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Trial Registration | ClinicalTrials.gov Identifier: | PMC10308298 | ||
Introduction | psychotic symptoms, Psychosis, First-episode psychosis, psychosis | REMISSION | First-episode psychosis is typically preceded by a prodrome characterized by nonspecific and attenuated psychotic symptoms and functional impairment. Ultrahigh risk criteria were introduced to prospectively identify this prodromal period.Unraveling the heterogeneity in the ultrahigh risk population is paramount to identify subgroups for whom treatments can be tailored.The current study (Staged Treatment in Early Psychosis [STEP]) aimed to evaluate the outcomes of a sequential multiple assignment randomized clinical trial (SMART) comprising support and problem solving (SPS), cognitive-behavioral case management (CBCM), and fluoxetine for individuals at ultrahigh risk for psychosis.Hypothesis 1. Open-label SPS would produce a remission rate of 50% (step 1), based on modeling using previous randomized clinical trial data.Hypothesis 2a. CBCM would result in significantly better functional outcome than SPS (step 2).Hypothesis 2b. In the CBCM group, baseline cognitive biases or vulnerabilities would predict remission and clinical outcome (including functioning) andHypothesis 2c. In the CBCM group, participants with better outcomes and those who remitted would show significantly greater change on these variables than those with worse outcomes and those who did not remit.Hypothesis 3. Antidepressant medication (when added to background CBCM) would result in significantly better clinical outcomes than placebo (step 3).Hypothesis 4. In those who remitted to step 1 and 2 treatments (SPS and CBCM), a maintenance treatment of SPS would result in a significantly lower rate of relapse than monitoring. | PMC10308298 |
Methods | PMC10308298 | |||
Study Design and Setting | The SMART design comprised 3 steps: open-label SPS (6 weeks), SPS vs CBCM (20 weeks), and CBCM with fluoxetine vs CBCM with placebo (26 weeks) (eFigure 1 in | PMC10308298 | ||
Participants | Prodromal Questionnaire-16 | Individuals seeking treatment were eligible for trial inclusion if they were aged 12 to 25 years, met ultrahigh risk criteria,Participants were screened using a standardized clinical assessment and the Prodromal Questionnaire-16 (PQ-16). | PMC10308298 | |
Randomization | Depression | REMISSION, BLIND | Randomization was based on computer-generated treatment allocations prepared by independent personnel. Participants who met remission criteria at the end of step 1 were randomized to SPS or monitoring; those who did not remit were randomized to CBCM or SPS. Assessors were blind to treatment allocation. Participants in the nonremission arm of the trial were randomized a second time based on remission status at the end of step 2. Those who remitted were randomized to SPS or monitoring; those who did not were randomized to CBCM with fluoxetine or CBCM with placebo, stratified by Montgomery-Åsberg Depression Rating Scale (MADRS) total score (lower than 21 vs 21 or higher). In step 3, assessors and participants were blind to treatment allocation. | PMC10308298 |
Treatments | PMC10308298 | |||
Monitoring | Clinicians monitored participants’ mental state and risk at 3, 6, 9, and 12 months postentry to step 1. Any deterioration in mental health was appropriately managed. | PMC10308298 | ||
SPS | REMISSION | Manualized supportive counseling and problem-solving strategies were delivered within a positive psychology framework. Sessions were 30 to 50 minutes (weekly to fortnightly). In the relapse prevention and remission trial arm, participants received monthly SPS for up to 12 months. | PMC10308298 | |
CBCM | CBCM, a specialized manualized psychosocial intervention, consisted of cognitive behavioral therapy (CBT) provided within a case management framework. | PMC10308298 | ||
Medications | Step 3 comprised 1 capsule of fluoxetine, 20 mg per day, or placebo, increasing to 40 mg per day or 2 placebo capsules after 6 weeks if clinical response was insufficient as judged by the treating psychiatrist. At 12 weeks, a fast-fail option was available for participants who had deteriorated or had not responded to treatment. Through a shared decision-making process, participants chose to either continue as randomized, increase the fluoxetine or placebo dosage, or receive an add-on of low-dose antipsychotic medication (quetiapine, 50-300 mg per day, or aripiprazole, 10-30 mg per day) or long-chain ω-3 fatty acids (2.8 g per day of marine fish oil in 4 × 0.7-g capsules containing approximately 1.4 g eicosapentanoic and docosahexanoic acid). | PMC10308298 | ||
Outcome Measures | For power purposes and sample size calculation,Other outcome measures included the Brief Psychiatric Rating Scale (BPRS);Therapy sessions were audio recorded with consent and independently rated for fidelity. Based on the minimum number of sessions provided for each treatment at each step, | PMC10308298 | ||
Statistical Analysis | The study was powered to detect a small to medium effect size (Cohen | PMC10308298 | ||
Results | PMC10308298 | |||
Participant Flow | Of 1343 individuals considered, 342 were included (198 female; mean [SD] age, 17.7 [3.1] years) ( | PMC10308298 | ||
Sample Demographic Characteristics at Baseline | Depression, perceptual abnormalities | Abbreviations: BPRS, Brief Psychiatric Rating Scale; CAARMS, Comprehensive Assessment of At-Risk Mental States; MADRS, Montgomery-Åsberg Depression Rating Scale; PACE, Personal Assessment and Crisis Evaluation; SANS, Scale for the Assessment of Negative Symptoms; SPS, support and problem solving; SOFAS, Social and Occupational Functioning Assessment Scale; TAFE, Technical and Further Education.Severity score ranges from 0 (never or absent) to 6 (psychotic and severe).Frequency score ranges from 0 (absent) to 6 (continuous).Composite score is the sum of the product of severity and frequency of the 4 subscales (unusual thought content, nonbizarre ideas, perceptual abnormalities, and disorganized speech). | PMC10308298 | |
CONSORT Diagram | Discontinuation rates were 17.8% (61 of 342; step 1), 47.7% (134 of 281; step 2), and 38.4% (53 of 138; step 3). Reasons for discontinuation are listed in eTable 1 in | PMC10308298 | ||
Hypothesis 1: Remission Rates | REMISSION | Remission rates (ie, sustained remission) across treatment arms at the end of steps 1, 2, and 3 were 8.5%, 10.3%, and 11.4%, respectively. The overall remission rate (ie, sustained remission at the end of at least one step) was 27.2%. There were no significant differences in remission rates between treatments at the end of step 2 (9.8% [CBCM] vs 10.7% [SPS]; | PMC10308298 | |
Hypothesis 2a: Effect of CBCM on Functioning and Clinical Measures | For the primary outcome, intent-to-treat analysis revealed no significant difference in mean scores on the Global Functioning: Social and Role scales between SPS and CBCM at 6 months ( | PMC10308298 | ||
General Linear Model Analysis Comparing Cognitive-Behavioral Case Management (CBCM) and Support and Problem Solving (SPS) at 6 Months and CBCM With Fluoxetine and CBCM With Placebo at 12 Months | Depression, perceptual abnormalities | INTERACTION | Abbreviations: AQoL, Assessment of Quality of Life; BPRS, Brief Psychiatric Rating Scale; CAARMS, Comprehensive Assessment of At-Risk Mental States; DACOBS, Davos Assessment of Cognitive Biases Scale; DS, disorganized speech; GF, Global Functioning Scale; MADRS, Montgomery-Åsberg Depression Rating Scale; NBI, nonbizarre ideas; PA, perceptual abnormalities; SANS, Scale for the Assessment of Negative Symptoms; SOFAS, Social and Occupational Functioning Assessment Scale; UTC, unusual thought content.Comparing SPS and CBCM with baseline score as a covariate.Comparing CBCM + placebo and CBCM + fluoxetine with baseline score as a covariate.Interaction between step 2 treatment (SPS/CBCM) and step 3 treatment (CBCM + placebo / CBCM + fluoxetine) with baseline score as a covariate.The mean sample sizes for each group over the multiple imputations.Missing data handled by multiple imputation. | PMC10308298 |
