scholarly journals Allowing for non-adherence to treatment in a randomized controlled trial of two antidepressants (citalopram versus reboxetine): an example from the GENPOD trial

2014 ◽  
Vol 44 (13) ◽  
pp. 2855-2866 ◽  
Author(s):  
N. J. Wiles ◽  
K. Fischer ◽  
P. Cowen ◽  
D. Nutt ◽  
T. J. Peters ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Outcome Data ◽  
Adherence To Treatment ◽  
Clinical Predictors ◽  
Intention To Treat ◽  
Weak Evidence ◽  
Primary Care Patients ◽  
Unbiased Estimates ◽  
Meta Analyses ◽  
Lower Adherence

BackgroundMeta-analyses suggest that reboxetine may be less effective than other antidepressants. Such comparisons may be biased by lower adherence to reboxetine and subsequent handling of missing outcome data. This study illustrates how to adjust for differential non-adherence and hence derive an unbiased estimate of the efficacy of reboxetine compared with citalopram in primary care patients with depression.MethodA structural mean modelling (SMM) approach was used to generate adherence-adjusted estimates of the efficacy of reboxetine compared with citalopram using GENetic and clinical Predictors Of treatment response in Depression (GENPOD) trial data. Intention-to-treat (ITT) analyses were performed to compare estimates of effectiveness with results from previous meta-analyses.ResultsAt 6 weeks, 92% of those randomized to citalopram were still taking their medication, compared with 72% of those randomized to reboxetine. In ITT analysis, there was only weak evidence that those on reboxetine had a slightly worse outcome than those on citalopram [adjusted difference in mean Beck Depression Inventory (BDI) scores: 1.19, 95% confidence interval (CI) –0.52 to 2.90, p = 0.17]. There was no evidence of a difference in efficacy when differential non-adherence was accounted for using the SMM approach for mean BDI (–0.29, 95% CI –3.04 to 2.46, p = 0.84) or the other mental health outcomes.ConclusionsThere was no evidence of a difference in the efficacy of reboxetine and citalopram when these drugs are taken and tolerated by depressed patients. The SMM approach can be implemented in standard statistical software to adjust for differential non-adherence and generate unbiased estimates of treatment efficacy for comparisons of two (or more) active interventions.

scholarly journals Maintained physical activity and physiotherapy in the management of distal arm pain: a randomised controlled trial

RMD Open ◽  
2019 ◽  
Vol 5 (1) ◽  
pp. e000810 ◽  
Author(s):  
Gareth T Jones ◽  
Gary J Macfarlane ◽  
Karen Walker-Bone ◽  
Kim Burton ◽  
Peter Heine ◽  
...  
Keyword(s):  
Back Pain ◽  
Controlled Trial ◽  
Complete Recovery ◽  
Outcome Data ◽  
Lower Probability ◽  
Intention To Treat ◽  
Arm Pain ◽  
Current Guidance ◽  
Randomised Controlled

ObjectivesThe epidemiology of distal arm pain and back pain are similar. However, management differs considerably: for back pain, rest is discouraged, whereas patients with distal arm pain are commonly advised to rest and referred to physiotherapy. We hypothesised that remaining active would reduce long-term disability and that fast-track physiotherapy would be superior to physiotherapy after time on a waiting list.MethodsAdults referred to community-based physiotherapy with distal arm pain were randomised to: advice to remain active while awaiting physiotherapy (typically delivered after 6–8 weeks); advice to rest while awaiting physiotherapy, or immediate treatment. Intention-to-treat analysis determined whether the probability of recovery at 26 weeks was greater among the active advice group, compared with those advised to rest and/or among those receiving immediate versus usually timed physiotherapy.Results538 of 1663 patients invited between February 2012 and February 2014 were randomised (active=178; rest=182; immediate physiotherapy=178). 81% provided primary outcome data, and complete recovery was reported by 60 (44%), 46 (32%) and 53 (35%). Those advised to rest experienced a lower probability of recovery (OR: 0.54; 95% CI 0.32 to 0.90) versus advice to remain active. However, there was no benefit of immediate physiotherapy (0.64; 95% CI 0.39 to 1.07).ConclusionsAmong patients awaiting physiotherapy for distal arm pain, advice to remain active results in better 26-week functional outcome, compared with advice to rest. Also, immediate physiotherapy confers no additional benefit in terms of disability, compared with physiotherapy delivered after 6–8 weeks waiting time. These findings question current guidance for the management of distal arm pain.

