Original Randomized Controlled Trial Research Articles

A 2-year follow-up to a randomized controlled trial on resistance training in postmenopausal women: vasomotor symptoms, quality of life and cardiovascular risk markers

BackgroundMost women experience vasomotor symptoms (VMS) during the menopausal transition. A 15-week resistance training intervention (RTI) significantly reduced moderate-to-severe VMS (MS-VMS) and improved health-related quality of life (HRQoL) and cardiovascular risk markers in postmenopausal women. Whether a short RTI could have long-term effects is unknown. We aimed to investigate whether there were intervention-dependent effects two years after a 15-week RTI on MS-VMS frequency, HRQoL, and cardiovascular risk markers in postmenopausal women.MethodsThis observational prospective cohort study is a follow-up to a randomized controlled trial (RCT) on a 15-week RTI in postmenopausal women (n = 57). The control group had unchanged low physical activity during these first 15 weeks. At the follow-up contact two years post-intervention, 35 women agreed to participate in an additional physical visit at the clinic with clinical testing, blood sampling, and magnetic resonance imaging, identical to the protocol at the baseline visit at the start of the RCT.ResultsAlthough all women showed reduced MS-VMS and increased moderate-to-vigorous physical activity (MVPA) over the 2-year follow-up compared to baseline, the groups from the original RCT (intervention group; IG, control group; CG) changed differently over time (p < 0.001 and p = 0.006, respectively) regarding MS-VMS. The IG maintained a significantly lower MS-VMS frequency than the CG at the 6-month follow-up. At the 2-year follow-up, there was no significant difference between the original RCT groups. No significant changes over time or differences between groups were found in HRQoL or cardiovascular risk markers. However, significant interactions between original RCT groups and time were found for visceral adipose tissue (p = 0.041), ferritin (p = 0.045), and testosterone (p = 0.010).ConclusionsA 15-week resistance training intervention reduced MS-VMS frequency up to six months post-intervention compared to a CG, but the effect was not maintained after two years. The RTI did neither contribute to preserved improvements of cardiovascular risk markers nor improved HRQoL after two years compared to a CG.Trial registrationClinical trials.gov registered ID: NCT01987778, trial registration date 2013–11-19.

Longer term follow-up of a randomized controlled trial on the role of compression after radiofrequency ablation of varicose veins

ObjectiveSeveral studies have shown that, in the short term, treatment outcomes following endothermal ablation of varicose veins without the prescription of post procedural compression are not inferior to outcomes when compression is routinely prescribed. This follow-up to our randomized controlled trial (RCT) published in 2020 explores whether the non-inferiority persists into the medium to long term. MethodsAll 94 patients from the RCT were recalled at 27 months after their initial radiofrequency ablation (RFA) procedure. The procedural details, randomization, and inclusion and exclusion criteria were described in the original RCT paper. Consent was obtained for further venous duplex ultrasound scan at 27 to 61 months after the initial procedure. The successful target vein closure at this juncture represented our primary outcome. Secondary outcomes include disease severity, measured using the Aberdeen Varicose Vein Severity Score (AVSS) and the Revised Venous Clinical Severity Score (RVCSS), post-procedural pain measured using Likert scale, and number of days taken for patients to return to work or normal activities. ResultsThirty-one of 48 patients (64.6%) in the compression group and 29 of 46 patients (63%) in the no-compression group were evaluated. The mean duration of follow-up was 43 and 42 months in the compression and no-compression group, respectively. The target vein occlusion rate evaluated at this longer-term follow up were 80.7% and 79.3% in the compression and no-compression groups, respectively. There was no significant difference between the two groups (P = .37). Secondary outcomes of quality of life and disease severity measured using AVSS and RVCSS showed no significant difference between the two groups (post-procedural AVSS mean score 5.2 in the compression group vs 8.3 in the no-compression group [95% confidence interval (CI), −7.3 to 1.1; P = .14]; post-procedural RVCSS mean score 1.5 in the compression group vs 1.8 in the no-compression group [95% CI, −1.1 to 0.7; P = .59]). Patient satisfaction was similar in both groups (mean score 6.4 in the compression group vs 5.9 in the no-compression group [95% CI, −0.22 to 1.17; P = .18]), and the number of days taken for patients to return to work were also comparable (mean of 11.9 days in the compression group vs 12.6 days in the no-compression group [95% CI, −7.7 to 6.2; P = .83]). ConclusionsThis study provided some evidence to support no additional benefit of compression use after RFA at a longer term follow-up of 3 years. However, larger, suitably powered studies would be beneficial to confirm this.

Developmental outcomes of children born through ICSI versus conventional IVF (cIVF) in couples with non-male factor infertility.

