Unblinded Group Research Articles

Continuous Glucose Monitoring Feedback in the Subsequent Development of Gestational Diabetes: A Pilot, Randomized, Controlled Trial in Pregnant Women.

This study evaluated the effects of receiving glucose feedback from continuous glucose monitoring (CGM) by intermittent scanning (unblinded group), and CGM with masked feedback (blinded group) in the subsequent development of gestational diabetes mellitus (GDM). This was a prospective, single-center, pilot, randomized controlled trial including n = 206 pregnant women in the first trimester of pregnancy with no prior diagnosis of type 1 or type 2 diabetes. The participants were randomized into the unblinded group or blinded group and wore the CGM in the first trimester of pregnancy (9-13 weeks), the second trimester of pregnancy (18-23 weeks), and late-second to early-third trimester (24-31 weeks). The primary outcome was GDM rate as diagnosed by the 75-g oral glucose tolerance test (OGTT) at 24 to 28 weeks. Over 47 months, 206 pregnant women were enrolled at 9 to 13 weeks. The unblinded group had a higher prevalence of women who developed GDM (21.5 vs. 14.9%; p > 0.05), compared to the blinded group. In the unblinded group compared to the blinded group, plasma glucose values were higher at 1 hour (median 7.7 [interquartile range {IQR}: 6.3-9.2] vs. 7.5 [6.3-8.7]) and 2 hours (6.3 [5.8-7.7] vs. 6.2 [5.3-7.2]), but lower at 0 hour (4.2 [4.0-4.5] vs. 4.3 [4.1-4.6]; p > 0.05). All these differences were not statistically significant. Glucose feedback from CGM wear in the first to the third trimester of pregnancy without personalized patient education failed to alter GDM rate. · Continuous glucose monitoring (CGM) is feasible for use in pregnant women.. · No significant difference in gestational diabetes rates with or without CGM feedback.. · Future clinical trials should incorporate CGM education and personalized guidance to enhance study outcomes..

Placebo effects of transcranial direct current stimulation on motor skill acquisition

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique used in neurorehabilitation to enhance motor training. However, its benefits to motor training can be difficult to reproduce across research studies. It is possible that the observed benefits of tDCS are not directly related to the intervention itself but rather to the brain-mind responses elicited by the treatment context, commonly known as a placebo effect. This study investigated the presence of a placebo effect of tDCS on motor training and explored potential underlying factors. Sixty-eight participants who were right-handed were randomly assigned to active tDCS, sham tDCS, or a no-stimulation control group. Double-blind active or sham tDCS was applied to the right primary motor cortex, while the unblinded control group received no stimulation. All participants completed 30 training trials of a functional upper-extremity motor task. Participants’ beliefs of tDCS, along with their prior knowledge of tDCS, were also collected. There was no significant difference in the amount of improvement on the motor task between the active and sham tDCS groups; however, both active and sham tDCS groups improved more than the control group, indicating a placebo effect. More motor task improvement was also associated with higher beliefs of tDCS (regardless of whether active or sham tDCS was received). This demonstrates a measurable placebo effect of tDCS on motor training, driven at least in part by treatment expectations or beliefs. Future tDCS studies should control for beliefs and other placebo-related factors.

Double Device Approach for Percutaneous Closure of Postmyocardial Infarction Ventricular Septal Defect

The benefit related to the use of preprocedural computed tomography angiography (CCTA) on top of periprocedural echocardiography to plan percutaneous left atrial appendage closure (LAAC) procedures is still unclear.The authors sought to evaluate the impact of preprocedural CCTA on LAAC procedural success.In the investigator-initiated SWISS-APERO (Comparison of Amplatzer Amulet and Watchman Device in Patients Undergoing Left Atrial Appendage Closure) trial, patients undergoing echocardiography-guided LAAC were randomly assigned to receive the Amulet (Abbott) or Watchman 2.5/FLX (Boston Scientific) device across 8 European centers. According to the study protocol ongoing at the time of the procedure, the first operators had (CCTA unblinded group) or did not have (CCTA blinded group) access to preprocedural CCTA images. In this post hoc analysis, we compared blinded vs unblinded procedures in terms of procedural success defined as complete left atrial appendage occlusion as evaluated at the end of LAAC (short-term) or at the 45-day follow-up (long-term) without procedural-related complications.Among 219 LAACs preceded by CCTA, 92 (42.1%) and 127 (57.9%) were assigned to the CCTA unblinded and blinded group, respectively. After adjusting for confounders, operator unblinding to preprocedural CCTA remained associated with a higher rate of short-term procedural success (93.5% vs 81.1%; P = 0.009; adjusted OR: 2.76; 95% CI: 1.05-7.29; P = 0.040) and long-term procedural success (83.7% vs 72.4%; P = 0.050; adjusted OR: 2.12; 95% CI: 1.03-4.35; P = 0.041).In a prospective multicenter cohort of clinically indicated echocardiography-guided LAACs, unblinding of the first operators to preprocedural CCTA images was independently associated with a higher rate of both short- and long-term procedural success. Further studies are needed to better evaluate the impact of preprocedural CCTA on clinical outcomes.

