Energy compensation following consumption of sugar-reduced products: a randomized controlled trial

PURPOSE: Consumption of sugar-reformulated products (commercially available foods and beverages that have been reduced in sugar content through reformulation) is a potential strategy for lowering sugar intake at a population level. The impact of sugar-reformulated products on body weight, energy balance (EB) dynamics and cardiovascular disease risk indicators has yet to be established. The REFORMulated foods (REFORM) study examined the impact of an 8-week sugar-reformulated product exchange on body weight, EB dynamics, blood pressure, arterial stiffness, glycemia and lipemia. METHODS: A randomized, controlled, double-blind, crossover dietary intervention study was performed with fifty healthy normal to overweight men and women (age 32.0 ± 9.8 year, BMI 23.5 ± 3.0 kg/m2) who were randomly assigned to consume either regular sugar or sugar-reduced foods and beverages for 8 weeks, separated by 4-week washout period. Body weight, energy intake (EI), energy expenditure and vascular markers were assessed at baseline and after both interventions. RESULTS: We found that carbohydrate (P < 0.001), total sugars (P < 0.001) and non-milk extrinsic sugars (P < 0.001) (% EI) were lower, whereas fat (P = 0.001) and protein (P = 0.038) intakes (% EI) were higher on the sugar-reduced than the regular diet. No effects on body weight, blood pressure, arterial stiffness, fasting glycemia or lipemia were observed. CONCLUSIONS: Consumption of sugar-reduced products, as part of a blinded dietary exchange for an 8-week period, resulted in a significant reduction in sugar intake. Body weight did not change significantly, which we propose was due to energy compensation.

An investigation of the shortcomings of the CONSORT 2010 statement for the reporting of group sequential randomised controlled trials: a methodological systematic review

Background It can be argued that adaptive designs are underused in clinical research. We have explored concerns related to inadequate reporting of such trials, which may influence their uptake. Through a careful examination of the literature, we evaluated the standards of reporting of group sequential (GS) randomised controlled trials, one form of a confirmatory adaptive design. Methods We undertook a systematic review, by searching Ovid MEDLINE from the 1st January 2001 to 23rd September 2014, supplemented with trials from an audit study. We included parallel group, confirmatory, GS trials that were prospectively designed using a Frequentist approach. Eligible trials were examined for compliance in their reporting against the CONSORT 2010 checklist. In addition, as part of our evaluation, we developed a supplementary checklist to explicitly capture group sequential specific reporting aspects, and investigated how these are currently being reported. Results Of the 284 screened trials, 68(24%) were eligible. Most trials were published in “high impact” peer-reviewed journals. Examination of trials established that 46(68%) were stopped early, predominantly either for futility or efficacy. Suboptimal reporting compliance was found in general items relating to: access to full trials protocols; methods to generate randomisation list(s); details of randomisation concealment, and its implementation. Benchmarking against the supplementary checklist, GS aspects were largely inadequately reported. Only 3(7%) trials which stopped early reported use of statistical bias correction. Moreover, 52(76%) trials failed to disclose methods used to minimise the risk of operational bias, due to the knowledge or leakage of interim results. Occurrence of changes to trial methods and outcomes could not be determined in most trials, due to inaccessible protocols and amendments. Discussion and Conclusions There are issues with the reporting of GS trials, particularly those specific to the conduct of interim analyses. Suboptimal reporting of bias correction methods could potentially imply most GS trials stopping early are giving biased results of treatment effects. As a result, research consumers may question credibility of findings to change practice when trials are stopped early. These issues could be alleviated through a CONSORT extension. Assurance of scientific rigour through transparent adequate reporting is paramount to the credibility of findings from adaptive trials. Our systematic literature search was restricted to one database due to resource constraints.

