Underpowered Studies Research Articles

Cognitive ageing is premature among a community sample of optimally treated people living with HIV.

ObjectivesEvidence of premature cognitive ageing amongst people living with HIV (PLHIV) remains controversial due to previous research limitations including underpowered studies, samples with suboptimal antiretroviral access, varying rate of virological control, high rate of AIDS, over‐representation of non‐community samples, and inclusion of inappropriate controls. The current study addresses these limitations, while also considering mental health and non‐HIV comorbidity burden to determine whether PLHIV showed premature cognitive ageing compared with closely comparable HIV‐negative controls.MethodsThis study enrolled 254 PLHIV [92% on antiretroviral therapy; 84% with HIV RNA < 50 copies/mL; 15% with AIDS) and 72 HIV‐negative gay and bisexual men [mean (SD) age = 49 (10.2) years] from a single primary care clinic in Sydney, Australia. Neurocognitive function was evaluated with the Cogstate Computerized Battery (CCB) at baseline and 6 months after. Linear mixed‐effects (LME) models examined main and interaction effects of HIV status and chronological age on the CCB demographically uncorrected global neurocognitive z‐score (GZS), adjusting for repeated testing, and then adjusting sequentially for HIV disease markers, mental health and comorbidities.ResultsHIV status and age interacted with a lower GZS (β = −0.43, P < 0.05). Higher level of anxiety symptoms (β = −0.11, P < 0.01), historical AIDS (β = −0.12, P < 0.05) and historical HIV brain involvement (β = −0.12, P < 0.05) were associated with lower GZS.ConclusionsWe found a robust medium‐sized premature ageing effect on cognition in a community sample with optimal HIV care. Our study supports routine screening of cognitive and mental health among PLHIV aged ≥ 50 years.

Response to “The Use of Non-Invasive Vagus Nerve Stimulation to Treat Respiratory Symptoms Associated with COVID-19: A Theoretical Hypothesis and Early Clinical Experience”

Response to “The Use of Non-Invasive Vagus Nerve Stimulation to Treat Respiratory Symptoms Associated with COVID-19: A Theoretical Hypothesis and Early Clinical Experience”

Therapeutic songwriting to address distress tolerance for adults on an acute care mental health unit: A pilot study

The Stress Vulnerability Model describes how stressors can function as a precursor for mental health episodes that may result in hospitalization. As such, it is crucial for people with mental health conditions to be able to anticipate and tolerate distress. The purpose of this pilot study was to determine the effects of a group therapeutic songwriting intervention on distress tolerance with adults in an acute care mental health setting. Due to the temporal parameters of acute mental health care in the United States, participants (N = 58) were cluster-randomized to a single songwriting session or control condition. Experimental participants composed lyrics for a two-verse blues song identifying causes of distress and how to tolerate them while living in the community. Results indicated no significant between-group difference. However, the songwriting condition tended to have slightly more favorable scores in all subscales (tolerance, absorption, appraisal, and regulation) and total distress tolerance than the control condition. While results of this underpowered pilot effectiveness study should be interpreted with caution, highly-structured group-based songwriting may be clinically relevant for addressing distress tolerance. Implications for clinical practice, limitations, and suggestions for future research are provided.

Effects of Plyometric Jump Training on Jump and Sprint Performance in Young Male Soccer Players: A Systematic Review and Meta-analysis.

