Crossover Pilot Trial Research Articles

The effect of Sailuotong (SLT) on neurocognitive and cardiovascular function in healthy adults: a randomised, double-blind, placebo controlled crossover pilot trial.

BackgroundSailuotong (SLT) is a standardised herbal medicine formula consisting of Panax ginseng, Ginkgo biloba, and Crocus sativus, and has been designed to enhance cognitive and cardiovascular function.MethodsUsing a randomised, double-blind, placebo controlled crossover design, this pilot study assessed the effect of treatment for 1 week with SLT and placebo (1 week washout period) on neurocognitive and cardiovascular function in healthy adults. Sixteen adults completed a computerised neuropsychological test battery (Compass), and had their electroencephalographic (EEG) activity and cardiovascular system function assessed. Primary outcome measures were cognitive test scores and oddball task event-related potential (ERP) component amplitudes. Secondary outcome measures were resting EEG spectral band amplitudes, and cardiovascular parameters.ResultsTreatment with SLT, compared to placebo, resulted in small improvements in working memory, a slight increase in auditory target (cf. nontarget) P3a amplitude, and a decrease in auditory N1 target (cf. nontarget) amplitude. There was no effect of SLT on EEG amplitude in delta, theta, alpha, or beta bands in both eyes open and eyes closed resting conditions, or on aortic and peripheral pulse pressure, and resting heartrate.ConclusionsFindings suggest that SLT has the potential to improve working memory performance in healthy adults; a larger sample size is needed to confirm this.Trial registrationAustralia New Zealand Clinical Trials Registry Trial Registration Id: ACTRN12610000947000.

The effect of five day dosing with THCV on THC-induced cognitive, psychological and physiological effects in healthy male human volunteers: A placebo-controlled, double-blind, crossover pilot trial.

Cannabis is mostly grown under illegal and unregulated circumstances, which seems to favour a product increasingly high in its main cannabinoid ∆-9-tetrahydrocannabinol (THC). ∆-9-tetrahydrocannabivarin (THCV) is a relatively untested cannabinoid which is said to be a cannabinoid receptor neutral antagonist, and may inhibit the effects of THC. To explore the safety and tolerability of repeated THCV administration and its effects on symptoms normally induced by THC in a sample of healthy volunteers. Ten male cannabis users (<25 use occasions) were recruited for this within-subjects, placebo-controlled, double-blind, cross-over pilot study. 10mg oral pure THCV or placebo were administered daily for five days, followed by 1mg intravenous THC on the fifth day. THCV was well tolerated and subjectively indistinguishable from placebo. THC did not significantly increase psychotic symptoms, paranoia or impair short-term memory, while still producing significant intoxicating effects. Delayed verbal recall was impaired by THC and only occurred under placebo condition (Z=-2.201, p=0.028), suggesting a protective effect of THCV. THCV also inhibited THC-induced increased heart rate (Z=-2.193, p=0.028). Nine out of ten participants reported THC under THCV condition (compared to placebo) to be subjectively weaker or less intense (χ(2)=6.4, p=0.011). THCV in combination with THC significantly increased memory intrusions (Z=-2.155, p=0.031). In this first study of THC and THCV, THCV inhibited some of the well-known effects of THC, while potentiating others. These findings need to be interpreted with caution due to a small sample size and lack of THC-induced psychotomimetic and memory-impairing effect, probably owing to the choice of dose.

Preliminary inconclusive results of a randomised double blinded cross-over pilot trial in long-term-care dwelling elderly assessing the feasibility of stochastic resonance whole-body vibration