In non-male factor infertile couples, are there any differences in the developmental outcomes between children born through ICSI and conventional IVF (cIVF)? In this preliminary study, ICSI and cIVF seem to have a comparable effect on developmental outcomes after 12 months in children born to non-male factor infertile couples. ICSI, an invasive technique, has raised concerns about potential developmental abnormalities in children. Limited data are available regarding the developmental outcomes of ICSI-conceived infants born to non-male factor infertile couples. This prospective cohort study involved a follow-up of all children aged 12 months or older who were born from pregnancies resulting from either ICSI or cIVF as part of a previous randomized controlled trial (RCT) (NCT03428919). In the original RCT, 1064 women were randomly assigned to the ICSI or cIVF groups (532 women for each group). Follow-up was conducted with 155 couples (195 children) in the ICSI group and 141 couples (185 children) in the cIVF group. The Vietnamese version of the Ages & Stages Third Edition Questionnaires (ASQ-3) and the Development Red Flags questionnaires were completed by the participants. A total of 141 (90.1%) women (177 children) in the ICSI group and 113 (80.1%) women (145 children) in the cIVF group returned fully completed questionnaires. The primary outcomes were the developmental outcomes based on responses to the ASQ-3 and the Red Flags questionnaire. The mean age of children at follow-up was 19.5 ± 5.0 months in the ICSI group and 19.3 ± 5.5 months in the cIVF group. The mean height and weight of children in both groups were similar. The overall proportion of children with any abnormal ASQ-3 score did not differ significantly between the ICSI and cIVF groups (16.9% vs 13.1%, P = 0.34). The proportion of children with Red Flag signs was also comparable between the two groups (6.2% vs 9.2%, P = 0.36, ICSI vs cIVF, respectively). Despite a reasonably high follow-up response rate, there is a potential risk of sampling bias, and overall, the number of children with developmental abnormalities was very small. The study relied solely on questionnaires as screening tools, rather than incorporating additional behavioral observations or physical developmental tests; this may have affected the statistical power and the significance of between-group comparisons. The current findings contribute to the existing evidence and support the comparative safety of ICSI and cIVF regarding early childhood development. However, more extensive and prolonged follow-up data for these children are needed to draw definitive conclusions. No external funding was received for this study, and no authors reported conflicting interests. NCT04866524 (clinicaltrials.gov).

Resumption of ovulation in anovulatory women with PCOS and obesity is associated with reduction of 11β-hydroxyandrostenedione concentrations.

Is resumption of ovulation after a 6-month lifestyle intervention in women with PCOS and obesity associated with differential changes in endocrine and metabolic parameters (weight, insulin resistance, anti-Müllerian hormone (AMH), and androgens) compared to women with PCOS who remained anovulatory? Resumption of ovulation after a 6-month lifestyle intervention in women with PCOS and obesity is associated with changes in serum 11β-hydroxyandrostenedione (11OHA4) concentrations. Lifestyle interventions have been shown to reduce clinical and biochemical hyperandrogenism in women with PCOS. Weight loss of 5-10% may reverse anovulatory status, thereby increasing natural conception rates. However, the mechanisms underlying why some women with PCOS remain anovulatory and others resume ovulation after weight loss are unclear. Reproductive characteristics at baseline and a greater degree of change in endocrine and metabolic features with lifestyle intervention may be crucial for ovulatory response. We used data and samples originating from an earlier randomized controlled trial (RCT), which examined the efficacy of a 6-month lifestyle intervention prior to infertility treatment compared to prompt infertility treatment on live birth rate in women with obesity. A total of 577 women with obesity (BMI > 29 kg/m2) were randomized between 2009 and 2012. Anovulatory women with PCOS who were allocated to the intervention arm of the original RCT (n = 95) were included in the current analysis. We defined women as having resumed ovulation (RO+) based on the following criteria: spontaneous pregnancy; or assignment to expectant management; or IUI in natural cycles as the treatment strategy after lifestyle intervention. Steroid hormones were measured using liquid chromatography tandem mass spectrometry. Generalized estimating equations with adjustment for baseline measures and interaction between group and time was used to examine differences in changes of endocrine and metabolic parameters between RO+ (n = 34) and persistently anovulatory women (RO-, n = 61) at 3 and 6 months after intervention. At baseline, the mean ± SD age was 27.5 ± 3.6 years in the RO+ group and 27.9 ± 4.1 years in the RO- group (P = 0.65), and the mean ± SD weights were 101.2 ± 9.5 kg and 105.0 ± 14.6 kg, respectively (P = 0.13). Baseline AMH concentrations showed significant differences between RO+ and RO- women (median and interquartile range [IQR] 4.7 [3.2; 8.3] versus 7.2 [5.3; 10.8] ng/ml, respectively). Baseline androgen concentrations did not differ between the two groups. During and after lifestyle intervention, both groups showed weight loss; changes in 11OHA4 were significantly different between the RO+ and RO groups (P-value for interaction = 0.03). There was a similar trend for SHBG (interaction P-value = 0.07), and DHEA-S (interaction P-value = 0.06), with the most pronounced differences observed in the first 3 months. Other parameters, such as AMH and FAI, decreased over time but with no difference between the groups. No high-resolution transvaginal ultrasonography was used to confirm ovulatory status at the end of the lifestyle program. The small sample size may limit the robustness of the results. Reduction of androgen concentrations during and after lifestyle intervention is associated with recovery of ovulatory cycles. If our results are confirmed in other studies, androgen concentrations could be monitored during lifestyle intervention to provide individualized recommendations on the timing of resumption of ovulation in anovulatory women with PCOS and obesity. The study was supported by a grant from ZonMw, the Dutch Organization for Health Research and Development (50-50110-96-518). The Department of Obstetrics and Gynecology of the UMCG received an unrestricted educational grant from Ferring Pharmaceuticals BV, The Netherlands. A.H. reports consultancy for the development and implementation of a lifestyle App MyFertiCoach developed by Ferring Pharmaceutical Company. All other authors have no conflicts to declare. The LIFEstyle RCT was registered at the Dutch trial registry (NTR 1530).

