Cerebral Microembolization During Aortic Valve Replacement Using Minimally Invasive or Conventional Extracorporeal Circulation: A Randomized Trial.

To compare intraoperative cerebral microembolic load between minimally invasive extracorporeal circulation (MiECC) and conventional extracorporeal circulation (CECC) during isolated surgical aortic valve replacement (SAVR), we conducted a randomized trial in patients undergoing primary elective SAVR at a tertiary referral hospital. The primary outcome was the procedural phase-related rate of high-intensity transient signals (HITS) on transcranial Doppler ultrasound. HITS rate was used as a surrogate of cerebral microembolism in pre-defined procedural phases in SAVR using MiECC or CECC with (+F) or without (-F) an oxygenator with integrated arterial filter. Forty-eight patients were randomized in a 1:1 ratio to MiECC or CECC. Due to intraprocedural Doppler signal loss (n = 3), 45 patients were included in final analysis. MiECC perfusion regimen showed a significantly increased HITS rate compared to CECC (by a factor of 1.75; 95% confidence interval, 1.19-2.56). This was due to different HITS rates in procedural phases from aortic cross-clamping until declamping [phase 4] (P = 0.01), and from aortic declamping until stop of extracorporeal perfusion [phase 5] (P = 0.05). Post hoc analysis revealed that MiECC-F generated a higher HITS rate than CECC+F (P = 0.005), CECC-F (P = 0.05) in phase 4, and CECC-F (P = 0.03) in phase 5, respectively. In open-heart surgery, MiECC is not superior to CECC with regard to gaseous cerebral microembolism. When using MiECC for SAVR, the use of oxygenators with integrated arterial line filter appears highly advisable. Only with this precaution, MiECC confers a cerebral microembolic load comparable to CECC during this type of open heart surgery.

Efficacy of an Internet-based, individually tailored smoking cessation program: A randomized trial

Introduction: Self-help computer-based programs are easily accessible and cost-effective interventions with a great recruitment potential. However, each program is different and results of meta-analyses may not apply to each new program; therefore, evaluations of new programs are warranted. The aim of this study was to assess the marginal efficacy of a computer-based, individually tailored program (the Coach) over and above the use of a comprehensive Internet smoking cessation website. Methods: A two-group randomized controlled trial was conducted. The control group only accessed the website, whereas the intervention group received the Coach in addition. Follow-up was conducted by e-mail after three and six months (self-administrated questionnaires). Of 1120 participants, 579 (51.7%) responded after three months and 436 (38.9%) after six months. The primary outcome was self-reported smoking abstinence over four weeks. Results: Counting dropouts as smokers, there were no statistically significant differences between intervention and control groups in smoking cessation rates after three months (20.2% vs. 17.5%, p¼0.25, odds ratio (OR)¼1.20) and six months (17% vs. 15.5%, p¼0.52, OR¼1.12). Excluding dropouts from the analysis, there were statistically significant differences after three months (42% vs. 31.6%, p¼0.01, OR¼1.57), but not after six months (46.1% vs. 37.8%, p¼0.081, OR¼1.41). The program also significantly increased motivation to quit after three months and self-efficacy after three and six months. Discussion: An individually tailored program delivered via the Internet and by e-mail in addition to a smoking cessation website did not significantly increase smoking cessation rates, but it increased motivation to quit and self-efficacy.

Treatment of partial-thickness burns: A prospective, randomized trial using Transcyte (TM)

Background: The purpose of the present study was to compare the effectiveness of three burns dressings (TransCyte, a bio-engineered skin substitute; Biobrane; and Silvazine cream (silver sulphadiazine and 0.2% chlorhexidine)), in treating children with partial-thickness burns. The primary objective was to determine the days until greater than or equal to90% re-epithelialization. The secondary objectives were to evaluate the number of wounds requiring autografting and the number of dressing changes/local wound care required. Methods: Study wounds were identified on each patient and the patients were randomized to receive TransCyte or Biobrane or Silvazine. Assessment of study wound closure began at 2 days after treatment and continued at least every other day thereafter until the wounds re-epithelialized or were autografted. A laser Doppler imaging system was used as an adjunct to assessing the depth of the burn. Results: Thirty-three patients with 58 wound sites enrolled in the study (TransCyte, n = 20, Biobrane, n = 17; Silvazine, n = 21). Mean time to re-epithelialization was 7.5 days for TransCyte, 9.5 days for Biobrane, and 11.2 days for Silvazine. The number of wounds requiring autografting were 5/21 (24%) for Silvazine, 3/17 (17%) for Biobrane, and 1/20 (5%) for TransCyte. Conclusions: When used in partial-thickness burns in children, TransCyte promotes fastest re-epithelialization and required less overall dressings then Biobrane or Silvazine. Patients who received Silvazine or Biobrane require more autografting than those treated with TransCyte.

