A new technique for simultaneous validation of two manual nonmercury auscultatory sphygmomanometers (A;D UM-101 and Accoson Greenlight 300) based on the International protocol

Auscultatory nonmercury manual devices seem good alternatives for the mercury sphygmomanometers in the clinic and for research settings, but individual internal validation of each device is time-consuming. The aim of this study was to validate a new technique capable of testing two devices simultaneously, based on the International protocol of the European Society of Hypertension.

A systematic review of medical interventions for oral submucous fibrosis and future research opportunities

Oral Diseases (2011) 17 (Suppl. 1), 42-57 Oral submucous fibrosis (OSF) is a chronic, insidious disease caused by areca nut use, and is associated with both significant morbidity (including pain and reduced oral opening) and an increased risk for malignancy. This systematic review explored and updated the current medical (i.e., non-surgical) interventions available for the management of OSF. Of the 27 published medical interventions, there were four randomized controlled trials. The overall quality of these randomized controlled studies was assessed using the GRADE approach and significant limitations that challenged the conclusions were found. However, this review was valuable in terms of identifying opportunities to provide recommendations for future research, in terms of the populations to research, the types of interventions needed, the types of outcomes to be measured, the study designs needed, and the infrastructure required to conduct studies. The next step is to initiate a pathway for a low-cost research plan leading to the development of a brief protocol for future clinical trials in this field, with an emphasis on conducting studies in regions of the world where OSF is prevalent.

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.

Protocol for a population-based study of rheumatic heart disease prevalence and cardiovascular outcomes among schoolchildren in Nepal

Rheumatic heart disease (RHD) remains a major contributor to morbidity and mortality in developing countries. The reported prevalence rates of RHD are highly variable and mainly attributable to differences in the sensitivity of either clinical screening to detect advanced heart disease or echocardiographic evaluation where disease is diagnosed earlier across a continuous spectrum. The clinical significance of diagnosis of subclinical RHD by echocardiographic screening and early implementation of secondary prevention has not been clearly established. METHODS AND ANALYSIS: The authors designed a cross-sectional survey to determine the prevalence of RHD in children from private and public schools between the age of 5 and 15 years in urban and rural areas of Eastern Nepal using both cardiac auscultation and echocardiographic evaluation. Children with RHD will be treated with secondary prevention and enrolled in a prospective cohort study. The authors will compare the prevalence rates by cardiac auscultation and echocardiography, determine risk factors associated with diagnosis and progression of RHD, investigate social and economic barriers for receiving adequate cardiac care and assess clinical outcomes with regular medical surveillance as a function of stage of disease at the time of diagnosis. Prospective clinical studies investigating the impact of secondary prevention for subclinical RHD on long-term clinical outcome will be of central relevance for future health resource utilisation in developing countries. ETHICS AND DISSEMINATION: The study was considered ethically uncritical and was given an exempt status by the ethics committee at University of Bern, Switzerland. The study has been submitted to the National Nepal Health Research Council and was registered with http://www.ClinicalTrials.gov (NCT01550068). The study findings will be reported in peer-reviewed publications. CLINICALTRIALS.GOV IDENTIFIER: NCT01550068.

Pancuronium dose refinement in experimental pigs used in cardiovascular research

To quantify the dose of pancuronium required to obtain moderate neuromuscular blockade as monitored by acceleromyography (NMB(mod) : train-of-four count of ≤2) as a part of a balanced anaesthetic protocol in pigs used in cardiovascular research.

Radiation metabolomics. 3. Biomarker discovery in the urine of gamma-irradiated rats using a simplified metabolomics protocol of gas chromatography-mass spectrometry combined with random forests machine learning algorithm

