Prehospital Tranexamic Acid for Severe Trauma.

BACKGROUND: Whether prehospital administration of tranexamic acid increases the likelihood of survival with a favorable functional outcome among patients with major trauma and suspected trauma-induced coagulopathy who are being treated in advanced trauma systems is uncertain. METHODS: We randomly assigned adults with major trauma who were at risk for trauma-induced coagulopathy to receive tranexamic acid (administered intravenously as a bolus dose of 1 g before hospital admission, followed by a 1-g infusion over a period of 8 hours after arrival at the hospital) or matched placebo. The primary outcome was survival with a favorable functional outcome at 6 months after injury, as assessed with the use of the Glasgow Outcome Scale-Extended (GOS-E). Levels on the GOS-E range from 1 (death) to 8 ("upper good recovery" [no injury-related problems]). We defined survival with a favorable functional outcome as a GOS-E level of 5 ("lower moderate disability") or higher. Secondary outcomes included death from any cause within 28 days and within 6 months after injury. RESULTS: A total of 1310 patients were recruited by 15 emergency medical services in Australia, New Zealand, and Germany. Of these patients, 661 were assigned to receive tranexamic acid, and 646 were assigned to receive placebo; the trial-group assignment was unknown for 3 patients. Survival with a favorable functional outcome at 6 months occurred in 307 of 572 patients (53.7%) in the tranexamic acid group and in 299 of 559 (53.5%) in the placebo group (risk ratio, 1.00; 95% confidence interval [CI], 0.90 to 1.12; P = 0.95). At 28 days after injury, 113 of 653 patients (17.3%) in the tranexamic acid group and 139 of 637 (21.8%) in the placebo group had died (risk ratio, 0.79; 95% CI, 0.63 to 0.99). By 6 months, 123 of 648 patients (19.0%) in the tranexamic acid group and 144 of 629 (22.9%) in the placebo group had died (risk ratio, 0.83; 95% CI, 0.67 to 1.03). The number of serious adverse events, including vascular occlusive events, did not differ meaningfully between the groups. CONCLUSIONS: Among adults with major trauma and suspected trauma-induced coagulopathy who were being treated in advanced trauma systems, prehospital administration of tranexamic acid followed by an infusion over 8 hours did not result in a greater number of patients surviving with a favorable functional outcome at 6 months than placebo. (Funded by the Australian National Health and Medical Research Council and others; PATCH-Trauma ClinicalTrials.gov number, NCT02187120.).

Dexamethasone for Cardiac Surgery: A Practice Preference-Randomized Consent Comparative Effectiveness Trial.

BACKGROUND: High-dose corticosteroids have been used to attenuate the inflammatory response to cardiac surgery and cardiopulmonary bypass, but patient outcome benefits remain unclear. Our primary aim was to determine whether using dexamethasone was superior to not using dexamethasone to increase the number of home days in the first 30 days after cardiac surgery. Our secondary aim was to evaluate efficiency, value and impact of the novel trial design. METHODS: This pragmatic, international trial incorporating a prerandomized consent design favoring local practice enrolled patients undergoing cardiac surgery across 7 hospitals in Australia and The Netherlands. Patients were randomly assigned to dexamethasone, 1 mg/kg, or not (control). The primary outcome was the number of days alive and at home up to 30 days after surgery ("home days"). Secondary outcomes included prolonged mechanical ventilation (>48 h), sepsis, renal failure, myocardial infarction, stroke and death. RESULTS: Of 2093 patients assessed for eligibility, 1951 were randomized (median age 63 years, 80% male). The median number of home days was 23.0 (IQR, 20.1 to 24.1) in the dexamethasone group and 23.1 (IQR, 20.1 to 24.6) in the no dexamethasone group; median difference 0.1 (95% CI, -0.3 to 0.5), P=0.66. The rates of prolonged mechanical ventilation, RR 0.72 (95% CI, 0.48 to 1.08), sepsis, RR 1.02 (95% CI, 0.57 to 1.82), renal failure, RR 0.94 (95% CI, 0.80 to 1.12), myocardial infarction, RR 1.20 (95% CI, 0.30 to 4.82), stroke, RR 1.06 (95% CI, 0.54 to 2.08), and death, RR 0.72 (95% CI, 0.22 to 2.35), were comparable between groups (all P>0.10). Dexamethasone reduced intensive care unit stay, median 29 (IQR, 22 to 50) h vs. 43 (24 to 72) h, P=0.004. Our novel trial design was highly efficient (89.3% enrolment). CONCLUSIONS: Among patients undergoing cardiac surgery, high-dose dexamethasone decreased intensive care unit stay but did not increase the number of home days after surgery.

