA™), in stenotic or occlusive iliac arterial lesions. This trial is designed as a prospective, randomized, multicenter trial to demonstrate a noninferiority of SCUBA™ stent to COMPLETE-SE™ stent following balloon angioplasty in iliac arterial lesions, and a total of 280 patients will be enrolled. The primary end point of this study is the rate of primary patency in the treated segment at 12 months after intervention as determined by catheter angiography, computed tomography angiography, or duplex ultrasound. The SENS-ILIAC trial will give powerful insight into whether the stent choice according to deployment mechanics would impact stent patency, geographic miss, or stent fracture in patients undergoing stent implantation in iliac artery lesions. National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT01834495 ), registration date: May 8, 2012.

Prospective, randomised, controlled trial comparing suture needle drainage and argon laser drainage of subretinal fluid.

PubMed Central

Aylward, G W; Orr, G; Schwartz, S D; Leaver, P K

1995-01-01

AIMS--This study was designed to compare suture needle drainage (SND) with argon laser drainage (ALD) of subretinal fluid. METHODS--A prospective, randomised, controlled, clinical trial was carried out on 93 patients undergoing external drainage of subretinal fluid during scleral buckling surgery for rhegmatogenous retinal detachment. The incidence of successful drainage, incidence of subretinal haemorrhage, incidence of retinal incarceration, and incidence of retinal perforation were determined. RESULTS--The success rate was 97.9% in the ALD group and 84.8% in the SND group (difference-13.1%, 95% CI-26.4% to 2.0%). The incidence of clinically significant subretinal haemorrhage was 4.3% in the ALD group compared with 28.3% in the SND group (difference 24.0%, 95% CI 7.6% to 40.4%). The incidence of incarceration was comparable in each group. There were no cases of retinal perforation. CONCLUSIONS--The use of ALD was associated with a higher rate of successful SRF drainage, and a lower incidence of clinically significant subretinal haemorrhage than SND. ALD is preferred when an endolaser is available. PMID:7547781

Immunomodulatory Effects of Adipose-Derived Stem Cells: Fact or Fiction?

PubMed Central

Leto Barone, Angelo A.; Khalifian, Saami; Lee, W. P. Andrew; Brandacher, Gerald

2013-01-01

Adipose-derived stromal cells (ASCs) are often referred to as adipose-derived stem cells due to their potential to undergo multilineage differentiation. Their promising role in tissue engineering and ability to modulate the immune system are the focus of extensive research. A number of clinical trials using ASCs are currently underway to better understand the role of such cell niche in enhancing or suppressing the immune response. If governable, such immunoregulatory role would find application in several conditions in which an immune response is present (i.e., autoimmune conditions) or feared (i.e., solid organ or reconstructive transplantation). Although allogeneic ASCs have been shown to prevent acute GvHD in both preclinical and clinical studies, their potential warrants further investigation. Well-designed and standardized clinical trials are necessary to prove the role of ASCs in the treatment of immune disorders or prevention of tissue rejection. In this paper we analyze the current literature on the role of ASCs in immunomodulation in vitro and in vivo and discuss their potential in regulating the immune system in the context of transplantation. PMID:24106704

Effect of cerebrolysin on gross motor function of children with cerebral palsy: a clinical trial.

PubMed

Nasiri, Jafar; Safavifar, Faezeh

2017-06-01

Gross motor dysfunction is considered as the most challenging problem in cerebral palsy (CP). It is proven that improvement of gross motor function could reduce CP-related disabilities and provide better quality of life in this group of patients. Therefore, the aim of this trial is to evaluate the effectiveness of cerebrolysin (CBL) on gross motor function of children with CP who are undergoing treatment. In this clinical trial study, paediatric patients aged 18-75 months with spastic diplegic or quadriplegic cerebral palsy, who were under rehabilitation therapy, were selected and randomly allocated in control and CBL groups. Patients in CBL group underwent treatment with standard rehabilitation therapy plus CBL. The latter was administrated intramuscularly as a single daily dose of 0.1 cc/kg for 10 days and then continued weekly for 4 months. Gross motor function of participants in the two studied groups, before and after trial, was evaluated and compared using the validated Persian version of gross motor function classification system-expanded and revised (GMFCS-E&R). During this trial, 108 patients with CP were evaluated for eligibility. From these, 50 patients were enrolled and randomly allocated in the CBL and control groups. Four months after trial, the mean level of GMFCS decreased significantly in the two groups (P < 0.05). However, it was significantly lower in the CBL group than in the control group (2.1 vs. 3.16, P < 0.05). The results of this trial indicated that CBL could improve gross motor function in patients with CP. This finding is consistent with neurotrophic and neuroprotective effects of CBL, which have been reported in various clinical trials in other neurological disorders. Further studies are recommended to establish the value of continued neuroprotection and to determine the pharmacokinetics/dynamics of CBL in this group of patients.

Obstetrician call schedule and obstetric outcomes among women eligible for a trial of labor after cesarean.

PubMed

Yee, Lynn M; Liu, Lilly Y; Grobman, William A

2017-01-01

Reducing cesarean deliveries is a major public health goal. The low rate of vaginal birth after cesarean has been attributed largely to a decrease in the likelihood of choosing a trial of labor after cesarean, despite evidence suggesting a majority of women with 1 prior low transverse cesarean are trial of labor after cesarean candidates. Although a number of reasons for this decrease have been explored, it remains unclear how systems issues such as physician call schedules influence delivery approach and mode in this context. The objective of the study was to investigate the relationship between obstetricians' call schedule and obstetric outcomes among women eligible for a trial of labor after cesarean. This is a retrospective cohort study of the likelihood of attempting a trial of labor after cesarean and achieving vaginal birth after cesarean among women with 1 prior low transverse cesarean delivery and a term, cephalic singleton gestation based on the delivering provider's call schedule. Attending obstetrician call schedules were classified as traditional or night float call. Night float call was defined as a schedule in which the provider had clinical responsibilities only for a day or night shift, without other clinical responsibilities before or after the period of responsibility for laboring patients. Call schedules are determined by individual provider groups. Bivariable analyses and random-effects logistic regression were used to examine the relationship between obstetricians' call schedule and the frequency of trial of labor after cesarean. Secondary outcomes including frequency of vaginal birth after cesarean and maternal and neonatal outcomes also were assessed. Of 1502 eligible patients, 556 (37%) were delivered by physicians in a night float call system. A total of 22.6% underwent a trial of labor after cesarean and 12.8% achieved vaginal birth after cesarean; the vaginal birth after cesarean rate for women attempting a trial of labor after cesarean was 56.5%. Women were more likely to undergo a trial of labor after cesarean (33.1% vs 16.5%, P < .001) and achieve vaginal birth after cesarean (18.7% vs 9.3%, P < .001) when cared for by physicians with a night float call schedule. Regression analyses demonstrated physicians with a night float call schedule remained significantly more likely to have patients undergo trial of labor after cesarean (adjusted odds ratio, 2.64, 95% confidence interval, 1.65-4.25) and experience vaginal birth after cesarean (adjusted odds ratio, 2.17, 95% confidence interval, 1.36-3.45) after adjusting for potential confounders. However, the likelihood of achieving vaginal birth after cesarean if a trial of labor after cesarean was attempted was not different based on provider call type (adjusted odds ratio, 0.96, 95% confidence interval, 0.57-1.62). Although women delivered by providers with a night float schedule were more likely to experience uterine rupture (1.8% vs 0.6%, P = .03), chorioamnionitis (4.3% vs 1.7%, P = .002), postpartum hemorrhage (7.6% vs 4.8%, P = .03), and neonates admitted to the neonatal intensive care unit (6.8% vs 3.9%, P = .01), these associations did not persist when the population was limited to women attempting trial of labor after cesarean. Although physicians working on a night float call system were significantly more likely to have patients with a prior cesarean undergo trial of labor after cesarean and achieve vaginal birth after cesarean, their patients also were more likely to experience maternal and neonatal morbidity. However, these differences did not persist when limiting analyses to women attempting a trial of labor after cesarean. Using a night float call schedule may be an effective measure to promote a trial of labor after cesarean and vaginal birth after cesarean. Copyright © 2016 Elsevier Inc. All rights reserved.

Trichuris suis ova in relapsing-remitting multiple sclerosis and clinically isolated syndrome (TRIOMS): study protocol for a randomized controlled trial.

PubMed

Rosche, Berit; Wernecke, Klaus-Dieter; Ohlraun, Stephanie; Dörr, Jan-Markus; Paul, Friedemann

2013-04-25

Trichuris suis ova is a probiotic treatment based on the hygiene hypothesis. It has been demonstrated as safe and effective in autoimmune inflammatory bowel diseases and clinical trials indicate that helminth infections also have an immunomodulatory effect in multiple sclerosis.We hypothesize that administering 2,500 Trichuris suis ova eggs orally every two weeks for 12 months is--due to its immunomodulatory and anti-inflammatory effect--significantly more effective than oral placebo in preventing new T2 and Gd+ lesions, as quantified by cerebral MRI and clinical examination, in relapsing-remitting multiple sclerosis and clinically isolated syndrome. Fifty patients with relapsing-remitting multiple sclerosis or clinically isolated syndrome with clinical activity, not undergoing any standard therapies, will be randomized 1:1 to Trichuris suis ova 2,500 eggs every two weeks or matching placebo. The safety, tolerability and effect on disease activity and in vivo mechanisms of action of Trichuris suis ova in MS will be assessed by neurological, laboratory and immunological exams and magnetic resonance imaging throughout the 12-month treatment period and over a follow-up period of 6 months. Various immunological analyses will be used to assess the overall patient immune response prior to and at varying time points following treatment with Trichuris suis ova. We anticipate that Trichuris suis ova will be well tolerated and more effective than the placebo in preventing new T2 and Gd+ lesions, as quantified by MRI. We also expect the Th1/Th17 proinflammatory response to shift towards the more anti-inflammatory Th2 response. This study has important clinical implications and will involve extensive research on the immunology of helminth therapy. ClinicalTrials.gov: NCT01413243.

The 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Second-generation drug-eluting stents (DES) have raised the bar of clinical performance. These stents are mostly made from cobalt chromium alloy. A newer generation DES has been developed from platinum chromium alloy, but clinical data regarding the efficacy and safety of the platinum chromium-based everolimus-eluting stent (PtCr-EES) is limited, with no comparison data against the cobalt chromium-based zotarolimus-eluting stent (CoCr-ZES). In addition, an antiplatelet regimen is an integral component of medical therapy after percutaneous coronary intervention (PCI). A 1-week duration of doubling the dose of clopidogrel (double-dose antiplatelet therapy (DDAT)) was shown to improve outcome at 1 month compared with conventional dose in acute coronary syndrome (ACS) patients undergoing PCI. However in Asia, including Korea, the addition of cilostazol (triplet antiplatelet therapy (TAT)) is used more commonly than doubling the dose of clopidogrel in high-risk patients. Methods In the 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial, approximately 3,750 patients are being prospectively and randomly assigned in a 2 × 2 factorial design according to the type of stent (PtCr-EES vs CoCr-ZES) and antiplatelet regimen (TAT vs DDAT). The first primary endpoint is target lesion failure at 1 year for the stent comparison, and the second primary endpoint is net clinical outcome at 1 month for comparison of antiplatelet therapy regimen. Discussion The HOST-ASSURE trial is the largest study yet performed to directly compare the efficacy and safety of the PtCr-EES versus CoCr-ZES in an 'all-comers' population. In addition, this study will also compare the clinical outcome of TAT versus DDAT for 1-month post PCI. Trial registration ClincalTrials.gov number NCT01267734. PMID:22463698

Prefrontal transcranial direct current stimulation (tDCS) as treatment for major depression: study design and methodology of a multicenter triple blind randomized placebo controlled trial (DepressionDC).

PubMed

Padberg, Frank; Kumpf, Ulrike; Mansmann, Ulrich; Palm, Ulrich; Plewnia, Christian; Langguth, Berthold; Zwanzger, Peter; Fallgatter, Andreas; Nolden, Jana; Burger, Max; Keeser, Daniel; Rupprecht, Rainer; Falkai, Peter; Hasan, Alkomiet; Egert, Silvia; Bajbouj, Malek

2017-12-01

Transcranial direct current stimulation (tDCS) has been proposed as novel treatment for major depressive disorder (MDD) based on clinical pilot studies as well as randomized controlled monocentric trials. The DepressionDC trial is a triple-blind (blinding of rater, operator and patient), randomized, placebo controlled multicenter trial investigating the efficacy and safety of prefrontal tDCS used as additive treatment in MDD patients who have not responded to selective serotonin reuptake inhibitors (SSRI). At 5 study sites, 152 patients with MDD receive a 6-weeks treatment with active tDCS (anode F3 and cathode F4, 2 mA intensity, 30 min/day) or sham tDCS add-on to a stable antidepressant medication with an SSRI. Follow-up visits are at 3 and 6 months after the last tDCS session. The primary outcome measure is the change of the Montgomery-Asberg Depression Rating Scale (MADRS) scores at week 6 post-randomisation compared to baseline. Secondary endpoints also cover other psychopathological domains, and a comprehensive safety assessment includes measures of cognition. Patients undergo optional investigations comprising genetic testing and functional magnetic resonance imaging (fMRI) of structural and functional connectivity. The study uses also an advanced tDCS technology including standard electrode positioning and recording of technical parameters (current, impedance, voltage) in every tDCS session. Aside reporting the study protocol here, we present a novel approach for monitoring technical parameters of tDCS which will allow quality control of stimulation and further analysis of the interaction between technical parameters and clinical outcome. The DepressionDC trial will hopefully answer the important clinical question whether prefrontal tDCS is a safe and effective antidepressant intervention in patients who have not sufficiently responded to SSRIs. ClinicalTrials.gov Identifier NCT0253016.

Clinical use of vaginal or rectally applied microbicides in patients suffering from HIV/AIDS.

PubMed

Gupta, Satish Kumar; Nutan

2013-10-22

Microbicides, primarily used as topical pre-exposure prophylaxis, have been proposed to prevent sexual transmission of HIV. This review covers the trends and challenges in the development of safe and effective microbicides to prevent sexual transmission of HIV Initial phases of microbicide development used such surfactants as nonoxynol-9 (N-9), C13G, and sodium lauryl sulfate, aiming to inactivate the virus. Clinical trials of microbicides based on N-9 and C31G failed to inhibit sexual transmission of HIV. On the contrary, N-9 enhanced susceptibility to sexual transmission of HIV-1. Subsequently, microbicides based on polyanions and a variety of other compounds that inhibit the binding, fusion, or entry of virus to the host cells were evaluated for their efficacy in different clinical setups. Most of these trials failed to show either safety or efficacy for prevention of HIV transmission. The next phase of microbicide development involved antiretroviral drugs. Microbicide in the form of 1% tenofovir vaginal gel when tested in a Phase IIb trial (CAPRISA 004) in a coitally dependent manner revealed that tenofovir gel users were 39% less likely to become HIV-infected compared to placebo control. However, in another trial (VOICE MTN 003), tenofovir gel used once daily in a coitally independent mode failed to show any efficacy to prevent HIV infection. Tenofovir gel is currently in a Phase III safety and efficacy trial in South Africa (FACTS 001) employing a coitally dependent dosing regimen. Further, long-acting microbicide-delivery systems (vaginal ring) for slow release of such antiretroviral drugs as dapivirine are also undergoing clinical trials. Discovering new markers as correlates of protective efficacy, novel long-acting delivery systems with improved adherence in the use of microbicides, discovering new compounds effective against a broad spectrum of HIV strains, developing multipurpose technologies incorporating additional features of efficacy against other sexually transmitted infections, and contraception will help in moving the field of microbicide development forward.

Clinical use of vaginal or rectally applied microbicides in patients suffering from HIV/AIDS

PubMed Central

Gupta, Satish Kumar; Nutan

2013-01-01

Microbicides, primarily used as topical pre-exposure prophylaxis, have been proposed to prevent sexual transmission of HIV. This review covers the trends and challenges in the development of safe and effective microbicides to prevent sexual transmission of HIV Initial phases of microbicide development used such surfactants as nonoxynol-9 (N-9), C13G, and sodium lauryl sulfate, aiming to inactivate the virus. Clinical trials of microbicides based on N-9 and C31G failed to inhibit sexual transmission of HIV. On the contrary, N-9 enhanced susceptibility to sexual transmission of HIV-1. Subsequently, microbicides based on polyanions and a variety of other compounds that inhibit the binding, fusion, or entry of virus to the host cells were evaluated for their efficacy in different clinical setups. Most of these trials failed to show either safety or efficacy for prevention of HIV transmission. The next phase of microbicide development involved antiretroviral drugs. Microbicide in the form of 1% tenofovir vaginal gel when tested in a Phase IIb trial (CAPRISA 004) in a coitally dependent manner revealed that tenofovir gel users were 39% less likely to become HIV-infected compared to placebo control. However, in another trial (VOICE MTN 003), tenofovir gel used once daily in a coitally independent mode failed to show any efficacy to prevent HIV infection. Tenofovir gel is currently in a Phase III safety and efficacy trial in South Africa (FACTS 001) employing a coitally dependent dosing regimen. Further, long-acting microbicide-delivery systems (vaginal ring) for slow release of such antiretroviral drugs as dapivirine are also undergoing clinical trials. Discovering new markers as correlates of protective efficacy, novel long-acting delivery systems with improved adherence in the use of microbicides, discovering new compounds effective against a broad spectrum of HIV strains, developing multipurpose technologies incorporating additional features of efficacy against other sexually transmitted infections, and contraception will help in moving the field of microbicide development forward. PMID:24174883

Effects of a pre-operative home-based inspiratory muscle training programme on perceived health-related quality of life in patients undergoing coronary artery bypass graft surgery.

PubMed

Valkenet, K; Trappenburg, J C A; Hulzebos, E H; van Meeteren, N L U; Backx, F J G

2017-09-01

Pre-operative inspiratory muscle training has been shown to decrease the incidence of postoperative pneumonia and length of hospital stay in patients undergoing coronary artery bypass graft surgery (CABG). This study investigated if this decrease acted as a mediator on the time course of quality of life. Complementary analyses of a published randomised controlled trial. The initial trial included patients awaiting CABG surgery at a Dutch university hospital. The secondary analyses used data from the initial trial for patients who had completed at least one quality-of-life questionnaire. Participants were allocated at random to the intervention group or the usual care group. The intervention group followed a home-based pre-operative inspiratory muscle training programme. Quality of life was measured at five time points. Between-group differences in quality-of-life scores were analysed using mixed linear modelling. The secondary analyses used data for 235 patients. In line with the initial trial, pneumonia and length of hospital stay were decreased significantly in the intervention group. The time courses for all patients showed significant improvements in quality of life after surgery compared with baseline. No significant differences in quality of life were observed over time between the two groups. Despite decreased incidence of pneumonia and length of hospital stay in the intervention group, this study did not find any improvements in quality of life due to the pre-operative home-based inspiratory muscle training programme. Clinical trial registration number ISRCTN17691887. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Beyond Stroke Prevention in Atrial Fibrillation: Exploring Further Unmet Needs with Rivaroxaban.

PubMed

Gibson, C M; Hankey, G J; Nafee, T; Welsh, R C

2018-03-22

With improved life expectancy and the aging population, the global burden of atrial fibrillation (AF) continues to increase, and with AF comes an estimated fivefold increased risk of ischaemic stroke. Prophylactic anticoagulant therapy is more effective in reducing the risk of ischaemic stroke in AF patients than acetylsalicylic acid or dual-antiplatelet therapy combining ASA with clopidogrel. Non-vitamin K antagonist oral anticoagulants are the standard of care for stroke prevention in patients with non-valvular AF. The optimal anticoagulant strategy to prevent thromboembolism in AF patients who are undergoing percutaneous coronary intervention and stenting, those who have undergone successful transcatheter aortic valve replacement and those with embolic stroke of undetermined source are areas of ongoing research. This article provides an update on three randomized controlled trials of rivaroxaban, a direct, oral factor Xa inhibitor, that are complete or are ongoing, in these unmet areas of stroke prevention: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in patients with Atrial Fibrillation who undergo Percutaneous Coronary Intervention (PIONEER AF-PCI) trial; the New Approach riVaroxaban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial and the Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO) trial. The data from these studies are anticipated to help address continuing challenges for a range of patients at risk of stroke. Schattauer.

Sham-controlled, randomized, feasibility trial of acupuncture for prevention of radiation-induced xerostomia among patients with nasopharyngeal carcinoma

PubMed Central

Meng, Zhiqiang; Garcia, M. Kay; Hu, Chaosu; Chiang, Joseph; Chambers, Mark; Rosenthal, David I.; Peng, Huiting; Wu, Caijun; Zhao, Qi; Zhao, Genming; Liu, Luming; Spelman, Amy; Palmer, J. Lynn; Wei, Qi; Cohen, Lorenzo

2013-01-01

Background Xerostomia (dry mouth) after head/neck radiation is a common problem among cancer patients. Quality of life (QOL) is impaired, and available treatments are of little benefit. This trial determined the feasibility of conducting a sham-controlled trial of acupuncture and whether acupuncture could prevent xerostomia among head/neck patients undergoing radiotherapy. Methods A sham controlled, feasibility trial was conducted at Fudan University Shanghai Cancer Center, Shanghai, China among patients with nasopharyngeal carcinoma undergoing radiotherapy. To determine feasibility of a sham procedure, 23 patients were randomized to real acupuncture (N = 11) or to sham acupuncture (N = 12). Patients were treated 3 times/week during their course of radiotherapy. Subjective measures were the Xerostomia Questionnaire (XQ) and MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN). Objective measures were unstimulated whole salivary flow rates (UWSFR) and stimulated salivary flow rates (SSFR). Patients were followed for 1 month after radiotherapy. Results XQ scores for acupuncture were significantly lower than sham controls starting in week 3 and lasted through the 1-month follow-up (all P’s < 0.001 except for week 3, which was 0.006), with clinically significant differences as follows: week 6 – RR 0.28 [95% CI, 0.10, 0.79]; week 11- RR 0.17 [95% CI, 0.03, 1.07]. Similar findings were seen for MDASI-HN scores and MDASI-Intrusion scores. Group differences for UWSFR and SSFR were not found. Conclusions In this small pilot study, true acupuncture given concurrently with radiotherapy significantly reduced xerostomia symptoms and improved QOL when compared with sham acupuncture. Large-scale, multi-center, randomized, placebo-controlled trials are now needed. PMID:22285177

Preconditioning, postconditioning and their application to clinical cardiology.

PubMed

Kloner, Robert A; Rezkalla, Shereif H

2006-05-01

Ischemic preconditioning is a well-established phenomenon first described in experimental preparations in which brief episodes of ischemia/reperfusion applied prior to a longer coronary artery occlusion reduce myocardial infarct size. There are ample correlates of ischemic preconditioning in the clinical realm. Preconditioning mimetic agents that stimulate the biochemical pathways of ischemic preconditioning and protect the heart without inducing ischemia have been examined in numerous experimental studies. However, despite the effectiveness of ischemic preconditioning and preconditioning mimetics for protecting ischemic myocardium, there are no preconditioning-based therapies that are routinely used in clinical medicine at the current time. Part of the problem is the need to administer therapy prior to the known ischemic event. Other issues are that percutaneous coronary intervention technology has advanced so far (with the development of stents and drug-eluting stents) that ischemic preconditioning or preconditioning mimetics have not been needed in most interventional cases. Recent clinical trials such as AMISTAD I and II (Acute Myocardial Infarction STudy of ADenosine) suggest that some preconditioning mimetics may reduce myocardial infarct size when given along with reperfusion or, as in the IONA trial, have benefit on clinical events when administered chronically in patients with known coronary artery disease. It is possible that some of the benefit described for adenosine in the AMISTAD 1 and 2 trials represents a manifestation of the recently described postconditioning phenomenon. It is probable that postconditioning--in which reperfusion is interrupted with brief coronary occlusions and reperfusion sequences--is more likely than preconditioning to be feasible as a clinical application to patients undergoing percutaneous coronary intervention for acute myocardial infarction.

Profile of neratinib and its potential in the treatment of breast cancer

PubMed Central

Feldinger, Katharina; Kong, Anthony

2015-01-01

The HER (ErbB) receptor tyrosine kinase receptors are implicated in many cancers and several anti-HER treatments are now approved. In recent years, a new group of compounds that bind irreversibly to the adenosine triphosphate binding pocket of HER receptors have been developed. One of these compounds, neratinib, has passed preclinical phases and is currently undergoing various clinical trials. This manuscript reviews the preclinical as well as clinical data on neratinib. As a pan-HER inhibitor, this irreversible tyrosine kinase inhibitor binds and inhibits the tyrosine kinase activity of epidermal growth factor receptors, EGFR (or HER1), HER2 and HER4, which leads to reduced phosphorylation and activation of downstream signaling pathways. Neratinib has been shown to be effective against HER2-overexpressing or mutant tumors in vitro and in vivo. Neratinib is currently being investigated in various clinical trials in breast cancers and other solid tumors, including those with HER2 mutation. Earlier studies have already shown promising clinical activity for neratinib. However, more translational research is required to investigate biomarkers that could help to predict response and resistance for selection of appropriate patients for treatment with neratinib, either as monotherapy or in combination with other drug(s). PMID:26089701

Profile of neratinib and its potential in the treatment of breast cancer.

PubMed

Feldinger, Katharina; Kong, Anthony

2015-01-01

The HER (ErbB) receptor tyrosine kinase receptors are implicated in many cancers and several anti-HER treatments are now approved. In recent years, a new group of compounds that bind irreversibly to the adenosine triphosphate binding pocket of HER receptors have been developed. One of these compounds, neratinib, has passed preclinical phases and is currently undergoing various clinical trials. This manuscript reviews the preclinical as well as clinical data on neratinib. As a pan-HER inhibitor, this irreversible tyrosine kinase inhibitor binds and inhibits the tyrosine kinase activity of epidermal growth factor receptors, EGFR (or HER1), HER2 and HER4, which leads to reduced phosphorylation and activation of downstream signaling pathways. Neratinib has been shown to be effective against HER2-overexpressing or mutant tumors in vitro and in vivo. Neratinib is currently being investigated in various clinical trials in breast cancers and other solid tumors, including those with HER2 mutation. Earlier studies have already shown promising clinical activity for neratinib. However, more translational research is required to investigate biomarkers that could help to predict response and resistance for selection of appropriate patients for treatment with neratinib, either as monotherapy or in combination with other drug(s).

Preventive medicines: vaccination, prophylaxis of infectious diseases, disinfectants.

PubMed

Heininger, Ulrich

2011-01-01

Immunizations belong to the most successful interventions in medicine. Like other drugs, vaccines undergo long periods of pre-clinical development, followed by careful clinical testing through study Phases I, II, and III before they receive licensure. A successful candidate vaccine will move on to be an investigational vaccine to undergo three phases of pre-licensure clinical trials in a stepwise fashion before it can be considered for approval, followed by an optional fourth phase of post-marketing assessment. The overall risk-benefit assessment of a candidate vaccine is very critical in making the licensure decision for regulatory authorities, supported by their scientific committees. It includes analyses of immunogenicity, efficacy, reactogenicity or tolerability, and safety of the vaccine. Public trust in vaccines is a key to the success of immunization programs worldwide. Maintaining this trust requires knowledge of the benefits and scientific understanding of real or perceived risks of immunizations. Under certain circumstances, pre- or post-exposure passive immunization can be achieved by administration of immunoglobulines. In terms of prevention of infectious diseases, disinfection can be applied to reduce the risk of transmission of pathogens from patient to patient, health-care workers to patients, patients to health-care workers, and objects or medical devices to patients.

Effects of Saffron on Cognition, Anxiety, and Depression in Patients Undergoing Coronary Artery Bypass Grafting: A Randomized Double-Blind Placebo-Controlled Trial.

PubMed

Moazen-Zadeh, Ehsan; Abbasi, Seyed Hesameddin; Safi-Aghdam, Hamideh; Shahmansouri, Nazila; Arjmandi-Beglar, Akram; Hajhosseinn Talasaz, Azita; Salehiomran, Abbas; Forghani, Saeedeh; Akhondzadeh, Shahin

2018-04-01

Cognitive decline, depression, and anxiety are among the major concerns in patients undergoing coronary artery bypass grafting (CABG). Crocus sativus L. (saffron) seems to be a promising candidate for treatment of these conditions. In this 12-week, randomized, double-blind, placebo-controlled clinical trial, men and women with on-pump CABG, who had Wechsler Memory Scale (WMS) score >70 and age <70 years, received either saffron capsules (15 mg/twice daily) or placebo. Patients were excluded if they had history of treatment with saffron or acetylcholinesterase inhibitors, comorbid neuropsychiatric disorders, serious medical conditions other than cardiovascular diseases, and hypersensitivity to herbal compounds. The primary outcome was defined as the difference in mean total score changes for WMS-Revised from the baseline to week 12 between the saffron and placebo groups. Secondary outcomes included difference in mean score changes from baseline to endpoint between the two treatment groups for Mini Mental Status Examination and subscales of Hospital Anxiety and Depression Scale ( www.irct.ir ; IRCT201408071556N63). No significant difference was detected in primary or secondary outcomes between the saffron and placebo groups. Also, no significant time × treatment interaction effect was found for any of the scales. The results of this trial do not support the hypothesis of potential benefits of saffron in treatment of CABG-related neuropsychiatric conditions.

Patient and family satisfaction levels in the intensive care unit after elective cardiac surgery: study protocol for a randomised controlled trial of a preoperative patient education intervention

PubMed Central

Leung, Patricia; Chiu, Chun Hung; Ho, Ka Man; Gomersall, Charles David; Underwood, Malcolm John

2016-01-01

Introduction Patients and their families are understandably anxious about the risk of complications and unfamiliar experiences following cardiac surgery. Providing information about postoperative care in the intensive care unit (ICU) to patients and families may lead to lower anxiety levels, and increased satisfaction with healthcare. The objectives of this study are to evaluate the effectiveness of preoperative patient education provided for patients undergoing elective cardiac surgery. Methods and analysis 100 patients undergoing elective coronary artery bypass graft, with or without valve replacement surgery, will be recruited into a 2-group, parallel, superiority, double-blinded randomised controlled trial. Participants will be randomised to either preoperative patient education comprising of a video and ICU tour with standard care (intervention) or standard education (control). The primary outcome measures are the satisfaction levels of patients and family members with ICU care and decision-making in the ICU. The secondary outcome measures are patient anxiety and depression levels before and after surgery. Ethics and dissemination Ethical approval has been obtained from the Joint Chinese University of Hong Kong—New Territories East Cluster Clinical Research Ethics Committee (reference number CREC 2015.308). The findings will be presented at conferences and published in peer-reviewed journals. Study participants will receive a 1-page plain language summary of results. Trial registration number ChiCTR-IOR-15006971. PMID:27334883

[Randomized controlled trial on the effectiveness of Corpitolinol 60 in the prevention of pressure sores in patients undergoing surgery].

PubMed

Chiari, Paolo; Giorgi, Sabina; Ugolini, Daniela; Montanari, Morena; Giudanella, Pietro; Gramantieri, Antonella; Collesi, Franca; Pau, Michelina; Smaldone, Maddalena; Matarasso, Maddalena; Mazzini, Cinzia; Russo, Francesca; Gazineo, Domenica; Fontana, Mirella; Taddia, Patrizia

2012-01-01

Randomized controlled trial on the effectiveness of Corpitolinol 60 in the prevention of pressure sores in surgical patients. The risk of pressure sores in surgical patients is widely recognised. The Corpitolinol 60 (Sanyréne®) applied on compressed areas seems to reduce the risk of pressure sores. To assess the efficacy of Corpitolinol 60 in preventing pressure sores in the operatory theatre. The open label randomized clinical trial was conducted in 5 operating theatres of Northen Italy. Patients were randomized to receive Corpitolinol 60 in areas undergoing compression. Experimental group and controls were treated with usual measures for preventing pressure sores. The lesions were staged according to NPUAP up to 24 hours after surgery. Three-hundred-one patients were randomized (155 in the Sanyréne® group and 143 controls). The main variables predictive of pressure sores risk (ASA class, sex, age, duration of the surgery, and BMI) were comparable across groups. At the end of the surgery 71 patients (23.8%) in the experimental group and 47 controls (30.8%) had a pressure sore (p 0.006; RR 1.81 IC95% 1.17-2.79). Twelve and 24 hours after surgery the differences between groups were not significant. The aim of reducing pressure sores was not reached for patients treated with Corpitolinol 60.

Extent of regional lymph node surgery and impact on outcomes in patients with early-stage breast cancer and limited axillary disease undergoing mastectomy.

PubMed

Picado, Omar; Khazeni, Kristina; Allen, Casey; Yakoub, Danny; Avisar, Eli; Kesmodel, Susan B

2018-06-05

Management of the axilla in patients with early-stage breast cancer (ESBC) has evolved. Recent trials support less extensive axillary surgery in patients undergoing mastectomy. We examine factors affecting regional lymph node (RLN) surgery and outcomes in patients with ESBC undergoing mastectomy. Women with clinical T1/2 N0 M0 invasive BC who underwent mastectomy with 1-2 positive nodes were selected from the National Cancer Database (2004-2015). Axillary surgery was defined by number of RLNs examined: 1-5 sentinel LN dissection (SLND), and ≥ 10 axillary LND (ALND). Binary logistic regression and survival analyses were performed to assess the association between axillary surgery and clinical characteristics, and overall survival (OS), respectively. 34,243 patients were included: 13,821 SLND (40%) and 20,422 ALND (60%). SLND significantly increased from 21% (2004) to 45% (2015) (p < .001). Independent factors associated with SLND were treatment year, non-Academic centers, geographic region, tumor histology, and postmastectomy radiotherapy (PMRT). Multivariable survival analysis showed that ALND was associated with better OS (HR 0.78, 95% CI 0.72-0.83, p < .001) relative to SLND; however, there was no difference in patients with LN micrometastases treated without RT (HR 0.87, 95% CI 0.73-1.05, p = .153) or patients receiving PMRT (HR 0.92, 95% CI 0.76-1.13, p = .433). SLND has significantly increased in patients undergoing mastectomy with limited axillary disease and is influenced by patient, tumor, and treatment factors. Survival outcomes did not differ by axillary treatment for patients with LN micrometastases treated without RT or patients who received PMRT. SLND may be considered in select patients with ESBC and limited axillary disease undergoing mastectomy.

An updated meta-analysis on the effectiveness of preoperative prophylactic antibiotics in patients undergoing breast surgical procedures.

PubMed

Sajid, Muhammad S; Hutson, Kristian; Akhter, Naved; Kalra, Lorain; Rapisarda, Ignacio F; Bonomi, Ricardo

2012-01-01

To systematically analyze published randomized trials on the effectiveness of preoperative prophylactic antibiotics in patients undergoing breast surgical procedures. Trials on the effectiveness of preoperative prophylactic antibiotics in patients undergoing breast surgery were selected and analyzed to generate summated data (expressed as risk ratio [RR]) by using RevMan 5.0. Nine randomized controlled trials encompassing 3720 patients undergoing breast surgery were retrieved from the electronic databases. The antibiotics group comprised a total of 1857 patients and non-antibiotics group, 1863 patients. There was no heterogeneity [χ(2) = 7.61, d.f. = 7, p < 0.37; I(2) = 8%] amongst trials. Therefore, in the fixed-effects model (RR, 0.64; 95% CI, 0.50-0.83; z = 3.48; p < 0.0005), the use of preoperative prophylactic antibiotics in patients undergoing breast surgical procedures was statistically significant in reducing the incidence of surgical site infection (SSI). Furthermore, in the fixed-effects model (RR, 1.30; 95% CI, 0.89-1.90; z = 1.37; p < 0.17), adverse reactions secondary to the use of prophylactic antibiotics was not statistically significant between the two groups. Preoperative prophylactic antibiotics significantly reduce the risk of SSI after breast surgical procedures. The risk of adverse reactions from prophylactic antibiotic administration is not significant in these patients. Therefore, preoperative prophylactic antibiotics in breast surgery patients may be routinely administered. Further research is required, however, on risk stratification for SSI, timing and duration of prophylaxis, and the need for prophylaxis in patients undergoing breast reconstruction versus no reconstruction. © 2012 Wiley Periodicals, Inc.

Effects of a psychoeducation intervention on fear and anxiety about surgery: randomized trial in patients undergoing coronary artery bypass grafting.

PubMed

Shahmansouri, Nazilla; Janghorbani, Mohsen; Salehi Omran, Abbas; Karimi, Abbas Ali; Noorbala, Ahmad Ali; Arjmandi, Akram; Nikfam, Sepideh

2014-01-01

The aim of this study was to examine the impact of a brief psychoeducation group intervention on fear and anxiety in patients undergoing the coronary artery bypass grafting (CABG). Sixty consecutive patients undergoing CABG for the first time were recruited for a clinical trial and randomized into two groups. The control group received routine care. The study group received a brief psychoeducation group intervention combined with routine care. The psychoeducation session consisted of a discussion of fear and anxiety in a psychotherapeutic atmosphere and relaxation techniques. Fear was scored with the Bypass Grafting Fear Scale (BGFS) and anxiety was scored with the Spielberger State Inventory (STAI) Questionnaire. The BGFS and the STAI were given to the patients the day after hospital admission and a day before the operation to measure fear and anxiety. Fear scores decreased in the psychoeducation group. Of the 29 patients treated with psychoeducation, the mean (SD) fear score decreased from 4.6 (1.7) at baseline to 2.8 (1.2) before the operation (p < .001). In the 31 patients who received routine care, there was a nonsignificant trend from 3.7 (1.9) to 4.1 (2.1) (p > .05). The mean difference in fear score before the operation was significantly lower in the psychoeducation group than the routine care group (mean difference -1.3; 95% CI, -2.1, -.2; p < .05). There were no differences in anxiety scores before the operation between the psychoeducation and routine care groups. In patients undergoing CABG, adding psychoeducation to routine care had a significant positive effect on fear but not on anxiety scores. A larger study of psychoeducation in these patients is warranted to assess the efficacy of this intervention in greater detail.

Compressive cryotherapy versus cryotherapy alone in patients undergoing knee surgery: a meta-analysis.

