Completed Randomized Clinical Trials Research Articles

Positive impacts of psychological pain treatments: Supplementary analyses of a randomized clinical trial.

Clinical trials often focus on symptom reduction as a primary outcome, overlooking positive psychology factors of potential importance although many individuals can and do live well with pain. The Patient-Reported Outcomes Measurement Information System (PROMIS) Psychosocial Illness Impact-Positive (PIIP) scale assesses perceptions of adaptive psychosocial functioning (e.g., coping and meaning-making) after illness onset. This study evaluated the effects of hypnosis (HYP), mindfulness meditation (MM), and pain psychoeducation (ED) on PIIP scores, using data from a completed randomized clinical trial (RCT) of complementary and integrative chronic pain interventions. We hypothesized that treatment effects on PIIP would mirror the RCT's primary pain intensity outcome, such that HYP and MM, relative to ED, would lead to greater improvements in PIIP during trial follow-up. Our sample included 262 Veterans who completed the PROMIS PIIP Short-Form 8a at pre- and posttreatment and at 3- and 6-month follow-up. Linear regression was used to test between-group differences in PIIP at each time point, controlling for baseline PIIP, average pain intensity, and baseline perceptions of prepain psychosocial functioning. There were no significant between-group differences in PIIP at posttreatment or 3-month follow-up. However, group differences emerged at 6-month follow-up: individuals randomized to MM and HYP showed improved PIIP relative to those randomized to ED. Positive psychosocial outcomes are a mostly untapped territory in clinical trials of pain interventions. The present work highlights the potential benefits of including positive psychology concepts in both research and clinical contexts, emphasizing the importance of understanding human flourishing in the presence of illness and disability. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Both clinical trial register and electronic bibliographic database searches were needed to identify randomized clinical trials for systematic reviews: an evaluation study

ObjectivesTo determine whether clinical trial register (CTR) searches can accurately identify a greater number of completed randomized clinical trials (RCTs) than electronic bibliographic database (EBD) searches for systematic reviews of interventions, and to quantify the number of eligible ongoing trials. Study Design and SettingWe performed an evaluation study and based our search for RCTs on the eligibility criteria of a systematic review that focused on the underrepresentation of people with chronic kidney disease in cardiovascular RCTs. We conducted a combined search of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform through the Cochrane Central Register of Controlled Trials to identify eligible RCTs registered up to June 1, 2023. We searched Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE for publications of eligible RCTs published up to June 5, 2023. Finally, we compared the search results to determine the extent to which the two sources identified the same RCTs. ResultsWe included 92 completed RCTs. Of these, 81 had results available. Sixty-six completed RCTs with available results were identified by both sources (81% agreement [95% CI: 71–88]). We identified seven completed RCTs with results exclusively by CTR search (9% [95% CI: 4–17]) and eight exclusively by EBD search (10% [95% CI: 5–18]). Eleven RCTs were completed but lacked results (four identified by both sources (36% [95% CI: 15–65]), one exclusively by EBD search (9% [95% CI: 1–38]), and six exclusively by CTR search (55% [95% CI: 28–79])). Also, we identified 42 eligible ongoing RCTs: 16 by both sources (38% [95% CI: 25–53]) and 26 exclusively by CTR search (62% [95% CI: 47–75]). Lastly, we identified four RCTs of unknown status by both sources. ConclusionCTR searches identify a greater number of completed RCTs than EBD searches. Both searches missed some included RCTs. Based on our case study, researchers (eg, information specialists, systematic reviewers) aiming to identify all available RCTs should continue to search both sources. Once the barriers to performing CTR searches alone are targeted, CTR searches may be a suitable alternative.

Technical and relational process in MI sessions with a sample of Hispanic/Latinx adults who engage in heavy drinking: A latent growth mediation model

The current study tests the Motivational Interviewing (MI) technical and relational hypotheses in a sample of Hispanic/Latinx adults (N = 276) who engage in heavy alcohol consumption. MI causal theory hypothesizes that therapist use of MI consistent skills (i.e., technical hypothesis) and embodiment of the MI Spirit (i.e., relational hypothesis) will elicit client change talk, which is a putative mechanism of positive client outcome after the session. We tested these associations in a rigorous parallel process latent growth curve mediation modeling framework. The data are from a completed randomized clinical trial of a culturally-adapted (CAMI) versus un-adapted MI targeting hazardous alcohol use and consequences. Results. The unconditional growth models for the mediator (i.e., proportion of change talk relative to sustain talk) and two study outcomes (i.e., percent of heavy drinking days; alcohol-related consequences) showed a linear effect over a 12-month period with a slower rate of growth at later timepoints. Contrary to expectations, the latent growth mediation models did not show relationships between MI-consistent skills (i.e., technical predictor) or latent MI Spirit (i.e., relational indicator) and the slope factor for proportion change talk. The slope factor for proportion change talk was also not associated with the slope factors for percent heavy drinking and consequences over follow-up. Conclusions. In this novel population for MI process analysis, the technical and relational hypotheses were not supported. Studies that are exploratory may be needed to further investigate the causal model in populations that are not often represented in MI process research.