Identifying Conversational Strategies for Psychiatrists in Discussing Substance Use with Adolescent Patients.

Child and adolescent psychiatrists are uniquely positioned to discuss substance use with high risk patients; however, there has been little research about these conversations and their characteristics. To identify communication strategies for navigating conversations about substance use with adolescent patients, we conducted 21 in-depth interviews with practicing child and adolescent psychiatrists. Findings from this study identify four strategies that child and adolescent psychiatrists reported as being successful: expressing empathy, avoiding resistance, honoring autonomy, and managing family involvement. In addition to describing these strategies, we briefly describe a theoretical framework that might help to explain the perceived success of these strategies, and we offer recommendations for how to apply our findings to improve psychiatric practice.

COVID-19 Pandemic Impact on Percutaneous Coronary Intervention for Acute Coronary Syndromes: An Australian Tertiary Centre Experience.

BACKGROUND: Countries who suffered large COVID-19 outbreaks reported a decrease in acute coronary syndrome (ACS) presentations and percutaneous coronary intervention (PCI). The impact of the pandemic in countries like Australia, with relatively small outbreaks yet significant social restrictions, is relatively unknown. There is also limited and conflicting data regarding the impact on clinical outcomes, symptom-to-door time (STDT) and door-to-balloon time (DTBT). METHODS: Consecutive ACS patients treated with PCI were prospectively recruited from a tertiary hospital network in Melbourne, Australia. The pre-pandemic period (11 March 2019-10 March 2020) was compared to the pandemic period (11 March 2020-10 May 2020) using an interrupted time series analysis with a primary endpoint of number PCI-treated ACS per day. Secondary endpoints included STDT, DTBT, total mortality and major adverse cardiac events (MACE). RESULTS: A total 984 ACS patients (14.8% during the pandemic period) received PCI. Mean number of PCI-treated ACS per day did not differ between the two periods (2.3 vs 2.4, p=0.61) with no difference in STDT [+51.3 mins, 95% confidence interval (CI) -52.4 to 154.9, p=0.33], 30-day mortality (5% vs 5.3%, p=0.86) or MACE (5.2% vs 6.1%, p=0.68). DTBT was significantly longer during the pandemic versus the pre-pandemic period (+18.1 mins, 95% CI 1.6-34.5, p=0.03) and improved with time (slope estimate: -0.76, 95% CI -1.62 to 0.10). CONCLUSIONS: Despite significant social restrictions imposed in Melbourne, numbers of ACS treated with PCI and 30-day outcomes were similar to pre-pandemic times. DTBT was significantly longer during the COVID-19 pandemic period, likely reflecting infection control measures, which reassuringly improved with time.

Macrophage migration inhibitory factor acts as a neurotrophin in the developing inner ear.

This study is the first to demonstrate that macrophage migration inhibitory factor (MIF), an immune system 'inflammatory' cytokine that is released by the developing otocyst, plays a role in regulating early innervation of the mouse and chick inner ear. We demonstrate that MIF is a major bioactive component of the previously uncharacterized otocyst-derived factor, which directs initial neurite outgrowth from the statoacoustic ganglion (SAG) to the developing inner ear. Recombinant MIF acts as a neurotrophin in promoting both SAG directional neurite outgrowth and neuronal survival and is expressed in both the developing and mature inner ear of chick and mouse. A MIF receptor, CD74, is found on both embryonic SAG neurons and adult mouse spiral ganglion neurons. Mif knockout mice are hearing impaired and demonstrate altered innervation to the organ of Corti, as well as fewer sensory hair cells. Furthermore, mouse embryonic stem cells become neuron-like when exposed to picomolar levels of MIF, suggesting the general importance of this cytokine in neural development.

