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Concept: Intention to treat analysis


BACKGROUND: The closed-loop stimulation (CLS) pacemaker algorithm is a system that permanently monitors the contractile state of the myocardium and converts the intrinsic information into rate regulation. The role that the CLS algorithm plays in the prevention of syncope recurrences still remains unclear. The aim of our prospective, randomised, single-bind, crossover study was to evaluate the effect of dual-chamber CLS in the prevention of syncope recurrence in patients with refractory vasovagal syncope (VVS) and a cardioinhibitory response to head-up tilt test (HUT) during a 36 months follow-up. METHOD SAND RESULTS: We studied 50 patients (mean age 53±5.1; 33 male) with the indication for permanent dual-chamber cardiac pacing for HUT-induced vasovagal cardioinhibitory syncope. They were randomised after 1 month of stabilisation period to CLS algorithm features programmed OFF or ON for 18 months each, using a crossover design. The number of syncopal and presyncopal episodes during active treatment was lower than those registered during no treatment (n syncopal episodes: 2 vs 15; p=0.007; n presincopal episodes: 5 vs 30; p = 0.004). Lead parameters remained stable over time, and there were no lead-related complications. CONCLUSIONS: Based on these 36 months follow-up data, it is concluded that dual-chamber CLS is an effective algorithm for preventing syncope recurrences in healthy patients with tilt-induced vasovagal cardioinhibitory syncope.

Concepts: Transcutaneous pacing, Clinical research, Parallel study, Intention to treat analysis, Optimal design, Repeated measures design, Crossover study, Clinical trial


The aim of the study was to evaluate the effects of synthetic feline interdigital semiochemical (FIS) on the induction of scratching behaviour in cats during a standardised behavioural test. The trial was a randomised blinded study on a single group of subjects, following a crossover design. The scratching behaviour of 19 cats was evaluated during a standardised test in which cats were introduced to an area with one scratching post. Each cat acted as its own control (receiving, at random, FIS then placebo or vice versa). The test lasted for 5 mins, after which the cat was left alone in the test area. Duration, frequency of scratching and latency of first scratching behaviour were noted. Two independent observers analysed the videos. Thirty-eight tests were recorded with a different scratching post each time (two tests per cat). The scratching post with the semiochemical was more scratched in duration and frequency by the cats involved in the study (intention to treat analysis). The same conclusion was found using per-protocol analysis, which included only cats that scratched during the test. Regarding latency, no significant difference was found between treatment and placebo. The results seem of interest in explaining the role of a FIS in inducing scratching behaviour on a scratching post. The semiochemical approach can modify the choice of areas selected spontaneously by cats, and could be used either as a preventive measure for a cat arriving at home or to control or change an inappropriate scratching behaviour.

Concepts: Castration, Standardized test, Felis, Felidae, Crossover study, Intention to treat analysis, Scratching post, Cat


To report two-year outcomes of a multi-center randomized controlled trial plus one-year results of a crossover trial after treatment with convective radiofrequency water vapor thermal energy for lower urinary tract symptoms due to benign prostatic hyperplasia.

Concepts: Intention to treat analysis, Clinical trial, Crossover study, Heat


No study has concurrently measured changes in free-living whole body protein metabolism and exercise performance during recovery from an acute bout of resistance exercise. We aimed to determine if whey protein ingestion enhances whole body net protein balance and recovery of exercise performance during overnight (10 h) and 24 h recovery after whole body resistance exercise in trained men. In a double-blind crossover design, 12 trained men (76 ± 8 kg, 24 ± 4 years old, 14% ± 5% body fat; means ± standard deviation (SD)) performed resistance exercise in the evening prior to consuming either 25 g of whey protein (PRO; MuscleTech 100% Whey) or an energy-matched placebo (CHO) immediately post-exercise (0 h), and again the following morning (~10 h of recovery). A third randomized trial, completed by the same participants, involving no exercise and no supplement served as a rested control trial (Rest). Participants ingested [(15)N]glycine to determine whole body protein kinetics and net protein balance over 10 and 24 h of recovery. Performance was assessed pre-exercise and at 0, 10, and 24 h of recovery using a battery of tests. Net protein balance tended to improve in PRO (P = 0.064; effect size (ES) = 0.61, PRO vs. CHO) during overnight recovery. Over 24 h, net balance was enhanced in PRO (P = 0.036) but not in CHO (P = 0.84; ES = 0.69, PRO vs. CHO), which was mediated primarily by a reduction in protein breakdown (PRO < CHO; P < 0.01. Exercise decreased repetitions to failure (REP), maximal strength (MVC), peak and mean power, and countermovement jump performance (CMJ) at 0 h (all P < 0.05 vs. Pre). At 10 h, there were small-to-moderate effects for enhanced recovery of the MVC (ES = 0.56), mean power (ES = 0.49), and CMJ variables (ES: 0.27-0.49) in PRO. At 24 h, protein supplementation improved MVC (ES = 0.76), REP (ES = 0.44), and peak power (ES = 0.55). In conclusion, whey protein supplementation enhances whole body anabolism, and may improve acute recovery of exercise performance after a strenuous bout of resistance exercise.