Non-pharmacological interventions for the treatment of post-stroke fatigue: A systematic review.

Post-stroke fatigue (PSF) affects 50% of stroke survivors. Current guidance on management of this condition is limited. This systematic review and meta-analysis aimed to identify and analyze all randomized clinical trials (RCTs) of non-pharmacological interventions for the treatment of PSF. Six electronic databases were searched from inception to January 2023 for English-language RCTs investigating the efficacy of non-pharmacological interventions versus passive controls in patients with PSF. The primary outcome was fatigue severity at the end of the intervention. The Cochrane risk-of-bias (ROB)2 tool was used to assess evidence quality. A total of 7990 records were retrieved, 333 studies were scrutinized, and 13 completed RCTs (484 participants) were included. Interventions included psychological therapies, physical therapies, and brain stimulation. Nine studies provided sufficient data for meta-analysis, of which seven also had follow-up data. Fatigue severity was lower in the intervention groups at the end of the intervention compared with control (participants = 310, standardized mean difference (SMD) = -0.57, 95% confidence intervals (CIs) (-0.87 to -0.28)) and at follow-up (participants = 112, SMD = -0.36, 95% CIs (-0.83 to 0.10)). Certainty in the effect estimate was downgraded to low for a serious ROB and imprecision. Subgroup analysis revealed significant benefits with physical therapy and brain stimulation but not psychological therapies, though sample sizes were low. Non-pharmacological interventions improved fatigue but the quality of evidence was low. Further RCTs are needed for PSF management.

The relationship between discrimination, alcohol use severity, and PTSD symptoms among Latinx heavy drinkers

IntroductionDiscrimination is linked to alcohol use severity among Latinx adults, who also show high prevalence rates of PTSD compared to non-Latinx adults. We know little about whether PTSD symptoms affects the relationship between discrimination and alcohol use severity. We hypothesized that the association between discrimination and alcohol use severity might differ by level of PTSD symptom severity. MethodsThis is a secondary cross-sectional analysis of data collected at baseline from a completed randomized clinical trial testing the relative efficacy of a culturally adapted motivational interview designed to address discrimination and drinking behavior against an unadapted motivational interview for Latinx adults. Eligible participants screened positive for the NIAAA Single Alcohol Screening Question for heavy drinking days, identified as Latinx, and were 18–65 years old. We assessed the Everyday Discrimination Scale, Primary Care PC-PTSD screener, Alcohol Use Disorder Identification Test, and the Short Acculturation Scale for Hispanics. The study analyzed the main and interactive effects of discrimination and PTSD symptoms on alcohol use severity, while controlling for age, sex, household income, and acculturation. ResultsAfter controlling for covariates in model 2, the interaction of discrimination and PTSD symptoms was significantly related to alcohol use severity. Simple slopes analysis indicated that discrimination was positively related to alcohol use severity among those with high (1 SD above the mean) but not low (1 SD below the mean) levels of PTSD symptoms. ConclusionsEvidence suggests that the experiences of discrimination were associated with alcohol use severity among those who reported more PTSD symptoms. Specifically, discrimination may have a stronger effect on alcohol use severity among Latinx adults who report more PTSD symptoms. Screening Latinx adults for heavy drinking days, discrimination, and PTSD symptoms is clinically important. Culturally adapted alcohol interventions that target discrimination may be particularly effective for Latinx individuals with more PTSD symptoms.

Integrative data analysis of clinical trials network studies to examine the impact of psychosocial treatments for Black people who use cocaine: Study protocol

BackgroundCocaine overdose death rates among Black people are higher than that of any other racial/ethnic group, attributable to synthetic opioids in the cocaine supply. Understanding the most effective psychostimulant use treatment interventions for Black people is a high priority. While some interventions have proven effective for the general population, their comparative effectiveness among Black people remains unknown. To address this gap, our NIDA-funded Clinical Trials Network (CTN) study (0125), will use Integrative Data Analysis (IDA) to examine treatment effectiveness across 9 CTN studies. This manuscript describes the study protocol for CTN-0125. MethodsOf the 59 completed randomized clinical trials in the CTN with available datasets, nine met our inclusion criteria: 1) behavioral intervention, 2) targeted cocaine use or use disorder, 3) included sub-samples of participants who self-identified as Black and 4) included outcome measures of cocaine and psychostimulant use and consequences. We aim to 1) estimate scale scores of cocaine use severity while considering study-level measurement non-invariance, 2) compare the effectiveness of psychosocial treatments for psychostimulant use, and 3) explore individual (e.g., concomitant opioid use, age, sex, employment, pre-treatment psychiatric status) and study-level moderators (e.g., attendance/retention) to evaluate subgroup differences in treatment effectiveness. ConclusionThe NIDA CTN provides a unique collection of studies that can offer insight into what interventions are most efficacious for Black people. Findings from our CTN-0125 study have the potential to substantially inform treatment approaches specifically designed for Black people who use psychostimulants.