White-coat hypertension.

1. Numerous studies have examined whether white-coat hypertension (WCHT) is associated with increased cardiovascular risk, but with definitions of WCHT that were not sufficiently robust, results have been inconsistent. The aim of the present review was to standardize the evidence by only including studies that used a definition of WCHT consistent with international guidelines. 2. Published studies were reviewed for data on vascular dysfunction, target organ damage, risk of future sustained hypertension and cardiovascular events. 3. White-coat hypertension has a population prevalence of approximately 15% and is associated with non-smoking and slightly elevated clinic blood pressure. Compared with normotensives, subjects with WCHT are at increased cardiovascular risk due to a higher prevalence of glucose dysregulation, increased left ventricular mass index and increased risk of future diabetes and hypertension. 4. In conclusion, management of a patient with WCHT should focus on cardiovascular risk factors, particularly glucose intolerance, not blood pressure alone.

A retrospective descriptive study of the characteristics of deliberate self-poisoning patients with single or repeat presentations to an Australian emergency medicine network in a one year period.

BACKGROUND: A proportion of deliberate self-poisoning (DSP) patients present repeatedly to the emergency department (ED). Understanding the characteristics of frequent DSP patients and their presentation is a first step to implementing interventions that are designed to prevent repeated self-poisoning. METHODS: All DSP presentations to three networked Australian ED's were retrospectively identified from the ED electronic medical record and hospital scanned medical records for 2011. Demographics, types of drugs ingested, emergency department length of stay and disposition for the repeat DSP presenters were extracted and compared to those who presented once with DSP in a one year period. Logistic regression was used to analyse repeat versus single DSP data. RESULTS: The study determined 755 single presenters and 93 repeat DSP presenters. The repeat presenters contributed to 321 DSP presentations. They were more likely to be unemployed (61.0% versus 39.9%, p = 0.008) and have a psychiatric illness compared to single presenters (36.6% versus 15.5%, p < 0.001). Repeat presenters were less likely to receive a toxicology consultation (11.5% versus 27.3%, p < 0.001) and were more likely to abscond from the ED (7.5% versus 3.4%, p = 0.004). Repeat presenters were more likely to ingest paracetamol and antipsychotics than single presenters. The defined daily dose for the most common antipsychotic ingested, quetiapine, was less in the repeat presenter group (median 1.9 [IQR: 1.3-3.5]) compared with the single presenter group (4 [1.4-9.5]), (OR 0.85, 95% CI 0.74-0.99). CONCLUSION: Patients who present repeatedly to the ED with DSP have pre-existing disadvantages, with increased likelihood of being unemployed and having a mental illness. These patients are also more likely to have health service inequities given the greater likelihood to abscond from the ED and lower likelihood of receiving toxicology consultation for their DSP. Early recognition of repeat DSP patients in the ED may facilitate the development of individualised care plans with the aim to reduce repeat episodes of self-poisoning and subsequent risk of successful suicide.

Treatment of Depression in Adolescents With Myasthenia Gravis.

Myasthenia gravis (MG) is an autoimmune disorder in which, most commonly, there is a production of autoantibodies against the nicotinic acetylcholinergic receptors at the neuromuscular junction, resulting in skeletal muscle weakness. For pediatric patients, literature addressing the psychiatric implications of MG and suitable treatment options for individuals with concurrent psychiatric illnesses is scarce. In this case report, an adolescent with MG and comorbid depression was treated following a suicide attempt via self-poisoning. The patient experienced an improvement of depressive symptoms upon initiating fluoxetine, despite concerns raised by previous studies suggesting that fluoxetine might block acetylcholine receptors at the neuromuscular junction with varying degrees of affinity, potentially worsening MG symptoms. In this case, our patient exhibited sustained control of her MG symptoms without exacerbation once she was started on fluoxetine. This case highlights the value of further investigation into the safety and efficacy of selective serotonin reuptake inhibitors (SSRIs) in the management of depression among pediatric patients with MG.

Characterizing neurological status in individuals with tetraplegia using transcutaneous spinal stimulation.

