Randomized controlled trial of full and brief cognitive-behaviour therapy and wait-list for paediatric obsessive-compulsive disorder

Background: Reviews and practice guidelines for paediatric obsessive-compulsive disorder (OCD) recommend cognitive-behaviour therapy (CBT) as the psychological treatment of choice, but note that it has not been sufficiently evaluated for children and adolescents and that more randomized controlled trials are needed. The aim of this trial was to evaluate effectiveness and optimal delivery of CBT, emphasizing cognitive interventions. Methods: A total of 96 children and adolescents with OCD were randomly allocated to the three conditions each of approximately 12 weeks duration: full CBT (average therapist contact: 12 sessions) and brief CBT (average contact: 5 sessions, with use of therapist-guided workbooks), and wait-list/delayed treatment. The primary outcome measure was the child version of the semi-structured interviewer-based Yale-Brown Obsessive Compulsive Scale. Clinical Trial registration: http://www.controlled-trials.com/ISRCTN/; unique identifier: ISRCTN29092580. Results: There was statistically significant symptomatic improvement in both treatment groups compared with the wait-list group, with no significant differences in outcomes between the two treatment groups. Controlled treatment effect sizes in intention-to-treat analyses were 2.2 for full CBT and 1.6 for brief CBT. Improvements were maintained at follow-up an average of 14 weeks later. Conclusions: The findings demonstrate the benefits of CBT emphasizing cognitive interventions for children and adolescents with OCD and suggest that relatively lower therapist intensity delivery with use of therapist-guided workbooks is an efficient mode of delivery.

Effects of acute consumption of a fruit and vegetable puree-based drink on vasodilation and oxidative status

Epidemiological studies indicate that diets rich in fruits and vegetables (F&V) are protective against cardiovascular diseases (CVD). Pureed F&V products retain many beneficial components, including flavonoids, carotenoids, vitamin C and dietary fibres. This study aimed to establish the physiological effects of acute ingestion of F&V puree-based drink (FVPD) on vasodilation, antioxidant status, phytochemical bioavailability and other CVD risk factors. 24 Subjects, aged 30-70 years, completed the randomised, single-blind, controlled, crossover test meal study. Subjects consumed 400 ml FVPD, or fruit-flavoured sugar-matched control, after following a low-flavonoid diet for 5 days. Blood and urine samples were collected throughout the study day and vascular reactivity was assessed at 90-minute intervals using laser Doppler iontophoresis (LDI). FVPD significantly increased plasma vitamin C (P=0.002) and total nitrate/nitrite (P=0.001) concentrations. There was a near significant time by treatment effect on ex vivo LDL oxidation (P=0.068), with a longer lag phase after consuming FVPD. During the 6 hours after juice consumption the antioxidant capacity of plasma increased significantly (P=0.003) and there was a simultaneous increase in plasma and urinary phenolic metabolites (P<0.05). There were significantly lower glucose and insulin peaks after ingestion of FVPD compared with control (P=0.019 and P=0.003) and a trend towards increased endothelium-dependent vasodilation following FVPD consumption (P=0.061). Overall, FVPD consumption significantly increased plasma vitamin C and total nitrate/nitrite concentrations, with a trend towards increased endothelium-dependent vasodilation. Pureed F&V products are useful vehicles for increasing micronutrient status, plasma antioxidant capacity and in vivo NO generation, which may contribute to CVD risk reduction.