OP52 Use Of Intention To Treat And Magnitude Of Treatment Effects

2019 ◽  
Vol 35 (S1) ◽  
pp. 12-13
Author(s):  
Susan Armijo-Olivo ◽  
Bruno Da costa ◽  
Chiara Arienti ◽  
Negrini Stefano
Keyword(s):  
Missing Data ◽  
Treatment Effects ◽  
Data Extraction ◽  
Outcome Data ◽  
Risk Of Bias ◽  
Intention To Treat ◽  
Perform Sensitivity Analysis ◽  
Meta Analyses ◽  
Drop Outs

IntroductionIntention to treat (ITT) is a gold standard strategy to analyze the results of randomized controlled trials (RCTs). ITT analysis has been considered a methodological indicator of the quality of clinical trials. The extent to which the use of ITT is related to the treatment effects observed in RCTs has not been rigorously explored. Therefore, the main objective of this study was to determine the association between biases related to attrition and missing data and the use of intention to treat principle, and changes in effect size estimates in RCTs.MethodsThis was a meta-epidemiological study. A random sample of RCTs included in meta-analyses was identified. Data extraction including assessments of the use of intention to treat principle, missing data and drop-outs was conducted independently by two reviewers. To determine the association between biases related to attrition, missing data, and the use of intention to treat and effect sizes, a two-level analysis was conducted using a meta-meta-analytic approach.ResultsThree-hundred and ninety-three trials included in 43 meta-analyses, analyzing 44,622 patients contributed to this study. From these, 134 trials (34.1%) used ITT and 218 (55.5%) did not use ITT. Trials which did not use the ITT principle, or which were assessed as having an inappropriate control of incomplete outcome data (based on the Cochrane risk of bias tool) tended to underestimate the treatment effect when compared with trials with adequate use of ITT (ES= -0.13; 95%CI -0.26, -0.01) or trials which were assessed as having an appropriate control of incomplete outcome (ES= -0.18; 95%CI -0.29, -0.08).ConclusionsOur results suggest that when evaluating risk of bias of primary RCTs, systematic reviewers should pay attention to these biases since they could underestimate treatment effects. Systematic reviewers should perform sensitivity analysis including trials with low risk of bias in these domains.

scholarly journals Long-Term Safety and Efficacy of Prebiotic Enriched Infant Formula—A Randomized Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1276
Author(s):  
Franka Neumer ◽  
Orenci Urraca ◽  
Joaquin Alonso ◽  
Jesús Palencia ◽  
Vicente Varea ◽  
...  
Keyword(s):  
Infant Formula ◽  
Controlled Trial ◽  
Fecal Microbiota ◽  
First Year ◽  
Double Blind Study ◽  
Double Blind ◽  
Term Infants ◽  
Intention To Treat ◽  
Prebiotic Oligosaccharides ◽  
First Year Of Life

The present study aims to evaluate the effects of an infant formula supplemented with a mixture of prebiotic short and long chain inulin-type oligosaccharides on health outcomes, safety and tolerance, as well as on fecal microbiota composition during the first year of life. In a prospective, multicenter, randomized, double-blind study, n = 160 healthy term infants under 4 months of age were randomized to receive either an infant formula enriched with 0.8 g/dL of Orafti®Synergy1 or an unsupplemented control formula until the age of 12 months. Growth, fever (>38 °C) and infections were regularly followed up by a pediatrician. Digestive symptoms, stool consistency as well as crying and sleeping patterns were recorded during one week each study month. Fecal microbiota and immunological biomarkers were determined from a subgroup of infants after 2, 6 and 12 months of life. The intention to treat (ITT) population consisted of n = 149 infants. Both formulae were well tolerated. Mean duration of infections was significantly lower in the prebiotic fed infants (p < 0.05). The prebiotic group showed higher Bifidobacterium counts at month 6 (p = 0.006), and higher proportions of Bifidobacterium in relation to total bacteria at month 2 and 6 (p = 0.042 and p = 0.013, respectively). Stools of infants receiving the prebiotic formula were softer (p < 0.05). Orafti®Synergy1 tended to beneficially impact total daily amount of crying (p = 0.0594). Supplementation with inulin-type prebiotic oligosaccharides during the first year of life beneficially modulates the infant gut microbiota towards higher Bifidobacterium levels at the first 6 months of life, and is associated with reduced duration of infections.