PubMed

Song, Mingzhi; Sun, Xiaohong; Tian, Xiliang; Zhang, Xianbin; Shi, Tieying; Sun, Ran; Dai, Wei

2016-01-01

This study aims to conduct a meta-analysis to identify and compare the effectiveness of compressive cryotherapy and cryotherapy alone for patients undergoing knee surgery. Postoperative management is an important guarantee for the success of surgery. Cryotherapy and compression are two common nursing techniques after knee surgery, and are considered to be effective for postoperative clinical symptoms such as local pain and swelling. However, no previous meta-analyses have compared the effectiveness of compressive cryotherapy and cryotherapy alone in patients undergoing knee surgery. A meta-analysis of randomized controlled trials (RCTs). We conducted a search in MEDLINE (via Pubmed, 1990-2014), EMBASE (via Elsevier, 1990-2014), Cochrane Central Register of Controlled Trials (The Cochrane Library, 1990-2014), CINAHL (1990-2014) and China National Knowledge Infrastructure (1990-2014) databases for RCTs published in English and Chinese. The primary outcome measure of interest was visual analog scale and girth measure. Finally, a meta-analysis was carried out using RevMan 5.3. Among the 593 RCTs, 10 RCTs were selected and included into this study. These studies included 522 patients who underwent knee surgery. Patients who underwent compressive cryotherapy tended to have less pain than patients who underwent cryotherapy alone at POD2 and POD3, while compressive cryotherapy had a strong tendency towards less swelling over cryotherapy alone at POD1 and POD2. However, there was no significant difference between compressive cryotherapy and cryotherapy alone at the intermediate stage of rehabilitation after knee surgery. All adverse reactions were recorded in all included RCTs. Current evidence suggests that compressive cryotherapy is beneficial to patients undergoing knee surgery at the early rehabilitation stage. At the last stage, the effectiveness of compressive cryotherapy and cryotherapy alone were found to be similar.

Which goal for fluid therapy during colorectal surgery is followed by the best outcome: near-maximal stroke volume or zero fluid balance?

PubMed

Brandstrup, B; Svendsen, P E; Rasmussen, M; Belhage, B; Rodt, S Å; Hansen, B; Møller, D R; Lundbech, L B; Andersen, N; Berg, V; Thomassen, N; Andersen, S T; Simonsen, L

2012-08-01

We aimed to investigate whether fluid therapy with a goal of near-maximal stroke volume (SV) guided by oesophageal Doppler (ED) monitoring result in a better outcome than that with a goal of maintaining bodyweight (BW) and zero fluid balance in patients undergoing colorectal surgery. In a double-blinded clinical multicentre trial, 150 patients undergoing elective colorectal surgery were randomized to receive fluid therapy after either the goal of near-maximal SV guided by ED (Doppler, D group) or the goal of zero balance and normal BW (Zero balance, Z group). Stratification for laparoscopic and open surgery was performed. The postoperative fluid therapy was similar in the two groups. The primary endpoint was postoperative complications defined and divided into subgroups by protocol. Analysis was performed by intention-to-treat. The follow-up was 30 days. The trial had 85% power to show a difference between the groups. The number of patients undergoing laparoscopic or open surgery and the patient characteristics were similar between the groups. No significant differences between the groups were found for overall, major, minor, cardiopulmonary, or tissue-healing complications (P-values: 0.79; 0.62; 0.97; 0.48; and 0.48, respectively). One patient died in each group. No significant difference was found for the length of hospital stay [median (range) Z: 5.00 (1-61) vs D: 5.00 (2-41); P=0.206]. Goal-directed fluid therapy to near-maximal SV guided by ED adds no extra value to the fluid therapy using zero balance and normal BW in patients undergoing elective colorectal surgery.

Alpha-2 adrenergic agonists for the prevention of cardiac complications among adults undergoing surgery.

PubMed

Duncan, Dallas; Sankar, Ashwin; Beattie, W Scott; Wijeysundera, Duminda N

2018-03-06

The surgical stress response plays an important role on the pathogenesis of perioperative cardiac complications. Alpha-2 adrenergic agonists attenuate this response and may help prevent postoperative cardiac complications. To determine the efficacy and safety of α-2 adrenergic agonists for reducing mortality and cardiac complications in adults undergoing cardiac surgery and non-cardiac surgery. We searched CENTRAL (2017, Issue 4), MEDLINE (1950 to April Week 4, 2017), Embase (1980 to May 2017), the Science Citation Index, clinical trial registries, and reference lists of included articles. We included randomized controlled trials that compared α-2 adrenergic agonists (i.e. clonidine, dexmedetomidine or mivazerol) against placebo or non-α-2 adrenergic agonists. Included trials had to evaluate the efficacy and safety of α-2 adrenergic agonists for preventing perioperative mortality or cardiac complications (or both), or measure one or more relevant outcomes (i.e. death, myocardial infarction, heart failure, acute stroke, supraventricular tachyarrhythmia and myocardial ischaemia). Two authors independently assessed trial quality, extracted data and independently performed computer entry of abstracted data. We contacted study authors for additional information. Adverse event data were gathered from the trials. We evaluated included studies using the Cochrane 'Risk of bias' tool, and the quality of the evidence underlying pooled treatment effects using GRADE methodology. Given the clinical heterogeneity between cardiac and non-cardiac surgery, we analysed these subgroups separately. We expressed treatment effects as pooled risk ratios (RR) with 95% confidence intervals (CI). We included 47 trials with 17,039 participants. Of these studies, 24 trials only included participants undergoing cardiac surgery, 23 only included participants undergoing non-cardiac surgery and eight only included participants undergoing vascular surgery. The α-2 adrenergic agonist studied was clonidine in 21 trials, dexmedetomidine in 24 trials and mivazerol in two trials.In non-cardiac surgery, there was high quality evidence that α-2 adrenergic agonists led to a similar risk of all-cause mortality compared with control groups (1.3% with α-2 adrenergic agonists versus 1.7% with control; RR 0.80, 95% CI 0.61 to 1.04; participants = 14,081; studies = 16). Additionally, the risk of cardiac mortality was similar between treatment groups (0.8% with α-2 adrenergic agonists versus 1.0% with control; RR 0.86, 95% CI 0.60 to 1.23; participants = 12,525; studies = 5, high quality evidence). The risk of myocardial infarction was probably similar between treatment groups (RR 0.94, 95% CI 0.69 to 1.27; participants = 13,907; studies = 12, moderate quality evidence). There was no associated effect on the risk of stroke (RR 0.93, 95% CI 0.55 to 1.56; participants = 11,542; studies = 7; high quality evidence). Conversely, α-2 adrenergic agonists probably increase the risks of clinically significant bradycardia (RR 1.59, 95% CI 1.18 to 2.13; participants = 14,035; studies = 16) and hypotension (RR 1.24, 95% CI 1.03 to 1.48; participants = 13,738; studies = 15), based on moderate quality evidence.There was insufficient evidence to determine the effect of α-2 adrenergic agonists on all-cause mortality in cardiac surgery (RR 0.52, 95% CI 0.26 to 1.04; participants = 1947; studies = 16) and myocardial infarction (RR 1.01, 95% CI 0.43 to 2.40; participants = 782; studies = 8), based on moderate quality evidence. There was one cardiac death in the clonidine arm of a study of 22 participants. Based on very limited data, α-2 adrenergic agonists may have reduced the risk of stroke (RR 0.37, 95% CI 0.15 to 0.93; participants = 1175; studies = 7; outcome events = 18; low quality evidence). Conversely, α-2 adrenergic agonists increased the risk of bradycardia from 6.4% to 12.0% (RR 1.88, 95% CI 1.35 to 2.62; participants = 1477; studies = 10; moderate quality evidence), but their effect on hypotension was uncertain (RR 1.19, 95% CI 0.87 to 1.64; participants = 1413; studies = 9; low quality evidence).These results were qualitatively unchanged in subgroup analyses and sensitivity analyses. Our review concludes that prophylactic α-2 adrenergic agonists generally do not prevent perioperative death or major cardiac complications. For non-cardiac surgery, there is moderate-to-high quality evidence that these agents do not prevent death, myocardial infarction or stroke. Conversely, there is moderate quality evidence that these agents have important adverse effects, namely increased risks of hypotension and bradycardia. For cardiac surgery, there is moderate quality evidence that α-2 adrenergic agonists have no effect on the risk of mortality or myocardial infarction, and that they increase the risk of bradycardia. The quality of evidence was inadequate to draw conclusions regarding the effects of alpha-2 agonists on stroke or hypotension during cardiac surgery.

Impact of Moringa oleifera lam. Leaf powder supplementation versus nutritional counseling on the body mass index and immune response of HIV patients on antiretroviral therapy: a single-blind randomized control trial.

PubMed

Tshingani, Koy; Donnen, Philippe; Mukumbi, Henri; Duez, Pierre; Dramaix-Wilmet, Michèle

2017-08-22

To achieve effective antiretroviral therapy (ART) outcomes, adherence to an antiretroviral regimen and a good immunometabolic response are essential. Food insecurity can act as a real barrier to adherence to both of these factors. Many people living with human immunodeficiency virus (PLHIV) treated with ART in the Democratic Republic of the Congo (DRC) are faced with nutritional challenges. A significant proportion are affected by under nutrition, which frequently leads to therapeutic failure. Some HIV care facilities recommend supplementation with Moringa oleifera (M.O.) Lam. leaf powder to combat marginal and major nutritional deficiencies. This study aims to assess the impact of M.O. Lam. leaf powder supplementation compared to nutritional counseling on the nutritional and immune status of PLHIV treated with ART. A single-blind randomized control trial was carried out from May to September 2013 at an outpatient clinic for HIV-infected patients in Kinshasa (DRC). Sixty adult patients who were at stable HIV/AIDS clinical staging 2, 3 or 4 according to the World Health Organization (WHO), and were undergoing ART were recruited. After random allocation, 30 patients in the Moringa intervention group (MG) received the M.O. Lam. leaf powder daily over 6 months, and 30 in the control group (CG) received nutritional counseling over the same period. Changes in the body mass index (BMI) were measured monthly and biological parameters were measured upon admission and at the end of the study for the patients in both groups. The two study groups were similar in terms of long-term nutritional exposure, sociodemographic, socioeconomic, clinical, and biological features. At 6 months follow-up, patients in the MG exhibited a significantly greater increase in BMI and albumin levels than those in the CG. The interaction between the sociodemographic, clinical, and biological characteristics of patients in the two groups was not significant, with the exception of professional activity. Under medical supervision, M.O. Lam. leaf powder supplementation may represent a readily available and effective local solution to improve the nutritional intake and nutritional status of PLHIV undergoing ART. The study was retrospectively registered in the Pan African Clinical Trial Registry on 15 May 2015, no. PACTR201505001076143.

A randomized controlled clinical trial to evaluate blood pressure changes in patients undergoing extraction under local anesthesia with vasopressor use.

PubMed

Uzeda, Marcelo José; Moura, Brenda; Louro, Rafael Seabra; da Silva, Licínio Esmeraldo; Calasans-Maia, Mônica Diuana

2014-05-01

The control of hypertensive patients' blood pressure and heart rate using vasoconstrictors during surgical procedures under anesthesia is still a major concern in everyday surgical practice. This clinical trial aimed to evaluate the variation of blood pressure and heart rate in nonhypertensive and controlled hypertensive voluntary subjects undergoing oral surgery under local anesthesia with lidocaine hydrochloride and epinephrine at 1:100,000 (Alphacaine; DFL, Brazil), performed in the Oral Surgery Department, Dentistry School, Fluminense Federal University. In total, 25 voluntary subjects were divided into 2 groups: nonhypertensive (n = 15) and controlled hypertensives (n = 10). Blood pressure and heart rate were measured at 4 different times: T0, in the waiting room; T1, after placement of the surgical drapes; T2, 10 minutes after anesthesia injection; and T3, at the end of the surgical procedure. A statistically significant difference (P < 0.05) between the groups was found at times T0 and T2 for the systolic pressure but only at time T0 for the diastolic pressure. The assessment of the heart rate of both groups showed a statistically significant difference (P < 0.05) at time T1. An analysis of the employed anesthetic volume indicated no statistically significant difference (P > 0.05) between the amount administered to nonhypertensive and hypertensive subjects. It was concluded that the local anesthetics studied could safely be used in controlled hypertensive and nonhypertensive patients in compliance with the maximum recommended doses.

Double versus single cervical cerclage for patients with recurrent pregnancy loss: a randomized clinical trial.

PubMed

Zolghadri, Jaleh; Younesi, Masoumeh; Asadi, Nasrin; Khosravi, Dezire; Behdin, Shabnam; Tavana, Zohre; Ghaffarpasand, Fariborz

2014-02-01

To compare the effectiveness of the double cervical cerclage method versus the single method in women with recurrent second-trimester delivery. In this randomized clinical trial, we included 33 singleton pregnancies suffering from recurrent second-trimester pregnancy loss (≥2 consecutive fetal loss during second-trimester or with a history of unsuccessful procedures utilizing the McDonald method), due to cervical incompetence. Patients were randomly assigned to undergo either the classic McDonald method (n = 14) or the double cerclage method (n = 19). The successful pregnancy rate and gestational age at delivery was also compared between the two groups. The two study groups were comparable regarding their baseline characteristics. The successful pregnancy rate did not differ significantly between those who underwent the double cerclage method or the classic McDonald cerclage method (100% vs 85.7%; P = 0.172). In the same way, the preterm delivery rate (<34 weeks of gestation) was comparable between the two study groups (10.5% vs 35.7%; P = 0.106). Those undergoing the double cerclage method had longer gestational duration (37.2 ± 2.6 vs 34.3 ± 3.8 weeks; P = 0.016). The double cervical cerclage method seems to provide better cervical support, as compared with the classic McDonald cerclage method, in those suffering from recurrent pregnancy loss, due to cervical incompetence. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

Preventive Effect of Glycyrrhiza Glabra Extract on Oral Mucositis in Patients Under Head and Neck Radiotherapy: A Randomized Clinical Trial

PubMed Central

Najafi, Shamsolmolok; Koujan, Soraiya Ebrahimpour; Manifar, Soheila; Kharazifard, Mohammad Javad; Kidi, Saba

2017-01-01

Objectives: About two-thirds of cancer patients undergo radiotherapy. Oral mucositis represents a major complication of radiotherapy, causing morbidity and mortality and decreasing the quality of life of patients. This study aimed to assess the preventive effect of Glycyrrhiza aqueous extract on oral mucositis in cancer patients under head and neck radiotherapy. Materials and Methods: In this double-blind clinical trial, 37 head and neck cancer patients were divided into intervention (n=19) group receiving Glycyrrhiza aqueous extract and control (n=18) group receiving placebo. Patients in the test group used Glycyrrhiza aqueous extract topically twice a day from the first day of starting radiotherapy until the end of the second week. Patients were examined in the first day of radiotherapy for any type of wound before treatment and those with oral ulcers before radiotherapy were excluded from the study. The grade of mucositis was determined using the classification by the World Health Organization. ANCOVA was performed to assess any difference between the two groups with regard to oral mucosal irritation and wound size after the intervention while controlling for the covariates such as sex and age. Results: Significant differences were found in the maximum grade of mucositis and oral mucosal irritation between the intervention and control groups (P<0.001). Conclusions: This study showed that aqueous extract of Glycyrrhiza can be effective for decreasing the severity of oral mucositis in head and neck cancer patients undergoing radiotherapy. PMID:29296112

The effect of relaxation techniques on edema, anxiety and depression in post-mastectomy lymphedema patients undergoing comprehensive decongestive therapy: A clinical trial.

PubMed

Abbasi, Bahareh; Mirzakhany, Navid; Angooti Oshnari, Leila; Irani, Ashkan; Hosseinzadeh, Samaneh; Tabatabaei, Seyed Mehdi; Haghighat, Shahpar

2018-01-01

Lymphedema is sometimes accompanied by high degrees of anxiety and depression. This study aimed to assess the effects of relaxation techniques on the level of edema, anxiety and depression in women undergoing Comprehensive Decongestive Therapy (CDT). This clinical trial compared two treatment methods in 31 women with post-mastectomy lymphedema, including 15 cases who received CDT and 16 who received RCDT (Relaxation plus CDT). The edema volume, anxiety and depression scores were compared at the first and last sessions of the first phase of the treatment and six weeks afterwards. The edema, anxiety and depression scores were 63.6%, 54.1% and 65.5% in the RCDT group and 60.7%, 31.4% and 35.2% in the CDT group. There were significant differences between the two groups in terms of the reduction in depression (p = 0.024) and anxiety (p = 0.011) scores throughout the study. This significant relationship was due to the differences in the depression score in the 3rd and 9th weeks of the study between the two groups. Similarly, anxiety levels differed significantly between the two groups at the 9th week of the study (P = 0.013). Relaxation techniques reduced the anxiety and depression scores and the volume of edema in the patients with lymphedema. The addition of this intervention to the therapeutic package for lymphedema patients requires further studies in terms of cost-effectiveness.

Safety and efficacy of turoctocog alfa (NovoEight®) during surgery in patients with haemophilia A: results from the multinational guardian™ clinical trials

PubMed Central

Santagostino, E; Lentz, S R; Misgav, M; Brand, B; Chowdary, P; Savic, A; Kilinc, Y; Amit, Y; Amendola, A; Solimeno, L P; Saugstrup, T; Matytsina, I

2015-01-01

Recombinant factor VIII (rFVIII) products provide a safe and efficacious replacement therapy for prevention and treatment of bleeding episodes in patients with haemophilia A. The present investigations from the multinational, open-label guardian™ clinical trials assessed the haemostatic response of turoctocog alfa (NovoEight®), a rFVIII product, in patients with severe haemophilia A (FVIII ≤ 1%) undergoing surgery. All patients had a minimum of 50 exposure days to any FVIII product prior to surgery and no history of inhibitors. A total of 41 procedures (13 orthopaedic, 19 dental and 9 general) were performed in 33 patients aged 4–59 years. Of the 41 procedures, 15 were major surgeries in 13 patients and 26 were minor surgeries in 21 patients. The success rate for haemostatic response was 100% (success was defined as ‘excellent’ or ‘good’ haemostatic outcome). Turoctocog alfa consumption on the day of surgery ranged from 27 to 153 IU kg−1. The mean daily dose declined over time, while retaining adequate FVIII coverage as measured by trough levels. Overall, no safety issues were identified. No thrombotic events were observed and none of the patients developed FVIII inhibitors. In conclusion, the present results show that turoctocog alfa was effective in controlling blood loss by obtaining a sufficient haemostatic response in patients with severe haemophilia A undergoing surgery. PMID:25273984

Safety and efficacy of turoctocog alfa (NovoEight®) during surgery in patients with haemophilia A: results from the multinational guardian™ clinical trials.

PubMed

Santagostino, E; Lentz, S R; Misgav, M; Brand, B; Chowdary, P; Savic, A; Kilinc, Y; Amit, Y; Amendola, A; Solimeno, L P; Saugstrup, T; Matytsina, I

2015-01-01

Recombinant factor VIII (rFVIII) products provide a safe and efficacious replacement therapy for prevention and treatment of bleeding episodes in patients with haemophilia A. The present investigations from the multinational, open-label guardian(™) clinical trials assessed the haemostatic response of turoctocog alfa (NovoEight(®)), a rFVIII product, in patients with severe haemophilia A (FVIII ≤ 1%) undergoing surgery. All patients had a minimum of 50 exposure days to any FVIII product prior to surgery and no history of inhibitors. A total of 41 procedures (13 orthopaedic, 19 dental and 9 general) were performed in 33 patients aged 4-59 years. Of the 41 procedures, 15 were major surgeries in 13 patients and 26 were minor surgeries in 21 patients. The success rate for haemostatic response was 100% (success was defined as 'excellent' or 'good' haemostatic outcome). Turoctocog alfa consumption on the day of surgery ranged from 27 to 153 IU kg(-1). The mean daily dose declined over time, while retaining adequate FVIII coverage as measured by trough levels. Overall, no safety issues were identified. No thrombotic events were observed and none of the patients developed FVIII inhibitors. In conclusion, the present results show that turoctocog alfa was effective in controlling blood loss by obtaining a sufficient haemostatic response in patients with severe haemophilia A undergoing surgery. © 2014 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Rosa Damascena oil improved sexual function and testosterone in male patients with opium use disorder under methadone maintenance therapy-results from a double-blind, randomized, placebo-controlled clinical trial.

PubMed

Farnia, Vahid; Tatari, Faeze; Alikhani, Mostafa; Shakeri, Jalal; Taghizadeh, Moshen; Karbasizadeh, Hassan; Sadeghi Bahmani, Dena; Holsboer-Trachsler, Edith; Brand, Serge

2017-07-01

Some patients with opioid use disorder (OUD) are treated with methadone maintenance therapy (MMT). However, as with opioids, methadone has major side-effects; sexual dysfunction is a particularly distressing such effect. Rosa Damascena oil has been shown to reduce subjective sexual dysfunction in patients with major depressive disorders, but its influence on testosterone has not so far been tested. The aim of the present study was to investigate the influence of Rosa Damascena oil on sexual dysfunction and testosterone levels among male patients with OUD and undergoing MMT. A total of 50 male patients (mean age: 40 years) diagnosed with OUD and receiving MMT were randomly assigned either to the Rosa Damascena oil (drops) or a placebo condition. At baseline, and four and eight weeks later, patients completed questionnaires covering sexual and erectile function. Blood samples to assess testosterone levels were taken at baseline and eight weeks later on completion of the study. Over time sexual dysfunction decreased, and testosterone increased in the Rosa Damascena oil, but not in the placebo condition. Sexual dysfunction scores and testosterone levels were not consistently related. Results from this double-blind, randomized, and placebo-controlled clinical trial showed that Rosa Damascena oil improved sexual function and testosterone levels among males with OUD and undergoing MMT. Copyright © 2017 Elsevier B.V. All rights reserved.

Chest physiotherapy during immediate postoperative period among patients undergoing upper abdominal surgery: randomized clinical trial.

PubMed

Manzano, Roberta Munhoz; Carvalho, Celso Ricardo Fernandes de; Saraiva-Romanholo, Beatriz Mangueira; Vieira, Joaquim Edson

2008-09-01

Abdominal surgical procedures increase pulmonary complication risks. The aim of this study was to evaluate the effectiveness of chest physiotherapy during the immediate postoperative period among patients undergoing elective upper abdominal surgery. This randomized clinical trial was performed in the post-anesthesia care unit of a public university hospital. Thirty-one adults were randomly assigned to control (n = 16) and chest physiotherapy (n = 15) groups. Spirometry, pulse oximetry and anamneses were performed preoperatively and on the second postoperative day. A visual pain scale was applied on the second postoperative day, before and after chest physiotherapy. The chest physiotherapy group received treatment at the post-anesthesia care unit, while the controls did not. Surgery duration, length of hospital stay and postoperative pulmonary complications were gathered from patients' medical records. The control and chest physiotherapy groups presented decreased spirometry values after surgery but without any difference between them (forced vital capacity from 83.5 +/- 17.1% to 62.7 +/- 16.9% and from 95.7 +/- 18.9% to 79.0 +/- 26.9%, respectively). In contrast, the chest physiotherapy group presented improved oxygen-hemoglobin saturation after chest physiotherapy during the immediate postoperative period (p < 0.03) that did not last until the second postoperative day. The medical record data were similar between groups. Chest physiotherapy during the immediate postoperative period following upper abdominal surgery was effective for improving oxygen-hemoglobin saturation without increased abdominal pain. Breathing exercises could be adopted at post-anesthesia care units with benefits for patients.

Pharmacologic Approaches Against Advanced Glycation End Products (AGEs) in Diabetic Cardiovascular Disease.

PubMed

Nenna, Antonio; Nappi, Francesco; Avtaar Singh, Sanjeet Singh; Sutherland, Fraser W; Di Domenico, Fabio; Chello, Massimo; Spadaccio, Cristiano

2015-05-01

Advanced Glycation End-Products (AGEs) are signaling proteins associated to several vascular and neurological complications in diabetic and non-diabetic patients. AGEs proved to be a marker of negative outcome in both diabetes management and surgical procedures in these patients. The reported role of AGEs prompted the development of pharmacological inhibitors of their effects, giving rise to a number of both preclinical and clinical studies. Clinical trials with anti-AGEs drugs have been gradually developed and this review aimed to summarize most relevant reports. Evidence acquisition process was performed using PubMed and ClinicalTrials.gov with manually checked articles. Pharmacological approaches in humans include aminoguanidine, pyridoxamine, benfotiamine, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statin, ALT-711 (alagebrium) and thiazolidinediones. The most recent promising anti-AGEs agents are statins, alagebrium and thiazolidinediones. The role of AGEs in disease and new compounds interfering with their effects are currently under investigation in preclinical settings and these newer anti-AGEs drugs would undergo clinical evaluation in the next years. Compounds with anti-AGEs activity but still not available for clinical scenarios are ALT-946, OPB-9195, tenilsetam, LR-90, TM2002, sRAGE and PEDF. Despite most studies confirm the efficacy of these pharmacological approaches, other reports produced conflicting evidences; in almost any case, these drugs were well tolerated. At present, AGEs measurement has still not taken a precise role in clinical practice, but its relevance as a marker of disease has been widely shown; therefore, it is important for clinicians to understand the value of new cardiovascular risk factors. Findings from the current and future clinical trials may help in determining the role of AGEs and the benefits of anti-AGEs treatment in cardiovascular disease.

Biosimilars in Inflammatory Bowel Disease: Facts and Fears of Extrapolation.

PubMed

Ben-Horin, Shomron; Vande Casteele, Niels; Schreiber, Stefan; Lakatos, Peter Laszlo

2016-12-01

Biologic drugs such as infliximab and other anti-tumor necrosis factor monoclonal antibodies have transformed the treatment of immune-mediated inflammatory conditions such as Crohn's disease and ulcerative colitis (collectively known as inflammatory bowel disease [IBD]). However, the complex manufacturing processes involved in producing these drugs mean their use in clinical practice is expensive. Recent or impending expiration of patents for several biologics has led to development of biosimilar versions of these drugs, with the aim of providing substantial cost savings and increased accessibility to treatment. Biosimilars undergo an expedited regulatory process. This involves proving structural, functional, and biological biosimilarity to the reference product (RP). It is also expected that clinical equivalency/comparability will be demonstrated in a clinical trial in one (or more) sensitive population. Once these requirements are fulfilled, extrapolation of biosimilar approval to other indications for which the RP is approved is permitted without the need for further clinical trials, as long as this is scientifically justifiable. However, such justification requires that the mechanism(s) of action of the RP in question should be similar across indications and also comparable between the RP and the biosimilar in the clinically tested population(s). Likewise, the pharmacokinetics, immunogenicity, and safety of the RP should be similar across indications and comparable between the RP and biosimilar in the clinically tested population(s). To date, most anti-tumor necrosis factor biosimilars have been tested in trials recruiting patients with rheumatoid arthritis. Concerns have been raised regarding extrapolation of clinical data obtained in rheumatologic populations to IBD indications. In this review, we discuss the issues surrounding indication extrapolation, with a focus on extrapolation to IBD. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Efficacy of Periarticular Injection With a Long-Acting Local Analgesic in Joint Arthroplasty.

PubMed

Barrington, John W

2015-10-01

Attention to patient satisfaction is critical in today's health care environment-satisfaction surveys inform the development of hospital performance standards and can influence an institution's rankings and reimbursement. The effectiveness of postoperative pain management can affect clinical outcomes and also influence the patient's perception of the overall surgical experience. Ample clinical- trial data now exist that demonstrate the benefits of periarticular injections as part of a multimodal regimen in patients undergoing joint arthroplasty. One option that surgeons now use widely is bupivacaine liposome injectable suspension (EXPAREL®, Pacira Pharmaceuticals, Inc), a long-acting local analgesic that the orthopedic surgeon can administer intraoperatively. The US Food and Drug Administration has approved liposomal bupivacaine for injection into the surgical site to produce postsurgical analgesia. The safety and efficacy of liposomal bupivacaine has been demonstrated in clinical studies in multiple types of surgical procedure, including double-blind, randomized, controlled clinical trials that involved over 1300 patients. In a case-control study comparing clinical and economic parameters before and after the introduction of liposomal bupivacaine as a component of the multimodal perioperative pain regimen for total joint arthroplasty, liposomal bupivacaine provided improved overall pain scores, an increase in patients reporting a pain score of 0, increased patient satisfaction, decreased length of stay, and a decrease in overall costs.

Sentinel Lymph Nodes for Breast Carcinoma: An Update on Current Practice

PubMed Central

Maguire, Aoife; Brogi, Edi

2016-01-01

Sentinel lymph node (SLN) biopsy has been established as the standard of care for axillary staging in patients with invasive breast carcinoma and clinically negative lymph nodes (cN0). Historically, all patients with a positive SLN underwent axillary lymph node dissection (ALND). The ACOSOG Z0011 trial showed that women with T1-T2 disease and cN0 who undergo breast conserving surgery and whole-breast radiotherapy can safely avoid ALND. The main goal of SLN examination should be to detect all macrometastases (>2mm). Gross sectioning SLNs at 2 mm intervals and microscopic examination of one H&E-stained section from each SLN block is the preferred method of pathologic evaluation of SLNs. The role and timing of SLN biopsy for patients having neoadjuvant chemotherapy is controversial and continues to be explored in clinical trials. SLN biopsies from patients with invasive breast carcinoma who have received neoadjuvant chemotherapy pose particular challenges for pathologists. PMID:26768036

The use of novel oral anticoagulants for thromboprophylaxis after elective major orthopedic surgery

PubMed Central

Rachidi, Saleh; Aldin, Ehab Saad; Greenberg, Charles; Sachs, Barton; Streiff, Michael; Zeidan, Amer M

2014-01-01

Venous thromboembolism is a common cause of morbidity and mortality among patients undergoing elective orthopedic surgery. Due to the high incidence of venous thromboembolism in this setting, perioperative anticoagulation is the recommended approach for thromboprophylaxis. Low molecular weight heparin (LMWH), fondaparinux and warfarin are the agents commonly used for thromboprophylaxis. The well-recognized limitations of warfarin and the inconvenience and discomfort associated with the subcutaneous administration of low molecular weight heparin and fondaparinux inspired intense investigation to develop novel oral anticoagulants (NOACs) with more predictable pharmacokinetics, fewer drug interactions and no need for regular laboratory monitoring. Three NOACs have been demonstrated to be effective for thromboprophylaxis after total hip arthroplasty (THA) and total knee arthroplasty (TKA) in large randomized controlled trials. Here we review the pharmacology of rivaroxaban, dabigatran, and apixaban, summarize the major clinical trials of these agents in thromboprophylaxis after THA and TKA, and discuss the clinical factors to be considered by providers when selecting a NOAC for their patients. PMID:24219550

[Assertiveness and peripheral intravenous catheters dwell time with ultrasonography-guided insertion in children and adolescents].

PubMed

Avelar, Ariane Ferreira Machado; Peterlini, Maria Angélica Sorgini; da Pedreira, Mavilde Luz Gonçalves

2013-06-01

Randomized controlled trial which aimed to verify whether the use of vascular ultrasound (VUS) increases assertiveness in the use of peripheral venous catheter in children, and the catheter dwell time, when compared to traditional puncture. Data were collected after approval of theethical merit. Children and adolescents undergoing VUS-guided peripheral intravenous (GVUS) or puncture guided by clinical assessment of the venous conditions(CG) were included in the study. Significance level was set at p< or =0.05. The sample was composed of 382 punctures, 188 (49.2%) in VUS Gand 194 (50.8%) in CG, performed in 335 children. Assertiveness was found in 73 (71.6%) GVUS catheters and in 84(71.8%) of the CG (p=0.970), and catheter dwell time presented a median of less than one day in both groups (p=0.121), showing nostatistically significant difference. VUS did not significantly influence the results of the dependent variables investigated. ClinicalTrials.govNCT00930254.

The Status of Contemporary Image-Guided Modalities in Oncologic Surgery

PubMed Central

Rosenthal, Eben L; Warram, Jason M; Bland, Kirby I; Zinn, Kurt R

2014-01-01

Surgical resection remains the cornerstone of therapy for patients with early stage solid malignancies and more than half of all cancer patients undergo surgery each year. The technical ability of the surgeon to obtain clear surgical margins at the initial resection remains crucial to improve overall survival and long-term morbidity. Current resection techniques are largely based on subjective and subtle changes associated with tissue distortion by invasive cancer. As a result, positive surgical margins occur in a significant portion of tumor resections, which is directly correlated with a poor outcome. A variety of cancer imaging techniques have been adapted or developed for intraoperative surgical guidance that have been shown to improve functional and oncologic outcomes in randomized clinical trials. There are also a large number of novel, cancer-specific contrast agents that are in early stage clinical trials and preclinical development that demonstrate significant promise to improve real-time detection of subclinical cancer in the operative setting. PMID:25599326

MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis.

PubMed

Kasivisvanathan, Veeru; Rannikko, Antti S; Borghi, Marcelo; Panebianco, Valeria; Mynderse, Lance A; Vaarala, Markku H; Briganti, Alberto; Budäus, Lars; Hellawell, Giles; Hindley, Richard G; Roobol, Monique J; Eggener, Scott; Ghei, Maneesh; Villers, Arnauld; Bladou, Franck; Villeirs, Geert M; Virdi, Jaspal; Boxler, Silvan; Robert, Grégoire; Singh, Paras B; Venderink, Wulphert; Hadaschik, Boris A; Ruffion, Alain; Hu, Jim C; Margolis, Daniel; Crouzet, Sébastien; Klotz, Laurence; Taneja, Samir S; Pinto, Peter; Gill, Inderbir; Allen, Clare; Giganti, Francesco; Freeman, Alex; Morris, Stephen; Punwani, Shonit; Williams, Norman R; Brew-Graves, Chris; Deeks, Jonathan; Takwoingi, Yemisi; Emberton, Mark; Moore, Caroline M

2018-05-10

Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P<0.001). The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .).

Health-related quality of life from a prospective randomised clinical trial of robot-assisted laparoscopic vs open radical cystectomy.

PubMed

Messer, Jamie C; Punnen, Sanoj; Fitzgerald, John; Svatek, Robert; Parekh, Dipen J

2014-12-01

To compare health-related quality-of-life (HRQoL) outcomes for robot-assisted laparoscopic radical cystectomy (RARC) with those of traditional open radical cystectomy (ORC) in a prospective randomised fashion. This was a prospective randomised clinical trial evaluating the HRQoL for ORC vs RARC in consecutive patients from July 2009 to June 2011. We administered the Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index questionnaire, validated to assess HRQoL, preoperatively and then at 3, 6, 9 and 12 months postoperatively. Scores for each domain and total scores were compared in terms of deviation from preoperative values for both the RARC and the ORC cohorts. Multivariate linear regression was used to assess the association between the type of radical cystectomy and HRQoL. At the time of the study, 47 patients had met the inclusion criteria, with 40 patients being randomised for analysis. The cohorts consisted of 20 patients undergoing ORC and 20 undergoing RARC, who were balanced with respect to baseline demographic and clinical features. Univariate analysis showed a return to baseline scores at 3 months postoperatively in all measured domains with no statistically significant difference among the various domains between the RARC and the ORC cohorts. Multivariate analysis showed no difference in HRQoL between the two approaches in any of the various domains, with the exception of a slightly higher physical well-being score in the RARC group at 6 months. There were no significant differences in the HRQoL outcomes between ORC and RARC, with a return of quality of life scores to baseline scores 3 months after radical cystectomy in both cohorts. © 2014 The Authors. BJU International © 2014 BJU International.

Clinical benefit of drugs targeting mitochondrial function as an adjunct to reperfusion in ST-segment elevation myocardial infarction: A meta-analysis of randomized clinical trials.

PubMed

Campo, Gianluca; Pavasini, Rita; Morciano, Giampaolo; Lincoff, A Michael; Gibson, C Michael; Kitakaze, Masafumi; Lonborg, Jacob; Ahluwalia, Amrita; Ishii, Hideki; Frenneaux, Michael; Ovize, Michel; Galvani, Marcello; Atar, Dan; Ibanez, Borja; Cerisano, Giampaolo; Biscaglia, Simone; Neil, Brandon J; Asakura, Masanori; Engstrom, Thomas; Jones, Daniel A; Dawson, Dana; Ferrari, Roberto; Pinton, Paolo; Ottani, Filippo

2017-10-01

To perform a systematic review and meta-analysis of randomized clinical trials (RCT) comparing the effectiveness of drugs targeting mitochondrial function vs. placebo in patients with ST-segment elevation myocardial infarction (STEMI) undergoing mechanical coronary reperfusion. Inclusion criteria: RCTs enrolling STEMI patients treated with primary percutaneous coronary intervention (PCI) and comparing drugs targeting mitochondrial function vs. placebo. Odds ratios (OR) were computed from individual studies and pooled with random-effect meta-analysis. Fifteen studies were identified involving 5680 patients. When compared with placebo, drugs targeting mitochondrial component/pathway were not associated with significant reduction of cardiovascular and all-cause mortality (OR 0.9, 95% CI 0.7-1.17 and OR 0.92, 95% CI 0.69-1.23, respectively). However, these agents significantly reduced hospital admission for heart failure (HF) (OR 0.64; 95% CI 0.45-0.92) and increased left ventricular ejection fraction (LVEF) (OR 1.44; 95% CI 1.15-1.82). After analysis for subgroups according to the mechanism of action, drugs with direct/selective action did not reduce any outcome. Conversely, those with indirect/unspecific action showed a significant effect on cardiovascular mortality (0.65, 95% CI 0.46-0.92), all-cause mortality (OR 0.69, 95% CI 0.52-0.92), hospital readmission for HF (OR 0.41, 95% CI 0.28-0.6) and LVEF (OR 1.49, 95% CI 1.09-2.05). Administration of drugs targeting mitochondrial function in STEMI patients undergoing primary PCI appear to have no effect on mortality, but may reduce hospital readmission for HF. The drugs with a broad-spectrum mechanism of action seem to be more effective in reducing adverse events. Copyright © 2017 Elsevier B.V. All rights reserved.

Recombinant luteinizing hormone priming in early follicular phase for women undergoing in vitro fertilization: systematic review and meta-analysis.

PubMed

Hu, Linli; Bu, Zhiqin; Wang, Keyan; Sun, Yingpu

2014-04-01

To investigate the effect of recombinant human luteinizing hormone supplementation (rLH priming) during the early follicular phase on in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) outcomes. In order to evaluate available evidence regarding the efficacy of rLH priming in IVF/ICSI procedures, a systematic review and meta-analysis was preformed. Searches were conducted on MEDLINE®, EMBASE and the Cochrane Database of Clinical Trials without language limitation, but were restricted to randomized controlled trials (RCTs). Three RCTs including 346 patients were included in this meta-analysis, which demonstrated that rLH priming did not increase ongoing pregnancy rate. Although less recombinant follicle-stimulating hormone (rFSH) was required and the oestradiol level was higher on the day of human chorionic gonadotropin administration in the rLH priming group, the numbers of oocytes retrieved and embryos produced were comparable between patients treated with rLH priming and those treated with rFSH alone. This systematic review and meta-analysis has demonstrated that at present there is insufficient evidence that patients undergoing IVF/ICSI may benefit from rLH priming during the early follicular phase.