Effects of non-host plant odour on Meligethes aeneus during immigration to oilseed rape

The use of semiochemicals for the manipulation of the pollen beetle, Meliethes aeneus (Fabricius) (Coleoptera: Nitidulidae), is being investigated for potential incorporation into a push-pull strategy for this pest, which damages oilseed rape, Brassica napus L. (Brassicaceae), throughout Europe. Previous laboratory behavioural studies using volatiles from non-host plants showed that M. aeneus is repelled by the odour of lavender, Lavendula angustifolia Mill. (Lamiaceae), essential oil. This article reports on semi-field and field trials to investigate this behaviour under more realistic conditions. Semi-field experiments were conducted to assess the relative importance of olfaction at different points in host location behaviour by M. aeneus. The results showed that oilseed rape plants treated with lavender odour were less colonised by M. aeneus in comparison with an untreated control, but that the treatment effect was much reduced if the lavender odour was applied after colonisation. The field experiment demonstrated that lavender odour caused a significant reduction in the number of adultM. aeneus infesting the oilseed rape plants in the treatment plots compared to the control plots. Overall, these findings are very encouraging for the future development of a push-pull pest control system.

Cortical thickness changes in the non-lesioned hemisphere associated with non-paretic arm immobilization in modified CI therapy

Recent evidence suggests that immobilization of the upper limb for 2–3 weeks induces changes in cortical thickness as well as motor performance. In constraint induced (CI) therapy, one of the most effective interventions for hemiplegia, the non-paretic arm is constrained to enforce the use of the paretic arm in the home setting. With the present study we aimed to explore whether non-paretic arm immobilization in CI therapy induces structural changes in the non-lesioned hemisphere, and how these changes are related to treatment benefit. 31 patients with chronic hemiparesis participated in CI therapy with (N = 14) and without (N = 17) constraint. Motor ability scores were acquired before and after treatment. Diffusion tensor imaging (DTI) data was obtained prior to treatment. Cortical thickness was measured with the Freesurfer software. In both groups cortical thickness in the contralesional primary somatosensory cortex increased and motor function improved with the intervention. However the cortical thickness change was not associated with the magnitude of motor function improvement. Moreover, the treatment effect and the cortical thickness change were not significantly different between the constraint and the non-constraint groups. There was no correlation between fractional anisotropy changes in the non-lesioned hemisphere and treatment outcome. CI therapy induced cortical thickness changes in contralesional sensorimotor regions, but this effect does not appear to be driven by the immobilization of the non-paretic arm, as indicated by the absence of differences between the constraint and the non-constraint groups. Our data does not suggest that the arm immobilization used in CI therapy is associated with noticeable cortical thinning.

Habitat manipulation in lowland rice-coconut cropping systems of the Philippines: an effective rodent pest management strategy?

BACKGROUND: Reduction of vegetation height is recommended as a management strategy for controlling rodent pests of rice in South-east Asia, but there are limited field data to assess its effectiveness. The breeding biology of the main pest species of rodent in the Philippines, Rattus tanezumi, suggests that habitat manipulation in irrigated rice–coconut cropping systems may be an effective strategy to limit the quality and availability of their nesting habitat. The authors imposed a replicated manipulation of vegetation cover in adjacent coconut groves during a single rice-cropping season, and added artificial nest sites to facilitate capture and culling of young. RESULTS: Three trapping sessions in four rice fields (two treatments, two controls) adjacent to coconut groves led to the capture of 176 R. tanezumi, 12Rattus exulans and seven Chrotomysmindorensis individuals. There was no significant difference in overall abundance between crop stages or between treatments, and there was no treatment effect on damage to tillers or rice yield. Only two R. tanezumi were caught at the artificial nest sites. CONCLUSION: Habitat manipulation to reduce the quality of R. tanezumi nesting habitat adjacent to rice fields is not effective as a lone rodent management tool in rice–coconut cropping systems.

Casein-derived lactotripeptides reduce systolic and diastolic blood pressure in a meta-analysis of randomised clinical trials