Even from a young age, modern soccer requires high levels of physical fitness development, particularly jumping and sprinting. Plyometric jump training (PJT), combined with young athletes' regular soccer sessions, has the potential to improve jumping and sprinting. However, studies exploring the effects of PJT are generally limited by small sample sizes. This problem of underpowered studies may, thus, be resolved by pooling study results in a meta-analysis. The objective of this systematic review with meta-analysis (SRMA) was to assess the effects of plyometric jump training (PJT) on jumping and sprinting among young male soccer players. The SRMA included peer-reviewed articles that incorporated PJT in healthy players (i.e., < 23years of age), a control group, and a measure of jumping or sprinting. Means and standard deviations of outcomes were converted to Hedges' g effect sizes (ES), using the inverse variance random-effects model. Moderator analyses were conducted for PJT duration, frequency, total number of sessions, participants' chronological age, and FIFA age categories (i.e., U-17 vs. U-20 vs. U-23). A multivariate random-effects meta-regression was also conducted. Thirty-three studies were included, comprising 1499 participants. PJT improved vertical jump tests (ES = 0.60-0.98; all p < 0.01) and linear sprint performance (ES = 0.60-0.98; p < 0.03). Interventions of > 7weeks and > 14 PJT sessions induced greater effects compared to PJT with ≤ 7weeks and ≤ 14 total sessions on 10-m sprint performance (between group p = 0.038). PJT is effective in improving jumping and sprinting performance among young male soccer players. Greater 10-m linear sprinting improvements were noted after interventions > 7-week duration and > 14 sessions, suggesting a greater return from exposure to longer PJT interventions, partially in support for the adoption of a long-term approach to athletic development in young athletes. However, with reference to the findings of the meta-regression, and those from the remaining subgroup and single factors analysis, a robust confirmation regarding the moderator role of participant's age or PJT configuration effects on young soccer player's fitness qualities needed.

Neuroanatomical Differences Among Sexual Offenders: A Targeted Review with Limitations and Implications for Future Directions.

As sexual assault and child sexual abuse continue to be worldwide public health concerns, research has continued to explore factors associated with sexual offending. Structural and functional neuroanatomical brain differences have been examined in an effort to differentiate sexual offenders and their behavior. This targeted review searched PubMed and Google Scholar for empirical studies using brain imaging techniques to examine possible structural or functional differences among control groups compared with at least one group of sexual offenders with contact offenses. This targeted review summarizes the structural and functional findings of 15 brain imaging studies (i.e., computed tomography, diffusion tensor imaging, magnetic resonance imaging, positron emission tomography, and functional magnetic resonance imaging), which suggest possible differences in brain size and gray matter volume, cortical thickness, white matter connectivity, and specific structural and functional differences among brain regions (fronto-temporal region, amygdala, prefrontal cortex, etc.). The methodological limitations of brain imaging studies and the associated findings with regard to sexual offenders are highlighted, as research indicates that many of the proposed differences in brain structure and function are not unique to this population. We further highlight several limitations to using neuroimaging studies to examine this population of interest, including publication bias, small sample size, underpowered studies, and all-male samples. As these results are mixed and findings are not seemingly unique to sexual offenders, we suggest future sexual offender research may benefit from focusing on more financially feasible options, such as neuropsychological assessment approaches, to assess for and attend to offenders' criminogenic and rehabilitative/therapeutic needs in alignment with the risk-need-responsivity model.

Emagnification: A tool for estimating effect-size magnification and performing design calculations in epidemiological studies

Artificial effect-size magnification (ESM) may occur in underpowered studies, where effects are reported only because they or their associated p-values have passed some threshold. Ioannidis (2008, Epidemiology 19: 640–648) and Gelman and Carlin (2014, Perspectives on Psychological Science 9: 641–651) have suggested that the plausibility of findings for a specific study can be evaluated by computation of ESM, which requires statistical simulation. In this article, we present a new command called emagnification that allows straightforward implementation of such simulations in Stata. The commands automate these simulations for epidemiological studies and enable the user to assess ESM routinely for published studies using user-selected, study-specific inputs that are commonly reported in published literature. The intention of the command is to allow a wider community to use ESMs as a tool for evaluating the reliability of reported effect sizes and to put an observed statistically significant effect size into a fuller context with respect to potential implications for study conclusions.

Trials and tribulations of coronavirus disease-2019 research: with a few bright lights in the fog.

Trials and tribulations of coronavirus disease-2019 research: with a few bright lights in the fog.