The pregnancy outcome of progestin-primed ovarian stimulation using 4 versus 10 mg of medroxyprogesterone acetate per day in infertile women undergoing in vitro fertilisation: a randomised controlled trial.

PubMed

Dong, J; Wang, Y; Chai, W R; Hong, Q Q; Wang, N L; Sun, L H; Long, H; Wang, L; Tian, H; Lyu, Q F; Lu, X F; Chen, Q J; Kuang, Y P

2017-06-01

To investigate the clinical outcome and endocrinological characteristics of progestin-primed ovarian stimulation (PPOS) using 4 versus 10 mg of medroxyprogesterone acetate (MPA) per day in infertile women with normal ovary reserve. A randomised parallel controlled trial. Tertiary-care academic medical centre. A cohort of 300 infertile women undergoing in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) treatment. Human menopausal gonadotropin (hMG; 225 iu per day) and MPA (group A, 10 mg per day; group B, 4 mg per day) were started simultaneously from cycle day 3 onwards. Ovulation was co-triggered by human chorionic gonadotropin (hCG; 1000 iu) and gonadotropin-releasing hormone agonist (GnRH agonist; 0.1 mg) when dominant follicles matured. Viable embryos were cryopreserved for later frozen embryo transfer (FET) in both groups. The primary outcome measure was the number of oocytes retrieved. Secondary outcomes included the incidence of a premature surge in luteinising hormone (LH), the number of viable embryos, and clinical pregnancy outcomes. The number of oocytes retrieved and viable embryos were similar between two groups (9.8 ± 6.3 versus 9.6 ± 5.9; 4.2 ± 2.6 versus 3.7 ± 3.0; P > 0.05). No significant difference was found in clinical pregnancy rate (58.0 versus 48.7%) and live birth rate per participant (48.7 versus 42.0%; P > 0.05). No premature LH surge and ovarian hyperstimulation syndrome (OHSS) occurred in either group. Progestin-primed ovarian stimulation (PPOS) using 4 or 10 mg of MPA per day was comparable in terms of the number of oocytes retrieved and pregnancy outcome after FET. The administration of 4 mg of MPA per day was sufficient to prevent an untimely LH rise in women undergoing IVF/ICSI treatment. An RCT confirmed similar pregnancy outcome in P-primed ovarian stimulation with a daily dose of 4 or 10 mg MPA. © 2017 Royal College of Obstetricians and Gynaecologists.

Enhanced labile plasma iron and outcome in acute myeloid leukaemia and myelodysplastic syndrome after allogeneic haemopoietic cell transplantation (ALLIVE): a prospective, multicentre, observational trial.

PubMed

Wermke, Martin; Eckoldt, Julia; Götze, Katharina S; Klein, Stefan A; Bug, Gesine; de Wreede, Liesbeth C; Kramer, Michael; Stölzel, Friedrich; von Bonin, Malte; Schetelig, Johannes; Laniado, Michael; Plodeck, Verena; Hofmann, Wolf-Karsten; Ehninger, Gerhard; Bornhäuser, Martin; Wolf, Dominik; Theurl, Igor; Platzbecker, Uwe

2018-05-01

The effect of systemic iron overload on outcomes after allogeneic haemopoietic cell transplantation (HCT) has been a matter of substantial debate. We aimed to investigate the predictive value of both stored (MRI-derived liver iron content) and biologically active iron (enhanced labile plasma iron; eLPI) on post-transplantation outcomes in patients with acute myeloid leukaemia or myelodysplastic syndrome undergoing allogenic HCT. The prospective, multicentre, observational, ALLogeneic Iron inVEstigators (ALLIVE) trial recruited patients at five centres in Germany. We enrolled patients with acute myeloid leukaemia or myelodysplastic syndrome undergoing allogeneic HCT. Patients underwent cytotoxic conditioning for a median of 6 days (IQR 6-7) before undergoing allogeneic HCT and were followed up for up to 1 year (±3 months) post-transplantation. eLPI was measured in serum samples with the FeROS eLPI kit (Aferrix, Tel-Aviv, Israel) and values greater than 0·4 μmol/L were considered to represent raised eLPI. Liver iron content was measured by MRI. The primary endpoints were the quantitative delineation of eLPI dynamics during allogeneic HCT and the correlation coefficient between liver iron content before HCT and dynamic eLPI (eLPI dyn ; maximum eLPI minus baseline eLPI). All patients with available data were included in all analyses. This is the final analysis of this completed trial, which is registered with ClinicalTrials.gov, number NCT01746147. Between Dec 13, 2012, and Dec 23, 2014, 112 patients underwent allogeneic HCT. Liver iron content before allogeneic HCT was not significantly correlated with eLPI dyn (ρ=0·116, p=0·22). Serum eLPI concentrations rapidly increased during conditioning, and most (79 [73%] of 108) patients had raised eLPI by the day of transplantation. Patients with a pretransplant liver iron content greater than or equal to 125 μmol/g had an increased incidence of non-relapse mortality (20%, 95% CI 14-26) compared with those with lower concentrations (7%, 2-12; p=0·039) at day 100. Patients who had raised eLPI at baseline also had a significantly increased incidence of non-relapse mortality at day 100 (33%, 15-52) compared with those who had normal eLPI at baseline (7%, 2-13; p=0·00034). eLPI is a possible biological mediator of iron-related toxicity. Peritransplantation eLPI-scavenging strategies could be explored in prospective interventional clinical trials for patients with systemic iron overload. The Technical University of Dresden and Novartis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Safety and efficacy of defibrotide for the treatment of severe hepatic veno-occlusive disease

PubMed Central

Ho, Vincent T.; Giralt, Sergio; Arai, Sally; Mineishi, Shin; Cutler, Corey; Antin, Joseph H.; Stavitzski, Nicole; Niederwieser, Dietger; Holler, Ernst; Carreras, Enric; Soiffer, Robert

2012-01-01

Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome, is a potentially life-threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem-cell transplantation (SCT). VOD may occur in up to 62% of patients undergoing SCT, with onset generally within the first month after SCT. In severe cases, 100-day mortality is in excess of 80%. Current management consists of best supportive care, with no agents to date approved for treatment in the USA or the EU. Defibrotide, a polydisperse oligonucleotide, has been shown in phase II and III trials to improve complete response and survival in patients undergoing SCT with severe VOD. This article reviews our current understanding of VOD, and examines recent clinical findings on defibrotide for the treatment and prophylaxis of VOD. PMID:23606935

Calcium and Vitamin D Supplementation and Loss of Bone Mineral Density in Women Undergoing Breast Cancer Therapy

PubMed Central

Datta, Mridul; Schwartz, Gary G.

2013-01-01

An unintended consequence of breast cancer therapies is an increased risk of osteoporosis due to accelerated bone loss. We conducted a systematic review of calcium and/or vitamin D (Ca±D) supplementation trials for maintaining bone mineral density (BMD) in women with breast cancer using the “before-after” data from the Ca±D supplemented comparison group of trials evaluating the effect of drugs such as bisphosphonates on BMD. Whether Ca±D supplements increase BMD in women undergoing breast cancer therapy has never been tested against an unsupplemented control group. However, results from 16 trials indicate that the Ca±D doses tested (500-1500 mg calcium; 200-1000 IU vitamin D) were inadequate to prevent BMD loss in these women. Cardiovascular disease is the main cause of mortality in women with breast cancer. Because calcium supplements may increase cardiovascular disease risk, future trials should evaluate the safety and efficacy of Ca±D supplementation in women undergoing breast cancer therapy. PMID:23932583

Manufacture of Clinical-Grade CD19-Specific T Cells Stably Expressing Chimeric Antigen Receptor Using Sleeping Beauty System and Artificial Antigen Presenting Cells

PubMed Central

Singh, Harjeet; Figliola, Matthew J.; Dawson, Margaret J.; Olivares, Simon; Zhang, Ling; Yang, Ge; Maiti, Sourindra; Manuri, Pallavi; Senyukov, Vladimir; Jena, Bipulendu; Kebriaei, Partow; Champlin, Richard E.; Huls, Helen; Cooper, Laurence J. N.

2013-01-01

Adoptive transfer of T cells expressing a CD19-specific chimeric antigen receptor (CAR) is being evaluated in multiple clinical trials. Our current approach to adoptive immunotherapy is based on a second generation CAR (designated CD19RCD28) that signals through a CD28 and CD3-ζ endodomain. T cells are electroporated with DNA plasmids from the Sleeping Beauty (SB) transposon/transposase system to express this CAR. Stable integrants of genetically modified T cells can then be retrieved when co-cultured with designer artificial antigen presenting cells (aAPC) in the presence of interleukin (IL)-2 and 21. Here, we reveal how the platform technologies of SB-mediated transposition and CAR-dependent propagation on aAPC were adapted for human application. Indeed, we have initiated clinical trials in patients with high-risk B-lineage malignancies undergoing autologous and allogeneic hematopoietic stem-cell transplantation (HSCT). We describe the process to manufacture clinical grade CD19-specific T cells derived from healthy donors. Three validation runs were completed in compliance with current good manufacturing practice for Phase I/II trials demonstrating that by 28 days of co-culture on γ-irradiated aAPC ∼1010 T cells were produced of which >95% expressed CAR. These genetically modified and propagated T cells met all quality control testing and release criteria in support of infusion. PMID:23741305

Idarucizumab (Praxbind) Formulary Review.

PubMed

Buchheit, Jessica; Reddy, Prabashni; Connors, Jean M

2016-09-01

Idarucizumab (Praxbind), a humanized monoclonal antibody fragment was granted accelerated approval from the Food and Drug Administration in October 2015 as the first agent to reverse the effects of a novel oral anticoagulant. The drug is indicated for dabigatran reversal in patients requiring emergency surgery/urgent procedures or with life-threatening or uncontrolled bleeding. In a randomized study with healthy volunteers, compared with placebo, idarucizumab reduced the clotting times for all tests assays (assessed pre-, end of-, and 24 hours after infusion), while the results for the placebo group remained unchanged. Another randomized clinical trial assessed the safety and efficacy of idarucizumab in patients with either overt bleeding or undergoing emergency surgery where hemostasis was required. This study is ongoing, but preliminary results showed reversal efficacy demonstrated a reasonable safety profile from the time of the infusion to 90 days after. The wholesale acquisition cost of two 2.5 g vials of idarucizumab is currently $3482.50. To treat 10 or 20 patients per year with a single 5 g dose is estimated to cost $34,825 and $69,650, respectively. In the clinical trial described above, approximately 20% of patients required a second dose, which would further increase the cost of use. In this formulary review for a health system's pharmacy and therapeutics committee, idarucizumab clinical trials and medication package insert were summarized and, after consulting with clinical experts from our institutions, practical recommendations for use were generated to ensure appropriate and safe use of this agent.

Advances in MRSA drug discovery: where are we and where do we need to be?

PubMed Central

Kurosu, Michio; Siricilla, Shajila; Mitachi, Katsuhiko

2013-01-01

Introduction Methicillin-resistant Staphylococcus aureus (MRSA) have been on the increase during the past decade, due to the steady growth of the elderly and immunocompromised patients, and the emergence of multi-drug-resistant (MDR) bacterial strains. Although, only a limited number of anti-MRSA drugs are available, a number of different combination antimicrobial drug regimens have been used to treat serious MRSA infections. Thus, addition of several new antistaphylococcal drugs into clinical practice should broaden therapeutic options. Because MRSA is one of the most common and problematic bacteria associated with increasing antimicrobial resistance, continuous efforts on discovery of lead compounds as well as development of alternative therapies and faster diagnostics to ensure effective antistaphylococcal therapy are required. Areas covered This article summarizes the FDA approved drugs to treat MRSA infections, the drugs in clinical trials, and the drug leads for MRSA and related Gram-positive bacterial infections. In addition, the mode of action of antistaphylococcal molecules and resistant mechanisms of some molecules are briefly discussed. Expert opinion The number of pipeline drugs presently undergoing clinical trials is not particularly encouraging. There are limited and rather expensive therapeutic options for the infections by MRSA in the critically ill. This review article provides an update on antistaphylococcal drugs in clinical trials and antibacterial molecules effective against Gram-positive bacteria including MRSA. The structural and biological information of antibacterials summarized here are very useful for designing drug leads to develop into new anti-MRSA drugs. PMID:23829425

Antibiotic prophylaxis for the prevention of methicillin-resistant Staphylococcus aureus (MRSA) related complications in surgical patients.

PubMed

Gurusamy, Kurinchi Selvan; Koti, Rahul; Wilson, Peter; Davidson, Brian R

2013-08-19

Risk of methicillin-resistant Staphylococcus aureus (MRSA) infection after surgery is generally low, but affects up to 33% of patients after certain types of surgery. Postoperative MRSA infection can occur as surgical site infections (SSIs), chest infections, or bloodstream infections (bacteraemia). The incidence of MRSA SSIs varies from 1% to 33% depending upon the type of surgery performed and the carrier status of the individuals concerned. The optimal prophylactic antibiotic regimen for the prevention of MRSA after surgery is not known. To compare the benefits and harms of all methods of antibiotic prophylaxis in the prevention of postoperative MRSA infection and related complications in people undergoing surgery. In March 2013 we searched the following databases: The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL); Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library); NHS Economic Evaluation Database (The Cochrane Library); Health Technology Assessment (HTA) Database (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We included only randomised controlled trials (RCTs) that compared one antibiotic regimen used as prophylaxis for SSIs (and other postoperative infections) with another antibiotic regimen or with no antibiotic, and that reported the methicillin resistance status of the cultured organisms. We did not limit our search for RCTs by language, publication status, publication year, or sample size. Two review authors independently identified the trials for inclusion in the review, and extracted data. We calculated the risk ratio (RR) with 95% confidence intervals (CI) for comparing binary outcomes between the groups and planned to calculated the mean difference (MD) with 95% CI for comparing continuous outcomes. We planned to perform meta-analysis using both a fixed-effect model and a random-effects model. We performed intention-to-treat analysis whenever possible. We included 12 RCTs, with 4704 participants, in this review. Eleven trials performed a total of 16 head-to-head comparisons of different prophylactic antibiotic regimens. Antibiotic prophylaxis was compared with no antibiotic prophylaxis in one trial. All the trials were at high risk of bias. With the exception of one trial in which all the participants were positive for nasal carriage of MRSA or had had previous MRSA infections, it does not appear that MRSA was tested or eradicated prior to surgery; nor does it appear that there was high prevalence of MRSA carrier status in the people undergoing surgery.There was no sufficient clinical similarity between the trials to perform a meta-analysis. The overall all-cause mortality in four trials that reported mortality was 14/1401 (1.0%) and there were no significant differences in mortality between the intervention and control groups in each of the individual comparisons. There were no antibiotic-related serious adverse events in any of the 561 people randomised to the seven different antibiotic regimens in four trials (three trials that reported mortality and one other trial). None of the trials reported quality of life, total length of hospital stay or the use of healthcare resources. Overall, 221/4032 (5.5%) people developed SSIs due to all organisms, and 46/4704 (1.0%) people developed SSIs due to MRSA.In the 15 comparisons that compared one antibiotic regimen with another, there were no significant differences in the proportion of people who developed SSIs. In the single trial that compared an antibiotic regimen with placebo, the proportion of people who developed SSIs was significantly lower in the group that received antibiotic prophylaxis with co-amoxiclav (or cefotaxime if allergic to penicillin) compared with placebo (all SSI: RR 0.26; 95% CI 0.11 to 0.65; MRSA SSI RR 0.05; 95% CI 0.00 to 0.83). In two trials that reported MRSA infections other than SSI, 19/478 (4.5%) people developed MRSA infections including SSI, chest infection and bacteraemia. There were no significant differences in the proportion of people who developed MRSA infections at any body site in these two comparisons. Prophylaxis with co-amoxiclav decreases the proportion of people developing MRSA infections compared with placebo in people without malignant disease undergoing percutaneous endoscopic gastrostomy insertion, although this may be due to decreasing overall infection thereby preventing wounds from becoming secondarily infected with MRSA. There is currently no other evidence to suggest that using a combination of multiple prophylactic antibiotics or administering prophylactic antibiotics for an increased duration is of benefit to people undergoing surgery in terms of reducing MRSA infections. Well designed RCTs assessing the clinical effectiveness of different antibiotic regimens are necessary on this topic.

Effect of Use of a Bougie vs Endotracheal Tube and Stylet on First-Attempt Intubation Success Among Patients With Difficult Airways Undergoing Emergency Intubation: A Randomized Clinical Trial.

PubMed

Driver, Brian E; Prekker, Matthew E; Klein, Lauren R; Reardon, Robert F; Miner, James R; Fagerstrom, Erik T; Cleghorn, Mitchell R; McGill, John W; Cole, Jon B

2018-05-16

The tracheal tube introducer, known as the bougie, is typically used to aid tracheal intubation in poor laryngoscopic views or after intubation attempts fail. The effect of routine bougie use on first-attempt intubation success is unclear. To compare first attempt intubation success facilitated by the bougie vs the endotracheal tube + stylet. The Bougie Use in Emergency Airway Management (BEAM) trial was a randomized clinical trial conducted from September 2016 through August 2017 in the emergency department at Hennepin County Medical Center, an urban, academic department in Minneapolis, Minnesota, where emergency physicians perform all endotracheal intubations. Included patients were 18 years and older who were consecutively admitted to the emergency department and underwent emergency orotracheal intubation with a Macintosh laryngoscope blade for respiratory arrest, difficulty breathing, or airway protection. Patients were randomly assigned to undergo the initial intubation attempt facilitated by bougie (n = 381) or endotracheal tube + stylet (n = 376). The primary outcome was first-attempt intubation success in patients with at least 1 difficult airway characteristic (body fluids obscuring the laryngeal view, airway obstruction or edema, obesity, short neck, small mandible, large tongue, facial trauma, or the need for cervical spine immobilization). Secondary outcomes were first-attempt success in all patients, first-attempt intubation success without hypoxemia, first-attempt duration, esophageal intubation, and hypoxemia. Among 757 patients who were randomized (mean age, 46 years; women, 230 [30%]), 757 patients (100%) completed the trial. Among the 380 patients with at least 1 difficult airway characteristic, first-attempt intubation success was higher in the bougie group (96%) than in the endotracheal tube + stylet group (82%) (absolute between-group difference, 14% [95% CI, 8% to 20%]). Among all patients, first-attempt intubation success in the bougie group (98%) was higher than the endotracheal tube + stylet group (87%) (absolute difference, 11% [95% CI, 7% to 14%]). The median duration of the first intubation attempt (38 seconds vs 36 seconds) and the incidence of hypoxemia (13% vs 14%) did not differ significantly between the bougie and endotracheal tube + stylet groups. In this emergency department, use of a bougie compared with an endotracheal tube + stylet resulted in significantly higher first-attempt intubation success among patients undergoing emergency endotracheal intubation. However, these findings should be considered provisional until the generalizability is assessed in other institutions and settings. clinicaltrials.gov Identifier: NCT02902146.

Efficacy and safety of Ding-Kun-Dan for female infertility patients with predicted poor ovarian response undergoing in vitro fertilization/intracytoplasmic sperm injection: study protocol for a randomized controlled trial.

PubMed

Ma, Saihua; Ma, Ruihong; Xia, Tian; Afnan, Masoud; Song, Xueru; Xu, Fengqin; Hao, Guimin; Zhu, Fangfang; Han, Jingpei; Zhao, Zhimei

2018-02-20

Women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) who have a predicted poor ovarian response (POR) present a challenge for reproductive medicine specialists. Traditional Chinese medicine (TCM) is commonly used in China for such patients, in the belief that it will improve the ovarian response and ultimately increase pregnancy rates. However, there is a lack of high-quality evidence about the effect of TCM on improving ovarian response in such patients. The purpose of this study is to evaluate ongoing viable pregnancy rate at 12 weeks' gestation and related indicators of ovarian response in fertile women who have a predicted poor ovarian response having immediate versus delayed IVF/ICSI after 3 months of Ding-Kun-Dan (DKD) pre-treatment. This study is a multicenter, randomized controlled, parallel-group, phase III, superiority clinical trial. Two hundred and seventy-eight eligible female infertility patients with POR will be included in the study and randomly allocated into an immediate treatment group and a DKD group in a 1:1 ratio. Both groups will receive IVF or ICSI as a standard treatment while in the DKD group, a commercially available Chinese medicine, DKD, will be administrated for 3 months before the IVF/ICSI cycle starts. The primary outcome of the study is the ongoing pregnancy rate at 12 weeks' gestation. The secondary outcomes include total gonadotropin dosage, duration of stimulation, estradiol (E 2 ) and progesterone (P) levels on human chorionic gonadotropin (hCG) trigger day, cycle cancellation rate, number of oocytes retrieved, high-quality embryo rate, biochemical pregnancy rate, the change of serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and E 2 levels and all side effects, safety outcomes, and any adverse events. The protocol was approved by the Ethics Committee of the First Teaching Hospital of Tianjin university of TCM (approval no. TYLL2017[K] 004). IVF/ICSI is increasingly used to treat couples desiring a baby. Many of these women will have poor ovarian function. In China, DKD is commonly used for these patients prior to undergoing IVF/ICSI. There is no effective treatment for poor ovarian response in Western medicine currently. It is important, therefore, to undertake this randomized control trial to determine whether DKD is effective or not. Chinese Clinical Trial Registry, ID: ChiCTR-IOR-17011697 . Registered on 19 June 2017.

Coronary Computed Tomography Angiography vs Functional Stress Testing for Patients With Suspected Coronary Artery Disease: A Systematic Review and Meta-analysis.

PubMed

Foy, Andrew J; Dhruva, Sanket S; Peterson, Brandon; Mandrola, John M; Morgan, Daniel J; Redberg, Rita F

2017-11-01

Coronary computed tomography angiography (CCTA) is a new approach for the diagnosis of anatomical coronary artery disease (CAD), but it is unclear how CCTA performs compared with the standard approach of functional stress testing. To compare the clinical effectiveness of CCTA with that of functional stress testing for patients with suspected CAD. A systematic literature search was conducted in PubMed and MEDLINE for English-language randomized clinical trials of CCTA published from January 1, 2000, to July 10, 2016. Researchers selected randomized clinical trials that compared a primary strategy of CCTA with that of functional stress testing for patients with suspected CAD and reported data on patient clinical events and changes in therapy. Two reviewers independently extracted data from and assessed the quality of the trials. This analysis followed the PRISMA statement for reporting systematic reviews and meta-analyses and used the Cochrane Collaboration's tool for assessing risk of bias in randomized trials. The Mantel-Haenszel method was used to conduct the primary analysis. Summary relative risks were calculated with a random-effects model. The outcomes of interest were all-cause mortality, cardiac hospitalization, myocardial infarction, invasive coronary angiography, coronary revascularization, new CAD diagnoses, and change in prescription for aspirin and statins. Thirteen trials were included, with 10 315 patients in the CCTA arm and 9777 patients in the functional stress testing arm who were followed up for a mean duration of 18 months. There were no statistically significant differences between CCTA and functional stress testing in death (1.0% vs 1.1%; risk ratio [RR], 0.93; 95% CI, 0.71-1.21) or cardiac hospitalization (2.7% vs 2.7%; RR, 0.98; 95% CI, 0.79-1.21), but CCTA was associated with a reduction in the incidence of myocardial infarction (0.7% vs 1.1%; RR, 0.71; 95% CI, 0.53-0.96). Patients undergoing CCTA were significantly more likely to undergo invasive coronary angiography (11.7% vs 9.1%; RR, 1.33; 95% CI, 1.12-1.59) and revascularization (7.2% vs 4.5%; RR, 1.86; 95% CI, 1.43-2.43). They were also more likely to receive a diagnosis of new CAD and to have initiated aspirin or statin therapy. Compared with functional stress testing, CCTA is associated with a reduced incidence of myocardial infarction but an increased incidence of invasive coronary angiography, revascularization, CAD diagnoses, and new prescriptions for aspirin and statins. Despite these differences, CCTA is not associated with a reduction in mortality or cardiac hospitalizations.

Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine.

PubMed

Malcolm, Benjamin J; Polanco, Martin; Barsuglia, Joseph P

2018-04-02

Opioid use disorder (OUD) is currently an epidemic in the United States (US) and ibogaine is reported to have the ability to interrupt opioid addiction by simultaneously mitigating withdrawal and craving symptoms. This study examined opioid withdrawal and drug craving scores in 50 participants with OUD undergoing a week-long detoxification treatment protocol with ibogaine. The Addiction Severity Index (ASI) was used for baseline characterization of participants' OUD. Clinical Opioid Withdrawal Scale (COWS), Subjective Opioid Withdrawal Scale (SOWS), and Brief Substance Craving Scale (BSCS) scores were collected at 48 and 24 hours prior to ibogaine administration, as well as 24 and 48 hours after ibogaine administration. At 48 hours following ibogaine administration, withdrawal and craving scores were significantly lowered in comparison to baseline: 78% of patients did not exhibit objective clinical signs of opioid withdrawal, 79% reported minimal cravings for opioids, and 68% reported subjective withdrawal symptoms in the mild range. Ibogaine appears to facilitate opioid detoxification by reducing opioid withdrawal and craving in participants with OUD. These results warrant further research using rigorous controlled trials.

Memantine before Mastectomy Prevents Post-Surgery Pain: A Randomized, Blinded Clinical Trial in Surgical Patients

PubMed Central

Morel, Véronique; Joly, Dominique; Villatte, Christine; Dubray, Claude; Durando, Xavier; Daulhac, Laurence; Coudert, Catherine; Roux, Delphine; Pereira, Bruno; Pickering, Gisèle

2016-01-01

Background Neuropathic pain following surgical treatment for breast cancer with or without chemotherapy is a clinical burden and patients frequently report cognitive, emotional and quality of life impairment. A preclinical study recently showed that memantine administered before surgery may prevent neuropathic pain development and cognitive dysfunction. With a translational approach, a clinical trial has been carried out to evaluate whether memantine administered before and after mastectomy could prevent the development of neuropathic pain, the impairment of cognition and quality of life. Method A randomized, pilot clinical trial included 40 women undergoing mastectomy in the Oncology Department, University Hospital, Clermont-Ferrand, France. Memantine (5 to 20 mg/day; n = 20) or placebo (n = 20) was administered for four weeks starting two weeks before surgery. The primary endpoint was pain intensity measured on a (0–10) numerical rating scale at three months post-mastectomy. Results Data analyses were performed using mixed models and the tests were two-sided, with a type I error set at α = 0.05. Compared with placebo, patients receiving memantine showed at three months a significant difference in post-mastectomy pain intensity, less rescue analgesia and a better emotional state. An improvement of pain symptoms induced by cancer chemotherapy was also reported. Conclusions This study shows for the first time the beneficial effect of memantine to prevent post-mastectomy pain development and to diminish chemotherapy-induced pain symptoms. The lesser analgesic consumption and better well-being of patients for at least six months after treatment suggests that memantine could be an interesting therapeutic option to diminish the burden of breast cancer therapy. Trial Registration Clinicaltrials.gov NCT01536314 PMID:27050431

Successful implementation of image-guided radiation therapy quality assurance in the Trans Tasman Radiation Oncology Group 08.01 PROFIT Study.

PubMed

Middleton, Mark; Frantzis, Jim; Healy, Brendan; Jones, Mark; Murry, Rebecca; Kron, Tomas; Plank, Ashley; Catton, Charles; Martin, Jarad

2011-12-01

The quality assurance (QA) of image-guided radiation therapy (IGRT) within clinical trials is in its infancy, but its importance will continue to grow as IGRT becomes the standard of care. The purpose of this study was to demonstrate the feasibility of IGRT QA as part of the credentialing process for a clinical trial. As part of the accreditation process for a randomized trial in prostate cancer hypofraction, IGRT benchmarking across multiple sites was incorporated. Each participating site underwent IGRT credentialing via a site visit. In all centers, intraprostatic fiducials were used. A real-time assessment of analysis of IGRT was performed using Varian's Offline Review image analysis package. Two-dimensional (2D) kV and MV electronic portal imaging prostate patient datasets were used, consisting of 39 treatment verification images for 2D/2D comparison with the digitally reconstructed radiograph derived from the planning scan. The influence of differing sites, image modality, and observer experience on IGRT was then assessed. Statistical analysis of the mean mismatch errors showed that IGRT analysis was performed uniformly regardless of institution, therapist seniority, or imaging modality across the three orthogonal planes. The IGRT component of clinical trials that include sophisticated planning and treatment protocols must undergo stringent QA. The IGRT technique of intraprostatic fiducials has been shown in the context of this trial to be undertaken in a uniform manner across Australia. Extending this concept to many sites with different equipment and IGRT experience will require a robust remote credentialing process. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Preventive PCI versus culprit lesion stenting during primary PCI in acute STEMI: a systematic review and meta-analysis

PubMed Central

Pandit, Anil; Aryal, Madan Raj; Aryal Pandit, Aashrayata; Hakim, Fayaz Ahmad; Giri, Smith; Mainali, Naba Raj; Sharma, Prashant; Lee, Howard R; Fortuin, F David; Mookadam, Farouk

2014-01-01

Aim The benefit of preventive percutaneous coronary intervention (PCI) in ST elevation myocardial infarction (STEMI) has been shown in randomised trials. However, all the randomised trials are underpowered to detect benefit in cardiac death. We aim to systematically review evidence on the cardiac mortality benefit of preventive PCI in patients presenting with acute STEMI in randomised patient populations. Methods PubMed, Scopus, Cochrane and clinicaltrials.gov databases were searched for studies published until 30 September 2013. The studies were limited to randomised clinical trials. Independent observers abstracted the data on outcomes, characteristics and qualities of studies included. Fixed effect model was employed for meta-analysis. Heterogeneity of studies included was analysed using I2 statistics. Results In three randomised clinical trials published, involving 748 patients with acute STEMI and multivessel disease, 416 patients were randomised to preventive PCI and 332 to culprit-only PCI. Patients undergoing preventive PCI had significant lower risk of cardiovascular deaths (pooled OR 0.39, 95% CI 0.18 to 0.83, p=0.01, I2=0%), repeat revascularisation (pooled OR 0.28, 95% CI 0.18 to 0.44, p=0.00001, I2=0%) and non-fatal myocardial infarction (pooled OR 0.38, 95% CI 0.20 to 0.75, p=0.005, I2=0%) compared with culprit-only revascularisation. Conclusions In patients presenting with acute STEMI and significant multivessel coronary artery disease, based on our data, preventive PCI is associated with lower risk of cardiovascular mortality compared with primary PCI of only the culprit artery. This finding needs to be confirmed in larger adequately powered randomised clinical trials. PMID:25332779

Rationale and design of the SAIL trial for intramuscular injection of allogeneic mesenchymal stromal cells in no-option critical limb ischemia.

PubMed

Wijnand, Joep G J; Teraa, Martin; Gremmels, Hendrik; van Rhijn-Brouwer, Femke C C; de Borst, Gert J; Verhaar, Marianne C

2018-02-01

Critical limb ischemia (CLI) represents the most severe form of peripheral artery disease and has an immense impact on quality of life, morbidity, and mortality. A considerable proportion of CLI patients are ineligible for revascularization, leaving amputation as the only option. Mesenchymal stromal cells (MSCs), because of their vasculoregenerative and immunomodulatory characteristics, have emerged as a potential new treatment. The primary objective of this trial is to investigate whether intramuscular administration of allogeneic bone marrow (BM)-derived MSCs is safe and potentially effective. The SAIL (allogeneic mesenchymal Stromal cells for Angiogenesis and neovascularization in no-option Ischemic Limbs) trial is a double-blind, placebo-controlled randomized clinical trial to investigate the effect of allogeneic BM-MSCs in patients with CLI who are not eligible for conventional revascularization. A total of 66 patients will be included and randomized (1:1) to undergo 30 intramuscular injections with either BM-MSCs (5 × 10 6 MSCs per injection) or placebo in the ischemic lower extremity. Primary outcome, that is, therapy success, a composite outcome consisting of mortality, limb status, clinical status, and changes in pain score, will be assessed at 6 months. All study-related procedures will take place in the University Medical Center Utrecht in The Netherlands. If our results indicate that intramuscular allogeneic BM-MSC therapy for CLI is safe and potentially effective, this will have important consequences for treatment of patients with CLI. A large multicenter clinical trial with longer follow-up focusing on hard end points should then be initiated to confirm these findings. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

A Randomised, Double Blind Trial of N-Acetylcysteine for Hearing Protection during Stapes Surgery

PubMed Central

Bagger-Sjöbäck, Dan; Strömbäck, Karin; Hakizimana, Pierre; Plue, Jan; Larsson, Christina; Hultcrantz, Malou; Papatziamos, Georgios; Smeds, Henrik; Danckwardt-Lillieström, Niklas; Hellström, Sten; Johansson, Ann; Tideholm, Bo; Fridberger, Anders

2015-01-01

Background Otosclerosis is a disorder that impairs middle ear function, leading to conductive hearing loss. Surgical treatment results in large improvement of hearing at low sound frequencies, but high-frequency hearing often suffers. A likely reason for this is that inner ear sensory cells are damaged by surgical trauma and loud sounds generated during the operation. Animal studies have shown that antioxidants such as N-Acetylcysteine can protect the inner ear from noise, surgical trauma, and some ototoxic substances, but it is not known if this works in humans. This trial was performed to determine whether antioxidants improve surgical results at high frequencies. Methods We performed a randomized, double-blind and placebo-controlled parallel group clinical trial at three Swedish university clinics. Using block-stratified randomization, 156 adult patients undergoing stapedotomy were assigned to intravenous N-Acetylcysteine (150 mg/kg body weight) or matching placebo (1:1 ratio), starting one hour before surgery. The primary outcome was the hearing threshold at 6 and 8 kHz; secondary outcomes included the severity of tinnitus and vertigo. Findings One year after surgery, high-frequency hearing had improved 2.7 ± 3.8 dB in the placebo group (67 patients analysed) and 2.4 ± 3.7 dB in the treated group (72 patients; means ± 95% confidence interval, p = 0.54; linear mixed model). Surgery improved tinnitus, but there was no significant intergroup difference. Post-operative balance disturbance was common but improved during the first year, without significant difference between groups. Four patients receiving N-Acetylcysteine experienced mild side effects such as nausea and vomiting. Conclusions N-Acetylcysteine has no effect on hearing thresholds, tinnitus, or balance disturbance after stapedotomy. Trial Registration ClinicalTrials.gov NCT00525551 PMID:25763866

Improving distress in dialysis (iDiD): a feasibility two-arm parallel randomised controlled trial of an online cognitive behavioural therapy intervention with and without therapist-led telephone support for psychological distress in patients undergoing haemodialysis

PubMed Central

Hudson, Joanna L; Moss-Morris, Rona; Game, David; Carroll, Amy; McCrone, Paul; Hotopf, Matthew; Yardley, Lucy; Chilcot, Joseph

2016-01-01

Introduction Psychological distress is common in end-stage kidney disease (ESKD) and is associated with poorer health outcomes. Cognitive behavioural therapy (CBT) is recommended in UK clinical guidelines for the management of depression in people with long-term conditions. Access to skilled therapists competent in managing the competing mental and physical health demands of ESKD is limited. Online CBT treatments tailored to the needs of the ESKD population offers a pragmatic solution for under-resourced services. This study examines the feasibility and acceptability of implementing a two-arm parallel randomised controlled trial of online CBT with (intervention arm) and without (control arm) therapist support to improve psychological distress in patients undergoing haemodialysis. Methods Patients will be screened for depression and anxiety while attending for their haemodialysis treatments. We aim to recruit 60 adult patients undergoing haemodialysis who meet criteria for mild to moderately severe symptoms of depression and/or anxiety. Patients will be randomised individually (using a 1:1 computerised sequence ratio) to either online CBT with therapist telephone support (intervention arm), or online CBT with no therapist (control arm). Outcomes include feasibility and acceptability descriptive data on rates of recruitment, randomisation, retention and treatment adherence. Self-report outcomes include measures of depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7), quality of life (Euro-QoL), service use (client service receipt inventory) and illness cognitions (brief illness perception questionnaire). A qualitative process evaluation will also be conducted. The statistician will be blinded to treatment allocation. Ethics and dissemination A National Health Service (NHS) research ethics committee approved the study. Data from this study will provide essential information for the design and testing of further interventions to ameliorate distress in patients undergoing dialysis. Any amendments to the protocol will be submitted to the NHS committee and study sponsor. Trial registration number NCT023528702; Pre-results. PMID:27072573

Information perception, wishes, and satisfaction in ambulatory cancer patients under active treatment: patient-reported outcomes with QLQ-INFO25

PubMed Central

Pinto, Ana Catarina; Ferreira-Santos, Fernando; Lago, Lissandra Dal; de Azambuja, Evandro; Pimentel, Francisco Luís; Piccart-Gebhart, Martine; Razavi, Darius

2014-01-01

Background Information is vital to cancer patients. Physician–patient communication in oncology presents specific challenges. The aim of this study was to evaluate self-reported information of cancer patients in ambulatory care at a comprehensive cancer centre and examine its possible association with patients’ demographic and clinical characteristics. Patients and methods This study included adult patients with solid tumours undergoing chemotherapy at the Institute Jules Bordet’s Day Hospital over a ten-day period. EORTC QLQ-C30 and QLQ-INFO25 questionnaires were administered. Demographic and clinical data were collected. Descriptive and inferential statistics were used. Results 101 (99%) fully completed the questionnaires. They were mostly Belgian (74.3%), female (78.2%), with a mean age of 56.9 ± 12.8 years. The most frequent tumour was breast cancer (58.4%). Patients were well-informed about the disease and treatments, but presented unmet information domains. The Jules Bordet patients desired more information on treatment side effects, long-term outcome, nutrition, and recurrence symptoms. Patients on clinical trials reported having received less information about their disease and less written information than patients outside clinical trials. Higher information levels were associated with higher quality of life (QoL) scores and higher patient satisfaction. Conclusion Patients were satisfied with the information they received and this correlated with higher QoL, but they still expressed unmet information wishes. Additional studies are required to investigate the quality of the information received by patients enrolled in clinical trials. PMID:24834120

Patient outcomes using Wii-enhanced rehabilitation after total knee replacement - the TKR-POWER study.