There is an urgent need to treat individuals with high blood pressure (BP) with effective dietary strategies. Previous studies suggest a small, but significant decrease in BP after lactotripeptides (LTP) ingestion, although the data are inconsistent. The study aim was to perform a comprehensive meta-analysis of data from all relevant randomised controlled trials (RCT). Medline, Cochrane library, EMBASE and Web of Science were searched until May 2014. Eligibility criteria were RCT that examined the effects of LTP on BP in adults, with systolic BP (SBP) and diastolic BP (DBP) as outcome measures. Thirty RCT met the inclusion criteria, which resulted in 33 sets of data. The pooled treatment effect for SBP was −2.95 mmHg (95% CI: −4.17, −1.73; p < 0.001), and for DBP was −1.51 mmHg (95% CI: −2.21, −0.80; p < 0.001). Sub-group analyses revealed that reduction of BP in Japanese studies was significantly greater, compared with European studies (p = 0.002 for SBP and p < 0.001 for DBP). The 24-h ambulatory BP (AMBP) response to LTP supplementation was statistically non-significant (p = 0.101 for SBP and p = 0.166 for DBP). Both publication bias and “small-study effect” were identified, which shifted the treatment effect towards less significant SBP and non-significant DBP reduction after LTP consumption. LTP may be effective in BP reduction, especially in Japanese individuals; however sub-group, meta-regression analyses and statistically significant publication biases suggest inconsistencies.

Sample size considerations in active-control non-inferiority trials with binary data based on the odds ratio

This paper presents an approximate closed form sample size formula for determining non-inferiority in active-control trials with binary data. We use the odds-ratio as the measure of the relative treatment effect, derive the sample size formula based on the score test and compare it with a second, well-known formula based on the Wald test. Both closed form formulae are compared with simulations based on the likelihood ratio test. Within the range of parameter values investigated, the score test closed form formula is reasonably accurate when non-inferiority margins are based on odds-ratios of about 0.5 or above and when the magnitude of the odds ratio under the alternative hypothesis lies between about 1 and 2.5. The accuracy generally decreases as the odds ratio under the alternative hypothesis moves upwards from 1. As the non-inferiority margin odds ratio decreases from 0.5, the score test closed form formula increasingly overestimates the sample size irrespective of the magnitude of the odds ratio under the alternative hypothesis. The Wald test closed form formula is also reasonably accurate in the cases where the score test closed form formula works well. Outside these scenarios, the Wald test closed form formula can either underestimate or overestimate the sample size, depending on the magnitude of the non-inferiority margin odds ratio and the odds ratio under the alternative hypothesis. Although neither approximation is accurate for all cases, both approaches lead to satisfactory sample size calculation for non-inferiority trials with binary data where the odds ratio is the parameter of interest.

Randomized control trials in an imperfect world

Randomized control trials (RCTs) have become increasingly important as an evidence-based method to evaluate interventions such as government programs and policy initiatives. Frequently, however, RCTs are characterized by ``imperfect compliance'' in that not all the subjects who are randomly assigned to take a treatment choose to do so. This could result in a failure to identify the treatment effect, or the impact of the treatment on the the population. However, useful information on treatment effectiveness can still be recovered by estimating ``bounds'' or a range of values in which treatment effectiveness can lie.

Intake, water consumption, ruminal fermentation, and stress response of beef heifers fed after different lengths of delays in the daily feed delivery time