Abstract TP79: Vagal Nerve Stimulation for Enhanced Stroke Recovery: Real-World Application in a Multidisciplinary Program

Introduction: Randomized-controlled trial (RCT) evidence has demonstrated the efficacy of vagal nerve stimulation (VNS) with paired rehabilitation for upper limb functional recovery after ischemic stroke. There remains a need to assess the generalizability of these findings to a broader population of stroke patients with chronic functional deficits. Hypothesis: VNS for upper limb recovery after stroke may be safely and effectively applied to diverse populations of patients in a multidisciplinary program. Methods: Patients at one center not included in the original RCT of VNS for stroke recovery were implanted with left-sided VNS, paired with six weeks of in-clinic therapy, as implemented in the original RCT. At the conclusion of in-clinic therapy, clinical benefit was assessed by improvement from baseline in the validated Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score for stroke recovery (maximum score of 66 equating to normal function). Results: All four patients included had chronic, stable functional deficits &gt;1.5 years after stroke when implanted with VNS at ages of 43, 61, 70, and 71. Three patients with ischemic stroke were included with FMA-UE improvements of 13 (baseline 45, left-sided deficits), 15 (baseline 36, right-sided deficits), and 6 (baseline 21, left-sided deficits). One patient was implanted 3.0 years after intracerebral hemorrhagic stroke, with an FMA-UE improvement of 14 (baseline 16, right-sided deficits). No procedural complications were seen. Conclusions: Vagal nerve stimulation paired with in-clinic therapy can have a profound impact on upper limb function in patients after stroke. All patients in this series achieved greater FMA-UE improvement than the mean improvement in the largest RCT of VNS for stroke recovery (5.0 ± 4.4 points). This pilot series of real world application of paired VNS for upper limb functional recovery after stroke demonstrates early feasibility, safety, and efficacy of this treatment.

Cognitive rehabilitation in paediatric acquired brain injury-A 2-year follow-up of a randomised controlled trial.

Goal management training (GMT), a metacognitive rehabilitation method that has been demonstrated to improve executive function (EF) in adults with acquired brain injury (ABI), could potentially be effective for children in the chronic phase of ABI. In a previously published randomised controlled trial (RCT), the efficacy of a paediatric adaptation of GMT (pGMT) compared to a psychoeducative control intervention (paediatric Brain Health Workshop, pBHW) was investigated. Comparable improvements in EF in both groups were found at 6-month follow-up. However, a specific effect of pGMT could not be conclusively proven. The present study reports 2-year follow-up data (T4; T1: baseline, T2: post-intervention, T3: 6-month follow-up, and T4: 2-year follow-up) from this original RCT. A total of 38 children and adolescents and also their parents completed questionnaires tapping into daily life EF. Explorative analyses were conducted comparing the 2-year follow-up data (T4) with the baseline (T1) and 6-month follow-up data (T3) for T4-participants in the two intervention groups (pGMT; n = 21, pBHW; n = 17), and we also assessed T4-participants vs. non-responders (n = 38) in the RCT. Primary outcome measures were the Behavioural Regulation Index (BRI) and the Metacognition Index (MI) derived from the Behaviour Rating Inventory of Executive Function (BRIEF) parent report. No difference between intervention groups was found (BRI, F = 2.25, p = 0.143, MI, F = 1.6, p = 0.213), and no time*group interaction (BRI, F = 0.07, p = 0.976, MI, F = 0.137, p = 0.937) could be seen at the 2-year follow-up. Nevertheless, both pGMT and the pBHW groups improved daily EF as measured by parental reports over time from the baseline to T4 (p = 0.034). T4 participants and non-responders shared similar baseline characteristics. Our results extend the findings from the 6-month follow-up previously published. Both pGMT and pBHW groups sustained their improvements in daily life EFs from the baseline, but additional effectiveness of pGMT relative to pBHW was not found.

Changes in a Digital Type 2 Diabetes Self-management Intervention During National Rollout: Mixed Methods Study of Fidelity