PubMed

Negus, J J; Cawthorne, D P; Chen, J S; Scholes, C J; Parker, D A; March, L M

2015-01-01

Home-based rehabilitation following total knee replacement surgery can be as effective as clinic-based or in-patient rehabilitation. The use of the Nintendo Wii has been postulated as a novel rehabilitation tool that adds an additional focus on balance and proprioception into the recovery protocol. The aim of the proposed clinical trial is to investigate the effectiveness of this novel rehabilitation tool, used at home for three months after total knee replacement surgery and to assess any lasting improvements in functional outcome at one year. This will be a randomised controlled trial of 128 patients undergoing primary total knee replacement. The participants will be recruited preoperatively from three surgeons at a single centre. There will be no change to the usual care provided until 6 weeks after the operation. Then participants will be randomised to either the Wii-Fit group or usual rehabilitative care group. Outcomes will be assessed preoperatively, a 6-week post surgery baseline and then at 18 weeks, 6 months and 1 year. The primary outcome is the change in self-reported WOMAC total score from week 6 to 18 weeks. Secondary outcomes include objective measures of strength, function and satisfaction scores. The results of this clinical trial will be directly relevant for implementation into clinical practice. If beneficial, this affordable technology could be used by many patients to rehabilitate at home. Not only could it optimize the outcomes from their total knee replacement surgery but decrease the need for clinic-based or outpatient therapy for the majority. (ACTRN12611000291987). Copyright © 2014 Elsevier Inc. All rights reserved.

The Role of Laboratory Testing in Differentiating Type 1 Diabetes from Type 2 Diabetes in Patients Undergoing Bariatric Surgery.

PubMed

Pilla, Scott J; Maruthur, Nisa M; Schweitzer, Michael A; Magnuson, Thomas H; Potter, James J; Clark, Jeanne M; Lee, Clare J

2018-01-01

It may be difficult to distinguish between adults with type 1 diabetes and type 2 diabetes by clinical assessment. In patients undergoing bariatric surgery, it is critical to correctly classify diabetes subtype to prevent adverse perioperative outcomes including diabetic ketoacidosis. This study aimed to determine whether testing for C-peptide and islet cell antibodies during preoperative evaluation for bariatric surgery could improve the classification of type 1 versus type 2 diabetes compared to clinical assessment alone. This is a retrospective analysis of the Improving Diabetes through Lifestyle and Surgery trial, which randomized patients with clinically diagnosed type 2 diabetes and BMI 30-40 kg/m 2 to medical weight loss or bariatric surgery; one participant was discovered to have type 1 diabetes after experiencing postoperative diabetic ketoacidosis. Using blood samples collected prior to study interventions, we measured islet cell antibodies and fasting/meal-stimulated C-peptide in all participants. The participant with type 1 diabetes was similar to the 11 participants with type 2 diabetes in age at diagnosis, adiposity, and glycemic control but had the lowest C-peptide levels. Among insulin-treated participants, fasting and stimulated C-peptide correlated strongly with the C-peptide area-under-the-curve on mixed meal tolerance testing (R = 0.86 and 0.88, respectively). Three participants, including the one with type 1 diabetes, were islet cell antibody positive. Clinical characteristics did not correctly identify type 1 diabetes in this study. Preoperative C-peptide testing may improve diabetes classification in patients undergoing bariatric surgery; further research is needed to define the optimal C-peptide thresholds.

Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: a randomised, double-blind, placebo-controlled phase II study.

PubMed

Becker, Richard C; Moliterno, David J; Jennings, Lisa K; Pieper, Karen S; Pei, Jinglan; Niederman, Alan; Ziada, Khaled M; Berman, Gail; Strony, John; Joseph, Diane; Mahaffey, Kenneth W; Van de Werf, Frans; Veltri, Enrico; Harrington, Robert A

2009-03-14

An antithrombotic drug is needed that safely reduces cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). We therefore assessed the tolerability and safety of SCH 530348-an oral platelet protease-activated receptor-1 antagonist. We randomly assigned patients aged 45 years or older and undergoing non-urgent PCI or coronary angiography with planned PCI to an oral loading dose of SCH 530348 (10 mg, 20 mg, or 40 mg) or matching placebo in a 3:1 ratio in a multicentre international study. Those in the SCH 530348 group who subsequently underwent PCI (primary PCI cohort) continued taking an oral maintenance dose (0.5 mg, 1.0 mg, or 2.5 mg per day), and patients in the placebo group continued placebo for 60 days. The primary endpoint was the incidence of clinically significant major or minor bleeding according to the thrombolysis in myocardial infarction (TIMI) scale. Both investigators and patients were unaware of treatment allocation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00132912. 257 patients were assigned to placebo and 773 to SCH 530348. The primary endpoint occurred in 2 (2%) of 129, 3 (3%) of 120, and 7 (4%) of 173 patients, respectively, in the SCH 530348 10 mg, 20 mg, and 40 mg groups compared with 5 (3%) of 151 patients in the placebo group (p=0.5786). TIMI major plus minor bleeding occurred in 3 (2%) of 136, 5 (4%) of 139, and 4 (3%) of 138 patients given SCH 530348 0.5 mg, 1.0 mg, and 2.5 mg once per day, respectively (p=0.7561). Oral SCH 530348 was generally well tolerated and did not cause increased TIMI bleeding, even when administered concomitantly with aspirin and clopidogrel. Further testing in phase III trials to accurately define the safety and efficacy of SCH 530348 is warranted.

Effect of nature-based sound therapy on agitation and anxiety in coronary artery bypass graft patients during the weaning of mechanical ventilation: A randomised clinical trial.

PubMed

Aghaie, Bahman; Rejeh, Nahid; Heravi-Karimooi, Majideh; Ebadi, Abbas; Moradian, Seyed Tayeb; Vaismoradi, Mojtaba; Jasper, Melanie

2014-04-01

Weaning from mechanical ventilation is a frequent nursing activity in critical care. Nature-based sound as a non-pharmacological and nursing intervention effective in other contexts may be an efficient approach to alleviating anxiety, agitation and adverse effects of sedative medication in patients undergoing weaning from mechanical ventilation. This study identified the effect of nature-based sound therapy on agitation and anxiety on coronary artery bypass graft patients during weaning from mechanical ventilation. A randomised clinical trial design was used. 120 coronary artery bypass graft patients aged 45-65 years undergoing weaning from mechanical ventilation were randomly assigned to intervention and control groups. Patients in the intervention group listened to nature-based sounds through headphones; the control group had headphones with no sound. Haemodynamic variables, anxiety levels and agitation were assessed using the Faces Anxiety Scale and Richmond Agitation Sedation Scale, respectively. Patients in both groups had vital signs recorded after the first trigger, at 20 min intervals throughout the procedure, immediately after the procedure, 20 min after extubation, and 30 min after extubation. Data were collected over 5 months from December 2012 to April 2013. The intervention group had significantly lower anxiety and agitation levels than the control group. Regarding haemodynamic variables, a significant time trend and interaction was reported between time and group (p<0.001). A significant difference was also found between the anxiety (p<0.002) and agitation (p<0.001) scores in two groups. Nature-based sound can provide an effective method of decreasing potential adverse haemodynamic responses arising from anxiety and agitation in weaning from mechanical ventilation in coronary artery bypass graft patients. Nurses can incorporate this intervention as a non-pharmacological intervention into the daily care of patients undergoing weaning from mechanical ventilation in order to reduce their anxiety and agitation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effective and safe mannitol administration in patients undergoing supratentorial tumor surgery: A prospective, randomized and double blind study.

PubMed

Akcil, Eren Fatma; Dilmen, Ozlem Korkmaz; Karabulut, Esra Sultan; Koksal, Serdar Selcuk; Altindas, Fatis; Tunali, Yusuf

2017-08-01

Although osmotic diuresis with mannitol is commonly used to provide brain relaxation, there is no consensus regarding its optimal dose and combination with loop diuretics. The aim of the present study is to evaluate the effects of mannitol and combination of furosemide with different doses of mannitol on brain relaxation and on blood electrolytes, lactate level, urine output, fluid balance and blood osmolarity in patients undergoing supratentorial tumor surgery. This prospective, randomized, double blind, placebo-controlled study included 51 patients (ASA I-III) scheduled for elective supratentorial craniotomy. Different doses and combinations of diuretics were administered after the bone flap removal. The Group 1 received mannitol at 0.5gkg -1 and furosemide at 0.5mgkg -1 , the Group 2 received mannitol at 1gkg -1 and furosemide at 0.5mgkg -1 , and the Group 3 received mannitol at 0.5gkg -1 and placebo. The primary end-point of the present study is to evaluate the effects of mannitol and combination of furosemide with different doses of mannitol on brain relaxation and the secondary end-points are to evaluate their effects on blood electrolytes, lactate level, urine output, fluid balance and blood osmolarity. This study shows that mannitol alone (0.5gkg -1 ), and the combinations of furosemide (0.5mgkg -1 ) with different doses of mannitol (0.5gkg -1 -1gkg -1 ) provides adequate brain relaxation. However, administration of furosemide with low or high doses of mannitol may cause reduction in the sodium and chloride levels as well as rise in the lactate level. Moreover it may cause high urine output and negative intra-operative fluid balance. Administration of 0.5gkg -1 mannitol provides adequate brain relaxation without causing systemic side effects in patients undergoing supratentorial tumor surgery. This study is registered to clinical trials (Clinical Trials.gov identifier NCT02712476). Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of the changes in blood glucose level during sedation with midazolam and propofol in implant surgery: a prospective randomized clinical trial.

PubMed

Kaviani, Nasser; Koosha, Farzad; Shahtusi, Mina

2014-09-01

Reducing the patients' stress can prevent, or at least, limit the increase in blood glucose level. The study compares the effect of propofol and midazolam on blood glucose level in the patients undergoing dental implant surgery. The effect of pre-operational stress on blood glucose level during the surgery is also evaluated. This prospective randomized clinical trial recruited 33 patients undergoing dental implant surgery and divided into two groups. Conscious sedation was performed by midazolam in one group and with propofol in another group. The pre-operational stress was scored and the blood glucose level was measured in 4 different stages; before the operation, two minutes after the local anesthetic injection; thirty minutes after the onset of operation and at the end of the operation. The results were analyzed by employing ANOVA and Pearson test. The p Value was adopted 0.05 and the confidence coefficient was assumed 95%. The average levels of the blood glucose in midazolam and propofol group were 93.82 mg/dl and 94 mg/dl before the operation which displayed a meaningful increase of blood glucose level in both groups as the operation went on. The values were 103.76 mg/dl for midazolam and 108.56 mg/dl for the propofol group (p< 0.05) at the end of the operation. No statistically significant difference was found in the average blood glucose level between two groups in the different stages of the operation (p= 0.466). The Pearson correlation coefficient test revealed a higher increase in the blood glucose level in the patients with a higher pre-operational stress score (r= 0.756, p< 0.001). Based on the results yielded by this study, patients who receive venous sedation, either by midazolam or propofol, experience increase in the blood glucose level while undergoing an operation. No statistically significant difference was detected between midazolam and propofol.

Interleukin-21: updated review of Phase I and II clinical trials in metastatic renal cell carcinoma, metastatic melanoma and relapsed/refractory indolent non-Hodgkin's lymphoma.

PubMed

Hashmi, Mehmood H; Van Veldhuizen, Peter J

2010-05-01

In advanced renal cell cancer and malignant melanoma, the current FDA approved immune modulators, such as IL-2, are the only agents which provide a durable complete remission. These responses, however, occur in < 10% of treated patients and their applicability is limited to selected patients because of their toxicity. The identification of new immunotherapeutic agents with an improved response rate and toxicity profile would represent a significant advancement in the treatment of these malignancies. This is a comprehensive review of IL-21 including its pharmacology and current developmental status. A literature review was performed using all PubMed listed publications involving IL-21, including original research articles, reviews and abstracts. It also includes a review of current ongoing trials and information from the official product website. Recombinant IL-21 (rIL-21) is a new immune modulator currently undergoing Phase I and II testing. It is a cytokine with a four helix structure that has structural and sequence homology to IL-2 and -15, but also possesses many unique biological properties. In this review, we evaluate the development, pharmacologic properties, safety profile and current clinical efficacy of rIL-21. rIL-21 has an acceptable safety profile and encouraging single agent activity in early phase renal cell carcinoma and melanoma clinical trials.

A Mechanomodulatory Device to Minimize Incisional Scar Formation

PubMed Central

Wong, Victor W.; Beasley, Bill; Zepeda, John; Dauskardt, Reinhold H.; Yock, Paul G.; Longaker, Michael T.; Gurtner, Geoffrey C.

2013-01-01

Objective To mechanically control the wound environment and prevent cutaneous scar formation. Approach We subjected various material substrates to biomechanical testing to investigate their ability to modulate skin behavior. Combinations of elastomeric materials, adhesives, and strain applicators were evaluated to develop topical stress-shielding devices. Noninvasive imaging modalities were utilized to characterize anatomic site-specific differences in skin biomechanical properties in humans. The devices were tested in a validated large animal model of hypertrophic scarring. Phase I within-patient controlled clinical trials were conducted to confirm their safety and efficacy in scar reduction in patients undergoing abdominoplasty surgery. Results Among the tested materials and device applicators, a polymer device was developed that effectively off-loaded high tension wounds and blocked pro-fibrotic pathways and excess scar formation in red Duroc swine. In humans, different anatomic sites exhibit unique biomechanical properties that may correlate with the propensity to form scars. In the clinical trial, utilization of this device significantly reduced incisional scar formation and improved scar appearance for up to 12 months compared with control incisions that underwent routine postoperative care. Innovation This is the first device that is able to precisely control the mechanical environment of incisional wounds and has been demonstrated in multiple clinical trials to significantly reduce scar formation after surgery. Conclusion Mechanomodulatory strategies to control the incisional wound environment can significantly reduce pathologic scarring and fibrosis after surgery. PMID:24527342

Local anesthetic wound infiltration for pain management after periacetabular osteotomy. A randomized, placebo-controlled, double-blind clinical trial with 53 patients.

PubMed

Bech, Rune D; Ovesen, Ole; Lindholm, Peter; Overgaard, Søren

2014-04-01

To our knowledge, there is no evidence to support the use of local infiltration analgesia (LIA) for postoperative pain relief after periacetabular osteotomy (PAO). We investigated the effect of wound infiltration with a long-acting local anesthetic (ropivacaine) for postoperative analgesia after PAO. We performed a randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov: NCT00815503) in 53 patients undergoing PAO to evaluate the effect of local anesthetic infiltration on postoperative pain and on postoperative opioid consumption. All subjects received intraoperative infiltration followed by 5 postoperative injections in 10-hour intervals through a multi-holed catheter placed at the surgical site. 26 patients received ropivacaine and 27 received saline. The intervention period was 2 days and the observational period was 4 days. All subjects received patient-controlled opioid analgesia without any restrictions on the total daily dose. Pain was assessed at specific postoperative time points and the daily opioid usage was registered. Infiltration with 75 mL (150 mg) of ropivacaine did not reduce postoperative pain or opioid requirements during the first 4 days. The clinical importance of ropivacaine as single component in postoperative treatment of pain is questionable, and we are planning further studies to explore the potential of LIA in larger volume-and also a multimodal regimen-to treat pain in this category of patients.

Methodological Quality of Randomized Clinical Trials of Respiratory Physiotherapy in Coronary Artery Bypass Grafting Patients in the Intensive Care Unit: a Systematic Review

PubMed Central

Lorscheitter, Jaqueline; Stein, Cinara; Plentz, Rodrigo Della Méa

2017-01-01

Objective To assess methodological quality of the randomized controlled trials of physiotherapy in patients undergoing coronary artery bypass grafting in the intensive care unit. Methods The studies published until May 2015, in MEDLINE, Cochrane and PEDro were included. The primary outcome extracted was proper filling of the Cochrane Collaboration's tool's items and the secondary was suitability to the requirements of the CONSORT Statement and its extension. Results From 807 studies identified, 39 were included. Most at CONSORT items showed a better adequacy after the statement's publication. Studies with positive outcomes presented better methodological quality. Conclusion The methodological quality of the studies has been improving over the years. However, many aspects can still be better designed. PMID:28977205

Effect of a perioperative, cardiac output-guided hemodynamic therapy algorithm on outcomes following major gastrointestinal surgery: a randomized clinical trial and systematic review.

PubMed

Pearse, Rupert M; Harrison, David A; MacDonald, Neil; Gillies, Michael A; Blunt, Mark; Ackland, Gareth; Grocott, Michael P W; Ahern, Aoife; Griggs, Kathryn; Scott, Rachael; Hinds, Charles; Rowan, Kathryn

2014-06-04

Small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm. To evaluate the clinical effectiveness of a perioperative, cardiac output-guided hemodynamic therapy algorithm. OPTIMISE was a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom. An updated systematic review and meta-analysis were also conducted including randomized trials published from 1966 to February 2014. Patients were randomly assigned to a cardiac output-guided hemodynamic therapy algorithm for intravenous fluid and inotrope (dopexamine) infusion during and 6 hours following surgery (n=368) or to usual care (n=366). The primary outcome was a composite of predefined 30-day moderate or major complications and mortality. Secondary outcomes were morbidity on day 7; infection, critical care-free days, and all-cause mortality at 30 days; all-cause mortality at 180 days; and length of hospital stay. Baseline patient characteristics, clinical care, and volumes of intravenous fluid were similar between groups. Care was nonadherent to the allocated treatment for less than 10% of patients in each group. The primary outcome occurred in 36.6% of intervention and 43.4% of usual care participants (relative risk [RR], 0.84 [95% CI, 0.71-1.01]; absolute risk reduction, 6.8% [95% CI, -0.3% to 13.9%]; P = .07). There was no significant difference between groups for any secondary outcomes. Five intervention patients (1.4%) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group. Findings of the meta-analysis of 38 trials, including data from this study, suggest that the intervention is associated with fewer complications (intervention, 488/1548 [31.5%] vs control, 614/1476 [41.6%]; RR, 0.77 [95% CI, 0.71-0.83]) and a nonsignificant reduction in hospital, 28-day, or 30-day mortality (intervention, 159/3215 deaths [4.9%] vs control, 206/3160 deaths [6.5%]; RR, 0.82 [95% CI, 0.67-1.01]) and mortality at longest follow-up (intervention, 267/3215 deaths [8.3%] vs control, 327/3160 deaths [10.3%]; RR, 0.86 [95% CI, 0.74-1.00]). In a randomized trial of high-risk patients undergoing major gastrointestinal surgery, use of a cardiac output-guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality. However, inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rates. isrctn.org Identifier: ISRCTN04386758.

Forced diuresis with matched hydration in reducing acute kidney injury during transcatheter aortic valve implantation (Reduce-AKI): study protocol for a randomized sham-controlled trial

PubMed Central

2014-01-01

Background Acute kidney injury (AKI) is observed in up to 41% of patients undergoing transcatheter aortic valve implantation (TAVI) and is associated with increased risk for mortality. The aim of the present study is to evaluate whether furosemide-induced diuresis with matched isotonic intravenous hydration using the RenalGuard system reduces AKI in patients undergoing TAVI. Methods/Design Reduce-AKI is a randomized sham-controlled study designed to examine the effect of an automated matched hydration system in the prevention of AKI in patients undergoing TAVI. Patients will be randomized in a 1:1 fashion to the RenalGuard system (active group) versus non-matched saline infusion (sham-controlled group). Both arms receive standard overnight saline infusion and N-acetyl cysteine before the procedure. Discussion The Reduce-AKI trial will investigate whether the use of automated forced diuresis with matched saline infusion is an effective therapeutic tool to reduce the occurrence of AKI in patients undergoing TAVI. Trial registration Clinicaltrials.gov: NCT01866800, 30 April 30 2013. PMID:24986373

Chinese herbal medicine (Ma Zi Ren Wan) for functional constipation: study protocol for a prospective, double-blinded, double-dummy, randomized controlled trial

PubMed Central

2013-01-01

Background Functional constipation is a common clinical complaint. Although the effectiveness of Ma Zi Ren Wan for alleviating functional constipation symptoms has been proven in a previous randomized placebo-controlled study, further evidence is needed to make clinical recommendations about Chinese herbal medicine. In particular, a comparison with conventional western medicine for functional constipation patients is needed. Methods/Design This is a prospective, double-blinded, double dummy, randomized, controlled trial. After a 2-week run-in period, eligible patients (Rome III) with excessive traditional Chinese medicine syndrome will randomly be assigned to the Chinese medicine arm (Ma Zi Ren Wan and western medicine placebo), western medicine arm (senna and Chinese medicine placebo) or placebo arm (Chinese medicine placebo and western medicine placebo). Patients will undergo an 8-week treatment and an 8-week follow-up. The primary outcome is the responder rate for complete spontaneous bowel movement (CSBM) during treatment. Patients with a mean increase of CSBM ≧1/week in comparison with their baselines are defined as responders. The secondary outcomes include responder rate during follow-up, changes of colonic transit as measured with radio-opaque markers, individual and global symptom assessments, and reported adverse effects. Discussion This study is the first study to compare a Chinese Herbal Medicine (Ma Zi Ren Wan) with a laxative that is commonly used in the clinical practice of western medicine, and with a placebo. This study will complete the investigation of Ma Zi Ren Wan for functional constipation, and should, therefore, suggest recommendations for clinical practice. Furthermore, the process of first conducting a systematic review, then implementing a dose determination study followed by a placebo-control trial, and finally, comparing traditional Chinese medicine with an active conventional medicine in a controlled trial can be a reference to other researches on Chinese medicine interventions in the future. Trial registration NCT01695850 PMID:24180235

Quality-of-Life (QOL) during Screening for Phase 1 Trial Studies in Patients with Advanced Solid Tumors and Its Impact on Risk for Serious Adverse Events.

PubMed

Anwar, Sidra; Tan, Wei; Hong, Chi-Chen; Admane, Sonal; Dozier, Askia; Siedlecki, Francine; Whitworth, Amy; DiRaddo, Ann Marie; DePaolo, Dawn; Jacob, Sandra M; Ma, Wen Wee; Miller, Austin; Adjei, Alex A; Dy, Grace K

2017-06-26

Background : Serious adverse events (SAEs) and subject replacements occur frequently in phase 1 oncology clinical trials. Whether baseline quality-of-life (QOL) or social support can predict risk for SAEs or subject replacement among these patients is not known. Methods : Between 2011-2013, 92 patients undergoing screening for enrollment into one of 22 phase 1 solid tumor clinical trials at Roswell Park Cancer Institute were included in this study. QOL Questionnaires (EORTC QLQ-C30 and FACT-G), Medical Outcomes Study Social Support Survey (MOSSSS), Charlson comorbidity scores (CCS) and Royal Marsden scores (RMS) were obtained at baseline. Frequency of dose limiting toxicities (DLTs), subject replacement and SAEs that occurred within the first 4 cycles of treatment were recorded. Fisher's exact test and Mann-Whitney-Wilcoxon test were used to study the association between categorical and continuous variables, respectively. A linear transformation was used to standardize QOL scores. p -value ≤ 0.05 was considered statistically significant. Results : Baseline QOL, MOSSSS, CCS and RMS were not associated with subject replacement nor DLTs. Baseline EORTC QLQ-C30 scores were significantly lower among patients who encountered SAEs within the first 4 cycles ( p = 0.04). Conclusions : Lower (worse) EORTC QLQ-C30 score at baseline is associated with SAE occurrence during phase 1 oncology trials.

Reducing bed rest time from five to three hours does not increase complications after cardiac catheterization: the THREE CATH Trial 1

PubMed Central

Matte, Roselene; Hilário, Thamires de Souza; Reich, Rejane; Aliti, Graziella Badin; Rabelo-Silva, Eneida Rejane

2016-01-01

Abstract Objective: to compare the incidence of vascular complications in patients undergoing transfemoral cardiac catheterization with a 6F introducer sheath followed by 3-hour versus 5-hour rest. Methods: randomized clinical trial. Subjects in the intervention group (IG) ambulated 3 hours after sheath removal, versus 5 hours in the control group (CG). All patients remained in the catheterization laboratory for 5 hours and were assessed hourly, and were contacted 24, 48, and 72 h after hospital discharge. Results: the sample comprised 367 patients in the IG and 363 in the GC. During cath lab stay, hematoma was the most common complication in both groups, occurring in 12 (3%) IG and 13 (4%) CG subjects (P=0.87). Bleeding occurred in 4 (1%) IG and 6 (2%) CG subjects (P=0.51), and vasovagal reaction in 5 (1.4%) IG and 4 (1.1%) CG subjects (P=0.75). At 24-h, 48-h, and 72-h bruising was the most commonly reported complication in both groups. None of the comparisons revealed any significant between-group differences. Conclusion: the results of this trial show that reducing bed rest time to 3 hours after elective cardiac catheterization is safe and does not increase complications as compared with a 5-hour rest. ClinicalTrials.gov Identifier: NCT-01740856 PMID:27463113

Reconstituted fresh whole blood improves clinical outcomes compared with stored component blood therapy for neonates undergoing cardiopulmonary bypass for cardiac surgery: a randomized controlled trial.

PubMed

Gruenwald, Colleen E; McCrindle, Brian W; Crawford-Lean, Lynn; Holtby, Helen; Parshuram, Christopher; Massicotte, Patricia; Van Arsdell, Glen

2008-12-01

This study compared the effects of reconstituted fresh whole blood against standard blood component therapy in neonates undergoing cardiac surgery. Patients less than 1 month of age were randomized to receive either reconstituted fresh whole blood (n = 31) or standard blood component therapy (n = 33) to prime the bypass circuit and for transfusion during the 24 hours after cardiopulmonary bypass. Primary outcome was chest tube drainage; secondary outcomes included transfusion needs, inotrope score, ventilation time, and hospital length of stay. Patients who received reconstituted fresh whole blood had significantly less postoperative chest tube volume loss per kilogram of body weight (7.7 mL/kg vs 11.8 mL/kg; P = .03). Standard blood component therapy was associated with higher inotropic score (6.6 vs 3.3; P = .002), longer ventilation times (164 hours vs 119 hours; P = .04), as well as longer hospital stays (18 days vs 12 days; P = .006) than patients receiving reconstituted fresh whole blood. Of the different factors associated with the use of reconstituted fresh whole blood, lower platelet counts at 10 minutes and at the end of cardiopulmonary bypass, older age of cells used in the prime and throughout bypass, and exposures to higher number of allogeneic donors were found to be independent predictors of poor clinical outcomes. Reconstituted fresh whole blood used for the prime, throughout cardiopulmonary bypass, and for all transfusion requirements within the first 24 hours postoperatively results in reduced chest tube volume loss and improved clinical outcomes in neonatal patients undergoing cardiac surgery.

Implementing an intravenous insulin protocol in your practice: practical advice to overcome clinical, administrative, and financial barriers.

PubMed

Kelly, Janet L; Hirsch, Irl B; Furnary, Anthony P

2006-01-01

Diabetes mellitus is the fourth most common comorbid condition among hospitalized patients, and 30% of patients undergoing open-heart surgery have diabetes. The link between hyperglycemia and poor outcome has been well described, and large clinical trials have shown that aggressive control of blood glucose with an insulin infusion can improve these outcomes. The barriers to implementing an insulin infusion protocol are numerous, despite the fact that doing so is paramount to clinical success. Barriers include safety concerns, such as fear of hypoglycemia, insufficient nursing staff to patient ratios, lack of administrative and physician support, various system and procedural issues, and resistance to change. Key steps to overcome the barriers include building support with multidisciplinary champions, involving key staff, educating staff, and administrators of the clinical and economic benefits of improving glycemic control, setting realistic goals, selecting a validated insulin infusion protocol, and internally marketing the success of the protocol.

Fluoxetine for Autistic Behaviors (FAB trial): study protocol for a randomized controlled trial in children and adolescents with autism.

PubMed

Mouti, Anissa; Reddihough, Dinah; Marraffa, Catherine; Hazell, Philip; Wray, John; Lee, Katherine; Kohn, Michael

2014-06-16

Serotonin reuptake inhibitors (SSRIs) are commonly prescribed off-label for children with autism. To date, clinical trials examining the use of SSRIs in autism have been limited by small sample sizes and inconclusive results. The efficacy and safety of SSRIs for moderating autistic behaviors is yet to be adequately examined to provide evidence to support current clinical practice. The aim of the Fluoxetine for Autistic Behaviors (FAB) study is to determine the efficacy and safety of low dose fluoxetine compared with placebo, for reducing the frequency and severity of repetitive stereotypic behaviors in children and adolescents with an autism spectrum disorder (ASD). The relationship between the effectiveness of fluoxetine treatment and serotonin transporter genotype will also be explored. The FAB study is a multicenter, double-blinded, randomized controlled trial, funded by the Australian Government's National Health and Medical Research Council (NHMRC) grant. Participants will be aged between 7.5 and 17 years with a confirmed diagnosis of ASD. Eligible participants will be randomized to either placebo or fluoxetine for a 16-week period. Medication will be titrated over the first four weeks. Reponses to medication will be monitored fortnightly using the Clinical Global Impressions Scale (CGI). The primary outcome measure is the Children's Yale-Brown Obsessive Compulsive Scale-Modified for Pervasive Developmental Disorders (CYBOCS-PDD), administered at baseline and 16 weeks. Secondary outcome measures include the Aberrant Behaviour Scale (ABC), the Spence Children's Anxiety Scale Parent Report (SCAS-P), and the Repetitive Behaviors Scale (RBS-R), measured at baseline and 16 weeks. Participants will be invited to undergo genetic testing for SLC6A4 allele variants using a cheek swab. Continuous outcomes, including the primary outcome will be compared between the active and placebo groups using unadjusted linear regression. Binary outcomes will be compared using unadjusted logistic regression. The FAB study is a large clinical trial to specifically investigate the efficacy of low dose fluoxetine for restricted, repetitive, and stereotyped behaviors in ASD. The outcomes of this study will contribute to evidence-based interventions used in clinical practice to assist children with ASD. Australian and New Zealand Clinical Trials Registry ACTRN12608000173392; registered on 9 April, 2008.

Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial.

PubMed

Montalescot, Gilles; Wiviott, Stephen D; Braunwald, Eugene; Murphy, Sabina A; Gibson, C Michael; McCabe, Carolyn H; Antman, Elliott M

2009-02-28

Mechanical reperfusion with stenting for ST-elevation myocardial infarction (STEMI) is supported by dual antiplatelet treatment with aspirin and clopidogrel. Prasugrel, a potent and rapid-acting thienopyridine, is a potential alternative to clopidogrel. We aimed to assess prasugrel versus clopidogrel in patients undergoing percutaneous coronary intervention (PCI) for STEMI. We undertook a double-blind, randomised controlled trial in 707 sites in 30 countries. 3534 participants presenting with STEMI were randomly assigned by interactive voice response system either prasugrel (60 mg loading, 10 mg maintenance [n=1769]) or clopidogrel (300 mg loading, 75 mg maintenance [n=1765]) and were unaware of the allocation. The primary endpoint was cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. Efficacy analyses were by intention to treat. Follow-up was to 15 months, with secondary analyses at 30 days. This trial is registered with ClinicalTrials.gov, number NCT00097591. At 30 days, 115 (6.5%) individuals assigned prasugrel had met the primary endpoint compared with 166 (9.5%) allocated clopidogrel (hazard ratio 0.68 [95% CI 0.54-0.87]; p=0.0017). This effect continued to 15 months (174 [10.0%] vs 216 [12.4%]; 0.79 [0.65-0.97]; p=0.0221). The key secondary endpoint of cardiovascular death, myocardial infarction, or urgent target vessel revascularisation was also significantly reduced with prasugrel at 30 days (0.75 [0.59-0.96]; p=0.0205) and 15 months (0.79 [0.65-0.97]; p=0.0250), as was stent thrombosis. Treatments did not differ with respect to thrombolysis in myocardial infarction (TIMI) major bleeding unrelated to coronary-artery bypass graft (CABG) surgery at 30 days (p=0.3359) and 15 months (p=0.6451). TIMI life-threatening bleeding and TIMI major or minor bleeding were also similar with the two treatments, and only TIMI major bleeding after CABG surgery was significantly increased with prasugrel (p=0.0033). In patients with STEMI undergoing PCI, prasugrel is more effective than clopidogrel for prevention of ischaemic events, without an apparent excess in bleeding.

Ultrasound guided aspiration of hydrosalpinx fluid versus salpingectomy in the management of patients with ultrasound visible hydrosalpinx undergoing IVF-ET: a randomized controlled trial.

PubMed

Fouda, Usama M; Sayed, Ahmed M; Abdelmoty, Hatem I; Elsetohy, Khaled A

2015-01-01

The aim of this study was to compare the efficacy of ultrasound guided aspiration of hydrosalpinx fluid at the time of oocyte retrieval with salpingectomy in the management of patients with ultrasound visible hydrosalpinx undergoing IVF-ET. One hundred and sixty patients with ultrasound visible hydrosalpinx were randomized into salpingectomy group and aspiration group using computer generated randomization list and sequentially numbered sealed envelopes containing allocation information written on a card. The clinical pregnancy rate per started cycle and the implantation rate were non- significantly higher in the salpingectomy group compared with the aspiration group [40% vs. 27.5% (p value = 0.132) and 18.95% vs. 12.82% (p value =0.124), respectively]. In the aspiration group, 34.21% of patients had rapid re-accumulation of the hydrosalpinx fluid (i.e. within first two weeks after embryo transfer). Whereas, the clinical pregnancy rate per transfer cycle and the implantation rate were significantly higher in salpingectomy group compared with the subgroup of patients with rapid re-accumulation of hydrosalpinx fluid [42.67% vs. 19.23% (p value = 0.036) and 18.95% vs. 7.58% (p value = 0.032), respectively], no significant differences were detected between the salpingectomy group and the subgroup of patients with no re-accumulation of hydrosalpinx fluid (42.67% vs. 34% (p value = 0.356) and 18.95% vs. 15.5% (p value = 0.457), respectively). The small sample size could be the cause of failure of detecting significant increase in implantation and pregnancy rates in salpingectomy group compared with aspiration group. Further larger randomized controlled trials are needed to determine whether salpingectomy is more effective than aspiration of hydrosalpinx fluid or not. Moreover, the data presented in this study suggested that rapid re-accumulation of hydrosalpinx fluid is an obstacle against successful implantation and the cause of lower success rate with ultrasound guided aspiration of hydrosalpinx fluid compared with salpingectomy. Clinical trials.gov ( NCT02008240 ), registered 8 December 2013.

Mobile phone messages to provide support to women during the home phase of medical abortion in South Africa: a randomised controlled trial.

PubMed

Constant, Deborah; de Tolly, Katherine; Harries, Jane; Myer, Landon

2014-09-01

Home use of misoprostol for medical abortion is more convenient for many women than in-clinic use but requires management of abortion symptoms at home without provider backup. This study evaluated whether automated text messages to women undergoing medical abortion can reduce anxiety and emotional discomfort, and whether the messages can better prepare women for symptoms they experience. A multisite randomized controlled trial was conducted in which women undergoing early medical abortion were allocated to receive standard of care (SOC) only (n=235) or SOC+a messaging intervention (n=234). Consenting women were interviewed at the clinic after taking mifepristone and again at their follow-up clinic visit 2-3 weeks later; the intervention group received text messages over the duration of this period. Emotional outcomes were evaluated using the Hospital Anxiety and Depression Scale, Adler's 12-item emotional scale and the Impact of Event Scale-Revised. Preparedness for the abortion symptoms and overall satisfaction with the procedure were assessed using 4-point Likert-type scales. Between baseline and follow-up, anxiety decreased more (p=0.013), and less emotional stress was experienced (adjusted for baseline anxiety, p=0.015), in the intervention compared to the SOC group. Participants in the intervention group were also more likely to report that they felt very well prepared for the bleeding (p<0.001), pain (p=0.042) and side effects (p=0.027) they experienced. Acceptability and other negative emotions relating to the abortion did not differ between study groups. Ninety-nine percent of the intervention group stated that they would recommend the messages to a friend having the same procedure. Text messages to women following mifepristone administration for early medical abortion may assist them in managing symptoms and appear highly acceptable to recipients. This randomized controlled trial provides evidence for the effectiveness of text messages following mifepristone administration in strengthening medical abortion care. The messages were associated with significant reductions in women's anxiety and stress during the abortion process; they improved preparedness for the abortion symptoms experienced and appeared highly acceptable. Copyright © 2014 Elsevier Inc. All rights reserved.

A Mobile App to Stabilize Daily Functional Activity of Breast Cancer Patients in Collaboration With the Physician: A Randomized Controlled Clinical Trial

PubMed Central

Egbring, Marco; Far, Elmira; Roos, Malgorzata; Dietrich, Michael; Brauchbar, Mathis; Kullak-Ublick, Gerd A

2016-01-01

Background The well-being of breast cancer patients and reporting of adverse events require close monitoring. Mobile apps allow continuous recording of disease- and medication-related symptoms in patients undergoing chemotherapy. Objective The aim of the study was to evaluate the effects of a mobile app on patient-reported daily functional activity in a supervised and unsupervised setting. Methods We conducted a randomized controlled study of 139 breast cancer patients undergoing chemotherapy. Patient status was self-measured using Eastern Cooperative Oncology Group scoring and Common Terminology Criteria for Adverse Events. Participants were randomly assigned to a control group, an unsupervised group that used a mobile app to record data, or a supervised group that used the app and reviewed data with a physician. Primary outcome variables were change in daily functional activity and symptoms over three outpatient visits. Results Functional activity scores declined in all groups from the first to second visit. However, from the second to third visit, only the supervised group improved, whereas the others continued to decline. Overall, the supervised group showed no significant difference from the first (median 90.85, IQR 30.67) to third visit (median 84.76, IQR 18.29, P=.72). Both app-using groups reported more distinct adverse events in the app than in the questionnaire (supervised: n=1033 vs n=656; unsupervised: n=852 vs n=823), although the unsupervised group reported more symptoms overall (n=4808) in the app than the supervised group (n=4463). Conclusions The mobile app was associated with stabilized daily functional activity when used under collaborative review. App-using participants could more frequently report adverse events, and those under supervision made fewer and more precise entries than unsupervised participants. Our findings suggest that patient well-being and awareness of chemotherapy adverse effects can be improved by using a mobile app in collaboration with the treating physician. ClinicalTrial ClinicalTrials.gov NCT02004496; https://clinicaltrials.gov/ct2/show/NCT02004496 (Archived by WebCite at http://www.webcitation.org/6k68FZHo2) PMID:27601354

The Effect of Patellar Thickness on Intraoperative Knee Flexion and Patellar Tracking in Patients With Arthrofibrosis Undergoing Total Knee Arthroplasty.

