Trauma deserts: distance from a trauma center, transport times, and mortality from gunshot wounds in Chicago.

OBJECTIVES: We examined whether urban patients who suffered gunshot wounds (GSWs) farther from a trauma center would have longer transport times and higher mortality. METHODS: We used the Illinois State Trauma Registry (1999-2009). Scene address data for Chicago-area GSWs was geocoded to calculate distance to the nearest trauma center and compare prehospital transport times. We used multivariate regression to calculate the effect on mortality of being shot more than 5 miles from a trauma center. RESULTS: Of 11,744 GSW patients during the study period, 4782 were shot more than 5 miles from a trauma center. Mean transport time and unadjusted mortality were higher for these patients (P < .001 for both). In a multivariate model, suffering a GSW more than 5 miles from a trauma center was associated with an increased risk of death (odds ratio = 1.23; 95% confidence interval = 1.02, 1.47; P = .03). CONCLUSIONS: Relative "trauma deserts" with decreased access to immediate care were found in certain areas of Chicago and adversely affected mortality from GSWs. These results may inform decisions about trauma systems planning and funding.

Wellness checks: Piloting a universal intervention for soldiers.

As part of an Army pilot program, mandatory annual wellness checks were initiated to introduce individuals to counseling and to support psychological resilience and thriving. The program was evaluated using a cross-sectional survey completed by 7,831 soldiers. Findings revealed that about half of soldiers who reported a wellness check rated the check at least moderately helpful in their professional and personal lives. Participants receiving a wellness check reported being more likely to report willingness to seek help if they were to have mental health problems and to report higher levels of resilience and thriving even after controlling for rank, age, education, months in the unit, and trait negative affect. Participants were also less likely to report stigma-related concerns compared to those who had not received a wellness check. Consistent with theory on the common factors in counseling and the contextual model of psychotherapy (Laska et al., 2014), feeling listened to and learning new skills partially mediated the association between perceived wellness check usefulness and study outcomes, although acquiring a new perspective about problems did not. While not a randomized trial, this evaluation suggests that wellness checks are associated with programmatic goals: improved attitudes toward care seeking, resilience, and thriving. Future work should consider ways to ensure counselors address therapeutic common factors and should use a randomized, longitudinal design. Study findings have implications for implementing programs like wellness checks for military personnel and others working in high-stress occupations like first responders. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Anaesthetics differentially modulate the trigeminocardiac reflex excitatory synaptic pathway in the brainstem.

The trigeminocardiac reflex (TCR) occurs upon excitation of the trigeminal nerve with a resulting bradycardia and hypotension. While several anaesthetics and analgesics have been reported to alter the incidence and strength of the TCR the mechanisms for this modulation are unclear. This study examines the mechanisms of action of ketamine, isoflurane and fentanyl on the synaptic TCR responses in both neurones in the spinal trigeminal interpolaris (Sp5I) nucleus and cardiac vagal neurones (CVNs) in the Nucleus Ambiguus (NA). Stimulation of trigeminal afferent fibres evoked an excitatory postsynaptic current (EPSC) in trigeminal neurones with a latency of 1.8 ± 0.1 ms, jitter of 625 µs, and peak amplitude of 239 ± 45 pA. Synaptic responses further downstream in the reflex pathway in the CVNs occurred with a latency of 12.1 ± 1.1 ms, jitter of 0.8-2 ms and amplitude of 57.8 ± 7.5 pA. The average conduction velocity to the Sp5I neurones was 0.94 ± 0.18 mm ms(-1) indicating a mixture of A-δ and C fibres. Stimulation-evoked EPSCs in both Sp5I and CVNs were completely blocked by AMPA/kainate and NMDA glutamatergic receptor antagonists. Ketamine (10 µm) inhibited the peak amplitude and duration in Sp5I as well as more distal synapses in the CVNs. Isoflurane (300 µm) significantly inhibited, while fentanyl (1 µm) significantly enhanced, EPSC amplitude and area in CVNs but had no effect on the responses in Sp5l neurones. These findings indicate glutamatergic excitatory synaptic pathways are critical in the TCR, and ketamine, isoflurane and fentanyl differentially alter the synaptic pathways via modulation of both AMPA/kainate and NMDA receptors at different synapses in the TCR.