Concepts: Clinical research, Repeated measures design, Clinical trial, Metabolism, Randomized controlled trial, Standard deviation, Intention to treat analysis, Crossover study


Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel ‘Breath Powered’ nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device.

Concepts: Intention to treat analysis, Optimal design, Repeated measures design, Clinical research, Crossover study, Clinical trial, Pharmacology, Psychology


PURPOSEThe vast majority of patients with cancer at the end of life receive parenteral hydration in hospitals and no hydration in hospice, with limited evidence supporting either practice. In this randomized controlled trial, we determined the effect of hydration on symptoms associated with dehydration, quality of life, and survival in patients with advanced cancer.Patients and methodsWe randomly assigned 129 patients with cancer from six hospices to receive parenteral hydration (normal saline 1 L per day) or placebo (normal saline 100 mL per day) daily over 4 hours. The primary outcome was change in the sum of four dehydration symptoms (fatigue, myoclonus, sedation and hallucinations, 0 = best and 40 = worst possible) between day 4 and baseline. Secondary outcomes included Edmonton Symptom Assessment Scale (ESAS), Memorial Delirium Assessment Scale (MDAS), Nursing Delirium Screening Scale (NuDESC), Unified Myoclonus Rating Scale (UMRS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Dehydration Assessment Scale, creatinine, urea, and overall survival. Intention-to-treat analysis was conducted to examine the change by day 4 ± 2 and day 7 ± 2 between groups.ResultsThe hydration (n = 63) and placebo (n = 66) groups had similar baseline characteristics. We found no significant differences between the two groups for change in the sum of four dehydration symptoms (-3.3 v -2.8, P = .77), ESAS (all nonsignificant), MDAS (1 v 3.5, P = .084), NuDESC (0 v 0, P = .13), and UMRS (0 v 0, P = .54) by day 4. Results for day 7, including FACIT-F, were similar. Overall survival did not differ between the two groups (median, 21 v 15 days, P = .83). CONCLUSIONHydration at 1 L per day did not improve symptoms, quality of life, or survival compared with placebo.

Concepts: Pharmacology, Clinical research, Fatigue, Symptoms, Intention to treat analysis, Medical terms, Epidemiology, Randomized controlled trial


Background:There is a need for interventions to promote uptake of breast screening throughout Europe.Methods:We performed a single-blind randomised controlled trial to test whether text-message reminders were effective. Two thousand two hundred and forty women receiving their first breast screening invitation were included in the study and randomly assigned in a 1 : 1 ratio to receive either a normal invitation only (n=1118) or a normal invitation plus a text-message reminder 48 h before their appointment (n=1122).Findings:In the intention-to-treat analysis, uptake of breast screening was 59.1% among women in the normal invitation group and 64.4% in the text-message reminder group (χ(2)=6.47, odds ratio (OR): 1.26, 95% confidence intervals (CI): 1.05-1.48, P=0.01). Of the 1122 women assigned to the text-message reminder group, only 456 (41%) had a mobile number recorded by their GP and were thereby sent a text. In the per-protocol analysis, uptake by those in the control group who had a mobile number recorded on the GP system was 59.77% and by those in the intervention group who were sent a reminder 71.7% (χ(2)=14.12, OR=1.71, 95% CI=1.29-2.26, P<0.01).Interpretation:Sending women a text-message reminder before their first routine breast screening appointment significantly increased attendance. This information can be used to allocate resources efficiently to improve uptake without exacerbating social inequalities.British Journal of Cancer advance online publication, 10 February 2015; doi:10.1038/bjc.2015.36

Concepts: Breast cancer, Student's t-distribution, Cancer, Confidence interval, Intention to treat analysis, Normal distribution, Randomized controlled trial, Epidemiology


Objective: This study was conducted to determine whether installation of sit-stand desks (SSDs) could lead to decreased sitting time during the workday among sedentary office workers. Methods: A randomized cross-over trial was conducted from January to April, 2012 at a business in Minneapolis. 28 (nine men, 26 full-time) sedentary office workers took part in a 4 week intervention period which included the use of SSDs to gradually replace 50% of sitting time with standing during the workday. Physical activity was the primary outcome. Mood, energy level, fatigue, appetite, dietary intake, and productivity were explored as secondary outcomes. Results: The intervention reduced sitting time at work by 21% (95% CI 18%-25%) and sedentary time by 4.8 min/work-hr (95% CI 4.1-5.4 min/work-hr). For a 40 h work-week, this translates into replacement of 8 h of sitting time with standing and sedentary time being reduced by 3.2 h. Activity level during non-work hours did not change. The intervention also increased overall sense of well-being, energy, decreased fatigue, had no impact on productivity, and reduced appetite and dietary intake. The workstations were popular with the participants. Conclusion: The SSD intervention was successful in increasing work-time activity level, without changing activity level during non-work hours.