Four rumen-fistulated Holstein heifers (134 +/- 1 kg initial BW) were used in a 4 x 4 Latin square design to determine the effects of delaying daily feed delivery time on intake, ruminal fermentation, behavior, and stress response. Each 3-wk experimental period was preceded by 1 wk in which all animals were fed at 0800 h. Feed bunks were cleaned at 0745 h and feed offered at 0800 h (T0, no delay), 0900 (T1), 1000 (T2), and 1100 (T3) from d1 to 21 with measurements taken during wk 1 and 3. Heifers were able to see each other at all times. Concentrate and barley straw were offered in separate compartments of the feed bunks, once daily and for ad libitum intake. Ruminal pH and saliva cortisol concentrations were measured at 0, 4, 8, and 12 h postfeeding on d 3 and 17 of each experimental period. Fecal glucocorticoid metabolites were measured on d 17. Increasing length of delay in daily feed delivery time resulted in a quadratic response in concentrate DMI (low in T1 and T2; P = 0.002), whereas straw DMI was greatest in T1 and T3 (cubic P = 0.03). Treatments affected the distribution of DMI within the day with a linear decrease observed between 0800 and 1200 h but a linear increase during nighttimes (2000 to 0800 h), whereas T1 and T2 had reduced DMI between 1200 and 1600 h (quadratic P = 0.04). Water consumption (L/d) was not affected but decreased linearly when expressed as liters per kilogram of DMI (P = 0.01). Meal length was greatest and eating rate slowest in T1 and T2 (quadratic P <= 0.001). Size of the first meal after feed delivery was reduced in T1 on d 1 (cubic P = 0.05) and decreased linearly on d 2 (P = 0.01) after change. Concentrate eating and drinking time (shortest in T1) and straw eating time (longest in T1) followed a cubic trend (P = 0.02). Time spent lying down was shortest and ruminating in standing position longest in T1 and T2. Delay of feeding time resulted in greater daily maximum salivary cortisol concentration (quadratic P = 0.04), which was greatest at 0 h in T1 and at 12 h after feeding in T2 (P < 0.05). Daily mean fecal glucocorticoid metabolites were greatest in T1 and T3 (cubic P = 0.04). Ruminal pH showed a treatment effect at wk 1 because of increased values in T1 and T3 (cubic P = 0.01). Delaying feed delivery time was not detrimental for rumen function because a stress response was triggered, which led to reduced concentrate intake, eating rate, and size of first meal, and increased straw intake. Increased salivary cortisol suggests that animal welfare is compromised.

Employment Protection Legislation and Firm Growth : Evidence from a Natural Experiment

A natural experiment is used to identify the causal relationship between employment protection legislation and fi…rm growth. The natural experiment occurred in Sweden in 2001, when an exemption made it possible for fi…rms with less than eleven employees to exclude two workers from the last-in-fi…rst-out principle when dismissing personnel. The estimated average treatment effect of the reform show that the number of employees increased with 0.135 percent in fi…rms with 5-9 employees relative to fi…rms with 10-15 employees, which corresponds to over 5,000 additional jobs per year created by the reform. Firms with ten employees, just below the size threshold, became 3.4 percent less likely to increase their workforce to a level surpassing the threshold, indicating that the last-in-…first-out rule prevented these …firms from growing. Thus, employment protection legislation seems to act as a growth barrier for small fi…rms.

Adrenaline increases skeletal muscle glycogenolysis, pyruvate dehydrogenase activation and carbohydrate oxidation during moderate exercise in humans

# 1.
To evaluate the role of adrenaline in regulating carbohydrate metabolism during moderate exercise, 10 moderately trained men completed two 20 min exercise bouts at 58 ± 2 % peak pulmonary oxygen uptake (̇V_o2,peak). On one occasion saline was infused (CON), and on the other adrenaline was infused intravenously for 5 min prior to and throughout exercise (ADR). Glucose kinetics were measured by a primed, continuous infusion of 6,6-[2H]glucose and muscle samples were obtained prior to and at 1 and 20 min of exercise.

# 2.
The infusion of adrenaline elevated (P < 0.01) plasma adrenaline concentrations at rest (pre-infusion, 0.28 ± 0.09; post-infusion, 1.70 ± 0.45 nmol l−1; means ±s.e.m.) and this effect was maintained throughout exercise. Total carbohydrate oxidation increased by 18 % and this effect was due to greater skeletal muscle glycogenolysis (P < 0.05) and pyruvate dehydrogenase (PDH) activation (P < 0.05, treatment effect). Glucose rate of appearance was not different between trials, but the infusion of adrenaline decreased (P < 0.05, treatment effect) skeletal muscle glucose uptake in ADR.

# 3.
During exercise muscle glucose 6-phosphate (G-6-P) (P = 0.055, treatment effect) and lactate (P < 0.05) were elevated in ADR compared with CON and no changes were observed for pyruvate, creatine, phosphocreatine, ATP and the calculated free concentrations of ADP and AMP.