Roxadustat for anemia in patients with end-stage renal disease incident to dialysis

2021 ◽  
Author(s):  
Robert Provenzano ◽  
Evgeny Shutov ◽  
Liubov Eremeeva ◽  
Svitlana Korneyeva ◽  
Lona Poole ◽  
...  
Keyword(s):  
Rescue Therapy ◽  
Controlled Trial ◽  
Epoetin Alfa ◽  
Open Label ◽  
Treatment Groups ◽  
Intention To Treat ◽  
Primary Endpoints ◽  
Stage Renal Disease ◽  
End Stage ◽  
Event Rates

Abstract Background We evaluated the efficacy and safety of roxadustat vs. epoetin alfa for the treatment of chronic kidney disease (CKD) related anemia in patients new to dialysis. Methods This was a phase 3, open-label, epoetin alfa-controlled trial. Eligible adults were on hemodialysis/peritoneal dialysis for ≥2 weeks and ≤4 months before randomization and had mean hemoglobin ≤10.0 g/dL. Primary endpoints were mean hemoglobin (g/dL) change from baseline averaged over weeks 28–52 regardless of rescue therapy (non-inferiority criterion: lower limit of 95% CI for treatment difference &gt; −0.75) and percentage of patients achieving a hemoglobin response between weeks 1–24 censored for rescue therapy (non-inferiority margin for between-group difference: −15%). Adverse events were monitored. Results The intention-to-treat population included patients randomized to roxadustat (n = 522) or epoetin alfa (n = 521). Mean (SD) hemoglobin changes from baseline averaged over weeks 28–52 were 2.57 (1.27) and 2.36 (1.21) in the roxadustat and epoetin alfa groups. Roxadustat was non-inferior (least-squares mean difference: 0.18 [95% CI: 0.08, 0.29]) to epoetin alfa. Percentages of patients with a hemoglobin response were 88.2% and 84.4% in the roxadustat and epoetin alfa groups. Roxadustat was non-inferior to epoetin alfa (treatment-group difference: 3.5% [95% CI: −0.7%, 7.7%]). Adverse event rates were comparable between treatment groups. Conclusions Roxadustat was efficacious for correcting and maintaining hemoglobin levels compared to epoetin alfa. Roxadustat had an acceptable safety profile.

Do Nutrition Education Approaches With Preschoolers and Their Caregivers Influence Retention of Biofortified Orange-Fleshed Sweetpotato on Farms?: Evidence From Homa Bay County, Kenya

2021 ◽  
pp. 037957212110254
Author(s):  
Sylvester O. Ojwang ◽  
David J. Otieno ◽  
Julius J. Okello ◽  
Penina Muoki ◽  
Rose A. Nyikal
Keyword(s):  
Nutrition Education ◽  
Early Childhood Development ◽  
Controlled Trial ◽  
Text Messages ◽  
Sub Saharan Africa ◽  
Childhood Development ◽  
Control Group ◽  
Micronutrient Deficiencies ◽  
Household Level ◽  
Intention To Treat

Background: Biofortified staples have been promoted widely in sub-Saharan Africa to combat micronutrient deficiencies. Contemporary projects are increasingly using elementary schools to target households with these foods. Objective: This study assessed the effects of integrated nutrition education approaches, targeting preschoolers and their caregivers, on retention of orange-fleshed sweetpotato (OFSP) on farms in the second season after lapse of free vine dissemination initiatives. Methods: Rural farming households, with preschoolers and no prior engagement with OFSP, were targeted. A multistage sample of 431 preschooler–caregiver pairs was recruited for a cluster-randomized controlled trial. After issuing routine OFSP promotion activities, 15 village-level clusters of the pairs were randomized into 1 control group (3 villages) and 3 treatment arms (4 villages each) for the interventions. Baseline and follow-up household-level survey data were collected from the caregivers. The interventions included: (1) OFSP-branded exercise books, posters, and a poem to preschoolers only; (2) OFSP-oriented mobile phone-mediated text messages to caregivers only; and (3) both 1 and 2 provided to individual households concurrently. Interventions 1 and 2 were single-channeled, while 3 was multichanneled. We estimated the intention-to-treat (ITT) and treatment-on-the-treated (TOT) effects using a binary logit model and a special regressor method, respectively. Results: Only the multichanneled nutrition education approach had significant effects (ITT = 0.167, P = .001; TOT = .243, P = .007) on the caregivers’ likelihood to retain OFSP on their farms. Conclusions: The finding implies that multichanneled agriculture-nutrition education interventions through Early Childhood Development institutions can be effective in ensuring sustainable adoption of OFSP.

scholarly journals Impact of Fatty Acid Supplementation on Cognitive Performance among United States (US) Military Officers: The Ranger Resilience and Improved Performance on Phospholipid-Bound Omega-3’s (RRIPP-3) Study

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1854
Author(s):  
Bernadette P. Marriott ◽  
Travis H. Turner ◽  
Joseph R. Hibbeln ◽  
Jill C. Newman ◽  
Marcie Pregulman ◽  
...  
Keyword(s):  
United States ◽  
Controlled Trial ◽  
The United States ◽  
Military Officers ◽  
Krill Oil ◽  
Omega 3 ◽  
Double Blind ◽  
Significant Group ◽  
Intention To Treat ◽  
Improved Performance