Efficacy of Telmisartan to Slow Growth of Small Abdominal Aortic Aneurysms

Currently there is no drug therapy for abdominal aortic aneurysm (AAA). To test the efficacy of the angiotensin receptor blocker telmisartan in slowing AAA growth in the Telmisartan in the Management of Abdominal Aortic Aneurysm (TEDY) trial. A randomized, double-blind, placebo-controlled trial recruited participants between September 6, 2011, and October 5, 2016, to evaluate the efficacy of telmisartan treatment in patients with AAA. Participants with 35- to 49-mm AAAs recruited from Australia, the Netherlands, and the US were randomized 1:1 to receive telmisartan, 40 mg, or identical placebo. Analyses were conducted according to intention-to-treat principles. Final follow-up was conducted on October 11, 2018, and data analysis was performed between June and November 2019. Telmisartan, 40 mg, or identical placebo. The primary outcome of the difference in AAA growth, assessed on core imaging laboratory-read ultrasonographic scanning, was tested with linear mixed-effects models. Other outcomes included effects on blood pressure, computed tomographic (CT)-measured AAA diameter and volume, time to AAA-related events (AAA repair or mortality due to AAA rupture), and health-related quality of life. Of 300 intended participants, 210 were enrolled and randomized to receive telmisartan (n = 107) or placebo (n = 103). Of patients included in the intention-to-treat analysis (telmisartan: n = 106, placebo: n = 101), 183 were men (88%); mean (SD) age was 73.5 (7.9) years. At 1 year, participants receiving telmisartan had mean lower systolic (8.9; 95% CI, 4.1-13.8 mm Hg; P < .001) and diastolic (7.0; 4.3-9.8 mm Hg; P < .001) blood pressure levels compared with participants receiving placebo. A total of 188 participants (91%) received at least 2 ultrasonographic scans and 133 participants (64%) had at least 2 CT scans. There was no significant difference in ultrasonographic-assessed AAA growth rates among those assigned telmisartan (1.68 mm/y) or placebo (1.78 mm/y): mean difference, -0.11 mm/y (95% CI, -0.60 to 0.38 mm/y; P = .66). Telmisartan had no significant effects on AAA growth assessed by CT-measured AAA diameter (mean difference, -0.01 mm/y; 95% CI, -0.02 to 0.01 mm/y; P = .23) or volume (mean difference, -0.02 cm3/y; 95% CI, -0.04 to 0.00 cm3/y; P = .11), AAA-related events (relative risk, 1.35; 95% CI, 0.54-3.35; P = .52), or health-related quality of life (mean difference in physical component score at 24 months, 0.4; 95% CI, 0.4-0.4; P = .80). Hypotensive symptoms (eg, syncope) were twice as common among participants receiving telmisartan compared with placebo (28 [26%] vs 13 [13%]; P = .02), but overall adverse event rates were otherwise similar for both groups. This underpowered study did not show a treatment effect for telmisartan on small AAA growth. Future trials will need to ensure adequate sample size and duration of follow-up. anzctr.org.au Identifier: ACTRN12611000931976; ClinicalTrials.gov Identifier: NCT01683084.

The articular and the craniocervical abnormalities are of confusing age of onset in patients with Maroteaux-Lamy disease (MPS VI).

Maroteaux-Lamy disease (MPS Type VI) is an autosomal recessive lysosomal storage disorder. Skeletal abnormalities are vast. Early recognition may facilitate timely diagnosis and intervention, leading to improved patient outcomes. The most challenging is when patients manifest a constellation of craniocervical and articular deformities with variable age of onset. We collected 15 patients with MPS VI (aged from 6 years-58 years). From within our practice in Pediatric Orthopedics, we present patients with MPS type VI who were found to manifest a diverse and confusing clinical presentations of hip deformities and cervical cord compression. Stem cell transplants were proposed as treatment tool and enzyme replacement therapy has been instituted in some patients. The spectrum of the clinical involvement in our group of patients was supported firstly via the clinical phenotype followed by assessment of the biochemical defect , which has been detected through the deficiency of N-acetylgalactosamine-4-sulfatase (arylsulphatase B) leading to increased excretion of dermatan sulphate. Secondly, through the molecular genetic results, which showed homozygous or compound heterozygous mutation in the ARSB gene on chromosome 5q14. Hip replacements and decompression operations have been performed to restore function and to alleviate pain in the former and life saving procedure in the latter. The efforts in searching for the etiological diagnosis in patients with skeletal dysplasia/MPSs has not been rewarding as many had anticipated. This emerged from several facts such as improper clinical documentation, missing diagnostic pointers in radiographic interpretations, limited knowledge in skeletal dysplasia and its variants, and the reliance on underpowered studies. Physicians and radiologists are required to appreciate and assess the diverse phenotypic and the radiographic variability of MPS VI. The importance of considering MPS in the differential diagnosis of other forms skeletal dysplasia is mandatory. Finally, we stress that the value of early diagnosis is to overcome dreadful complications.