BackgroundThis randomised double-blinded controlled cross-over pilot study examined feasibility and preliminary effects of stochastic resonance whole-body vibration training applied in long term care elderly.FindingsNine long term care elderly were recruited and randomized to group A (6 Hz, Noise 4 SR-WBV/ Sham) or B (Sham / 1 Hz, Noise 1 SR-WBV). Feasibility outcomes included recruitment rate, attrition, adherence and safety. Physical performance outcomes focused on the Expanded Timed Get Up-and-Go (ETGUG) test, the Short Physical Performance Battery (SPPB), and lower extremity muscle strength.Of 24 subjects initially approached 9 started and 5 completed the study resulting in 37.5 recruitment, 44.4 attrition and 81.7 % adherence rates. No adverse events were reported. There is more evidence of improved performance levels in the SR-WBV treatment group with significant differences in average change for isometric rate of force development (p = 0.016 left leg; p = 0.028 right leg). No statistical significance was reached for other parameters.ConclusionsThe findings of this study indicate that the used training protocol for long term care elderly is feasible, however, requires more closely monitoring of participants; e.g. needs protocol modifications that target improved compliance with the intervention in this setting. SR-WBV shows beneficial effects on physical performance for those adhering to the intervention.Trial registrationU.S. National Institutes of Health NCT01543243Electronic supplementary materialThe online version of this article (doi:10.1186/s11556-015-0150-y) contains supplementary material, which is available to authorized users.

Prevention of Morbidity in sickle cell disease--qualitative outcomes, pain and quality of life in a randomised cross-over pilot trial of overnight supplementary oxygen and auto-adjusting continuous positive airways pressure (POMS2a): study protocol for a randomised controlled trial.

BackgroundSickle cell anaemia (SCA) is an inherited disorder of haemoglobin. Patients experience long-term health care problems, affecting quality of life (QOL) including frequent acute pain, which is difficult to document in trials except as hospital admissions. Pilot data suggests that overnight respiratory support, either supplementary oxygen or auto-adjusting continuous positive airways pressure (APAP), is safe and may have clinical benefit. This pilot trial aims to determine which intervention is more acceptable to participants and whether there are other advantages of one over the other, e.g. in respiratory function or haematological parameters, before conducting the Phase 2 trial of overnight respiratory support funded by the National Institutes of Health Research.Methods/DesignThis is a pilot cross-over interventional trial with the order of interventions decided by simple randomization. Ten adults (age over 18 years) and 10 children (aged between 8 and 18 years) with homozygous sickle cell disease (haemoglobin SS, HbSS), recruited regardless of symptoms of sleep-disordered breathing, will undergo overnight pulse oximetry and will have two interventions, overnight oxygen and APAP, for a week each in randomised order with a washout week between interventions. Participants will complete online diaries via an iPad throughout the 29 days of the study and will complete QOL questionnaires and have measurement of haematology, biochemistry, spirometry and lung volumes (adults only) at 3 time points, at baseline and after each intervention, as well as in-depth semi-structured qualitative interviews after each intervention, carried out by an experienced psychologist. Both qualitative and statistical methods will be used to analyze the data. The primary outcome is qualitative data looking at participant experience from the transcribed interviews after each intervention. The participant’s view on feasibility, acceptability and preference will specifically be explored. The QOL, laboratory and lung function data will be compared with baseline for each arm.DiscussionPatient and public involvement is an integral part of this trial and the key outcome is the qualitative result, which is dependent on obtaining good quality data to advise on participant feasibility, acceptability and preference. This is being addressed by using a standard interview. The development of a pain endpoint is another important outcome and collecting daily measurements is likely to be challenging. Research results will be used to inform design of the Phase 2 trial.Trial registration ISRCTN46078697 18 July 2014Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0883-y) contains supplementary material, which is available to authorized users.

Effect of vitamin E supplementation on HDL function by haptoglobin genotype in type 1 diabetes: results from the HapE randomized crossover pilot trial.