"Healthy Living for People with type 2 Diabetes (HeLP-Diabetes)" was a theory-based digital self-management intervention for people with type 2 diabetes mellitus that encouraged behavior change using behavior change techniques (BCTs) and promoted self-management. HeLP-Diabetes was effective in reducing HbA1c levels in a randomized controlled trial (RCT). National Health Service (NHS) England commissioned a national rollout of HeLP-Diabetes in routine care (now called "Healthy Living"). Healthy Living presents a unique opportunity to examine the fidelity of the national rollout of an intervention originally tested in an RCT. This research aimed to describe the Healthy Living BCT and self-management content and features of intervention delivery, compare the fidelity of Healthy Living with the original HeLP-Diabetes intervention, and explain the reasons for any fidelity drift during national rollout through qualitative interviews. Content analysis of Healthy Living was conducted using 3 coding frameworks (objective 1): the BCT Taxonomy v1, a new coding framework for assessing self-management tasks, and the Template for Intervention Description and Replication. The extent to which BCTs and self-management tasks were included in Healthy Living was compared with published descriptions of HeLP-Diabetes (objective 2). Semistructured interviews were conducted with 9 stakeholders involved in the development of HeLP-Diabetes or Healthy Living to understand the reasons for any changes during national rollout (objective 3). Qualitative data were thematically analyzed using a modified framework approach. The content analysis identified 43 BCTs in Healthy Living. Healthy Living included all but one of the self-regulatory BCTs ("commitment") in the original HeLP-Diabetes intervention. Healthy Living was found to address all areas of self-management (medical, emotional, and role) in line with the original HeLP-Diabetes intervention. However, 2 important changes were identified. First, facilitated access by a health care professional was not implemented; interviews revealed this was because general practices had fewer resources in comparison with the RCT. Second, Healthy Living included an additional structured web-based learning curriculum that was developed by the HeLP-Diabetes team but was not included in the original RCT; interviews revealed that this was because of changes in NHS policy that encouraged referral to structured education. Interviewees described how the service provider had to reformat the content of the original HeLP-Diabetes website to make it more usable and accessible to meet the multiple digital standards required for implementation in the NHS. The national rollout of Healthy Living had good fidelity to the BCT and self-management content of HeLP-Diabetes. Important changes were attributable to the challenges of scaling up a digital intervention from an RCT to a nationally implemented intervention, mainly because of fewer resources available in practice and the length of time since the RCT. This study highlights the importance of considering implementation throughout all phases of intervention development.

Clinical and biochemical endpoints and predictors of response to plasma exchange in septic shock: results from a randomized controlled trial

BackgroundRecently, a randomized controlled trial (RCT) demonstrated rapid but individually variable hemodynamic improvement with therapeutic plasma exchange (TPE) in patients with septic shock. Prediction of clinical efficacy in specific sepsis treatments is fundamental for individualized sepsis therapy.MethodsIn the original RCT, patients with septic shock of < 24 h duration and norepinephrine (NE) requirement ≥ 0.4 μg/kg/min received standard of care (SOC) or SOC + one single TPE. Here, we report all clinical and biological endpoints of this study. Multivariate mixed-effects modeling of NE reduction was performed to investigate characteristics that could be associated with clinical response to TPE.ResultsA continuous effect of TPE on the reduction in NE doses over the initial 24 h was observed (SOC group: estimated NE dose reduction of 0.005 µg/kg/min per hour; TPE group: 0.018 µg/kg/min per hour, p = 0.004). Similarly, under TPE, serum lactate levels, continuously decreased over the initial 24 h in the TPE group, whereas lactate levels increased under SOC (p = 0.001). A reduction in biomarkers and disease mediators (such as PCT (p = 0.037), vWF:Ag (p < 0.001), Angpt-2 (p = 0.009), sTie-2 (p = 0.005)) along with a repletion of exhausted protective factors (such as AT-III (p = 0.026), Protein C (p = 0.012), ADAMTS-13 (p = 0.008)) could be observed in the TPE but not in the SOC group. In a multivariate mixed effects model, increasing baseline lactate levels led to greater NE dose reduction effects with TPE as opposed to SOC (p = 0.004).ConclusionsAdjunctive TPE is associated with the removal of injurious mediators and repletion of consumed protective factors altogether leading to preserved hemodynamic stabilization in refractory septic shock. We identified that baseline lactate concentration as a potential response predictor might guide future designing of large RCTs that will further evaluate TPE with regard to hard endpoints.Trial registration Retrospectively registered 18th January 2020 at clinicaltrials.gov (Identifier: NCT04231994).

Child saliva microbiota and caries: a randomized controlled maternal education trial in rural Uganda

Undernutrition is a public health challenge in sub-Saharan countries, including Uganda. In a previous randomized controlled trial (RCT) with a nutrition, hygiene and stimulation education intervention among mothers of 6 months’ old children, we found less caries in the intervention group when the children were 36 months of age. We now examined the effects of (i) the intervention on the microbiota, (ii) microbiota on caries, and (iii) the intervention and microbiota on caries. The original RCT comprised 511 mother/child pairs whereas in the current study we had access to data from 344/511 (67%) children aged 36 months. The saliva microbiota was determined using 16S rRNA gene sequencing. Carious lesions (a proxy for dental health) were identified using close-up intra-oral photographs of the upper front teeth. Statistical models were used to determine host-microbiota associations. The intervention had a significant effect on the microbiota, e.g. an increase in Streptococcus abundance and decreases in Alloprevotella and Tannerella. Significant associations between the microbiota and dental caries were identified: Positive associations of Capnocytophaga and Tannerella suggest that these taxa may be deleterious to dental health while negative associations of Granulicatella, Fusobacterium, and Abiotrophia suggest taxa potentially beneficial or benign contributors to dental health. Based on taxonomic profiles, the effects of the intervention and microbiota on dental health may be independent of one another. Educational interventions with emphasis on nutrition and oral hygiene may provide a feasible strategy to decrease progression of childhood caries in low-resource settings.