Impact of Preprocedural Computed Tomography on Left Atrial Appendage Closure Success: A Swiss-Apero Trial Subanalysis

BackgroundThe benefit related to the use of preprocedural computed tomography angiography (CCTA) on top of periprocedural echocardiography to plan percutaneous left atrial appendage closure (LAAC) procedures is still unclear. ObjectivesThe authors sought to evaluate the impact of preprocedural CCTA on LAAC procedural success. MethodsIn the investigator-initiated SWISS-APERO (Comparison of Amplatzer Amulet and Watchman Device in Patients Undergoing Left Atrial Appendage Closure) trial, patients undergoing echocardiography-guided LAAC were randomly assigned to receive the Amulet (Abbott) or Watchman 2.5/FLX (Boston Scientific) device across 8 European centers. According to the study protocol ongoing at the time of the procedure, the first operators had (CCTA unblinded group) or did not have (CCTA blinded group) access to preprocedural CCTA images. In this post hoc analysis, we compared blinded vs unblinded procedures in terms of procedural success defined as complete left atrial appendage occlusion as evaluated at the end of LAAC (short-term) or at the 45-day follow-up (long-term) without procedural-related complications. ResultsAmong 219 LAACs preceded by CCTA, 92 (42.1%) and 127 (57.9%) were assigned to the CCTA unblinded and blinded group, respectively. After adjusting for confounders, operator unblinding to preprocedural CCTA remained associated with a higher rate of short-term procedural success (93.5% vs 81.1%; P = 0.009; adjusted OR: 2.76; 95% CI: 1.05-7.29; P = 0.040) and long-term procedural success (83.7% vs 72.4%; P = 0.050; adjusted OR: 2.12; 95% CI: 1.03-4.35; P = 0.041). ConclusionsIn a prospective multicenter cohort of clinically indicated echocardiography-guided LAACs, unblinding of the first operators to preprocedural CCTA images was independently associated with a higher rate of both short- and long-term procedural success. Further studies are needed to better evaluate the impact of preprocedural CCTA on clinical outcomes.

700-P: Use of Continuous Glucose Monitoring Does Not Alter Hypoglycemic Awareness in Patients with Type 2 Diabetes Mellitus

Background: There is limited evidence of continuous glucose monitoring (CGM) in patients with type 2 diabetes (T2D) . CGM use improves HbA1c and quality of life, however scant evidence exists on the effect of CGM use on hypoglycemia awareness in patients with T2D. Selecting patients with T2D at high risk and low risk for hypoglycemia, we hypothesized that CGM use would improve hypoglycemia awareness. Methods: We conducted a 16 week, single center, randomized study on patients [n=40, 50% females, mean (SD) age 59 years (12.5) , BMI 34.kg/m2 (8.1) ] with T2D [screening HbA1c 7.6% (1.2) ] who were deemed to be either high risk (n=22) or low risk (n=18) for hypoglycemia over 5 years using our previously established scoring system. Each participant wore 2 CGM sensors. Within each risk category, participants were randomized to wearing either 1 unblinded+1 blinded sensor (Freestyle Libre/Freestyle Libre Pro) or 2 blinded sensors (2 Freestyle Libre Pro) . Every 2 weeks was an in-person visit for CGM replacement. Clarke and Gold questionnaires were performed at the screening visit (week 0) , visit 4 (week 8) and visit 8 (week 16) . Participants in the unblinded CGM group were instructed to use the CGM as they wished. Participants in the blinded CGM group were instructed to continue with their usual finger stick program. Result: At baseline, there were no differences in the Gold or Clark questionnaires between participants at high or low risk for hypoglycemia over 5 years. At end-intervention, no differences were noted in the Gold or Clark questionnaires regardless of CGM assignment or baseline hypoglycemia risk category. The trajectory of Gold or Clark scores over the study were also not significantly different between groups regardless of CGM assignment or baseline hypoglycemia risk category. Conclusion: In patients with T2D, the use of an unblinded CGM did not affect the awareness of hypoglycemia, even in patients at high risk for hypoglycemia, as assessed by Gold and Clark scores. Disclosure A.Mehfooz: None. Y.Lee: None. Q.Wang: None. L.S.Chow: Other Relationship; Dexcom, Inc.

Effect of yoga on glycemia and lipid parameters in type-2 diabetes: a meta-analysis.

