Placebo effects in randomized trials of pharmacological and neurostimulation interventions for mental disorders: An umbrella review.

There is a growing literature exploring the placebo response within specific mental disorders, but no overarching quantitative synthesis of this research has analyzed evidence across mental disorders. We carried out an umbrella review of meta-analyses of randomized controlled trials (RCTs) of biological treatments (pharmacotherapy or neurostimulation) for mental disorders. We explored whether placebo effect size differs across distinct disorders, and the correlates of increased placebo effects. Based on a pre-registered protocol, we searched Medline, PsycInfo, EMBASE, and Web of Knowledge up to 23.10.2022 for systematic reviews and/or meta-analyses reporting placebo effect sizes in psychopharmacological or neurostimulation RCTs. Twenty meta-analyses, summarising 1,691 RCTs involving 261,730 patients, were included. Placebo effect size varied, and was large in alcohol use disorder (g = 0.90, 95% CI [0.70, 1.09]), depression (g = 1.10, 95% CI [1.06, 1.15]), restless legs syndrome (g = 1.41, 95% CI [1.25, 1.56]), and generalized anxiety disorder (d = 1.85, 95% CI [1.61, 2.09]). Placebo effect size was small-to-medium in obsessive-compulsive disorder (d = 0.32, 95% CI [0.22, 0.41]), primary insomnia (g = 0.35, 95% CI [0.28, 0.42]), and schizophrenia spectrum disorders (standardized mean change = 0.33, 95% CI [0.22, 0.44]). Correlates of larger placebo response in multiple mental disorders included later publication year (opposite finding for ADHD), younger age, more trial sites, larger sample size, increased baseline severity, and larger active treatment effect size. Most (18 of 20) meta-analyses were judged 'low' quality as per AMSTAR-2. Placebo effect sizes varied substantially across mental disorders. Future research should explore the sources of this variation. We identified important gaps in the literature, with no eligible systematic reviews/meta-analyses of placebo response in stress-related disorders, eating disorders, behavioural addictions, or bipolar mania.

Placebo Effects Are Small on Average in the 7.5% CO2 Inhalational Model of Generalized Anxiety.

BACKGROUND: Anxiety disorders are highly prevalent and socio-economically costly. Novel pharmacological treatments for these disorders are needed because many patients do not respond to current agents or experience unwanted side effects. However, a barrier to treatment development is the variable and large placebo response rate seen in trials of novel anxiolytics. Despite this, the mechanisms that drive placebo responses in anxiety disorders have been little investigated, possibly due to low availability of convenient experimental paradigms. We aimed to develop and test a novel protocol for inducing placebo anxiolysis in the 7.5% CO2 inhalational model of generalized anxiety in healthy volunteers. METHODS: Following a baseline 20-minute CO2 challenge, 32 healthy volunteers were administered a placebo intranasal spray labelled as either the anxiolytic "lorazepam" or "saline." Following this, participants surreptitiously underwent a 20-minute inhalation of normal air. Post-conditioning, a second dose of the placebo was administered, after which participants completed another CO2 challenge. RESULTS: Participants administered sham "lorazepam" reported significant positive expectations of reduced anxiety (P = .001), but there was no group-level placebo effect on anxiety following CO2 challenge post-conditioning (Ps > .350). Surprisingly, we found many participants exhibited unexpected worsening of anxiety, despite positive expectations. CONCLUSIONS: Contrary to our hypothesis, our novel paradigm did not induce a placebo response, on average. It is possible that effects of 7.5% CO2 inhalation on prefrontal cortex function or behavior in line with a Bayesian predictive coding framework attenuated the effect of expectations on subsequent placebo response. Future studies are needed to explore these possibilities.

Efficacy of neurostimulation across mental disorders: systematic review and meta-analysis of 208 randomized controlled trials.