Changes in physical activity following a genetic-based internet-delivered personalized intervention: randomized controlled trial (Food4Me)

Background: There is evidence that physical activity (PA) can attenuate the influence of the fat mass- and obesity-associated (FTO) genotype on the risk to develop obesity. However, whether providing personalized information on FTO genotype leads to changes in PA is unknown. Objective: The purpose of this study was to determine if disclosing FTO risk had an impact on change in PA following a 6-month intervention. Methods: The single nucleotide polymorphism (SNP) rs9939609 in the FTO gene was genotyped in 1279 participants of the Food4Me study, a four-arm, Web-based randomized controlled trial (RCT) in 7 European countries on the effects of personalized advice on nutrition and PA. PA was measured objectively using a TracmorD accelerometer and was self-reported using the Baecke questionnaire at baseline and 6 months. Differences in baseline PA variables between risk (AA and AT genotypes) and nonrisk (TT genotype) carriers were tested using multiple linear regression. Impact of FTO risk disclosure on PA change at 6 months was assessed among participants with inadequate PA, by including an interaction term in the model: disclosure (yes/no) × FTO risk (yes/no). Results: At baseline, data on PA were available for 874 and 405 participants with the risk and nonrisk FTO genotypes, respectively. There were no significant differences in objectively measured or self-reported baseline PA between risk and nonrisk carriers. A total of 807 (72.05%) of the participants out of 1120 in the personalized groups were encouraged to increase PA at baseline. Knowledge of FTO risk had no impact on PA in either risk or nonrisk carriers after the 6-month intervention. Attrition was higher in nonrisk participants for whom genotype was disclosed (P=.01) compared with their at-risk counterparts. Conclusions: No association between baseline PA and FTO risk genotype was observed. There was no added benefit of disclosing FTO risk on changes in PA in this personalized intervention. Further RCT studies are warranted to confirm whether disclosure of nonrisk genetic test results has adverse effects on engagement in behavior change.

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.

Efficacy of high intensity diode laser as an adjunct to non-surgical periodontal treatment: a randomized controlled trial

The high intensity diode laser has been studied in periodontics for the reduction of subgingival bacteria in non-surgical treatment. Our study evaluated the bacterial effect as well as changes in periodontal clinical parameters promoted by root scaling and planing associated with this wavelength. Twenty-seven patients randomly assigned in two groups underwent root scaling and planing on the tested sites, and only the experimental group received the diode laser irradiation. Among the clinical parameters studied, the clinical probing depth (CPD) and the clinical attachment level (CAL) resulted in significant enhancement in the control group when compared with the experimental group (P = 0.014 and P = 0.039, respectively). The results were similar for both groups regarding the plaque index (PI) and bleeding on probing (BP). No significant difference in the microbiological parameters was observed between the control and experimental groups. It was possible to conclude that the high power diode laser adjunct to the non-surgical periodontal treatment did not promote additional effects to the conventional periodontal treatment.

The effectiveness of proactive telephone support provided to breastfeeding mothers of preterm infants : study protocol for a randomized controlled trial

Background: Although breast milk has numerous benefits for infants' development, with greater effects in those born preterm (at < 37 gestational weeks), mothers of preterm infants have shorter breastfeeding duration than mothers of term infants. One of the explanations proposed is the difficulties in the transition from a Neonatal Intensive Care Unit (NICU) to the home environment. A person-centred proactive telephone support intervention after discharge from NICU is expected to promote mothers' sense of trust in their own capacity and thereby facilitate breastfeeding. Methods/design: A multicentre randomized controlled trial has been designed to evaluate the effectiveness and cost-effectiveness of person-centred proactive telephone support on breastfeeding outcomes for mothers of preterm infants. Participating mothers will be randomized to either an intervention group or control group. In the intervention group person-centred proactive telephone support will be provided, in which the support team phones the mother daily for up to 14 days after hospital discharge. In the control group, mothers are offered a person-centred reactive support where mothers can phone the breastfeeding support team up to day 14 after hospital discharge. The intervention group will also be offered the same reactive telephone support as the control group. A stratified block randomization will be used; group allocation will be by high or low socioeconomic status and by NICU. Recruitment will be performed continuously until 1116 mothers (I: 558 C: 558) have been included. Primary outcome: proportion of mothers exclusively breastfeeding at eight weeks after discharge. Secondary outcomes: proportion of breastfeeding (exclusive, partial, none and method of feeding), mothers satisfaction with breastfeeding, attachment, stress and quality of life in mothers/partners at eight weeks after hospital discharge and at six months postnatal age. Data will be collected by researchers blind to group allocation for the primary outcome. A qualitative evaluation of experiences of receiving/providing the intervention will also be undertaken with mothers and staff. Discussion: This paper presents the rationale, study design and protocol for a RCT providing person-centred proactive telephone support to mothers of preterm infants. Furthermore, with a health economic evaluation, the cost-effectiveness of the intervention will be assessed. Trial registration: NCT01806480