Time to Benefit of Sodium-Glucose Cotransporter-2 Inhibitors Among Patients With Heart Failure

ImportanceEmerging evidence has consistently demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart failure (HF) hospitalization and cardiovascular (CV) death among patients with HF. However, it remains unclear how long a patient needs to live to potentially benefit from SGLT2 inhibitors in this population.ObjectivesTo estimate the time to benefit from SGLT2 inhibitors among patients with HF.Design, Setting, and ParticipantsThis comparative effectiveness study systematically searched PubMed for completed randomized clinical trials about SGLT2 inhibitors and patients with HF published until September 5, 2022; 5 trials with the year of publication ranging from 2019 to 2022 were eventually included. Statistical analysis was performed from April to October 2022.InterventionAddition of SGLT2 inhibitors or placebo to guideline-recommended therapy.Main Outcomes and MeasuresThe primary outcome was the time to first event of CV death or worsening HF, which was broadly comparable across the included trials.ResultsFive trials consisting of 21 947 patients with HF (7837 [35.7%] were female; mean or median age older than 65 years within each trial) were included. SGLT2 inhibitors significantly reduced the risk of worsening HF or CV death (hazard ratio [HR], 0.77 [95% CI, 0.73-0.82]). Time to first nominal statistical significance (P < .05) was 26 days (0.86 months), and statistical significance was sustained from day 118 (3.93 months) onwards. A mean of 0.19 (95% CI, 0.12-0.35) months were needed to prevent 1 worsening HF or CV death per 500 patients with SGLT2 inhibitors (absolute risk reduction [ARR], 0.002). Likewise, 0.66 (95% CI, 0.43-1.13) months was estimated to avoid 1 event per 200 patients with SGLT2 inhibitors (ARR, 0.005), 1.74 (95% CI, 1.07-2.61) months to avoid 1 event per 100 patients (ARR, 0.010), and 4.96 (95% CI, 3.18-7.26) months to avoid 1 event per 50 patients (ARR, 0.020). Further analyses indicated a shorter time to benefit for HF hospitalization and among patients with diabetes or HF with reduced ejection fraction.Conclusions and RelevanceIn this comparative effectiveness research study of estimating the time to benefit from SGLT2 inhibitors among patients with HF, a rapid clinical benefit in reducing CV death or worsening HF was found, suggesting that their use may be beneficial for most individuals with HF.

Unpublished completed obstetric randomized clinical trials registered at ClinicalTrials.gov: how big is this issue?

A portion of obstetrical randomized clinical trials (RCTs) registered at ClinicalTrials.gov are not published in peer-reviewed journals. To compare the characteristics of completed published versus unpublished randomized clinical trials in obstetrics registered on ClinicalTrials.gov, and to identify barriers to publication. This cross-sectional study queried ClinicalTrials.gov for all completed obstetrical randomized clinical trials registered between January 1, 2009, and December 31, 2018. For each completed obstetrical RCT, we abstracted the following registration fields from ClinicalTrials.gov: ClinicalTrials.gov identifier; recruitment status; trial start and completion dates; study results; type of intervention; study phase; enrollment size; funder type; location; and facilities. Calculated variables included time to completion. In May 2021, we used PubMed and Google Scholar to identify the publication status of completed trials, and we compared the characteristics of published vs. unpublished RCTs. The corresponding authors' email addresses for the unpublished studies were collected from ClinicalTrials.gov and departmental websites. Between September 2021- March 2022, authors of these completed but unpublished obstetrical RCTs were contacted and invited to respond to a survey examining perceptions of barriers to publication, responses of which were collected and presented as counts and percentages. Of the 647 obstetrical randomized clinical trials marked as completed on ClinicalTrials.gov, 378 (58%) were published, and 269 (42%) were unpublished. Unpublished trials were more likely to have an enrollment size of <50 participants (14.5% published, 25.3% unpublished; P < 0.001), and less likely to be conducted at multiple sites (25.4% vs. 17.5%; p < 0.02). The main barriers to publication reported in the survey by authors whose trials were not published included: lack of time (30%), change in employment or completion of training (25%), and results that were not of statistical significance (15%). Among the obstetrical randomized clinical trials registered and marked as completed on ClinicalTrials.gov, over 40% were unpublished. Unpublished trials were more likely to be smaller studies, conducted by researchers who reported experiencing a lack of time as the most common barrier to study publication.

Standards of Specialized Diabetes Care / Edited by Dedov I.I., Shestakova M.V., Mayorov A.Yu. 11th Edition