Non-invasive brain stimulation (NIBS), including transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS), is a potentially effective treatment strategy for a number of mental conditions. However, no quantitative evidence synthesis of randomized controlled trials (RCTs) of TMS or tDCS using the same criteria including several mental conditions is available. Based on 208 RCTs identified in a systematic review, we conducted a series of random effects meta-analyses to assess the efficacy of NIBS, compared to sham, for core symptoms and cognitive functioning within a broad range of mental conditions. Outcomes included changes in core symptom severity and cognitive functioning from pre- to post-treatment. We found significant positive effects for several outcomes without significant heterogeneity including TMS for symptoms of generalized anxiety disorder (SMD = -1.8 (95% CI: -2.6 to -1), and tDCS for symptoms of substance use disorder (-0.73, -1.00 to -0.46). There was also significant effects for TMS in obsessive-compulsive disorder (-0.66, -0.91 to -0.41) and unipolar depression symptoms (-0.60, -0.78 to -0.42) but with significant heterogeneity. However, subgroup analyses based on stimulation site and number of treatment sessions revealed evidence of positive effects, without significant heterogeneity, for specific TMS stimulation protocols. For neurocognitive outcomes, there was only significant evidence, without significant heterogeneity, for tDCS for improving attention (-0.3, -0.55 to -0.05) and working memory (-0.38, -0.74 to -0.03) in individuals with schizophrenia. We concluded that TMS and tDCS can benefit individuals with a variety of mental conditions, significantly improving clinical dimensions, including cognitive deficits in schizophrenia which are poorly responsive to pharmacotherapy.

Single center experience and literature review of kidney transplantation from non-ideal donors with acute kidney injury: Risk and reward.

INTRODUCTION: There is limited experience transplanting kidneys from either expanded criteria donors (ECD) or donation after circulatory death (DCD) deceased donors with terminal acute kidney injury (AKI). METHODS: AKI kidneys were defined by a donor terminal serum creatinine level >2.0 mg/dL whereas non-ideal deceased donor (NIDD) kidneys were defined as AKI/DCD or AKI/ECDs. RESULTS: From February 2007 to March 2023, we transplanted 266 single AKI donor kidneys including 29 from ECDs, 29 from DCDs (n = 58 NIDDs), and 208 from brain-dead standard criteria donors (SCDs). Mean donor age (43.7 NIDD vs. 33.5 years SCD), KDPI (66% NIDD vs. 45% SCD), and recipient age (57 NIDD vs. 51 years SCD) were higher in the NIDD group (all p < .01). Mean waiting times (17.8 NIDD vs. 24.2 months SCD) and dialysis duration (34 NIDD vs. 47 months SCD) were shorter in the NIDD group (p < .05). Delayed graft function (DGF, 48%) and 1-year graft survival (92.7% NIDD vs. 95.9% SCD) was similar in both groups. Five-year patient and kidney graft survival rates were 82.1% versus 89.9% and 82.1% versus 75.2% (both p = NS) in the NIDD versus SCD groups, respectively. CONCLUSIONS: The use of kidneys from AKI donors can be safely liberalized to include selected ECD and DCD donors.

Long-term outcomes of kidney transplantation from deceased donors with terminal acute kidney injury: Single center experience and literature review.

INTRODUCTION: Long-term outcomes of kidney transplantation from deceased donors (DDKTs) with terminal acute kidney injury (AKI) are not well defined. METHODS: Single center retrospective review of DDKTs from 1/31/07-12/31/19. AKI kidneys were defined by a doubling of the donor's admission serum creatinine (SCr) level AND a terminal SCr ≥2.0 mg/dl. RESULTS: A total of 188 AKI DDKTs were performed, including 154 from brain-dead standard criteria donors (SCD). Mean donor age was 36 years and mean Kidney Donor Profile Index was 50%; mean admission and terminal SCr levels were 1.3 and 3.1 mg/dl, respectively. With a mean follow-up of 94 months (median 89 months), overall patient (both 71.3%) and graft survival (54% AKI vs. 57% non-AKI) rates were comparable to concurrent DDKTs from brain-dead non-AKI SCDs (n = 769). Delayed graft function (DGF) was higher in AKI kidney recipients (47% vs. 20% non-AKI DDKTs, p < .0001). DGF was associated with lower graft survival in recipients of both AKI and non-AKI SCD kidneys but the impact was earlier and more pronounced in non-AKI recipients. CONCLUSIONS: Despite having more than twice the incidence of DGF, kidneys from deceased donors with terminal AKI have long-term outcomes comparable to non-AKI SCD kidneys and represent a safe and effective method to expand the donor pool.