Is cognitive behaviour therapy applicable to individuals diagnosed with bipolar depression or suboptimal mood stabilizer treatment: a secondary analysis of a large pragmatic effectiveness trial

BackgroundEfficacy trials of medications and/or psychological interventions for bipolar disorders (BD) aim to recruit homogenous samples of patients who are euthymic and such populations show high levels of adherence to the treatments offered. This study describes a secondary analysis of a large-scale multi-centre pragmatic effectiveness randomized controlled trial (RCT) of cognitive behaviour therapy plus treatment as usual (CBT) or treatment as usual alone (TAU) and explores outcomes in individuals who were: (i) recruited in depressive episodes, or (ii) receiving suboptimal doses of or no mood stabilizers (MS).MethodsData were extract on two separate subsamples (out of 253 RCT participants). Sample 1 comprised 67 individuals in a depressive episode (CBT: 34; TAU: 33); Sample 2 comprised 39 individuals receiving suboptimal MS treatment (CBT: 19; TAU: 20). Survival analyses (adjusted for confounding variables) were used to explore recovery in Sample 1 and relapse in Sample 2.ResultsIn Sample 1 (individuals with depression), Cox proportional hazards regression model revealed that the median time to recovery was significantly shorter in the CBT group (10 weeks; 95% confidence intervals (CI) 8, 17) compared to the TAU group (17 weeks; 95% CI 9, 30) [Adjusted Hazard Ratio (HR) 1.89; 95% CI 1.04, 3.4; p < 0.035]. In Sample 2 (suboptimal MS), the median time to any relapse was significantly longer in the CBT group compared to the TAU group (~ 35 versus ~ 20 weeks; Adjusted HR 2.01; 95% CI 1.01, 3.96; p < 0.05) with the difference in survival time to first depressive relapse also reaching statistical significance (X2 = 14.23, df 6, p 0.027).ConclusionsAdjunctive use of CBT appears to have benefits for individuals diagnosed with BD who are highly representative of the patients seen in routine clinical practice, but often excluded from efficacy RCTs. However, as this is a secondary analysis of 42% of the original RCT sample, it is important to replicate these findings in independent larger scale studies specifically designed for purpose.

Trauma and Outcomes of Mentalization-Based Therapy for Individuals With Borderline Personality Disorder.

Recent meta-analyses suggest that many patients with borderline personality disorder have a history of complex trauma. Although trauma is central in mentalization-based approaches to the understanding of borderline personality disorder, surprisingly little is known about the effects of trauma on outcomes of mentalization-based treatment (MBT). This article investigates the prevalence and impact of childhood trauma among patients with borderline personality disorder participating in a randomized controlled trial (RCT) comparing day hospital MBT (MBT-DH) and intensive outpatient MBT (MBT-IOP). All 114 patients from the original multicenter RCT in the Netherlands were included in this study. Childhood trauma was assessed at baseline (with the Childhood Trauma Questionnaire), and its impact on symptom severity, interpersonal functioning, and borderline pathology was investigated through multilevel modeling for 36 months after the start of treatment. Childhood trauma was common among patients with borderline personality disorder referred to MBT, with more than 85% meeting cutoff criteria for substantial childhood trauma. Childhood trauma had little impact on outcomes of either MBT-DH or MBT-IOP in terms of improved borderline personality disorder features or interpersonal functioning. However, patients with substantial childhood trauma seemed to improve more rapidly with MBT-DH, as compared with MBT-IOP, in terms of symptom severity. In addition, patients with a history of emotional neglect showed more rapid changes in symptoms of borderline personality disorder with MBT-DH compared with MBT-IOP. Findings are discussed in the context of a social communicative approach to borderline personality disorder, with a focus on the need to address trauma in MBT.

The effect of protein supplements on weight loss, body composition, protein status, and micronutrients post laparoscopic sleeve gastrectomy (LSG): A Randomised Controlled Trial (RCT)

BackgroundLow protein intake post-bariatric surgery can result in protein malnutrition, and muscle mass loss. Authors aim to assess the effect of protein supplements on weight loss, body composition, and micronutrient status following LSG. MethodsThis is a double-blinded RCT conducted between February/2017 to January/2018. Eligible post LSG patients were randomized into the intervention group who received daily protein supplements containing 20 g of protein and placebo group received zero protein supplements. Both groups received a standardized diet. Weight loss, body composition, and micronutrient status were analyzed at 1, 3, and 6 months. Results48 participants were included in the final analysis (intervention: 21 and placebo:27). Excess weight loss percentage (EWL%) at 6 months was comparable between both groups (69.44 ± 21.99% and 71.40 ± 19.27% respectively). No significant difference observed in the anthropometric parameters. There was an increase in muscle mass and a decrease in muscle mass loss in the intervention group throughout the study period. However, these changes were not statistically significant. There was a significant increase in total protein (P=0.027) and magnesium (P=0.008) in the intervention group at 3 months. Albumin and iron levels were significantly higher at 6 months in the intervention group (P=0.036 &P=0.028 respectively). Other micronutrients did not differ at any time point between both groups. ConclusionProtein supplements resulted in significant improvement in total protein, albumin, magnesium, and iron levels post LSG. Although not significant, protein supplements helped in maintaining the muscle mass and preventing muscle mass loss. Original articleThis RCT is an original article and provides a level 2 evidence.