Dear Colleagues!We are glad to present the 11th Edition of the Standards of Specialized Diabetes Care. These evidence-based guidelines were designed to standardize and facilitate diabetes care in all regions of the Russian Federation.The Standards are updated on the regular basis to incorporate new data and relevant recommendations from national and international clinical societies, including World Health Organization Guidelines (WHO), International Diabetes Federation (IDF), European Association for the Study of Diabetes (EASD), American Diabetes Association (ADA), American Association of Clinical Endocrinologists (AACE), International Society for Pediatric and Adolescent Diabetes (ISPAD) and Russian Association of Endocrinologists (RAE). Current edition of the “Standards” also integrates results of completed randomized clinical trials, as well as findings from the national studies of diabetes mellitus (DM), conducted in close partnership with a number of Russian hospitals.Latest data indicates that prevalence of DM in the world increased during the last decade more than two-fold, reaching some 537 million patients by the end of 2021. According to the current estimation by the International Diabetes Federation, 643 million patients will be suffering from DM by 2030 and 783 million by 2045.Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian Federal Diabetes Register, there are at least 4 962 762 patients with DM in this country on 01.01.2023 (3,42% of population) with 92,3% (4 581 990) – Type 2 DM, 5,6% (277 092) – Type 1 DM and 2,1% (103 680) – other types of DM, including 8 758 women with gestational DM. However, these results underestimate real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) confirmed that 54% of patients with Type 2 DM are undiagnosed. So real number of patients with DM in Russia is 11-12 million patients (about 7% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they don’t receive any treatment and have high risk of vascular complications.Severe consequences of the global pandemic of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death.In accordance with the Federal Law № 489-FZ of 25.12.2018 medical care should be provided on the basis of the clinical recommendations. Therefore, clinical recommendations posted in the rubricator of the Ministry of Health of the Russian Federation (https://cr.minzdrav.gov.ru) being the priority.This edition of the Algorithms for Specialized Care for Patients with Diabetes Mellitus contains the main information from the clinical guidelines for the management of diabetes mellitus in adults and children (“Type 1 Diabetes in Children (2022)”, “Type 1 Diabetes in Adults (2022)”, “Type 2 diabetes mellitus in children (2021)”, “Type 2 diabetes mellitus in adults (2022)”), as well as the updated data.New information has been added about indications for using of antihyperglycemic drugs and their instructional restrictions; algorithm of treatment of type 2 diabetes mellitus has been updated; clarifications have been made on the range of glycemic control in pregnant women; information on the treatment of diabetic complications and the management of pediatric patients has been added. In 2023, Russian diabetology suffered an unbearable loss - Alexander Yuryevich Mayorov, who was the executive editor of the previous issues and an active participant of the work on all the previous editions of “Algorithms” from the moment they were founded, passed away. This publication is dedicated to the memory of Alexander Yuryevich, who was an example of the service to patients and medicine, a friend, teacher, mentor, generously sharing his knowledge and the sample of the execution of the medical duty to all of us. On behalf of the Working Group

Selective Publication within Vascular Surgery: Characteristics of Discontinued and Unpublished Randomized Clinical Trials

Discontinued and unpublished randomized clinical trials (RCTs) are common resulting in biased publication and loss of potential knowledge. The magnitude of selective publication within vascular surgery remains unknown. RCT relevant to vascular surgery registered (01/01/2010-10/31/2019) on ClinicalTrials.gov were included. Trials ending normally with conclusion of participant treatment and examination were considered completed whereas discontinued trials stopped early. Publications were identified through automatically indexed PubMed citations on ClinicalTrials.gov or manually identified on PubMed or Google Scholar >30months after the completion date, the date the final participant was examined, allowing time for publication. Of 108 RCT (n=37, 837), 22.2% (24/108) were discontinued, including 16.7% (4/24) stopped prior to and 83.3% (20/24) after starting enrollment. Only 28.4% of estimated enrollment was achieved for all discontinued RCT. Nineteen (79.2%) investigators provided a reason for discontinuation, which most commonly included poor enrollment (45.8%), inadequate supplies or funding (12.5%), and trial design concerns (8.3%). Of the 20 trials terminated following enrollment, 20.0% (4/20) were published in peer-reviewed journals and 80.0% (16/20) failed to reach publication. Of the 77.8% trials completed, 75.0% (63/84) were published and 25.0% (21/84) remain unpublished. In a multivariate regression of completed trials, industry funding was significantly associated with decreased likelihood of peer-reviewed publication (OR=0.18, (95% CI 0.05-0.71), P=0.01). Of the discontinued and completed trials remaining unpublished, 62.5% and 61.9% failed to report results on ClinicalTrials.gov, respectively, encompassing a total of 4,788 enrollees without publicly available results. Nearly 25% of registered vascular RCT were discontinued. Of completed RCT, 25% remain unpublished with industry funding associated with decreased likelihood of publication. This study identifies opportunities to report all findings for completed and discontinued vascular surgery RCT, whether industry sponsored, or investigator initiated.

Intervention strategies in early childhood to prevent celiac disease-a mini-review.

A higher intake of gluten during childhood is associated with increased risk of celiac disease, and the incidence of celiac disease peaks shortly after the time point when associations with higher gluten intake during the second and third year of life occur. Additional environmental factors are most likely necessary for celiac disease to develop. It is hypothesized that gastrointestinal infections increase gut permeability and exposure to gluten. Alternatively, infections may lead to gut dysbiosis and chronic inflammation, with leakage of self-antigens that mimic gluten peptides that leads to an autoimmune-like response. Different gluten interventions to prevent celiac disease have been proposed. Early clinical studies suggested an optimal time point introducing gluten between 4 and 6 months of age while the infant is being breastfed. However, later clinical trials on reduced gluten intake given to infants have shown no protection from celiac disease if gluten introduction was delayed or if gluten was introduced in small amounts during the child's first year of life. Still, more randomized clinical trials (RCTs) are warranted to answer the question if a reduced amount of gluten, not only at the time of introduction during infancy but also in a longer time frame, will prevent children at genetic risk from having lifelong celiac disease. It needs to be clarified whether dietary interventions are effective strategies to be proposed as future prevention of celiac disease in the general population. The present mini-review provides an overview of ongoing or completed RCTs that have focused on interventions during early childhood with the aim of preventing celiac disease.