Prior systematic reviews on yoga and diabetes have given conflicting results. They have been limited by inclusion of uncontrolled unblinded single group observational studies. No reviews are available which have used the Cochrane methodology and GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. This meta-analysis evaluated the efficacy of yoga on glycaemia and lipids in T2DM using the Cochrane methodology and GRADE approach. Major repositories were searched to pick randomized controlled trials involving T2DM patients receiving yoga. Primary outcome was to evaluate changes in fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c). Secondary outcomes were to evaluate changes in post-prandial plasma glucose (PPG), total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Sub-group analysis involving people undergoing structured exercise regimen (SER) versus those undergoing standard diabetes care in controls was done. Data from 13 studies involving 1440 patients were analysed. Compared to controls, individuals doing yoga had significantly lower FPG [mean difference (MD) -17.22mg/dl (95% CI: -26.19 - -8.26mg/dl); p < 0.01; considerable heterogeneity (CH); low certainty of evidence (LCE)], PPG [MD -27.77mg/dl (95% CI: -35.73 - -19.81mg/dl); p < 0.01; low heterogeneity; moderate certainty of evidence (MCE)], TC [MD -19.48mg/dl (95% CI: -31.97 - -6.99mg/dl); p < 0.01; CH; LCE], triglycerides [MD -12.99mg/dl (95% CI: -23.74 - -2.25mg/dl); p < 0.01; CH; LCE], LDL-C [MD -11.71mg/dl (95% CI: -17.49 - -5.93mg/dl); p < 0.01; I2= 69% CH; LCE] and significantly higher HDL-C [MD 4.58mg/dl (95% CI: 3.98-5.18mg/dl); p < 0.01; low heterogeneity; MCE]. On sub-group analysis, where yoga was compared to SER, FPG was significantly lower in yoga group. Yoga improves glycaemia and lipid parameters in T2DM with additional benefits seen both in people doing/not doing structured exercise. The online version contains supplementary material available at 10.1007/s40200-021-00751-0.

Comparison of Right Colon Adenoma Miss Rates Between Water Exchange and Carbon Dioxide Insufflation: A Prospective Randomized Controlled Trial.

To test the hypothesis that water exchange (WE), when compared with carbon dioxide (CO2) insufflation, significantly reduces the right colon adenoma miss rate (rAMR) in a blinded randomized controlled trial with cap-assisted colonoscopy. The unblinded consecutive group observational data showed that WE significantly decreased rAMR. The unblinded data are limited by potential bias. Consecutive patients aged 45 years or more were randomized to undergo insertion with WE or CO2. Withdrawal and polypectomy were performed with CO2 in both groups to the hepatic flexure. The colonoscope was reinserted to the cecum. A second colonoscopist re-examined the right colon. The second colonoscopist was unaware, but made a guess, of the initial insertion method. The number of additional adenomas divided by the total number detected in both examinations equaled rAMR. Among 262 patients (131/group), demographic variables were similar. The body mass index was significantly higher in the WE group. Compared with CO2, WE significantly decreased rAMR [18.0% (33/183) vs. 34.6% (62/179), P=0.0025] and right colon serrated polyp miss rate [17.4% (27/155) vs. 39.3% (33/84), P=0.002]. Multivariate logistic regression analysis showed that WE was an independent predictor of rAMR (odds ratio, 0.42; 95% confidence interval, 0.21-0.86), and so was ≥2 adenomas in the right colon (odds ratio, 2.35; 95% confidence interval, 1.17-4.76). Whether the second colonoscopist guessed the insertion method correctly or not, and demographic and procedure variables were not associated with rAMR. The randomized controlled trial validated unblinded observational data showing that WE significantly decreased rAMR and right colon serrated polyp miss rate (clinical trial registration number: NCT03845933).