O18 LONG-TERM CROSSOVER RATE FROM WATCHFUL WAITING TO SURGERY OF INITIALLY MIDLY SYMPTOMATIC OR ASYMPTOMATIC INGUINAL HERNIAS IN MEN AGES 50 YEARS AND OLDER

Abstract Aim Inguinal hernia (IH) belongs to the most common surgical pathology worldwide. Approximately, one third of patients are asymptomatic. Watchful waiting (WW) has been regarded as a justifiable treatment option, but doubts still exist since high crossover (CO) rates to surgery may occur. The aim of this study is to assess the CO rates after 13-year follow-up of our randomized controlled trial (RCT). Material and Methods In our original study, 496 men with an asymptomatic or mildly symptomatic IH were randomly assigned to elective repair or WW. A retrospective review was conducted of patients initially assigned to WW. Primary outcome was CO rate to surgery. Secondary outcomes included reason for crossing over and time between initial randomisation and the CO to surgery. Results In the original RCT, 95 of 262 WW patients electively crossed over to surgery (35.4%) after 32.9 months. Currently, 212 of the 262 (81.0%) WW patients were reviewed, and 133/212 (62.7%) crossed over to surgery. Median follow-up was 13 years (range, 8-15 years). Mean time to CO was 35.2 months SD (40.8). Motivations for crossing over to surgery were predominantly due to progression of symptoms (83.5%), and in 8 (3.8%) cases due to an emergency event. Conclusions In the presented population, WW on the long-term remains a safe strategy, saving one third of patients an operation, although CO to surgery will likely occur. Insights into the natural course of untreated inguinal hernia that are valuable during patient counseling can be offered in the form of long-term CO rate due to progression of symptoms.

Expressed emotion and long-term outcome among adolescents with anorexia nervosa.

The purpose of the current study is to examine expressed emotion (EE) and long-term treatment outcome among adolescents participating in a randomized controlled trial (RCT) for treatment of anorexia nervosa (AN). It was hypothesized that patients with high EE parents at baseline would show more severe symptoms at end-of-treatment, 12-month follow-up, and 4-year follow-up than patients from low EE families. Secondary data analysis was conducted of original RCT data from a two-site eating disorder treatment trial conducted in the United States. Participants were 121 adolescents with AN who completed measures of EE, eating disorder psychopathology, depression, and self-esteem. Generalized estimating equations showed that participants who were in the Low EE group achieved a more accelerated drop in depression scores in the context of treatment (first 12 months) than participants in the High EE group. No other significant Group × Time interactions were found. Findings suggest that high parental EE at baseline does not indicate that adolescent patients with AN will fare poorly 4 years later.

Long-Term Impact of Arteriovenous Fistula Ligation on Cardiac Structure and Function in Kidney Transplant Recipients: A 5-Year Follow-Up Observational Cohort Study.

The long-term effects of arteriovenous fistula (AVF) ligation on cardiovascular structure following kidney transplantation remain uncertain. A prospective randomized, controlled trial (RCT) examined the effect of AVF ligation at 6 months on cardiovascular magnetic resonance imaging (CMR)-derived parameters in 27 kidney transplant recipients compared with 27 controls. A mean decrease in left ventricular mass (LVM) of 22.1 g (95% CI, 15.0 to 29.1) was observed compared with an increase of 1.2 g (95% CI, -4.8 to 7.2) in the control group (P<0.001). We conducted a long-term follow-up observational cohort study in the treated cohort to determine the evolution of CMR-derived parameters compared with those documented at 6 months post-AVF ligation. We performed CMR at long-term follow-up in the AVF ligation observational cohort from our original RCT published in 2019. Results were compared with CMR at 6 months postintervention. The coprimary end point was the change in CMR-derived LVM and LVM index at long-term follow-up from imaging at 6 months postindex procedure. At a median of 5.1 years (interquartile range, 4.7-5.5 years), 17 patients in the AVF ligation group were studied with repeat CMR with a median duration to follow-up imaging of 5.1 years (IQR, 4.7-5.5 years). Statistically significant further reductions in LVM (-17.6±23.0 g, P=0.006) and LVM index (-10.0±13.0 g/m2, P=0.006) were documented. The benefit of AVF ligation on LVM and LVM index regression appears to persist long term. This has the potential to lead to a significant reduction in cardiovascular mortality.

Open-label placebo for chronic low back pain: a 5-year follow-up.

Long-term follow-up of patients treated with open-label placebo (OLP) are nonexistent. In this article, we report a 5-year follow-up of a 3-week OLP randomized controlled trial (RCT) in patients with chronic low back pain. We recontacted the participants of original RCT and reassessed their pain, disability, and use of pain medication. We obtained follow-up data from 55 participants (82% of those who took OLP during the parent RCT), with a mean elapsed time between the end of the 3 weeks placebo trial and the follow-up interview of 55 months (SD = 7.85). We found significant reductions in both pain and disability between the baseline assessment immediately before the 3 weeks trial with placebo pills and the original trial endpoint (P < 0.00001 for the 2 primary outcomes of pain and disability). At the 5-year follow-up, we found no significant differences in either outcome between original trial endpoint and follow-up. Improvements persisted after 5 years and were accompanied by substantial reductions compared with baseline in the use of pain medication (from 87% to 38%), comprising analgesics (from 80% to 31%), antidepressants (from 24% to 11%), and benzodiazepines (from 15% to 5%). By contrast, the use of alternative approaches to pain management increased (from 18% to 29%). Although the reduction in pain and medication is comparable with the improvements that occurred in the original study, a major limitation of this long-term follow-up is the absence of controls for spontaneous improvement and new cointerventions. Nonetheless, our data suggest that reductions in pain and disability after OLP may be long lasting.