PubMed

Kim, Abraham D; Shah, Vivek M; Scott, Richard D

2016-05-01

We evaluated the intraoperative effect of patellar thickness on intraoperative passive knee flexion and patellar tracking during total knee arthroplasty (TKA) in patients with preoperative arthrofibrosis and compared them to patients with normal preoperative range of motion (ROM) documented in a prior study. Routine posterior cruciate ligament-retaining TKA was performed in a total of 34 knees, 23 with normal ROM and 11 with arthrofibrosis, defined as ≤100° of passive knee flexion against gravity under anesthesia. Once clinical balance and congruent patellar tracking were established, custom trial patellar components thicker than the standard trial by 2-mm increments (2-8 mm) were sequentially placed and trialed. Passive flexion against gravity was recorded using digital photograph goniometry. Gross mechanics of patellofemoral tracking were visually assessed. On average, passive knee flexion decreased 2° for every 2-mm increment of patellar thickness (P < .0001), which was similar to patients with normal preoperative ROM. In addition, increased patellar thickness had no gross effect on patellar subluxation and tilt in patients with arthrofibrosis as well as those with normal ROM. Patellar thickness had a modest effect on intraoperative passive flexion and no effect on patellar tracking in patients with arthrofibrosis undergoing TKA. There was no marked difference in intraoperative flexion and patellar tracking between patients with arthrofibrosis and patients with normal preoperative ROM. Copyright © 2016 Elsevier Inc. All rights reserved.

Rationale and design of a trial to personalize risk assessment in familial coronary artery disease.

PubMed

Marwick, Thomas H; Whitmore, Kristyn; Nicholls, Stephen J; Stanton, Tony; Mitchell, Geoffrey; Tonkin, Andrew; Blizzard, Christopher; Neil, Amanda; Jones, Catherine; Watts, Gerald F

2018-05-01

The lifetime risk of coronary artery disease (CAD) is doubled in people with a family history of premature disease, yet this risk is not captured in most 5- or 10-year risk assessment algorithms. Coronary artery calcium scoring (CCS) is a marker of subclinical CAD risk, which has been shown in observational studies to provide prognostic information that is incremental to clinical assessment; is relatively inexpensive; and is performed with a small radiation dose. However, the use of CCS in guiding prevention is not strongly supported by guidelines. Showing definitive evidence of the efficacy and cost-effectiveness of CCS is therefore of importance. The proposed randomized controlled trial of the use of CCS will be targeted to 40- to 70-year-old first-degree relatives of patients with CAD onset <60 years old or second-degree relatives of patients with onset <50 years old. Control patients will undergo standard risk scoring and be blinded to CCS results. In the intervention group, primary prevention in patients undergoing CCS will be informed by this score. At 3 years, effectiveness will be assessed on change in plaque volume at computed tomography coronary angiography, the extent of which has been strongly linked to outcome. The CAUGHT-CAD trial will provide evidence to inform the guidelines regarding the place of CCS in decision making regarding primary prevention of patients with a family history of premature disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of wet-cupping on blood pressure in hypertensive patients: a randomized controlled trial.

PubMed

Aleyeidi, Nouran A; Aseri, Khaled S; Matbouli, Shadia M; Sulaiamani, Albaraa A; Kobeisy, Sumayyah A

2015-11-01

Although cupping remains a popular treatment modality worldwide, its efficacy for most diseases, including hypertension, has not been scientifically evaluated. We aimed to determine the efficacy of wet-cupping for high blood pressure, and the incidence of the procedure's side effects in the intervention group. This is a randomized controlled trial conducted in the General Practice Department at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, between May 2013 and February 2014. There were two groups (40 participants each): intervention group undergoing wet-cupping (hijama) in addition to conventional hypertension treatment, and a control group undergoing only conventional hypertension treatment. Three wet-cupping sessions were performed every other day. The mean systolic and diastolic blood pressures were measured using a validated automatic sphygmomanometer. The follow-up period was 8 weeks. Wet-cupping provided an immediate reduction of systolic blood pressure. After 4 weeks of follow-up, the mean systolic blood pressure in the intervention group was 8.4 mmHg less than in the control group (P=0.046). After 8 weeks, there were no significant differences in blood pressures between the intervention and control groups. In this study, wet-cupping did not result in any serious side effects. Wet-cupping therapy is effective for reducing systolic blood pressure in hypertensive patients for up to 4 weeks, without serious side effects. Wet-cupping should be considered as a complementary hypertension treatment, and further studies are needed. ClinicalTrials.gov Identifier NCT01987583.

Impact of pre-existing or new-onset atrial fibrillation on 30-day clinical outcomes following transcatheter aortic valve replacement: Results from the BRAVO 3 randomized trial.

PubMed

Hengstenberg, Christian; Chandrasekhar, Jaya; Sartori, Samantha; Lefevre, Thierry; Mikhail, Ghada; Meneveau, Nicolas; Tron, Christophe; Jeger, Raban; Kupatt, Christian; Vogel, Birgit; Farhan, Serdar; Sorrentino, Sabato; Sharma, Madhav; Snyder, Clayton; Husser, Oliver; Boekstegers, Peter; Hambrecht, Rainer; Widder, Julian; Hildick-Smith, David; De Carlo, Marco; Wijngaard, Peter; Deliargyris, Efthymios; Bernstein, Debra; Baber, Usman; Mehran, Roxana; Anthopoulos, Prodromos; Dangas, George

2017-11-15

Prior studies have suggested that patients with atrial fibrillation (AF) undergoing transcatheter aortic valve replacement (TAVR) are at higher risk for adverse cardiovascular events. Whether procedural bivalirudin compared with unfractionated heparin (UFH) has a beneficial effect on early outcomes in these patients is unknown. We examined for the effect of baseline or new-onset AF within 30 days of TAVR and explored for the effect of bivalirudin versus UFH by AF status, on 30-day outcomes from the BRAVO 3 trial. The BRAVO-3 trial multicenter randomized trial included 802 patients undergoing transfemoral TAVR randomized to bivalirudin or UFH. We compared AF and no-AF groups and examined for 30-day Bleeding Academic Research Consortium type ≥3b bleeding, major vascular complications and all ischemic endpoints. Adjusted outcomes were analyzed using logistic regression methods. Of the study population, 41.4% (n = 332) patients had baseline or new-onset AF within 30 days of TAVR, whereas 58.6% (n = 470) had no AF. Patients with AF had greater prevalence of renal dysfunction, lower left ventricular ejection fraction, and higher euroSCORE I compared with their counterparts without AF. Among AF and no-AF patients, there were no significant baseline differences between bivalirudin and UFH groups. At 30 days the incidence of death (6.0 vs. 4.5%, P = 0.324) and stroke (3.9 vs. 2.6%, P = 0.274) was similar in AF vs. no-AF patients. However, new-onset AF (n = 38) was associated with significantly greater crude risk of 30-day stroke compared with no AF (HR 4.49, 95% CI 1.37-14.67). Regardless of AF status, there were no differences in 30-day death (P-int = 0.652) or stroke (P-int = 0.066) by anticoagulation type. Prior or new-onset AF is noted in more than one-third of patients undergoing transfemoral TAVR. Despite greater baseline comorbidities than non-AF patients, AF was not associated with significantly higher risk of adjusted 30-day outcomes. In the BRAVO 3 trial, early outcomes were similar regardless of anticoagulant strategy in each group. © 2017 Wiley Periodicals, Inc.

Precision medicine and lymphoma.

PubMed

Heward, James A; Kumar, Emil A; Korfi, Koorosh; Okosun, Jessica; Fitzgibbon, Jude

2018-05-05

The treatment of the germinal center lymphomas, diffuse large B cell (DLBCL) and follicular lymphoma, has changed little beyond the introduction of immunochemotherapies. However, there exists a substantial group of patients within both diseases for which improvements in care will involve appropriate tailoring of treatment. DLBCL consists of two major subtypes with striking differences in their clinical outcomes paralleling their underlying genetic heterogeneity. Recent studies have seen advances in the stratification of germinal center lymphomas, through comprehensive profiling of 1001 DLBCLs alongside refinements in the identification of high-risk follicular lymphoma patients using m7-FLIPI and 23G models. A new wave of novel therapeutic agents is now undergoing clinical trials for germinal center lymphomas, with BCR and EZH2 inhibitors demonstrating preferential benefit in subgroups of patients. The emergence of cell-free DNA has raised the possibility of dynamic disease monitoring to potentially mitigate the complexity of spatial and temporal heterogeneity, whilst predicting tumor evolution in real time. Altogether knowledge of the genomic landscape of germinal center lymphomas is offering welcome opportunities in patient risk stratification and therapeutics. The challenge ahead is to establish how best to combine upfront or dynamic prognostication with precision therapies, while retaining practicality in clinical trials and the real-world setting.

Prospective Randomized Trial Comparing Embryo Transfers of Cases with and without Catheter Rotation during Its Withdrawal.

PubMed

Yayla Abide, Cigdem; Ozkaya, Enis; Sanverdi, Ilhan; Bostancı Ergen, Evrim; Kurek Eken, Meryem; Devranoglu, Belgin; Bilgiç, Bulent Emre; Kilicci, Cetin; Kayatas Eser, Semra

2018-05-14

To compare embryo transfer (ET) technique based on catheter rotation during its withdrawal in cases with unexplained infertility in a prospective, randomized trial (NCT03097042). Two hundred intracytoplasmic sperm injection (ICSI) patients undergoing ET with cleaving or blastocyst-stage fresh embryos were randomized into 2 groups: cases with (n = 100), and without (n = 100) catheter rotation during its withdrawal. Groups were matched for age and some clinical parameters. A soft catheter was used to transfer a single embryo with catheter rotation during its withdrawal in the study group and without rotation in the control. The use of a stiff catheter or tenaculum was not needed in any case. Groups were compared in terms of cycle characteristics and clinical pregnancy rates. Pregnancy rate was significantly higher in the study group (41 vs. 26%, p = 0.04). Clinical pregnancy rate was also significantly higher in the study group (39 vs. 25%, OR 1.9 [1.1-3.5], p = 0.05). On the other hand, the ongoing pregnancy rate was similar between the 2 groups (33 vs. 23%, p = 0.2). Catheter rotation during its withdrawal may be associated with increased pregnancy and clinical pregnancy rates; however, the difference in ongoing pregnancy rates did not reach statistical significance. © 2018 S. Karger AG, Basel.

Clinical Advancements in the Targeted Therapies against Liver Fibrosis

PubMed Central

Nagórniewicz, Beata; Prakash, Jai

2016-01-01

Hepatic fibrosis, characterized by excessive accumulation of extracellular matrix (ECM) proteins leading to liver dysfunction, is a growing cause of mortality worldwide. Hepatocellular damage owing to liver injury leads to the release of profibrotic factors from infiltrating inflammatory cells that results in the activation of hepatic stellate cells (HSCs). Upon activation, HSCs undergo characteristic morphological and functional changes and are transformed into proliferative and contractile ECM-producing myofibroblasts. Over recent years, a number of therapeutic strategies have been developed to inhibit hepatocyte apoptosis, inflammatory responses, and HSCs proliferation and activation. Preclinical studies have yielded numerous targets for the development of antifibrotic therapies, some of which have entered clinical trials and showed improved therapeutic efficacy and desirable safety profiles. Furthermore, advancements have been made in the development of noninvasive markers and techniques for the accurate disease assessment and therapy responses. Here, we focus on the clinical developments attained in the field of targeted antifibrotics for the treatment of liver fibrosis, for example, small molecule drugs, antibodies, and targeted drug conjugate. We further briefly highlight different noninvasive diagnostic technologies and will provide an overview about different therapeutic targets, clinical trials, endpoints, and translational efforts that have been made to halt or reverse the progression of liver fibrosis. PMID:27999454

Advances in MRSA drug discovery: where are we and where do we need to be?

PubMed

Kurosu, Michio; Siricilla, Shajila; Mitachi, Katsuhiko

2013-09-01

Methicillin-resistant Staphylococcus aureus (MRSA) have been on the increase during the past decade, due to the steady growth of the elderly and immunocompromised patients, and the emergence of multidrug-resistant (MDR) bacterial strains. Although there are a limited number of anti-MRSA drugs available, a number of different combination antimicrobial drug regimens have been used to treat serious MRSA infections. Thus, the addition of several new antistaphylococcal drugs into clinical practice should broaden clinician's therapeutic options. As MRSA is one of the most common and problematic bacteria associated with increasing antimicrobial resistance, continuous efforts for the discovery of lead compounds as well as development of alternative therapies and faster diagnostics are required. This article summarizes the FDA-approved drugs to treat MRSA infections, the drugs in clinical trials, and the drug leads for MRSA and related Gram-positive bacterial infections. In addition, the article discusses the mode of action of antistaphylococcal molecules and the resistant mechanisms of some molecules. The number of pipeline drugs presently undergoing clinical trials is not particularly encouraging. There are limited and rather expensive therapeutic options for MRSA infections in the critically ill. Further research efforts are required for effective phage therapy on MRSA infections in clinical use, which seem to be attractive therapeutic options for the future.

Piezoelectric Versus Conventional Rotary Techniques for Impacted Third Molar Extraction

PubMed Central

Jiang, Qian; Qiu, Yating; Yang, Chi; Yang, Jingyun; Chen, Minjie; Zhang, Zhiyuan

2015-01-01

Abstract Impacted third molars are frequently encountered in clinical work. Surgical removal of impacted third molars is often required to prevent clinical symptoms. Traditional rotary cutting instruments are potentially injurious, and piezosurgery, as a new osteotomy technique, has been introduced in oral and maxillofacial surgery. No consistent conclusion has been reached regarding whether this new technique is associated with fewer or less severe postoperative sequelae after third molar extraction. The aim of this study was to compare piezosurgery with rotary osteotomy techniques, with regard to surgery time and the severity of postoperative sequelae, including pain, swelling, and trismus. We conducted a systematic literature search in the Cochrane Library, PubMed, Embase, and Google Scholar. The eligibility criteria of this study included the following: the patients were clearly diagnosed as having impacted mandibular third molars; the patients underwent piezosurgery osteotomy, and in the control group rotary osteotomy techniques, for removing impacted third molars; the outcomes of interest include surgery time, trismus, swelling or pain; the studies are randomized controlled trials. We used random-effects models to calculate the difference in the outcomes, and the corresponding 95% confidence interval. We calculated the weighted mean difference if the trials used the same measurement, and a standardized mean difference if otherwise. A total of seven studies met the eligibility criteria and were included in our analysis. Compared with rotary osteotomy, patients undergoing piezosurgery experienced longer surgery time (mean difference 4.13 minutes, 95% confidence interval 2.75–5.52, P < 0.0001). Patients receiving the piezoelectric technique had less swelling at postoperative days 1, 3, 5, and 7 (all Ps ≤0.023). Additionally, there was a trend of less postoperative pain and trismus in the piezosurgery groups. The number of included randomized controlled trials and the sample size of each trial were relatively small, double blinding was not possible, and cost analysis was unavailable due to a lack of data. Our meta-analysis indicates that although patients undergoing piezosurgery experienced longer surgery time, they had less postoperative swelling, indicating that piezosurgery is a promising alternative technique for extraction of impacted third molars. PMID:26469902

Fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery.

PubMed

Cheng, Yao; Ye, Mingxin; Xiong, Xianze; Peng, Su; Wu, Hong Mei; Cheng, Nansheng; Gong, Jianping

2016-02-15

Postoperative pancreatic fistula is one of the most frequent and potentially life-threatening complications following pancreatic resections. Fibrin sealants are introduced to reduce postoperative pancreatic fistula by some surgeons. However, the use of fibrin sealants during pancreatic surgery is controversial. To assess the safety, effectiveness, and potential adverse effects of fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery. We searched The Cochrane Library (2015, Issue 7), MEDLINE (1946 to 26 August 2015), EMBASE (1980 to 26 August 2015), Science Citation Index Expanded (1900 to 26 August 2015), and Chinese Biomedical Literature Database (CBM) (1978 to 26 August 2015). We included all randomized controlled trials that compared fibrin sealant group (fibrin glue or fibrin sealant patch) versus control group (no fibrin sealant or placebo) in people undergoing pancreatic surgery. Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes (or a Peto odds ratio for very rare outcomes), and the mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). We included nine trials involving 1095 participants who were randomized to the fibrin sealant group (N = 550) and the control group (N = 545) after pancreatic surgery. All of the trials were at high risk of bias. There was no evidence of differences in overall postoperative pancreatic fistula (fibrin sealant 29.6%; control 31.0%; RR 0.93, 95% CI 0.71 to 1.21; P = 0.58; nine studies; low-quality evidence), postoperative mortality (3.1% versus 2.1%; Peto OR 1.29, 95% CI 0.59 to 2.82; P = 0.53; eight studies; very low-quality evidence), overall postoperative morbidity (29.6% versus 28.9%; RR 1.04, 95% CI 0.82 to 1.32; P = 0.77; five studies), reoperation rate (8.7% versus 10.7%; RR 0.80, 95% CI 0.53 to 1.21; P = 0.29; five studies), or length of hospital stay (12.9 days versus 13.1 days; MD -0.73 days, 95% CI -2.20 to 0.74; P = 0.331; six studies) between the groups. The proportion of postoperative pancreatic fistula that was clinically significant was not mentioned in most trials. On inclusion of trials that clearly distinguished clinically significant fistulas, there was inadequate evidence to establish the effect of fibrin sealants on clinically significant postoperative pancreatic fistula (9.4% versus 13.4%; RR 0.72, 95% CI 0.42 to 1.21; P = 0.21; three studies). Quality of life and cost effectiveness were not reported in any of the trials. Based on the current available evidence, fibrin sealants do not seem to prevent postoperative pancreatic fistula in people undergoing pancreatic surgery.

Cervical auscultation in the diagnosis of oropharyngeal aspiration in children: a study protocol for a randomised controlled trial.

PubMed

Frakking, Thuy T; Chang, Anne B; O'Grady, Kerry-Ann F; Walker-Smith, Katie; Weir, Kelly A

2013-11-07

Oropharyngeal aspiration (OPA) can lead to recurrent respiratory illnesses and chronic lung disease in children. Current clinical feeding evaluations performed by speech pathologists have poor reliability in detecting OPA when compared to radiological procedures such as the modified barium swallow (MBS). Improved ability to diagnose OPA accurately via clinical evaluation potentially reduces reliance on expensive, less readily available radiological procedures. Our study investigates the utility of adding cervical auscultation (CA), a technique of listening to swallowing sounds, in improving the diagnostic accuracy of a clinical evaluation for the detection of OPA. We plan an open, unblinded, randomised controlled trial at a paediatric tertiary teaching hospital. Two hundred and sixteen children fulfilling the inclusion criteria will be randomised to one of the two clinical assessment techniques for the clinical detection of OPA: (1) clinical feeding evaluation only (CFE) group or (2) clinical feeding evaluation with cervical auscultation (CFE + CA) group. All children will then undergo an MBS to determine radiologically assessed OPA. The primary outcome is the presence or absence of OPA, as determined on MBS using the Penetration-Aspiration Scale. Our main objective is to determine the sensitivity, specificity, negative and positive predictive values of 'CFE + CA' versus 'CFE' only compared to MBS-identified OPA. Early detection and appropriate management of OPA is important to prevent chronic pulmonary disease and poor growth in children. As the reliability of CFE to detect OPA is low, a technique that can improve the diagnostic accuracy of the CFE will help minimise consequences to the paediatric respiratory system. Cervical auscultation is a technique that has previously been documented as a clinical adjunct to the CFE; however, no published RCTs addressing the reliability of this technique in children exist. Our study will be the first to establish the utility of CA in assessing and diagnosing OPA risk in young children. Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12613000589785.

A targeted decision aid for the elderly to decide whether to undergo colorectal cancer screening: development and results of an uncontrolled trial

PubMed Central

2010-01-01

Background Competing causes of mortality in the elderly decrease the potential net benefit from colorectal cancer screening and increase the likelihood of potential harms. Individualized decision making has been recommended, so that the elderly can decide whether or not to undergo colorectal cancer (CRC) screening. The objective is to develop and test a decision aid designed to promote individualized colorectal cancer screening decision making for adults age 75 and over. Methods We used formative research and cognitive testing to develop and refine the decision aid. We then tested the decision aid in an uncontrolled trial. The primary outcome was the proportion of patients who were prepared to make an individualized decision, defined a priori as having adequate knowledge (10/15 questions correct) and clear values (25 or less on values clarity subscale of decisional conflict scale). Secondary outcomes included overall score on the decisional conflict scale, and preferences for undergoing screening. Results We enrolled 46 adults in the trial. The decision aid increased the proportion of participants with adequate knowledge from 4% to 52% (p < 0.01) and the proportion prepared to make an individualized decision from 4% to 41% (p < 0.01). The proportion that preferred to undergo CRC screening decreased from 67% to 61% (p = 0. 76); 7 participants (15%) changed screening preference (5 against screening, 2 in favor of screening) Conclusion In an uncontrolled trial, the elderly participants appeared better prepared to make an individualized decision about whether or not to undergo CRC screening after using the decision aid. PMID:20849625

Comparing the effects of relaxation technique and inhalation aromatherapy on fatigue in patients undergoing hemodialysis.

PubMed

Hassanzadeh, Mohammadali; Kiani, Fatemeh; Bouya, Salehoddin; Zarei, Mohammad

2018-05-01

This study aimed to compare the effects of relaxation techniques on fatigue in hemodialysis patients. This clinical trial study was conducted on 105 hemodialysis patients. The subjects were categorized into three groups as: relaxation, aromatherapy and control. In the relaxation group, Benson muscle relaxation techniques were employed; in the aromatherapy group, the inhalation of two drops of 5% lavender essential oil used and the control group only received regular healthcare actions. Data collected by using brief fatigue inventory, before and after the intervention. Results of the current study indicated significant differences in the mean of changes in fatigue scores before and after the intervention between the relaxation and aromatherapy groups, but the difference was insignificant in the control group. Aromatherapy with lavender essential oil can decrease the level of fatigue in the patients undergoing hemodialysis compared to Benson relaxation techniques. Copyright © 2018 Elsevier Ltd. All rights reserved.

Autogenic training reduces anxiety after coronary angioplasty: a randomized clinical trial.

PubMed

Kanji, N; White, A R; Ernst, E

2004-03-01

Autogenic training (AT) is a method of autosuggestion with some potential for reducing anxiety. This study tests whether AT lowers anxiety levels experienced by patients undergoing coronary angioplasty. Fifty-nine patients were randomly assigned to receive regular AT or no such therapy as an adjunct to standard care for 5 months. The primary outcome measure was State Anxiety at 2 months. Qualitative information was generated by face-to-face interviews. State Anxiety showed a significant intergroup difference both at 2 and 5 months. This finding was corroborated by secondary outcome measures, for example, quality of life, and by qualitative information about patients' experiences. The results do not allow us to determine whether the observed effects are specific to AT or of a nonspecific nature. Our results suggest that AT may have a role in reducing anxiety of patients undergoing coronary angioplasty.

Safety of 6-month duration of dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndromes: Rationale and design of the Smart Angioplasty Research Team-safety of 6-month duration of Dual Antiplatelet Therapy after percutaneous coronary intervention in patients with acute coronary syndromes (SMART-DATE) prospective multicenter randomized trial.

PubMed

Lee, Joo Myung; Cho, Deok-Kyu; Hahn, Joo-Yong; Song, Young Bin; Park, Taek Kyu; Oh, Ju-Hyeon; Lee, Jin Bae; Doh, Joon-Hyung; Kim, Sang-Hyun; Yang, Jeong Hoon; Choi, Jin-Ho; Choi, Seung-Hyuck; Lee, Sang Hoon; Gwon, Hyeon-Cheol

2016-12-01

Dual antiplatelet therapy (DAPT) is a fundamental treatment that optimizes clinical outcomes after percutaneous coronary intervention, especially in patients with acute coronary syndrome (ACS). Although current international guidelines recommend DAPT for at least 12 months after implantation of a drug-eluting stent in patients with ACS, these recommendations are not based on randomized controlled trials dedicated to ACS population. The SMART-DATE trial is a prospective, multicenter, randomized, and open-label study to demonstrate the noninferiority of 6-month DAPT compared with 12 months or longer DAPT in patients with ACS undergoing percutaneous coronary intervention. A total of 2,700 patients will undergo prospective, random assignment to either of the DAPT duration groups. To minimize the bias from different stent devices, the type of stents will be randomly assigned (everolimus-eluting stents, zotarolimus-eluting stents, or biolimus A9-eluting stents). The primary end point is a composite of all-cause death, myocardial infarction, and cerebrovascular events at 18 months after the index procedure. The major secondary end points are definite/probable stent thrombosis defined by the Academic Research Consortium and bleeding defined by Bleeding Academic Research Consortium type 2-5. The SMART-DATE randomized trial is the first study exploring the safety of 6-month DAPT compared with conventional 12-month or longer DAPT dedicated to patients with ACS after second-generation drug-eluting stent implantation. Copyright © 2016 Elsevier Inc. All rights reserved.

Safety of Simultaneous Coronary Artery Bypass Grafting and Carotid Endarterectomy Versus Isolated Coronary Artery Bypass Grafting: A Randomized Clinical Trial.

PubMed

Weimar, Christian; Bilbilis, Konstantinos; Rekowski, Jan; Holst, Torulv; Beyersdorf, Friedhelm; Breuer, Martin; Dahm, Manfred; Diegeler, Anno; Kowalski, Arne; Martens, Sven; Mohr, Friedrich W; Ondrášek, Jiri; Reiter, Beate; Roth, Peter; Seipelt, Ralf; Siggelkow, Markus; Steinhoff, Gustav; Moritz, Anton; Wilhelmi, Mathias; Wimmer-Greinecker, Gerhard; Diener, Hans-Christoph; Jakob, Heinz; Ose, Claudia; Scherag, Andre; Knipp, Stephan C

2017-10-01

The optimal operative strategy in patients with severe carotid artery disease undergoing coronary artery bypass grafting (CABG) is unknown. We sought to investigate the safety and efficacy of synchronous combined carotid endarterectomy and CABG as compared with isolated CABG. Patients with asymptomatic high-grade carotid artery stenosis ≥80% according to ECST (European Carotid Surgery Trial) ultrasound criteria (corresponding to ≥70% NASCET [North American Symptomatic Carotid Endarterectomy Trial]) who required CABG surgery were randomly assigned to synchronous carotid endarterectomy+CABG or isolated CABG. To avoid unbalanced prognostic factor distributions, randomization was stratified by center, age, sex, and modified Rankin Scale. The primary composite end point was the rate of stroke or death at 30 days. From 2010 to 2014, a total of 129 patients were enrolled at 17 centers in Germany and the Czech Republic. Because of withdrawal of funding after insufficient recruitment, enrolment was terminated early. At 30 days, the rate of any stroke or death in the intention-to-treat population was 12/65 (18.5%) in patients receiving synchronous carotid endarterectomy+CABG as compared with 6/62 (9.7%) in patients receiving isolated CABG (absolute risk reduction, 8.8%; 95% confidence interval, -3.2% to 20.8%; P WALD =0.12). Also for all secondary end points at 30 days and 1 year, there was no evidence for a significant treatment-group effect although patients undergoing isolated CABG tended to have better outcomes. Although our results cannot rule out a treatment-group effect because of lack of power, a superiority of the synchronous combined carotid endarterectomy+CABG approach seems unlikely. Five-year follow-up of patients is still ongoing. URL: https://www.controlled-trials.com. Unique identifier: ISRCTN13486906. Copyright © 2017 The Author(s).

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.

Preoperative analgesics for additional pain relief in children and adolescents having dental treatment.

PubMed

Ashley, Paul F; Parekh, Susan; Moles, David R; Anand, Prabhleen; MacDonald, Laura C I

2016-08-08

Fear of dental pain is a major barrier to treatment for children who need dental care. The use of preoperative analgesics has the potential to reduce postoperative discomfort and intraoperative pain. We reviewed the available evidence to determine whether further research is warranted and to inform the development of prescribing guidelines. This is an update of a Cochrane review published in 2012. To assess the effects of preoperative analgesics for intraoperative or postoperative pain relief (or both) in children and adolescents undergoing dental treatment without general anaesthesia or sedation. We searched the following electronic databases: Cochrane Oral Health's Trials Register (to 5 January 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2015, Issue 12), MEDLINE via OVID (1946 to 5 January 2016), EMBASE via OVID (1980 to 5 January 2016), LILACS via BIREME (1982 to 5 January 2016) and the ISI Web of Science (1945 to 5 January 2016). We searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials to 5 January 2016. There were no restrictions regarding language or date of publication in the searches of the electronic databases. We handsearched several specialist journals dating from 2000 to 2011.We checked the reference lists of all eligible trials for additional studies. We contacted specialists in the field for any unpublished data. Randomised controlled clinical trials of analgesics given before dental treatment versus placebo or no analgesics in children and adolescents up to 17 years of age. We excluded children and adolescents having dental treatment under sedation (including nitrous oxide/oxygen) or general anaesthesia. Two review authors assessed titles and abstracts of the articles obtained from the searches for eligibility, undertook data extraction and assessed the risk of bias in the included studies. We assessed the quality of the evidence using GRADE criteria. We included five trials in the review, with 190 participants in total. We did not identify any new studies for inclusion from the updated search in January 2016.Three trials were related to dental treatment, i.e. restorative and extraction treatments; two trials related to orthodontic treatment. We did not judge any of the included trials to be at low risk of bias.Three of the included trials compared paracetamol with placebo, only two of which provided data for analysis (presence or absence of parent-reported postoperative pain behaviour). Meta-analysis of the two trials gave arisk ratio (RR) for postoperative pain of 0.81 (95% confidence interval (CI) 0.53 to 1.22; two trials, 100 participants; P = 0.31), which showed no evidence of a benefit in taking paracetamol preoperatively (52% reporting pain in the placebo group versus 42% in the paracetamol group). One of these trials was at unclear risk of bias, and the other was at high risk. The quality of the evidence is low. One study did not have any adverse events; the other two trials did not mention adverse events.Four of the included trials compared ibuprofen with placebo. Three of these trials provided useable data. One trial reported no statistical difference in postoperative pain experienced by the ibuprofen group and the control group for children undergoing dental treatment. We pooled the data from the other two trials, which included participants who were having orthodontic separator replacement without a general anaesthetic, to determine the effect of preoperative ibuprofen on the severity of postoperative pain. There was a statistically significant mean difference in severity of postoperative pain of -13.44 (95% CI -23.01 to -3.88; two trials, 85 participants; P = 0.006) on a visual analogue scale (0 to 100), which indicated a probable benefit for preoperative ibuprofen before this orthodontic procedure. However, both trials were at high risk of bias. The quality of the evidence is low. Only one of the trials reported adverse events (one participant from the ibuprofen group and one from the placebo group reporting a lip or cheek biting injury). From the available evidence, we cannot determine whether or not preoperative analgesics are of benefit in paediatric dentistry for procedures under local anaesthetic. There is probably a benefit in using preoperative analgesics prior to orthodontic separator placement. The quality of the evidence is low. Further randomised clinical trials should be completed with appropriate sample sizes and well defined outcome measures.

Comparisons of Patient Demographics in Prospective Sports, Shoulder, and National Database Initiatives.

PubMed

Saltzman, Bryan M; Cvetanovich, Gregory L; Bohl, Daniel D; Cole, Brian J; Bach, Bernard R; Romeo, Anthony A

2016-09-01

There has been increased emphasis in orthopaedics on high-quality prospective research to provide evidence-based treatment guidelines, particularly in sports medicine/shoulder surgery. The external validity of these studies has not been established, and the generalizability of the results to clinical practice in the United States is unknown. Comparison of patient demographics in major prospective studies of arthroscopic sports and shoulder surgeries to patients undergoing the same procedures in the National Surgical Quality Improvement Program (NSQIP) database will show substantial differences to question the generalizability and external validity of those studies. Cross-sectional study; Level of evidence, 3. This study utilized patients undergoing arthroscopic anterior cruciate ligament reconstruction (ACLR), meniscectomy (MX), rotator cuff repair (RCR), and shoulder stabilization (SS) from the NSQIP database (2005-2013). Two prospective studies (either randomized controlled trials or, in 1 case, a major cohort study) were identified for each of the 4 procedures for comparison. Demographic variables available for comparison in both the identified prospective studies and the NSQIP included age, sex, and body mass index (BMI). From the NSQIP database, 5576 ACLR patients, 18,882 MX patients, 7282 RCR patients, and 993 SS patients were identified. The comparison clinical studies included cohort sizes as follows: ACLR, n = 121 and 2683; MX, n = 146 and 330; RCR, n = 90 and 103; SS, n = 88 and 196. Age differed significantly between the NSQIP and the patients in 6 of the 8 prospective clinical studies. Sex differed significantly between the NSQIP and the patients in 7 of the 8 prospective clinical studies. BMI differed significantly between the NSQIP and the patients of all 4 of the prospective clinical studies that reported this demographic variable. Significant differences exist for patient age, sex, and BMI between patients included in major sports medicine/shoulder prospective studies and corresponding patients undergoing the same procedures in a nationwide database of academic and community centers in the United States. Future work is needed to understand whether major prospective clinical studies-frequently performed in high-volume, specialized practices-are truly indicative of the types of patients treated and expected results in the general orthopaedic practice. This study additionally argues for the importance of initiating a national registry dedicated to patients undergoing orthopaedic procedures in the United States.

Optimizing Radiation Therapy Quality Assurance in Clinical Trials: A TROG 08.03 RAVES Substudy

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

Trada, Yuvnik, E-mail: yuvnik@gmail.com; Kneebone, Andrew; Paneghel, Andrea

2015-12-01

Purpose: To explore site- and clinician-level factors associated with protocol violations requiring real-time-review (RTR) resubmission in a multicenter clinical trial to help tailor future quality assurance (QA) protocols. Methods and Materials: RAVES (Radiation Therapy–Adjuvant vs Early Salvage) (Trans-Tasman Radiation Oncology Group 08.03) is a randomized trial comparing adjuvant with early salvage radiation therapy in men with positive surgical margins or pT3 disease after prostatectomy. Quality assurance in RAVES required each clinician and site to submit a credentialing dummy run (DR) and for each patient's radiation therapy plan to undergo external RTR before treatment. Prospectively defined major violations from trial protocol requiredmore » remedy and resubmission. Site and clinician factors associated with RTR resubmission were examined using hierarchical modeling. Results: Data were collected from 171 consecutive patients, treated by 46 clinicians at 32 hospitals. There were 47 RTR resubmissions (27%) due to 65 major violations. The relative rate of resubmission decreased by 29% per year as the study progressed (odds ratio OR. 0.71, P=.02). The majority of resubmissions were due to contouring violations (39 of 65) and dosimetric violations (22 of 65). For each additional patient accrued, significant decreases in RTR resubmission were seen at both clinician level (OR 0.75, P=.02) and site level (OR 0.72, P=.01). The rate of resubmission due to dosimetric violations was only 1.6% after the first 5 patients. Use of IMRT was associated with lower rates of resubmission compared with 3-dimensional conformal radiation therapy (OR 0.38, P=.05). Conclusion: Several low- and high-risk factors that may assist with tailoring future clinical trial QA were identified. Because the real-time resubmission rate was largely independent of the credentialing exercise, some form of RTR QA is recommended. The greatest benefit from QA was derived early in trial activation and clinician experience.« less

Rationale and design of a multicentre, prospective, randomised, controlled clinical trial to evaluate the efficacy of the adipose graft transposition procedure in patients with a myocardial scar: the AGTP II trial.

PubMed

Gastelurrutia, Paloma; Gálvez-Montón, Carolina; Cámara, Maria Luisa; Bustamante-Munguira, Juan; García-Pavia, Pablo; Avanzas, Pablo; Alberto San Román, J; Pascual-Figal, Domingo; Teresa, Eduardo de; Crespo-Leiro, Maria G; Manito, Nicolás; Núñez, Julio; Fernández-Avilés, Francisco; Caballero, Ángel; Teis, Albert; Lupón, Josep; Brugada, Ramón; Martín, Carlos; Silva, Jacobo; Revilla-Orodea, Ana; Cánovas, Sergio J; Melero, Jose M; Cuenca-Castillo, Jose J; Gonzalez-Pinto, Angel; Bayes-Genis, Antoni

2017-08-04

Cardiac adipose tissue is a source of progenitor cells with regenerative capacity. Studies in rodents demonstrated that the intramyocardial delivery of cells derived from this tissue improves cardiac function after myocardial infarction (MI). We developed a new reparative approach for damaged myocardium that integrates the regenerative properties of cardiac adipose tissue with tissue engineering. In the adipose graft transposition procedure (AGTP), we dissect a vascularised flap of autologous pericardial adipose tissue and position it over the myocardial scarred area. Following encouraging results in acute and chronic MI porcine models, we performed the clinical trial (NCT01473433, AdiFLAP trial) to evaluate safety in patients with chronic MI undergoing coronary artery bypass graft. The good safety profile and trends in efficacy warranted a larger trial. The AGTP II trial (NCT02798276) is an investigator initiated, prospective, randomised, controlled, multicentre study to assess the efficacy of the AGTP in 108 patients with non-revascularisable MI. Patients will be assigned to standard clinical practice or the AGTP. The primary endpoint is change in necrotic mass ratio by gadolinium enhancement at 91 and 365 days. Secondary endpoints include improvement in regional contractibility by MRI at 91 and 365 days; changes in functional MRI parameters (left ventricular ejection fraction, left and right ventricular geometric remodelling) at 91 and 365 days; levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) at 7, 91 and 365 days; appearance of arrhythmias from 24 hour Holter monitoring at 24 hours, and at 91 and 365 days; all cause death or re-hospitalisation at 365 days; and cardiovascular death or re-hospitalisation at 365 days. The institutional review board approved the trial which will comply with the Declaration of Helsinki. All patients will provide informed consent. It may offer a novel, effective and technically simple technique for patients with no other therapeutic options. The results will be submitted to indexed medical journals and national and international meetings. ClinicalTrials.gov: NCT02798276, pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Risk of Acute Kidney Injury in Patients Randomized to a Restrictive Versus Liberal Approach to Red Blood Cell Transfusion in Cardiac Surgery: A Substudy Protocol of the Transfusion Requirements in Cardiac Surgery III Noninferiority Trial.