How to do clinical trials in the ICU

Site-initiated clinical trials are challenging, particularly with vulnerable populations like ICU patients. But they can be useful if you can answer “Yes” to these questions: (1) Could the answer change practice? (2) Does my ICU see enough of these patients to answer the question? (3) Can I treat both the investigational and control group patients in a fair manner? Other approaches to ICU clinical research, such as joining another multicenter clinical trial and observational (prospective or retrospective) studies whose answers have explanatory power may also be valuable.Regarding changing practice: The trial's answer should be important enough that any intensivist treating such a patient would care about it. Examples of questions that probably aren't important enough are: (1) Is there a difference in ARDS outcome if the tidal volume is 4, 6, or 8 mL/kg?, (2) Is knee-high pneumatic compression inferior to thigh-high pneumatic compression for thromboembolism prophylaxis in anticoagulant-contraindicated patients?, and (3) Do piperacillin-tazobactam and cefepime have equivalent efficacy for empiric coverage of hospital-acquired infections? The first question probably has a patient-specific, non-generalizable answer; the second, with small “dose” differences has high risk of being a negative study; the third answer likely depends on local organisms, and equivalence studies require very large patient numbers.Studies whose answers probably could change practice include: (1) Does adding Extracorporeal CO2 Removal (ECCO2R) to intubated ventilation in combined respiratory and metabolic acidosis improve survival/shorten ventilator time?, and (2) Does extracorporeal CPR (ECPR) for witnessed out-of-hospital cardiac arrest with a shockable rhythm save lives? Regarding the ECCO2R proposal, current practice involves hyperventilating high-dead-space patients, pressors, bicarbonate infusion, maybe dialysis, and outcomes are poor. ECCO2R can reduce ventilatory and alkalinizing/dialysis requirements1. Regarding the ECPR proposal, current survival rates reported after 60 min of CPR without ECPR for possibly salvageable patients are 9%; with ECPR, 22%. Moreover, there are no clinical trials published2.The second criterion is important because if your site doesn't see enough patients, coordination with multiple centers and delay can imperil completion. Estimating sample size early for feasibility is important. For the ECCO2R proposal, an estimate for 30-day survival of such patients is 25%. To double survival to 50%, 2-sided p = 0.05, with 80% power, sample size is 65/group, 130 patients altogether. For the ECPR proposal, an estimate without ECPR is 5% survival after an hour of CPR. To raise survival to 25%, 2-sided p = 0.05, with 80% power, sample size is 58/group, 116 patients. These numbers may be practically achieved in some centers after 2-3 years, when the answers will still be pertinent.The third criterion addresses whether the question is practical: Can a protocol fair to patients be devised and executed? For both ECCO2R and ECPR proposals, the protocols must (1) Establish criteria to assure no prolongation of life just to favor one unblinded group or another, and (2) Establish a process to assure uniform patient entrance and procedures among participating physicians and centers. Careful thought and collegial consultation at the start of study planning is important for helping ICU patients with your clinical research. Preparing the final study report similarly requires close attention and consultation3.

Follow up after sample size re-estimation in a breast cancer randomized trial for disease-free survival

BackgroundWhile the clinical trials and statistical methodology literature on sample size re-estimation (SSRE) is robust, evaluation of SSRE procedures following the completion of a clinical trial has been sparsely reported. In blinded sample size re-estimation, only nuisance parameters are re-estimated, and the blinding of the current trial treatment effect is preserved. Blinded re-estimation procedures are well-accepted by regulatory agencies and funders. We review our experience of sample size re-estimation in a large international, National Institutes of Health funded clinical trial for adjuvant breast cancer treatment, and evaluate our blinded sample size re-estimation procedure for this time-to-event trial. We evaluated the SSRE procedure by examining assumptions made during the re-estimation process, estimates resulting from re-estimation, and the impact on final trial results with and without the addition of participants, following sample size re-estimation.MethodsWe compared the control group failure probabilities estimated at the time of SSRE to estimates used in the original planning, to the final un-blinded control group failure probability estimates for those included in the SSRE procedure (SSRE cohort), and to the final total control group failure probability estimates. The impact of re-estimation on the final comparison between randomized treatment groups is evaluated for those in the originally planned cohort (n = 340) and for the combination of those recruited in the originally planned cohort and those added after re-estimation (n = 509).ResultsVery little difference is observed between the originally planned cohort and all randomized patients in the control group failure probabilities over time or in the overall hazard ratio estimating treatment effect (originally planned cohort HR 1.25 (0.86, 1.79); all randomized cohort HR 1.24 95% CI (0.91, 1.68)). At the time of blinded SSRE, the estimated control group failure probabilities at 3 years (0.24) and 5 years (0.40) were similar to those for the SSRE cohort once un-blinded (3 years, 0.22 (0.16, 0.30); 5 years, 0.33 (0.26, 0.41)).ConclusionsWe found that our re-estimation procedure performed reasonably well in estimating the control group failure probabilities at the time of re-estimation. Particularly for time-to-event outcomes, pre-planned blinded SSRE procedures may be the best option to aid in maintaining power.Trial registrationClinicalTrials.gov, NCT00201851. Registered on 9 September 2005. Retrospectively registered.

Double-blind study of visual imagery in grapheme-color synesthesia

Synesthesia is an atypical perceptual phenomenon that has been associated with generalized differences in other cognitive and perceptual domains. Given similarities in the qualitative nature of synesthetic experiences to visual imagery perceptions, several studies have sought to examine whether synesthetes demonstrate increased visual imagery abilities. Using subjective imagery questionnaires, some studies have identified superior imaging abilities in synesthetes, while others have not. However, because most research on synesthesia uses un-blinded group membership prior to data collection, such methods for studying group differences may be prone to participant and experimenter biases (e.g., a motivated synesthete may rate themselves as having stronger visual imagery abilities due to their own bias and perceived experimenter expectations). To address this issue, we demonstrate the feasibility of double-blind designs in synesthesia research, applied here to examine differences in subjectively reported levels of imagery usage and intensity. Prior to identifying synesthetes' and non-synesthetes' group membership (in order to eliminate the potential for bias), subjects completed two common measures of visual imagery experiences. Using this approach, we replicated findings of greater visual imagery usage in synesthetes on the Spontaneous Use of Imagery Scale (SUIS) measure, but not of enhanced imagery abilities on the standardized Vividness of Visual Imagery Questionnaire (VVIQ) measure. The present study strengthens prior evidence that synesthesia is associated with heightened visual imagery and demonstrates the utility of double-blind designs in order to limit biases and promote further replicability of other findings in research on synesthesia.

