Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions.

INTRODUCTION: Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare-related interventions. METHODS AND ANALYSIS: The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: (1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, (2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, (3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in, (4) a consensus meeting to select checks to be included in a draft tool and to determine its format and (5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies and will help patients by protecting them from the influence of false data on their healthcare. ETHICS AND DISSEMINATION: The University of Manchester ethics decision tool was used, and this returned the result that ethical approval was not required for this project (30 September 2022), which incorporates secondary research and surveys of professionals about subjects relating to their expertise. Informed consent will be obtained from all survey participants. All results will be published as open-access articles. The final tool will be made freely available.

Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions.

Introduction: Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INSPECT-SR project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare related interventions. Methods and analysis: The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: 1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, 2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, 3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in 4) a consensus meeting to select checks to be included in a draft tool and to determine its format, 5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies, and will help patients by protecting them from the influence of false data on their healthcare.

Correction of scientific literature: Too little, too late!

The Coronavirus Disease 2019 (COVID-19) pandemic has highlighted the limitations of the current scientific publication system, in which serious post-publication concerns are often addressed too slowly to be effective. In this Perspective, we offer suggestions to improve academia's willingness and ability to correct errors in an appropriate time frame.

The new normal? Redaction bias in biomedical science.

A concerning amount of biomedical research is not reproducible. Unreliable results impede empirical progress in medical science, ultimately putting patients at risk. Many proximal causes of this irreproducibility have been identified, a major one being inappropriate statistical methods and analytical choices by investigators. Within this, we formally quantify the impact of inappropriate redaction beyond a threshold value in biomedical science. This is effectively truncation of a dataset by removing extreme data points, and we elucidate its potential to accidentally or deliberately engineer a spurious result in significance testing. We demonstrate that the removal of a surprisingly small number of data points can be used to dramatically alter a result. It is unknown how often redaction bias occurs in the broader literature, but given the risk of distortion to the literature involved, we suggest that it must be studiously avoided, and mitigated with approaches to counteract any potential malign effects to the research quality of medical science.

Cortical thickness and resting-state cardiac function across the lifespan: A cross-sectional pooled mega-analysis.

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.

How Podcasts Can Benefit Scientific Communities.

Podcasts are emerging as popular fora for discussing science. Here, we describe how podcasts can benefit scientific communities by disseminating career-specific information that is often unwritten and hidden to those outside academic social knowledge networks. We also provide practical advice on how scientists can launch their own podcasts.

Social Robots for Hospitalized Children.

BACKGROUND AND OBJECTIVES: Social robots (SRs) are increasingly present in medical and educational contexts, but their use in inpatient pediatric settings has not been demonstrated in studies. In this study, we aimed to (1) describe the introduction of SR technology into the pediatric inpatient setting through an innovative partnership among a pediatric teaching hospital, robotics development, and computational behavioral science laboratories and (2) present feasibility and acceptability data. METHODS: Fifty-four children ages 3 to 10 years were randomly exposed to 1 of 3 interventions: (1) interactive SR teddy bear; (2) tablet-based avatar version of the bear; or (3) plush teddy bear with human presence. We monitored intervention enrollment and completion patterns, obtained qualitative feedback on acceptability of SR use from child life-specialist stakeholders, and assessed children's positive and negative affect, anxiety, and pain intensity pre- and postintervention. RESULTS: The intervention was well received and appeared feasible, with 93% of those enrolled completing the study (with 80% complete parent data). Children exposed to the SR reported more positive affect relative to those who received a plush animal. SR interactions were characterized by greater levels of joyfulness and agreeableness than comparison interventions. Child life specialist stakeholders reported numerous potential benefits of SR technology in the pediatric setting. CONCLUSIONS: The SR appears to be an engaging tool that may provide new ways to address the emotional needs of hospitalized children, potentially increasing access to emotionally targeted interventions. Rigorous development and validation of SR technology in pediatrics could ultimately lead to scalable and cost-effective tools to improve the patient care experience.

An analysis of stereotypical motor movements and cardiovascular coupling in individuals on the autism spectrum.