Hypotheses 2b and 2c: Effect of Baseline Cognitive Biases or Vulnerabilities on Remission and Treatment Outcome | While this hypothesis was intended to be restricted to the CBCM group, CBCM did not produce superior outcomes or greater improvement on cognitive biases or vulnerabilities than SPS (The correlation between baseline DACOBS total and 6-month outcomes and between change in DACOBS total and change in outcomes among those who did not remit at step 1 is presented in eTable 2 in | PMC10308298 | ||
Hypothesis 3: Effect of Antidepressant Medication on Clinical Outcome | Both treatment arms (CBCM with fluoxetine and CBCM with placebo) showed improvement by the end of step 3, with no significant difference on any measure ( | PMC10308298 | ||
Changes in Mean Symptom and Functioning Scores From Baseline to the End of Step 3 | Depression | Circles represent individual participant data. Fluoxetine or placebo commenced at 6 months (start of step 3). AQoL indicates assessment of quality of life; BPRS, Brief Psychiatric Rating Scale; CBCM, cognitive-behavioral case management; DACOBS, Davos Assessment of Cognitive Biases Scale; MADRS, Montgomery-Åsberg Depression Rating Scale; SANS, Scale for the Assessment of Negative Symptoms; SOFAS, Social and Occupational Functioning Assessment Scale. | PMC10308298 | |
Hypothesis 4: Relapse Rates and Outcomes of Participants Who Remitted | Six-month relapse rates were higher in the SPS group (59.8%) than monitoring (16.9%) among participants who remitted at step 1 (Six-month SOFAS scores significantly differed between SPS and monitoring among participants who remitted at step 1 (effect size, 0.91; 95% CI, 0.95-19.6; | PMC10308298 | ||
Transition to Psychosis | The Kaplan-Meier–estimated 12-month transition rate was 13.5% (95% CI, 9.1-18.0). The log-rank test indicated no significant difference between groups at 6 and 12 months ( | PMC10308298 | ||
Overall Treatment Effect and Complete-Case and Per-Protocol Analyses | Across the entire sample, small to medium effect sizes were found at 6 and 12 months on measures of symptoms and functioning (eTable 6 in | PMC10308298 | ||
Treatment Adherence and Fidelity | The mean (SD) number of sessions attended was 2.3 (1.5) and 5.7 (3.9) for SPS at steps 1 and 2, respectively, and 6.2 (3.7) at step 2 and 6.0 (4.2) at step 3 for CBCM. A total of 199 recordings (65 participants; 24 clinicians) were rated for fidelity, a mean (SD) of 3.1 (2.1) per participant and 8.3 (9.3) per clinician. The probability that each type of treatment was given as intended was estimated to be 0.95 (95% CI, 0.88-0.98) for SPS and 0.59 (95% CI, 0.51-0.67) for CBCM, indicating higher fidelity to SPS ( | PMC10308298 | ||
Adverse Events | ADVERSE EVENTS | Few adverse and serious adverse events occurred. No significant group differences were observed (eTable 17 in | PMC10308298 | |
Discussion | STAR*D, Depression, psychosis | SECONDARY, REMISSION | This is the first SMART trial to be conducted in the ultrahigh risk population. The primary outcome of functioning at the end of step 2 was selected for sample size and power calculations; however, results should be considered as a whole, spanning all steps. For the primary outcome, there was no difference between CBCM and SPS. While the sample overall showed modest functional and symptomatic improvement over 12 months, remission rates were lower than expected, the transition rate was slightly higher than anticipated, and there was no significant difference between groups on the secondary outcomes. Even when remission was achieved, it was difficult to maintain, and continuing supportive therapy did not reduce relapse rates compared to monitoring. While the monitoring group showed greater improvement in 6-month SOFAS scores than SPS, this was likely due to 4 outliers in the SPS group whose 6-month SOFAS outcomes were worse than the other individuals who remitted at step 1. The findings suggest that enhancing the intensity of treatment with psychological interventions (CBCM) or antidepressant medication in real-world youth mental health services does not produce benefit over continuing simpler care for a longer period. However, some caution is needed given the following caveats.First, the bar for remission was high, although appropriately so, requiring sustained symptomatic and functional improvement. If remission had been based on symptomatic improvement only, the overall remission rate would have increased to 41.2% (compared to 27.2%).Second, the rate of treatment discontinuation was substantial (18% at step 1, 48% at step 2, and 38% at step 3). However, this rate was comparable to that of the seminal Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial,Third, adherence to psychological therapy and medication and fidelity to CBCM were suboptimal. These challenges are common in psychotherapy trials.A positive note is that transition to psychosis was significantly lower among participants who remitted (3.3%) than those who did not (17.4%). While this may indicate that trials with transition as the primary outcome may enroll an enriched sample by filtering out those with early remission, relapse to ultrahigh risk positive status was common. Although all treatment arms showed a trend of symptomatic and functional improvement by the end of steps 2 and 3, improvement was typically modest, slow to emerge, and somewhat fragile. The lack of a no-treatment comparison group makes firm conclusions difficult.While some caution is warranted, and needs-based care should continue to be provided to all patients at ultrahigh risk, the findings indicate the need for further sequential randomized trials examining existing treatments with improved adherence and fidelity and for the development of innovative, more effective treatments and enhanced modes of delivery. This could include virtual reality; neurofeedback; higher-fidelity CBT; individual placement and support; biotherapies (eg, cannabidiol, | PMC10308298 |
Strengths and Limitations | psychosis | To our knowledge, this is the largest ultrahigh risk for psychosis trial to date, reflecting the utility of primary care youth mental health platforms, particularly when recruiting medication-naive participants. However, the treatment provided was insufficient for a large proportion of our sample. Despite high dropout rates, the achieved sample sizes (192 at step 2 and 92 at step 3) were similar to original expectations because of the higher than expected nonremission rates. The moderate fidelity to CBCM, the low adherence to medication, and high degree of treatment discontinuation and missing data may have limited the ability to test hypotheses and identify benefits of treatments. | PMC10308298 | |
Conclusions | REMISSION | Enhancing the intensity of treatment with psychological interventions or medications was challenging to implement with fidelity and adherence in this largely primary care-based sample but nevertheless could not be demonstrated to produce any benefit over and above continuing a simpler form of care. Low remission and high relapse rates confirm the sustained vulnerability and substantial morbidity of the ultrahigh risk population and highlight the need to conduct further adaptive trials, develop new treatments, provide sustained specialist care, and identify subgroups for whom treatments can be tailored. | PMC10308298 | |