Influence of donor and recipient sex on outcomes following simultaneous pancreas-kidney transplantation in the new millennium: Single-center experience and review of the literature.

INTRODUCTION: The influence of sex on outcomes following simultaneous pancreas-kidney transplantation (SPKT) in the modern era is uncertain. METHODS: We retrospectively studied 255 patients undergoing SPKT from 11/2001 to 8/2020. Cases were stratified according to donor (D) sex, recipient (R) sex, 4 D/R sex categories, and D/R sex-matched versus mismatched. RESULTS: D-male was associated with slightly higher patient (p = .08) and kidney (p = .002) but not pancreas (p = .23) graft survival rates (GSR) compared to D-female. There were no differences in recipient outcomes other than slightly higher pancreas thrombosis (8% R-female vs. 4.2% R-male, p = .28) and early relaparotomy rates in female recipients (38% R-female vs. 29% R-male, p = .14). When analyzing the 4 D/R sex categories, the two D-male groups had higher kidney GSRs compared to the two D-female groups (p = .01) whereas early relaparotomy and pancreas thrombosis rates were numerically higher in the D-female/R-female group compared to the other three groups. Finally, there were no significant differences in outcomes between sex-matched and sex-mismatched groups although overall survival outcomes were lower with female donors irrespective of recipient sex. CONCLUSIONS: The influence of D/R sex following SPKT is subject to multiple confounding issues but survival rates appear to be higher in D-male/R-male and lower in D-female/R-male categories.

Does dialysis modality or duration influence outcomes in simultaneous pancreas-kidney transplant recipients? Single center experience and review of the literature.

AIM: The influence of dialysis modality and duration on outcomes following simultaneous pancreas-kidney transplantation (SPKT) remains uncertain. METHODS: We performed a single-center retrospective review in 255 SPKT recipients according to dialysis modality (55 preemptive/no dialysis-ND, 70 peritoneal dialysis-PD, 130 hemodialysis-HD) and duration (55 none, 137 < 2 years, 41 2-4 years, 22 > 4 years). RESULTS: Mean follow-up was 9.4 years (median 9.2 years). Early (3-month) relaparotomy rate (20% ND vs. 36% PD/HD, p = .03) was lower in ND patients. There were no differences in early graft loss, patient survival, overall or death-censored kidney or pancreas graft survival rates (GSR) at 1 or 10 years follow-up. When analyzing dialysis duration, there were no differences in rates of pancreas thrombosis or early pancreas graft loss. Kidney delayed graft function (DGF) was lower in the ND/short dialysis groups combined (1.0%), compared to the intermediate/long dialysis groups combined (9.5%, p = .003). Early relaparotomy rates were higher with longer duration of dialysis (p = .045 between ND and >4 years of dialysis). Patient survival in the long dialysis group was 50% compared to 69.5% in the other three groups combined (p = .09). However, both overall and death-censored kidney and pancreas GSR were comparable. CONCLUSIONS: Preemptively transplanted patients had a lower incidence of kidney DGF and relaparotomy whereas patient survival was slightly lower with longer dialysis vintage prior to SPKT. Dialysis modality and duration did not influence either overall or death-censored pancreas or kidney GSR in patients with short waiting times, low KDPI donor organs, and dialysis duration up to 4 years.