Studies have assessed omega-3 fatty acids and cognitive decline among older adults and cognitive development among children, although less is known about cognitive or neurological effects among young adults. We examined whether omega-3 supplementation from krill oil could improve cognition and resilience among young military officers compared to a control. This double-blind, placebo-controlled trial enrolled 555 officers (mean age 23.4 ± 2.8, 98.6% male) entering the United States (US) Army Infantry Basic Officer Leaders Course (IBOLC) with the intention to complete the US Ranger Course. Volunteer participants consumed eight dietary supplements daily of krill oil containing 2.3 g omega-3 or control (macadamia nut oil) over an approximate 20-week period. Cognitive functioning, resilience, and mood were assessed during a well-rested period at approximately 14 weeks and after a battlefield simulation at 16 weeks. Blood spot samples were collected to monitor compliance and dietary intake was assessed. All hypotheses were tested using both ‘Intention to Treat’ (ITT) and ‘As Per Protocol’ (APP) approaches. Of the 555 randomized individuals, 245 (44.1%) completed the study. No statistically significant group-by-time interactions indicating treatment effect were found on any outcomes. Poor compliance was indicated by lower than expected omega-3 elevations in the treatment group, and may have contributed to a failure to detect a response.

scholarly journals Effect of Inquiry-Based Stress Reduction (IBSR) Intervention on Well-Being, Resilience and Burnout of Teachers during the COVID-19 Pandemic

2021 ◽  
Vol 18 (7) ◽  
pp. 3689
Author(s):  
Tzofnat Zadok-Gurman ◽  
Ronit Jakobovich ◽  
Eti Dvash ◽  
Keren Zafrani ◽  
Benjamin Rolnik ◽  
...  
Keyword(s):  
Stress Reduction ◽  
Controlled Trial ◽  
Intervention Group ◽  
Well Being ◽  
Stressful Events ◽  
Control Group ◽  
Subjective Well Being ◽  
Intention To Treat ◽  
School Year ◽  
Blended Intervention

Objective: The COVID-19 pandemic has had a major impact on teachers professional and personal lives. Our primary aim was to assess the effect of a blended Inquiry-Based Stress Reduction (IBSR), an emerging mindfulness and cognitive reframing intervention on teacher’s well-being. Our secondary aims were to assess the effect of IBSR on resilience, burnout, mindfulness, and stress among teachers during the COVID-19 pandemic. Methods: The study was a prospective controlled trial with an intervention group (N = 35) and a comparison control group (N = 32). The intervention took place in the Jerusalem District throughout the school year from November 2019 to May 2020. The sessions were conducted in blended learning that included traditional learning (face-to-face) and online learning. Data was analyzed on an intention-to-treat basis. Results: IBSR blended intervention enhanced the resilience and improved the subjective and psychological well-being of teachers in spite of the breakout of the COVID-19 pandemic and the first lockdown in Israel. Simultaneously the control group suffered from enhanced burnout levels and a decline in psychological and subjective well-being. Conclusions: Implementation of IBSR blended intervention during the school year may benefit teachers’ well-being and ability to flourish, even during stressful events such as the COVID-19 pandemic.

scholarly journals Social Volunteering in Aging Adults Increases Regions of the Amygdala and Correlates With Enhanced Generativity

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 795-795
Author(s):  
Michelle Carlson
Keyword(s):  
Social Engagement ◽  
Controlled Trial ◽  
Well Being ◽  
Health Study ◽  
Brain Health ◽  
Volunteer Program ◽  
Intention To Treat ◽  
Intervention Impact ◽  
Aging Adults ◽  
The Brain

Abstract The Brain Health Study (BHS) of the Baltimore Experience Corps Trial (BECT) examined whether a randomized, controlled trial of an intergenerational social volunteer program, entitled Experience Corps, increased subregions of the amygdala related to socioemotional memory and risk for Alzheimer’s disease in aging adults. We further assessed functional correlates of these intervention-related changes and changes in aging adults’ developmental need to be generative, or, to give back to the well-being of others. The BHS simultaneously randomized 112 men and women (59 intervention; 53 control) within BECT to evaluate intervention impact on biomarkers of brain health at baseline and annual follow-ups during the two-year trial. Intention-to-treat analyses revealed program-specific increases in the shape of the centromedial and basomedial regions of the left amygdala (p’s≤0.05 adjusted), which were correlated with increases in generativity (p’s =0.06). Meaningful social engagement buffered amygdalar declines important to preservation of emotionally salient memory and risk for dementia. Part of a symposium sponsored by Brain Interest Group.

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