Abstract Radiation metabolomics employing mass spectral technologies represents a plausible means of high-throughput minimally invasive radiation biodosimetry. A simplified metabolomics protocol is described that employs ubiquitous gas chromatography-mass spectrometry and open source software including random forests machine learning algorithm to uncover latent biomarkers of 3 Gy gamma radiation in rats. Urine was collected from six male Wistar rats and six sham-irradiated controls for 7 days, 4 prior to irradiation and 3 after irradiation. Water and food consumption, urine volume, body weight, and sodium, potassium, calcium, chloride, phosphate and urea excretion showed major effects from exposure to gamma radiation. The metabolomics protocol uncovered several urinary metabolites that were significantly up-regulated (glyoxylate, threonate, thymine, uracil, p-cresol) and down-regulated (citrate, 2-oxoglutarate, adipate, pimelate, suberate, azelaate) as a result of radiation exposure. Thymine and uracil were shown to derive largely from thymidine and 2'-deoxyuridine, which are known radiation biomarkers in the mouse. The radiation metabolomic phenotype in rats appeared to derive from oxidative stress and effects on kidney function. Gas chromatography-mass spectrometry is a promising platform on which to develop the field of radiation metabolomics further and to assist in the design of instrumentation for use in detecting biological consequences of environmental radiation release.

Effect of ascent protocol on acute mountain sickness and success at Muztagh Ata, 7546 m

Bloch, Konrad E., Alexander J. Turk, Marco Maggiorini, Thomas Hess, Tobias Merz, Martina M. Bosch, Daniel Barthelmes, Urs Hefti, Jacqueline Pichler, Oliver Senn, and Otto D. Schoch. Effect of ascent protocol on acute mountain sickness and success at Muztagh Ata, 7546 m. High Alt. Med. Biol. 10:25-32, 2009.-Data on acclimatization during expedition-style climbing to > 5000 m are scant. We evaluated the hypothesis that minor differences in ascent protocol influence acute mountain sickness (AMS) symptoms and mountaineering success in climbers to Muztagh Ata (7546 m), Western China. We performed a randomized, controlled trial during a high altitude medical research expedition to Muztagh Ata. Thirty-four healthy mountaineers (mean age 45 yr, 7 women) were randomized to follow one of two protocols, ascending within 15 or 19 days to the summit of Muztagh Ata at 7546 m, respectively. The main outcome measures, AMS symptom scores and the number of proceeding climbers, were assessed daily. Mean +/- SD AMS-C scores of 16 climbers randomized to slow ascent were 0.06 +/- 0.18, 0.26 +/- 0.08, 0.41 +/- 0.45, 0.53 +/- 0.77 at camps I (5533 m), II (6265 m), III (6865 m), and the summit (7546 m), respectively. Corresponding values in 18 climbers randomized to fast ascent were significantly higher: 0.17 +/- 0.23, 0.43 +/- 0.75, 0.49 +/- 0.36, and 0.69 +/- 0.54 (p < 0.008, vs. slow ascent in regression analysis accounting for weather-related protocol deviation). Climbers randomized to slow ascent were able to ascend according to the protocol without AMS for significantly more days than climbers randomized to fast ascent (p = 0.04, Kaplan-Meier analysis). More climbers randomized to slow ascent were successful in reaching the highest camp at 6865 m without AMS (odds ratio 9.5; 95% confidence interval 1.02 to 89). In climbers ascending to very high altitudes, differences of a few days in acclimatization have a significant impact on symptom severity, the prevalence of AMS, and mountaineering success. ClinicalTrials.gov Identifier NCT00603122.

Conception Rate Using the Select-Synch Protocol in Combination with a Lower Dose Progesterone-Releasing Intravaginal Insert (1.38 g) in Swiss Dairy Cows

Background: Synchronization programs have become standard in the dairy industry. In Switzerland, these programs are used but newly. The objective of this study was A) to estimate the pregnancy rate after a Select-Synch protocol in- cluding a low dosage of progesterone in CIDR (1.38 g). As a second step B) this pregnancy rate should be compared to cows from another Swiss study that used a Select-Synch protocol with the 1.9 g insert (Rudolph et al., 2011). Methods: A) 196 cows were included in the study. Cows received a CIDR 1.38 g and 2.5 ml of buserelin i.m. on d 0. On d 7, the CIDR insert was removed and 5 ml of dinoprost was administered i.m. On d 0 a milk sample for progesterone analysis was taken. Pregnancy was determined at or more than 35 days after artificial insemination. B) The 1.38 g group and the 1.9 g group were compared as to cow and farm factors, number of preceding AI’s, gynecological and uterine pretreat- ment and treatment itself. A forward selection procedure was used (test result considered significant if p-value  0.05). Results: A) The pregnancy rate, using the Select-Synch protocol with the CIDR 1.38 g was 44.4%. B) The CIDR 1.9 g Select-Synch group revealed a pregnancy rate of 50.4% (Rudolph et al., 2011). Significant differences between the groups were not found. Conclusion: The 1.38 g CIDR-Select-Synch protocol may be recommended for multiparous dairy cows. The pregnancy rate compared to the 1.9 g CIDR-Select-Synch protocol was 8% lower, but this difference was not significant.