One of the core diagnostic features of autism spectrum disorder (ASD) is engagement in stereotypical motor movements, although the etiology of this repetitive behavior is unknown. Since the 1960s, it has been hypothesized that stereotypical motor movements serve a homeostatic regulation function, and thereby a putative coupling mechanism to cardiovascular arousal. However, to date, surprisingly few reports explicitly assess cardio-somatic coupling and stereotypical motor movements. The present exploratory study investigates coupling of stereotypical body rocking and hand flapping to heart rate and heart rate variability (HRV) in a convenience sample (n = 10) of children and young adults with moderate to profound ASD. Motor movements were recorded via video and three-axis accelerometry, and simultaneous electrocardiographic signals were obtained to determine cardiovascular indices at or around the onset of naturalistically occurring stereotypy. Analysis of the heart rate revealed both repetitive body rocking and hand flapping in particular were found to associate with a strikingly similar cardiovascular pattern of acceleration and deceleration unrelated to physical demands associated with the movements themselves. Furthermore, neither type of stereotypical movement provoked directional change in heart rate variability. The implications of these results and opportunities for future research are discussed.

The voluntary control of piloerection.

Autonomic nervous systems in the human body are named for their operation outside of conscious control. One rare exception is voluntarily generated piloerection (VGP)-the conscious ability to induce goosebumps-whose physiological study, to our knowledge, is confined to three single-individual case studies. Very little is known about the physiological nature and emotional correlates of this ability. The current manuscript assesses physiological, emotional, and personality phenomena associated with VGP in a sample of thirty-two individuals. Physiological descriptions obtained from the sample are consistent with previous reports, including stereotypical patterns of sensation and action. Most participants also reported that their VGP accompanies psychological states associated with affective states (e.g., awe) and experience (e.g., listening to music), and higher than typical openness to new experiences. These preliminary findings suggest that this rare and unusual physiological ability interacts with emotional and personality factors, and thus merits further study.

Arterial structure and function in patients with acute coronary syndrome after 1­year treatment.

INTRODUCTION    The modification of arterial stiffness and intima-media thickness (IMT) is controversial in patients with clinically significant atherosclerosis. OBJECTIVES    We evaluated the effects of 1­year pharmacological therapy on arterial stiffness and IMT in survivors of non­ST­segment elevation myocardial infarction (NSTEMI) who were treated according to current clinical guidelines. PATIENTS AND METHODS    A total of 298 patients with NSTEMI (median age, 64 years; 85 women) were enrolled to this study. Local (carotid) arterial stiffness and IMT were measured noninvasively before discharge and after 12 months of contemporary pharmacological treatment according to current clinical guidelines. The study group was divided into patients with normal systolic blood pressure (BP) (<140 mm Hg) and those with increased systolic BP (≥140 mm Hg) at 12 months. The results were presented as median (25th-75th percentile). RESULTS    There were no significant changes in local arterial stiffness between patients with normal and those with increased systolic BP (8.9 m/s [7.9-10.9 m/s] vs 8.7 m/s [7.8-10.1 m/s] at baseline and 9.6 m/s [8.3-11.0 m/s] vs 10.4 m/s [9.1-12.4 m/s] at 12 months, P = 0.67 and P = 0.05, respectively); however, a significant reduction in IMT was found in both groups (777 µm [664-896 µm] vs 715 µm [619-841 µm] at baseline and 818 µm [720-962 µm] vs 760 µm [674-897 µm] at 12 months, P = 0.0003 and P = 0.001, respectively). Arterial stiffness and IMT were affected by age and mean BP; however, adjustment for these variables did not affect the obtained results in multivariate models. CONCLUSIONS    The 1­year pharmacological treatment of patients after NSTEMI was associated with a significant reduction in IMT but had no effect on the properties of the arterial structure.

Prognosis after acute coronary syndrome in relation with ventricular-arterial coupling and left ventricular strain.

BACKGROUND: The value of modern non-invasive indices of the left ventricle (LV) and arterial system function, and their interaction for determining prognosis in contemporarily treated patients with acute coronary syndrome (ACS) is not well established. The study aimed to determine the association of ventricular-arterial (VA) coupling, LV global longitudinal peak systolic strain (GLPSS), global strain rate (GSR) and end-diastolic volume at end-diastolic pressure 30mmHg (V30) with long-term clinical outcomes in patients with ACS. METHODS: Echocardiography was applied in 569 ACS patients followed up for >12months after hospitalization. Univariate Cox proportional hazard regression models adjusted to various clinical factors, including reduced LV ejection fraction <40%, were used to compare patients between the first and third tertiles of various indices of LV and arterial systems function and their interaction for the prediction of a combined end-point (defined as either stroke, myocardial infarction or death). Results are presented as hazard ratio (HR) with 95% confidence interval (CI). RESULTS: There were 57 clinical outcomes during a median follow-up of 625days. Increased VA coupling >1.68 (HR 2.4; 95% CI: 1.04-5.6); V30>107mL (HR 4.5; 95% CI: 1.9-10.6), GLPSS > -12.8% (HR 2.4; 95% CI: 1.02-5.7), GSR > -0.96 1/s (HR 3.8; 95% CI: 1.6-9.1) were robustly associated with increased hazard. CONCLUSIONS: With a sample of contemporarily treated ACS patients, abnormal values of non-invasive indices of LV function and their interaction with arterial system, predict adverse clinical outcomes, independently of LV ejection fraction.

