Gross total resection rates in contemporary glioblastoma surgery: results of an institutional protocol combining 5-aminolevulinic acid intraoperative fluorescence imaging and brain mapping

Complete resection of contrast-enhancing tumor has been recognized as an important prognostic factor in patients with glioblastoma and is a primary goal of surgery. Various intraoperative technologies have recently been introduced to improve glioma surgery.

Effect of comprehensive cardiac rehabilitation after heart valve surgery (CopenHeartVR): study protocol for a randomised clinical trial

Background Heart valve diseases are common with an estimated prevalence of 2.5% in the Western world. The number is rising due to an ageing population. Once symptomatic, heart valve diseases are potentially lethal, and heavily influence daily living and quality of life. Surgical treatment, either valve replacement or repair, remains the treatment of choice. However, post surgery, the transition to daily living may become a physical, mental and social challenge. We hypothesise that a comprehensive cardiac rehabilitation programme can improve physical capacity and self-assessed mental health and reduce hospitalisation and healthcare costs after heart valve surgery. Methods A randomised clinical trial, CopenHeartVR, aims to investigate whether cardiac rehabilitation in addition to usual care is superior to treatment as usual after heart valve surgery. The trial will randomly allocate 210 patients, 1:1 intervention to control group, using central randomisation, and blinded outcome assessment and statistical analyses. The intervention consists of 12 weeks of physical exercise, and a psycho-educational intervention comprising five consultations. Primary outcome is peak oxygen uptake (VO2 peak) measured by cardiopulmonary exercise testing with ventilatory gas analysis. Secondary outcome is self-assessed mental health measured by the standardised questionnaire Short Form 36. Also, long-term healthcare utilisation and mortality as well as biochemistry, echocardiography and cost-benefit will be assessed. A mixed-method design is used to evaluate qualitative and quantitative findings encompassing a survey-based study before the trial and a qualitative pre- and post-intervention study. Discussion The study is approved by the local regional Research Ethics Committee (H-1-2011-157), and the Danish Data Protection Agency (j.nr. 2007-58-0015).

Psychological interventions for acute pain after open heart surgery (Protocol)

The objectives are as follows: To assess the efficacy of psychological interventions as an adjunct to standard surgical care compared to standard surgical care or attention control in adults undergoing open heart surgery.

Validity of an automatic measure protocol in distal femur for allograft selection from a three-dimensional virtual bone bank system

Osteoarticular allograft is one possible treatment in wide surgical resections with large defects. Performing best osteoarticular allograft selection is of great relevance for optimal exploitation of the bone databank, good surgery outcome and patient’s recovery. Current approaches are, however, very time consuming hindering these points in practice. We present a validation study of a software able to perform automatic bone measurements used to automatically assess the distal femur sizes across a databank. 170 distal femur surfaces were reconstructed from CT data and measured manually using a size measure protocol taking into account the transepicondyler distance (A), anterior-posterior distance in medial condyle (B) and anterior-posterior distance in lateral condyle (C). Intra- and inter-observer studies were conducted and regarded as ground truth measurements. Manual and automatic measures were compared. For the automatic measurements, the correlation coefficients between observer one and automatic method, were of 0.99 for A measure and 0.96 for B and C measures. The average time needed to perform the measurements was of 16 h for both manual measurements, and of 3 min for the automatic method. Results demonstrate the high reliability and, most importantly, high repeatability of the proposed approach, and considerable speed-up on the planning.

Double-blinded, randomized controlled trial comparing real versus placebo acupuncture to improve tolerance of diagnostic esophagogastroduodenoscopy without sedation: a study protocol