Factors affecting patient recruitment to trials: qualitative research in general practice.

BackgroundPatient recruitment to clinical research is often challenging and, when inadequate, can result in delayed or underpowered studies. Recruitment problems were experienced during a study of women with heavy menstrual bleeding in general practice (the MIRA trial). Although efforts were made to reduce the burden of the study for those participating, patient recruitment was still an issue.AimTo identify the barriers and facilitators associated with patient recruitment to clinical trials, as experienced by GPs.Design & settingA qualitative study was performed in Dutch general practice, using semi-structured interviews.MethodGPs participating in the MIRA trial were selected by purposive sampling and interviewed until saturation was reached. Three independent researchers performed data coding and thematic analysis. Consensus on the identified themes was reached by discussion among the researchers.ResultsSixteen GPs were interviewed. The following factors were noted to influence recruitment: the incidence of the disease under study; awareness of the study; attitude towards scientific research; perceived burden for the patient; usual care by the GP; time investment; characteristics of the GP and their practice; and patient experience of research participation.ConclusionThe identified barriers and facilitators associated with patient recruitment highlight the areas in which future studies can be improved. Indeed, benefits could be gained by simply ensuring that study procedures are clear, by requiring limited (time) investment from the GP, and by investing in personal communication and reminders to keep the GP motivated and interested. Placing greater importance on scientific research during the GP training programme could also serve as a means to motivate future GPs to integrate scientific research in their clinical practice.

Genome-Wide Association Study Reveals a Novel Association Between MYBPC3 Gene Polymorphism, Endurance Athlete Status, Aerobic Capacity and Steroid Metabolism.

BackgroundThe genetic predisposition to elite athletic performance has been a controversial subject due to the underpowered studies and the small effect size of identified genetic variants. The aims of this study were to investigate the association of common single-nucleotide polymorphisms (SNPs) with endurance athlete status in a large cohort of elite European athletes using GWAS approach, followed by replication studies in Russian and Japanese elite athletes and functional validation using metabolomics analysis.ResultsThe association of 476,728 SNPs of Illumina DrugCore Gene chip and endurance athlete status was investigated in 796 European international-level athletes (645 males, 151 females) by comparing allelic frequencies between athletes specialized in sports with high (n = 662) and low/moderate (n = 134) aerobic component. Replication of results was performed by comparing the frequencies of the most significant SNPs between 242 and 168 elite Russian high and low/moderate aerobic athletes, respectively, and between 60 elite Japanese endurance athletes and 406 controls. A meta-analysis has identified rs1052373 (GG homozygotes) in Myosin Binding Protein (MYBPC3; implicated in cardiac hypertrophic myopathy) gene to be associated with endurance athlete status (P = 1.43 × 10−8, odd ratio 2.2). Homozygotes carriers of rs1052373 G allele in Russian athletes had significantly greater VO2max than carriers of the AA + AG (P = 0.005). Subsequent metabolomics analysis revealed several amino acids and lipids associated with rs1052373 G allele (1.82 × 10–05) including the testosterone precursor androstenediol (3beta,17beta) disulfate.ConclusionsThis is the first report of genome-wide significant SNP and related metabolites associated with elite athlete status. Further investigations of the functional relevance of the identified SNPs and metabolites in relation to enhanced athletic performance are warranted.