# 4.
The data demonstrate that elevated plasma adrenaline levels during moderate exercise in untrained men increase skeletal muscle glycogen breakdown and PDH activation, which results in greater carbohydrate oxidation. The greater muscle glycogenolysis appears to be due to increased glycogen phosphorylase transformation whilst the increased PDH activity cannot be readily explained. Finally, the decreased glucose uptake observed during exercise in ADR is likely to be due to the increased intracellular G-6-P and a subsequent decrease in glucose phosphorylation.

Use of calcium or calcuim in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis

Background:  Whether calcium supplementation can reduce osteoporotic fractures is uncertain. We did a meta-analysis to include all the randomised trials in which calcium, or calcium in combination with vitamin D, was used to prevent fracture and osteoporotic bone loss.

Methods:  We identified 29 randomised trials (n=63 897) using electronic databases, supplemented by a hand-search of reference lists, review articles, and conference abstracts. All randomised trials that recruited people aged 50 years or older were eligible. The main outcomes were fractures of all types and percentage change of bone-mineral density from baseline. Data were pooled by use of a random-effect model.

Findings:  In trials that reported fracture as an outcome (17 trials, n=52 625), treatment was associated with a 12% risk reduction in fractures of all types (risk ratio 0·88, 95% CI 0·83–0·95; p=0·0004). In trials that reported bone-mineral density as an outcome (23 trials, n=41 419), the treatment was associated with a reduced rate of bone loss of 0·54% (0·35–0·73; p<0·0001) at the hip and 1·19% (0·76–1·61%; p<0·0001) in the spine. The fracture risk reduction was significantly greater (24%) in trials in which the compliance rate was high (p<0·0001). The treatment effect was better with calcium doses of 1200 mg or more than with doses less than 1200 mg (0·80 vs 0·94; p=0·006), and with vitamin D doses of 800 IU or more than with doses less than 800 IU (0·84 vs 0·87; p=0·03).

Interpretation:  Evidence supports the use of calcium, or calcium in combination with vitamin D supplementation, in the preventive treatment of osteoporosis in people aged 50 years or older. For best therapeutic effect, we recommend minimum doses of 1200 mg of calcium, and 800 IU of vitamin D (for combined calcium plus vitamin D supplementation).

Feed intake, growth, plasma glucose and urea nitrogen concentration, and cacass traits of lambs fed isoenergetic amounts of canola meal, soybean meal, and fish meal with forage based diet.

This experiment was conducted to examine the effect of feeding small, isoenergetic amounts of supplements containing high protein and functional lipid components, rather than the greater amounts of cereal and/or legume grains usually fed during the dry season in Australia, on dry matter intake (DMI), growth performance, plasma metabolites, and fat deposition in lambs consuming low quality roughage. Thirty two crossbred wether lambs ([Merino × Border Leicester] × Poll Dorset) were divided into four groups by stratified randomization according to liveweight (26–33 kg). After a 7-day adaptation to a hay diet (lucerne hay:oaten hay; 30:70), lambs were allocated to four treatments consisting of (1) basal diet of lucerne hay:oat hay (20:80; metabolizable energy (ME) = 7.0 MJ/kg DM), Basal; (2) basal + canola meal (84 g per day), CM; (3) basal + soymeal (75 g per day), SM; or (4) basal + fishmeal (80 g per day), FM. Daily hay and supplement DMI, and weekly liveweight were recorded during a 53-day experimental study. Blood samples were taken on day 1 and pre- and post-feeding on days 30 and 53 to measure changes in plasma glucose and plasma urea nitrogen (PUN) concentration. At the end of the experiment, lambs were slaughtered and hot carcass weight (HCW) recorded; cold carcass fatness (total muscle and adipose tissue depth at 12th rib, 110 mm from midline; GR) was determined at 24 h postmortem. Total DMI was increased (P < 0.001) in CM, SM and FM treatments, but basal hay DMI intake was only increased (P < 0.01) in CM and FM treatments compared with Basal treatment. This resulted in significant (P < 0.01) increases in metabolizable energy (ME) and crude protein (CP) intakes in all supplemented treatments, with the highest intakes recorded in the FM treatment. Liveweight gain (LWG) was significantly increased in CM and SM (P < 0.05) and FM (P < 0.01) treatments but HCW was significantly (P < 0.01) heavier slaughter only in the FM treatment. Feed conversion efficiency (P < 0.001) and GR fat at depth (P < 0.05) was reduced in all supplement treatments compared with Basal. Plasma glucose concentration was significantly (P < 0.05) increased after feeding in all treatments but there was no treatment effect. PUN was significantly increased over time in the supplemented treatments compared with the Basal treatment; there was no significant difference between supplement treatments by day 53. Results show that feeding small amounts of high protein and lipid-containing supplements improves production responses and are beneficial in producing carcasses with more lean compared with carcasses from lambs fed a low quality hay diet.