A Randomized Controlled Trial Evaluating a Community-Based Diabetes Optimization Program for Patients Awaiting Elective Cardiac Surgery

Background: The diabetes prevalence varies from 7%-20% among Cardiovascular Surgery (CS) patients. The patients with suboptimal glycaemic control are at a higher risk of postoperative morbidity and mortality. Objective: To explore feasibility and effectiveness of preoperative Diabetes Optimization Program (DOP). Design: Unblinded parallel group randomized controlled trial. Methods: Between 2013 to 2015, consecutive, consenting elective CS patients with HbA1C>7% were randomized to Standard of Care (SOC) group or to the DOP group. The DOP is a community-based diabetes education and optimization program. The SOC includes diabetes care from their Primary Care Physician (PCP). Outcome: The primary outcome was DOP feasibility. Secondarily, rate of change in HbA1C between the groups over the study period was evaluated. The DOP feasibility was assessed through the participants’ consent and adherence rate and generalized estimating equation was used for secondary outcomes analyses. Results: Thirty three out of 57 patients consented to participate in the study (consent rate 58%); 19 randomized to SOC group and 14 to the DOP group. The DOP group protocol adherence rate was 71%. There was no difference in the rate of HbA1C change between the groups over time (p=0.994). Conclusion: Providing preoperative diabetes optimization, through intervention such as DOP, for elective CS patients is feasible. Even so, its effectiveness reducing HbA1C appears comparable to the SOC in this feasibility trial. Perhaps, a shared diabetes care including the primary care provider and an integrated diabetes education and management program would resonate with the identified patients’ preference, with higher diabetes optimization efficacy.

A pilot randomized controlled trial of EKG for neonatal resuscitation.

BackgroundThe seventh edition of the American Academy of Pediatrics Neonatal Resuscitation Program recommends the use of a cardiac monitor in infants that need resuscitation. Previous trials have shown that EKG heart rate is available before pulse rate from a pulse oximeter. To date no trial has looked at how the availability of electrocardiogram (EKG) affects clinical interventions in the delivery room.ObjectiveTo determine whether the availability of an EKG heart rate value and tracing to the clinical team has an effect on physiologic measures and related interventions during the stabilization of preterm infants.Design/MethodsForty (40) premature infants enrolled in a neuro-monitoring study (The Neu-Prem Trial: NCT02605733) who had an EKG monitor available were randomized to have the heart rate information from the bedside EKG monitor either displayed or not displayed to the clinical team. Heart rate, oxygen saturation, FiO2 and mean airway pressure from a data acquisition system were recorded every 2 seconds. Results were averaged over 30 seconds and the differences analyzed using two-tailed t-test. Interventions analyzed included time to first change in FiO2, first positive pressure ventilation, first increase in airway pressure, and first intubation.ResultsThere were no significant differences in time to clinical interventions between the blinded and unblinded group, despite the unblinded group having access to a visible heart rate at 66 +/- 20 compared to 114 +/- 39 seconds for the blinded group (p < .0001). Pulse rate from oximeter was lower than EKG heart rate during the first 2 minutes of life, but this was not significant.Conclusion(s)EKG provides an earlier, and more accurate heart rate than pulse rate from an oximeter during stabilization of preterm infants, allowing earlier intervention. All interventions were started earlier in the unblinded EKG group but these numbers were not significant in this small trial. Earlier EKG placement before pulse oximeter placement may affect other interventions, but this needs further study.

Continuous Glucose Monitoring in Very Preterm Infants: A Randomized Controlled Trial.