Abstract P009: Plasma concentrations of multiple oxysterols and risk of colorectal adenomas

Abstract Oxysterols are metabolites of cholesterol and intermediates in pathways for primary bile acid synthesis that regulate homeostasis of cholesterol, fatty acids, and glucose by interacting with widely expressed nuclear receptors. These metabolites are generated throughout the body, either enzymatically or from oxidative stress, and are detectable in peripheral circulation at concentrations much lower than total cholesterol. We previously reported that circulating 27-hydroxycholesterol (27-OHC), the most abundant oxysterol in circulation and an endogenous selective estrogen receptor modulator, may be a risk factor for colorectal adenomas. Here, we report on four other circulating oxysterols: 25-hydroxycholesterol (25-OHC), 24(S)-hydroxycholesterol (24(S)-OHC), 7ɑ-hydroxycholesterol (7ɑ-OHC), and 4β-hydroxycholesterol (4β-OHC). We used high-sensitivity liquid chromatography-mass spectrometry to measure oxysterol concentrations in fasting plasma collected at baseline from 1,440 participants of the Vitamin D/Calcium Polyp Prevention Study, a completed randomized clinical trial that enrolled men and women recently diagnosed with colorectal adenomas with follow-up timed to colonoscopic surveillance intervals. Advanced adenomas were defined as tubulovillous or villous lesions, ≥1 cm in diameter, with high-grade dysplasia, or invasive adenocarcinoma. Risk ratios (RR) with 95% confidence intervals (CI) of new colorectal adenomas occurring during follow-up were estimated using repeated-measures log-linear regression for log-transformed circulating oxysterols. Primary analyses adjusted for multiple potential confounding factors and the five circulating oxysterols simultaneously, including 27-OHC. One geometric standard deviation (SD) higher circulating 7ɑ-OHC at the time of initial adenoma diagnosis was associated with 9% and 20% higher subsequent risk of any adenomas and advanced adenomas, respectively (RR of any adenomas per SD circulating 7ɑ-OHC, 1.09; 95% CI, 1.03-1.15 and RR of advanced adenomas, 1.20; 95% CI, 1.04-1.39). The positive association with adenoma risk that we previously reported for circulating 27-OHC persisted controlling for the other oxysterols including 7ɑ-OHC (RR of any adenomas per SD circulating 27-OHC 1.07; 95% CI, 0.99-1.15 and RR of advanced adenomas, 1.23; 95% CI, 1.03-1.48). No statistically significant associations were observed for circulating 25-OHC, 24(S)-OHC, and 4β-OHC. We conclude that circulating 7ɑ-OHC and 27-OHC may be independently associated with colorectal adenoma risk. Given these two oxysterols are the initial products of the classic (neutral) and alternative (acidic) pathways for primary bile acid synthesis, respectively, our findings provide additional evidence in support of a role for bile acids in the development of colorectal neoplasia. Novel colorectal cancer prevention strategies may target oxysterol formation. Citation Format: Michael N. Passarelli, Bonne M. Thompson, Jeffrey G. McDonald, Thomas J. Palys, Judy R. Rees, Elizabeth L. Barry, John A. Baron. Plasma concentrations of multiple oxysterols and risk of colorectal adenomas. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P009.

Abstract C108: Evaluating the relationship between physical activity and quality of life in a diverse sample of breast cancer survivors with lymphedema

Abstract Background: Compared with White breast cancer survivors, Black breast cancer survivors are more likely to experience adverse cancer treatment effects (e.g., pain and swelling from lymphedema) and suboptimal quality of life. Aerobic exercise has been shown to reduce the risk of breast cancer-related lymphedema. Physical activity has been documented to improve quality of life in predominantly White cancer survivors. However, little is known about the benefits of physical activity on quality of life among Black breast cancer survivors. In addition, there is limited evidence on the link between physical activity and quality of life over time by race in breast cancer survivors. Purpose: The primary objective of this study was to investigate the effect of physical activity on quality of life (social wellbeing, emotional/mental wellbeing, and relationship and body image) in White and Black breast cancer survivors with lymphedema. Methods: Linear mixed effects models were tested on an existing data source in a subset of participants in the control and exercise group of a 12-month completed randomized clinical trial. Results: There were 173 participants included in this analysis, averaging 59 years of age; about 33% of the participants were Black women. There were no significant differences in the quality of life outcomes between the control and exercise groups at 12 months. Exercise improved emotional/mental wellbeing and body image as it relates to social barriers at 12 months in Black and White breast cancer survivors, but the changes in these outcomes over time were only statistically significant in White breast cancer survivors (p&amp;lt;0.05). Conclusions: Results show that physical activity can improve certain domains of quality of life (e.g., emotional/mental wellbeing) over time in Black breast cancer survivors. However, the significance of the effect on quality of life (e.g., emotional/mental wellbeing) was isolated to White breast cancer survivors. After further analysis, the effects on quality of life are likely to be significant in a larger sample of Black women. Implications for Cancer Survivors: Physical activity can be used as a non-pharmaceutical intervention to enhance quality of life among subgroups of breast cancer survivors, possibly including Black women. Citation Format: Natasha R. Burse, Erik Lehman, Vernon M. Chinchilli, Yendelela L. Cuffee, Linda A. Wray, Eugene J. Lengerich, Kathryn H. Schmitz. Evaluating the relationship between physical activity and quality of life in a diverse sample of breast cancer survivors with lymphedema [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C108.