References | REMISSION | Trial protocolClick here for additional data file.eMethodseTable 1. Reasons for treatment discontinuation (%)eTable 2. Pearson correlation between baseline DACOBS total and 6-month outcomes and between change in DACOBS total and change in outcomes (Step 1 non-remitters)eTable 3. 12-month outcomes of the fast-fail groupeTable 4. General linear model analysis comparing SPS and monitoring (Step 1 remitters) at 6 and 12 months with data handled using multiple imputationeTable 5. General linear model analysis comparing SPS and monitoring (Step 2 remitters) at 12 months with data handled using multiple imputationeTable 6. Effect sizes (Cohen’s d) at 6 and 12 months across the entire sampleeTable 7. Complete-case and per-protocol analysis comparing CBCM and SPS at 6 monthseTable 8. Complete-case and per-protocol analysis comparing CBCM+fluoxetine and CBCM+placebo at 12 monthseTable 9. Complete-case and per-protocol analysis of remission rateseTable 10. Complete-case and per-protocol analysis comparing relapse rates between SPS and monitoring (Step 1 remitters) at 6 and 12 monthseTable 11. Complete-case and per-protocol analysis comparing relapse rates between SPS and monitoring (Step 2 remitters) at 12 months using logistic regressioneTable 12. Complete-case and per-protocol analysis comparing SPS and monitoring (Step 1 remitters) at 6 monthseTable 13. Complete-case and per-protocol analysis comparing SPS and monitoring (Step 1 remitters) at 12 monthseTable 14. Complete-case and per-protocol analysis comparing SPS and monitoring (Step 2 remitters) at 12 monthseTable 15. Kaplan-Meier estimated transition rates (complete-case and per-protocol analysis)eTable 16. Treatment adherence rateseTable 17. Adverse eventseFigure 1. Changes in mean symptom and functioning scores from baseline to the end of Step 2eFigure 2. Changes in mean CAARMS severity scores from baseline to the end of Step 2 (panel A) and Step 3 (panel B)eFigure 3. Changes in mean CAARMS frequency scores from baseline to the end of Step 2 (panel A) and Step 3 (panel B)Click here for additional data file.Data sharing statementClick here for additional data file. | PMC10308298 | |
Methods | We leveraged the Early Life Interventions for Childhood Growth and Development in Tanzania (ELICIT) trial, a randomized double-blind placebo-controlled trial of antimicrobial therapy with azithromycin and nitazoxanide provided quarterly to infants from 6 to 15 months of age. We tested 5,479 stool samples at time points across the study for 34 enteropathogens using quantitative PCR. | PMC10734999 | ||
Results | There was substantial carriage of enteropathogens in stool. Azithromycin administration led to reductions in | PMC10734999 | ||
Conclusion | infections | INFECTIONS | The antimicrobial intervention of quarterly azithromycin plus or minus nitazoxanide led to only transient decreases in enteric infections with | PMC10734999 |
Data Availability | All relevant data are within the paper and its | PMC10734999 | ||
Introduction | infections | CNS INFECTIONS, INFECTIONS | Early enteric infections in children in low-resource settings are an established risk factor for poor growth [This background formed the rationale for the Early Life Interventions for Childhood Growth and Development in Tanzania (ELICIT) trial, a randomized double-blind placebo-controlled trial of antimicrobial therapy provided to infants [Here, we examine the results of qPCR testing for 34 enteric pathogens on stool samples collected at five timepoints. Specifically, we tested stool collected at 6 months (prior to the first dose of azithromycin or placebo), 6.5 months (two weeks after receiving azithromycin or placebo), 12 months (3 months after receiving azithromycin or placebo), 12.5 months (2 weeks after receiving azithromycin and nitazoxanide or placebo) and 18 months (3 months after receiving azithromycin and nitazoxanide or placebo). This sampling time frame allowed us to assess the extent to which the antimicrobial intervention had an effect on enteric infections and to interpret the lack of effect of this antimicrobial regimen on childhood growth. | PMC10734999 |
Methods | PMC10734999 | |||
Study enrollment and interventions | The ELICIT study methods have been previously reported in detail [ | PMC10734999 | ||
Data and sample collection | Use of non-study antibiotics by study children, defined as any antibiotic that was not part of the study intervention, was identified using a standardized questionnaire at monthly visits. Child lengths using measuring boards and weights using digital scales were measured every three months. Stool samples were collected at 6, 6.5, 12, 12.5, and 18 months of age, and 1,141 children contributed at least 1 sample. The 6 and 12 month samples were required to be collected prior to administration of study antimicrobials. The study protocol was approved by the National Institute for Medical Research (NIMR) of Tanzania and the Tanzanian Food and Drug Administration (TFDA) and the Institutional Review Board at the University of Virginia. Mothers gave written informed consent to participate either during pregnancy or at the time of enrollment. The study was registered at ClinicalTrials.gov: NCT03268902. | PMC10734999 | ||
Stool testing | Procedures for sample extraction and testing have been previously detailed [ | PMC10734999 | ||
Statistical analysis | enteric infection | REGRESSION | Pathogens with an overall prevalence of at least 5% were included in the analyses of pathogen carriage. At a prevalence of 5% in the placebo arm, we had 80% power to detect a prevalence in the antimicrobial arm of 1.8%, a 3.2% difference; at a prevalence of 20%, we had 80% power to detect a prevalence of 13.6% in the antimicrobial arm, a 6.4% difference. To assess whether missing pathogen data were associated with treatment arm, we fit a logistic regression model with treatment arm as the predictor, adjusted for collection time. To estimate risk differences, we used g-computation via the R package riskCommunicator with Poisson regression, with clustering by individual to account for repeated measures, to estimate the effect of treatment arm on the absolute difference in pathogen detection at each time point [To assess whether the benefit of treatment was restricted to children who had an enteric infection, we evaluated whether the effect of treatment arm on short-term changes in growth (LAZ and WAZ) differed depending on baseline detection of each pathogen in the 6- or 12-month (pretreatment) stool samples. For this analysis, we restricted to children who had complete follow-up including growth outcomes at 18 months of age. We fit a generalized linear model with a Gaussian distribution to estimate the difference in length at 9 and 15 months (three months after antibiotic treatment) between treatment arms in subgroups defined by baseline detection of each pathogen. Adjustment covariates included pretreatment length and calendar month of birth based on previously observed differences in growth by birth month [We then estimated the association between antimicrobial treatment arm and detection of the macrolide resistance conferring genes | PMC10734999 |
Results | The baseline characteristics of the children in this study are summarized in | PMC10734999 | ||
Sample testing by qPCR, receipt of non-study antibiotics, and anthropometry by intervention arm. | There was substantial detection of enteric pathogens as we have noted previously [ | PMC10734999 | ||
Overall pathogen prevalence in the stool of ELICIT children at 6, 12, and 18 months by qPCR. | enteropathogen, enteroaggregative | Y axis shows prevalence or proportion positive. EAEC = enteroaggregative We examined the effect of receiving study antimicrobial versus placebo on enteropathogen carriage. | PMC10734999 | |
Difference in enteropathogen detection in the antibiotic versus placebo arms at 6, 6.5, 12, 12.5, and 18 months. | PENICILLINS | X axis is the absolute difference in pathogen prevalence between the antibiotic and placebo arms. Negative values to the left of 0.0 represent lower carriage in the active arm.Because children frequently received non-study antibiotics, we examined the effect of receiving such antibiotics on pathogens as well. Penicillins were the most frequently used class, followed by metronidazole, sulfonamides, and macrolides ( | PMC10734999 | |