Feasibility, acceptability and practicality of transcranial stimulation in obsessive compulsive symptoms (FEATSOCS): A randomised controlled crossover trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive form of neurostimulation with potential for development as a self-administered intervention. It has shown promise as a safe and effective treatment for obsessive compulsive disorder (OCD) in a small number of studies. The two most favourable stimulation targets appear to be the left orbitofrontal cortex (L-OFC) and the supplementary motor area (SMA). We report the first study to test these targets head-to-head within a randomised sham-controlled trial. Our aim was to inform the design of future clinical research studies, by focussing on the acceptability and safety of the intervention, feasibility of recruitment, adherence to and tolerability of tDCS, and the size of any treatment-effect. METHODS: FEATSOCS was a randomised, double-blind, sham-controlled, cross-over, multicentre study. Twenty adults with DSM-5-defined OCD were randomised to treatment, comprising three courses of clinic-based tDCS (SMA, L-OFC, Sham), randomly allocated and delivered in counterbalanced order. Each course comprised four 20-min 2 mA stimulations, delivered over two consecutive days, separated by a 'washout' period of at least four weeks. Assessments were carried out by raters who were blind to stimulation-type. Clinical outcomes were assessed before, during, and up to four weeks after stimulation. Patient representatives with lived experience of OCD were actively involved at all stages. RESULTS: Clinicians showed willingness to recruit participants and recruitment to target was achieved. Adherence to treatment and study interventions was generally good, with only two dropouts. There were no serious adverse events, and adverse effects which did occur were transient and mostly mild in intensity. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores were numerically improved from baseline to 24 h after the final stimulation across all intervention groups but tended to worsen thereafter. The greatest effect size was seen in the L-OFC arm, (Cohen's d = -0.5 [95% CI -1.2 to 0.2] versus Sham), suggesting this stimulation site should be pursued in further studies. Additional significant sham referenced improvements in secondary outcomes occurred in the L-OFC arm, and to a lesser extent with SMA stimulation. CONCLUSIONS: tDCS was acceptable, practicable to apply, well-tolerated and appears a promising potential treatment for OCD. The L-OFC represents the most promising target based on clinical changes, though the effects on OCD symptoms were not statistically significant compared to sham. SMA stimulation showed lesser signs of promise. Further investigation of tDCS in OCD is warranted, to determine the optimal stimulation protocol (current, frequency, duration), longer-term effectiveness and brain-based mechanisms of effect. If efficacy is substantiated, consideration of home-based approaches represents a rational next step. TRIAL REGISTRATION: ISRCTN17937049. https://doi.org/10.1186/ISRCTN17937049.

Functional Neuroimaging Correlates of Placebo Response in Patients With Depressive or Anxiety Disorders: A Systematic Review.

BACKGROUND: The mechanisms underlying placebo effects of psychotropic drugs remain poorly understood. We carried out the first, to our knowledge, systematic review of functional neuroimaging correlates of placebo response in adults with anxiety/depressive disorders. METHODS: We systematically searched a large set of databases up to February 2021 based on a pre-registered protocol (PROSPERO CRD42019156911). We extracted neuroimaging data related to clinical improvement following placebo or related to placebo mechanisms. We did not perform a meta-analysis due to the small number of included studies and significant heterogeneity in study design and outcome measures. RESULTS: We found 12 relevant studies for depressive disorders and 4 for anxiety disorders. Activity in the ventral striatum, rostral anterior cingulate cortex and other default mode network regions, orbitofrontal cortex, and dorsolateral prefrontal cortex correlated with placebo antidepressant responses. Activity in regions of the default mode network, including posterior cingulate cortex, was associated with placebo anxiolysis. There was also evidence for possible involvement of the endogenous opioid, dopamine, and serotonin systems in placebo antidepressant and anxiolytic effects. CONCLUSIONS: Several brain regions and molecular systems may be involved in these placebo effects. Further adequately powered studies exploring causality and controlling for confounders are required.

Improved surgical outcomes following simultaneous pancreas-kidney transplantation in the contemporary era.