The role of the relational context and therapists' technical behaviors in brief motivational interviewing sessions for heavy alcohol consumption: Findings from a sample of Latinx adults

IntroductionMotivational interviewing (MI) theory and process research highlights the role of therapist technical and relational behaviors in predicting client in-session statements for or against behavior change (i.e., change and sustain talk, respectively). These client statements, in turn, have been shown to predict intervention outcomes. The current study examines sequential associations between therapist behaviors and client change and sustain talk in a sample of Latinx individuals who engage in heavy alcohol consumption. DataData are from a completed randomized clinical trial of a culturally adapted (CAMI) versus unadapted MI targeting alcohol use and consequences among Latinx individuals. MethodThe study collected observational coding data with the Motivational Interviewing Skill Code (MISC 2.5, i.e., therapist behaviors and global ratings) and the Client Language Assessment – Proximal/Distal (CLA-PD, i.e., client language). Frequentist and Bayesian sequential analyses examined the relationship among nine different categories of therapist behaviors and three different categories of client language (i.e., change talk, sustain talk, neutral). We examined odds ratios and conditional probabilities for the direction, magnitude, and significance of the association between the use of MI technical behaviors and subsequent client statements about change. The study compared these same transitional associations between low/average (i.e., <4) and high (i.e., ≥4) MI Spirit sessions. ResultsThe pattern of results was replicated across both analytic frameworks. Questions and reflections about change talk versus sustain talk versus neutral statements showed greater odds of predicting the intended client response (i.e., change talk, sustain talk, neutral, respectively) compared to other possible client responses. Conditional probabilities for these transitions were high, ranging from 0.55 to.88. The magnitude of certain technical transitions significantly differed between low/average and high MI Spirit sessions. ConclusionsAnalyses supported the hypothesized associations between therapist use of technical MI behaviors and client change language within this Latinx sample. Analyses of MI Spirit as a moderator of these transitions showed partial support.

Evaluating the time toxicity of cancer treatment in the CCTG CO.17 randomized clinical trial (RCT).

248 Background: Most individual treatments for advanced cancer are associated with modest survival benefits. The time spent in pursuing these treatments can be substantial. We have previously developed a pragmatic and patient-centered metric of these time costs, which we term ‘’time toxicity’’, as any day with physical healthcare system contact. This includes outpatient visits (e.g., for bloodwork, scans, infusions, urgent care), emergency room visits, and overnight stays in a healthcare facility. Herein we sought to assess time toxicity in a completed RCT. Methods: We conducted a secondary analysis of the Canadian Cancer Trials Group CO.17 RCT that evaluated weekly cetuximab infusions vs supportive care alone in 572 patients with advanced colorectal cancer. CO.17 recruited participants in Canada, Australia and New Zealand. Initial results reported a 6-week improvement in median overall survival (OS) with cetuximab (6.1 vs 4.6 months, p = 0.005). Subsequent analyses reported that OS benefit was restricted to and significantly more in patients with K-ras wild-type tumors. We calculated patient-level time toxicity by analyzing treatment, follow-up, and resource utilization forms. We considered a day without physical healthcare contact as a ‘’home day’’. Thus, for a patient, OS was time toxic days + home days. We compared medians of time measures across arms, and stratified results by K-ras status. Results: In the overall population, median time toxic days were higher in the cetuximab arm (28, vs 10, p &lt; 0.001), although median home days were not statistically different (140, vs 121, p = 0.09). The proportion of time toxic days (time toxic days/OS) were significantly more with cetuximab (18%, vs 6%, p &lt; 0.001). Of the 28 time toxic days in the overall cetuximab arm, 14 (50%) were protocol-related (e.g., scheduled infusions etc). Stratified results are in the table. Conclusions: Time toxicity can be extracted through secondary analyses of RCTs. In CO.17, despite an overall OS-benefit with cetuximab, home days were statistically similar across arms. In the K-ras-mutated group, cetuximab was associated with numerically similar OS but more time toxic days. In the K-ras-wild type group, cetuximab was associated with higher home days. Thus, time toxicity data need not always be sobering. Time toxicity measures can supplement traditional survival endpoints in RCTs to guide patient-oncologist decision-making. Cooperative group RCTs are well positioned for such analyses. Clinical trial information: NCT00079066. [Table: see text]

Standards of specialized diabetes care. Edited by Dedov I.I., Shestakova M.V., Mayorov A.Yu. 10th edition