Difference in pathogen detection in children that recently received non-study antibiotics. | X axis is the absolute difference in those that received non-study antibiotics during the month prior to 6, 12, and 18 months versus those that did not receive non-study antibiotics. Negative values to the left of 0.0 represent lower carriage with receipt of non-study antibiotics.We examined whether a growth benefit was observed with study antimicrobial in the children who carried the enteric pathogens that have most consistently been associated with growth deficits, namely | PMC10734999 | ||
Difference in 3 month growth outcomes by treatment arm stratified by pathogen detection at 6 and 12 months of age. | Shown are the subset of children at 6 and 12 months with We also tested for carriage of antimicrobial resistance genes by qPCR within this customized TAC card. Receiving antimicrobials rather than placebo slightly increased the risk of detecting the macrolide resistance genes | PMC10734999 | ||
Discussion | ETEC diarrhea, intestinal infections, infections, reinfections, ETEC | INFECTIONS, INTESTINAL INFECTIONS | The ELICIT trial administered single-dose azithromycin plus or minus nitazoxanide quarterly to infants under the hypothesis that antibiotic treatment of the intestinal infections associated with poor growth could reduce child stunting. In the primary analysis no effect on childhood growth or stunting was seen at 18 months of age [First, we did observe a clear and large effect of azithromycin on It was surprising to not see an effect of azithromycin against ETEC, as this antibiotic clearly has shown an effect on ETEC diarrhea [Therefore the underlying hypothesis of the ELICIT study was not able to be completely tested, as it remains possible that a better antimicrobial regimen that better and more durably reduces the pathogens associated with poor growth (There was a suggestion of improved weight-for-age Z score and length-for-age Z score in the subset of children infected with Limitations of this work include that our sampling frame only tested stools at 6 monthly time points so we do not know the kinetics of how long the azithromycin effect lasted or how quickly reinfections occurred. Additionally, the PCR approach could detect prolonged shedding of pathogens killed after antibiotics which could also obscure an antimicrobial effect.In sum, the antimicrobial regimen tested in this study was not as effective as expected in treating the candidate enteropathogens. We do not believe that periodic azithromycin mass drug administration is the proper tool to improve childhood growth, at least in this setting, since the aggressive regimens of antimicrobial required to reduce enteric infections would carry complex risks and antimicrobial resistance. The suggestion that reducing | PMC10734999 |
Supporting information | PMC10734999 | |||
Pathogens and gene targets tested by PCR in this study. | (DOCX)Click here for additional data file. | PMC10734999 | ||
Complete ELICIT TAC data. | (CSV)Click here for additional data file. | PMC10734999 | ||
ELICIT TAC data dictionary. | (CSV)Click here for additional data file. | PMC10734999 | ||
Difference in pathogen detection in the nicotinamide versus placebo arms at 6, 6.5, 12, 12.5, and 18 months. | X axis is the absolute reduction in pathogen prevalence between the nicotinamide–placebo. Negative values to the left of 0.0 represent reduction with nicotinamide. 95% confidence intervals are included.(DOCX)Click here for additional data file. | PMC10734999 | ||
Prevalence of non-study antibiotic use by drug class and month. | (DOCX)Click here for additional data file. | PMC10734999 | ||
References | PMC10734999 | |||
Background | ’ learning | Medical trainees often encounter situations that trigger emotional reactions which may hinder learning. Evidence of this effect on medical trainees is scarce and whether it could be counteracted is unclear. This study investigated the effect of negative emotions on medical residents’ learning and whether cognitive reappraisal counteracts it. | PMC9883942 | |
Methods | Ninety-nine medical residents participated in a three-phase experiment consisting of: (1) | PMC9883942 | ||
Results | Study time significantly varied between conditions ( | PMC9883942 | ||
Conclusion | Negative emotions can adversely affect medical residents’ learning. The effect of emotions was not counteracted by cognitive reappraisal, which has been successfully employed to regulate emotions in other domains. Further research to examine emotion regulation strategies appropriate for medical education is much needed. | PMC9883942 | ||
Supplementary Information | The online version contains supplementary material available at 10.1186/s12909-022-03996-2. | PMC9883942 | ||
Keywords | PMC9883942 | |||
Background | anger, ’ learning | Emotionally difficult situations are unavoidable in medical training. Students and doctors have reported experiencing negative emotions such as sadness when watching a patient’s suffering, fear of making mistakes, or anger when witnessing colleagues’ unprofessional behaviour [How could emotions affect residents’ learning? Research in cognitive psychology has described several mechanisms through which both positive and negative emotions can interfere with cognitive processes involved in learning. For example, positive emotions are known to trigger a “global processing” style that makes it easier to see the “big picture” in a situation and to increase learners’ ability to think flexibly [In the residency training, emotions can interfere with cognitive processes, such as attention and perception, for example, when a resident studies an online material about a patient’s problem. If attention is deviated to other tasks such as processing of emotions, integration of the to-be-learned information into knowledge structures stored in memory will suffer [This evidence points to the importance of assisting residents in dealing with commonly experienced emotions, thereby allowing them to benefit from learning opportunities. Possibly relevant here are strategies that have been investigated by research on Emotion Regulation. A well-known model of Emotion Regulation (ER) [One promising intervention seems to be The present study had a two-folded purpose. We examined (i) whether negative emotions hinder learning of scientific information, and (ii) whether this impact (if any) was counteracted by an intervention based on cognitive reappraisal. Residents watched either a neutral or an emotional videoclip, the latter either followed by cognitive reappraisal or not. Subsequently, all residents studied a relevant medical text and took a recall test. Consistently with the study purpose, the main outcome measurement was test score. To get insight on the residents’ engagement with the learning task, we also measured cognitive engagement and study time. Based on previous research [ | PMC9883942 | |
Methods | PMC9883942 | |||
Design | This study was an experiment consisting of three tasks: (I) an Experiment design and tasks flow | PMC9883942 | ||
Participants | Participants were ninety-nine first-year internal medicine residentsAll participants signed informed consent forms. The study protocol was approved by the Research Ethics Committee of the São Paulo University (659.347 in 21/05/2014). | PMC9883942 | ||
Materials and procedure | The study was presented to the participants as two separate, unrelated studies, from two different institutions. The emotion induction procedure was presented as a study on the use of fictitious videoclips in medical education whereas the learning task and the test were purportedly a study on the suitability of new medical discoveries to residents’ education. This procedure was used to prevent participants knowing that we were studying the effect of emotions on learning, which could trigger attempts to control that effect [Before the study started, participants were randomly assigned ( | PMC9883942 | ||