PubMed

Garg, Amit X; Shehata, Nadine; McGuinness, Shay; Whitlock, Richard; Fergusson, Dean; Wald, Ron; Parikh, Chirag; Bagshaw, Sean M; Khanykin, Boris; Gregory, Alex; Syed, Summer; Hare, Gregory M T; Cuerden, Meaghan S; Thorpe, Kevin E; Hall, Judith; Verma, Subodh; Roshanov, Pavel S; Sontrop, Jessica M; Mazer, C David

2018-01-01

When safe to do so, avoiding blood transfusions in cardiac surgery can avoid the risk of transfusion-related infections and other complications while protecting a scarce resource and reducing costs. This protocol describes a kidney substudy of the Transfusion Requirements in Cardiac Surgery III (TRICS-III) trial, a multinational noninferiority randomized controlled trial to determine whether the risk of major clinical outcomes in patients undergoing planned cardiac surgery with cardiopulmonary bypass is no greater with a restrictive versus liberal approach to red blood cell transfusion. The objective of this substudy is to determine whether the risk of acute kidney injury is no greater with a restrictive versus liberal approach to red blood cell transfusion, and whether this holds true in patients with and without preexisting chronic kidney disease. Multinational noninferiority randomized controlled trial conducted in 73 centers in 19 countries (2014-2017). Patients (~4800) undergoing planned cardiac surgery with cardiopulmonary bypass. The primary outcome of this substudy is perioperative acute kidney injury, defined as an acute rise in serum creatinine from the preoperative value (obtained in the 30-day period before surgery), where an acute rise is defined as ≥26.5 μmol/L in the first 48 hours after surgery or ≥50% in the first 7 days after surgery. We will report the absolute risk difference in acute kidney injury and the 95% confidence interval. We will repeat the primary analysis using alternative definitions of acute kidney injury, including staging definitions, and will examine effect modification by preexisting chronic kidney disease (defined as a preoperative estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m 2 ). It is not possible to blind patients or providers to the intervention; however, objective measures will be used to assess outcomes, and outcome assessors will be blinded to the intervention assignment. Substudy results will be reported by the year 2018. This substudy will provide generalizable estimates of the risk of acute kidney injury of a restrictive versus liberal approach to red blood cell transfusion in the presence of anemia during cardiac surgery done with cardiopulmonary bypass. www.clinicaltrials.gov; clinical trial registration number NCT 02042898.

Sphincter of Oddi botulinum toxin injection to prevent pancreatic fistula after distal pancreatectomy.

PubMed

Hackert, Thilo; Klaiber, Ulla; Hinz, Ulf; Kehayova, Tzveta; Probst, Pascal; Knebel, Phillip; Diener, Markus K; Schneider, Lutz; Strobel, Oliver; Michalski, Christoph W; Ulrich, Alexis; Sauer, Peter; Büchler, Markus W

2017-05-01

Postoperative pancreatic fistula represents the most important complication after distal pancreatectomy. The aim of this study was to evaluate the use of a preoperative endoscopic injection of botulinum toxin into the sphincter of Oddi to prevent postoperative pancreatic fistula (German Clinical Trials Register number: DRKS00007885). This was an investigator-initiated, prospective clinical phase I/II trial with an exploratory study design. We included patients who underwent preoperative endoscopic sphincter botulinum toxin injection (100 units of Botox). End points were the feasibility, safety, and postoperative outcomes, including postoperative pancreatic fistula within 30 days after distal pancreatectomy. Botulinum toxin patients were compared with a control collective of patients undergoing distal pancreatectomy without botulinum toxin injection by case-control matching in a 1:1 ratio. Between February 2015 and February 2016, 29 patients were included. All patients underwent successful sphincter of Oddi botulinum toxin injection within a median of 6 (range 0-10) days before operation. One patient had an asymptomatic, self-limiting (48 hours) increase in serum amylase and lipase after injection. Distal pancreatectomy was performed in 24/29 patients; 5 patients were not resectable. Of the patients receiving botulinum toxin, 7 (29%) had increased amylase levels in drainage fluid on postoperative day 3 (the International Study Group of Pancreatic Surgery definition of postoperative pancreatic fistula grade A) without symptoms or need for reintervention. Importantly, no clinically relevant fistulas (International Study Group of Pancreatic Surgery grades B/C) were observed in botulinum toxin patients compared to 33% postoperative pancreatic fistula grade B/C in case-control patients (P < .004). Preoperative sphincter of Oddi botulinum toxin injection is a novel and safe approach to decrease the incidence of clinically relevant postoperative pancreatic fistula after distal pancreatectomy. The results of the present trial suggest its efficacy in the prevention of clinically relevant postoperative pancreatic fistula and are validated currently in the German Federal Government-sponsored, multicenter, randomized controlled PREBOT trial. Copyright © 2016 Elsevier Inc. All rights reserved.

Hand-suture versus stapling for closure of loop ileostomy: HASTA-Trial: a study rationale and design for a randomized controlled trial

PubMed Central

2011-01-01

Background Colorectal cancer is the second most common tumor in developed countries, with a lifetime prevalence of 5%. About one third of these tumors are located in the rectum. Surgery in terms of low anterior resection with mesorectal excision is the central element in the treatment of rectal cancer being the only option for definite cure. Creating a protective diverting stoma prevents complications like anastomotic failure and meanwhile is the standard procedure. Bowel obstruction is one of the main and the clinically and economically most relevant complication following closure of loop ileostomy. The best surgical technique for closure of loop ileostomy has not been defined yet. Methods/Design A study protocol was developed on the basis of the only randomized controlled mono-center trial to solve clinical equipoise concerning the optimal surgical technique for closure of loop ileostomy after low anterior resection due to rectal cancer. The HASTA trial is a multi-center pragmatic randomized controlled surgical trial with two parallel groups to compare hand-suture versus stapling for closure of loop ileostomy. It will include 334 randomized patients undergoing closure of loop ileostomy after low anterior resection with protective ileostomy due to rectal cancer in approximately 20 centers consisting of German hospitals of all level of health care. The primary endpoint is the rate of bowel obstruction within 30 days after ileostomy closure. In addition, a set of surgical and general variables including quality of life will be analyzed with a follow-up of 12 months. An investigators meeting with a practical session will help to minimize performance bias and enforce protocol adherence. Centers are monitored centrally as well as on-site before and during recruitment phase to assure inclusion, treatment and follow up according to the protocol. Discussion Aim of the HASTA trial is to evaluate the efficacy of hand-suture versus stapling for closure of loop ileostomy in patients with rectal cancer. Trial registration German Clinical Trial Register Number: DRKS00000040 PMID:21303515

A pragmatic multi-centre randomised controlled trial of fluid loading in high-risk surgical patients undergoing major elective surgery--the FOCCUS study.

PubMed

Cuthbertson, Brian H; Campbell, Marion K; Stott, Stephen A; Elders, Andrew; Hernández, Rodolfo; Boyers, Dwayne; Norrie, John; Kinsella, John; Brittenden, Julie; Cook, Jonathan; Rae, Daniela; Cotton, Seonaidh C; Alcorn, David; Addison, Jennifer; Grant, Adrian

2011-01-01

Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery. This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome. A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective. Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care. Prospective Clinical Trials, ISRCTN32188676.

Endometrial scratching in women with implantation failure after a first IVF/ICSI cycle; does it lead to a higher live birth rate? The SCRaTCH study: a randomized controlled trial (NTR 5342).

PubMed

van Hoogenhuijze, N E; Torrance, H L; Mol, F; Laven, J S E; Scheenjes, E; Traas, M A F; Janssen, C; Cohlen, B; Teklenburg, G; de Bruin, J P; van Oppenraaij, R; Maas, J W M; Moll, E; Fleischer, K; van Hooff, M H; de Koning, C; Cantineau, A; Lambalk, C B; Verberg, M; Nijs, M; Manger, A P; van Rumste, M; van der Voet, L F; Preys-Bosman, A; Visser, J; Brinkhuis, E; den Hartog, J E; Sluijmer, A; Jansen, F W; Hermes, W; Bandell, M L; Pelinck, M J; van Disseldorp, J; van Wely, M; Smeenk, J; Pieterse, Q D; Boxmeer, J C; Groenewoud, E R; Eijkemans, M J C; Kasius, J C; Broekmans, F J M

2017-07-21

Success rates of assisted reproductive techniques (ART) are approximately 30%, with the most important limiting factor being embryo implantation. Mechanical endometrial injury, also called 'scratching', has been proposed to positively affect the chance of implantation after embryo transfer, but the currently available evidence is not yet conclusive. The primary aim of this study is to determine the effect of endometrial scratching prior to a second fresh in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle on live birth rates in women with a failed first IVF/ICSI cycle. Multicenter randomized controlled trial in Dutch academic and non-academic hospitals. A total of 900 women will be included of whom half will undergo an endometrial scratch in the luteal phase of the cycle prior to controlled ovarian hyperstimulation using an endometrial biopsy catheter. The primary endpoint is the live birth rate after the 2 nd fresh IVF/ICSI cycle. Secondary endpoints are costs, cumulative live birth rate (after the full 2 nd IVF/ICSI cycle and over 12 months of follow-up); clinical and ongoing pregnancy rate; multiple pregnancy rate; miscarriage rate and endometrial tissue parameters associated with implantation failure. Multiple studies have been performed to investigate the effect of endometrial scratching on live birth rates in women undergoing IVF/ICSI cycles. Due to heterogeneity in both the method and population being scratched, it remains unclear which group of women will benefit from the procedure. The SCRaTCH trial proposed here aims to investigate the effect of endometrial scratching prior to controlled ovarian hyperstimulation in a large group of women undergoing a second IVF/ICSI cycle. NTR 5342 , registered July 31 st , 2015. Version 4.10, January 4th, 2017.

Effect of protective ventilation on postoperative pulmonary complications in patients undergoing general anaesthesia: a meta-analysis of randomised controlled trials.

PubMed

Tao, Tianzhu; Bo, Lulong; Chen, Feng; Xie, Qun; Zou, Yun; Hu, Baoji; Li, Jinbao; Deng, Xiaoming

2014-06-24

To determine whether anaesthetised patients undergoing surgery could benefit from intraoperative protective ventilation strategies. MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to February 2014. Eligible studies evaluated protective ventilation versus conventional ventilation in anaesthetised patients without lung injury at the onset of mechanical ventilation. The primary outcome was the incidence of postoperative pulmonary complications. Included studies must report at least one of the following end points: the incidence of atelectasis or acute lung injury or pulmonary infections. Four studies (594 patients) were included. Meta-analysis using a random effects model showed a significant decrease in the incidence of atelectasis (OR=0.36; 95% CI 0.22 to 0.60; p<0.0001; I(2)=0%) and pulmonary infections (OR=0.30; 95% CI 0.14 to 0.68; p=0.004; I(2)=20%) in patients receiving protective ventilation. Ventilation with protective strategies did not reduce the incidence of acute lung injury (OR=0.40; 95% CI 0.07 to 2.15; p=0.28; I(2)=12%), all-cause mortality (OR=0.77; 95% CI 0.33 to 1.79; p=0.54; I(2)=0%), length of hospital stay (weighted mean difference (WMD)=-0.52 day, 95% CI -4.53 to 3.48 day; p=0.80; I(2)=63%) or length of intensive care unit stay (WMD=-0.55 day, 95% CI -2.19 to 1.09 day; p=0.51; I(2)=39%). Intraoperative use of protective ventilation strategies has the potential to reduce the incidence of postoperative pulmonary complications in patients undergoing general anaesthesia. Prospective, well-designed clinical trials are warranted to confirm the beneficial effects of protective ventilation strategies in surgical patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effect of protective ventilation on postoperative pulmonary complications in patients undergoing general anaesthesia: a meta-analysis of randomised controlled trials

PubMed Central

Tao, Tianzhu; Bo, Lulong; Chen, Feng; Xie, Qun; Zou, Yun; Hu, Baoji; Li, Jinbao; Deng, Xiaoming

2014-01-01

Objective To determine whether anaesthetised patients undergoing surgery could benefit from intraoperative protective ventilation strategies. Methods MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to February 2014. Eligible studies evaluated protective ventilation versus conventional ventilation in anaesthetised patients without lung injury at the onset of mechanical ventilation. The primary outcome was the incidence of postoperative pulmonary complications. Included studies must report at least one of the following end points: the incidence of atelectasis or acute lung injury or pulmonary infections. Results Four studies (594 patients) were included. Meta-analysis using a random effects model showed a significant decrease in the incidence of atelectasis (OR=0.36; 95% CI 0.22 to 0.60; p<0.0001; I2=0%) and pulmonary infections (OR=0.30; 95% CI 0.14 to 0.68; p=0.004; I2=20%) in patients receiving protective ventilation. Ventilation with protective strategies did not reduce the incidence of acute lung injury (OR=0.40; 95% CI 0.07 to 2.15; p=0.28; I2=12%), all-cause mortality (OR=0.77; 95% CI 0.33 to 1.79; p=0.54; I2=0%), length of hospital stay (weighted mean difference (WMD)=−0.52 day, 95% CI −4.53 to 3.48 day; p=0.80; I2=63%) or length of intensive care unit stay (WMD=−0.55 day, 95% CI −2.19 to 1.09 day; p=0.51; I2=39%). Conclusions Intraoperative use of protective ventilation strategies has the potential to reduce the incidence of postoperative pulmonary complications in patients undergoing general anaesthesia. Prospective, well-designed clinical trials are warranted to confirm the beneficial effects of protective ventilation strategies in surgical patients. PMID:24961718

Randomized Trial of Studer Pouch versus T-Pouch Orthotopic Ileal Neobladder in Patients with Bladder Cancer.

PubMed

Skinner, Eila C; Fairey, Adrian S; Groshen, Susan; Daneshmand, Siamak; Cai, Jie; Miranda, Gus; Skinner, Donald G

2015-08-01

The need to prevent reflux in the construction of an orthotopic ileal neobladder is controversial. We designed the USC-STAR trial to determine whether the T-pouch neobladder that included an antireflux mechanism was superior to the Studer pouch in patients with bladder cancer undergoing radical cystectomy. This single center, randomized, controlled trial recruited patients with clinically nonmetastatic bladder cancer scheduled to undergo radical cystectomy with neobladder. Eligible patients were randomly assigned to undergo T-pouch or Studer ileal orthotopic neobladder. Treatment assignment was not masked. The primary end point was change in renal function from baseline to 3 years. The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation was used to calculate the estimated glomerular filtration rate. Between February 2002 and November 2009, 237 patients were randomly assigned to T-pouch ileal orthotopic neobladder and 247 to Studer ileal orthotopic neobladder. Baseline characteristics did not differ between the groups. Between baseline and 3 years the estimated glomerular filtration rate decreased by 6.4 ml/minute/1.73 m(2) in the Studer group and 6.6 ml/minute/1.73 m(2) in the T-pouch group (p=0.35). Multivariable analysis showed that type of ileal orthotopic neobladder was not independently associated with 3-year renal function (p=0.63). However, baseline estimated glomerular filtration rate, age and urinary tract obstruction were independently associated with 3-year decline in renal function. Cumulative risk of urinary tract infection and overall late complications were not different between the groups, but the T-pouch was associated with an increased risk of secondary diversion related surgeries. T-pouch ileal orthotopic neobladder with an antireflux mechanism did not prevent a moderate reduction in renal function observed at 3 years compared to the Studer pouch, but did result in an increase in diversion related secondary surgical procedures. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Operative hysteroscopy versus vacuum aspiration for incomplete spontaneous abortion (HY-PER): study protocol for a randomized controlled trial.

PubMed

Huchon, Cyrille; Koskas, Martin; Agostini, Aubert; Akladios, Cherif; Alouini, Souhail; Bauville, Estelle; Bourdel, Nicolas; Fernandez, Hervé; Fritel, Xavier; Graesslin, Olivier; Legendre, Guillaume; Lucot, Jean-Philippe; Matheron, Isabelle; Panel, Pierre; Raiffort, Cyril; Fauconnier, Arnaud

2015-08-19

Incomplete spontaneous abortions are defined by the intrauterine retention of the products of conception after their incomplete or partial expulsion. This condition may be managed by expectant care, medical treatment or surgery. Vacuum aspiration is currently the standard surgical treatment in most centers. However, operative hysteroscopy has the advantage over vacuum aspiration of allowing the direct visualization of the retained conception product, facilitating its elective removal while limiting surgical complications. Inadequately powered retrospective studies reported subsequent fertility to be higher in patients treated by operative hysteroscopy than in those treated by vacuum aspiration. These data require confirmation in a randomized controlled trial comparing fertility rates between women undergoing hysteroscopy and those undergoing vacuum aspiration for incomplete spontaneous abortion. After providing written informed consent, 572 women with incomplete spontaneous abortion recruited from 15 centers across France will undergo randomization by a centralized computer system for treatment by either vacuum aspiration or operative hysteroscopy. Patients will not be informed of the type of treatment that they receive and will be cared for during their hospital stay in accordance with standard practices at each center. The patients will be monitored for pregnancy or adverse effects by a telephone conversation or questionnaire sent by e-mail or post over a period of two years. In cases of complications, failure of the intervention or diagnosis of uterine cavity disease, patient care will be left to the discretion of the medical center team. If our hypothesis is confirmed, this study will provide evidence that the use of operative hysteroscopy can increase the number of pregnancies continuing beyond 22 weeks of gestation in the two-year period following incomplete spontaneous abortion without increasing the incidence of morbidity and peri- and postoperative complications. The standard surgical treatment of this condition would thus be modified. This study would therefore have a large effect on the surgical management of incomplete spontaneous abortion. ClinicalTrials.gov Identifier: NCT02201732 ; registered on 17 July 2014.

Specific immunotherapy in ovarian cancer: a systematic review.

PubMed

Alipour, Soroush; Zoghi, Samaneh; Khalili, Nastaran; Hirbod-Mobarakeh, Armin; Emens, Leisha A; Rezaei, Nima

2016-10-01

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Several approaches of active and passive immunotherapy for EOC have been studied. The aim of this systematic review was to assess the clinical efficacy of specific immunotherapy in patients with EOC. We found 4524 references in seven databases and we included ten controlled clinical trials with 2285 patients with EOC reporting five active immunotherapeutic agents and three passive immunotherapies. Meta-analysis of six studies showed that overall there was not any significant difference in overall survival and recurrence-free survival between patients undergoing specific immunotherapy and those in control group. Most of the studies we evaluated reported a positive outcome from treatment with specific immunotherapy, although this was not significant.

Probiotic Supplementation in Morbid Obese Patients Undergoing One Anastomosis Gastric Bypass-Mini Gastric Bypass (OAGB-MGB) Surgery: a Randomized, Double-Blind, Placebo-Controlled, Clinical Trial.

PubMed

Karbaschian, Zohreh; Mokhtari, Zeinab; Pazouki, Abdolreza; Kabir, Ali; Hedayati, Mahdi; Moghadam, Somayeh Soleymanzadeh; Mirmiran, Parvin; Hekmatdoost, Azita

2018-05-03

Bariatric surgery is known as one of the most effective treatments for sustainable weight loss; however, it may be associated with some complications. This study was designed to examine the effects of probiotic supplementation on some morbidities related to this surgery. This was a placebo-controlled, double-blind, randomized clinical trial on morbid obese patients referred for One Anastomosis Gastric Bypass- Mini Gastric Bypass (OAGB-MGB) surgery to a tertiary referral center. Patients were assigned to receive a probiotic supplement (Familact®) or placebo from 4 weeks prior to surgery to 12 weeks after surgery. Anthropometric, biochemical, and inflammatory indices were evaluated at the beginning and the end of the study. At the end of study, significant improvements in some serum inflammatory markers, vitamin D status, and anthropometric measurements were observed (p < 0.05), which were significantly more in probiotic group rather than placebo group (p < 0.05). Moreover, significant improvements in glycemic indices and lipid profile were observed in both groups; however, these changes were not significantly different between the groups. There was no significant difference in serum levels of vitamin B 12 , folate, and homocysteine between groups at week 16 of the study. Our results indicate that probiotic supplementation promotes inflammatory markers, body weight loss, and status of vitamin D in patients undergoing OAGB-MGB bypass. Whether these findings will sustain in longer treatment duration remained to be elucidated in future studies. This study has been registered at Clinicaltrial.gov with registration number NCT02708589.

Nerve stimulator-guided sciatic-femoral nerve block in raptors undergoing surgical treatment of pododermatitis.

PubMed

d'Ovidio, Dario; Noviello, Emilio; Adami, Chiara

2015-07-01

To describe the nerve stimulator-guided sciatic-femoral nerve block in raptors undergoing surgical treatment of pododermatitis. Prospective clinical trial. Five captive raptors (Falco peregrinus) aged 6.7 ± 1.3 years. Anaesthesia was induced and maintained with isoflurane in oxygen. The sciatic-femoral nerve block was performed with 2% lidocaine (0.05 mL kg(-1) per nerve) as the sole intra-operative analgesic treatment. Intraoperative physiological variables were recorded every 10 minutes from endotracheal intubation until the end of anaesthesia. Assessment of intraoperative nociception was based on changes in physiological variables above baseline values, while evaluation of postoperative pain relied on species-specific behavioural indicators. The sciatic-femoral nerve block was feasible in raptors and the motor responses following electrical stimulation of both nerves were consistent with those reported in mammalian species. During surgery no rescue analgesia was required. The anaesthesia plane was stable and cardiorespiratory variables did not increase significantly in response to surgical stimulation. Iatrogenic complications, namely nerve damage and local anaesthetic toxicity, did not occur. Recovery was smooth and uneventful. The duration (mean ± SD) of the analgesic effect provided by the nerve block was 130 ± 20 minutes. The sciatic-femoral nerve block as described in dogs and rabbits can be performed in raptors as well. Further clinical trials with a control groups are required to better investigate the analgesic efficacy and the safety of this technique in raptors. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Is fusion necessary for thoracolumbar burst fracture treated with spinal fixation? A systematic review and meta-analysis.

PubMed

Diniz, Juliete M; Botelho, Ricardo V

2017-11-01

OBJECTIVE Thoracolumbar fractures account for 90% of spinal fractures, with the burst subtype corresponding to 20% of this total. Controversy regarding the best treatment for this condition remains. The traditional surgical approach, when indicated, involves spinal fixation and arthrodesis. Newer studies have brought the need for fusion associated with internal fixation into question. Not performing arthrodesis could reduce surgical time and intraoperative bleeding without affecting clinical and radiological outcomes. With this study, the authors aimed to assess the effect of fusion, adjuvant to internal fixation, on surgically treated thoracolumbar burst fractures. METHODS A search of the Medline and Cochrane Central Register of Controlled Trials databases was performed to identify randomized trials that compared the use and nonuse of arthrodesis in association with internal fixation for the treatment of thoracolumbar burst fractures. The search encompassed all data in these databases up to February 28, 2016. RESULTS Five randomized/quasi-randomized trials, which involved a total of 220 patients and an average follow-up time of 69.1 months, were included in this review. No significant difference between groups in the final scores of the visual analog pain scale or Low Back Outcome Scale was detected. Surgical time and blood loss were significantly lower in the group of patients who did not undergo fusion (p < 0.05). Among the evaluated radiological outcomes, greater mobility in the affected segment was found in the group of those who did not undergo fusion. No significant difference between groups in the degree of kyphosis correction, loss of kyphosis correction, or final angle of kyphosis was observed. CONCLUSIONS The data reviewed in this study suggest that the use of arthrodesis did not improve clinical outcomes, but it was associated with increased surgical time and higher intraoperative bleeding and did not promote significant improvement in radiological parameters.

A randomised controlled trial of an exercise plus behaviour change intervention in people with multiple sclerosis: the step it up study protocol.

PubMed

Coote, Susan; Gallagher, Stephen; Msetfi, Rachel; Larkin, Aidan; Newell, John; Motl, Robert W; Hayes, Sara

2014-12-21

Exercise has consistently yielded short-term, positive effects on health outcomes in people with multiple sclerosis (MS). However, these effects have not been maintained in the long-term. Behaviour change interventions aim to promote long-term positive lifestyle change. This study, namely, "Step it Up" will compare the effect of an exercise plus Social Cognitive Theory (SCT)-based behaviour change intervention with an exercise plus control education intervention on walking mobility among people with MS. People with a diagnosis of MS who walk independently, score of 0-3 on the Patient Determined Disease Steps, who have not experienced an MS relapse or change in their MS medication in the last 12 weeks and who are physically inactive will be randomised to one of two study conditions. The experimental group will undergo a 10-week exercise plus SCT-based behavioural change intervention. The control group will undergo a 10-week exercise plus education intervention to control for contact. Participants will be assessed at weeks 1, 12, 24 and 36. The primary outcome will be walking mobility. Secondary outcomes will include: aerobic capacity, lower extremity muscle strength, participant adherence to the exercise programme, self-report exercise intensity, self-report enjoyment of exercise, exercise self-efficacy, outcome expectations for exercise, goal-setting for exercise, perceived benefits and barriers to exercise, perceptions of social support, physical and psychological impact of MS and fatigue. A qualitative evaluation of Step it Up will be completed among participants post-intervention. This randomised controlled trial will examine the effectiveness of an exercise plus SCT-based behaviour change intervention on walking mobility among people with MS. To this end, Step it Up will serve to inform future directions of research and clinical practice with regard to sustainable exercise interventions for people with MS. ClinicalTrials.gov, NCT02301442.

Liposomal Bupivacaine During Robotic Colpopexy and Posterior Repair: A Randomized Controlled Trial.

PubMed

Yeung, Jennifer; Crisp, Catrina C; Mazloomdoost, Donna; Kleeman, Steven D; Pauls, Rachel N

2018-01-01

To evaluate the effect of liposomal bupivacaine on postoperative pain among patients undergoing robotic sacrocolpopexy with posterior repair. This was a randomized, patient-blinded, placebo-controlled trial of women undergoing robotic sacrocolpopexy with posterior repair. Liposomal bupivacaine or normal saline placebo was injected into laparoscopic and vaginal incisions at completion of surgery. Perioperative care was standardized. Visual analog scales were collected at 4, 18, and 24 hours postoperatively in hospital. Starting on postoperative day 1, participants completed twice-daily pain scales and a pain medication diary up until the evening of postoperative day 3. The primary outcome was a 20-mm change in the visual analog scale 18 hours postoperatively. Secondary measures included additional pain scores, satisfaction, and narcotic use. Sample size calculation revealed that 32 patients per arm were required to detect the 20-mm difference with 90% power and an α of 0.05. To allocate for dropout, a goal of 70 was set. Between March 2015 and April 2016, 100 women were screened and 70 women were enrolled: 35 women were randomized to liposomal bupivacaine and 35 to placebo, of whom 64 (91%) were included in the final analysis: 33 liposomal bupivacaine and 31 placebo. No difference in demographics, surgical data, or satisfaction between groups was noted. Median VAS at 18 hours after surgery was not statistically different in those who received liposomal bupivacaine compared with normal saline (15 mm compared with 20 mm; P=.52). Other pain scales and total morphine equivalents were also similar (P=.90). In this study of robotic sacrocolpopexy with posterior repair, there were no differences in pain scores or narcotic use between liposomal bupivacaine and placebo injected into laparoscopic and vaginal incisions. Given its lack of clinical benefit, routine use of liposomal bupivacaine is not supported for this surgical intervention. ClinicalTrials.gov, NCT02449915.

Frequency, predictors, and consequences of crossing over to revascularization within 12 months of randomization to optimal medical therapy in the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial.

PubMed

Spertus, John A; Maron, David J; Cohen, David J; Kolm, Paul; Hartigan, Pam; Weintraub, William S; Berman, Daniel S; Teo, Koon K; Shaw, Leslee J; Sedlis, Steven P; Knudtson, Merril; Aslan, Mihaela; Dada, Marcin; Boden, William E; Mancini, G B John

2013-07-01

In the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, some patients with stable ischemic heart disease randomized to optimal medical therapy (OMT) crossed over to early revascularization. The predictors and outcomes of patients who crossed over from OMT to revascularization are unknown. We compared characteristics of OMT patients who did and did not undergo revascularization within 12 months and created a Cox regression model to identify predictors of early revascularization. Patients' health status was measured with the Seattle Angina Questionnaire. To quantify the potential consequences of initiating OMT without percutaneous coronary intervention, we compared the outcomes of crossover patients with a matched cohort randomized to immediate percutaneous coronary intervention. Among 1148 patients randomized to OMT, 185 (16.1%) underwent early revascularization. Patient characteristics independently associated with early revascularization were worse baseline Seattle Angina Questionnaire scores and healthcare system. Among 156 OMT patients undergoing early revascularization matched to 156 patients randomized to percutaneous coronary intervention, rates of mortality (hazard ratio=0.51 [0.13-2.1]) and nonfatal myocardial infarction (hazard ratio=1.9 [0.75-4.6]) were similar, as were 1-year Seattle Angina Questionnaire scores. OMT patients, however, experienced worse health status over the initial year of treatment and more unstable angina admissions (hazard ratio=2.8 [1.1-7.5]). Among COURAGE patients assigned to OMT alone, patients' angina, dissatisfaction with their current treatment, and, to a lesser extent, their health system were associated with early revascularization. Because early crossover was not associated with an increase in irreversible ischemic events or impaired 12-month health status, these findings support an initial trial of OMT in stable ischemic heart disease with close follow-up of the most symptomatic patients. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00007657.

Detailed analysis of periprocedural strokes in patients undergoing intracranial stenting in Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS).

PubMed

Fiorella, David; Derdeyn, Colin P; Lynn, Michael J; Barnwell, Stanley L; Hoh, Brian L; Levy, Elad I; Harrigan, Mark R; Klucznik, Richard P; McDougall, Cameron G; Pride, G Lee; Zaidat, Osama O; Lutsep, Helmi L; Waters, Michael F; Hourihane, J Maurice; Alexandrov, Andrei V; Chiu, David; Clark, Joni M; Johnson, Mark D; Torbey, Michel T; Rumboldt, Zoran; Cloft, Harry J; Turan, Tanya N; Lane, Bethany F; Janis, L Scott; Chimowitz, Marc I

2012-10-01

Enrollment in the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial was halted due to the high risk of stroke or death within 30 days of enrollment in the percutaneous transluminal angioplasty and stenting arm relative to the medical arm. This analysis focuses on the patient and procedural factors that may have been associated with periprocedural cerebrovascular events in the trial. Bivariate and multivariate analyses were performed to evaluate whether patient and procedural variables were associated with cerebral ischemic or hemorrhagic events occurring within 30 days of enrollment (termed periprocedural) in the percutaneous transluminal angioplasty and stenting arm. Of 224 patients randomized to percutaneous transluminal angioplasty and stenting, 213 underwent angioplasty alone (n=5) or with stenting (n=208). Of these, 13 had hemorrhagic strokes (7 parenchymal, 6 subarachnoid), 19 had ischemic stroke, and 2 had cerebral infarcts with temporary signs within the periprocedural period. Ischemic events were categorized as perforator occlusions (13), embolic (4), mixed perforator and embolic (2), and delayed stent occlusion (2). Multivariate analyses showed that higher percent stenosis, lower modified Rankin score, and clopidogrel load associated with an activated clotting time above the target range were associated (P ≤ 0.05) with hemorrhagic stroke. Nonsmoking, basilar artery stenosis, diabetes, and older age were associated (P ≤ 0.05) with ischemic events. Periprocedural strokes in SAMMPRIS had multiple causes with the most common being perforator occlusion. Although risk factors for periprocedural strokes could be identified, excluding patients with these features from undergoing percutaneous transluminal angioplasty and stenting to lower the procedural risk would limit percutaneous transluminal angioplasty and stenting to a small subset of patients. Moreover, given the small number of events, the present data should be used for hypothesis generation rather than to guide patient selection in clinical practice. Clinical Trial Registration Information- URL: http://clinicaltrials.gov. Unique Identifier: NCT00576693.

Bivalirudin therapy is associated with improved clinical and economic outcomes in ST-elevation myocardial infarction patients undergoing percutaneous coronary intervention: results from an observational database.

PubMed

Pinto, Duane S; Ogbonnaya, Augustina; Sherman, Steven A; Tung, Patricia; Normand, Sharon-Lise T

2012-01-01

Randomized trials show improved outcomes among acute coronary syndrome patients treated with bivalirudin. The objective of this analysis was to compare clinical and economic outcomes in ST-elevation myocardial infarction (STEMI) patients encountered in routine clinical practice undergoing primary percutaneous coronary intervention (PPCI), treated with bivalirudin or heparin+GP IIb/IIIa receptor inhibitor (heparin+GPI). STEMI admissions from January 1, 2004 through March 31, 2008 among patients receiving PPCI and bivalirudin or heparin+GPI in the Premier hospital database were identified. The probability of receiving bivalirudin was estimated using individual and hospital variables; using propensity scores, each bivalirudin patient was matched to 3 heparin+GPI treated patients. The primary outcome was in-hospital death. Rates of bleeding, transfusion, length of stay, and in-hospital cost were secondary outcomes. There were 59,917 STEMI PPCIs receiving bivalirudin (n=6735) or heparin+GPI (n=53,182). Seventy-nine percent of bivalirudin patients matched, resulting in 21,316 STEMI PPCIs for analysis. Compared with heparin+GPI patients, bivalirudin patients had fewer deaths (3.2% versus 4.0%; P=0.011) and less inpatient bleeding (clinically apparent bleeding [6.9% versus 10.5%, P<0.0001], clinically apparent bleeding with transfusion [1.6% versus 3.0%, P<0.0001], and transfusion [5.9% versus 7.6%, P<0.0001]). Patients receiving bivalirudin had shorter average length of stay (mean 4.3 versus 4.5 days; P<0.0001), with lower in-hospital cost (mean $18,640 versus $19,967 [median $14,462 versus $16,003], P<0.0001). This large "real-world" retrospective analysis demonstrates that bivalirudin therapy compared with heparin+GPI is associated with a lower rate of inpatient death, inpatient bleeding, and decreased overall in-hospital cost in STEMI patients undergoing PPCI.

Cranberry juice capsules and urinary tract infection post surgery: Results of a randomized trial

PubMed Central

Foxman, Betsy; Cronenwett, Ms. Anna E.W.; Spino, Cathie; Berger, Mitchell B.; Morgan, Daniel M.

2015-01-01

Objective The risk of urinary tract infection (UTI) among women undergoing elective gynecologic surgery where a catheter is placed is high: 10 to 64% following catheter removal. We conducted the first randomized, double-blind, placebo-controlled trial of the therapeutic efficacy of cranberry juice capsules in preventing UTI post surgery. Study Design We recruited patients from a single hospital between August 2011 and January 2013. Eligible participants were undergoing elective gynecologic surgery that did not involve a fistula repair or vaginal mesh removal. 160 patients were randomized and received two cranberry juice capsules two times a day, equivalent to two 8-ounce servings of cranberry juice, for 6 weeks after surgery, or matching placebo. The primary endpoint was the proportion of participants who experienced clinically-diagnosed and treated UTI with or without positive urine culture. Kaplan-Meier plots and logrank tests compared the two treatment groups. Results The occurrence of UTI was significantly lower in the cranberry treatment group compared to the placebo group (15/80 (19%) versus 30/80 (38%); OR=0.38; 95% CI: 0.19, 0.79; p=0.008). After adjustment for known confounders, including frequency of intermittent self-catheterization in the post- operative period, the protective effects of cranberry remained (OR=0.42; 95% CI: 0.18, 0.94). There were no treatment differences in the incidence of adverse events; including gastrointestinal upset (56% vs. 61% for cranberry vs. placebo). Conclusions Among women undergoing elective benign gynecologic surgery involving urinary catheterization, use of cranberry extract tablets during the postoperative period reduced the rate of UTI by half. PMID:25882919

Multicentre double-blind randomized controlled trial of perhexiline as a metabolic modulator to augment myocardial protection in patients with left ventricular hypertrophy undergoing cardiac surgery.

PubMed

Senanayake, Eshan L; Howell, Neil J; Ranasinghe, Aaron M; Drury, Nigel E; Freemantle, Nick; Frenneaux, Michael; Oelofse, Tessa; Green, David; Wilson, Ian C; Rooney, Stephen J; Mascaro, Jorge; Graham, Timothy R; Bhudia, Sunil; Lewis, Michael; Pagano, Domenico

2015-09-01

Patients undergoing cardiac surgery require adequate myocardial protection. Manipulating myocardial metabolism may improve the extent of myocardial protection. Perhexiline has been shown to be an effective anti-anginal agent due to its metabolic modulation properties by inhibiting the uptake of free fatty acids into the mitochondrion, and thereby promoting a more efficient carbohydrate-driven myocardial metabolism. Metabolic modulation may augment myocardial protection, particularly in patients with left ventricular hypertrophy (LVH) known to have a deranged metabolic state and are at risk of poor postoperative outcomes. This study aimed to evaluate the role of perhexiline as an adjunct in myocardial protection in patients with LVH secondary to aortic stenosis (AS), undergoing an aortic valve replacement (AVR). In a multicentre double-blind randomized controlled trial of patients with AS undergoing AVR ± coronary artery bypass graft surgery, patients were randomized to preoperative oral therapy with either perhexiline or placebo. The primary end point was incidence of inotrope use to improve haemodynamic performance due to a low cardiac output state during the first 6 h of reperfusion, judged by a blinded end points committee. Secondary outcome measures included haemodynamic measurements, electrocardiographic and biochemical markers of new myocardial injury and clinical safety outcome measures. The trial was halted early on the advice of the Data Safety and Monitoring Board. Sixty-two patients were randomized to perhexiline and 65 to placebo. Of these, 112 (54 perhexiline and 48 placebo) patients received the intervention, remained in the trial at the time of the operation and were analysed. Of 110 patients who achieved the primary end point, 30 patients (16 perhexiline and 14 placebo) had inotropes started appropriately; there was no difference in the incidence of inotrope usage OR of 1.65 [confidence interval (CI): 0.67-4.06] P = 0.28. There was no difference in myocardial injury as evidenced by electrocardiogram odds ratio (OR) of 0.36 (CI: 0.07-1.97) P = 0.24 or postoperative troponin release. Gross secondary outcome measures were comparable between the groups. Perhexiline as a metabolic modulator to enhance standard myocardial protection does not provide an additional benefit in haemodynamic performance or attenuate myocardial injury in the hypertrophied heart secondary to AS. The role of perhexiline in cardiac surgery is limited. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Memantine before Mastectomy Prevents Post-Surgery Pain: A Randomized, Blinded Clinical Trial in Surgical Patients.