Dear Colleagues!We are glad to present the 10th Edition (revised) of the Standards of Specialized Diabetes Care. These evidence-based guidelines were designed to standardize and facilitate diabetes care in all regions of the Russian Federation.The Standards are updated on the regular basis to incorporate new data and relevant recommendations from national and international clinical societies, including World Health Organization Guidelines (WHO, 2011, 2013), International Diabetes Federation (IDF, 2011, 2012, 2013), European Association for the Study of Diabetes (EASD 2018, 2019), American Diabetes Association (ADA, 2018, 2019, 2021), American Association of Clinical Endocrinologists (AACE, 2020, 2021), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2018) and Russian Association of Endocrinologists (RAE, 2019). Current edition of the “Standards” also integrates results of completed randomized clinical trials (ADVANCE, ACCORD, VADT, UKPDS, SAVOR, TECOS, LEADER, EXAMINE, ELIXA, SUSTAIN, DEVOTE, EMPA-REG OUTCOME, CANVAS, DECLARE, CARMELINA, REWIND, CREDENCE, CAROLINA, DAPA-CKD, DAPA-HF, EMPEROR-Reduced trial, VERIFY, VERTIS CV, PIONEER, etc.), as well as findings from the national studies of diabetes mellitus (DM), conducted in close partnership with a number of Russian hospitals.Latest data indicates that prevalence of DM in the world increased during the last decade more than two-fold, reaching some 537 million patients by the end of 2021. According to the current estimation by the International Diabetes Federation, 643 million patients will be suffering from DM by 2030 and 784 million by 2045.Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian Federal Diabetes Register, there are at least 4 871 863 patients with DM in this country on 01.01.2021 (3,34% of population) with 92,3% (4 498 826)–Type 2 DM, 5,6% (271 468)–Type 1 DM and 2,1% (101 569)–other types of DM, including 9 729 women with gestational DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) confirmed that only 54% of Type 2 DM are diagnosed. So real number of patients with DM in Russia is 10 million patients (about 7% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they don’t receive any treatment and have high risk of vascular complications.Severe consequences of the global pandemic of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death.In сurrent edition of the “Standards”:New goals of glycemic control for continuous glucose monitoring (time in range, below range and above range, glucose variability) are given.It also features updated guidelines on stratification of treatment in newly diagnosed Type 2 diabetes.In the recommendations for the personalization of the choice of antidiabetic agents, it is taken into account that in certain clinical situations (the presence of atherosclerotic cardiovascular diseases and their risk factors, chronic heart failure, chronic kidney disease, obesity, the risk of hypoglycemia) certain classes of hypoglycemic agents (or individual drugs) have proven advantages.Indications for the use of antidiabetic agents in chronic kidney disease are expanded.Information about insulin pump therapy is added.Recommendations on vaccination are added.An algorithm for replacing some insulin preparations with others is given.This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discussions held at national meetings and forums. These guidelines are intended for endocrinologists, primary care physicians, pediatricians and other medical professionals involved in the treatment of DM.Compared with previous edition of the Standards of Specialized Diabetes Care edited by Dedov I.I., Shestakova M.V., ­Mayorov A.Yu., 10th edition, Moscow, 2021 (signed for printing on 10.09.2021) a number of changes have been made.On behalf of the Working Group

Abstract P2-11-05: Generating real-world external comparators for randomized clinical trials (RCTs) in metastatic breast cancer (mBC) using electronic health records (EHRs)

Abstract Objectives: Real-world data (RWD) from the routine care of patients with cancer captured through EHRs is a valuable resource for research. Understanding the relationship between characteristics and outcomes of patients treated in the real world and those treated in clinical trials is essential to produce evaluable trial-like populations using RWD in oncology for research and regulatory purposes. Methods: This study used: a) RWD from the Flatiron Health EHR-derived, de-identified, longitudinal database (comprising patient-level structured and unstructured data, curated via technology-enabled abstraction selected from approximately 280 US cancer clinics [~800 sites of care]) and b) patient-level data from three completed RCTs (PALOMA-2, MONALEESA-2, and MONARCH-3) including patients with previously untreated hormone receptor positive (HR+), HER2/neu negative (HER2-) mBC, then separately pooled across the trials into two treatment groups, patients who received aromatase inhibitor monotherapy (AI) or a CDK4/6 inhibitor + AI. Key eligibility criteria were similar across the RCTs and were used to select a real world external cohort (rwEC) initiating AI monotherapy on or prior to 11 Nov 2015 (end of MONARCH-3 enrollment period). Patients from the rwEC were matched separately to the control arm and experimental arm patients from the pooled RCT using propensity score method (PSM). The propensity score was estimated by a logistic regression using baseline covariates of age, race, site of disease (visceral, non-visceral), Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0, 1), and metastatic disease (recurrent, new). The matching ratio was 1:1 without replacement with calipers. Covariate balance was measured by the absolute standardized mean difference (ASMD). Due to the high percentage of missing ECOG PS data, matching was repeated 100 times with imputed ECOG PS. The impact of including additional key covariates for propensity matching such as number of disease sites, bone-only disease, and prior endocrine therapy was assessed. Results: There were 1326 patients with HR+, HER2- mBC selected from the EHR-derived database who received first-line AI therapy and 1827 patients randomized in the RCTs (1106 and 721 patients for experimental and control arms, respectively). With 100 matching iterations, 563 rwEC patients on average (range, 547-572) were matched to the RCTs control arm, and 753 rwEC patients on average (range: 741-761) were matched to the RCTs experimental arm. Prior to matching, the ASMD varied widely across all prespecified baseline covariates (4.3 for the rwEC vs. RCTs control arm, 2.6 for the rwEC vs. RCTs experimental arm). After matching was performed, across all baseline covariates used in the PSM, the ASMD was reduced to be under 0.12 for the rwEC vs. RCTs control arm, and under 0.2 for the rwEC vs. RCTs experimental arm in more than 90% of the matching iterations. Analyses looking at the additional baseline covariates to the propensity matching resulted in similar ASMDs. Conclusions: EHR-derived RWD can be used to generate a cohort of patients with similar baseline characteristics to those treated on RCT. The next step in our trial emulation framework is to analyze the comparability of outcomes between these two matched cohorts. Citation Format: Laleh Amiri-Kordestani, Xin Gao, Shrujal Baxi, Erik Bloomquist, Jonathan Bryan, Lynn Howie, Catherine Keane, Paul G. Kluetz, Christy Osgood, Prashni Paliwal, Donna R. Rivera, James Roose, Julie Schneider, Harpreet Singh, Shenghui Tang, Lijun Zhang, Julia A. Beaver. Generating real-world external comparators for randomized clinical trials (RCTs) in metastatic breast cancer (mBC) using electronic health records (EHRs) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-11-05.