Emotion induction procedure | We opted to use a vicarious experience to induce negative emotions for ethical reasons. Experimental research has commonly employed films to elicit standardized emotional responses [After watching the videoclip, participants answered 6 questions to check if our manipulation worked (Additional file Subsequently, participants in the N and E conditions read a short description of the videoclip they had watched. Participants in the E-CR condition were asked to engage in cognitive reappraisal. Briefly, the instructions acknowledged that the participant might have found the video disturbing but benefits could also be extracted from the difficult situations one experiences and requested the participant to (i) look at the experience from a different perspective and try to identify how the resident in the video could have benefited from the it for his/her professional development, and (ii) write down at least one possible positive outcome from the experience. | PMC9883942 | ||
Learning task | SCHMIDT, CARDIAC ARREST | After completing the above-mentioned tasks (purportedly, Study 1) participants were requested to open the second envelope (purportedly, Study 2), which contained a 930-word text on oxidative damage during cardiac arrest. The text was prepared to by considering the participants’ prior knowledge to avoid ceiling effects and the relationship with the videoclip content (an incident with a patient undergoing cardiac arrest). The text was used in a previous study with similar participants [Written instructions asked participants to read the text as they would usually read any chapter in a medical textbook, writing down the starting and ending time using a digital clock visible in the room. They were informed that they could use as much time as needed and, when finished, answered whether they already had knowledge of the content (Yes/No).Subsequently, the participants filled in the Situational Cognitive Engagement Scale, an instrument that assesses involvement with learning tasks devised and validated by Rotgans and Schmidt [ | PMC9883942 | |
Testing task | After completing the learning task, the participants were requested to write down everything that they could remember from the text. Learning about a certain topic progresses through the enrichment of the semantic network of concepts related to that topic stored in the person’s memory. The more effective the learning, the more concepts could be recalled hence the number of concepts recalled offers a measure of learning [Finally, participants provided demographic information. | PMC9883942 | ||
Data analysis | Sample uniformity between the three experimental conditions with respect to gender and age was checked by performing, respectively, a chi-square test and a one-way ANOVA. Participants’ familiarity with the situation portrayed in the videoclips (item #1 Additional file Two measurements checked our manipulation: the average score of the two items of the questionnaire about the participant’s perception of the resident’s feeling (Additional file Two measurements of Finally, For all comparisons, the level of significance was set at | PMC9883942 | ||
Discussion | ’ learning [, cognitive reappraisal, ’ | This experimental study had a two-fold purpose: (1) examining whether the finding of a previous study [What concerns the first study purpose, these results are in line with findings of a previous study that showed participants under the influence of negative emotions to invest less time to study the learning material and to learn less from it relative to peers in a neutral emotional state [Negative emotions have been shown to hinder undergraduate students’ learning [With regards to the second purpose of the study, the intervention designed to minimize the impact of negative emotions did not work out as expected. As a possible ‘antidote’ to the effect of negative emotions, we used cognitive reappraisal, which previous studies have shown to be an efficient emotional regulation tool [At least three possible explanations for this failure can be raised. A first explanation derives from the intensity of the emotional reaction to the video and the consequent engagement in the cognitive reappraisal effort [A second possible explanation is that undetected ER strategies may have been employed by some participants in the emotional-without-antidote condition even without receiving instructions. Previous research describes adaptive ER as the flexibility to switch between different strategies and select the most appropriate one for the situation at hand [A third possible explanation could be that the specific form of cognitive reappraisal used was inadequate. It could be that reframing the harsh treatment received by the resident in the videoclip, for example, as resulting from the committee members’ own vulnerabilities and poor self-control would result in better ER outcomes.Further research should examine whether the cognitive reappraisal strategy would be effective when it is more strongly prompted, for example, because the situation provokes more intense emotional reactions. Another possible development would be to include a preliminary phase testing different cognitive reappraisal formulations. Different designs using the same strategy (cognitive reappraisal) before participants watch the video could give more insight on factors influencing its effectiveness. Furthermore, new studies with a similar experimental paradigm, should test different ER strategies.This study has limitations. First, we used self-report to measure emotions, which raises questions about the participants’ awareness of their emotional states and their willingness to disclose them. Physiological measurements would have been more accurate, but they would reveal the measurement of emotional responses, potentially interfering with their free course. Second, we tested a convenience sample of residents from one school, which may have precluded adequate power to make borderline differences in the test scores reach the significance level and restricts generalization of the findings. Third, we assessed overall emotional status as a manipulation check without differentiating between discrete negative emotions, which may have affected sensitivity to detect differences between conditions, including regarding the effect of cognitive reappraisal. However, it can be questioned whether this would affect the results, considering the very close test scores of the two emotional conditions. Finally, we only examined knowledge acquisition as measured by a recall test, and it is unclear whether the findings apply to other types of learning, where cognitive reappraisal could help. | PMC9883942 | |
Conclusion | ’ learning | Summing up, the present study replicates previous findings that negative emotions adversely impact medical residents’ subsequent learning. To get a better understanding of how to manage this effect, further research is called for. Apparently, these emotional states are harder to regulate than we assumed. Our ER intervention, although successfully applied in other domains, failed to diminish the negative effect of emotions on medical trainees’ learning. It is reasonable to hypothesise that real situations present an even bigger challenge, eliciting stronger negative emotions. This emphasizes the relevance of pursuing this line of investigation to reveal ER interventions suitable for medical education. Having access to an effective intervention would enhance trainees’ learning opportunities, their well-being and ultimately their ability to offer appropriate care to their patients. | PMC9883942 | |