11. Long-term outcomes following intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: five-year treatment results from a prospective randomized double-blind sham-controlled multicenter study

BACKGROUND CONTEXT Current literature suggests that degenerated or damaged vertebral endplates are a significant cause of vertebrogenic chronic low back pain (CLBP). Modic changes are one objective MRI biomarker for this specific subset of patients. Intraosseous basivertebral nerve (BVN) ablation, using radiofrequency energy under image guidance, was compared to a sham control in a randomized controlled trial (RCT) and demonstrated superiority at 12 months. Two-year data from the treatment arm of this RCT showed maintenance of clinical improvements at 2 years following ablation of the BVN. PURPOSE This study reports the 5-year clinical outcomes in this cohort of patients. STUDY DESIGN/SETTING Prospective, open label, single arm five-year follow-up of the SMART RCT. The primary requirements for inclusion in the original RCT were CLBP with a duration greater than 6 months; CLBP nonresponsive to at least 6 months of nonsurgical management; and Modic Type 1 or 2 changes at the vertebral endplates of the levels targeted for treatment. BVN ablation was performed under image guidance in an outpatient setting for those patients randomized to the treatment arm. PATIENT SAMPLE This five-year follow-up study was conducted in the U.S. at the 13 study sites that treated patients in the original RCT. In the US BVN ablation arm, 117 patients were successfully treated and targeted, and comprise the per protocol (PP) population for this study. OUTCOME MEASURES Patient-reported outcomes of Oswestry Disability Index (ODI), visual analog score (VAS), responder rates, postablation treatments, and patient satisfaction were collected. The primary outcome was mean change in ODI from baseline. Comparisons between the postablation and baseline values were performed using a paired t-test at the 0.05 level of significance. METHODS A single telephonic study visit was conducted by an independent research nurse between June 2019 to November 2019 (a minimum of 5 years post-BVN ablation). Self-reported patient outcomes were collected via interview using validated questionnaires that were sent in advance of the visit. No additional interventions were required in the 5-year+ follow-up study. RESULTS One hundred of the 117 US treated patients (retention rate 85%) were available for review with a mean follow-up of 6.4 years (range 5.4 to 7.8 years). Mean ODI score significantly improved from 42.81 to 16.86 at 5 years of follow-up, a reduction of 25.95 points (p 50% reduction in pain, 47% reported a >75% reduction in pain, and 34% reported complete pain resolution. Responder rates were maintained at five years with 75% of patients exceeding a combined threshold of ≥15-point ODI and ≥2-point VAS for function and pain improvement, and 65% reporting they had returned to their pre– low back pain activity level. CONCLUSIONS CLBP patients treated with BVN ablation exhibit sustained clinical improvements in function and pain with high responder rates at a mean of 6.4 years following treatment. BVN ablation appears to be a durable, minimally invasive treatment for the relief of vertebrogenic CLBP. FDA DEVICE/DRUG STATUS Intracept procedure (Approved for this indication).

Contamination and washing of cloth masks and risk of infection among hospital health workers in Vietnam: a post hoc analysis of a randomised controlled trial.

BackgroundIn a previous randomised controlled trial (RCT) in hospital healthcare workers (HCWs), cloth masks resulted in a higher risk of respiratory infections compared with medical masks. This was the only published RCT of cloth masks at the time of the COVID-19 pandemic.ObjectiveTo do a post hoc analysis of unpublished data on mask washing and mask contamination from the original RCT to further understand poor performance of the two-layered cotton cloth mask used by HCWs in that RCT.Setting14 secondary-level/tertiary-level hospitals in Hanoi, Vietnam.ParticipantsA subgroup of 607 HCWs aged ≥18 years working full time in selected high-risk wards, who used a two-layered cloth mask and were part of a randomised controlled clinical trial comparing medical masks and cloth masks.InterventionWashing method for cloth masks (self-washing or hospital laundry). A substudy of contamination of a sample of 15 cloth and medical masks was also conducted.Outcome measureInfection rate over 4 weeks of follow up and viral contamination of masks tested by multiplex PCR.ResultsViral contamination with rhinovirus was identified on both used medical and cloth masks. Most HCW (77% of daily washing) self-washed their masks by hand. The risk of infection was more than double among HCW self-washing their masks compared with the hospital laundry (HR 2.04 (95% CI 1.03 to 4.00); p=0.04). There was no significant difference in infection between HCW who wore cloth masks washed in the hospital laundry compared with medical masks (p=0.5).ConclusionsUsing self-reported method of washing, we showed double the risk of infection with seasonal respiratory viruses if masks were self-washed by hand by HCWs. The majority of HCWs in the study reported hand-washing their mask themselves. This could explain the poor performance of two layered cloth masks, if the self-washing was inadequate. Cloth masks washed in the hospital laundry were as protective as medical masks. Both cloth and medical masks were contaminated, but only cloth masks were reused in the study, reiterating the importance of daily washing of reusable cloth masks using proper method. A well-washed cloth mask can be as protective as a medical mask.Trial resgistration numberACTRN12610000887077.

Thyroid function in neonates conceived after hysterosalpingography with iodinated contrast.