Concepts: Parallel study, Intention to treat analysis, Clinical trial, Optimal design, Repeated measures design, Crossover study, Obesity


OBJECTIVE: To assess the efficacy of tart cherry juice in treating pain and other features of knee osteoarthritis (OA). METHODS: 58 non-diabetic patients with Kellgren grade 2-3 OA were randomized to begin treatment with cherry juice or placebo. Two 8 oz bottles of tart cherry juice or placebo were consumed daily for 6 weeks with a 1 week washout period before switching treatments (crossover design). Western Ontario McMaster Osteoarthritis Index (WOMAC) scores and walking times were recorded prior to and after each treatment period. Additionally, plasma urate, creatinine and high sensitivity C-reactive protein (hsCRP) were recorded at baseline, after the first treatment period and after the second treatment period. Acetaminophen was allowed as a rescue drug and self reported after each treatment period. Treatment effect was examined with repeated measures ANOVA using an intention-to-treat analysis. RESULTS: There were 5 withdrawals during the cherry juice treatment (4 adverse events) and 7 withdrawals during the placebo treatment (3 adverse events). WOMAC scores decreased significantly (P<0.01) after the cherry juice treatment but not after the placebo treatment (P=0.46); differences between treatments were not significant (P=0.16). hsCRP declined during the cherry juice treatment versus placebo (P<0.01). The decline in hsCRP was associated with WOMAC improvement (P<0.01). Walking time, acetominophen use, plasma urate and creatnine were unaffected by treatments. CONCLUSIONS: Tart cherry juice provided symptom relief for patients with mild to moderate knee OA, but this effect was not significantly greater than placebo. Tart cherry juice lowered hsCRP levels and this effect was associated with improved WOMAC scores.

Concepts: Randomized controlled trial, Osteoarthritis, Pharmacology, Intention to treat analysis, Repeated measures design, Clinical research, Clinical trial, Crossover study


IMPORTANCE On July 1, 2011, the Accreditation Council for Graduate Medical Education implemented further restrictions of its 2003 regulations on duty hours and supervision. It remains unclear if the 2003 regulations improved trainee well-being or patient safety. OBJECTIVE To determine the effects of the 2011 Accreditation Council for Graduate Medical Education duty hour regulations compared with the 2003 regulations concerning sleep duration, trainee education, continuity of patient care, and perceived quality of care among internal medicine trainees. DESIGN AND SETTING Crossover study design in an academic research setting. PARTICIPANTS Medical house staff. INTERVENTION General medical teams were randomly assigned using a sealed-envelope draw to an experimental model or a control model. MAIN OUTCOME MEASURES We randomly assigned 4 medical house staff teams (43 interns) using a 3-month crossover design to a 2003-compliant model of every fourth night overnight call (control) with 30-hour duty limits or to one of two 2011-compliant models of every fifth night overnight call (Q5) or a night float schedule (NF), both with 16-hour duty limits. We measured sleep duration using actigraphy and used admission volumes, educational opportunities, the number of handoffs, and satisfaction surveys to assess trainee education, continuity of patient care, and perceived quality of care. RESULTS The study included 560 control, 420 Q5, and 140 NF days that interns worked and 834 hospital admissions. Compared with controls, interns on NF slept longer during the on call period (mean, 5.1 vs 8.3 hours; P = .003), and interns on Q5 slept longer during the postcall period (mean, 7.5 vs 10.2 hours; P = .05). However, both the Q5 and NF models increased handoffs, decreased availability for teaching conferences, and reduced intern presence during daytime work hours. Residents and nurses in both experimental models perceived reduced quality of care, so much so with NF that it was terminated early. CONCLUSIONS AND RELEVANCE Compared with a 2003-compliant model, two 2011 duty hour regulation-compliant models were associated with increased sleep duration during the on-call period and with deteriorations in educational opportunities, continuity of patient care, and perceived quality of care.

Concepts: Residency, Intention to treat analysis, Medicine, Model organism, Clinical trial, Crossover study, Medical school, Physician