Background Sedation prior to performance of diagnostic esophagogastroduodenoscopy (EGDE) is widespread and increases patient comfort. But 98% of all serious adverse events during EGDEs are ascribed to sedation. The S3 guideline for sedation procedures in gastrointestinal endoscopy published in 2008 in Germany increases patient safety by standardization. These new regulations increase costs because of the need for more personnel and a prolonged discharge procedure after examinations with sedation. Many patients have difficulties to meet the discharge criteria regulated by the S3 guideline, e.g. the call for a second person to escort them home, to resign from driving and working for the rest of the day, resulting in a refusal of sedation. Therefore, we would like to examine if an acupuncture during elective, diagnostic EGDEs could increase the comfort of patients refusing systemic sedation. Methods/Design A single-center, double blinded, placebo controlled superiority trial to compare the success rates of elective, diagnostic EGDEs with real and placebo acupuncture. All patients aged 18 years or older scheduled for elective, diagnostic EGDE who refuse a systemic sedation are eligible. 354 patients will be randomized. The primary endpoint is the rate of successful EGDEs with the randomized technique. Intervention: Real or placebo acupuncture before and during EGDE. Duration of study: Approximately 24 months. Discussion Organisation/Responsibility The ACUPEND - Trial will be conducted in accordance with the protocol and in compliance with the moral, ethical, and scientific principles governing clinical research as set out in the Declaration of Helsinki (1989) and Good Clinical Practice (GCP). The Interdisciplinary Endoscopy Center (IEZ) of the University Hospital Heidelberg is responsible for design and conduct of the trial, including randomization and documentation of patients' data. Data management and statistical analysis will be performed by the independent Institute for Medical Biometry and Informatics (IMBI) and the Center of Clinical Trials (KSC) at the Department of General, Visceral and Transplantation Surgery, University of Heidelberg.

Evaluation of the isoflurane-sparing effects of lidocaine infusion during umbilical surgery in calves

OBJECTIVE: To evaluate the isoflurane-sparing effects of lidocaine administered by constant rate infusion (CRI) during umbilical surgery in calves. STUDY DESIGN: Randomized 'blinded' prospective clinical study. ANIMALS: Thirty calves (mean 4.7 +/- SD 2.5 weeks old) undergoing umbilical surgery. METHODS: After premedication with xylazine (0.1 mg kg(-1) , IM), anaesthesia was induced with ketamine (4 mg kg(-1) , IV) and maintained with isoflurane in O(2) administered through a circle breathing system. The calves were assigned randomly to receive a bolus of 2 mg kg(-1) lidocaine IV after induction of anaesthesia, followed by CRI of 50 mug kg(-1) minute(-1) (group L, n=15) or a bolus and CRI of 0.9% sodium chloride (NaCl, group S, n=15). End-tidal isoflurane was adjusted to achieve adequate depth of anaesthesia. Heart rate, direct arterial blood pressure and body temperature were measured intraoperatively. Groups were compared by t- tests, anova or Mann-Whitney rank sum test as appropriate. RESULTS: The end-tidal concentration of isoflurane (median, IQR) was significantly lower in group L [1.0% (0.94-1.1)] compared to group S [1.2% (1.1-1.5)], indicating a 16.7% reduction in anaesthetic requirement during lidocaine CRI. Cardiopulmonary parameters and recovery times did not differ significantly between groups. CONCLUSION AND CLINICAL RELEVANCE: Lidocaine CRI may be used as a supplement to inhalation anaesthesia during umbilical surgery in calves in countries where such a protocol would be within the legal requirements for veterinary use in food animals. This study did not show any measurable benefit to the calves other than a reduction in isoflurane requirement.

Closed-loop control of mean arterial blood pressure during surgery with alfentanil: clinical evaluation of a novel model-based predictive controller

