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).

Effect of standardized training on the reliability of the Cochrane risk of bias assessment tool: a study protocol

BACKGROUND The Cochrane risk of bias (RoB) tool has been widely embraced by the systematic review community, but several studies have reported that its reliability is low. We aim to investigate whether training of raters, including objective and standardized instructions on how to assess risk of bias, can improve the reliability of this tool. We describe the methods that will be used in this investigation and present an intensive standardized training package for risk of bias assessment that could be used by contributors to the Cochrane Collaboration and other reviewers. METHODS/DESIGN This is a pilot study. We will first perform a systematic literature review to identify randomized clinical trials (RCTs) that will be used for risk of bias assessment. Using the identified RCTs, we will then do a randomized experiment, where raters will be allocated to two different training schemes: minimal training and intensive standardized training. We will calculate the chance-corrected weighted Kappa with 95% confidence intervals to quantify within- and between-group Kappa agreement for each of the domains of the risk of bias tool. To calculate between-group Kappa agreement, we will use risk of bias assessments from pairs of raters after resolution of disagreements. Between-group Kappa agreement will quantify the agreement between the risk of bias assessment of raters in the training groups and the risk of bias assessment of experienced raters. To compare agreement of raters under different training conditions, we will calculate differences between Kappa values with 95% confidence intervals. DISCUSSION This study will investigate whether the reliability of the risk of bias tool can be improved by training raters using standardized instructions for risk of bias assessment. One group of inexperienced raters will receive intensive training on risk of bias assessment and the other will receive minimal training. By including a control group with minimal training, we will attempt to mimic what many review authors commonly have to do, that is-conduct risk of bias assessment in RCTs without much formal training or standardized instructions. If our results indicate that an intense standardized training does improve the reliability of the RoB tool, our study is likely to help improve the quality of risk of bias assessments, which is a central component of evidence synthesis.

Corneal cross-linking in keratoconus using the standard and rapid treatment protocol: differences in demarcation line and 12-month outcomes.

PURPOSE To compare the occurrence rate and depth of the demarcation line and topographical outcome after corneal cross-linking (CXL) for keratoconus using two different treatment protocols. METHODS A retrospective analysis of 131 eyes with progressive keratoconus treated with CXL using riboflavin and UV-A was performed. Eyes were treated either with the standard Dresden protocol (30 minutes irradiation, 3 mW/cm(2), UV-XTM 1000) or a rapid protocol (10 minutes irradiation, 9 mW/cm(2), UV-XTM 2000). The presence and depth of the corneal demarcation line was assessed with an anterior segment optical coherence tomography device 1 month after CXL by a masked observer. Corneal topography and tomography was performed at baseline and at 12-month follow-up with Pentacam and the TMS (Topographic Modeling System) device. RESULTS In the standard protocol group, 76.5% (62/81) of treated corneas revealed a demarcation line 1 month after CXL, whereas such a demarcation line was observed in only 22% (11/50) of eyes treated with the rapid protocol (P < 0.0001). The demarcation line was significantly more superficial in the rapid protocol group (P = 0.004). Corneal topography values between baseline and 12 months after CXL showed a mean change of -0.76 diopters (D) in Kmax (SD ± 2.7) in the standard protocol group versus a mean change of +0.72 D in Kmax (SD ± 1.5) in the rapid protocol (P = 0.007). CONCLUSIONS The rapid CXL protocol negatively influences the occurrence and depth of the demarcation line 1 month after CXL. Our results show a negative effect on the topographical outcome 1 year after CXL.

A next-generation tissue microarray (ngTMA) protocol for biomarker studies

Biomarker research relies on tissue microarrays (TMA). TMAs are produced by repeated transfer of small tissue cores from a 'donor' block into a 'recipient' block and then used for a variety of biomarker applications. The construction of conventional TMAs is labor intensive, imprecise, and time-consuming. Here, a protocol using next-generation Tissue Microarrays (ngTMA) is outlined. ngTMA is based on TMA planning and design, digital pathology, and automated tissue microarraying. The protocol is illustrated using an example of 134 metastatic colorectal cancer patients. Histological, statistical and logistical aspects are considered, such as the tissue type, specific histological regions, and cell types for inclusion in the TMA, the number of tissue spots, sample size, statistical analysis, and number of TMA copies. Histological slides for each patient are scanned and uploaded onto a web-based digital platform. There, they are viewed and annotated (marked) using a 0.6-2.0 mm diameter tool, multiple times using various colors to distinguish tissue areas. Donor blocks and 12 'recipient' blocks are loaded into the instrument. Digital slides are retrieved and matched to donor block images. Repeated arraying of annotated regions is automatically performed resulting in an ngTMA. In this example, six ngTMAs are planned containing six different tissue types/histological zones. Two copies of the ngTMAs are desired. Three to four slides for each patient are scanned; 3 scan runs are necessary and performed overnight. All slides are annotated; different colors are used to represent the different tissues/zones, namely tumor center, invasion front, tumor/stroma, lymph node metastases, liver metastases, and normal tissue. 17 annotations/case are made; time for annotation is 2-3 min/case. 12 ngTMAs are produced containing 4,556 spots. Arraying time is 15-20 hr. Due to its precision, flexibility and speed, ngTMA is a powerful tool to further improve the quality of TMAs used in clinical and translational research.

Venepuncture during head-up tilt testing in patients with suspected vasovagal syncope - implications for the test protocol.

BACKGROUND AND PURPOSE Head-up tilt (HUT) testing is a widely used diagnostic tool in patients with suspected vasovagal syncope (VVS). However, no gold standard exists for this examination and the various protocols used have a limited sensitivity and specificity. Our aim was to determine the sensitivity of a sequential HUT testing protocol including venepuncture (VP) and sublingual nitroglycerin application. METHODS This was a retrospective analysis of the diagnostic gain of a sequential HUT testing protocol including VP applied 10 min after the start of HUT testing and sublingual application of nitroglycerin 20 min after the start of the test protocol in 106 patients with a final diagnosis of VVS. The sensitivity of the test protocol was compared between patients with positive and negative history for VP induced VVS. RESULTS Overall, pre-syncope or syncope occurred in 68 patients (64.2%). Only 17% of all patients fainted spontaneously within 10 min of passive HUT. Another 39.6% fainted within 20 min. Application of nitroglycerin after 20 min of HUT evoked syncope in another 7.5% until the end of 45 min of HUT. The sensitivity of the test protocol for evoking (pre-)syncope was 94.4% in patients with a positive history for VP associated VVS and 58% in patients with a negative history (P < 0.01**); 85.7% of patients with a positive history and 42.9% of patients with a negative history fainted within 20 min of HUT testing (P < 0.01**). CONCLUSIONS Implementation of VP in sequential HUT testing protocols allows the sensitivity of HUT testing to be increased, especially in patients with a positive history for VP associated VVS.