Addition of cue exposure to cognitive-behaviour therapy for alcohol misuse: a randomized trial with dysphoric drinkers

Aim To test whether addition of moderation-orientated cue exposure (CE) or CE after dysphoric mood induction ( emotional CE, ECE) improved outcomes above those from cognitive-behaviour therapy alone (CBT) in people who drank when dysphoric. Design Multi-site randomized controlled trial comparing CBT with CBT + CE and CBT + ECE. Setting Out-patient rooms in academic treatment units in Brisbane and Sydney, Australia. Participants People with alcohol misuse and problems controlling consumption when dysphoric (n = 163). Those with current major depressive episode were excluded. Intervention Eight weekly 75-minute sessions of individual treatment for alcohol problems were given to all participants, with CBT elements held constant across conditions. From session 2, CBT + CE participants resisted drinking while exposed to alcohol cues, with two priming doses of their preferred beverage being given in some sessions. After an initial CE session, CBT + ECE participants recalled negative experiences before undertaking CE, to provide exposure to emotional cues of personal relevance. Measurements Alcohol consumption, related problems, alcohol expectancies, self-efficacy and depression. Results Average improvements were highly significant across conditions, with acceptable maintenance of effects over 12 months. Both treatment retention and effects on alcohol consumption were progressively weaker in CBT + CE and CBT + ECE than in CBT alone. Changes in alcohol dependence and depression did not differ across conditions. Conclusions These data do not indicate that addition of clinic-based CE to standard CBT improves outcomes. A different approach to the management of craving may be required.

Ranibizumab versus Bevacizumab to treat neovascular age-related macular degeneration:one-year findings from the IVAN Randomized Trial

PURPOSE: To compare the efficacy and safety of ranibizumab and bevacizumab intravitreal injections to treat neovascular age-related macular degeneration (nAMD). DESIGN: Multicenter, noninferiority factorial trial with equal allocation to groups. The noninferiority limit was 3.5 letters. This trial is registered (ISRCTN92166560). PARTICIPANTS: People >50 years of age with untreated nAMD in the study eye who read =25 letters on the Early Treatment Diabetic Retinopathy Study chart. METHODS: We randomized participants to 4 groups: ranibizumab or bevacizumab, given either every month (continuous) or as needed (discontinuous), with monthly review. MAIN OUTCOME MEASURES: The primary outcome is at 2 years; this paper reports a prespecified interim analysis at 1 year. The primary efficacy and safety outcome measures are distance visual acuity and arteriothrombotic events or heart failure. Other outcome measures are health-related quality of life, contrast sensitivity, near visual acuity, reading index, lesion morphology, serum vascular endothelial growth factor (VEGF) levels, and costs. RESULTS: Between March 27, 2008 and October 15, 2010, we randomized and treated 610 participants. One year after randomization, the comparison between bevacizumab and ranibizumab was inconclusive (bevacizumab minus ranibizumab -1.99 letters, 95% confidence interval [CI], -4.04 to 0.06). Discontinuous treatment was equivalent to continuous treatment (discontinuous minus continuous -0.35 letters; 95% CI, -2.40 to 1.70). Foveal total thickness did not differ by drug, but was 9% less with continuous treatment (geometric mean ratio [GMR], 0.91; 95% CI, 0.86 to 0.97; P = 0.005). Fewer participants receiving bevacizumab had an arteriothrombotic event or heart failure (odds ratio [OR], 0.23; 95% CI, 0.05 to 1.07; P = 0.03). There was no difference between drugs in the proportion experiencing a serious systemic adverse event (OR, 1.35; 95% CI, 0.80 to 2.27; P = 0.25). Serum VEGF was lower with bevacizumab (GMR, 0.47; 95% CI, 0.41 to 0.54; P

A randomized trial of specialized versus standard neck physiotherapy in cervical dystonia

We thank: the patients who took part; Monsieur John-Pierre Bleton for training the physiotherapists; Gladys McPherson (Senior IT Manager), Adesoji Adeyemi (programmer) and Diana Collins (data entry) from the Centre for Healthcare Randomised Trials, University of Aberdeen who provided the randomisation and database service; and the funders including The Dystonia Society, the RS Macdonald Charitable Trust, The Sir Halley Stewart Trust, The Foyle Foundation and The Garfield Weston Foundation. The Dystonia Society and other funders had no role in the design, conduct, analysis or writing of the report or the decision to submit the manuscript.