Transcutaneous spinal stimulation (TSS) is emerging as a valuable tool for electrophysiological and clinical assessment. This study had the objective of examining the recruitment patterns of upper limb (UL) motor pools through the delivery of TSS above and below a spinal lesion. It also aimed to explore the connection between the recruitment pattern of UL motor pools and the neurological and functional status following spinal cord injury (SCI). In eight participants with tetraplegia due to cervical SCI, TSS was delivered to the cervical spinal cord between the spinous processes of C3-C4 and C7-T1 vertebrae, and spinally evoked motor potentials in UL muscles were characterized. We found that responses observed in UL muscles innervated by motor pools below the level of injury demonstrated relatively reduced sensitivity to TSS compared to those above the lesion, were asymmetrical in the majority of muscles, and were dependent on the level, extent, and side of SCI. Overall, our findings indicate that electrophysiological data acquired through TSS can offer insights into the extent of UL functional asymmetry, disruptions in neural pathways, and changes in motor control following SCI. This study suggests that such electrophysiological data can supplement clinical and functional assessment and provide further insight regarding residual motor function in individuals with SCI.

Transcutaneous spinal stimulation provides characterization of neurological status in individuals with tetraplegia.

Transcutaneous spinal stimulation (TSS) is emerging as a valuable tool for electrophysiological and clinical assessment. This study had the objective of examining the recruitment patterns of upper limb (UL) motor pools through the delivery of TSS above and below a spinal lesion. It also aimed to explore the connection between the recruitment pattern of UL motor pools and the neurological and functional status following spinal cord injury (SCI). In eight participants with tetraplegia due to cervical SCI, TSS was delivered to the cervical spinal cord between the spinous processes of C3-C4 and C7-T1 vertebrae, and spinally evoked motor potentials in UL muscles were characterized. We found that responses observed in UL muscles innervated by motor pools below the level of injury demonstrated relatively reduced sensitivity to TSS compared to those above the lesion, were asymmetrical in the majority of muscles, and were dependent on the level, extent, and side of SCI. Overall, our findings indicate that electrophysiological data acquired through TSS can offer insights into the extent of UL functional asymmetry, disruptions in neural pathways, and changes in motor control following SCI. This study suggests that such electrophysiological data can supplement clinical and functional assessment and provide further insight regarding residual motor function in individuals with SCI.

Combinatorial Effects of Transcutaneous Spinal Stimulation and Task-Specific Training to Enhance Hand Motor Output after Paralysis.

Background: Despite the positive results in upper limb (UL) motor recovery after using electrical neuromodulation in individuals after cervical spinal cord injury (SCI) or stroke, there has been limited exploration of potential benefits of combining task-specific hand grip training with transcutaneous electrical spinal stimulation (TSS) for individuals with UL paralysis. Objectives: This study investigates the combinatorial effects of task-specific hand grip training and noninvasive TSS to enhance hand motor output after paralysis. Methods: Four participants with cervical SCI classified as AIS A and B and two participants with cerebral stroke were recruited in this study. The effects of cervical TSS without grip training and during training with sham stimulation were contrasted with hand grip training with TSS. TSS was applied at midline over cervical spinal cord. During hand grip training, 5 to 10 seconds of voluntary contraction were repeated at a submaximum strength for approximately 10 minutes, three days per week for 4 weeks. Signals from hand grip dynamometer along with the electromyography (EMG) activity from UL muscles were recorded and displayed as visual feedback. Results: Our case study series demonstrated that combined task-specific hand grip training and cervical TSS targeting the motor pools of distal muscles in the UL resulted in significant improvements in maximum hand grip strength. However, TSS alone or hand grip training alone showed limited effectiveness in improving grip strength. Conclusion: Task-specific hand grip training combined with TSS can result in restoration of hand motor function in paralyzed upper limbs in individuals with cervical SCI and stroke.

Exploratory examination of the effects of d-amphetamine on active-state functional connectivity: Influence of impulsivity and sensation-seeking status.

