Hemorrhage control prior to shock onset is increasingly recognized as a time-critical intervention. Although tourniquets (TQs) have been demonstrated to save lives, less is known about the physiologic parameters underlying successful TQ application beyond palpation of distal pulses. The current study directly visualized distal arterial occlusion via ultrasonography and measured associated pressure and contact force.

Fifteen tactical officers participated as live models for the study. Arterial occlusion was performed using a standard adult blood pressure (BP) cuff and a Combat Application Tourniquet Generation 7 (CAT7) TQ, applied sequentially to the left mid-bicep. Arterial flow cessation was determined by radial artery palpation and brachial artery pulsed wave doppler ultrasound (US) evaluation. Steady state maximal generated force was measured using a thin-film force sensor.

The mean (95% CI) systolic blood pressure (SBP) required to occlude palpable distal pulse was 112.9mmHg (109-117); contact force was 23.8N [Newton] (22.0-25.6). Arterial flow was visible via US in 100% of subjects despite lack of palpable pulse. The mean (95% CI) SBP and contact force to eliminate US flow were 132mmHg (127-137) and 27.7N (25.1-30.3). The mean (95% CI) number of windlass turns to eliminate a palpable pulse was 1.3 (1.0-1.6) while 1.6 (1.2-1.9) turns were required to eliminate US flow.

Loss of distal radial pulse does not indicate lack of arterial flow distal to upper extremity TQ. On average, an additional one-quarter windlass turn was required to eliminate distal flow. Blood pressure and force measurements derived in this study may provide data to guide future TQ designs and inexpensive, physiologically accurate TQ training models.

Area-level residential instability (ARI), an index of social fragmentation, has been shown to explain the association between urbanicity and psychosis. Urban upbringing has been shown to be associated with decreased gray matter volumes (GMV)s of brain regions corresponding to the right caudal middle frontal gyrus (CMFG) and rostral anterior cingulate cortex (rACC).

We hypothesize that greater ARI will be associated with reduced right posterior CMFG and rACC GMVs.

Data were collected at baseline as part of the North American Prodrome Longitudinal Study. Counties where participants resided during childhood were geographically coded using the US Censuses to area-level factors. ARI was defined as the percentage of residents living in a different house five years ago. Generalized linear mixed models tested associations between ARI and GMVs.

This study included 29 HC and 64 CHR-P individuals who were aged 12 to 24 years, had remained in their baseline residential area, and had magnetic resonance imaging scans. ARI was associated with reduced right CMFG (adjusted β = -0.258; 95% CI = -0.502 – -0.015) and right rACC volumes (adjusted β = -0.318; 95% CI = -0.612 – -0.023). The interaction terms (ARI X diagnostic group) in the prediction of both brain regions were not significant, indicating that the relationships between ARI and regional brain volumes held for both CHR-P and HCs.

Like urban upbringing, ARI may be an important social environmental characteristic that adversely impacts brain regions related to schizophrenia.

No significant relationships.

Behaviors typical of body-focused repetitive behavior disorders such as trichotillomania (TTM) and skin-picking disorder (SPD) are often associated with pleasure or relief, and with little or no physical pain, suggesting aberrant pain perception. Conclusive evidence about pain perception and correlates in these conditions is, however, lacking.

A multisite international study examined pain perception and its physiological correlates in adults with TTM (n = 31), SPD (n = 24), and healthy controls (HCs; n = 26). The cold pressor test was administered, and measurements of pain perception and cardiovascular parameters were taken every 15 seconds. Pain perception, latency to pain tolerance, cardiovascular parameters and associations with illness severity, and comorbid depression, as well as interaction effects (group × time interval), were investigated across groups.

There were no group differences in pain ratings over time (P = .8) or latency to pain tolerance (P = .8). Illness severity was not associated with pain ratings (all P > .05). In terms of diastolic blood pressure (DBP), the main effect of group was statistically significant (P = .01), with post hoc analyses indicating higher mean DBP in TTM (95% confidence intervals [CI], 84.0-93.5) compared to SPD (95% CI, 73.5-84.2; P = .01), and HCs (95% CI, 75.6-86.0; P = .03). Pain perception did not differ between those with and those without depression (TTM: P = .2, SPD: P = .4).

The study findings were mostly negative suggesting that general pain perception aberration is not involved in TTM and SPD. Other underlying drivers of hair-pulling and skin-picking behavior (eg, abnormal reward processing) should be investigated.