Individual patient data meta‐analysis assessing the adverse event profile of Alzheimer dementia randomized clinical trials

AbstractBackgroundRegular reporting and monitoring of Adverse Events (AE) and Serious Adverse Event (SAE) are a crucial part of all randomized, controlled clinical trials, providing an assessment of the intervention’s safety profile. This process of adverse event surveillance is critical for participant’s safety and data quality. Knowledge and previous experience from Alzheimer’s disease (AD) trials is necessary in order to assess whether an AE/SAE is currently observed in a trial can occur (and at what frequency) in the placebo arm of the study or may be unique to the test agent. The overarching aim of this project is to evaluate the AE profile observed in the placebo arms in AD randomized clinical trials through a systematic review and meta‐analysis.MethodWe evaluated the safety profiles in placebo‐arm AD trials, we combined Individual Patient Data (IPD) using AE and SAE data from completed randomized clinical trials (RCT) AD trials conducted by the Alzheimer’s Disease Cooperative Study (ADCS). We used descriptive statistics, summarizing baseline participant demographics and AE patient level outcomes at the study level. Meta‐analyses using a Negative‐Binomial model were undertaken to determine the pooled risk ratios (RR) of AE and SAE rates.ResultThe placebo arms of five 18‐month RCTs were included in this meta‐analysis with a pooled sample size of 749 participants. The estimated number of adverse events per participant across the five studies ranged from 1.93 events to 7.05 events per participant. Meta‐analysis of the total number of AEs a participant experiences for the duration of an 18‐month trial was estimated to be 3.85 events (95% confidence interval: (1.54, 9.32)). Similar analyses on the number of SAEs a participant is expected to experience was 0.18 events (0.04, 0.94) per participant.ConclusionThe IPD meta‐analysis models give an indication of the AE profiles we can expect to observe in the placebo arm of future AD trials. We will extend this work by looking at AE classification types and what common types of AEs occur across trials.

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

BackgroundConvalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX).MethodsIn this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence.ResultsA total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis.ConclusionsConvalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

Seeing the forest for the trees: Predicting attendance in trials for co-occurring PTSD and substance use disorders with a machine learning approach.

Objective: High dropout rates are common in randomized clinical trials (RCTs) for comorbid posttraumatic stress disorder and substance use disorders (PTSD + SUD). Optimizing attendance is a priority for PTSD + SUD treatment development, yet research has found few consistent associations to guide responsive strategies. In this study, we employed a data-driven pipeline for identifying salient and reliable predictors of attendance. Method: In a novel application of the iterative Random Forest algorithm (iRF), we investigated the association of individual level characteristics and session attendance in a completed RCT for PTSD + SUD (n = 70; women = 22 [31.4%]). iRF identified a group of potential predictor candidates for the total trial sessions attended; then, a Poisson regression model assessed the association between the iRF-identified factors and attendance. As a validation set, a parallel regression of significant predictors was conducted on a second, independent RCT for PTSD + SUD (n = 60; women = 48 [80%]). Results: Two testable hypotheses were derived from iRF's variable importance measures. Faster within-treatment improvement of PTSD symptoms was associated with greater session attendance with age moderating this relationship (p = .01): faster PTSD symptom improvement predicted fewer sessions attended among younger patients and more sessions among older patients. Full-time employment was also associated with fewer sessions attended (p = .02). In the validation set, the interaction between age and speed of PTSD improvement was significant (p = .05) and the employment association was not. Conclusions: Results demonstrate the potential of data-driven methods to identifying meaningful predictors as well as the dynamic contribution of symptom change during treatment to understanding RCT attendance. (PsycInfo Database Record (c) 2021 APA, all rights reserved).