Acknowledgements | This study could not have been performed without the help and cooperation of the medical residents at the School of Medicine at University of Sao Paulo, Brazil (2017) for their participation and effort in completing the study tasks.We also thank Dr Chin An Lin for his valuable advice and cooperation and the preceptors (2017) for their valuable help and dedication acting as research assistants during data collection. | PMC9883942 | ||
Authors’ contributions | TK contributed to the conception and design of the study, the data collection, analysis and interpretation, drafted the first version of the manuscript and revised the manuscript. SM contributed to the conception and design of the study, the data analysis and interpretation, critically revised the manuscript for important intellectual content and supervised the study. MPTN contributed to the preparation of materials, data collection, analysis and interpretation and critical revision of the manuscript for important intellectual content. WWB contributed to the conception and design of the study, data analysis and interpretation and critical revision of the paper for important intellectual content. HGS contributed to the conception and design of the study, data analysis and interpretation, critically revised the manuscript for important intellectual content and supervised the study. The author(s) read and approved the final manuscript. | PMC9883942 | ||
Authors’ information | Erasmus, psychiatric | SCHMIDT | Telma Kremer, MSc, PhD is a clinical psychologist graduated at São Paulo University, with a Master in Health Professions Education from Maastricht University and a PhD at the Institute of Medical Education Research Rotterdam, Erasmus MC, The Netherlands.Sílvia Mamede, MD, PhD, is associate professor at the Institute of Medical Education Research Rotterdam, Erasmus MC and at the Department of Psychology, Education and Child Studies at Erasmus University Rotterdam, The Netherlands.Maria do Patrocinio T. Nunes, MD, PhD is an associate professor at the Department of Medicine of the School of Medicine, University of São Paulo, Brazil.Walter W. van den Broek, MD, PhD, is the Director of Medical Education, Director of psychiatric residency training, Erasmus University Rotterdam, The Netherlands.Henk Schmidt is a professor of psychology at Erasmus University’s faculty of social sciences. | PMC9883942 |
Funding | None. | PMC9883942 | ||
Availability of data and materials | The data analysed during the present study are available from the corresponding author upon reasonable request. | PMC9883942 | ||
Declarations | PMC9883942 | |||
Ethics approval and consent to participate | All participants signed informed consent forms. The study protocol was approved by the Research Ethics Committee of the São Paulo University (659.347 in 21/05/2014). All methods were performed in accordance with the relevant guidelines and regulations. | PMC9883942 | ||
Consent for publication | Not applicable. | PMC9883942 | ||
Competing interests | The authors declare that they have no competing interests. | PMC9883942 | ||
References | PMC9883942 | |||
Background | emphysema | LUNG, EMPHYSEMA | Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months. | PMC10133584 |
Methods | airflow obstruction, lung volume reduction, dyspnoea | DISEASE | This multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population. | PMC10133584 |
Results | 88 participants (48% female, mean± | PMC10133584 | ||
Introduction | death, lobar atelectasis, COPD, heterogeneous emphysema | COPD | COPD is a common and often disabling condition which is now the third largest cause of death worldwide [An alternative lung volume reduction approach is endobronchial placement of valves to the airways supplying the most emphysematous lobe causing it to deflate. This form of bronchoscopic lung volume reduction (BLVR) can produce lobar atelectasis and is intended to achieve similar benefits to LVRS but with less morbidity [People with heterogeneous emphysema and an absence of collateral ventilation may therefore benefit from either BLVR or LVRS, but there are no direct comparison data on the relative value of the two procedures to guide clinical decision making. The aim of our study was to determine whether LVRS produces a health benefit at 1 year that is sufficiently greater [ | PMC10133584 |
Methods | PMC10133584 | |||
Study design and participants | airflow obstruction, COPD | COPD | The CELEB study was a multicentre, randomised controlled, parallel-group superiority trial in which patients with COPD who were considered by a lung volume reduction multidisciplinary team (MDT) meeting to be suitable candidates for both forms of targeted lung reduction therapy, and who did not have collateral ventilation on Chartis assessment (PulmonX, Redwood City, CA, USA), were randomised to either BLVR or unilateral LVRS (Ethical approval was obtained from Fulham Research Ethics Committee (London, UK) (REC reference: 16/LO/0286). The trial protocol has been published previously [Participants were recruited at five UK hospital sites which had an established MDT meeting dedicated to identifying suitable candidates for lung volume reduction: Royal Brompton Hospital (London), Glenfield Hospital (Leicester), St Bartholomew's Hospital (London), Northern General Hospital (Sheffield) and Golden Jubilee National Hospital (Glasgow).Eligibility criteria: significant airflow obstruction (forced expiratory volume in 1 s (FEVExclusion criteria: smoked in previous 3 months [All participants were assumed to be medically optimised and required to have undergone a course of pulmonary rehabilitation within the 12 months preceding trial enrolment. The clinical MDT then decided on whether a patient was suitable for both interventions and if there was equipoise between the two options. It was only after this point in the normal clinical process that a trial screening visit was arranged and written informed consent was obtained. | PMC10133584 |
Randomisation and masking | Randomisation to the treatment arm occurred only after the MDT meeting and once participants had undergone a fibreoptic bronchoscopy to allow for assessment of the presence of collateral ventilation using the Chartis system. People who were collateral ventilation-positive exited the study as valves would not be effective, so there was no longer equipoise ( | PMC10133584 | ||
Procedures | LVRS, to remove the most emphysematous part of the target lung, was carried out by a thoracic surgeon under general anaesthesia, primarily using either unilateral video-assisted thoracoscopic surgery or unilateral robot-assisted surgery. Where required, an open thoracotomy was performed at the discretion of the surgeon. As per usual clinical practice, participants initially went to the high dependency unit post-operatively and were transferred to ward-based care as soon as deemed medically stable, for further post-operative management, prior to discharge.BLVR, placing Zephyr endobronchial valves (PulmonX) to occlude the target lobe, was performed | PMC10133584 | ||
Outcomes | airflow obstruction | DISEASE | The primary outcome for the trial was the between-group difference in i-BODE score from baseline to 12 months post-procedure. This composite measure of disease severity is made up of body mass index (BMI), airflow obstruction (FEV | PMC10133584 |
Statistical analysis | Sample size calculation was based on a study comparing change in BODE score 3 months post-LVRS between survivors and non-survivors at 5 years [Changes in outcome measures between groups were analysed using independent t-tests where normally distributed, otherwise the Wilcoxon rank-sum (Mann–Whitney) test was used. Treatment effect was reported as difference between means with associated 95% confidence intervals or the Hodges–Lehman estimate with its associated 95% confidence intervals. All analyses were performed according to a predefined statistical analysis plan [ | PMC10133584 | ||