BACKGROUND: In contrast to hypnosis, there is no surrogate parameter for analgesia in anesthetized patients. Opioids are titrated to suppress blood pressure response to noxious stimulation. The authors evaluated a novel model predictive controller for closed-loop administration of alfentanil using mean arterial blood pressure and predicted plasma alfentanil concentration (Cp Alf) as input parameters. METHODS: The authors studied 13 healthy patients scheduled to undergo minor lumbar and cervical spine surgery. After induction with propofol, alfentanil, and mivacurium and tracheal intubation, isoflurane was titrated to maintain the Bispectral Index at 55 (+/- 5), and the alfentanil administration was switched from manual to closed-loop control. The controller adjusted the alfentanil infusion rate to maintain the mean arterial blood pressure near the set-point (70 mmHg) while minimizing the Cp Alf toward the set-point plasma alfentanil concentration (Cp Alfref) (100 ng/ml). RESULTS: Two patients were excluded because of loss of arterial pressure signal and protocol violation. The alfentanil infusion was closed-loop controlled for a mean (SD) of 98.9 (1.5)% of presurgery time and 95.5 (4.3)% of surgery time. The mean (SD) end-tidal isoflurane concentrations were 0.78 (0.1) and 0.86 (0.1) vol%, the Cp Alf values were 122 (35) and 181 (58) ng/ml, and the Bispectral Index values were 51 (9) and 52 (4) before surgery and during surgery, respectively. The mean (SD) absolute deviations of mean arterial blood pressure were 7.6 (2.6) and 10.0 (4.2) mmHg (P = 0.262), and the median performance error, median absolute performance error, and wobble were 4.2 (6.2) and 8.8 (9.4)% (P = 0.002), 7.9 (3.8) and 11.8 (6.3)% (P = 0.129), and 14.5 (8.4) and 5.7 (1.2)% (P = 0.002) before surgery and during surgery, respectively. A post hoc simulation showed that the Cp Alfref decreased the predicted Cp Alf compared with mean arterial blood pressure alone. CONCLUSION: The authors' controller has a similar set-point precision as previous hypnotic controllers and provides adequate alfentanil dosing during surgery. It may help to standardize opioid dosing in research and may be a further step toward a multiple input-multiple output controller.

Adequacy of an early arterial phase low-volume contrast protocol in 64-detector computed tomography angiography for aortoiliac aneurysms

PURPOSE: This retrospective study was conducted to determine whether a low-volume contrast medium protocol provides sufficient enhancement for 64-detector computed tomography angiography (CTA) in patients with aortoiliac aneurysms. METHODS: Evaluated were 45 consecutive patients (6 women; mean age, 72 +/- 6 years) who were referred for aortoiliac computed tomography angiography between October 2005 and January 2007. Group A (22 patients; creatinine clearance, 64.2 +/- 8.1 mL/min) received 50 mL of the contrast agent. Group B (23 patients; creatinine clearance, 89.4 +/- 7.3 mL/min) received 100 mL of the contrast agent. The injection rate was 3.5 mL/s, followed by 30 mL of saline at 3.5 mL/s. Studies were performed on the same 64-detector computed tomography scanner using a real-time bolus-tracking technique. Quantitative analysis was performed by determination of mean vascular attenuation at 10 regions of interest from the suprarenal aorta to the common femoral artery by one reader blinded to type and amount of contrast agent and compared using the Student t test. Image quality according to a 4-point scale was assessed in consensus by two readers blinded to type and amount of contrast medium and compared using the Mann-Whitney test. Multivariable adjustments were performed using ordinal regression analysis. RESULTS: Mean total attenuation did not differ significantly between both groups (196.5 +/- 33.0 Hounsfield unit [HU] in group A and 203.1 +/- 44.2 HU in group B; P = .57 by univariate and P > .05 by multivariable analysis). Accordingly, attenuation at each region of interest was not significantly different (P > .35). Image quality was excellent or good in all patients. No significant differences in visual assessment were found comparing both contrast medium protocols (P > .05 by univariate and by multivariable analysis). CONCLUSIONS: Aortoiliac aneurysm imaging can be performed with substantially reduced amounts of contrast medium using 64-detector computed tomography angiography technology.

Drug-eluting or bare-metal stents for large coronary vessel stenting? The BASKET-PROVE (PROspective Validation Examination) trial: study protocol and design