Impaired glucose control in very preterm infants is associated with increased morbidity, mortality, and poor neurologic outcome. Strategies based on insulin titration have been unsuccessful in achieving euglycemia in absence of an increase in hypoglycemia and mortality. We sought to assess whether glucose administration guided by continuous glucose monitoring (CGM) is more effective than standard of care blood glucose monitoring in maintaining euglycemia in very preterm infants. Fifty newborns ≤32 weeks' gestation or with birth weight ≤1500 g were randomly assigned (1:1) within 48-hours from birth to receive computer-guided glucose infusion rate (GIR) with or without CGM. In the unblinded CGM group, the GIR adjustments were driven by CGM and rate of glucose change, whereas in the blinded CGM group the GIR was adjusted by using standard of care glucometer on the basis of blood glucose determinations. Primary outcome was percentage of time spent in euglycemic range (72-144 mg/dL). Secondary outcomes were percentage of time spent in mild (47-71 mg/dL) and severe (<47 mg/dL) hypoglycemia; percentage of time in mild (145-180 mg/dL) and severe (>180 mg/dL) hyperglycemia; and glucose variability. Neonates in the unblinded CGM group had a greater percentage of time spent in euglycemic range (median, 84% vs 68%, P < .001) and decreased time spent in mild (P = .04) and severe (P = .007) hypoglycemia and in severe hyperglycemia (P = .04) compared with the blinded CGM group. Use of CGM also decreased glycemic variability (SD: 21.6 ± 5.4 mg/dL vs 27 ± 7.2 mg/dL, P = .01; coefficient of variation: 22.8% ± 4.2% vs 27.9% ± 5.0%; P < .001). CGM-guided glucose titration can successfully increase the time spent in euglycemic range, reduce hypoglycemia, and minimize glycemic variability in preterm infants during the first week of life.

Multitarget stool DNA test: clinical performance and impact on yield and quality of colonoscopy for colorectal cancer screening

Multitarget stool DNA (MT-sDNA) testing is now approved by the U.S. Food and Drug Administration for average-risk colorectal cancer screening. Trials leading to its approval used blinded colonoscopy as the reference standard. In the postapproval screen setting, the clinical performance and impact of MT-sDNA testing on unblinded colonoscopy has not been described. We measured the impact that knowledge of a positive MT-sDNA test result has on colonoscopy yield and quality. The unblinded group comprised all patients with positive MT-sDNA results on screening from September 1, 2014 to September 30, 2015 at a single tertiary center. Off-label test patients were excluded. The blinded group included all MT-sDNA-positive participants in a preapproval screening study from the same center. Detailed colonoscopy findings and withdrawal times were recorded. There were 172 MT-sDNA-positive patients in the unblinded group and 72 in the blinded group. Moretotal adenomatous/sessile serrated polyps (70% vs 53%, P= .013) and advanced neoplasms (28% vs 21%, P= .27) were detected in unblinded than in blinded groups. Median numbers of polyps detected were 2 (IQR, 1-4) and 1 (IQR, 0-2) in unblinded and blinded groups, respectively (P= .0007). Among polyps detected, flat or slightly raised lesions in the right side of the colon were proportionately more frequent with unblinded (40%) than with blinded examinations (9%) (P= .0017). Median withdrawal time was 19 minutes (IQR, 13-29) in the unblinded group compared with 13 minutes (IQR, 10-20) in the blinded group (P= .0001). Knowledge of a positive MT-sDNA result appears to have a beneficial impact on the diagnostic yield and quality of subsequent colonoscopy.

Feasibility, acceptability and uptake rates of gestational diabetes mellitus screening in primary care vs secondary care: findings from a randomised controlled mixed methods trial.

It is postulated that uptake rates for gestational diabetes mellitus (GDM) screening would be improved if offered in a setting more accessible to the patient. The aim of this study was to evaluate the proportion of uptake of GDM screening in the primary vs secondary care setting, and to qualitatively explore the providers' experiences of primary care screening provision. This mixed methods study was composed of a quantitative unblinded parallel group randomised controlled trial and qualitative interview trial. The primary outcome was the proportion of uptake of screening in both the primary and secondary care settings. All pregnant women aged 18 years or over, with sufficient English and without a diagnosis or diabetes or GDM, who attended for their first antenatal appointment at one of three hospital sites along the Irish Atlantic seaboard were eligible for inclusion in this study. Seven hundred and eighty-one pregnant women were randomised using random permutated blocks to receive a 2 h 75 g OGTT in either a primary (n = 391) or secondary care (n = 390) setting. Semi-structured interviews were conducted with 13 primary care providers. Primary care providers who provided care to the population covered by the three hospital sites involved were eligible for inclusion. Statistically significant differences were found between the primary care (n = 391) and secondary care (n = 390) arms for uptake (52.7% vs 89.2%, respectively; effect size 36.5 percentage points, 95% CI 30.7, 42.4; p < 0.001), crossover (32.5% vs 2.3%, respectively; p < 0.001) and non-uptake (14.8% vs 8.5%, respectively; p = 0.005). There were no significant differences in uptake based on the presence of a practice nurse or the presence of multiple general practitioners in the primary care setting. There was evidence of significant relationship between probability of uptake of screening and age (p < 0.001). Primary care providers reported difficulties with the conduct of GDM screening, despite recognising that the community was the most appropriate location for screening. Currently, provision of GDM screening in primary care in Ireland, despite its acknowledged benefits, is unfeasible due to poor uptake rates, poor rates of primary care provider engagement and primary care provider concerns. http://isrctn.org ISRCTN02232125 FUNDING: This study was funded by the Health Research Board (ICE2011/03).