Recent advances in diagnostic research identified that individuals with higher impulsivity and sensation-seeking scores tend to report more positive subjective responses to stimulant drugs such as amphetamine. The current exploratory study hypothesized that differences in underlying mesocorticolimbic circuitry may mediate the relationship between personality and responses to stimulants due to its previously established implication in reward processes as well as the overlap between its dopaminergic projections and the pharmacodynamics of many stimulants. Forty participants (20 female) were recruited with relatively high- and low-impulsivity and sensation-seeking scores as defined by the Zuckerman-Kuhlman Personality Questionnaire (Form IIIR; Zuckerman, Kuhlman, Joireman, Teta, & Kraft, 1993) for a double-blind, placebo-controlled, intranasal amphetamine administration study conducted within an MRI scanner. Active state seed-to-voxel connectivity analyses assessed the effects of amphetamine, personality, subjective responses to amphetamine, and their interactions with mesocorticolimbic seeds on data collected during monetary incentive delay and go/no-go task performance. Results indicated that amphetamine administration largely disrupted brain activity as evidenced by connectivity values shifting toward no correlation among brain stem, striatal, and frontal cortex regions. Additionally, associations of impulsivity and connectivity between ventral tegmental and medial orbitofrontal as well as lateral orbitofrontal and putamen regions were inverted from negative to positive during the placebo and amphetamine conditions, respectively. Personality was unrelated to subjective responses to amphetamine. Results are interpreted as providing evidence of underlying differences in mesocorticolimbic circuitry being a potential target for requisite diagnostic and treatment strategies implicated with stimulant use disorders, but further research is needed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cervical transcutaneous spinal stimulation for spinal motor mapping.

Transcutaneous spinal stimulation (TSS) is a promising approach to restore upper-limb (UL) functions after spinal cord injury (SCI) in humans. We sought to demonstrate the selectivity of recruitment of individual UL motor pools during cervical TSS using different electrode placements. We demonstrated that TSS delivered over the rostrocaudal and mediolateral axes of the cervical spine resulted in a preferential activation of proximal, distal, and ipsilateral UL muscles. This was revealed by changes in motor threshold intensity, maximum amplitude, and the amount of post-activation depression of the evoked responses. We propose that an arrangement of electrodes targeting specific UL motor pools may result in superior efficacy, restoring more diverse motor activities after neurological injuries and disorders, including severe SCI.

Noise overstimulation of young adult UMHET4 mice accelerates age-related hearing loss.

Many factors contribute to hearing loss commonly found in older adults. There can be natural aging of cellular elements, hearing loss previously induced by environmental factors such as noise or ototoxic drugs as well as genetic and epigenetic influences. Even when noise overstimulation does not immediately cause permanent hearing loss it has recently been shown to increase later age-related hearing loss (ARHL). The present study further investigated this condition in the UMHET4 mouse model by comparing a small arms fire (SAF)-like impulse noise exposure that has the greatest immediate effect in more apical cochlear regions to a broadband noise (BBN) exposure that has the greatest immediate effect in more basal cochlear regions. Both noise exposures were given at levels that only induced temporary auditory brainstem response (ABR) threshold shifts (TS). Mice were noise exposed at 5 months of age followed by ABR assessment at 6, 12, 18, 21, and 24 months of age. Mice that received the SAF-like impulse noise had accelerated age-related TS at 4 kHz that appeared at 12 months of age (significantly increased compared to no-noise controls). This increased TS at 4 kHz continued at 18 and 21 months but was no longer significantly greater at 24 months of age. The SAF-like impulse noise also induced a significantly greater mean TS at 48 kHz, first appearing at 18 months of age and continuing to be significantly greater than controls at 21 and 24 months. The BBN induced a different pace and pattern of enhanced age-related ABR TS. The mean TS for the BBN group first became significantly greater than controls at 18 months of age and only at 48 kHz. It remained significantly greater than controls at 21 months but was no longer significantly greater at 24 months of age. Results, therefore, show different influences on ARHL for the two different noise exposure conditions. Noise-induced enhancement appears to provide more an acceleration than overall total increase in ARHL.

Hyperbaric Oxygen for Lower Limb Trauma (HOLLT): an international multi-centre randomised clinical trial.