BACKGROUND: Based on a subgroup analysis of 18-month BAsel Stent Kosten Effektivitäts Trial (BASKET) outcome data, we hypothesized that very late (> 12 months) stent thrombosis occurs predominantly after drug-eluting stent implantation in large native coronary vessel stenting. METHODS: To prove or refute this hypothesis, we set up an 11-center 4-country prospective trial of 2260 consecutive patients treated with > or = 3.0-mm stents only, randomized to receive Cypher (Johnson ; Johnson, Miami Lakes, FL), Vision (Abbott Vascular, Abbott Laboratories, IL), or Xience stents (Abbott Vascular). Only patients with left main or bypass graft disease, in-stent restenosis or stent thrombosis, in need of nonheart surgery, at increased bleeding risk, without compliance/consent are excluded. All patients are treated with dual antiplatelet therapy for 12 months. The primary end point will be cardiac death/nonfatal myocardial infarction after 24 months with further follow-up up to 5 years. RESULTS: By June 12, 229 patients (10% of the planned total) were included with a baseline risk similar to that of the same subgroup of BASKET (n = 588). CONCLUSIONS: This study will answer several important questions of contemporary stent use in patients with large native vessel stenting. The 2-year death/myocardial infarction-as well as target vessel revascularization-and bleeding rates in these patients with a first- versus second-generation drug-eluting stent should demonstrate the benefit or harm of these stents compared to cobalt-chromium bare-metal stents in this relevant, low-risk group of everyday patients. In addition, a comparison with similar BASKET patients will allow to estimate the impact of 12- versus 6-month dual antiplatelet therapy on these outcomes.

Differences across health care systems in outcome and cost-utility of surgical and conservative treatment of chronic low back pain: a study protocol

BACKGROUND: There is little evidence on differences across health care systems in choice and outcome of the treatment of chronic low back pain (CLBP) with spinal surgery and conservative treatment as the main options. At least six randomised controlled trials comparing these two options have been performed; they show conflicting results without clear-cut evidence for superior effectiveness of any of the evaluated interventions and could not address whether treatment effect varied across patient subgroups. Cost-utility analyses display inconsistent results when comparing surgical and conservative treatment of CLBP. Due to its higher feasibility, we chose to conduct a prospective observational cohort study. METHODS: This study aims to examine if1. Differences across health care systems result in different treatment outcomes of surgical and conservative treatment of CLBP2. Patient characteristics (work-related, psychological factors, etc.) and co-interventions (physiotherapy, cognitive behavioural therapy, return-to-work programs, etc.) modify the outcome of treatment for CLBP3. Cost-utility in terms of quality-adjusted life years differs between surgical and conservative treatment of CLBP.This study will recruit 1000 patients from orthopaedic spine units, rehabilitation centres, and pain clinics in Switzerland and New Zealand. Effectiveness will be measured by the Oswestry Disability Index (ODI) at baseline and after six months. The change in ODI will be the primary endpoint of this study.Multiple linear regression models will be used, with the change in ODI from baseline to six months as the dependent variable and the type of health care system, type of treatment, patient characteristics, and co-interventions as independent variables. Interactions will be incorporated between type of treatment and different co-interventions and patient characteristics. Cost-utility will be measured with an index based on EQol-5D in combination with cost data. CONCLUSION: This study will provide evidence if differences across health care systems in the outcome of treatment of CLBP exist. It will classify patients with CLBP into different clinical subgroups and help to identify specific target groups who might benefit from specific surgical or conservative interventions. Furthermore, cost-utility differences will be identified for different groups of patients with CLBP. Main results of this study should be replicated in future studies on CLBP.

A standardized protocol for the prevention of clinically relevant venous air embolism during neurosurgical interventions in the semisitting position

OBJECTIVE: We report the results and complications associated with standardized intraoperative management designed for the prevention of hemodynamically relevant venous air embolism during surgery performed in the semisitting position. METHODS: A protocol for preoperative evaluation and intraoperative monitoring was developed and applied in 187 consecutive patients who underwent surgery in the semisitting position between 1999 and 2004. The protocol included preoperative transesophageal echocardiography examination (TEE), intraoperative TEE monitoring, catheterization of the right atrium and a combination of fluid input, positive end expiratory pressure, and standardized positioning aiming at a positive pressure in the transverse and sigmoid sinuses. Data were collected retrospectively from the charts and intraoperative anesthesiological protocols of the patients for the incidence of clinically relevant air embolism (i.e., TEE-diagnosed air embolism plus a decrease in end tidal CO2 or hemodynamic changes) and other complications related to the semisitting position. RESULTS: Three cases (1.6%) of relevant venous air embolism occurred in 187 patients. Only 1 case (0.5%) was hemodynamically relevant, with temporary arterial blood pressure decrease and heart rate increase. Pneumatocephalus leading to lethargy was a frequent postoperative finding, which resolved spontaneously in all except 1 patient with epileptic seizure and oculomotor nerve palsy attributable to space-occupying subdurally trapped air, which had to be treated surgically. There was no permanent morbidity or mortality related to the semisitting position. CONCLUSION: Fear of massive venous air embolism is one reason for dramatic decline in the use of the semisitting position in neurosurgical practice. We found that strict adherence to a standardized protocol using TEE monitoring before and during surgery; exclusion of patients with patent foramen ovale; and a combination of positive end expiratory pressure, fluid input, and a standardized position aiming a positive pressure in the transverse and sigmoid sinuses helped to greatly minimize this complication to a rate of 0.5% for hemodynamically relevant events.