BACKGROUND: Complications leading to early technical failure have been the Achilles' heel of simultaneous pancreas-kidney transplantation (SPKT). The study purpose was to analyze longitudinally our experience with early surgical complications following SPKT with an emphasis on changes in practice that improved outcomes in the most recent era. STUDY DESIGN: Single center retrospective review of all SPKTs from 11/1/01 to 8/12/20 with enteric drainage. Early relaparotomy was defined as occurring within 3 months of SPKT. Patients were stratified into two sequential eras: Era 1 (E1): 11/1/01-5/30/13; Era 2 (E2) 6/1/13-8/12/20 based on changes in practice that occurred pursuant to donor age and pancreas cold ischemia time (CIT). RESULTS: 255 consecutive SPKTs were analyzed (E1, n = 165; E2, n = 90). E1 patients received organs from older donors (mean E1 27.3 vs. E2 23.1 years) with longer pancreas cold CITs) (mean E1 16.1 vs. E2 13.3 h, both p < .05). E1 patients had a higher early relaparotomy rate (E1 43.0% vs. E2 14.4%) and were more likely to require allograft pancreatectomy (E1 9.1% vs. E2 2.2%, both p < .05). E2 patients underwent systemic venous drainage more frequently (E1 8% vs. E2 29%) but pancreas venous drainage did not influence either relaparotomy or allograft pancreatectomy rates. The most common indications for early relaparotomy in E1 were allograft thrombosis (11.5%) and peri-pancreatic phlegmon/abscess (8.5%) whereas in E2 were thrombosis, pancreatitis/infection, and bowel obstruction (each 3%). CONCLUSION: Maximizing donor quality (younger donors) and minimizing pancreas CIT are paramount for reducing early surgical complications following SPKT.

Evaluation of the orthopaedic trauma association open fracture classification (OTA-OFC) as an outcome prediction tool in open tibial shaft fractures.

INTRODUCTION: It was the goal of this study to determine if the Orthopaedic Trauma Association Open Fracture Classification (OTA-OFC) correlates with complication rates and to determine if it can be used as a predictive tool in the treatment of open tibial shaft fractures. MATERIALS AND METHODS: Retrospective review from two high-volume level 1 trauma centers of open tibial shaft fractures over a 5 year period. Variables of interest included OTA-OFC, type of wound closure, 90-day wound complication, unplanned re-operation, non-union, and amputation. RESULTS: 501 consecutive open tibial shaft fractures. 57.3% (n = 287) were closed primarily; local soft tissue advancement/rotational flap was used in 9.6% (n = 48); free soft tissue transfer used in 22.8% (n = 114); 8.6% (n = 43) required amputation. Of those followed for 90 days (n = 419), 45 (9.0%) had a wound complication, of which 40 (8%) required an unplanned reoperation. 40 (8.0%) patients went on to a documented non-union. All OTA-OFC classification groups significantly correlated with type of definitive closure (r = 0.18-0.81, p < 0.05) with OTA-OFC skin showing the strongest correlation (r = 0.81). OTA-OFC bone loss weakly correlated with wound complication (r = 0.12, p = 0.02) and no OTA-OFC classification correlated with the need for an unplanned secondary procedure. OTA-OFC skin, muscle and arterial all weakly correlated with non-union (r = 0.18-0.25, p < 0.05). OTA-OFC muscle was predictive of non-union (OR = OR = 2.2, 95% CI = 1.2-4.1) and amputation (OR 9.3, 95% CI = 3.7-23.7). OTA-OFC arterial was also predictive of amputation (OR 4.8, 95% CI = 2.5-9.3). CONCLUSIONS: The OTA-OFC correlates variably with the type of definitive closure, the development of a 90-day wound complication, and the occurrence of a non-union. Importantly, OTA-OFC muscle classification is predictive of non-union while both OTA-OFC muscle and arterial were predictive of amputation.

Preoperative Opioid Use Is Associated With Persistent Use, Readmission and Postoperative Complications After Arthroscopic Knee Surgery.

PURPOSE: To evaluate factors associated with prolonged opioid use after arthroscopic knee surgery and to identify associations between preoperative usage and postoperative complications. METHODS: The MarketScan commercial database was searched to identify patients who underwent arthroscopic knee surgery from 2005 to 2014 (based on Current Procedure Terminology code). Preoperative comorbidities including Diagnostic and Statistical Manual of Mental Disorders mental health disorders, chronic pain, chronic regional pain syndrome, obesity, tobacco use, non-narcotic medications and diabetes were queried and documented. Patients who filled opioid prescriptions 1 to 3 months before surgery were identified. Patients who filled opioid prescriptions after surgery were identified. Adjusted odds ratios and 95% confidence intervals were calculated using multivariable logistic regression analysis to determine factors associated with prolonged postoperative opioid use. RESULTS: In total, 1,012,486 patients who underwent arthroscopic knee surgery were identified, and we determined which of these patients were on preoperative opioids. Preoperative opioid usage was associated with a statistically significant increased risk of usage out to 1 year. There was a statistically significant association between postoperative usage and preoperative variables (mental health diagnosis, smokers, chronic pain, chronic regional pain syndrome, and use of non-narcotic medications). There was a statistically significant association between preoperative opioid use and 90-day readmission and postoperative complications. CONCLUSION: In this study, we found that patients taking opioids 1 to 3 months before arthroscopic knee surgery have increased risk of postoperative use. Additionally, chronic opioid use, chronic pain, or use of non-narcotic medications has the highest risk of postoperative opioid use. Finally, preoperative use was associated with an increased risk of 90-day readmission. EVIDENCE: Prognostic Level IV Evidence.