STUDY QUESTIONDoes exposure to preconceptional hysterosalpingography (HSG) with iodinated oil-based contrast affect neonatal thyroid function as compared to iodinated water-based contrast?SUMMARY ANSWERPreconceptional HSG with iodinated contrast did not influence the neonatal thyroid function.WHAT IS KNOWN ALREADYHSG is a commonly applied tubal patency test during fertility work-up in which either oil- or water-based contrast is used. Oil-based contrast contains more iodine compared to water-based contrast. A previous study in an East Asian population found an increased risk of congenital hypothyroidism (CH) in neonates whose mothers were exposed to high amounts of oil-based contrast during HSG.STUDY DESIGN, SIZE, DURATIONThis is a retrospective data analysis of the H2Oil study, a randomized controlled trial (RCT) comparing HSG with the use of oil- versus water-based contrast during fertility work-up. After an HSG with oil-based contrast, 214 women had an ongoing pregnancy within 6 months leading to a live birth compared to 155 women after HSG with water-based contrast.PARTICIPANTS/MATERIALS, SETTING, METHODSOf the 369 women who had a live born infant, 208 consented to be approached for future research and 138 provided informed consent to collect data on the thyroid function tests of their offspring (n = 140). Thyroid function tests of these children were retrieved from the Dutch neonatal screening program, which includes the assessment of total thyroxine (T4) in all newborns, followed by thyroid-stimulating hormone only in those with a T4 level of ≤ −0.8 SD score. Furthermore, amount of contrast medium used and time between HSG and conception were compared between the two study groups.MAIN RESULTS AND THE ROLE OF CHANCEData were collected from 140 neonates conceived after HSG with oil-based (n = 76) or water-based (n = 64) contrast. The median T4 concentration was 87.0 nmol/l [76.0–96.0] in the oil group and 90.0 nmol/l [78.0–106.0] in the water group (P = 0.13). None of the neonates had a positive screening result for CH.The median amount of contrast medium used was 9.0 ml [interquartile range (IQR), 6.0–11.8] in the oil-group and 10.0 ml [IQR, 7.5–14.0] in the water group (P = 0.43). No influence of the amount of contrast on the effect of contrast group on T4 concentrations was found (P-value for interaction, 0.37).LIMITATIONS, REASONS FOR CAUTIONA relatively small sample size and possible attrition at follow-up are limitations of this study. Although our results suggest that the use of iodinated contrast media for HSG is safe for the offspring, the impact of a decrease in maternal thyroid function on offspring neurodevelopment could not be excluded, as data on maternal thyroid function after HSG and during conception were lacking.WIDER IMPLICATIONS OF THE FINDINGSAs HSG with oil-based contrast does not affect thyroid function of the offspring, there is no reason to withhold this contrast to infertile women undergoing HSG. Future studies should investigate whether HSG with iodinated contrast influences the periconceptional maternal thyroid function and, consequently, offspring neurodevelopment.STUDY FUNDING/COMPETING INTEREST(S)This study received no funding. The original H2Oil RCT was an investigator-initiated study that was funded by the two academic institutions (Academic Medical Center and VU University Medical Center) of the Amsterdam UMC. The funders had no role in study design, collection, analysis and intrepretation of the data. I.R. reports receiving travel fee from Guerbet. C.B.L. reports speakers fee from Ferring in the past and research grants from Ferring, Merck and Guerbet. K.D. reports receiving travel fee and speakers fee from Guerbet. B.W.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck KGaA and Guerbet and travel and research grants from Merck KGaA and Guerbet. V.M. reports receiving travel fee and speakers fee as well as research grants from Guerbet. The other authors do not report conflicts of interest.TRIAL REGISTRATION NUMBERNetherlands Trial Register NTR 7526 (Neonates born after the H2Oil study), NTR 3270 (original H2Oil study), www.trialregister.nl

Burn scar outcome at six and 12 months after injury in children with partial thickness scalds: Effects of dressing treatment.

In line with other researchers in the field of burns' care, we think that research investigating the long-term outcome of scars is largely lacking. As scarring is of the utmost importance to the patient, clinicians who treat burns must aim to find treatments that lead to a good end result. The aim of this study was to study scar outcomes at six and 12 months after injury. It is an extension of a previous randomised controlled trial (RCT) in which two dressings (porcine xenograft and silver foam dressing) were examined with respect to their ability to help heal partial thickness scalds. Children aged six months - six years with acute partial thickness scalds, on the trunk, or extremities, or both, were included. In the previous study, the silver foam was found to have significantly shorter healing times than the xenograft. Children were assessed at six and 12 months after injury for this study, and photographs were taken of the burn site, and both the patient and observer scar assessment scale (POSAS) and the Vancouver scar scale (VSS) were completed and evaluated by blinded observers. Of the 58 children from the original RCT, 39 returned to the clinic for evaluation of their scars at six months, and 34 at 12 months after injury. There were no differences in POSAS, VSS total scores, or incidence of hypertrophic scarring between the different dressings. Fifteen children were assessed as having hypertrophic scarring, all of whom had healing times that had extended beyond 14 days. This study compared burn scarring after two different treatments for burns in children with partial-thickness scalds and the data suggested that neither dressing had a more favourable impact on scar outcome. The conclusion is, however, tempered by the non-return of all the patients to the follow up. However, as anticipated, regardless of the dressing used, longer healing times were associated with higher scar scores (more scarring) and hypertrophic scarring.