Early re-do surgery for glioblastoma is a feasible and safe strategy to achieve complete resection of enhancing tumor.

BACKGROUND Complete resection of enhancing tumor as assessed by early (<72 hours) postoperative MRI is regarded as the optimal result in glioblastoma surgery. As yet, there is no consensus on standard procedure if post-operative imaging reveals unintended tumor remnants. OBJECTIVE The current study evaluated the feasibility and safety of an early re-do surgery aimed at completing resections with the aid of 5-ALA fluorescence and neuronavigation after detection of enhancing tumor remnants on post-operative MRI. METHODS From October 2008 to October 2012 a single center institutional protocol offered a second surgery within one week to patients with unintentional incomplete glioblastoma resection. We report on the feasibility of the use 5-ALA fluorescence guidance, the extent of resection (EOR) rates and complications of early re-do surgery. RESULTS Nine of 151 patients (6%) with glioblastoma resections had an unintentional tumor remnant with a volume >0.175 cm(3). 5-ALA guided re-do surgery completed the resection (CRET) in all patients without causing neurological deficits, infections or other complications. Patients who underwent a re-do surgery remained hospitalized between surgeries, resulting in a mean length of hospital stay of 11 days (range 7-15), compared to 9 days for single surgery (range 3-23; p=0.147). CONCLUSION Our early re-do protocol led to complete resection of all enhancing tumor in all cases without any new neurological deficits and thus provides a similar oncological result as intraoperative MRI (iMRI). The repeated use of 5-ALA induced fluorescence, used for identification of small remnants, remains highly sensitive and specific in the setting of re-do surgery. Early re-do surgery is a feasible and safe strategy to complete unintended subtotal resections.

Myocardial Infarction - Stress PRevention INTervention (MI-SPRINT) to reduce the incidence of posttraumatic stress after acute myocardial infarction through trauma-focused psychological counseling: study protocol for a randomized controlled trial

BACKGROUND Posttraumatic Stress Disorder (PTSD) may occur in patients after exposure to a life-threatening illness. About one out of six patients develop clinically relevant levels of PTSD symptoms after acute myocardial infarction (MI). Symptoms of PTSD are associated with impaired quality of life and increase the risk of recurrent cardiovascular events. The main hypothesis of the MI-SPRINT study is that trauma-focused psychological counseling is more effective than non-trauma focused counseling in preventing posttraumatic stress after acute MI. METHODS/DESIGN The study is a single-center, randomized controlled psychological trial with two active intervention arms. The sample consists of 426 patients aged 18 years or older who are at 'high risk' to develop clinically relevant posttraumatic stress symptoms. 'High risk' patients are identified with three single-item questions with a numeric rating scale (0 to 10) asking about 'pain during MI', 'fear of dying until admission' and/or 'worrying and feeling helpless when being told about having MI'. Exclusion criteria are emergency heart surgery, severe comorbidities, current severe depression, disorientation, cognitive impairment and suicidal ideation. Patients will be randomly allocated to a single 45-minute counseling session targeting either specific MI-triggered traumatic reactions (that is, the verum intervention) or the general role of psychosocial stress in coronary heart disease (that is, the control intervention). The session will take place in the coronary care unit within 48 hours, by the bedside, after patients have reached stable circulatory conditions. Each patient will additionally receive an illustrated information booklet as study material. Sociodemographic factors, psychosocial and medical data, and cardiometabolic risk factors will be assessed during hospitalization. The primary outcome is the interviewer-rated posttraumatic stress level at three-month follow-up, which is hypothesized to be at least 20% lower in the verum group than in the control group using the t-test. Secondary outcomes are posttraumatic stress levels at 12-month follow-up, and psychosocial functioning and cardiometabolic risk factors at both follow-up assessments. DISCUSSION If the verum intervention proves to be effective, the study will be the first to show that a brief trauma-focused psychological intervention delivered within a somatic health care setting can reduce the incidence of posttraumatic stress in acute MI patients. TRIAL REGISTRATION ClinicalTrials.gov: NCT01781247.