Haptoglobin (Hp) genotype 2-2 increases cardiovascular diabetes complications. In type 2 diabetes, α-tocopherol was shown to lower cardiovascular risk in Hp 2-2, potentially through HDL function improvements. Similar type 1 diabetes data are lacking. We conducted a randomized crossover pilot of α-tocopherol supplementation on HDL function [i.e., cholesterol efflux (CE) and HDL-associated lipid peroxides (LP)] and lipoprotein subfractions in type 1 diabetes. Hp genotype was assessed in members of two Allegheny County, PA, type 1 diabetes registries and the CACTI cohort; 30 were randomly selected within Hp genotype, and 28 Hp 1-1, 31 Hp 2-1 and 30 Hp 2-2 were allocated to daily α-tocopherol or placebo for 8weeks with a 4-week washout. Baseline CE decreased with the number of Hp 2 alleles (p-trend=0.003). There were no differences in LP or lipoprotein subfractions. In intention-to-treat analysis stratified by Hp, α-tocopherol increased CE in Hp 2-2 (β=0.79, p=0.03) and LP in Hp 1 allele carriers (β Hp 1-1=0.18, p=0.05; β Hp 2-1=0.21, p=0.07); reduced HDL particle size (β=-0.07, p=0.03) in Hp 1-1 carriers; increased LDL particle concentration in Hp 1-1; and decreased it in Hp 2-2 carriers. However, no significant interactions were observed by Hp. In this type 1 diabetes study, HDL function worsened with the number of Hp 2 alleles. α-Tocopherol improved HDL function in Hp 2-2 carriers and appeared to adversely affect lipid peroxides and lipoprotein subfractions among Hp 1 allele carriers. As no significant interactions were observed, findings require replication in larger studies.

Pharmacodynamic effects of atorvastatin vs. rosuvastatin in coronary artery disease patients with normal platelet reactivity while on dual antiplatelet therapy — The PEARL randomized cross-over study

Background: Ranolazine decreases the frequency of arrhythmias during the acute phases of ischemic heart disease (IHD), but it remains unknown if it has similar effects in the chronic phase of the disease. We performed a prospective, randomized, cross-over pilot trial to test the hypothesis that chronic treatment with ranolazine can reduce the incidence of documented arrhythmias and the related symptoms of palpitation in stable patients with IHD. Methods: We randomized 105 patients with stable IHD and symptoms of angina and palpitations already on therapy with betablockers and/or calcium antagonists to ranolazine (750 mg bid, N = 53) or placebo (N = 52) for 30 days (until T-1). After a washout period to avoid any carryover effect, cross-over was performed,and patients were switched to the other drug which was continued for 30 days (until T-2). All patients underwent symptomlimited exercise stress testing and 48-hour ECG Holter monitoring at T1 and T2. During the study period, patients were told to use a OmronN® portable ECG monitor HCG-801 device in case of symptoms of palpitations. Results: Ranolazine reduced the number of anginal episodes more commonly than placebo (5 ± 8 episodes/30 days vs. 21 ± 24 episodes/30 day, p = 0.001) and increased exercise durations at 1 mm ST-segment depression (514 ± 211 s vs. 402 ± 287 s, p = 0.025) and at onset of angina (614 ± 199 s vs. 519 ± 151 s, p = 0.007) at stress testing. These effects were coupled by significant decreases with ranolazine as compared with placebo treatment periods in the occurrence of frequent (N1000 beats) supraventricular arrhythmias (33% vs 52%, p = 0.01) and complex ventricular arrhythmias (17% vs 30%, p = 0.045). Complete resolution of symptoms of palpitations was significantly more common with ranolazine than placebo (31/53 vs 16/52 patients, p = 0.008). Also, portable ECG recordings showed that arrhythmias were less common during ranolazine vs. placebo, with significant decreases in number (7 ± 10 episodes/30 days vs. 23 ± 29 episodes/30 day, p = 0.001) and duration (10 ± 18 min/ 30 days vs. 19 ± 21 min/30 day, p = 0.021) of symptomatic arrhythmic episodes. No severe side effects were recorded during the trial period. Conclusion: The antianginal and antiischemic properties of ranolazine are paralleled by significant decreases in the occurrence of both arrhythmias and the related symptoms of palpitations in stable patients with IHD. (ClinicalTrials.gov identifier: NCT01495520).