Nicotine Exposure Via Electronic Cigarettes Significantly Impedes Biomechanical Healing Properties of Tendon Healing in a Rat Model.

PURPOSE: To evaluate the biomechanical and histologic effects on Achilles tendon repair of inhaled combusted tobacco versus nicotine exposure via electronic cigarette versus a control group in a small-animal model (Sprague-Dawley rat). METHODS: Fifty-four Sprague-Dawley rats were randomized into 3 groups: combusted tobacco, e-cigarettes, or control. Experimental rats were exposed to research cigarettes or e-cigarette vapor in a smoking chamber for 4 weeks. Surgical transection and repair of the Achilles tendon were then completed, followed by 2 additional weeks of exposure. Achilles tendons were harvested, and biomechanical tensile testing was performed. Histologic evaluation was completed, including hematoxylin-eosin staining, trichrome staining, and immunohistochemistry analysis for type I and type III collagen. RESULTS: The control group showed the highest mean tensile load to failure, at 41.0 ± 10.4 N (range, 18.3-55.1 N); the cigarette cohort had the second highest mean, at 37.3 ± 11.1 N (range, 14.0-54.7 N); and finally, the vaping group had the lowest mean, at 32.3 ± 8.4 N (range, 17.8-45.1 N). One-way analysis of variance showed a significant difference in load to failure when comparing the control group with the e-cigarette group (P = .026). No statistical difference was detected between the control group and cigarette group (P = .35) or between the e-cigarette group and cigarette group (P = .23). Stiffness and qualitative histologic analysis showed no difference among groups. CONCLUSIONS: This investigation shows that in a rat model, nicotine exposure via e-cigarette significantly impedes the biomechanical healing properties of Achilles tendon surgical repair. CLINICAL RELEVANCE: The results indicate that although e-cigarettes are often used as a perceived "safer" alternative to smoking, their use may have a detrimental effect on tendon load to failure.

Brain Functional Connectivity Correlates of Response in the 7.5% CO2 Inhalational Model of Generalized Anxiety Disorder: A Pilot Study.

BACKGROUND: The 7.5% CO2 inhalational model can be used to explore potential treatments for generalized anxiety disorder. However, it is unknown how inter-individual variability in the functional architecture of negative affective valence systems might relate to anxiogenic response in this model. METHODS: A total of 13 healthy volunteers underwent functional magnetic resonance imaging during a passive emotional face perception task. We explored task-evoked functional connectivity in the potential threat system through generalized psychophysiological interaction analysis. Within 7 days, these participants underwent prolonged 7.5% CO2 inhalation, and results from the generalized psychophysiological interaction analysis were correlated with CO2 outcome measures. RESULTS: Functional connectivity between ventromedial prefrontal cortex and right amygdala positively correlated with heart rate and subjective anxiety, while connectivity between midcingulate cortex and left amygdala negatively correlated with anxiety during CO2 challenge. CONCLUSIONS: Response to CO2 challenge correlated with task-evoked functional connectivity in the potential threat system. Further studies should assess whether this translates into clinical populations.

Why we need more research into the placebo response in psychiatry.