INTRODUCTION: Hyperbaric oxygen treatment (HBOT) is sometimes used in the management of open fractures and severe soft tissue crush injury, aiming to reduce complications and improve outcomes. METHODS: Patients with open tibial fractures were randomly assigned within 48 hours of injury to receive standard trauma care or standard care plus 12 sessions of HBOT. The primary outcome was the incidence of necrosis or infection or both occurring within 14 days of injury. RESULTS: One-hundred and twenty patients were enrolled. Intention to treat primary outcome occurred in 25/58 HBOT assigned patients and 34/59 controls (43% vs 58%, odds ratio (OR) 0.55, 95% confidence interval (CI) 0.25 to 1.18, P = 0.12). Tissue necrosis occurred in 29% of HBOT patients and 53% of controls (OR 0.35, 95% CI 0.16 to 0.78, P = 0.01). There were fewer late complications in patients receiving HBOT (6/53 vs 18/52, OR 0.22, 95% CI 0.08 to 0.64, P = 0.007) including delayed fracture union (5/53 vs 13/52, OR 0.31, 95% CI 0.10 to 0.95, P = 0.04). Quality of life measures at one and two years were superior in HBOT patients. The mean score difference in short form 36 was 2.90, 95% CI 1.03 to 4.77, P = 0.002, in the short musculoskeletal function assessment (SMFA) was 2.54, 95% CI 0.62 to 4.46, P = 0.01; and in SMFA daily activities was 19.51, 95% CI 0.06 to 21.08, P = 0.05. CONCLUSIONS: In severe lower limb trauma, early HBOT reduces tissue necrosis and the likelihood of long-term complications, and improves functional outcomes. Future research should focus on optimal dosage and whether HBOT has benefits for other injury types.

Progesterone effects on the discriminative stimulus, subjective and performance effects of triazolam in healthy, premenopausal women.

There is accumulating evidence that sex plays a critical role in drug abuse. Female sex hormones have been shown to affect central nervous system function and modulate the effects of drugs of abuse. For example, γ-aminobutyric acid type A (GABA(A)) receptor function is positively modulated by progesterone metabolites. There is evidence from preclinical in-vitro and in-vivo studies as well as some clinical research suggesting that progesterone and its metabolites may enhance the behavioral effects of benzodiazepines, which also serve as positive modulators of GABA(A) receptors. The purpose of this experiment was to determine the independent and combined discriminative stimulus, subjective and psychomotor effects of progesterone and triazolam in healthy adult premenopausal women. Oral micronized progesterone (100 mg), triazolam (0.06, 0.12 and 0.25 mg/70 kg) and placebo were administered to healthy, premenopausal women (n=9) under conditions of low circulating sex hormones. Triazolam alone functioned as a discriminative stimulus and produced prototypical sedative-like effects (e.g., performance impairment, enhanced reports of sedative effects). Progesterone alone produced sedative-like effects on several subjective and performance measures, and the dose combination effects of progesterone and triazolam on several subjective measures of drug effect were similar to the summation of the two drug effects in isolation. Progesterone did not substitute for or modify the discriminative stimulus effects of triazolam. These results suggest that the parent hormone, progesterone, and triazolam have discordant neuropharmacological mechanisms of action. Additional research is necessary to determine the degree to which neurosteroids influence sex differences in benzodiazepine use and abuse.

Assessing adolescent tobacco use in a substance use treatment program with self-report and biological measures.

Tobacco use in adolescents can alter their lifetime health outcomes. Despite the importance of early identification and treatment, adolescent tobacco use, including that of electronic vapor products (e.g., e-cigarettes), is often missed. In a state-funded substance use treatment program, we added biological measures, including urinary cotinine and exhaled carbon monoxide to self-report measures to assess recent and lifetime tobacco use. We conducted a retrospective review of the de-identified charts to examine the feasibility of screening for self-report and biological measures of tobacco use. Self-report, urinary cotinine, and exhaled carbon monoxide samples were obtained at every visit, including intake and follow-up. There were 52 adolescents with a total of 400 clinic visits to the program. Of those 400 visits, 258 included self-reported tobacco use and 142 included a denial of using any form of tobacco. However, of those 142 visits with a negative self-report of tobacco, 31 tested positive for cotinine and 6 had positive exhaled carbon monoxide. Although 111 of the 142 had negative cotinine, 5 had positive carbon monoxide, but all of those self-reported recent cannabis use. Despite using a sensitive measure of self-report of tobacco use, almost 22% of visits had a discordant self-report with a biological measure that indicated tobacco use. Considering the lifelong impact of adolescent tobacco use, clinicians should consider augmenting self-report with biological measures of tobacco use. Identification of tobacco use in adolescents with substance use can assist clinicians in providing education about tobacco use, such as electronic vapor products, and individualizing treatments.