Ranolazine reduces symptoms of palpitations and documented arrhythmias in patients with ischemic heart disease — The RYPPLE randomized cross-over trial

Background: Ranolazine decreases the frequency of arrhythmias during the acute phases of ischemic heart disease (IHD), but it remains unknown if it has similar effects in the chronic phase of the disease. We performed a prospective, randomized, cross-over pilot trial to test the hypothesis that chronic treatment with ranolazine can reduce the incidence of documented arrhythmias and the related symptoms of palpitation in stable patients with IHD. Methods: We randomized 105 patients with stable IHD and symptoms of angina and palpitations already on therapy with betablockers and/or calcium antagonists to ranolazine (750 mg bid, N = 53) or placebo (N = 52) for 30 days (until T-1). After a washout period to avoid any carryover effect, cross-over was performed,and patients were switched to the other drug which was continued for 30 days (until T-2). All patients underwent symptomlimited exercise stress testing and 48-hour ECG Holter monitoring at T1 and T2. During the study period, patients were told to use a OmronN® portable ECG monitor HCG-801 device in case of symptoms of palpitations. Results: Ranolazine reduced the number of anginal episodes more commonly than placebo (5 ± 8 episodes/30 days vs. 21 ± 24 episodes/30 day, p = 0.001) and increased exercise durations at 1 mm ST-segment depression (514 ± 211 s vs. 402 ± 287 s, p = 0.025) and at onset of angina (614 ± 199 s vs. 519 ± 151 s, p = 0.007) at stress testing. These effects were coupled by significant decreases with ranolazine as compared with placebo treatment periods in the occurrence of frequent (N1000 beats) supraventricular arrhythmias (33% vs 52%, p = 0.01) and complex ventricular arrhythmias (17% vs 30%, p = 0.045). Complete resolution of symptoms of palpitations was significantly more common with ranolazine than placebo (31/53 vs 16/52 patients, p = 0.008). Also, portable ECG recordings showed that arrhythmias were less common during ranolazine vs. placebo, with significant decreases in number (7 ± 10 episodes/30 days vs. 23 ± 29 episodes/30 day, p = 0.001) and duration (10 ± 18 min/ 30 days vs. 19 ± 21 min/30 day, p = 0.021) of symptomatic arrhythmic episodes. No severe side effects were recorded during the trial period. Conclusion: The antianginal and antiischemic properties of ranolazine are paralleled by significant decreases in the occurrence of both arrhythmias and the related symptoms of palpitations in stable patients with IHD. (ClinicalTrials.gov identifier: NCT01495520).

Local delivery of thrombolytics before thrombectomy in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention — The DISSOLUTION randomized trial

Background: Ranolazine decreases the frequency of arrhythmias during the acute phases of ischemic heart disease (IHD), but it remains unknown if it has similar effects in the chronic phase of the disease. We performed a prospective, randomized, cross-over pilot trial to test the hypothesis that chronic treatment with ranolazine can reduce the incidence of documented arrhythmias and the related symptoms of palpitation in stable patients with IHD. Methods: We randomized 105 patients with stable IHD and symptoms of angina and palpitations already on therapy with betablockers and/or calcium antagonists to ranolazine (750 mg bid, N = 53) or placebo (N = 52) for 30 days (until T-1). After a washout period to avoid any carryover effect, cross-over was performed,and patients were switched to the other drug which was continued for 30 days (until T-2). All patients underwent symptomlimited exercise stress testing and 48-hour ECG Holter monitoring at T1 and T2. During the study period, patients were told to use a OmronN® portable ECG monitor HCG-801 device in case of symptoms of palpitations. Results: Ranolazine reduced the number of anginal episodes more commonly than placebo (5 ± 8 episodes/30 days vs. 21 ± 24 episodes/30 day, p = 0.001) and increased exercise durations at 1 mm ST-segment depression (514 ± 211 s vs. 402 ± 287 s, p = 0.025) and at onset of angina (614 ± 199 s vs. 519 ± 151 s, p = 0.007) at stress testing. These effects were coupled by significant decreases with ranolazine as compared with placebo treatment periods in the occurrence of frequent (N1000 beats) supraventricular arrhythmias (33% vs 52%, p = 0.01) and complex ventricular arrhythmias (17% vs 30%, p = 0.045). Complete resolution of symptoms of palpitations was significantly more common with ranolazine than placebo (31/53 vs 16/52 patients, p = 0.008). Also, portable ECG recordings showed that arrhythmias were less common during ranolazine vs. placebo, with significant decreases in number (7 ± 10 episodes/30 days vs. 23 ± 29 episodes/30 day, p = 0.001) and duration (10 ± 18 min/ 30 days vs. 19 ± 21 min/30 day, p = 0.021) of symptomatic arrhythmic episodes. No severe side effects were recorded during the trial period. Conclusion: The antianginal and antiischemic properties of ranolazine are paralleled by significant decreases in the occurrence of both arrhythmias and the related symptoms of palpitations in stable patients with IHD. (ClinicalTrials.gov identifier: NCT01495520).