Women's acceptability of misoprostol treatment for incomplete abortion by midwives and physicians : secondary outcome analysis from a randomized controlled equivalence trial at district level in Uganda

OBJECTIVE: This study aimed to assess women´s acceptability of diagnosis and treatment of incomplete abortion with misoprostol by midwives, compared with physicians. METHODS: This was an analysis of secondary outcomes from a multi-centre randomized controlled equivalence trial at district level in Uganda. Women with first trimester incomplete abortion were randomly allocated to clinical assessment and treatment with misoprostol by a physician or a midwife. The randomisation (1:1) was done in blocks of 12 and stratified for health care facility. Acceptability was measured in expectations and satisfaction at a follow up visit 14-28 days following treatment. Analysis of women's overall acceptability was done using a generalized linear mixed-effects model with an equivalence range of -4% to 4%. The study was not masked. The trial is registered at ClinicalTrials.org, NCT 01844024. RESULTS: From April 2013 to June 2014, 1108 women were assessed for eligibility of which 1010 were randomized (506 to midwife and 504 to physician). 953 women were successfully followed up and included in the acceptability analysis. 95% (904) of the participants found the treatment satisfactory and overall acceptability was found to be equivalent between the two study groups. Treatment failure, not feeling calm and safe following treatment, experiencing severe abdominal pain or heavy bleeding following treatment, were significantly associated with non-satisfaction. No serious adverse events were recorded. CONCLUSIONS: Treatment of incomplete abortion with misoprostol by midwives and physician was highly, and equally, acceptable to women. TRIAL REGISTRATION: ClinicalTrials.gov NCT01844024.

Acceptability of home-assessment post medical abortion and medical abortion in a low-resource setting in Rajasthan, India : Secondary outcome analysis of a non-inferiority randomized controlled trial

Background: Studies evaluating acceptability of simplified follow-up after medical abortion have focused on high-resource or urban settings where telephones, road connections, and modes of transport are available and where women have formal education. Objective: To investigate women's acceptability of home-assessment of abortion and whether acceptability of medical abortion differs by in-clinic or home-assessment of abortion outcome in a low-resource setting in India. Design: Secondary outcome of a randomised, controlled, non-inferiority trial. Setting Outpatient primary health care clinics in rural and urban Rajasthan, India. Population: Women were eligible if they sought abortion with a gestation up to 9 weeks, lived within defined study area and agreed to follow-up. Women were ineligible if they had known contraindications to medical abortion, haemoglobin < 85mg/l and were below 18 years. Methods: Abortion outcome assessment through routine clinic follow-up by a doctor was compared with home-assessment using a low-sensitivity pregnancy test and a pictorial instruction sheet. A computerized random number generator generated the randomisation sequence (1: 1) in blocks of six. Research assistants randomly allocated eligible women who opted for medical abortion (mifepristone and misoprostol), using opaque sealed envelopes. Blinding during outcome assessment was not possible. Main outcome measures: Women's acceptability of home-assessment was measured as future preference of follow-up. Overall satisfaction, expectations, and comparison with previous abortion experiences were compared between study groups. Results: 731 women were randomized to the clinic follow-up group (n = 353) or home-assessment group (n = 378). 623 (85%) women were successfully followed up, of those 597 (96%) were satisfied and 592 (95%) found the abortion better or as expected, with no difference between study groups. The majority, 355 (57%) women, preferred home-assessment in the event of a future abortion. Significantly more women, 284 (82%), in the home-assessment group preferred home-assessment in the future, as compared with 188 (70%) of women in the clinic follow-up group, who preferred clinic follow-up in the future (p < 0.001). Conclusion: Home-assessment is highly acceptable among women in low-resource, and rural, settings. The choice to follow-up an early medical abortion according to women's preference should be offered to foster women's reproductive autonomy.