Parametric conditional frailty models for recurrent cardiovascular events in the lipid study

Background Analysis of recurrent event data is frequently needed in clinical and epidemiological studies. An important issue in such analysis is how to account for the dependence of the events in an individual and any unobserved heterogeneity of the event propensity across individuals.Methods We applied a number of conditional frailty and nonfrailty models in an analysis involving recurrent myocardial infarction events in the Long-Term Intervention with Pravastatin in Ischaemic Disease study. A multiple variable risk prediction model was developed for both males and females. Results A Weibull model with a gamma frailty term fitted the data better than other frailty models for each gender. Among nonfrailty models the stratified survival model fitted the data best for each gender. The relative risk estimated by the elapsed time model was close to that estimated by the gap time model. We found that a cholesterol-lowering drug, pravastatin (the intervention being tested in the trial) had significant protective effect against the occurrence of myocardial infarction in men (HR¼0.71, 95% CI0.60–0.83). However, the treatment effect was not significant in women due to smaller sample size (HR¼0.75, 95% CI 0.51–1.10). There were no significant interactions between the treatment effect and each recurrent MI event (p¼0.24 for men and p¼0.55 for women). The risk of developing an MI event for a male who had an MI event during follow-up was about 3.4 (95% CI 2.6–4.4) times the risk compared with those who did not have an MI event. The corresponding relative risk for a female was about 7.8 (95% CI 4.4–13.6). Limitations The number of female patients was relatively small compared with their male counterparts, which may result in low statistical power to find real differences in the effect of treatment and other potential risk factors.Conclusions The conditional frailty model suggested that after accounting for all the risk factors in the model, there was still unmeasured heterogeneity of the risk for myocardial infarction, indicating the effect of subject-specific risk factors. These risk prediction models can be used to classify cardiovascular disease patients into different risk categories and may be useful for the most effective targeting of preventive therapies for cardiovascular disease.

Bivariate variance-component analysis, with application to systolic blood pressure and total cholesterol levels in the Framingham Heart Study

Background :
The correlations between systolic blood pressure (SBP) and total cholesterol levels (CHOL) might result from genetic or environmental factors that determine variation in the phenotypes and are shared by family members. Based on 330 nuclear families in the Framingham Heart Study, we used a multivariate normal model, implemented in the software FISHER, to estimate genetic and shared environmental components of variation and genetic and shared environmental correlation between the phenotypes. The natural logarithm of the phenotypes measured at the last visit in both Cohort 1 and 2 was used in the analyses. The antihypertensive treatment effect was corrected before adjustment of the systolic blood pressure for age, sex, and cohort.
Results :
The univariate correlation coefficient was statistically significant for sibling pairs and parent-offspring pairs, but not significant for spouse pairs. In the bivariate analysis, the cross-trait correlation coefficients were not statistically significant for all relative pairs. The shared environmental correlation was statistically significant, but the genetic correlation was not significant.
Conclusion :
There is no significant evidence for a close genetic correlation between systolic blood pressure and total cholesterol levels. However, some shared environmental factors may determine the variation of both phenotypes.