PubMed

Morel, Véronique; Joly, Dominique; Villatte, Christine; Dubray, Claude; Durando, Xavier; Daulhac, Laurence; Coudert, Catherine; Roux, Delphine; Pereira, Bruno; Pickering, Gisèle

2016-01-01

Neuropathic pain following surgical treatment for breast cancer with or without chemotherapy is a clinical burden and patients frequently report cognitive, emotional and quality of life impairment. A preclinical study recently showed that memantine administered before surgery may prevent neuropathic pain development and cognitive dysfunction. With a translational approach, a clinical trial has been carried out to evaluate whether memantine administered before and after mastectomy could prevent the development of neuropathic pain, the impairment of cognition and quality of life. A randomized, pilot clinical trial included 40 women undergoing mastectomy in the Oncology Department, University Hospital, Clermont-Ferrand, France. Memantine (5 to 20 mg/day; n = 20) or placebo (n = 20) was administered for four weeks starting two weeks before surgery. The primary endpoint was pain intensity measured on a (0-10) numerical rating scale at three months post-mastectomy. Data analyses were performed using mixed models and the tests were two-sided, with a type I error set at α = 0.05. Compared with placebo, patients receiving memantine showed at three months a significant difference in post-mastectomy pain intensity, less rescue analgesia and a better emotional state. An improvement of pain symptoms induced by cancer chemotherapy was also reported. This study shows for the first time the beneficial effect of memantine to prevent post-mastectomy pain development and to diminish chemotherapy-induced pain symptoms. The lesser analgesic consumption and better well-being of patients for at least six months after treatment suggests that memantine could be an interesting therapeutic option to diminish the burden of breast cancer therapy. Clinicaltrials.gov NCT01536314.

Multidisciplinary rehabilitation program in recently hospitalized patients with heart failure and preserved ejection fraction: rationale and design of a randomized controlled trial.

PubMed

Koifman, Edward; Grossman, Ehud; Elis, Avishay; Dicker, Dror; Koifman, Bella; Mosseri, Morris; Kuperstein, Rafael; Goldenberg, Ilan; Kamerman, Tamir; Levine-Tiefenbrun, Nava; Klempfner, Robert

2014-12-01

Heart failure with preserved ejection fraction (HFpEF) comprises a large portion of heart failure patients and portends poor prognosis with similar outcome to heart failure with reduced ejection fraction (HFrEF). Thus far, no medical therapy has been shown to improve clinical outcome in this common condition. The study is a randomized-controlled, multicenter clinical trial aimed to determine whether early posthospitalization comprehensive cardiac rehabilitation (CR) including exercise training (ET) in recently hospitalized HFpEF patients reduces the composite end point of all-cause mortality and hospitalizations in comparison with usual care (UC). After undergoing baseline evaluation, patients are randomized to either UC or to ambulatory comprehensive CR program. Patients in the CR arm will participate in a 6-month biweekly ET program according to a predefined protocol, in addition to a complementary home exercise prescribed by a specialist in CR. Exercise training will include endurance and low-intensity resistance training. Patients in the UC arm will be followed up at the outpatient clinic, with management according to current heart failure guidelines. Physician follow-up visits will be conducted at 3, 6, and 12 months for assessment of adherence to therapy and ET, functional status, quality of life, and clinical events. Secondary end points will include quality-of-life questionnaire, economic end points, blood pressure, and hemoglobin A1C levels. Cardiac rehabilitation and ET are relatively inexpensive and accessible and can be beneficial in HFpEF patients. Our trial is designed to evaluate the impact of early posthospitalization comprehensive rehabilitation program on clinical end points of mortality, hospitalization, and quality of life in HFpEF patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Review of the contemporary cytotoxic and biologic combinations available for the treatment of metastatic breast cancer.

PubMed

Tkaczuk, Katherine H Rak

2009-01-01

Treatment of metastatic breast cancer (MBC) with > or =2 chemotherapeutic agents concurrently has been shown to increase response rates, often at the cost of a substantial increase in toxicity, and with minimal impact on the overall survival. However, some combinations of the newer cytotoxic agents, as well as combinations of chemotherapeutic agents and targeted biologic anticancer agents, can produce synergistic efficacy with a manageable toxicity profile. The aims of this work were to provide an overview of the currently approved combination regimens available for the treatment of MBC and to consider the clinical data supporting other drug combinations that may supplement the current therapeutic choices in the near future. Literature searches were performed using MEDLINE/PubMed, with a focus on combination therapies for the treatment of MBC that are approved by the US Food and Drug Administration (FDA) or in Phase III clinical trials. The National Institutes of Health's Clinical Trial Registry was searched for relevant ongoing clinical trials in specific areas. Bibliographies were also searched for additional relevant material. Preference was given to recently published, larger, well-designed clinical trials that influence current prescribing practices. Phase I and II studies, and/or studies older than 10 years (ie, published earlier than 1999), were afforded less emphasis or were disregarded. Combinations of taxanes with capecitabine or gemcitabine, and ixabepilone plus capecitabine, are approved by the FDA as combination regimens for the treatment of MBC. The use of targeted therapies such as trastuzumab, bevacizumab, or lapatinib in combination with taxanes (for the former two) or capecitabine (for lapatinib) is also approved. Several investigational drug combinations are also currently undergoing evaluation in clinical trials, including combinations of bevacizumab and gemcitabine with capecitabine or alternative taxanes. Although results from Phase I and II studies are largely encouraging so far, the data from ongoing Phase III studies will ultimately dictate changes in clinical practice. It seems unlikely that any single agent or combination regimen will emerge as superior in all patients with MBC, given the heterogeneous nature of the disease and patient population. New combination regimens for MBC may broaden the range of treatment options currently available to delay disease progression for as long as possible. Copyright 2009 Excerpta Medica Inc. All rights reserved.

Virtual reality for acute pain reduction in adolescents undergoing burn wound care: a prospective randomized controlled trial.

PubMed

Kipping, Belinda; Rodger, Sylvia; Miller, Kate; Kimble, Roy M

2012-08-01

Effective pain management remains a challenge for adolescents during conscious burn wound care procedures. Virtual reality (VR) shows promise as a non-pharmacological adjunct in reducing pain. This study assessed off-the-shelf VR for (1) its effect on reducing acute pain intensity during adolescent burn wound care, and (2) its clinical utility in a busy hospital setting. Forty-one adolescents (11-17 years) participated in this prospective randomized controlled trial. Acute pain outcomes including adolescent self-report, nursing staff behavioral observation, caregiver observation and physiological measures were collected. Length of procedure times and adolescent reactions were also recorded to inform clinical utility. Nursing staff reported a statistically significant reduction in pain scores during dressing removal, and significantly less rescue doses of Entonox given to those receiving VR, compared to those receiving standard distraction. For all other pain outcomes and length of treatment, there was a trend for lower pain scores and treatment times for those receiving VR, but these differences were not statistically significant. Despite only minimal pain reduction achieved using off-the-shelf VR, other results from this trial and previous research on younger children with burns suggest a customized, adolescent and hospital friendly device may be more effective in pain reduction. Copyright © 2012. Published by Elsevier Ltd.

Epidural Dexamethasone for Postoperative Analgesia in Patients Undergoing Unilateral Inguinal Herniorrhaphy: A Comparative Study

PubMed Central

Razavizadeh, M. R.; Heydarian, N.; Atoof, F.

2017-01-01

Background. This study was designed to evaluate the effect of adding dexamethasone to epidural bupivacaine on postoperative analgesia in unilateral inguinal herniorrhaphy. Methods. Forty-four patients were enrolled in this double-blind, clinical trial study. Patients were randomly allocated into dexamethasone or control group. In the dexamethasone group, patients received 18 ml of bupivacaine 0.5% and 2 ml (8 mg) of dexamethasone; in the control group, patients received 18 ml of bupivacaine 0.5% and 2 ml of normal saline. The onset of sensory block and its duration and incidence of nausea and vomiting were recorded. Results. The onset of epidural anesthesia was significantly more rapid in the dexamethasone group than in the control group (P < 0.001). Duration of analgesia was markedly prolonged in the dexamethasone group than in the control group (P < 0.001). Five patients (22.7%) in the control group had nausea in the first hour after the procedure (P = 0.048). None of the patients in the dexamethasone group had nausea. None of our patients had vomiting in the two groups. Conclusions. This study showed that adding dexamethasone to bupivacaine significantly prolongs the duration of postoperative analgesia. This trial is registered with Iranian Registry of Clinical Trials (IRCT) number IRCT2012062910137N1. PMID:28348504

Current and future treatment of chest pain of presumed esophageal origin.

PubMed

Schmulson, Max J; Valdovinos, Miguel Angel

2004-03-01

Patients with chest pain of presumed esophageal origin should be reassured and should undergo an esophageal manometry study. In patients with spastic esophageal disorders, a trial with calcium channel blockers or low-dose antidepressants used as visceral analgesics is the best approach. Inpatients with non GERD-related, nonspastic esophageal motility disorder, low-dose antidepressants seem reasonable. Anxiolytics are useful in patients with panic disorders, and psychological interventions (eg, cognitive-behavioral therapy) are also valuable, mainly in patients in whom reassurance is not sufficient to avoid the misinterpretation of their symptoms. In the future, visceral sensitivity modifying agents such as serotoninergic agonists or antagonists may become the cornerstone of therapy in patients with chest pain of presumed esophageal origin. Combinations of different approaches, such as proton pump inhibitors and psychotropic or antinociceptive agents, should also be evaluated in clinical trials.

Cognitive-behavioral based physical therapy for patients with chronic pain undergoing lumbar spine surgery: a randomized controlled trial

PubMed Central

Archer, Kristin R.; Devin, Clinton J.; Vanston, Susan W.; Koyama, Tatsuki; Phillips, Sharon; George, Steven Z.; McGirt, Matthew J.; Spengler, Dan M.; Aaronson, Oran S.; Cheng, Joseph S.; Wegener, Stephen T.

2015-01-01

The purpose of this study was to determine the efficacy of a cognitive-behavioral based physical therapy (CBPT) program for improving outcomes in patients following lumbar spine surgery. A randomized controlled trial was conducted in 86 adults undergoing a laminectomy with or without arthrodesis for a lumbar degenerative condition. Patients were screened preoperatively for high fear of movement using the Tampa Scale for Kinesiophobia. Randomization to either CBPT or an Education program occurred at 6 weeks after surgery. Assessments were completed pre-treatment, post-treatment and at 3 month follow-up. The primary outcomes were pain and disability measured by the Brief Pain Inventory and Oswestry Disability Index. Secondary outcomes included general health (SF-12) and performance-based tests (5-Chair Stand, Timed Up and Go, 10 Meter Walk). Multivariable linear regression analyses found that CBPT participants had significantly greater decreases in pain and disability and increases in general health and physical performance compared to the Education group at 3 month follow-up. Results suggest a targeted CBPT program may result in significant and clinically meaningful improvement in postoperative outcomes. CBPT has the potential to be an evidence-based program that clinicians can recommend for patients at-risk for poor recovery following spine surgery. PMID:26476267

Early results of an in vivo trial of ESS in thyroid cancer

NASA Astrophysics Data System (ADS)

Rosen, Jennifer E.; Goukassian, Ilona D.; A'Amar, Ousama M.; Bigio, Irving J.; Lee, Stephanie L.

2012-02-01

Introduction: Thyroid cancer is the most common endocrine malignancy. The current gold standard for diagnosis, fine-needle aspiration (FNA) biopsy, yields 10-25% of indeterminate cytology results, leading to patients undergoing thyroidectomy for diagnosis. We assessed the technical potential of a miniaturized in vivo ESS (elastic light scattering spectroscopy) probe, built into an FNA needle assembly, to differentiate benign from malignant thyroid nodules. Methods: Under IRB approval, 15 patients in the endocrine clinic undergoing FNAB of a thyroid nodule had collection of ESS data using our novel miniaturized FNA probe. Using final surgical pathology as our gold standard, data post processing and visual inspection was completed. Results: 225 spectra were grouped and analyzed (120 benign, 30 malignant and 75 from indeterminate cytology). ESS probes demonstrated excellent reproducibility in use. Initial analysis of these preliminary data is promising, indicating distinction of spectral ESS features between malignant and benign conditions. Conclusion(s): An in vivo trial of an invasive miniaturized integrated ESS biopsy probe is acceptable to patients, and collection of ESS data is feasible and reliable. With development of a disease-specific algorithm, ESS could potentially be used as an in-situ real time intra-operative diagnostic tool or as a minimally invasive adjunct to conventional FNA cytology.

Liposomal bupivacaine: an innovative nonopioid local analgesic for the management of postsurgical pain.

PubMed

Candiotti, Keith

2012-09-01

Local anesthetics are a cornerstone of multimodal pain control strategies in the surgical setting as they have a long history of use and an established safety profile. Although effective, their duration of action is relatively short, which usually leads to the use of other agents, such as opioids, for effective postsurgical pain control in most patients. A medical need exists to extend the duration of analgesia with local anesthetics to help reduce the reliance on opioids in the postsurgical setting. Liposomal bupivacaine uses a product delivery platform to release bupivacaine slowly over 96 hours after infiltration at the surgical site. Liposomal bupivacaine was compared with placebo in two pivotal, multicenter, randomized, double-blind, parallel-group trials in 189 adults undergoing soft-tissue surgery (hemorrhoidectomy) and 193 adults undergoing orthopedic surgery (bunionectomy). Among patients undergoing hemorrhoidectomy, liposomal bupivacaine significantly reduced cumulative pain scores for up to 72 hours (primary end point) as measured by the area under the curve of pain scores on the numeric rating scale (p<0.0001), reduced overall opioid consumption (p ≤ 0.0006), increased the proportion of patients who did not receive opioids (p<0.0008), delayed time to first opioid by more than 13 hours (p<0.0001), and was associated with significantly higher rates of patient satisfaction (p=0.0007) compared with placebo. Similarly, in patients undergoing bunionectomy, liposomal bupivacaine significantly reduced total consumption of rescue opioids (p=0.0077) and cumulative pain scores as measured by the area under the curve of pain scores on the numeric rating scale (p=0.0005) during the first 24 postsurgical hours (primary end point) relative to placebo. Furthermore, liposomal bupivacaine also significantly delayed the time to first use of opioid rescue (p<0.0001) and increased the proportion of patients requiring no rescue opioid treatment (p ≤ 0.0404) compared with placebo. The most common adverse events with liposomal bupivacaine were nausea, vomiting, and constipation. No adverse effects on the QTc interval or cardiac safety signal have been detected in the clinical trial development program (823 patients) when liposomal bupivacaine was infiltrated into the surgical site. The beneficial effects of liposomal bupivacaine on postsurgical pain management and opioid use, significantly reducing both, are likely to translate into improved clinical and economic outcomes. © 2012 Pharmacotherapy Publications, Inc.

Antiepileptic drugs as prophylaxis for postcraniotomy seizures.

PubMed

Greenhalgh, Janette; Weston, Jennifer; Dundar, Yenal; Nevitt, Sarah J; Marson, Anthony G

2018-05-23

This is an updated version of the Cochrane Review previously published in Issue 3, 2015.The incidence of seizures following supratentorial craniotomy for non-traumatic pathology has been estimated to be between 15% to 20%; however, the risk of experiencing a seizure appears to vary from 3% to 92% over a five-year period. Postoperative seizures can precipitate the development of epilepsy; seizures are most likely to occur within the first month of cranial surgery. The use of antiepileptic drugs (AEDs) administered pre- or postoperatively to prevent seizures following cranial surgery has been investigated in a number of randomised controlled trials (RCTs). To determine the efficacy and safety of AEDs when used prophylactically in people undergoing craniotomy and to examine which AEDs are most effective. For the latest update we searched the following databases on 26 June 2017: Cochrane Epilepsy Group Specialized Register, the CENTRAL, MEDLINE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). We did not apply any language restrictions. We included RCTs of people with no history of epilepsy who were undergoing craniotomy for either therapeutic or diagnostic reasons. We included trials with adequate randomisation methods and concealment; these could either be blinded or unblinded parallel trials. We did not stipulate a minimum treatment period, and we included trials using active drugs or placebo as a control group. Three review authors (JW, JG, YD) independently selected trials for inclusion and performed data extraction and risk of bias assessments. We resolved any disagreements through discussion. Outcomes investigated included the number of participants experiencing seizures (early (occurring within first week following craniotomy), and late (occurring after first week following craniotomy)), the number of deaths and the number of people experiencing disability and adverse effects. Due to the heterogeneous nature of the trials, we did not combine data from the included trials in a meta-analysis; we presented the findings of the review in narrative format. Visual comparisons of outcomes are presented in forest plots. We included 10 RCTs (N = 1815), which were published between 1983 and 2015. Three trials compared a single AED (phenytoin) with placebo or no treatment. One three-armed trial compared two AEDs (phenytoin, carbamazepine) with no treatment. A second three-armed trial compared phenytoin, phenobarbital with no treatment. Of these five trials comparing AEDs with placebo or no treatment, two trials reported a statistically significant advantage for AED treatment compared to controls for early seizure occurrence; all other comparisons showed no clear or statistically significant differences between AEDs and control treatment. None of the trials that were head-to-head comparisons of AEDs (phenytoin versus sodium valproate, phenytoin versus phenobarbital, levetiracetam versus phenytoin, zonisamide versus phenobarbital) reported any statistically significant differences between treatments for either early or late seizure occurrence.Incidences of death were reported in only five trials. One trial reported statistically significantly fewer deaths in the carbamazepine and no-treatment groups compared with the phenytoin group after 24 months of treatment, but not after six months of treatment. Incidences of adverse effects of treatment were poorly reported; however, three trials did show that significantly more adverse events occurred on phenytoin compared to valproate, placebo, or no treatment. No trials reported any results relating to functional outcomes such as disability.We considered the evidence to be of low quality for all reported outcomes due to methodological issues and variability of comparisons made in the trials. There is limited, low-quality evidence to suggest that AED treatment administered prophylactically is either effective or not effective in the prevention of postcraniotomy (early or late) seizures. The current evidence base is limited due to the different methodologies employed in the trials and inconsistencies in the reporting of outcomes including deaths and adverse events. Further evidence from good-quality, contemporary trials is required in order to assess the clinical effectiveness of prophylactic AED treatment compared to placebo or no treatment, or other AEDs in preventing postcraniotomy seizures in this select group of patients.

Prevention of Contrast-Induced Acute Kidney Injury by Furosemide With Matched Hydration in Patients Undergoing Interventional Procedures: A Systematic Review and Meta-Analysis of Randomized Trials.

PubMed

Putzu, Alessandro; Boscolo Berto, Martina; Belletti, Alessandro; Pasotti, Elena; Cassina, Tiziano; Moccetti, Tiziano; Pedrazzini, Giovanni

2017-02-27

The objective of this meta-analysis of randomized trials was to evaluate if the administration of furosemide with matched hydration using the RenalGuard System reduces contrast-induced acute kidney injury (CI-AKI) in patients undergoing interventional procedures. CI-AKI is a serious complication following angiographic procedures and a powerful predictor of unfavorable early and long-term outcomes. Online databases were searched up to October 1, 2016, for randomized controlled trials. The primary outcome was the incidence of CI-AKI, and the secondary outcomes were need for renal replacement therapy, mortality, stroke, and adverse events. A total of four trials (n = 698) published between 2011 and 2016 were included in the analysis and included patients undergoing percutaneous coronary procedures and transcatheter aortic valve replacement. RenalGuard therapy was associated with a lower incidence of CI-AKI compared with control treatment (27 of 348 [7.76%] patients vs. 75 of 350 [21.43%] patients; odds ratio [OR]: 0.31; 95% confidence interval [CI]: 0.19 to 0.50; I 2  = 4%; p < 0.00001) and with a lower need for renal replacement therapy (2 of 346 [0.58%] patients vs. 12 of 348 [3.45%] patients; OR: 0.19; 95% CI: 0.05 to 0.76; I 2  = 0%; p = 0.02). No major adverse events occurred in patients undergoing RenalGuard therapy. The main finding of this meta-analysis is that furosemide with matched hydration by the RenalGuard System may reduce the incidence of CI-AKI in high-risk patients undergoing percutaneous coronary intervention or transcatheter aortic valve replacement. However, further independent high-quality randomized trials should elucidate the effectiveness and safety of this prophylactic intervention in interventional cardiology. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The contemporary management of penetrating splenic injury.

PubMed

Berg, Regan J; Inaba, Kenji; Okoye, Obi; Pasley, Jason; Teixeira, Pedro G; Esparza, Michael; Demetriades, Demetrios

2014-09-01

Selective non-operative management (NOM) is standard of care for clinically stable patients with blunt splenic trauma and expectant management approaches are increasingly utilised in penetrating abdominal trauma, including in the setting of solid organ injury. Despite this evolution of clinical practice, little is known about the safety and efficacy of NOM in penetrating splenic injury. Trauma registry and medical record review identified all consecutive patients presenting to LAC+USC Medical Center with penetrating splenic injury between January 2001 and December 2011. Associated injuries, incidence and nature of operative intervention, local and systemic complications and mortality were determined. During the study period, 225 patients experienced penetrating splenic trauma. The majority (187/225, 83%) underwent emergent laparotomy. Thirty-eight clinically stable patients underwent a deliberate trial of NOM and 24/38 (63%) were ultimately managed without laparotomy. Amongst patients failing NOM, 3/14 (21%) underwent splenectomy while an additional 6/14 (42%) had splenorrhaphy. Hollow viscus injury (HVI) occurred in 21% of all patients failing NOM. Forty percent of all NOM patients had diaphragmatic injury (DI). All patients undergoing delayed laparotomy for HVI or a splenic procedure presented symptomatically within 24h of the initial injury. No deaths occurred in patients undergoing NOM. Although the vast majority of penetrating splenic trauma requires urgent operative management, a group of patients does present without haemodynamic instability, peritonitis or radiologic evidence of hollow viscus injury. Management of these patients is complicated as over half may remain clinically stable and can avoid laparotomy, making them potential candidates for a trial of NOM. HVI is responsible for NOM failure in up to a fifth of these cases and typically presents within 24h of injury. Delayed laparotomy, within this limited time period, did not appear to increase mortality nor preclude successful splenic salvage. In clinically stable patients, diagnostic laparoscopy remains essential to evaluate and repair occult DI. As NOM for penetrating abdominal trauma becomes more common, multi-centre data is needed to more accurately define the principles of patient selection and the limitations and consequences of this approach in the setting of splenic injury. Copyright © 2014 Elsevier Ltd. All rights reserved.

Does flushing the endometrial cavity with follicular fluid after oocyte retrieval affect pregnancy rates in subfertile women undergoing intracytoplasmic sperm injection? A randomized controlled trial.

PubMed

Hashish, N M; Badway, H S; Abdelmoty, H I; Mowafy, A; Youssef, M A F M

2014-05-01

Follicular fluid of mature oocytes is rich in growth factors and cytokines that may exert paracrine and autocrine effects on implantation. The aim of this study was to investigate if flushing the endometrial cavity with follicular fluid after oocyte retrieval improved pregnancy rates in subfertile women undergoing intracytoplasmic sperm injection (ICSI). One hundred subfertile women undergoing ICSI between April 2012 and September 2012 at the centre for reproductive medicine, Cairo University, Egypt were enrolled in this open label, parallel randomized controlled study. Patients were randomized into two groups at the start of treatment using a computer-generated programme and sealed opaque envelopes: the follicular fluid group (n=50) and the control group (n=50). Inclusion criteria were: age 20-38 years; basal follicle-stimulating hormone <10mIU/ml; body mass index <35kg/m(2); and ostradiol >1000pg/ml and <4000pg/ml on the day of human chorionic gonadotrophin administration. Exclusion criteria were: evidence of endometriosis; uterine myoma; hydrosalpinges; endocrinological disorders; history of implantation failure in previous in-vitro fertilization/ICSI cycles; and severe male factor infertility. Clinical pregnancy and implantation rates were higher in the follicular fluid group compared with the control group [354% (17/48) vs 319% (15/47); p=0718] and (18.6% vs 11.3%; p=0.153), respectively. However, the difference was not statistically significant. Flushing the endometrial cavity with follicular fluid after oocyte retrieval neither improved nor adversely affected clinical pregnancy and implantation rates in subfertile women undergoing ICSI. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Xenon as an Adjuvant to Propofol Anesthesia in Patients Undergoing Off-Pump Coronary Artery Bypass Graft Surgery: A Pragmatic Randomized Controlled Clinical Trial.

PubMed

Al Tmimi, Layth; Devroe, Sarah; Dewinter, Geertrui; Van de Velde, Marc; Poortmans, Gert; Meyns, Bart; Meuris, Bart; Coburn, Mark; Rex, Steffen

2017-10-01

Xenon was shown to cause less hemodynamic instability and reduce vasopressor needs during off-pump coronary artery bypass (OPCAB) surgery when compared with conventionally used anesthetics. As xenon exerts its organ protective properties even in subanesthetic concentrations, we hypothesized that in patients undergoing OPCAB surgery, 30% xenon added to general anesthesia with propofol results in superior hemodynamic stability when compared to anesthesia with propofol alone. Fifty patients undergoing elective OPCAB surgery were randomized to receive general anesthesia with 30% xenon adjuvant to a target-controlled infusion of propofol or with propofol alone. The primary end point was the total intraoperative dose of norepinephrine required to maintain an intraoperative mean arterial pressure >70 mm Hg. Secondary outcomes included the perioperative cardiorespiratory profile and the incidence of adverse and serious adverse events. Adding xenon to propofol anesthesia resulted in a significant reduction of norepinephrine required to attain the predefined hemodynamic goals (cumulative intraoperative dose: median [interquartile range]: 370 [116-570] vs 840 [335-1710] µg, P = .001). In the xenon-propofol group, significantly less propofol was required to obtain a similar depth of anesthesia as judged by clinical signs and the bispectral index (propofol effect site concentration [mean ± SD]: 1.8 ± 0.5 vs 2.8 ± 0.3 mg, P≤ .0001). Moreover, the xenon-propofol group required significantly less norepinephrine during the first 24 hours on the intensive care unit (median [interquartile range]: 1.5 [0.1-7] vs 5 [2-8] mg, P = .048). Other outcomes and safety parameters were similar in both groups. Thirty percent xenon added to propofol anesthesia improves hemodynamic stability by decreasing norepinephrine requirements in patients undergoing OPCAB surgery.

Insufficient evidence of benefit regarding mortality due to albumin substitution in HCC-free cirrhotic patients undergoing large volume paracentesis.

PubMed

Kütting, Fabian; Schubert, Jens; Franklin, Jeremy; Bowe, Andrea; Hoffmann, Vera; Demir, Muenevver; Pelc, Agnes; Nierhoff, Dirk; Töx, Ulrich; Steffen, Hans-Michael

2017-02-01

Current guidelines for clinical practice recommend the infusion of human albumin after large volume paracentesis. After inspecting the current evidence behind this recommendation, we decided to conduct a systematic review and meta-analysis in order to address the effect of albumin on mortality and morbidity in the context of large volume paracentesis. We performed a comprehensive search of large databases and abstract books of conference proceedings up to March 15th 2016 for randomized controlled trials, testing the infusion of human albumin against alternatives (vs no treatment, vs plasma expanders; vs vasoconstrictors) in HCC-free patients suffering from cirrhosis. We analyzed these trials with regard to mortality, changes in plasma renin activity (PRA), hyponatremia, renal impairment, recurrence of ascites with consequential re-admission into hospital and additional complications. We employed trial sequential analysis in order to calculate the number of patients required in controlled trials to be able to determine a statistically significant advantage of the administration of one agent over another with regard to mortality. We were able to include 21 trials totaling 1277 patients. While the administration of albumin prevents a rise in PRA as well as hyponatremia, no improvement in strong clinical endpoints such as mortality could be demonstrated. Trial sequential analysis showed that at least 1550 additional patients need to be recruited into RCTs and analyzed with regard to this question in order to detect or disprove a 25% mortality effect. There is insufficient evidence that the infusion of albumin after LVP significantly lowers mortality in HCC-free patients with advanced liver disease. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Image-guided total-marrow irradiation using helical tomotherapy in patients with multiple myeloma and acute leukemia undergoing hematopoietic cell transplantation.

PubMed

Wong, Jeffrey Y C; Rosenthal, Joseph; Liu, An; Schultheiss, Timothy; Forman, Stephen; Somlo, George

2009-01-01

Total-body irradiation (TBI) has an important role in patients undergoing hematopoietic cell transplantation (HCT), but is associated with significant toxicities. Targeted TBI using helical tomotherapy results in reduced doses to normal organs, which predicts for reduced toxicities compared with standard TBI. Thirteen patients with multiple myeloma were treated in an autologous tandem transplantation Phase I trial with high-dose melphalan, followed 6 weeks later by total-marrow irradiation (TMI) to skeletal bone. Dose levels were 10, 12, 14, and 16 Gy at 2 Gy daily/twice daily. In a separate allogeneic HCT trial, 8 patients (5 with acute myelogenous leukemia, 1 with acute lymphoblastic leukemia, 1 with non-Hodgkin's lymphoma, and 1 with multiple myeloma) were treated with TMI plus total lymphoid irradiation plus splenic radiotherapy to 12 Gy (1.5 Gy twice daily) combined with fludarabine/melphalan. For the 13 patients in the tandem autologous HCT trial, median age was 54 years (range, 42-66 years). Median organ doses were 15-65% that of the gross target volume dose. Primarily Grades 1-2 acute toxicities were observed. Six patients reported no vomiting; 9 patients, no mucositis; 6 patients, no fatigue; and 8 patients, no diarrhea. For the 8 patients in the allogeneic HCT trial, median age was 52 years (range, 24-61 years). Grades 2-3 nausea, vomiting, mucositis, and diarrhea were observed. In both trials, no Grade 4 nonhematologic toxicity was observed, and all patients underwent successful engraftment. This study shows that TMI using helical tomotherapy is clinically feasible. The reduced acute toxicities observed compare favorably with those seen with standard TBI. Initial results are encouraging and warrant further evaluation as a method to dose escalate with acceptable toxicity or to offer TBI-containing regimens to patients unable to tolerate standard approaches.

The effects of neoadjuvant chemoradiotherapy and an in-hospital exercise training programme on physical fitness and quality of life in locally advanced rectal cancer patients (The EMPOWER Trial): study protocol for a randomised controlled trial.

PubMed

Loughney, Lisa; West, Malcolm A; Kemp, Graham J; Rossiter, Harry B; Burke, Shaunna M; Cox, Trevor; Barben, Christopher P; Mythen, Michael G; Calverley, Peter; Palmer, Daniel H; Grocott, Michael P W; Jack, Sandy

2016-01-13

The standard treatment pathway for locally advanced rectal cancer is neoadjuvant chemoradiotherapy (CRT) followed by surgery. Neoadjuvant CRT has been shown to decrease physical fitness, and this decrease is associated with increased post-operative morbidity. Exercise training can stimulate skeletal muscle adaptations such as increased mitochondrial content and improved oxygen uptake capacity, both of which are contributors to physical fitness. The aims of the EMPOWER trial are to assess the effects of neoadjuvant CRT and an in-hospital exercise training programme on physical fitness, health-related quality of life (HRQoL), and physical activity levels, as well as post-operative morbidity and cancer staging. The EMPOWER Trial is a randomised controlled trial with a planned recruitment of 46 patients with locally advanced rectal cancer and who are undergoing neoadjuvant CRT and surgery. Following completion of the neoadjuvant CRT (week 0) prior to surgery, patients are randomised to an in-hospital exercise training programme (aerobic interval training for 6 to 9 weeks) or a usual care control group (usual care and no formal exercise training). The primary endpoint is oxygen uptake at lactate threshold ([Formula: see text] at [Formula: see text]) measured using cardiopulmonary exercise testing assessed over several time points throughout the study. Secondary endpoints include HRQoL, assessed using semi-structured interviews and questionnaires, and physical activity levels assessed using activity monitors. Exploratory endpoints include post-operative morbidity, assessed using the Post-Operative Morbidity Survey (POMS), and cancer staging, assessed by using magnetic resonance tumour regression grading. The EMPOWER trial is the first randomised controlled trial comparing an in-hospital exercise training group with a usual care control group in patients with locally advanced rectal cancer. This trial will allow us to determine whether exercise training following neoadjuvant CRT can improve physical fitness and activity levels, as well as other important clinical outcome measures such as HRQoL and post-operative morbidity. These results will aid the design of a large, multi-centre trial to determine whether an increase in physical fitness improves clinically relevant post-operative outcomes. ClinicalTrials.gov NCT01914068 (received: 7 June 2013). University Hospital Southampton NHS Foundation Trust.

Impact of pectoral nerve block on postoperative pain and quality of recovery in patients undergoing breast cancer surgery: A randomised controlled trial.

PubMed

Kamiya, Yoshinori; Hasegawa, Miki; Yoshida, Takayuki; Takamatsu, Misako; Koyama, Yu

2018-03-01

In recent years, thoracic wall nerve blocks, such as the pectoral nerve (PECS) block and the serratus plane block have become popular for peri-operative pain control in patients undergoing breast cancer surgery. The effect of PECS block on quality of recovery (QoR) after breast cancer surgery has not been evaluated. To evaluate the ability of PECS block to decrease postoperative pain and anaesthesia and analgesia requirements and to improve postoperative QoR in patients undergoing breast cancer surgery. Randomised controlled study. A tertiary hospital. Sixty women undergoing breast cancer surgery between April 2014 and February 2015. The patients were randomised to receive a PECS block consisting of 30 ml of levobupivacaine 0.25% after induction of anaesthesia (PECS group) or a saline mock block (control group). The patients answered a 40-item QoR questionnaire (QoR-40) before and 1 day after breast cancer surgery. Numeric Rating Scale score for postoperative pain, requirement for intra-operative propofol and remifentanil, and QoR-40 score on postoperative day 1. PECS block combined with propofol-remifentanil anaesthesia significantly improved the median [interquartile range] pain score at 6 h postoperatively (PECS group 1 [0 to 2] vs. Control group 1 [0.25 to 2.75]; P = 0.018]. PECS block also reduced propofol mean (± SD) estimated target blood concentration to maintain bispectral index (BIS) between 40 and 50 (PECS group 2.65 (± 0.52) vs. Control group 3.08 (± 0.41) μg ml; P < 0.001) but not remifentanil consumption (PECS group 10.5 (± 4.28) vs. Control group 10.4 (± 4.68) μg kg h; P = 0.95). PECS block did not improve the QoR-40 score on postoperative day 1 (PECS group 182 [176 to 189] vs. Control group 174.5 [157.75 to 175]). In patients undergoing breast cancer surgery, PECS block combined with general anaesthesia reduced the requirement for propofol but not that for remifentanil, due to the inability of the PECS block to reach the internal mammary area. Further, PECS block improved postoperative pain but not the postoperative QoR-40 score due to the factors that cannot be measured by analgesia immediately after surgery, such as rebound pain. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000013435).

Managing Attribute—Value Clinical Trials Data Using the ACT/DB Client—Server Database System

PubMed Central

Nadkarni, Prakash M.; Brandt, Cynthia; Frawley, Sandra; Sayward, Frederick G.; Einbinder, Robin; Zelterman, Daniel; Schacter, Lee; Miller, Perry L.

1998-01-01

ACT/DB is a client—server database application for storing clinical trials and outcomes data, which is currently undergoing initial pilot use. It stores most of its data in entity—attribute—value form. Such data are segregated according to data type to allow indexing by value when possible, and binary large object data are managed in the same way as other data. ACT/DB lets an investigator design a study rapidly by defining the parameters (or attributes) that are to be gathered, as well as their logical grouping for purposes of display and data entry. ACT/DB generates customizable data entry. The data can be viewed through several standard reports as well as exported as text to external analysis programs. ACT/DB is designed to encourage reuse of parameters across multiple studies and has facilities for dictionary search and maintenance. It uses a Microsoft Access client running on Windows 95 machines, which communicates with an Oracle server running on a UNIX platform. ACT/DB is being used to manage the data for seven studies in its initial deployment. PMID:9524347

AAV capsid CD8+ T-cell epitopes are highly conserved across AAV serotypes

PubMed Central

Hui, Daniel J; Edmonson, Shyrie C; Podsakoff, Gregory M; Pien, Gary C; Ivanciu, Lacramioara; Camire, Rodney M; Ertl, Hildegund; Mingozzi, Federico; High, Katherine A; Basner-Tschakarjan, Etiena

2015-01-01

Adeno-associated virus (AAV) has become one of the most promising vectors in gene transfer in the last 10 years with successful translation to clinical trials in humans and even market approval for a first gene therapy product in Europe. Administration to humans, however, revealed that adaptive immune responses against the vector capsid can present an obstacle to sustained transgene expression due to the activation and expansion of capsid-specific T cells. The limited number of peripheral blood mononuclear cells (PBMCs) obtained from samples within clinical trials allows for little more than monitoring of T-cell responses. We were able to identify immunodominant major histocompatibility complex (MHC) class I epitopes for common human leukocyte antigen (HLA) types by using spleens isolated from subjects undergoing splenectomy for non-malignant indications as a source of large numbers of lymphocytes and restimulating them with single AAV capsid peptides in vitro. Further experiments confirmed that these epitopes are naturally processed and functionally relevant. The design of more effective and less immunogenic AAV vectors, and precise immune monitoring of vector-infused subjects, are facilitated by these findings. PMID:26445723

AAV capsid CD8+ T-cell epitopes are highly conserved across AAV serotypes.

PubMed

Hui, Daniel J; Edmonson, Shyrie C; Podsakoff, Gregory M; Pien, Gary C; Ivanciu, Lacramioara; Camire, Rodney M; Ertl, Hildegund; Mingozzi, Federico; High, Katherine A; Basner-Tschakarjan, Etiena

2015-01-01

Adeno-associated virus (AAV) has become one of the most promising vectors in gene transfer in the last 10 years with successful translation to clinical trials in humans and even market approval for a first gene therapy product in Europe. Administration to humans, however, revealed that adaptive immune responses against the vector capsid can present an obstacle to sustained transgene expression due to the activation and expansion of capsid-specific T cells. The limited number of peripheral blood mononuclear cells (PBMCs) obtained from samples within clinical trials allows for little more than monitoring of T-cell responses. We were able to identify immunodominant major histocompatibility complex (MHC) class I epitopes for common human leukocyte antigen (HLA) types by using spleens isolated from subjects undergoing splenectomy for non-malignant indications as a source of large numbers of lymphocytes and restimulating them with single AAV capsid peptides in vitro. Further experiments confirmed that these epitopes are naturally processed and functionally relevant. The design of more effective and less immunogenic AAV vectors, and precise immune monitoring of vector-infused subjects, are facilitated by these findings.