Manual and electroacupuncture for labour pain : study design of a longitudinal randomized controlled trial

Introduction. Results from previous studies on acupuncture for labour pain are contradictory and lack important information on methodology. However, studies indicate that acupuncture has a positive effect on women's experiences of labour pain. The aim of the present study was to evaluate the efficacy of two different acupuncture stimulations, manual or electrical stimulation, compared with standard care in the relief of labour pain as the primary outcome. This paper will present in-depth information on the design of the study, following the CONSORT and STRICTA recommendations. Methods. The study was designed as a randomized controlled trial based on western medical theories. Nulliparous women with normal pregnancies admitted to the delivery ward after a spontaneous onset of labour were randomly allocated into one of three groups: manual acupuncture, electroacupuncture, or standard care. Sample size calculation gave 101 women in each group, including a total of 303 women. A Visual Analogue Scale was used for assessing pain every 30 minutes for five hours and thereafter every hour until birth. Questionnaires were distributed before treatment, directly after the birth, and at one day and two months postpartum. Blood samples were collected before and after the first treatment. This trial is registered at ClinicalTrials.gov: NCT01197950.

High volume peritoneal dialysis vs daily hemodialysis: A randomized, controlled trial in patients with acute kidney injury

There is no consensus in the literature on the best renal replacement therapy (RRT) in acute kidney injury (AKI), with both hemodialysis (HD) and peritoneal dialysis (PD) being used as AKI therapy. However, there are concerns about the inadequacy of PD as well as about the intermittency of HD complicated by hemodynamic instability. Recently, continuous replacement renal therapy (CRRT) have become the most commonly used dialysis method for AKI around the world. A prospective randomized controlled trial was performed to compare the effect of high volume peritoneal dialysis (HVPD) with daily hemodialysis (DHD) on AKI patient survival. A total of 120 patients with acute tubular necrosis (ATN) were assigned to HVPD or DHD in a tertiary-care university hospital. The primary end points were hospital survival rate and renal function recovery, with metabolic control as the secondary end point. Sixty patients were treated with HVPD and 60 with DHD. The HVPD and DHD groups were similar for age ( 64.2 +/- 19.8 and 62.5 +/- 21.2 years), gender ( male: 72 and 66%), sepsis ( 42 and 47%), hemodynamic instability ( 61 and 63%), severity of AKI ( Acute Tubular Necrosis-Index Specific Score (ATN-ISS): 0.68 +/- 0.2 and 0.66 +/- 0.2), Acute Physiology, Age, and Chronic Health Evaluation Score (APACHE II) (26.9 +/- 8.9 and 24.1 +/- 8.2), pre-dialysis BUN (116.4 +/- 33.6 and 112.6 +/- 36.8mg per 100 ml), and creatinine ( 5.8 +/- 1.9 and 5.9 +/- 1.4 mg per 100 ml). Weekly delivered Kt/V was 3.6 +/- 0.6 in HVPD and 4.7 +/- 0.6 in DHD ( P<0.01). Metabolic control, mortality rate ( 58 and 53%), and renal function recovery ( 28 and 26%) were similar in both groups, whereas HVPD was associated with a significantly shorter time to the recovery of renal function. In conclusion, HVPD and DHD can be considered as alternative forms of RRT in AKI.