Evaluating the optimal timing of surgical antimicrobial prophylaxis: study protocol for a randomized controlled trial

BACKGROUND Surgical site infections are the most common hospital-acquired infections among surgical patients. The administration of surgical antimicrobial prophylaxis reduces the risk of surgical site infections . The optimal timing of this procedure is still a matter of debate. While most studies suggest that it should be given as close to the incision time as possible, others conclude that this may be too late for optimal prevention of surgical site infections. A large observational study suggests that surgical antimicrobial prophylaxis should be administered 74 to 30 minutes before surgery. The aim of this article is to report the design and protocol of a randomized controlled trial investigating the optimal timing of surgical antimicrobial prophylaxis.Methods/design: In this bi-center randomized controlled trial conducted at two tertiary referral centers in Switzerland, we plan to include 5,000 patients undergoing general, oncologic, vascular and orthopedic trauma procedures. Patients are randomized in a 1:1 ratio into two groups: one receiving surgical antimicrobial prophylaxis in the anesthesia room (75 to 30 minutes before incision) and the other receiving surgical antimicrobial prophylaxis in the operating room (less than 30 minutes before incision). We expect a significantly lower rate of surgical site infections with surgical antimicrobial prophylaxis administered more than 30 minutes before the scheduled incision. The primary outcome is the occurrence of surgical site infections during a 30-day follow-up period (one year with an implant in place). When assuming a 5 surgical site infection risk with administration of surgical antimicrobial prophylaxis in the operating room, the planned sample size has an 80% power to detect a relative risk reduction for surgical site infections of 33% when administering surgical antimicrobial prophylaxis in the anesthesia room (with a two-sided type I error of 5%). We expect the study to be completed within three years. DISCUSSION The results of this randomized controlled trial will have an important impact on current international guidelines for infection control strategies in the hospital. Moreover, the results of this randomized controlled trial are of significant interest for patient safety and healthcare economics.Trial registration: This trial is registered on ClinicalTrials.gov under the identifier NCT01790529.

Acupuncture for post anaesthetic recovery and postoperative pain: study protocol for a randomised controlled trial.

BACKGROUND We report on the design and implementation of a study protocol entitled Acupuncture randomised trial for post anaesthetic recovery and postoperative pain - a pilot study (ACUARP) designed to investigate the effectiveness of acupuncture therapy performed in the perioperative period on post anaesthetic recovery and postoperative pain. METHODS/DESIGN The study is designed as a randomised controlled pilot trial with three arms and partial double blinding. We will compare (a) press needle acupuncture, (b) no treatment and (c) press plaster acupressure in a standardised anaesthetic setting. Seventy-five patients scheduled for laparoscopic surgery to the uterus or ovaries will be allocated randomly to one of the three trial arms. The total observation period will begin one day before surgery and end on the second postoperative day. Twelve press needles and press plasters are to be administered preoperatively at seven acupuncture points. The primary outcome measure will be time from extubation to 'ready for discharge' from the post anaesthesia care unit (in minutes). The 'ready for discharge' end point will be assessed using three different scores: the Aldrete score, the Post Anaesthetic Discharge Scoring System and an In-House score. Secondary outcome measures will comprise pre-, intra- and postoperative variables (which are anxiety, pain, nausea and vomiting, concomitant medication). DISCUSSION The results of this study will provide information on whether acupuncture may improve patient post anaesthetic recovery. Comparing acupuncture with acupressure will provide insight into potential therapeutic differences between invasive and non-invasive acupuncture techniques. TRIAL REGISTRATION NCT01816386 (First received: 28 October 2012).