Leap motion controlled videogame-based therapy for rehabilitation of elderly patients with subacute stroke: a feasibility pilot study

Background:The leap motion controller (LMC) is a new optoelectronic system for capturing motion of both hands and controlling a virtual environment. Differently from previous devices, it optoelectronically tracks the fine movements of fingers neither using glows nor markers.Objective:This pilot study explored the feasibility of adapting the LMC, developed for videogames, to neurorehabilitation of elderly with subacute stroke.Methods:Four elderly patients (71.50 ± 4.51 years old) affected by stroke in subacute phase were enrolled and tested in a cross-over pilot trial in which six sessions of 30 minutes of LMC videogame-based therapy were added on conventional therapy. Measurements involved participation to the sessions, evaluated by means of the Pittsburgh Rehabilitation Participation Scale, hand ability and grasp force evaluated respectively by means of the Abilhand Scale and by means of the dynamometer.Results:Neither adverse effects nor spasticity increments were observed during LMC training. Participation to the sessions was excellent in three patients and very good in one patient during the LMC trial. In this period, patients showed a significantly higher improvement in hand abilities (P = 0.028) and grasp force (P = 0.006).Conclusions:This feasibility pilot study was the first one using leap motion controller for conducting a videogame-based therapy. This study provided a proof of concept that LMC can be a suitable tool even for elderly patients with subacute stroke. LMC training was in fact performed with a high level of active participation, without adverse effects, and contributed to increase the recovery of hand abilities.

The effects of TeacrineTM, a nature-identical purine alkaloid, on subjective measures of cognitive function, psychometric and hemodynamic indices in healthy humans: a randomized, double-blinded crossover pilot trial

Background Aside from caffeine, there is a relative dearth of evidence regarding natural ingredients that enhance subjective “energy” levels. We have studied a unique, naturally occurring purine alkaloid, present in Camellia assamica variety kucha tea (amongst other botanical sources) that acts on both adenosinergic and dopaminergic pathways that appears to influence multiple neurochemical pathways. As a first step in a series of experiments, we examined the effects of TeaCrine, a nature-identical, chemically equivalent bioactive compound known as theacrine (1,3,7,9-tetramethyluric acid), in humans.

PC-FACS

PC-FACS

Phosphorus supplement alters postprandial lipemia of healthy male subjects: a pilot cross-over trial.

BackgroundEpidemiological studies have found a U-shaped relationship between serum phosphorus and cardiovascular disease (CVD). The mechanism(s) behind such a relationship are poorly understood. Phosphorus (P) is reported to improve insulin sensitivity, which is involved in lipid metabolism, and thus we were interested in determining the impact of phosphorus ingestion on postprandial lipemia, a recognized CVD risk factor.FindingsA within–subject study design was conducted, whereby 8 healthy male subjects received a high fat meal (330Kcal; 69% energy from fat; 35 mg of phosphorus) with placebo or phosphorus (500 mg) in a random order. Postprandial blood samples (~10 ml) were collected every hour for 6 hours after meal ingestion. Changes in different parameters were analyzed using a 2-factor repeated-measure ANOVA. In the phosphorus (P) supplemented group, postprandial serum P increased (p = 0.00), while changes in insulin, non-esterified fatty acids (NEFA) and triglyceride (TG) were not significantly different than that of placebo. Concurrently, phosphorus supplementation increased postprandial concentrations of apolipoprotein B48 (ApoB48) (p < 0.05) and decreased that of apolipoprotein B100 (ApoB100) (p < 0.05).ConclusionsPhosphorus supplementation (500 mg) of the meal seems to alter the different components of postprandial lipemia. These findings highlight the potential role of phosphorus in CVD.