While comorbidity of clinical high-risk for psychosis (CHR-P) status and social anxiety is well-established, it remains unclear how social anxiety and positive symptoms covary over time in this population. The present study aimed to determine whether there are more than one covariant trajectory of social anxiety and positive symptoms in the North American Prodrome Longitudinal Study cohort (NAPLS 2) and, if so, to test whether the different trajectory subgroups differ in terms of genetic and environmental risk factors for psychotic disorders and general functional outcome.

In total, 764 CHR individuals were evaluated at baseline for social anxiety and psychosis risk symptom severity and followed up every 6 months for 2 years. Application of group-based multi-trajectory modeling discerned three subgroups based on the covariant trajectories of social anxiety and positive symptoms over 2 years.

One of the subgroups showed sustained social anxiety over time despite moderate recovery in positive symptoms, while the other two showed recovery of social anxiety below clinically significant thresholds, along with modest to moderate recovery in positive symptom severity. The trajectory group with sustained social anxiety had poorer long-term global functional outcomes than the other trajectory groups. In addition, compared with the other two trajectory groups, membership in the group with sustained social anxiety was predicted by higher levels of polygenic risk for schizophrenia and environmental stress exposures.

Together, these analyses indicate differential relevance of sustained v. remitting social anxiety symptoms in the CHR-P population, which in turn may carry implications for differential intervention strategies.

Trichotillomania (TTM) and skin picking disorder (SPD) are common and often debilitating mental health conditions, grouped under the umbrella term of body-focused repetitive behaviors (BFRBs). Recent clinical subtyping found that there were three distinct subtypes of TTM and two of SPD. Whether these clinical subtypes map on to any unique neurobiological underpinnings, however, remains unknown.

Two hundred and fifty one adults [193 with a BFRB (85.5% [n = 165] female) and 58 healthy controls (77.6% [n = 45] female)] were recruited from the community for a multicenter between-group comparison using structural neuroimaging. Differences in whole brain structure were compared across the subtypes of BFRBs, controlling for age, sex, scanning site, and intracranial volume.

When the subtypes of TTM were compared, low awareness hair pullers demonstrated increased cortical volume in the lateral occipital lobe relative to controls and sensory sensitive pullers. In addition, impulsive/perfectionist hair pullers showed relative decreased volume near the lingual gyrus of the inferior occipital–parietal lobe compared with controls.

These data indicate that the anatomical substrates of particular forms of BFRBs are dissociable, which may have implications for understanding clinical presentations and treatment response.

We evaluated the safety and feasibility of high-intensity interval training via a novel telemedicine ergometer (MedBIKE™) in children with Fontan physiology.

The MedBIKE™ is a custom telemedicine ergometer, incorporating a video game platform and live feed of patient video/audio, electrocardiography, pulse oximetry, and power output, for remote medical supervision and modulation of work. There were three study phases: (I) exercise workload comparison between the MedBIKE™ and a standard cardiopulmonary exercise ergometer in 10 healthy adults. (II) In-hospital safety, feasibility, and user experience (via questionnaire) assessment of a MedBIKE™ high-intensity interval training protocol in children with Fontan physiology. (III) Eight-week home-based high-intensity interval trial programme in two participants with Fontan physiology.

There was good agreement in oxygen consumption during graded exercise at matched work rates between the cardiopulmonary exercise ergometer and MedBIKE™ (1.1 ± 0.5 L/minute versus 1.1 ± 0.5 L/minute, p = 0.44). Ten youth with Fontan physiology (11.5 ± 1.8 years old) completed a MedBIKE™ high-intensity interval training session with no adverse events. The participants found the MedBIKE™ to be enjoyable and easy to navigate. In two participants, the 8-week home-based protocol was tolerated well with completion of 23/24 (96%) and 24/24 (100%) of sessions, respectively, and no adverse events across the 47 sessions in total.

The MedBIKE™ resulted in similar physiological responses as compared to a cardiopulmonary exercise test ergometer and the high-intensity interval training protocol was safe, feasible, and enjoyable in youth with Fontan physiology. A randomised-controlled trial of a home-based high-intensity interval training exercise intervention using the MedBIKE™ will next be undertaken.

To evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis.

In the 12-week ARM-TD and AIM-TD studies, the odds of response to deutetrabenazine treatment were higher than the odds of response to placebo at all response levels, and there were low rates of overall adverse events and discontinuations associated with deutetrabenazine.

Patients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration and a long-term maintenance phase. The cumulative proportion of AIMS responders from baseline was assessed. Response was defined as a percent improvement from baseline for each patient from 10% to 90% in 10% increments. AlMS score was assessed by local site ratings for this analysis.