A self-managed single exercise programme versus usual physiotherapy treatment for rotator cuff tendinopathy: a randomised controlled trial (the SELF study)

Objectives: To evaluate the clinical effectiveness of a self-managed single exercise programme versus usual physiotherapy treatment for rotator cuff tendinopathy. Design: Multi-centre pragmatic unblinded parallel group randomised controlled trial. Setting: UK National Health Service. Participants: Patients with a clinical diagnosis of rotator cuff tendinopathy. Interventions: The intervention was a programme of self-managed exercise prescribed by a physiotherapist in relation to the most symptomatic shoulder movement. The control group received usual physiotherapy treatment. Main outcome measures: The primary outcome measure was the Shoulder Pain & Disability Index (SPADI) at three months. Secondary outcomes included the SPADI at six and twelve months. Results: A total of 86 patients (self-managed loaded exercise n=42; usual physiotherapy n=44) were randomised. Twenty-six patients were excluded from the analysis because of lack of primary outcome data at the 3 months follow-up, leaving 60 (n=27; n=33) patients for intention to treat analysis. For the primary outcome, the mean SPADI score at three months was 32.4 (SD 20.2) for the self-managed group, and 30.7 (SD 19.7) for the usual physiotherapy treatment group; mean difference adjusted for baseline score: 3.2 (95% Confidence interval -6.0 to +12.4 P = 0.49). By six and twelve months there remained no significant difference between the groups. Conclusions: This study does not provide sufficient evidence of superiority of one intervention over the other in the short-, mid- or long-term and hence a self-management programme based around a single exercise appears comparable to usual physiotherapy treatment.

72 * Contact force timing reduces pulmonary vein reconnection, early results from the smart AF trial

Introduction: The addition of contact force (CF) sensing information may facilitate wide area circumferential ablation (WACA). We present data from an interim analysis of the first multicentre randomised controlled trial studying the impact of (CF) sensing information on the ablation of paroxysmal atrial fibrillation (AF). Method: At 7 UK centres, patients undergoing first time paroxysmal AF ablation were randomised to ablation with or without CF data available to the operator. The planned recruitment is 120 patients with 1 year follow up. Using a 3D mapping system and the SmartTouch CF-sensing catheter (Biosense Webster), all patients underwent WACA. Following this, a wait time of 60 minutes was observed before checking for acute electrical pulmonary vein (PV) reconnection. If the PV remained isolated at 60 minutes 18mg adenosine was administered intravenously. The primary end point was acute PV reconnection whether spontaneous or adenosine induced. Each PV was assessed separately, though in cases of a common trunk these were taken as one vein. Where procedures were terminated prematurely for whatever reason, PVs that remained isolated but had not completed the 1 hour waiting period were excluded from the analysis of acute PV reconnection. Follow up is ongoing and outcomes are not reported here. Results: Currently, 91 of 120 patients have been recruited (44 randomised to blinded group, 47 to unblinded group). The mean age was 59±10years, 52.7% male, CHA2DS2VASC 1.5±1.6, duration of AF 36 (6-289) months. There were no significant differences in baseline characteristics between groups. There were no significant differences in the procedural parameters for the procedures as a whole (Table) or for the same parameters for each PV pair separately (p>0.05). There was a significant reduction in the proportion of pulmonary veins that reconnected acutely in the unblinded group, and this was driven by a reduction in left sided reconnections (Table). There were two tamponades and one minor pericardial effusion, all in the unblinded arm (p=0.24). Conclusion: Based on our interim analysis, addition of contact force sensing data had no impact on procedure time, fluoroscopy use, or the amount of ablation used, but did reduce the rate of acute pulmonary vein reconnection suggesting more effective application of ablation lesions. Whether this translates to improved success rates will be assessed on completion of the study. | | CF Blinded Group | CF Unblinded Group | p-value | | ------------------------------------------------ | ---------------- | ------------------ | ------- | | Total Procedure Time in mins | 196(127-310) | 193 (125-337) | 0.7 | | Total Fluoroscopy Time in mins | 13 (1-54) | 10 (1-60) | 0.9 | | Total Fluoroscopy Dose in cGy.cm2 | 947 (98-47000) | 826 (48-42860) | 0.9 | | Total Radiofrequency Ablation Time in seconds | 2289 (977-4420) | 2446 (1262-5571) | 0.2 | | Total Pulmonary Vein Reconnections at 60 minutes | 48/173 (28%) | 31/172 (18%) | 0.04 | | Left Pulmonary Vein Reconnections at 60 minutes | 28/88 (32%) | 12/87 (14%) | 0.0065 | | Right Pulmonary Vein Reconnections at 60 minutes | 20/85 (24%) | 19/85 (22%) | 1 |

Telephone follow-up by nurse following total knee arthroplasty - protocol for a randomized clinical trial (NCT 01771315).