Placebos are not inert, but exert measurable biological effects. The placebo response in psychiatric illness is important and clinically relevant, but remains poorly understood. In this paper, we review current knowledge about the placebo response in psychiatric medicine and identify research directions for the future. We argue that more research is needed into the placebo response in psychiatric medicine for three broad reasons. First, awareness of factors that cause placebo response, for whom, and when, within clinical trials will allow us to better evidence efficacy of new treatments. Second, by understanding how placebo mechanisms operate in the clinic, we can take advantage of these to optimise the effects of current treatments. Finally, exploring the biological mechanisms of placebo effects might reveal tractable targets for novel treatment development.

Intramedullary Fixation of Both Bone Forearm Fractures in Children and Adolescents: Healing Correlates With Development of the Olecranon Apophysis.

BACKGROUND: The purpose of this study was to determine whether healing of both bone forearm (BBFA) fractures in children and adolescents is associated with the stage of the olecranon apophysis development as described by the Diméglio modification of the Sauvegrain method. METHODS: Records were reviewed from 2 children's hospitals from 1997 to 2008 to identify all patients younger than 18 years of age who had BBFA fractures treated with intramedullary nail fixation. Sixty-three patients were identified meeting inclusion and exclusion criteria. The stage of the olecranon apophysis was noted on the lateral radiograph at the time of the injury. Data were statistically analyzed to assess the olecranon stage at which the increased rate of delayed union becomes more prevalent using the receiver operating characteristic curve. Time to union, complications, and need for reoperation were recorded for each group. RESULTS: One thousand three hundred ninety-eight patient records were reviewed with 63 patients meeting the inclusion criteria. Using a receiver operating characteristic curve, a cutoff of olecranon stage > 3 (stages 4 to 7) was a significant predictor of the increased rate of delayed union time compared with olecranon stages 0 to 3 (P=0.004). Non-healing-related complication rates for each group were 2/28 (7.1%) for olecranon stages and 0 to 3 and 6/35 (17.1%) for olecranon stages 4 to 7. CONCLUSIONS: The rate of delayed union for BBFA fractures that have been treated with intramedullary nail fixation is increased in children with more mature olecranon apophyses as compared with those with younger olecranon stages. We propose the use of the stage of olecranon apophysis development when choosing the surgical approach and implant for when treating operative BBFA fractures in children. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Sagittal ankle position does not affect axial CT measurements of the syndesmosis in a cadaveric model.

BACKGROUND: The purpose of this study was to evaluate the effect of ankle plantarflexion and the axial location of measurement on quantitative syndesmosis assessment. METHODS: Twelve fresh-frozen cadaveric specimens were secured in three positions of ankle plantarflexion (0°, 15°, and 30°) using an ankle-spanning external fixator and underwent CT scans at each position. Syndesmotic measurements were obtained on axial images using three previously described methods (six measurements) at the level of the tibial plafond and 1 cm proximal to the plafond. Method 1 evaluated the distance between the most anterior and posterior aspects of the fibula and tibia. Method 2 measured medial-lateral diastasis of the anterior and posterior aspects of the fibula, and fibular anterior-posterior translation. Method 3 evaluated axial rotation of the fibula. All measurements were performed by two independent observers. Inter-rater reliability of each measurement was evaluated using intra-class coefficients. Repeated measures analysis of variance (RM-ANOVA) was performed to evaluate within-specimen differences in measurements obtained at varying ankle positions. RESULTS: The anterior incisura component of method 1 demonstrated poor-to-moderate inter-rater reliability across all ankle positions and at both measurement locations. Inter-rater reliability was highest for method 2, especially when measured 1 cm proximal to the plafond. Method 3 demonstrated moderate reliability 1 cm proximal to the plafond. After correcting for multiple comparisons, RM-ANOVA and pairwise analysis revealed that none of the measurements changed significantly with varying ankle position. CONCLUSION: The inter-rater reliability of the most common method of syndesmotic evaluation (method 1) was found to be lower than in previous studies. The most reliable syndesmotic evaluation can be made by measuring diastasis and anteroposterior translation 1 cm proximal to the plafond (method 2). Ankle position from 0° to 30° of plantarflexion did not change the measurements obtained. LEVEL OF EVIDENCE: IV.

The impact of cognitive load on processing efficiency and performance effectiveness in anxiety: evidence from event-related potentials and pupillary responses.