The Physical Activity 4 Everyone Cluster Randomized Trial : 2-Year Outcomes of a School Physical Activity Intervention Among Adolescents

Acknowledgments The Physical Activity 4 Everyone intervention trial was funded by the New South Wales Ministry of Health through the New South Wales Health Promotion Demonstration Research Grants Scheme and conducted by Hunter New England Population Health (a unit of the Hunter New England Local Health District), in collaboration with the University of Newcastle and University of Wollongong. Infrastructure support was provided by Hunter Medical Research Institute. The research team acknowledges the importance of making research data publically available. Access to the accelerometer data from this study may be made available to external collaborators following the development of data transfer agreements. Further results arising from the study can be found at www.goodforkids.nsw.gov.au/high-schools/.

The Effect of Propofol Versus Isoflurane Anesthesia on Human Cerebrospinal Fluid Markers of Alzheimer's Disease: Results of a Randomized Trial.

BACKGROUND: Preclinical studies have found differential effects of isoflurane and propofol on the Alzheimer's disease (AD)-associated markers tau, phosphorylated tau (p-tau) and amyloid-β (Aβ). OBJECTIVE: We asked whether isoflurane and propofol have differential effects on the tau/Aβ ratio (the primary outcome), and individual AD biomarkers. We also examined whether genetic/intraoperative factors influenced perioperative changes in AD biomarkers. METHODS: Patients undergoing neurosurgical/otolaryngology procedures requiring lumbar cerebrospinal fluid (CSF) drain placement were prospectively randomized to receive isoflurane (n = 21) or propofol (n = 18) for anesthetic maintenance. We measured perioperative CSF sample AD markers, performed genotyping assays, and examined intraoperative data from the electronic anesthesia record. A repeated measures ANOVA was used to examine changes in AD markers by anesthetic type over time. RESULTS: The CSF tau/Aβ ratio did not differ between isoflurane- versus propofol-treated patients (p = 1.000). CSF tau/Aβ ratio and tau levels increased 10 and 24 h after drain placement (p = 2.002×10-6 and p = 1.985×10-6, respectively), mean CSF p-tau levels decreased (p = 0.005), and Aβ levels did not change (p = 0.152). There was no interaction between anesthetic treatment and time for any of these biomarkers. None of the examined genetic polymorphisms, including ApoE4, were associated with tau increase (n = 9 polymorphisms, p > 0.05 for all associations). CONCLUSION: Neurosurgery/otolaryngology procedures are associated with an increase in the CSF tau/Aβ ratio, and this increase was not influenced by anesthetic type. The increased CSF tau/Aβ ratio was largely driven by increases in tau levels. Future work should determine the functional/prognostic significance of these perioperative CSF tau elevations.

Randomized Trial for a Mobile Health Approach to Increase Uptake of Cervical Cancer Screening in Tanzania

Background: Largely due to low availability and uptake of screening in low- and middle-income countries, cervical cancer is the second ranked cancer among women in these countries. This is a tragedy because cervical cancer is one of the most preventable carcinomas. This thesis will investigate behaviour change methods, which capitalize on the recent exponential increase in ownership of mobile phones in Tanzania, to increase uptake of cervical cancer screening (CCS) in the Kilimanjaro region of Tanzania. Objectives: 1) To evaluate the effectiveness of behaviour change messages delivered via short message service (SMS) on the uptake of CCS in the Kilimanjaro region; 2) to evaluate the effectiveness of a transportation eVoucher on the uptake of CCS in the Kilimanjaro region; 3) to explore characteristics associated with CCS uptake in the Kilimanjaro region; and 4) to determine the attitudes towards and perceived benefit of behaviour change SMS messages and eVouchers intended to increase uptake of CCS. Methods: In the Kilimanjaro Region, 853 women participated in a randomized controlled trial. Baseline data was collected through self-report through systematic stratified random sampling. Participants were randomized to one of three groups: a control group, a group receiving behaviour change messages delivered via SMS, or a group receiving a travel eVoucher and identical SMS as the SMS group. A fieldworker recorded participants attending screening at the CCS clinics and administered a post-screening survey. The follow-up period was two months from the time of the participant’s enrolment. Logistic regression (both for the combined and stratified data sets) was used to determine associations between the behaviour change interventions, baseline characteristics and cervical cancer screening uptake. Results: All participants receiving SMS messages (SMS or eVoucher group) were more likely to attend cervical cancer screening in comparison with the control group. 83% of participants who attended screening shared the information contained in the messages with others. Conclusions: Behaviour change messages delivered via SMS and transportation eVouchers have the potential to increase uptake of cervical cancer screening in the Kilimanjaro region of Tanzania. Harnessing this potential will require implementing these interventions alongside other methods to achieve maximum impact.