Rivastigmine for Refractory REM Behavior Disorder in Mild Cognitive Impairment

Mild Cognitive Impairment (MCI) and REM Behavior Disorder (RBD) are both associated with a degeneration of ponto-medullary cholinergic pathways. We conducted a placebo-controlled, cross-over pilot trial of Rivastigmine (RVT) in 25 consecutive patients with MCI, who presented RBD refractory to conventional first-line treatments (melatonin up to 5 mg/day and clonazepam up to 2 mg/day). RVT treatment was followed by a significant reduction of RBD episodes when compared with placebo. Our data suggest that, in MCI patients with RBD resistant to conventional therapies (muscle relaxants benzodiazepines or melatonin,) treatment with RVT may induce a reduction in the frequency of RBD episodes compared to placebo.

Somatropin treatment of spinal muscular atrophy: A placebo-controlled, double-blind crossover pilot study

In preclinical studies growth hormone and its primary mediator IGF-1 have shown potential to increase muscle mass and strength. A single patient with spinal muscular atrophy reported benefit after compassionate use of growth hormone. Therefore we evaluated the efficacy and safety of growth hormone treatment for spinal muscular atrophy in a multicenter, randomised, double-blind, placebo-controlled, crossover pilot trial. Patients (n=19) with type II/III spinal muscular atrophy were randomised to receive either somatropin (0.03mg/kg/day) or placebo subcutaneously for 3months, followed by a 2-month wash-out phase before 3months of treatment with the contrary remedy. Changes in upper limb muscle strength (megascore for elbow flexion and hand-grip in Newton) were assessed by hand-held myometry as the primary measure of outcome. Secondary outcome measures included lower limb muscle strength, motor function using the Hammersmith Functional Motor Scale and other functional tests for motor function and pulmonary function. Somatropin treatment did not significantly affect upper limb muscle strength (point estimate mean: 0.08N, 95% confidence interval (CI:−3.79;3.95, p=0.965), lower limb muscle strength (point estimate mean: 2.23N, CI:−2.19;6.63, p=0.302) or muscle and pulmonary function. Side effects occurring during somatropin treatment corresponded with well-known side effects of growth hormone substitution in patients with growth hormone deficiency. In this pilot study, growth hormone treatment did not improve muscle strength or function in patients with spinal muscular atrophy type II/III.

Local delivery of thrombolytics before thrombectomy in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention - the dissolution randomized trial