Anxiety has been associated with poor attentional control, as reflected in lowered performance on experimental measures of executive attention and inhibitory control. Recent conceptualisations of anxiety propose that individuals who report elevated anxiety symptoms worry about performance and will exert greater cognitive effort to complete tasks well, particularly when cognitive demands are high. Across two experiments, we examined the effect of anxiety on task performance and across two load conditions using (1) measures of inhibitory control (behavioural reaction times and eye-movement responses) and (2) task effort with pupillary and electrocortical markers of effort (CNV) and inhibitory control (N2). Experiment 1 used an oculomotor-delayed-response task that manipulated load by increasing delay duration to create a high load, relative to a low load, condition. Experiment 2 used a Go/No-Go task and load was manipulated by decreasing the No-Go probabilities (i.e., 20% No-Go in the high load condition and 50% No-Go in the low load condition). Experiment 1 showed individuals with high (vs. low) anxiety made more antisaccade errors across load conditions, and made more effort during the high load condition, as evidenced by greater frontal CNV and increased pupillary responses. In Experiment 2, individuals with high anxiety showed increased effort (irrespective of cognitive load), as characterised by larger pupillary responses. In addition, N2 amplitudes were sensitive to load only in individuals with low anxiety. Evidence of reduced performance effectiveness and efficiency across electrophysiological, pupillary, and oculomotor systems in anxiety provides some support for neurocognitive models of frontocortical attentional dysfunction in anxiety.

Clinical Outcomes of Hyperplantarflexion Variant Compared With Supination External Rotation Ankle Fractures: A Matched-Cohort Analysis.

Recent literature has reported an uncategorized hyperplantarflexion variant ankle fracture characterized by a posteromedial fragment separate from the posterior or medial malleolar fragments. The current study sought to determine whether the outcomes for surgically treated hyperplantarflexion variant fractures are similar to the more common supination external rotation (SER) IV fractures. A prospective registry of operatively treated ankle fractures was queried to create 2 age- and gender-matched cohorts: hyperplantarflexion variant and SER IV fractures. Each cohort had 23 patients (18 females), and matched pairs were within 2 years of age at the date of surgery. Patient demographics, comorbidities, and Foot and Ankle Outcomes Scores at minimum 12 months after the index surgery were compared. The cohorts were similar with respect to body mass index, the length of the clinical follow-up, medical comorbidities, dislocation rate, and postoperative articular incongruity (p > .05). Patient-reported outcomes demonstrated no statistically or clinically significant differences within any domain and were as follows: symptoms (70.8 versus 77.8, p = .11), pain (80.7 versus 85.0, p = .33), activities of daily living (83.7 versus 89.2, p = .23), sports (67.4 versus 73.4, p = .33), and quality of life (57.3 versus 63.9, p = .24) for the hyperplantarflexion and SER IV groups, respectively. No significant differences were found in the rang`e of motion for dorsiflexion (17.7° versus 18.1°, p = .52) or for plantarflexion (48.6° versus 47.1°, p = .71). Patients treated surgically for hyperplantarflexion variant ankle fractures have similar 1-year clinical outcomes when compared with the more common SER IV fracture patterns, provided that the injury is correctly identified preoperatively and treated appropriately.

The Effect of Prefrontal Transcranial Direct Current Stimulation on Attention Network Function in Healthy Volunteers.

OBJECTIVES: The effect of acute transcranial direct current stimulation (tDCS) on cortical attention networks remains unclear. We examined the effect of 20 min of 2 mA dorsolateral prefrontal cortex tDCS (bipolar balanced montage) on the efficiency of alerting, orienting and executive attention networks measured by the attention network test. MATERIALS AND METHODS: A between-subjects stratified randomized design compared active tDCS vs. sham tDCS on attention network function in healthy young adults. RESULTS: Executive attention was greater following active vs. sham stimulation (d = 0.76) in the absence of effects on alerting, orienting, or global RT or error rates. Group differences were not moderated by state-mood. CONCLUSION(S): Twenty minutes of active 2 mA tDCS over left DLPFC is associated with greater executive attention in healthy humans.