Antioxidant therapy to prevent preeclampsia - A Randomized controlled trial

OBJECTIVE: To study whether antioxidant supplementation will reduce the incidence of preeclampsia among patients at increased risk.METHODS: A randomized, placebo-controlled, double-blind clinical trial was conducted at four Brazilian sites. Women between 12 0/7 weeks and 19 6/7 weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomly assigned to daily treatment with both vitamin C (1,000 mg) and vitamin E (400 International Units) or placebo. Analyses were adjusted for clinical site and risk group (prior preeclampsia, chronic hypertension, or both). A sample size of 734 would provide 80% power to detect a 40% reduction in the risk of preeclampsia, assuming a placebo group rate of 21% and alpha=.05. The a level for the final analysis, adjusted for interim looks, was 0.0458.RESULTS: Outcome data for 707 of 739 randomly assigned patients revealed no significant reduction in the rate of preeclampsia (study drug, 13.8% [49 of 355] compared with placebo, 15.6% [55 of 352], adjusted risk ratio 0.87 [95.42% confidence interval 0.61-1.25]). There were no differences in mean gestational age at delivery or rates of perinatal mortality, abruptio placentae, pre-term delivery, and small for gestational age or low birth weight infants. Among patients without chronic hypertension, there was a slightly higher rate of severe preeclampsia in the study group (study drug, 6.5% [11 of 170] compared with placebo, 2.4% [4 of 168], exact P=.11, odds ratio 2.78, 95% confidence interval 0.79-12.62).CONCLUSION: This trial failed to demonstrate a benefit of antioxidant supplementation in reducing the rate of preeclampsia among'patients with chronic hypertension and/or prior preeclampsia.

Randomized controlled trial on prevention of postcesarean infection using penicillin and cephalothin in Brazil

Background. There is a need to assess the effects of different antibiotic administration models on infectious complications among women from low-income populations who undergo cesarean delivery, and the cost benefit. Design. Randomized, blinded controlled clinical trial study of a single preoperative dose of cephalothin, versus a postcesarean scheme for infection prophylaxis, versus no antibiotics. Methods. The setting was a tertiary Brazilian center with 1,500 deliveries annually. Pregnant women (n = 600) with an indication for emergency or elective cesarean section were randomly allocated consecutively to one of three groups and treated as follows: Group 1 (n = 200), no antibiotics; Group 2 (n = 200), the standard antibiotics scheme followed at this center; Group 3 (n = 200), a single dose of intravenous cephalothin 2 g, intraoperatively. Main outcome measurements. Prevalences of wound infection, puerperal and postcesarean infections, and costs of antibiotics used. Results. Antibiotics reduced the incidence of puerperal infection, but did not change the percentages of wound and postcesarean infections and no use of antibiotics increased the puerperal infection risk sixfold. Cephalothin reduced the relative risk of puerperal infection by 89% (95% confidence interval: 7-87%). Penicillin reduced it by 78%, but this was not statistically significant. No deaths occurred. The costs of the two schemes were similar (almost US$1.00). Conclusions. Prophylactic cephalothin use was associated with decreased postcesarean puerperal infection and presented a cost benefit.

A randomized controlled trial of homeopathic treatment of weaned piglets in a commercial swine herd

Aim: To evaluate the zootechnic performance and occurrence of diarrhea in piglets in the week post-weaning comparing supplementation with sucrose saline which contained or did not contain added homeopathic medicine.Method. Animals were randomly divided into three groups of 24 piglets each. The control group did not receive any treatment. Another group received sucrose saline, and the third group received sucrose saline with homeopathic medicine added, in the period of zero to seven days post-weaning. The homeopathic treatment consisted of Echinacea angustifolia, Avena sativa, Ignatia amara, Calcarea carbonica, all 6cH. Piglets were weighed daily for weight gain or loss, and observed for diarrhea and feed intake.Results: Animals receiving sucrose saline alone and sucrose saline with homeopathy had less weight loss than control (p = 0.017, p = 0.0001 respectively). There was no statistical difference in relation to overall incidence of diarrhea or food consumption. These data suggest that the supplementation with sucrose saline with added homeopathic medicine in the first seven days post-weaning may be an useful option to reduce weight loss in weaned piglets. Homeopathy (2008) 97, 202-205.