Background: Ranolazine decreases the frequency of arrhythmias during the acute phases of ischemic heart disease (IHD), but it remains unknown if it has similar effects in the chronic phase of the disease. We performed a prospective, randomized, cross-over pilot trial to test the hypothesis that chronic treatment with ranolazine can reduce the incidence of documented arrhythmias and the related symptoms of palpitation in stable patients with IHD. Methods: We randomized 105 patients with stable IHD and symptoms of angina and palpitations already on therapy with betablockers and/or calcium antagonists to ranolazine (750 mg bid, N = 53) or placebo (N = 52) for 30 days (until T-1). After a washout period to avoid any carryover effect, cross-over was performed,and patients were switched to the other drug which was continued for 30 days (until T-2). All patients underwent symptomlimited exercise stress testing and 48-hour ECG Holter monitoring at T1 and T2. During the study period, patients were told to use a OmronN® portable ECG monitor HCG-801 device in case of symptoms of palpitations. Results: Ranolazine reduced the number of anginal episodes more commonly than placebo (5 ± 8 episodes/30 days vs. 21 ± 24 episodes/30 day, p = 0.001) and increased exercise durations at 1 mm ST-segment depression (514 ± 211 s vs. 402 ± 287 s, p = 0.025) and at onset of angina (614 ± 199 s vs. 519 ± 151 s, p = 0.007) at stress testing. These effects were coupled by significant decreases with ranolazine as compared with placebo treatment periods in the occurrence of frequent (N1000 beats) supraventricular arrhythmias (33% vs 52%, p = 0.01) and complex ventricular arrhythmias (17% vs 30%, p = 0.045). Complete resolution of symptoms of palpitations was significantly more common with ranolazine than placebo (31/53 vs 16/52 patients, p = 0.008). Also, portable ECG recordings showed that arrhythmias were less common during ranolazine vs. placebo, with significant decreases in number (7 ± 10 episodes/30 days vs. 23 ± 29 episodes/30 day, p = 0.001) and duration (10 ± 18 min/ 30 days vs. 19 ± 21 min/30 day, p = 0.021) of symptomatic arrhythmic episodes. No severe side effects were recorded during the trial period. Conclusion: The antianginal and antiischemic properties of ranolazine are paralleled by significant decreases in the occurrence of both arrhythmias and the related symptoms of palpitations in stable patients with IHD. (ClinicalTrials.gov identifier: NCT01495520).

Facilitated tucking on pain in pre-term newborns during neonatal intensive care: A single blinded randomized controlled cross-over pilot trial

To determine the effect of facilitated tucking (FT) on pain in preterm newborns during heel stick procedure done as a part of neonatal intensive care. This randomized controlled cross-over pilot study included 20 preterm newborns of both sexes between gestational ages (GA) of 28 and 36 weeks based upon the eligibility criteria. Pain was measured using Premature Infant Pain Profile (PIPP) following both heel stick with FT and without FT. The newborns had a lower PIPP score at 30 seconds (Mean, SD: 8.80, 3.82), 60 seconds (Mean, SD: 7.55, 3.28), 90 seconds (Mean, SD: 7.25, 3.06) and 120 seconds (Mean, SD: 6.65, 3.05) when heel stick was done with FT compared to the same procedure done without FT at 30 seconds (Mean, SD: 11.20, 3.44), 60 seconds (Mean, SD: 10.75, 3.24), 90 seconds (Mean, SD: 10.60, 3.22) and 120 seconds (Mean, SD: 10.50, 3.15). A (2 X 4) factorial ANOVA showed a statistically significant difference between these two procedures in all the time periods viz., 30 seconds (p=0.044), 60 seconds (p=0.004), 90 seconds (p=0.002) and 120 seconds (p< 0.0001) at 0.05 level in PIPP score and favoring FT. FT is an effective non-pharmacological pain management in preterm newborns during routine neonatal intensive care.

Open label, randomized, crossover pilot trial of high-resolution, relational, resonance-based, electroencephalic mirroring to relieve insomnia.

Effective noninvasive interventions for insomnia are needed. High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM™) is a noninvasive, electroencephalography (EEG)-based method to facilitate greater client-unique, autocalibrated improvements of balance and harmony in cortical neural oscillations. This study explores using HIRREM for insomnia. Twenty subjects, with an Insomnia Severity Index (ISI) score of ≥15 (14 women, mean age 45.4, mean ISI 18.6), were enrolled in this randomized, unblinded, wait-list control, crossover, superiority study. Subjects were randomized to receive 8–12 HIRREM sessions over 3 weeks, plus usual care (HUC), or usual care alone (UC). Pre- and post-HIRREM data collection included ISI (primary outcome), and many secondary, exploratory measures (CES-D, SF-36, HR, BP, neurocognitive testing, and VAS scales). The UC group later crossed over to receive HIRREM. ISI was also repeated 4–6 weeks post-HIRREM. All subjects completed the primary intervention period. Analysis for differential change of ISI in the initial intervention period for HUC versus UC showed a drop of 10.3 points (95% CI: −13.7 to −6.9, P < 0.0001, standardized effect size of 2.68). Key secondary outcomes included statistically identical differential change for the crossed-over UC group, and persistence of the effect on the ISI up to > 4 weeks post-HIRREM. Differential change in the HUC group was also statistically significant for CES-D (−8.8, 95% CI: −17.5 to −0.1, P = 0.047), but other exploratory outcomes were not statistically significant. For all receiving HIRREM (n = 19), decreased high-frequency total power was seen in the bilateral temporal lobes. No adverse events were seen. This pilot clinical trial, the first using HIRREM as an intervention, suggests that HIRREM is feasible and effective for individuals having moderate-to-severe insomnia, with clinically relevant, statistically significant benefits based on differential change in the ISI. Effects persisted for 4 weeks after completion of HIRREM. Larger controlled clinical trials are warranted.