Outcomes of optical coherence tomography compared with intravascular ultrasound and with angiography to guide coronary stent implantation: one-year results from the ILUMIEN III: OPTIMIZE PCI trial.

In the ILUMIEN III trial, among 450 randomised patients with non-complex lesions undergoing percutaneous coronary intervention (PCI), optical coherence tomography (OCT) guidance led to greater stent expansion than angiography guidance, similar minimal stent area compared to both intravascular ultrasound (IVUS) guidance and angiography guidance, and lower rates of uncorrected dissection and malapposition than both IVUS guidance and angiography guidance. Whether these differences impact on clinical outcomes is unknown. The aim of the present study was to report the 12-month clinical follow-up data from the ILUMIEN III study. OCT-guided PCI, using an external elastic lamina-based protocol, was compared to operator-directed IVUS-guided or angiography-guided PCI. Target lesion failure (TLF) and major adverse cardiovascular events (MACE) at 12 months were adjudicated by a blinded clinical events committee. There were no significant differences in the rates of TLF (2.0% OCT, 3.7% IVUS, 1.4% angiography), MACE (9.8% OCT, 9.1% IVUS, 7.9% angiography), or any of the individual components of these outcomes among the groups. No independent predictors of 12-month stent-related clinical events were identified from final OCT. In this underpowered study, OCT-guided PCI of non-complex lesions did not show a statistical difference in clinical outcomes at 12 months compared with IVUS or angiography guidance. An appropriately powered trial, including only complex patients and lesions, is underway to substantiate the potential clinical benefit of OCT-guided PCI. NCT02471586.

Abstract 03: Model regularization and considerations: Tuning dynamic borrowing in a hybrid clinical trial under Bayesian and frequentist framework

Abstract There has been growing interest in leveraging existing external control data to facilitate clinical trial inferences and decision making. In recent years, the quality of real-world data (RWD) improved significantly, allowing it to be considered for being used as an external control. Borrowing by directly pooling from such external controls to underpowered randomized study has a potential to lead to biased estimates, and a dynamic borrowing framework is recommended to better control false positive outcomes (Lewis et al., 2019). However, the parameter tuning of Bayesian methods of dynamic borrowing remains challenging in order to optimize trial operating characteristics. To provide a general guidance on prior selection and parameter tuning, we implemented and evaluated multiple popular Bayesian prior settings through computational simulations and provided a described relationship to the corresponding frequentist model with regularization. Recommended prior distribution characteristics and practical considerations are proposed. Note: This abstract was not presented at the conference. Citation Format: Ruilin Li, Jiawen Zhu, Jane Fridlyand. Model regularization and considerations: Tuning dynamic borrowing in a hybrid clinical trial under Bayesian and frequentist framework [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 03.

Breast cancer and the black swan.

Most current research in cancer is attempting to find ways of preventing patients from dying after metastatic relapse. Driven by data and analysis, this project is an approach to solve the problem upstream, i.e., to prevent relapse.This project started with the unexpected observation of bimodal relapse patterns in breast and a number of other cancers. This was not explainable with the current cancer paradigm that has guided cancer therapy and early detection for many years. After much analysis using computer simulation and input from a number of medical specialties, we eventually came to the conclusion that the surgery to remove the primary tumour produced systemic inflammation for a week after surgery. This systemic inflammation apparently caused exits of cancer cells and micrometastases from dormant states and resulted in relapses in the first 3 years post-surgery.It was determined in a retrospective study that the common inexpensive perioperative non-steroidal anti-inflammatory drug (NSAID) ketorolac could curtail the early relapse events after breast cancer surgery. A second retrospective study strongly confirmed this but an apparently underpowered prospective study showed no advantage.We are analysing these data and are now proposing to test the perioperative NSAID at Beth Israel Deaconess Medical Centre with triple-negative breast cancer (TNBC) patients, the category that could respond best to the perioperative NSAID. If this works as well as we expect, we would then transfer this technology to low- and/or middle-incomes countries (LMICs), starting with Nigeria where early onset type of TNBC is common. There is an unmet need in LMICs, especially in countries like Nigeria (190 million population), for a means to prevent surgery induced relapse that we are attempting to resolve.This work aims, thus, to describe eventual mechanisms, and ways to test a solution addressing an unmet need. But first, we consider the context, including within an historical perspective, important to explain how and why a Kuhnian paradigm shift may be considered.