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).

A new methodological protocol for the use of dendrogeomorphological data in flood risk analysis

Dendrogeomorphology uses information sources recorded in the roots, trunks and branches of trees and bushes located in the fluvial system to complement (or sometimes even replace) systematic and palaeohydrological records of past floods. The application of dendrogeomorphic data sources and methods to palaeoflood analysis over nearly 40 years has allowed improvements to be made in frequency and magnitude estimations of past floods. Nevertheless, research carried out so far has shown that the dendrogeomorphic indicators traditionally used (mainly scar evidence), and their use to infer frequency and magnitude, have been restricted to a small, limited set of applications. New possibilities with enormous potential remain unexplored. New insights in future research of palaeoflood frequency and magnitude using dendrogeomorphic data sources should: (1) test the application of isotopic indicators (16O/18O ratio) to discover the meteorological origin of past floods; (2) use different dendrogeomorphic indicators to estimate peak flows with 2D (and 3D) hydraulic models and study how they relate to other palaeostage indicators; (3) investigate improved calibration of 2D hydraulic model parameters (roughness); and (4) apply statistics-based cost–benefit analysis to select optimal mitigation measures. This paper presents an overview of these innovative methodologies, with a focus on their capabilities and limitations in the reconstruction of recent floods and palaeofloods.

Efficacy of a dilemma-focused intervention for unipolar depression: study protocol for a multicenter randomized controlled trial

BACKGROUND: Depression is one of the more severe and serious health problems because of its morbidity, disabling effects and for its societal and economic burden. Despite the variety of existing pharmacological and psychological treatments, most of the cases evolve with only partial remission, relapse and recurrence.Cognitive models have contributed significantly to the understanding of unipolar depression and its psychological treatment. However, success is only partial and many authors affirm the need to improve those models and also the treatment programs derived from them. One of the issues that requires further elaboration is the difficulty these patients experience in responding to treatment and in maintaining therapeutic gains across time without relapse or recurrence. Our research group has been working on the notion of cognitive conflict viewed as personal dilemmas according to personal construct theory. We use a novel method for identifying those conflicts using the repertory grid technique (RGT). Preliminary results with depressive patients show that about 90% of them have one or more of those conflicts. This fact might explain the blockage and the difficult progress of these patients, especially the more severe and/or chronic. These results justify the need for specific interventions focused on the resolution of these internal conflicts. This study aims to empirically test the hypothesis that an intervention focused on the dilemma(s) specifically detected for each patient will enhance the efficacy of cognitive behavioral therapy (CBT) for depression. DESIGN: A therapy manual for a dilemma-focused intervention will be tested using a randomized clinical trial by comparing the outcome of two treatment conditions: combined group CBT (eight, 2-hour weekly sessions) plus individual dilemma-focused therapy (eight, 1-hour weekly sessions) and CBT alone (eight, 2-hour group weekly sessions plus eight, 1-hour individual weekly sessions). METHOD: Participants are patients aged over 18 years meeting diagnostic criteria for major depressive disorder or dysthymic disorder, with a score of 19 or above on the Beck depression inventory, second edition (BDI-II) and presenting at least one cognitive conflict (implicative dilemma or dilemmatic construct) as assessed using the RGT. The BDI-II is the primary outcome measure, collected at baseline, at the end of therapy, and at 3- and 12-month follow-up; other secondary measures are also used. DISCUSSION: We expect that adding a dilemma-focused intervention to CBT will increase the efficacy of one of the more prestigious therapies for depression, thus resulting in a significant contribution to the psychological treatment of depression. TRIAL REGISTRATION: ISRCTN92443999; ClinicalTrials.gov Identifier: NCT01542957.

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.