343 patients enrolled in the extension study (111 patients received placebo in the parent study and 232 patients received deutetrabenazine). At Week 54 (n=145; total daily dose [mean±standard error]: 38.1±0.9mg), 63% of patients receiving deutetrabenazine achieved ≥30% response, 48% of patients achieved ≥50% response, and 26% achieved ≥70% response. At Week 80 (n=66; total daily dose: 38.6±1.1mg), 76% of patients achieved ≥30% response, 59% of patients achieved ≥50% response, and 36% achieved ≥70% response. Treatment was generally well tolerated.

Patients who received long-term treatment with deutetrabenazine achieved response rates higher than those observed in positive short-term studies, indicating clinically meaningful long-term treatment benefit.

Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California, USA.

Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.

To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years.

In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine.

Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week106).

343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon.

These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients.

Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California,USA

Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel

Much of the interest in youth at clinical high risk (CHR) of psychosis has been in understanding conversion. Recent literature has suggested that less than 25% of those who meet established criteria for being at CHR of psychosis go on to develop a psychotic illness. However, little is known about the outcome of those who do not make the transition to psychosis. The aim of this paper was to examine clinical symptoms and functioning in the second North American Prodrome Longitudinal Study (NAPLS 2) of those individuals whose by the end of 2 years in the study had not developed psychosis.

In NAPLS-2 278 CHR participants completed 2-year follow-ups and had not made the transition to psychosis. At 2-years the sample was divided into three groups – those whose symptoms were in remission, those who were still symptomatic and those whose symptoms had become more severe.

There was no difference between those who remitted early in the study compared with those who remitted at one or 2 years. At 2-years, those in remission had fewer symptoms and improved functioning compared with the two symptomatic groups. However, all three groups had poorer social functioning and cognition than healthy controls.

A detailed examination of the clinical and functional outcomes of those who did not make the transition to psychosis did not contribute to predicting who may make the transition or who may have an earlier remission of attenuated psychotic symptoms.

Attenuated positive symptom syndrome (APSS), characterized by ‘putatively prodromal’ attenuated psychotic-like pathology, indicates increased risk for psychosis. Poor premorbid social adjustment predicts severity of APSS symptoms and predicts subsequent psychosis in APSS-diagnosed individuals, suggesting application for improving detection of ‘true’ prodromal youth who will transition to psychosis. However, these predictive associations have not been tested in controls and therefore may be independent of the APSS diagnosis, negating utility for improving prediction in APSS-diagnosed individuals.

Association between premorbid social maladjustment and severity of positive, negative, disorganized, and general APSS symptoms was tested in 156 individuals diagnosed with APSS and 76 help-seeking (non-APSS) controls enrolled in the Enhancing the Prospective Prediction of Psychosis (PREDICT) study using prediction analysis.

Premorbid social maladjustment was associated with social anhedonia, reduced expression of emotion, restricted ideational richness, and deficits in occupational functioning, independent of the APSS diagnosis. Associations between social maladjustment and suspiciousness, unusual thought content, avolition, dysphoric mood, and impaired tolerance to normal stress were uniquely present in participants meeting APSS criteria. Social maladjustment was associated with odd behavior/appearance and diminished experience of emotions and self only in participants who did not meet APSS criteria.

Predictive associations between poor premorbid social adjustment and attenuated psychotic-like pathology were identified, a subset of which were indicative of high risk for psychosis. This study offers a method for improving risk identification while ruling out low-risk individuals.

Cognitive deficits are a core feature of schizophrenia, and impairments in most domains are thought to be stable over the course of the illness. However, cross-sectional evidence indicates that some areas of cognition, such as visuospatial associative memory, may be preserved in the early stages of psychosis, but become impaired in later established illness stages. This longitudinal study investigated change in visuospatial and verbal associative memory following psychosis onset.

In total 95 first-episode psychosis (FEP) patients and 63 healthy controls (HC) were assessed on neuropsychological tests at baseline, with 38 FEP and 22 HCs returning for follow-up assessment at 5–11 years. Visuospatial associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery Visuospatial Paired-Associate Learning task, and verbal associative memory was assessed using Verbal Paired Associates subtest of the Wechsler Memory Scale - Revised.

Visuospatial and verbal associative memory at baseline did not differ significantly between FEP patients and HCs. However, over follow-up, visuospatial associative memory deteriorated significantly for the FEP group, relative to healthy individuals. Conversely, verbal associative memory improved to a similar degree observed in HCs. In the FEP cohort, visuospatial (but not verbal) associative memory ability at baseline was associated with functional outcome at follow-up.

Areas of cognition that develop prior to psychosis onset, such as visuospatial and verbal associative memory, may be preserved early in the illness. Later deterioration in visuospatial memory ability may relate to progressive structural and functional brain abnormalities that occurs following psychosis onset.