BackgroundDue to shorter hospitalization, patients have to take responsibility for their rehabilitation period at a very early stage. The objective of this trial is to study the effects of two treatment schemes following total knee arthroplasty: conventional treatment following discharge from hospital and early follow-up by telephone consultations in addition to conventional treatment following discharge from hospital. The ultimate aim is to increase the effectiveness of the treatment by improving patients' health status, promote self-efficacy, and reduce the number of acute visits to the orthopaedic outpatient clinic during the rehabilitation period.Method/designThe design is a randomized un-blinded parallel group clinical trial conducted at the Department of Orthopaedic Surgery, Gentofte Hospital, the Capital Region of Denmark. In total, 116 patients will be allocated by an external randomization program to 2 groups: an intervention group following usual treatment after discharge supplemented by a nurse managed structured follow-up consultation conducted by telephone 4 and 14 days after discharge from hospital and a control group following treatment as usual. The consultations are structured by key subjects relevant to assess the health status according to the VIPS-model (the Swedish acronym for the concepts Well-being, Integrity, Prevention and Safety). The content of the consultations can vary according to the patients´ individual situations and needs. All consultations are conducted by the researcher responsible for the trial.The effect is measured 1, 3, 6 and 12 months post-surgery. The primary outcome is self-reported physical function measured by The Western Ontario and McMaster Universities Arthritis Index. Secondary outcomes are self-reported health-related quality of life, general self-efficacy and the number of acute visits to the orthopaedic outpatient clinic.DiscussionThe result of this trial is expected to provide new knowledge to support the development of targeted and effective follow-up after total knee arthroplasty in order to improve the patients´ health-related knowledge and skills of being able to take actively part in their illness and improve their health status.Trial registrationClinicalTrials.gov: NCT01771315

Sedation Levels During Propofol Administration for Outpatient Colonoscopies

The levels of sedation required for patients to comfortably undergo colonoscopy with propofol were examined. One hundred patients undergoing colonoscopy with propofol were enrolled. In addition to standard-of-care monitoring, sedation level was monitored with the Patient State Index (PSI) obtained from a brain function monitor, transcutaneous carbon dioxide (tcpCO2) was monitored with the TCM TOSCA monitor, and end-tidal carbon dioxide was monitored via nasal cannula. The Ramsay Sedation Score (RSS) was also assessed and recorded. After baseline data were obtained from the first 40 consecutive patients enrolled in the study, the remaining 60 patients were randomized into two groups. In one group the PSI value was blinded from the anesthesiologist and in the second group the PSI was visible and the impact of this information on the management of the sedation was analyzed. Overall 96% of patients reached levels of deep sedation and 89% reached levels of general anesthesia. When comparing the blinded to PSI versus unblinded groups, the blinded group had a significantly lower PSI and higher RSS and tcpCO2, indicating the blinded group was maintained at a deeper sedation level with more respiratory compromise than the unblinded group. Patients undergoing colonoscopy under propofol sedation delivered by a bolus technique are frequently taken to levels of general anesthesia and are at risk for respiratory depression, airway obstruction, and hemodynamic compromise.

Self-managed loaded exercise versus usual physiotherapy treatment for rotator cuff tendinopathy: a pilot randomised controlled trial

ObjectivesRotator cuff tendinopathy is a common source of shoulder pain characterised by persistent and/or recurrent problems for a proportion of sufferers. The aim of this study was to pilot the methods proposed to conduct a substantive study to evaluate the effectiveness of a self-managed loaded exercise programme versus usual physiotherapy treatment for rotator cuff tendinopathy. DesignA single-centre pragmatic unblinded parallel group pilot randomised controlled trial. SettingOne private physiotherapy clinic, northern England. ParticipantsTwenty-four participants with rotator cuff tendinopathy. InterventionsThe intervention was a programme of self-managed loaded exercise. The control group received usual physiotherapy treatment. Main outcomesBaseline assessment comprised the Shoulder Pain and Disability Index (SPADI) and the Short-Form 36, repeated three months post randomisation. ResultsThe recruitment target was met and the majority of participants (98%) were willing to be randomised. 100% retention was attained with all participants completing the SPADI at three months. Exercise adherence rates were excellent (90%). The mean change in SPADI score was −23.7 (95% CI −14.4 to −33.3) points for the self-managed exercise group and −19.0 (95% CI −6.0 to −31.9) points for the usual physiotherapy treatment group. The difference in three month SPADI scores was 0.1 (95% CI −16.6 to 16.9) points in favour of the usual physiotherapy treatment group. ConclusionsIn keeping with previous research which indicates the need for further evaluation of self-managed loaded exercise for rotator cuff tendinopathy, these methods and the preliminary evaluation of outcome offer a foundation and stimulus to conduct a substantive study.