Reporting bias in breast reconstruction clinical trials: Which and when clinical trials get published.

BACKGROUND: Reporting bias refers to the phenomenon in which the reporting of research findings is influenced by the nature of the results. Without the totality of evidence, clinical practice may be misguided. The objective of this work was to examine the extent of reporting bias in clinical trials of breast reconstruction surgery. METHODS: We searched and extracted data from all completed breast reconstruction clinical trials published in ClinicalTrials.gov from database inception to August 2020. Investigators sought to identify published full manuscripts of the registered trials. The primary outcome was classified as positive or nonpositive and trials were classified as industry or nonindustry funded. Time to publication in a peer-reviewed journal was computed and compared using time-to-event analysis. Trial characteristics associated with publication were evaluated using logistic regression. RESULTS: A total of 156 clinical trials were identified, of which, 53 trials were published. The median time to publication was 22 months (IQR, 13-35 months). Industry-funded studies were associated with a longer time to publication (HR = 2.4, p = 0.023) and publication in lower-impact journals (OR = 3.7, p = 0.048). Randomized clinical trials were associated with faster times to publication than nonrandomized studies (aHR = 3.2, p = 0.030). Statistical significance and the effect size were not associated with time to publication. CONCLUSIONS: We found no evidence that industry-funded trials were more likely to report a positive primary outcome. However, industry-funded trials were associated with a longer time to publication and publication in lower-impact journals.

Estimating the Minimal Clinically Important Difference on the Visual Analogue Scale for Carpometacarpal Thumb Joint Osteoarthritis.

BACKGROUND: The minimal clinically important difference (MCID) is the smallest perceived treatment effect that patients deem clinically significant. There is currently no agreement on an appropriate MCID for the pain visual analogue scale (VAS) in the context of thumb osteoarthritis (OA). METHODS: We approximated MCIDs using a distribution-based approach that pooled standard deviations (SDs) associated with baseline mean values of the pain VAS (0-100 mm). We extracted the data from randomized controlled trials (RCTs) included in a systematic review of adults with long-term OA of the thumb. We excluded RCTs that did not report baseline SD values. The MCIDs were derived at 0.4 and 0.5 SDs of the pooled SD and compared with previously published MCIDs for the pain VAS in OA. RESULTS: A total of 403 patients were pooled from 7 RCTs for the analysis. The mean baseline VAS pain score was 5.6 cm. We derived an MCID of 0.72 cm at 0.4 SDs and 0.91 cm at 0.5 SDs using baseline SDs. We found that MCIDs derived from a distribution-based approach approximated published MCIDs for the VAS for pain for OA in the knee and hip. CONCLUSION: The authors propose that a change of 0.7 to 0.9 cm on the VAS is clinically meaningful in the context of long-term OA of the thumb.

Synergistic Benefits of Combined Aerobic and Cognitive Training on Fluid Intelligence and the Role of IGF-1 in Chronic Stroke.

BACKGROUND: Paired exercise and cognitive training have the potential to enhance cognition by "priming" the brain and upregulating neurotrophins. METHODS: Two-site randomized controlled trial. Fifty-two patients >6 months poststroke with concerns about cognitive impairment trained 50 to 70 minutes, 3× week for 10 weeks with 12-week follow-up. Participants were randomized to 1 of 2 physical interventions: Aerobic (>60% VO2peak using <10% body weight-supported treadmill) or Activity (range of movement and functional tasks). Exercise was paired with 1 of 2 cognitive interventions (computerized dual working memory training [COG] or control computer games [Games]). The primary outcome for the 4 groups (Aerobic + COG, Aerobic + Games, Activity + COG, and Activity + Games) was fluid intelligence measured using Raven's Progressive Matrices Test administered at baseline, posttraining, and 3-month follow-up. Serum neurotrophins collected at one site (N = 30) included brain-derived neurotrophic factor (BDNF) at rest (BDNFresting) and after a graded exercise test (BDNFresponse) and insulin-like growth factor-1 at the same timepoints (IGF-1rest, IGF-1response). RESULTS: At follow-up, fluid intelligence scores significantly improved compared to baseline in the Aerobic + COG and Activity + COG groups; however, only the Aerobic + COG group was significantly different (+47.8%) from control (Activity + Games -8.5%). Greater IGF-1response at baseline predicted 40% of the variance in cognitive improvement. There was no effect of the interventions on BDNFresting or BDNFresponse; nor was BDNF predictive of the outcome. CONCLUSIONS: Aerobic exercise combined with cognitive training improved fluid intelligence by almost 50% in patients >6 months poststroke. Participants with more robust improvements in cognition were able to upregulate higher levels of serum IGF-1 suggesting that this neurotrophin may be involved in behaviorally induced plasticity.

A Bout of High Intensity Interval Training Lengthened Nerve Conduction Latency to the Non-exercised Affected Limb in Chronic Stroke.

Objective: Evaluate intensity-dependent effects of a single bout of high intensity interval training (HIIT) compared to moderate intensity constant-load exercise (MICE) on corticospinal excitability (CSE) and effects on upper limb performance in chronic stroke. Design: Randomized cross-over trial. Setting: Research laboratory in a tertiary rehabilitation hospital. Participants: Convenience sample of 12 chronic stroke survivors. Outcome measures: Bilateral CSE measures of intracortical inhibition and facilitation, motor thresholds, and motor evoked potential (MEP) latency using transcranial magnetic stimulation. Upper limb functional measures of dexterity (Box and Blocks Test) and strength (pinch and grip strength). Results: Twelve (10 males; 62.50 ± 9.0 years old) chronic stroke (26.70 ± 23.0 months) survivors with moderate level of residual impairment participated. MEP latency from the ipsilesional hemisphere was lengthened after HIIT (pre: 24.27 ± 1.8 ms, and post: 25.04 ± 1.8 ms, p = 0.01) but not MICE (pre: 25.49 ± 1.10 ms, and post: 25.28 ± 1.0 ms, p = 0.44). There were no significant changes in motor thresholds, intracortical inhibition or facilitation. Pinch strength of the affected hand decreased after MICE (pre: 8.96 ± 1.9 kg vs. post: 8.40 ± 2.0 kg, p = 0.02) but not after HIIT (pre: 8.83 ± 2.0 kg vs. post: 8.65 ± 2.2 kg, p = 0.29). Regardless of type of aerobic exercise, higher total energy expenditure was associated with greater increases in pinch strength in the affected hand after exercise (R2 = 0.31, p = 0.04) and decreases in pinch strength of the less affected hand (R2 = 0.26 p = 0.02). Conclusion: A single bout of HIIT resulted in lengthened nerve conduction latency in the affected hand that was not engaged in the exercise. Longer latency could be related to the cross-over effects of fatiguing exercise or to reduced hand spasticity. Somewhat counterintuitively, pinch strength of the affected hand decreased after MICE but not HIIT. Regardless of the structure of exercise, higher energy expended was associated with pinch strength gains in the affected hand and strength losses in the less affected hand. Since aerobic exercise has acute effects on MEP latency and hand strength, it could be paired with upper limb training to potentiate beneficial effects.