Performance and subjective effects of diazepam and d-amphetamine in high and low sensation seekers.

Although sensation-seeking status is associated with age of initiation and amount of drug use among adolescents, and sensitivity to the behavioral and reinforcing effects of drugs among young adults, it is unclear whether sensation-seeking status among adolescents is predictive of sensitivity to the pharmacological effects of drugs (i.e. abuse potential) as adults. This study examined the acute behavioral effects of oral diazepam and d-amphetamine in young adults, ages 18-21 years, who had consistently scored in the highest or lowest third of their grade-based cohort on a modified Sensation Seeking Scale that was completed annually between ages 10 and 14 years. Healthy participants completed 16 7.5-h test days, with test days separated by a minimum of 48 h. Each day, assessments consisting of computer task performance, verbal report of drug effects, and cardiovascular measures were completed 0, 50, 110, 170, 230, and 290 min after drug administration. Placebo and three active doses of diazepam and d-amphetamine (2.5, 5.0 and 10.0 mg/70 kg) were tested under double-blind conditions according to a randomized-block design. Typical stimulant and sedative effects were obtained with d-amphetamine and diazepam, respectively. Drug effects varied as a function of sensation-seeking status, with magnitude of effects on cardiovascular function, task performance, and report of positive drug effects being greater among high sensation seekers, and report of negative drug effects being greater among low sensation seekers. Adolescents who report high levels of sensation seeking on a consistent basis are more sensitive to pharmacological effects of stimulant and sedative drugs that are associated with abuse potential as young adults.

Modulation of the discriminative stimulus effects of triazolam across the menstrual cycle phase in healthy pre-menopausal women.

Pre-clinical studies indicate that changes in progesterone levels across menstrual cycle phases modulate the behavioral effects of sedative drugs acting at GABA(A) receptor sites. In this study, seven healthy women learned to discriminate triazolam (0.25 mg/70 kg) from placebo. After acquiring the discrimination, a range of triazolam doses (0.00, 0.06, 0.12 and 0.25 mg/70 kg) was tested during the early follicular and mid-luteal menstrual cycle phases. During the mid-luteal phase, when progesterone levels were elevated, 0.12 mg/70 kg triazolam was identified as the active triazolam training dose (0.25 mg/70 kg), whereas 0.12 mg/70 kg triazolam was identified as placebo during the early follicular phase, when progesterone levels were low. Triazolam engendered prototypical sedative effects on subjective effect, performance and cardiovascular measures that were generally independent of cycle phase. These results suggest that the discriminative stimulus effects of the positive GABA(A) modulator, triazolam, are sensitive to menstrual cycle phase in healthy adult women.

Caffeine use: association with nicotine use, aggression, and other psychopathology in psychiatric and pediatric outpatient adolescents.

The objective of this study was to evaluate the relationship between caffeine use, other drug use, and psychopathology in adolescents, using self-report measures. The study group consisted of 132 adolescents (average age 14.01 +/- 2.06 years, 52% female, 19% African American, 5% other categories, 76% Caucasian). Most (47%) were recruited from a child psychiatry clinic with emphasis on youth with disruptive disorders, with 35% from an adolescent pediatric clinic with emphasis on prevention of risk-taking behavior and 18% from a pediatric clinic for families with limited resources. Subjects were consecutively recruited before or after regular clinic visits. Consent was obtained from parents and assent from the youth. High caffeine consumption was associated with daily cigarette use; aggressive behavior; conduct, attention deficit/hyperactivity, and social problems; and increased somatic complaints in adolescents.