Results | death, illness or injury, pneumothorax, atelectasis, lung volume reduction, disability/incapacity, deaths, COPD, coronavirus disease 2019 | SUBCUTANEOUS EMPHYSEMA, CORONAVIRUS DISEASE 2019, PNEUMOTHORAX, ADVERSE EVENTS, ATELECTASIS, COMPLICATION, ACUTE EXACERBATION OF COPD, COPD, SECONDARY, EVENTS, COMPLICATIONS | Between 16 September 2016 and 22 July 2019, 163 patients were assessed for their eligibility to be enrolled in the trial. Of 149 patients who were screened and thought on the basis of their CT scan to be collateral ventilation-negative, 38 (26%) were collateral ventilation-positive on Chartis assessment and nine (6%) had a low flow or indeterminate Chartis. 88 eligible participants were randomly assigned to either LVRS (n=41) or BLVR (n=47) (Trial profile. BLVR: bronchoscopic lung volume reduction; LVRS: lung volume reduction surgery.Baseline characteristics of whole cohort and by treatment allocationData are presented as mean±80 participants received treatment (34 LVRS/46 BLVR). Six randomised to the LVRS group and one randomised to the BLVR group decided against having the procedure post-randomisation and therefore exited the trial prior to treatment. One trial participant randomised to the LVRS group died before surgery was performed. These participants were not included in the intention-to-treat analysis. Follow-up of patients was interrupted due to the coronavirus disease 2019 (COVID-19) pandemic. Some in-person research visits were missed as they were not possible or considered unsafe in this vulnerable patient group. Where able, outcomes were collected over the phone. The COVID-19 pandemic also meant that access to some trial data was delayed, because research staff had been redeployed. Survival data at 12 months were available for all participants. Outcome data were available for 71 participants at 3 months (32 LVRS/39 BLVR) and 63 participants at 12 months (26 LVRS/37 BLVR). Complete primary end-point data (all i-BODE items at 12 months) were available for 49 participants (21 LVRS/28 BLVR) (At 12 months post-procedure both intervention groups showed an improvement in i-BODE score (LVRS −1.10±1.44 Effect of lung volume reduction interventions on i-BODE score. Data are presented as mean±Primary and secondary outcomes: change from baseline to 12 months follow-upChange from baseline data are presented as number of participants data collected for, followed by mean±Effect of lung volume reduction procedures on i-BODE score component measures: a) body mass index (BMI), b) forced expiratory volume in 1 s (FEVResponders based on minimal clinically important difference (MCID) for the i-BODE index (complete case analysis). Each bar represents an individual subject. Blue bars represent subjects that met or exceeded the MCID for the i-BODE index (−1 point). Black bars represent subjects who did not meet the MCID. Dotted line represents the MCID. Red bars represent those patients that either crossed over or had valves removed, where data was collected. LVRS: lung volume reduction surgery; BLVR: bronchoscopic lung volume reduction.Responders based on minimal clinically important difference (MCID): i-BODE index components (complete case analysis). Each bar represents an individual subject. Blue bars represent subjects that met or exceeded the MCID for the specific outcome: a) body mass index (BMI) (no established MCID), b) forced expiratory volume in 1 s (FEVResponders based on minimal clinically important difference (MCID): important secondary outcomes (complete case analysis). Each bar represents an individual subject. Blue bars represent subjects that met or exceeded the MCID for a) residual volume (RV) % pred (−6.1%) and b) COPD Assessment Test (CAT) score (−2 points). Black bars represent subjects who did not meet the MCID. Dotted line represents the MCID. Red bars represent those patients that either crossed over or had valves removed, where data was collected. BLVR: bronchoscopic lung volume reduction; LVRS: lung volume reduction surgery.Both the LVRS and BLVR groups showed improvements in all secondary outcomes: RV % pred (LVRS −36.1% (95% CI −54.6– −10%) There were no differences at baseline between those with and without complete data at 12 months (Median (IQR) length of stay for the initial procedure was 9 (16.5) days in the LVRS group and 3 (2) days in the BLVR group (p=0.006). There were two deaths during the 12-month follow-up period. One occurred in the BLVR arm 44 days after valve insertion due to complications related to the procedure and one in the LVRS arm at 5 months post-intervention due to a non-infective acute exacerbation of COPD which was not thought to be related. At 12 months follow-up there were 29 respiratory-related adverse events in 17 participants undergoing LVRS (50.0%) The most common complication was subcutaneous emphysema (29.3%) in the LVRS group and pneumothorax (30.4%) in the BLVR group. Of those who had a pneumothorax, nine (81.8%) occurred while still an inpatient post-procedure, median (IQR) time to onset 2 (3) days and drain removed after median (IQR) 10 (12) days. The median (IQR) number of days with a chest drain post-LVRS was 8.0 (11.0) days. 26 (59.1%) BLVR patients achieved complete lobar atelectasis and a further 10 (21.7%) partial atelectasis. Seven (15.0%) BLVR recipients required at least one further bronchoscopy or procedure following initial intervention and four (8.7%) crossed over to LVRS, within the 12-month follow-up period. In the LVRS arm, two (4.9%) required a further bronchoscopy or procedure and one (2.4%) crossed over to BLVR. Safety outcomes are presented in Safety outcomesData are presented as n (%) or n. LVRS: lung volume reduction surgery; BLVR: bronchoscopic lung volume reduction; AE: acute exacerbation; NIV: non-invasive ventilation; ICU: intensive care unit. Serious adverse events were events leading to death, hospitalisation or prolongation of existing hospitalisation, persistent or significant disability/incapacity, or to serious deterioration in health that resulted in a life-threatening illness or injury, a permanent impairment of a body structure or body function. Prolonged length of stay defined as >10 days in LVRS and >4 days in BLVR. | PMC10133584 |
Discussion | death, emphysema, COPD, pulmonary hypertension, hyperinflation | ADVERSE EVENTS, DISEASE, EMPHYSEMA, COPD, SECONDARY, PULMONARY HYPERTENSION | The CELEB trial is the first randomised controlled trial to compare the effects of LVRS with BLVR. We found that surgery was not substantially superior to bronchoscopic treatment in patients with intact fissures and that both were similarly safe. Both approaches produced a clinically meaningful reduction in hyperinflation and similar improvements, assessed using either the i-BODE composite index or its individual components, were seen in both treatment arms at 1-year post-procedure. The initial length of hospital stay was longer following LVRS, but the BLVR group were more likely to have undergone a further intervention. There were also no significant differences found between the two groups in other secondary outcome measures (FFMI, physical activity experience and steps per day), with the exception of the CAT score which favoured LVRS at 12 months.The use of a composite measure is considered a more meaningful way to evaluate prognosis and response to disease-modifying interventions than FEVThe greater the reduction in lung volume following lung volume reduction intervention, the greater the improvement in other outcomes such as lung function, exercise capacity and quality of life [The improvement in gas trapping observed in both study arms was accompanied by improvements in participants’ experience of physical activity assessed using the c-PPAC score of two to three times the established MCID of 6 points (c-PPAC Amount: LVRS 18.3 Safety outcomes were similar, with no statistical differences in adverse events between the two groups. There was no peri-operative (30-day) mortality in either group and a