Gel of chamomile vs. urea cream to prevent acute radiation dermatitis in patients with head and neck cancer: a randomized controlled trial.

PubMed

Ferreira, Elaine Barros; Ciol, Marcia A; Vasques, Christiane Inocêncio; Bontempo, Priscila de Souza Maggi; Vieira, Nayara Narley Pires; Silva, Luis Felipe Oliveira E; Avelino, Samuel Ramalho; Dos Santos, Marcos Antônio; Dos Reis, Paula Elaine Diniz

2016-08-01

To compare a gel made with chamomile (Chamomilla recutita) with a cream of urea as an intervention to delay the time to occurrence of radiation dermatitis. Radiation dermatitis is one of the most common adverse effects of radiotherapy in patients with head and neck cancer. It is characterized by erythema, itching, pain, skin breakage and burning sensation, and there is no consensus on how to prevent it. The study is a randomized controlled clinical trial. We will recruit 48 individuals with head and neck cancer who will be starting their radiotherapy and randomize them to receive either gel of chamomile or cream of urea, as an intervention for prevention of radiation dermatitis. Social-demographic data will be collected at baseline, and clinical data will be collected before the initiation of radiotherapy. Participants will be followed weekly to assess development of radiation dermatitis. The protocol is funded by Conselho Nacional de Pesquisa e Desenvolvimento Científico (Brazil). The study was approved by a research ethics committee. Given the clinical relevance of preventing radiation dermatitis and the lack of evidence supporting specific preventive interventions, it is important to study new products that might be efficacious to prevent this complication. This article presents the protocol of a randomized controlled trial comparing a gel made with chamomile (intervention) with a cream of urea (control) to prevent radiation dermatitis in patients with head and neck cancer undergoing radiotherapy. © 2016 John Wiley & Sons Ltd.

Validating abortion procedure coding in Canadian administrative databases.

PubMed

Samiedaluie, Saied; Peterson, Sandra; Brant, Rollin; Kaczorowski, Janusz; Norman, Wendy V

2016-07-12

The British Columbia (BC) Ministry of Health collects abortion procedure data in the Medical Services Plan (MSP) physician billings database and in the hospital information Discharge Abstracts Database (DAD). Our study seeks to validate abortion procedure coding in these databases. Two randomized controlled trials enrolled a cohort of 1031 women undergoing abortion. The researcher collected database includes both enrollment and follow up chart review data. The study cohort was linked to MSP and DAD data to identify all abortions events captured in the administrative databases. We compared clinical chart data on abortion procedures with health administrative data. We considered a match to occur if an abortion related code was found in administrative data within 30 days of the date of the same event documented in a clinical chart. Among 1158 abortion events performed during enrollment and follow-up period, 99.1 % were found in at least one of the administrative data sources. The sensitivities for the two databases, evaluated using a gold standard, were 97.7 % (95 % confidence interval (CI): 96.6-98.5) for the MSP database and 91.9 % (95 % CI: 90.0-93.4) for the DAD. Abortion events coded in the BC health administrative databases are highly accurate. Single-payer health administrative databases at the provincial level in Canada have the potential to offer valid data reflecting abortion events. ClinicalTrials.gov Identifier NCT01174225 , Current Controlled Trials ISRCTN19506752 .

Effects of red-cell storage duration on patients undergoing cardiac surgery.

PubMed

Steiner, Marie E; Ness, Paul M; Assmann, Susan F; Triulzi, Darrell J; Sloan, Steven R; Delaney, Meghan; Granger, Suzanne; Bennett-Guerrero, Elliott; Blajchman, Morris A; Scavo, Vincent; Carson, Jeffrey L; Levy, Jerrold H; Whitman, Glenn; D'Andrea, Pamela; Pulkrabek, Shelley; Ortel, Thomas L; Bornikova, Larissa; Raife, Thomas; Puca, Kathleen E; Kaufman, Richard M; Nuttall, Gregory A; Young, Pampee P; Youssef, Samuel; Engelman, Richard; Greilich, Philip E; Miles, Ronald; Josephson, Cassandra D; Bracey, Arthur; Cooke, Rhonda; McCullough, Jeffrey; Hunsaker, Robert; Uhl, Lynne; McFarland, Janice G; Park, Yara; Cushing, Melissa M; Klodell, Charles T; Karanam, Ravindra; Roberts, Pamela R; Dyke, Cornelius; Hod, Eldad A; Stowell, Christopher P

2015-04-09

Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion. We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge. The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%, respectively (P=0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group. The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).

In vivo light dosimetry for HPPH-mediated pleural PDT

NASA Astrophysics Data System (ADS)

Dimofte, Andreea; Zhu, Timothy C.; Finlay, Jarod C.; Cullighan, Melissa; Edmonds, Christine E.; Friedberg, Joseph S.; Cengel, Keith; Hahn, Stephen M.

2010-02-01

This study examines the light fluence (rate) delivered to patients undergoing pleural PDT as a function of treatment time, treatment volume and surface area. The accuracy of treatment delivery is analyzed as a function of the calibration accuracies of each isotropic detector and the calibration integrating sphere. The patients studied here are enrolled in a Phase I clinical trial of HPPH-mediated PDT for the treatment of non-small cell lung cancer with pleural effusion. Patients are administered 4mg per kg body weight HPPH 24-48 hours before the surgery. Patients undergoing photodynamic therapy (PDT) are treated with light therapy with a fluence of 15-60 J/cm2 at 661nm. Fluence rate (mW/cm2) and cumulative fluence (J/cm2) is monitored at 7 different sites during the entire light treatment delivery. Isotropic detectors are used for in-vivo light dosimetry. The anisotropy of each isotropic detector was found to be within 15%. The mean fluence rate delivery and treatment time are recorded. A correlation between the treatment time and the treatment volume is established. The result can be used as a clinical guideline for future pleural PDT treatment.

Systemic inflammation and oxidative stress post-lung resection: Effect of pretreatment with N-acetylcysteine.

PubMed

Bastin, Anthony J; Davies, Nathan; Lim, Eric; Quinlan, Greg J; Griffiths, Mark J

2016-01-01

N-acetylcysteine has been used to treat a variety of lung diseases, where is it thought to have an antioxidant effect. In a randomized placebo-controlled double-blind study, the effect of N-acetylcysteine on systemic inflammation and oxidative damage was examined in patients undergoing lung resection, a human model of acute lung injury. Eligible adults were randomized to receive preoperative infusion of N-acetylcysteine (240 mg/kg over 12 h) or placebo. Plasma thiols, interleukin-6, 8-isoprostane, ischaemia-modified albumin, red blood cell glutathione and exhaled breath condensate pH were measured pre- and post-operatively as markers of local and systemic inflammation and oxidative stress. Patients undergoing lung resection and one-lung ventilation exhibited significant postoperative inflammation and oxidative damage. Postoperative plasma thiol concentration was significantly higher in the N-acetylcysteine-treated group. However, there was no significant difference in any of the measured biomarkers of inflammation or oxidative damage, or in clinical outcomes, between N-acetylcysteine and placebo groups. Preoperative administration of N-acetylcysteine did not attenuate postoperative systemic or pulmonary inflammation or oxidative damage after lung resection. NCT00655928 at ClinicalTrials.gov. © 2015 Asian Pacific Society of Respirology.

Transcranial direct current stimulation improves neurorehabilitation of task-specific dystonia: a pilot study.

PubMed

Rosset-Llobet, Jaume; Fàbregas-Molas, Sílvia; Pascual-Leone, Alvaro

2014-03-01

Sensory-motor returning (SMR) can help the symptoms of task-specific focal hand dystonia. However, effects vary across patients and take many sessions. Here, we present proof of principle evidence that transcranial direct current stimulation (tDCS) can enhance these effects. We compared the effects of a combined tDCS-SMR protocol (n=4 patients) with the efficacy of SMR alone (n=30 patients). All 4 patients treated with the combined protocol showed greater improvement than those undergoing SMR alone. Results encourage a larger, parallel-group clinical trial with sham tDCS control.

Study design and rationale for Optimal aNtiplatelet pharmacotherapy guided by bedSIDE genetic or functional TESTing in elective percutaneous coronary intervention patients (ONSIDE TEST): a prospective, open-label, randomised parallel-group multicentre trial (NCT01930773).

PubMed

Kołtowski, Łukasz; Aradi, Daniel; Huczek, Zenon; Tomaniak, Mariusz; Sibbing, Dirk; Filipiak, Krzysztof J; Kochman, Janusz; Balsam, Paweł; Opolski, Grzegorz

2016-01-01

High platelet reactivity (HPR) and presence of CYP2C19 loss-of-function alleles are associated with higher risk for periprocedural myocardial infarction in clopidogrel-treated patients undergoing percutaneous coronary intervention (PCI). It is unknown whether personalised treatment based on platelet function testing or genotyping can prevent such complications. The ONSIDE-TEST is a multicentre, prospective, open-label, randomised controlled clinical trial aiming to assess if optimisation of antiplatelet therapy based on either phenotyping or genotyping is superior to conventional care. Patients will be randomised into phenotyping, genotyping, or control arms. In the phenotyping group, patients will be tested with the VerifyNow P2Y12 assay before PCI, and patients with a platelet reactivity unit greater than 208 will be switched over to prasugrel, while others will continue on clopidogrel therapy. In the genotyping group, carriers of the *2 loss-of-function allele will receive prasugrel for PCI, while wild-type subjects will be treated with clopidogrel. Patients in the control arm will be treated with standard-dose clopidogrel. The primary endpoint of the study is the prevalence of periprocedural myocardial injury within 24 h after PCI in the controls as compared to the phenotyping and genotyping group. Secondary endpoints include cardiac death, myocardial infarction, definite or probable stent thrombosis, or urgent repeat revascularisation within 30 days of PCI. Primary safety outcome is Bleeding Academic Research Consortium (BARC) type 3 and 5 bleeding during 30 days of PCI. The ONSIDE TEST trial is expected to verify the clinical utility of an individualised antiplatelet strategy in preventing periprocedural myocardial injury by either phenotyping or genotyping. ClinicalTrials.gov: NCT01930773.

The efficacy of sodium benzoate as an adjunctive treatment in early psychosis - CADENCE-BZ: study protocol for a randomized controlled trial.

PubMed

Ryan, Alex; Baker, Andrea; Dark, Frances; Foley, Sharon; Gordon, Anne; Hatherill, Sean; Stathis, Stephen; Saha, Sukanta; Bruxner, George; Beckman, Martin; Richardson, Drew; Berk, Michael; Dean, Olivia; McGrath, John; Group, Cadence Working; Scott, James

2017-04-07

Psychotic disorders affect up to 3% of the population and are often chronic and disabling. Innovation in the pharmacological treatment of psychosis has remained stagnant in recent decades. In order to improve outcomes for those with psychotic disorders, we present a protocol for the trial of a common food preservative, sodium benzoate, as an adjunctive treatment in early psychosis. Persons experiencing early psychosis (n = 160) will be recruited through hospitals and community mental health services in Queensland, Australia. Patients will be randomized to receive either 12-week treatment with 1000 mg (500 mg twice daily (BD)) sodium benzoate or placebo. Patients will undergo fortnightly outcome assessments, in addition to weekly ongoing capacity to consent, drug compliance and safety assessments. The primary outcome measure is the Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcomes are Global Assessment of Function (GAF), Assessment of Quality of Life Scale (AQOL), the Activity and Participation Questionnaire (APQ6), International Physical Activity Questionnaires (IPAQ), Simple Physical Activity Questionnaire (SIMPAQ), Physical Activity Questionnaire, Clinical Global Impression (CGI), Hamilton Depression rating Scale-17 items (HDRS), Opiate Treatment Index (OTI) and the Patients' Global Impression of Improvement (PGI-I). As a tertiary objective, changes from baseline to endpoint in to serum markers related to D-alanine, L-alanine, D-serine, L-serine, glycine and glutamate will be investigated. Consumers and clinicians are keen to help develop better treatments for those with psychosis. This study, part of the wider Cadence clinical trials platform will examine if a safe and accessible food preservative can help optimize outcomes in those with psychosis. Australian New Zealand Clinical Trials registry (ANZCTR), ACTRN12615000187549 . Registered on 26 February 2015.

Contemporary Reflections on the Safety of Long-Term Aspirin Treatment for the Secondary Prevention of Cardiovascular Disease

PubMed Central

Fanaroff, Alexander C.; Roe, Matthew T.

2018-01-01

Aspirin has been the cornerstone of therapy for the secondary prevention treatment of patients with cardiovascular disease since landmark trials were completed in the late 1970s and early 1980s that demonstrated the efficacy of aspirin for reducing the risk of ischemic events. Notwithstanding the consistent benefits demonstrated with apirin for both acute and chronic cardiovascular disease, there are a number of toxicities associated with aspirin that have been showcased by recent long-term clinical trials that have included an aspirin monotherapy arm. As an inhibitor of cyclooxygenase, aspirin impairs gastric mucosal protective mechanisms. Prior trials have shown that up to 15–20% of patients developed gastrointestinal symptoms with aspirin monotherapy and roughly 1% of patients per year had a clinically significant bleeding event, including 1 in 1000 patients who suffered an intracranial or fatal bleed. These risks have been shown to be compounded for patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI), who are also treated with other anti-thrombotic agents during the acute care/procedural period, as well as for an extended time period afterwards. Given observations of substantial increases in bleeding rates from many prior long-term clinical trials that have evaluated aspirin together with other oral platelet inhibitors or oral anti-coagulants, the focus of contemporary research has pivoted towards tailored anti-thrombotic regimens that attempt to either shorten the duration of exposure to aspirin or replace aspirin with an alternative anti-thrombotic agent. While these shifts are occurring, the safety profile of aspirin when used for the secondary prevention treatment of patients with established cardiovascular disease deserves further consideration. PMID:27028617

Methods of preventing bacterial sepsis and wound complications after liver transplantation.

PubMed

Gurusamy, Kurinchi Selvan; Nagendran, Myura; Davidson, Brian R

2014-03-05

Bacterial sepsis and wound complications after liver transplantation increase mortality, morbidity, or hospital stay and are likely to increase overall transplant costs. All liver transplantation patients receive antibiotic prophylaxis. This is an update of our 2008 Cochrane systematic review on the same topic in which we identified seven randomised clinical trials. To assess the benefits and harms of different methods aimed at preventing bacterial sepsis and wound complications in people undergoing liver transplantation. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded to February 2013. We included only randomised clinical trials irrespective of language or publication status. We excluded quasi-randomised and other observational studies for assessment of benefits, but not for harms. Two review authors collected the data independently. We calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) using fixed-effect and the random-effects models based on available-case analysis. We identified only seven trials for inclusion, including 614 participants. Only one trial was of low risk of bias risk. Overall, the quality of evidence was very low. There were five comparisons in the seven trials: selective bowel decontamination versus inactive control; selective bowel decontamination versus prebiotics with probiotics; selective bowel decontamination versus prebiotics; prebiotics with probiotics versus prebiotics; and granulocyte-colony stimulating factor (G-CSF) versus control. Four trials compared selective bowel decontamination versus placebo or no treatment. In one trial, participants were randomised to selective bowel decontamination, active lactobacillus with fibres (probiotic with prebiotic), or to inactivated lactobacillus with fibres (prebiotic). In one trial, active lactobacillus with fibres (probiotic with prebiotic) was compared with inactive lactobacillus with fibres (prebiotic). In the remaining trial, different doses of G-CSF and placebo were compared. There was no trial comparing different antibiotic prophylactic regimens in people undergoing liver transplantation. Most trials included adults undergoing elective liver transplantation. There was no significant difference in proportion of people who died or required retransplantation between the intervention and control groups in any of the five comparison groups. MORTALITY There were no differences between 190 participants (three trials); 5/87 (adjusted proportion: 6.2%) in selective bowel decontamination group versus 7/103 (6.8%) in inactive control group; RR 0.91 (95% CI 0.31 to 2.72); 63 participants (one trial); 0/32 (0%) in selective bowel decontamination group versus 0/31 (0%) in prebiotics with probiotics group; RR - not estimable; 64 participants (one trial); 0/32 (0%) in selective bowel decontamination group versus 0/32 (0%) in prebiotics group; RR - not estimable; 129 participants (two trials); 0/64 (0%) in prebiotics with probiotics group versus 0/65 (0%) in prebiotics group; RR - not estimable; and 194 participants (one trial); 22/124 (17.7%) in G-CSF group versus 10/70 (14.3%) in placebo group; RR 1.24 (95% 0.62 to 2.47). RETRANSPLANTATION There were no differences between 132 participants (two trials); 4/58 (adjusted proportion: 6.9%) in selective bowel decontamination group versus 6/74 (8.1%) in inactive control group; RR 0.85 (95% CI 0.26 to 2.85); 63 participants (one trial); 1/32 (3.1%) in selective bowel decontamination group versus 0/31 (0%) in prebiotics with probiotics group; RR 2.91 (0.12 to 68.81); 64 participants (one trial); 1/32 (3.1%) in selective bowel decontamination group versus 0/32 (0%) in prebiotics group; RR 3.00 (95% CI 0.13 to 71.00); 129 participants (two trials); 0/64 (0%) in prebiotics with probiotics group versus 1/65 (1.5%) in prebiotics group; RR 0.33 (95% CI 0.01 to 7.9); and 194 participants (one trial); 10/124 (7.1%) in G-CSF group versus 5/70 (7.1%) in placebo group; RR 1.13 (95% CI 0.4 to 3.17).There was no significant difference in the graft rejections, intensive therapy unit stay, or hospital stay between the intervention and control groups in any of the comparisons. Overall, 193/611 participants (31.6%) developed infective complications. The proportion of people who developed infective complications and the number of infective complication episodes were significantly higher in the selective bowel decontamination group than in the prebiotics with probiotics group (1 study; 63 participants; 15/32 (46.9%) in selective bowel decontamination group versus 4/31 (12.9%) in prebiotics with probiotics group; RR 3.63; 95% CI 1.36 to 9.74 and 23/32 participants (0.72 infective complications per participant) in selective bowel decontamination group versus 4/31 participants (0.13 infective complications per participant) in prebiotics with probiotics group; rate ratio 5.58; 95% CI 1.94 to 16.09). There was no significant difference between the proportion of participants who developed infection and the number of infection episodes between the intervention group and control group in any of the other comparisons.No trials reported quality of life and overall serious adverse events. Currently, there is no clear evidence for any intervention offering significant benefits in the reduction of bacterial infections and wound complications in liver transplantation. Selective bowel decontamination may even increase the rate of infections compared with prebiotics with probiotics. The confidence intervals were wide and further randomised clinical trials of low risk of bias are necessary.

Differential effects of aprotinin and tranexamic acid on outcomes and cytokine profiles in neonates undergoing cardiac surgery.

PubMed

Graham, Eric M; Atz, Andrew M; Gillis, Jenna; Desantis, Stacia M; Haney, A Lauren; Deardorff, Rachael L; Uber, Walter E; Reeves, Scott T; McGowan, Francis X; Bradley, Scott M; Spinale, Francis G

2012-05-01

Factors contributing to postoperative complications include blood loss and a heightened inflammatory response. The objective of this study was to test the hypothesis that aprotinin would decrease perioperative blood product use, reduce biomarkers of inflammation, and result in improved clinical outcome parameters in neonates undergoing cardiac operations. This was a secondary retrospective analysis of a clinical trial whereby neonates undergoing cardiac surgery received either aprotinin (n = 34; before May 2008) or tranexamic acid (n = 42; after May 2008). Perioperative blood product use, clinical course, and measurements of cytokines were compared. Use of perioperative red blood cells, cryoprecipitate, and platelets was reduced in neonates receiving aprotinin compared with tranexamic acid (P < .05). Recombinant activated factor VII use (2/34 [6%] vs 18/42 [43%]; P < .001), delayed sternal closure (12/34 [35%] vs 26/42 [62%]; P = .02), and inotropic requirements at 24 and 36 hours (P < .05) were also reduced in the aprotinin group. Median duration of mechanical ventilation was reduced compared with tranexamic acid: 2.9 days (interquartile range: 1.7-5.1 days) versus 4.2 days (2.9-5.2 days), P = .04. Production of tumor necrosis factor and interleukin-2 activation were attenuated in the aprotinin group at 24 hours postoperatively. No differential effects on renal function were seen between agents. Aprotinin, compared with tranexamic acid, was associated with reduced perioperative blood product use, improved early indices of postoperative recovery, and attenuated indices of cytokine activation, without early adverse effects. These findings suggest that aprotinin may have unique effects in the context of neonatal cardiac surgery and challenge contentions that antifibrinolytics are equivalent with respect to early postoperative outcomes. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Differential effects of aprotinin and tranexamic acid on outcomes and cytokine profiles in neonates undergoing cardiac surgery

PubMed Central

Graham, Eric M.; Atz, Andrew M.; Gillis, Jenna; DeSantis, Stacia M.; Haney, A. Lauren; Deardorff, Rachael L.; Uber, Walter E.; Reeves, Scott T.; McGowan, Francis X.; Bradley, Scott M.; Spinale, Francis G.

2011-01-01

Objective Factors contributing to postoperative complications include blood loss and a heightened inflammatory response. The objective of this study was to test the hypothesis that aprotinin would decrease perioperative blood product use, reduce biomarkers of inflammation, and result in improved clinical outcome parameters in neonates undergoing cardiac operations. Methods This was a secondary retrospective analysis of a clinical trial whereby neonates undergoing cardiac surgery received either aprotinin (n = 34; before May 2008) or tranexamic acid (n = 42; after May 2008). Perioperative blood product use, clinical course, and measurements of cytokines were compared. Results Use of perioperative red blood cells, cryoprecipitate, and platelets was reduced in neonates receiving aprotinin compared with tranexamic acid (P < .05). Recombinant activated factor VII use (2/34 [6%] vs 18/42 [43%]; P < .001), delayed sternal closure (12/34 [35%] vs 26/42 [62%]; P = .02), and inotropic requirements at 24 and 36 hours (P < .05) were also reduced in the aprotinin group. Median duration of mechanical ventilation was reduced compared with tranexamic acid: 2.9 days (interquartile range: 1.7–5.1 days) versus 4.2 days (2.9–5.2days), P = .04. Production of tumor necrosis factor and interleukin-2 activation were attenuated in the aprotinin group at 24 hours postoperatively. No differential effects on renal function were seen between agents. Conclusions Aprotinin, compared with tranexamic acid, was associated with reduced perioperative blood product use, improved early indices of postoperative recovery, and attenuated indices of cytokine activation, without early adverse effects. These findings suggest that aprotinin may have unique effects in the context of neonatal cardiac surgery and challenge contentions that antifibrinolytics are equivalent with respect to early postoperative outcomes. PMID:22075061

[A Randomized Controlled Clinical Trial for Electroacupuncture Treatment of Post-surgical Gastrointestinal Dysfunction in Patients Undergoing Laparotomy].

PubMed

Pan, Hui; Li, Jia; Zhao, Yu; Li, Ning

2016-10-25

To evaluate the clinical efficacy of electroacupuncture (EA) stimulation of Zusanli (ST 36) and Neiguan (PC 6) in the treatment of persistent postoperative gastrointestinal dysfunction in patients undergoing laparotomy. A total of 60 laparotomy patients were enlisted in the present study and were randomly divided into conventional treatment group (control) and EA group ( n =30 in each group). Patients of the EA group were treated by conventional treatment and EA stimulation (2 Hz, 1-10 mA) of bilateral ST 36 and PC 6 for 30 min, once daily for 5 days, and patients of the control group treated by conventional treatment (pre- and post-surgical fasting, measures for gastrointestinal decompression, electrolyte stabilization, parenteral nutrition support, and anti-infection in necessity, etc). The first postoperative flatus and defecation time, postoperative hospital stays,abdominal bloating grading (0-4 points, i.e. Likert scale), and adverse events were recorded and evaluated. After the treatment, the first postoperative flatus and defecation time, and hospital stay time and abdominal bloating scores from the 2 nd to the 5 th day post-surgery in the EA group were significantly lower than those of the control group ( P <0.05). The abdominal bloating scores of the two groups were gradually and obviously decreased from the 2 nd day on in comparison with pre-treatment ( P <0.05). Of the two 30 cases in the control and EA groups, 5 and 14 were cured in their clinical symptoms, 15 and 13 experienced marked improvement, 7 and 3 were effective, 2 and 0 invalid, with the effective rates being 66.7% and 90.0%, respectively. EA is effective in improving persistent postoperative gastrointestinal dysfunction in cancer patients undergoing laparotomy.

Does Patient Preference Measurement in Decision Aids Improve Decisional Conflict? A Randomized Trial in Men with Prostate Cancer.

PubMed

Shirk, Joseph D; Crespi, Catherine M; Saucedo, Josemanuel D; Lambrechts, Sylvia; Dahan, Ely; Kaplan, Robert; Saigal, Christopher

2017-12-01

Shared decision making (SDM) has been advocated as an approach to medical decision making that can improve decisional quality. Decision aids are tools that facilitate SDM in the context of limited physician time; however, many decision aids do not incorporate preference measurement. We aim to understand whether adding preference measurement to a standard patient educational intervention improves decisional quality and is feasible in a busy clinical setting. Men with incident localized prostate cancer (n = 122) were recruited from the Greater Los Angeles Veterans Affairs (VA) Medical Center urology clinic, Olive View UCLA Medical Center, and Harbor UCLA Medical Center from January 2011 to May 2015 and randomized to education with a brochure about prostate cancer treatment or software-based preference assessment in addition to the brochure. Men undergoing preference assessment received a report detailing the relative strength of their preferences for treatment outcomes used in review with their doctor. Participants completed instruments measuring decisional conflict, knowledge, SDM, and patient satisfaction with care before and/or after their cancer consultation. Baseline knowledge scores were low (mean 62%). The baseline mean total score on the Decisional Conflict Scale was 2.3 (±0.9), signifying moderate decisional conflict. Men undergoing preference assessment had a significantly larger decrease in decisional conflict total score (p = 0.023) and the Perceived Effective Decision Making subscale (p = 0.003) post consult compared with those receiving education only. Improvements in satisfaction with care, SDM, and knowledge were similar between groups. Individual-level preference assessment is feasible in the clinic setting. Patients with prostate cancer who undergo preference assessment are more certain about their treatment decisions and report decreased levels of decisional conflict when making these decisions.

Remote Ischemic Preconditioning Fails to Benefit Pediatric Patients Undergoing Congenital Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials.

PubMed

Tie, Hong-Tao; Luo, Ming-Zhu; Li, Zhen-Han; Wang, Qian; Wu, Qing-Chen; Li, Qiang; Zhang, Min

2015-10-01

Remote ischemic preconditioning (RIPC) has been proven to reduce the ischemia-reperfusion injury. However, its effect on children receiving congenital cardiac surgery (CCS) was inconsistent. We therefore performed the current meta-analysis of randomized controlled trials (RCTs) to comprehensively evaluate the effect of RIPC in pediatric patients undergoing CCS.PubMed, Embase, and Cochrane library were searched to identify RCTs assessing the effect of RIPC in pediatric patients undergoing CCS. The outcomes included the duration of mechanical ventilation (MV), intensive care unit (ICU) length of stay, postoperative cardiac troponin (cTnI) level, hospital length of stay (HLOS), postoperative inotropic score, and mortality. Subgroup and sensitivity analysis were also performed as predesigned. The meta-analysis was performed with random-effects model despite of heterogeneity. Sensitivity and subgroup analysis were predesigned to identify the robustness of the pooled estimate.Nine RCTs with 697 pediatric patients were included in the meta-analysis. Overall, RIPC failed to alter clinical outcomes of duration of MV (standard mean difference [SMD] -0.03, 95% confidence interval [CI] -0.23-0.17), ICU length of stay (SMD -0.22, 95% CI -0.47-0.04), or HLOS (SMD -0.14, 95% CI -0.55-0.26). Additionally, RIPC could not reduce postoperative cTnI (at 4-6 hours: SMD -0.25, 95% CI -0.73-0.23; P = 0.311; at 20-24 hours: SMD 0.09, 95% CI -0.51-0.68; P = 0.778) or postoperative inotropic score (at 4-6 hours: SMD -0.19, 95% CI -0.51-0.14; P = 0.264; at 24 hours: SMD -0.15, 95% CI -0.49-0.18; P = 0.365).RIPC may have no beneficial effects in children undergoing CCS. However, this finding should be interpreted with caution because of heterogeneity and large-scale RCTs are still needed.

Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery.

PubMed

Myles, Paul S; Smith, Julian A; Forbes, Andrew; Silbert, Brendan; Jayarajah, Mohandas; Painter, Thomas; Cooper, D James; Marasco, Silvana; McNeil, John; Bussières, Jean S; McGuinness, Shay; Byrne, Kelly; Chan, Matthew T V; Landoni, Giovanni; Wallace, Sophie

2017-01-12

Tranexamic acid reduces the risk of bleeding among patients undergoing cardiac surgery, but it is unclear whether this leads to improved outcomes. Furthermore, there are concerns that tranexamic acid may have prothrombotic and proconvulsant effects. In a trial with a 2-by-2 factorial design, we randomly assigned patients who were scheduled to undergo coronary-artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. Of the 4662 patients who were enrolled and provided consent, 4631 underwent surgery and had available outcomes data; 2311 were assigned to the tranexamic acid group and 2320 to the placebo group. A primary outcome event occurred in 386 patients (16.7%) in the tranexamic acid group and in 420 patients (18.1%) in the placebo group (relative risk, 0.92; 95% confidence interval, 0.81 to 1.05; P=0.22). The total number of units of blood products that were transfused during hospitalization was 4331 in the tranexamic acid group and 7994 in the placebo group (P<0.001). Major hemorrhage or cardiac tamponade leading to reoperation occurred in 1.4% of the patients in the tranexamic acid group and in 2.8% of the patients in the placebo group (P=0.001), and seizures occurred in 0.7% and 0.1%, respectively (P=0.002 by Fisher's exact test). Among patients undergoing coronary-artery surgery, tranexamic acid was associated with a lower risk of bleeding than was placebo, without a higher risk of death or thrombotic complications within 30 days after surgery. Tranexamic acid was associated with a higher risk of postoperative seizures. (Funded by the Australian National Health and Medical Research Council and others; ATACAS Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639 .).

In vivo light dosimetry for pleural PDT

NASA Astrophysics Data System (ADS)

Dimofte, Andreea; Zhu, Timothy C.; Finlay, Jarod C.; Culligan, Melissa; Edmonds, Christine E.; Friedberg, Joseph S.; Cengel, Keith; Hahn, Stephen M.

2009-02-01

In-vivo light Dosimetry for patients undergoing photodynamic therapy (PDT) is one of the important dosimetry quantities critical for predicting PDT outcome. This study examines the light fluence (rate) delivered to patients undergoing pleural PDT as a function of treatment time, treatment volume and surface area, and its accuracy as a function of the calibration accuracies of each isotropic detector and the calibration integrating sphere. The patients studied here were enrolled in Phase II clinical trial of Photofrin-mediated PDT for the treatment of non-small cell lung cancer with pleural effusion. The ages of the patients studied varied from 34 to 69 year old. All patients were administered 2mg per kg body weight Photoprin 24 hours before the surgery. Patients undergoing photodynamic therapy (PDT) are treated with laser light with a light fluence of 60 J/cm^2 at 630nm. Fluence rate (mW/cm^2) and cumulative fluence (J/cm^2) was monitored at 7 different sites during the entire light treatment delivery. Isotropic detectors were used for in-vivo light dosimetry. The anisotropy of each isotropic detector was found to be within 30%. The mean fluence rate delivery varied from 37.84 to 94.05 mW/cm^2 and treatment time varied from 1762 to 5232s. We have established a correlation between the treatment time and the treatment volume. The results are discussed using an integrating sphere theory and the measured tissue optical properties. The result can be used as a clinical guideline for future pleural PDT treatment.

A meta-analysis of randomised controlled trials on preoperative oral carbohydrate treatment in elective surgery.

PubMed

Awad, Sherif; Varadhan, Krishna K; Ljungqvist, Olle; Lobo, Dileep N

2013-02-01

Whilst preoperative carbohydrate treatment (PCT) results in beneficial physiological effects, the effects on postoperative clinical outcomes remain unclear and were studied in this meta-analysis. Prospective studies that randomised adult non-diabetic patients to either PCT (≥50 g oral carbohydrates 2-4 h pre-anaesthesia) or control (fasted/placebo) were included. The primary outcome was length of hospital stay. Secondary outcomes included development of postoperative insulin resistance, complications, nausea and vomiting. Methodological quality was assessed using GRADEpro® software. Twenty-one randomised studies of 1685 patients (733 PCT: 952 control) were included. No overall difference in length of stay was noted for analysis of all studies or subgroups of patients undergoing surgery with an expected hospital stay ≤2 days or orthopaedic procedures. However, patients undergoing major abdominal surgery following PCT had reduced length of stay [mean difference, 95% confidence interval: -1.08 (-1.87 to -0.29); I² = 60%, p = 0.007]. PCT reduced postoperative insulin resistance with no effects on in-hospital complications over control (risk ratio, 95% confidence interval, 0.88 (0.50-1.53), I² = 41%; p = 0.640). There was significant heterogeneity amongst studies and, therefore, quality of evidence was low to moderate. PCT may be associated with reduced length of stay in patients undergoing major abdominal surgery, however, the included studies were of low to moderate quality. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Inhaled methoxyflurane for pain and anxiety relief during burn wound care procedures: an Australian case series.

PubMed

Wasiak, Jason; Mahar, Patrick D; Paul, Eldho; Menezes, Hana; Spinks, Anneliese B; Cleland, Heather

2014-02-01

Pain is a common and significant feature of burn injury. The use of intravenous opioids forms the mainstay of procedural burn pain management, but in an outpatient setting, the demand for novel agents that do not require parenteral access, are easy to administer and have a rapid onset are urgently needed. One such agent is the inhaled anaesthetic agent, methoxyflurane (MF). The aim of this study was to conduct a pilot investigation into the clinical effectiveness of MF inhaler on pain and anxiety scores in patients undergoing burn wound care procedures in an outpatient setting. A prospective case series involved recruiting patients undergoing a burn wound care procedure in an ambulatory burn care setting. Pain and anxiety were assessed using numerical rating scales. Overall, median numerical pain rating score was significantly higher post-dressing [pre-dressing: 2; interquartile range (IQR): 1-3 versus post-dressing: 3; IQR 1·5-4; P = 0·01], whereas median numerical anxiety score significantly reduced following the dressing (pre-dressing: 5; IQR 4-7 versus post-dressing: 2; IQR 1-2; P < 0·001). Our study suggests that there is a role for MF in the pain management armamentarium in those undergoing burn care procedures in the ambulatory care setting. However, there is an urgent need for larger case series and randomised controlled trials to determine its overall clinical effectiveness. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: first-line interventions.

PubMed

Karam, A; Ledermann, J A; Kim, J-W; Sehouli, J; Lu, K; Gourley, C; Katsumata, N; Burger, R A; Nam, B-H; Bacon, M; Ng, C; Pfisterer, J; Bekkers, R L M; Casado Herráez, A; Redondo, A; Fujiwara, H; Gleeson, N; Rosengarten, O; Scambia, G; Zhu, J; Okamoto, A; Stuart, G; Ochiai, K

2017-04-01

The consensus statements regarding first-line therapies in women with ovarian cancer, reached at the Fifth Ovarian Cancer Consensus Conference held in Tokyo, Japan, in November 2015 are reported. Three topics were reviewed and the following statements are recommended: (i) Surgery: the subgroups that should be considered in first-line ovarian cancer clinical trials should be (a) patients undergoing primary debulking surgery and (b) patients receiving neo-adjuvant chemotherapy. The amount of residual disease following surgery should further stratify patients into those with absent gross residual disease and others. (ii) Control arms for chemotherapy: for advanced stage ovarian cancer the standard is intravenous 3-weekly carboplatin and paclitaxel. Acceptable alternatives, which should be stratified variables in trials when more than one regimen is offered, include weekly paclitaxel plus 3-weekly carboplatin, the addition of bevacizumab to 3-weekly carboplatin and paclitaxel, and intraperitoneal therapy. (iii) Trial Endpoints: overall survival is the preferred primary endpoint for first-line clinical trials with or without a maintenance component. Progression-free survival (PFS) is an alternative primary endpoint, but if PFS is chosen overall survival must be measured as a secondary endpoint and PFS must be supported by additional endpoints, including predefined patient reported outcomes and time to first or second subsequent therapy. For neoadjuvant therapy, additional 'window of opportunity' endpoints should be included. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Protocol for a pilot, randomised, double-blinded, placebo-controlled trial of prophylactic use of tranexamic acid for preventing postpartum haemorrhage (TAPPH-1)

PubMed Central

Alam, Asim; Bopardikar, Ameya; Au, Shelly; Barrett, Jon; Callum, Jeannie; Kiss, Alex; Choi, Stephen

2017-01-01

Introduction Postpartum haemorrhage (PPH) is the leading cause of maternal morbidity and mortality worldwide. Despite the availability of multiple uterotonic agents, the incidence of PPH continues to rise. Tranexamic acid (TXA) has been shown to be a safe, effective and inexpensive therapeutic option for the treatment of PPH, however, its use prophylactically in mitigating the risk of PPH is unknown. This pragmatic randomised prospective trial assesses the feasibility and safety of administering TXA at the time of delivery for the prevention of PPH. Methods and analysis A pilot pragmatic randomised double-blinded placebo-controlled trial will be performed. 58 singleton parturients at term >32 weeks, undergoing either spontaneous vaginal delivery, or caesarean section will be randomised to receive 1 g of TXA or placebo (0.9% saline) intravenously. The primary outcome assessed will be the feasibility of administrating TXA, along with collecting data regarding safety of drug administration. The groups will also be analysed on efficacy of mitigating the onset of PPH and clinically relevant variables. Demographic, feasibility, safety and clinical endpoints will be summarised and the appropriate measures of central tendency and dispersion will be presented. Ethics and dissemination This protocol was approved by the Sunnybrook Health Sciences Centre Research Ethics Board (number: 418-2016). The results will be disseminated in a peer-reviewed journal and at scientific meetings. Trial registration number NCT03069859; Pre-results. PMID:29025850