Genetics of diabetes mellitus and diabetes complications.

Diabetes is one of the fastest growing diseases worldwide, projected to affect 693 million adults by 2045. Devastating macrovascular complications (cardiovascular disease) and microvascular complications (such as diabetic kidney disease, diabetic retinopathy and neuropathy) lead to increased mortality, blindness, kidney failure and an overall decreased quality of life in individuals with diabetes. Clinical risk factors and glycaemic control alone cannot predict the development of vascular complications; numerous genetic studies have demonstrated a clear genetic component to both diabetes and its complications. Early research aimed at identifying genetic determinants of diabetes complications relied on familial linkage analysis suited to strong-effect loci, candidate gene studies prone to false positives, and underpowered genome-wide association studies limited by sample size. The explosion of new genomic datasets, both in terms of biobanks and aggregation of worldwide cohorts, has more than doubled the number of genetic discoveries for both diabetes and diabetes complications. We focus herein on genetic discoveries for diabetes and diabetes complications, empowered primarily through genome-wide association studies, and emphasize the gaps in research for taking genomic discovery to the next level.

Remdesivir for COVID-19: challenges of underpowered studies

In The Lancet, Yeming Wang and colleagues1 report a randomised trial of remdesivir (200 mg on day 1 followed by 100 mg on days 2–10, in single daily infusions) versus placebo for adults with severe coronavirus disease 2019 (COVID-19) in ten hospitals in Wuhan, China. The authors report on 236 patients (140 [59%] men and 96 [41%] women; median age 65 years [IQR 56–71]), with inconclusive findings on the primary outcome of time to clinical improvement, defined as a two-point improvement on a 6-point ordinal scale,2 a hazard ratio of 1·23 (95% CI 0·87–1·75; favouring remdesivir), and median observation times of 21 days (IQR 13–28) in the remdesivir group versus 23 days (15–28) in the placebo group (a non-significant difference).

The effectiveness of digital multimedia presentation of trial information on recruitment and retention of patients: Protocol for a study within a trial (SWAT).

Background: Studies within trials (SWATs) present an opportunity to examine design factors that may impact on the successful delivery of trials. One area in need of research is trial recruitment. Recruiting patients to trials is a major challenge facing trialists. Failure to meet recruitment targets can result in delays and underpowered studies. This SWAT evaluates the effectiveness of hand-held digital multimedia presentation of trial information and standard written patient information to potential participants on recruitment and retention to a host trial. Methods: This is the protocol for SWAT 15, a two-group, embedded parallel randomised controlled trial (RCT) (ISRCTN12838042) designed within a host trial - the SATIN trial (ISRCTN88111427), a RCT designed for implementation in the Irish primary care setting. The SWAT eligibility criteria was determined by the host trial. General practices who agree to participate in the host trial will provide women (participants) who are willing to consider participating in the host trial with either a multimedia digital information resource facilitated through a handheld tablet device, plus a written participant information leaflet (Intervention) or a written participant information leaflet (comparator). Outcomes are recruitment and retention to the host SATIN trial and participant’s quality of decision-making. Discussion: Although designed to be implemented in a host trial, the host trial, was suspended and therefore this SWAT was not implemented. The protocol and the lessons learnt whilst developing it offer guidance to researchers who wish to answer similar research questions in the future in a similar context or setting. Trial registration: ISRCTN Registry ISRCTN12838042 (11/10/2017)

Screening for Cognitive Frailty Using Short Cognitive Screening Instruments: Comparison of the Chinese Versions of the MoCA and Qmci Screen.