single death in each arm by 12 months. This rate is not more than would be expected without intervention in patients with this severity of disease and indeed a low mortality rate is expected given the survival benefit associated with effective lung volume reduction in people with COPD [Although LVRS required a longer initial hospital stay, it was associated with fewer subsequent procedures and more participants crossed over in the BLVR group (LVRS 1 (2.4%) We acknowledge a number of limitations and methodological issues with the present study. First, the findings relate to a very specific COPD phenotype, namely people who were considered to be suitable for both interventions, and cannot therefore be extrapolated to all people being considered for lung volume reduction. Some individuals have a non-anatomical pattern of emphysema where surgery may be more effective. Others may have comorbidities such as pulmonary hypertension that could preclude LVRS but where valve treatment could be considered. Second, although this first head-to-head study did not demonstrate that LVRS was substantially more effective than BLVR to an extent that would change existing clinical equipoise, that does not necessarily mean that they are equivalent and further larger trials will need to address this. Third, due in large part to the logistical difficulties conducting clinical visits during the COVID-19 pandemic, although we had complete data for survival, there were missing data for some end-points. However, the sensitivity analysis using a prespecified multiple imputation approach to missing data supports the headline findings of the study ( | PMC10133584 |
Conclusions | COPD | COPD | The results of this study do not support the hypothesis that LVRS is a substantially superior treatment compared with BLVR, in terms of health outcomes achieved 1 year post-procedure. These broadly similar results at 12 months were obtained with a longer length of stay initially for LVRS but with less need for subsequent interventions than was the case with valve placement. The findings should help the lung volume reduction MDT to frame treatment options for patients and guide discussions around shared decision making, in individuals with severe COPD who are suitable for both LVRS and BLVR. | PMC10133584 |
Shareable PDF | COPD | COPD, THORACIC | This one-page PDF can be shared freely online.Shareable PDF Full list of study investigators on the CELEB trial: Royal Brompton Hospital (London): Sara C. Buttery, Winston Banya, Simon Jordan, Samuel V. Kemp, Adam Lewis, Pallav L. Shah, Nicholas S. Hopkinson, Sofina Begum, Michael I. Polkey, Matthew Pavitt, Karthi Srikanthan, Justin Garner, Matthew Hind, Carol Ridge, Sujal Desai, Jennifer Quint. Glenfield Hospital (Leicester): Neil J. Greening, Lorna Latimer, Sridhar Rathinam, Michael C. Steiner. St Bartholomew's Hospital (London): Kelvin Lau, David Waller. Northern General Hospital (Sheffield): Rod Lawson, Sara Tenconi, Kay Housley. Golden Jubilee National Hospital (Glasgow): Alan J.B. Kirk, Rocco Bilancia, Elizabeth Boyd, Julie Buckley, Elaine Matthews.Author contributions: N.S. Hopkinson wrote the study protocol, and obtained ethics approval and authorisation. S.C. Buttery, S.V. Kemp, P.L. Shah, D. Waller, S. Jordan, W. Banya and M.C. Steiner were involved in trial design and revisions of the final protocol. S.C. Buttery, A. Lewis, L. Latimer, K. Housley, E. Boyd and J. Buckley carried out all research visits and randomisation. P.L. Shah, R. Bilancia, S. Jordan, S.V. Kemp, A.J.B. Kirk, K. Lau, S. Rathinam, S. Tenconi and D. Waller carried out the trial procedures and management of the patients involved in the trial. J. Moxham acted as trial committee chair. S.C. Buttery and A. Lewis provided trial oversight, and S.C. Buttery wrote the first draft of the manuscript. N.S. Hopkinson, S.C. Buttery and W. Banya have directly accessed and verified the data report. W. Banya carried out the statistical analysis and production of graphs for the manuscript. All authors contributed to study design, study conduct, interpretation and revising the manuscript. All authors have agreed on the final manuscript and accept final responsibility to submit for publication.This article has an editorial commentary: This study was prospectively registered at the Conflict of interest: D. Waller reports lecture honoraria from PulmonX Ltd, outside the submitted work. N.J. Greening reports grants from GSK, consulting fees from Genentech, lecture honoraria from AstraZeneca and Chiesi, travel support from Chiesi, outside the submitted work. P.L. Shah reports lecture honoraria from PulmonX Ltd, outside the submitted work. R. Bilancia reports lecture honoraria and travel support from Intuitive, outside the submitted work. R. Lawson is a Member of British Thoracic Society COPD Specialist Advisory group, a Member of South Yorkshire Clinical Senate, and a Member of South Yorkshire and Bassetlaw Respiratory Clinical Network, outside the submitted work. All other authors have nothing to disclose.Support statement: This project was funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit Programme (grant reference number PB-PG-1014-35051). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Imperial College London will support the reporting of this manuscript. Trial sponsor representative: Patrik Pettersson, Royal Brompton and Harefield NHS Foundation Trust, Royal Brompton Hospital. The funder of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. Funding information for this article has been deposited with the | PMC10133584 |
References | PMC10133584 | |||
Introduction | muscle mass, fatigue | BLOOD, DISEASE, CONTRACTIONS | In recent years, electrical muscle stimulation (EMS) devices have been developed as a complementary training technique that is novel, attractive, and time-saving for physical fitness and rehabilitation. While it is known that EMS training can improve muscle mass and strength, most studies have focused on the elderly or specific patient populations. The aim of this study was to investigate the effects of frequency-specific EMS combined with resistance exercise training for 8 weeks on muscle mass, strength, power, body composition, and parameters related to exercise fatigue. Additionally, we aimed to evaluate the feasibility and safety of EMS as an exercise aid to improve body composition. We recruited 14 male and 14 female subjects who were randomly assigned to two groups with gender parity (seven male and seven female/group): (1) no EMS group (age: 21.6 ± 1.7; height: 168.8 ± 11.8 cm; weight: 64.2 ± 14.4 kg) and (2) daily EMS group (age: 21.8 ± 2.0; height: 167.8 ± 9.9 cm; weight: 68.5 ± 15.5 kg). The two groups of subjects were very similar with no significant difference. Blood biochemical routine analysis was performed every 4 weeks from pre-intervention to post-intervention, and body composition, muscle strength, and explosive power were evaluated 8 weeks before and after the intervention. We also performed an exercise challenge analysis of fatigue biochemical indicators after 8 weeks of intervention. Our results showed that resistance exercise training combined with daily EMS significantly improved muscle mass (Regular exercise training is known to promote physical and mental health, improve physiological metabolism, and reduce the risk of disease (Previous research has shown that voluntary maximal muscle contractions can contribute to muscle growth without the use of external loads, but not all produce high levels of voluntary effort (In recent years, EMS training has also gained popularity among healthy individuals and even competitive athletes (Despite substantial evidence that EMS benefits muscle performance, there is considerable variability in the findings regarding its effects on body composition and body fat ( | PMC10586320 |
Materials and Methods | PMC10586320 |
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