Worry is associated with robust reductions in heart rate variability: a transdiagnostic study of anxiety psychopathology.

BACKGROUND: Individuals with anxiety disorders display reduced resting-state heart rate variability (HRV), although findings have been contradictory and the role of specific symptoms has been less clear. It is possible that HRV reductions may transcend diagnostic categories, consistent with dimensional-trait models of psychopathology. Here we investigated whether anxiety disorders or symptoms of anxiety, stress, worry and depression are more strongly associated with resting-state HRV. METHODS: Resting-state HRV was calculated in participants with clinical anxiety (n = 25) and healthy controls (n = 58). Symptom severity measures of worry, anxiety, stress, and depression were also collected from participants, regardless of diagnosis. RESULTS: Participants who fulfilled DSM-IV criteria for an anxiety disorder displayed diminished HRV, a difference at trend level significance (p = .1, Hedges' g = -.37, BF10 = .84). High worriers (Total n = 41; n = 22 diagnosed with an anxiety disorder and n = 19 not meeting criteria for any psychopathology) displayed a robust reduction in resting state HRV relative to low worriers (p = .001, Hedges' g = -.75, BF10 = 28.16). CONCLUSIONS: The specific symptom of worry - not the diagnosis of an anxiety disorder - was associated with the most robust reductions in HRV, indicating that HRV may provide a transdiagnostic biomarker of worry. These results enhance understanding of the relationship between the cardiac autonomic nervous system and anxiety psychopathology, providing support for dimensional-trait models consistent with the Research Domain Criteria framework.

Young children's affective responses to another's distress: dynamic and physiological features.

Two descriptive studies set out a new approach for exploring the dynamic features of children's affective responses (sadness and interest-worry) to another's distress. In two samples (N(study1) = 75; N(study2) = 114), Kindergarten children were shown a video-vignette depicting another child in distress and the temporal pattern of spontaneous expressions were examined across the unfolding vignette. Results showed, in both study 1 and 2, that sadness and interest-worry had distinct patterns of elicitation across the events of the vignette narrative and there was little co-occurrence of these affects within a given child. Temporal heart rate changes (study 2) were closely aligned to the events of the vignette and, furthermore, affective responses corresponded to distinctive physiological response profiles. The implications of distinct temporal patterns of elicitation for the meaning of sadness and interest-worry are discussed within the framework of emotion regulation and empathy.

Considerations in the assessment of heart rate variability in biobehavioral research.

Heart rate variability (HRV) refers to various methods of assessing the beat-to-beat variation in the heart over time, in order to draw inference on the outflow of the autonomic nervous system. Easy access to measuring HRV has led to a plethora of studies within emotion science and psychology assessing autonomic regulation, but significant caveats exist due to the complicated nature of HRV. Firstly, both breathing and blood pressure regulation have their own relationship to social, emotional, and cognitive experiments - if this is the case are we observing heart rate (HR) changes as a consequence of breathing changes? Secondly, experiments often have poor internal and external controls. In this review we highlight the interrelationships between HR and respiration, as well as presenting recommendations for researchers to use when collecting data for HRV assessment. Namely, we highlight the superior utility of within-subjects designs along with the importance of establishing an appropriate baseline and monitoring respiration.

Everything Hertz: methodological issues in short-term frequency-domain HRV.

Frequency analysis of the electrocardiographic RR interval is a common method of quantifying autonomic outflow by measuring the beat-to-beat modulation of the heart (heart rate variability; HRV). This review identifies a series of problems with the methods of doing so-the interpretation of low-frequency spectral power, the multiple use of equivalent normalized low frequency (LFnu), high frequency (HFnu) and ratio (LF/HF) terms, and the lack of control over extraneous variables, and reviews research in the calendar year 2012 to determine their prevalence and severity. Results support the mathematical equivalency of ratio units across studies, a reliance on those variables to explain autonomic outflow, and insufficient control of critical experimental variables. Research measurement of HRV has a substantial need for general methodological improvement.