BackgroundCognitive frailty describes cognitive impairment associated with physical decline. Few studies have explored whether short cognitive screens identify frailty. We examined the diagnostic accuracy of the Chinese versions of the Quick Mild Cognitive Impairment (Qmci-CN) screen and Montreal Cognitive Assessment (MoCA-CN) in identifying cognitive frailty.MethodsNinety-five participants with cognitive symptoms [47 with mild cognitive impairment (MCI), 34 with subjective cognitive disorder, and 14 with dementia] were included from two outpatient rehabilitation clinics. Energy (work intensity) and physical activity levels were recorded. Cognitive frailty was diagnosed by an interdisciplinary team using the IANA/IAGG consensus criteria, stratified on the Clinical Frailty Scale (CFS). Instruments were administered sequentially and randomly by trained assessors, blind to the diagnosis.ResultsThe mean age of the sample was 62.6 ± 10.2 years; median CFS score was 4 ± 1 and 36 (38%) were cognitively frail. The Qmci-CN had similar accuracy in differentiating the non-frail from cognitively frail compared to the MoCA-CN, AUC 0.82 versus 0.74, respectively (p = 0.19). At its optimal cut-off (≤55/100), the Qmci-CN provided a sensitivity of 83% and specificity of 67% versus 91% and 51%, respectively, for the MoCA-CN (≤23/30). Neither was accurate in separating MCI from cognitive frailty but both accurately separated cognitive frailty from dementia.ConclusionEstablished short cognitive screens may be useful in identifying cognitive frailty in Chinese adults with cognitive complaints but not in separating MCI from cognitive frailty. The Qmci-CN had similar accuracy to the MoCA-CN and a shorter administration time in this small and under-powered study, necessitating the need for adequately powered studies in different healthcare settings.

The effectiveness of digital multimedia presentation of trial information on recruitment and retention of patients: Protocol for a study within a trial (SWAT).

Background: Studies within trials (SWATs) present an opportunity to examine design factors that may impact on the successful delivery of trials. One area in need of research is trial recruitment. Recruiting patients to trials is a major challenge facing trialists. Failure to meet recruitment targets can result in delays and underpowered studies. This SWAT evaluates the effectiveness of hand-held digital multimedia presentation of trial information and standard written patient information to potential participants on recruitment and retention to a host trial. Methods: This is the protocol for SWAT 15, a two-group, embedded parallel randomised controlled trial (RCT) (ISRCTN12838042) designed within a host trial - the SATIN trial (ISRCTN88111427), a RCT designed for implementation in the Irish primary care setting. The SWAT eligibility criteria was determined by the host trial. General practices who agree to participate in the host trial will provide women (participants) who are willing to consider participating in the host trial with either a multimedia digital information resource facilitated through a handheld tablet device, plus a written participant information leaflet (Intervention) or a written participant information leaflet (comparator). Outcomes are recruitment and retention to the host SATIN trial and participant's quality of decision-making. Discussion: Although designed to be implemented in a host trial, the host trial, was suspended and therefore this SWAT was not implemented. The protocol and the lessons learnt whilst developing it offer guidance to researchers who wish to answer similar research questions in the future in a similar context or setting. Trial registration: ISRCTN Registry ISRCTN12838042 (11/10/2017).

Why does perfectionism confer risk for depressive symptoms? A meta-analytic test of the mediating role of stress and social disconnection

The stress generation model posits perfectionistic concerns and perfectionistic strivings generate stress and, in turn, depression. Alternatively, the Perfectionism Social Disconnection Model (PSDM) maintains perfectionistic concerns and perfectionistic strivings confer risk for depression through social disconnection. However, inconsistent findings, underpowered studies, and overreliance on cross-sectional designs have obscured understanding of the mediating role of stress and social disconnection in the perfectionism–depression link. We addressed this by conducting the first meta-analytic test of the stress generation model and PSDM. Our search yielded 18 longitudinal studies (N = 5,568) involving community adults, undergraduates, medical students, and psychiatric patients. Results revealed perfectionistic concerns predicted increased depression through social disconnection and stress, whereas perfectionistic strivings predicted increased depression through social disconnection, but not stress.