Natriuretic peptide-based screening and collaborative care for heart failure:the STOP-HF randomized trial

IMPORTANCE: Prevention strategies for heart failure are needed.

OBJECTIVE: To determine the efficacy of a screening program using brain-type natriuretic peptide (BNP) and collaborative care in an at-risk population in reducing newly diagnosed heart failure and prevalence of significant left ventricular (LV) systolic and/or diastolic dysfunction.

DESIGN, SETTING, AND PARTICIPANTS: The St Vincent's Screening to Prevent Heart Failure Study, a parallel-group randomized trial involving 1374 participants with cardiovascular risk factors (mean age, 64.8 [SD, 10.2] years) recruited from 39 primary care practices in Ireland between January 2005 and December 2009 and followed up until December 2011 (mean follow-up, 4.2 [SD, 1.2] years).

INTERVENTION: Patients were randomly assigned to receive usual primary care (control condition; n=677) or screening with BNP testing (n=697). Intervention-group participants with BNP levels of 50 pg/mL or higher underwent echocardiography and collaborative care between their primary care physician and specialist cardiovascular service.

MAIN OUTCOMES AND MEASURES: The primary end point was prevalence of asymptomatic LV dysfunction with or without newly diagnosed heart failure. Secondary end points included emergency hospitalization for arrhythmia, transient ischemic attack, stroke, myocardial infarction, peripheral or pulmonary thrombosis/embolus, or heart failure.

RESULTS: A total of 263 patients (41.6%) in the intervention group had at least 1 BNP reading of 50 pg/mL or higher. The intervention group underwent more cardiovascular investigations (control, 496 per 1000 patient-years vs intervention, 850 per 1000 patient-years; incidence rate ratio, 1.71; 95% CI, 1.61-1.83; P<.001) and received more renin-angiotensin-aldosterone system-based therapy at follow-up (control, 49.6%; intervention, 56.5%; P=.01). The primary end point of LV dysfunction with or without heart failure was met in 59 (8.7%) of 677 in the control group and 37 (5.3%) of 697 in the intervention group (odds ratio [OR], 0.55; 95% CI, 0.37-0.82; P = .003). Asymptomatic LV dysfunction was found in 45 (6.6%) of 677 control-group patients and 30 (4.3%) of 697 intervention-group patients (OR, 0.57; 95% CI, 0.37-0.88; P = .01). Heart failure occurred in 14 (2.1%) of 677 control-group patients and 7 (1.0%) of 697 intervention-group patients (OR, 0.48; 95% CI, 0.20-1.20; P = .12). The incidence rates of emergency hospitalization for major cardiovascular events were 40.4 per 1000 patient-years in the control group vs 22.3 per 1000 patient-years in the intervention group (incidence rate ratio, 0.60; 95% CI, 0.45-0.81; P = .002).

CONCLUSION AND RELEVANCE: Among patients at risk of heart failure, BNP-based screening and collaborative care reduced the combined rates of LV systolic dysfunction, diastolic dysfunction, and heart failure.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00921960.

Self-refraction, ready-made glasses and quality of life among rural myopic Chinese children: a non-inferiority randomized trial.

PURPOSE: To study, for the first time, the effect of wearing ready-made glasses and glasses with power determined by self-refraction on children's quality of life. METHODS: This is a randomized, double-masked non-inferiority trial. Children in grades 7 and 8 (age 12-15 years) in nine Chinese secondary schools, with presenting visual acuity (VA) ≤6/12 improved with refraction to ≥6/7.5 bilaterally, refractive error ≤-1.0 D and <2.0 D of anisometropia and astigmatism bilaterally, were randomized to receive ready-made spectacles (RM) or identical-appearing spectacles with power determined by: subjective cycloplegic retinoscopy by a university optometrist (U), a rural refractionist (R) or non-cycloplegic self-refraction (SR). Main study outcome was global score on the National Eye Institute Refractive Error Quality of Life-42 (NEI-RQL-42) after 2 months of wearing study glasses, comparing other groups with the U group, adjusting for baseline score. RESULTS: Only one child (0.18%) was excluded for anisometropia or astigmatism. A total of 426 eligible subjects (mean age 14.2 years, 84.5% without glasses at baseline) were allocated to U [103 (24.2%)], RM [113 (26.5%)], R [108 (25.4%)] and SR [102 (23.9%)] groups, respectively. Baseline and endline score data were available for 398 (93.4%) of subjects. In multiple regression models adjusting for baseline score, older age (p = 0.003) and baseline spectacle wear (p = 0.016), but not study group assignment, were significantly associated with lower final score. CONCLUSION: Quality of life wearing ready-mades or glasses based on self-refraction did not differ from that with cycloplegic refraction by an experienced optometrist in this non-inferiority trial.