Take a walk in the park? A cross-over pilot trial comparing brisk walking in two different environments: Park and urban

ObjectiveThe objective of the present study is to investigate whether differences exist between a 30minute brisk walk taken in two different environments in order to determine which environment best facilitates current physical activity guidelines: park or urban. MethodsIn this randomised cross-over pilot study, participants performed a self-timed 30minute brisk walk in two different environments, park and urban, in Glasgow, Scotland (October 2009 to January 2010). Cadence, recorded using the activPAL™ activity monitor, was used to measure intensity. Outcome measures were: mean cadence; moderate-to-vigorous physical activity time accumulated in bouts lasting ≥10min; number of walking breaks; and duration. ResultsA convenience sample of 40 healthy adults was recruited: 16 males, 24 females, mean age 22.9 (5.5) years. The mean cadence for the whole walk was higher in the park: 119.3 (8.3) vs. 110.9 (8.9) steps/min. Participants accumulated more moderate‐to‐vigorous physical activity in ≥10minute bouts during park walks: 25.5 (9.6) [median (interquartile range)] vs. 14.0 (20.3) min. There was no difference in self-timed duration between locations. ConclusionParticipants accumulated more moderate‐to‐vigorous physical activity in bouts ≥10min in duration on park walks due to the lack of interruptions in walking. Hence the park environment better facilitated the achievement of current physical activity guidelines. Further research involving a larger, more heterogeneous sample is recommended.

Does acupuncture activate endogenous analgesia in chronic whiplash‐associated disorders? A randomized crossover trial

Many patients with chronic pain, including those with chronic whiplash-associated disorders (WAD), show features of central sensitization. Randomized trials examining whether treatments are able to influence the process of central sensitization in patients with chronic WAD are emerging. Therefore, the present study aimed at examining whether acupuncture results in activation of endogenous analgesia and relief in symptoms in patients with chronic WAD. In this randomized crossover pilot trial with blinded assessors, each patient (n = 39) received two treatment sessions of identical duration, with acupuncture and relaxation therapy randomly crossed over in visit 2. Primary outcome measurement included immediate activation of endogenous analgesia i.e., pressure pain sensitivity and conditioned pain modulation. Secondary outcome measurements included pain relief and reduced disability level. Local pressure pain sensitivity at baseline and during conditioned pain modulation decreased significantly more following acupuncture compared with relaxation (time × group interactions: p < 0.001), both in the neck and at a site distinct from the painful region. When comparing the effects of acupuncture versus relaxation, no differences were observed on conditioned pain modulation, temporal summation of pressure pain, neck disability or symptom severity (all p-values >0.05). It was shown that one session of acupuncture treatment results in acute improvements in pressure pain sensitivity in the neck and calf of patients with chronic WAD. Acupuncture had no effect on conditioned pain modulation or temporal summation of pressure pain. Both acupuncture and relaxation appear to be well-tolerated treatments for people with chronic WAD. These findings suggest that acupuncture treatment activates endogenous analgesia in patients with chronic WAD.

Acupoint Injection of vitamin K1 for primary dysmenorrhoea: feasibility and acceptability results of a pilot crossover trial in the US

Acupoint Injection of vitamin K1 for primary dysmenorrhoea: feasibility and acceptability results of a pilot crossover trial in the US