A conserved cysteine residue in the third transmembrane domain is essential for homomeric 5-HT3 receptor function.

The cysteine (Cys) residue at position 312 in the third transmembrane domain (M3) is conserved among 5-hydroxytryptamine type 3 (5-HT(3)) receptor subunits and many other subunits of the nicotinic acetylcholine (nACh) related Cys-loop receptor family, including most of the gamma-aminobutyric acid type A (GABA(A)) and glycine receptor subunits. To elucidate a possible role for the Cys-312 in human 5-HT(3)A receptors, we replaced it with alanine and expressed the 5-HT(3)A(C312A) mutant in HEK293 cells. The mutation resulted in an absence of 5-HT-induced whole-cell current without reducing homopentamer formation, surface expression or 5-HT binding. The 5-HT(3)A(C312A) mutant, when co-expressed with the wild-type 5-HT(3)A subunit, did not affect functional expression of receptors, suggesting that the mutant is not dominant negative. Interestingly, co-expression of 5-HT(3)A(C312A) with 5-HT(3)B led to surface expression of heteropentamers that mediated small 5-HT responses. This suggests that the Cys-312 is essential for homomeric but not heteromeric receptor gating. To further investigate the relationship between residue 312 and gating we replaced it with amino acids located at the equivalent position within other Cys-loop subunits that are either capable or incapable of forming functional homopentamers. Replacement of 5-HT(3)A Cys-312 by Gly or Leu (equivalent residues in the nACh receptor delta and gamma subunits) abolished and severely attenuated function, respectively, whereas replacement by Thr or Ser (equivalent residues in nACh receptor alpha7 and GABA(A) subunits) supported robust function. Thus, 5-HT(3)A residue 312 and equivalent polar residues in the M3 of other Cys-loop subunits are essential determinants of homopentameric gating.

Direct subunit-dependent multimodal 5-hydroxytryptamine3 receptor antagonism by methadone.

Homomeric 5-hydroxytryptamine (5-HT)(3A) and heteromeric 5-HT(3AB) receptors mediate rapid excitatory responses to serotonin in the central and peripheral nervous systems. The alkaloid morphine, in addition to being a mu-opioid receptor agonist, is a potent competitive inhibitor of 5-HT(3) receptors. We examined whether methadone, an opioid often used to treat morphine dependence, also exhibited 5-HT(3) receptor antagonist properties. Racemic (R/S)-methadone inhibited currents mediated by human homomeric 5-HT(3A) receptors (IC(50) = 14.1 +/- 2.5 microM). Incorporation of the 5-HT(3B) subunit into heteromeric 5-HT(3AB) receptors reduced the potency of inhibition by (R/S)-methadone (IC(50) = 41.1 +/- 0.9 microM). (R/S)-Methadone also increased apparent desensitization of both 5-HT(3) receptor subtypes. The inhibition of the 5-HT(3A) receptor was competitive; however, incorporation of the 5-HT(3B) subunit caused the appearance of inhibition that was insurmountable by 5-HT. In the absence of rapid desensitization, when dopamine was used as an agonist of 5-HT(3AB) receptors, the inhibition by (R/S)-methadone was voltage-dependent. The antagonist and desensitization-enhancing effects of (R/S)-methadone were shared by pure (R)- and (S)-methadone enantiomers, which had similar actions on 5-HT-evoked currents mediated by 5-HT(3) receptors. However, (R)-methadone exhibited a larger voltage-dependent inhibition of dopamine-evoked currents mediated by 5-HT(3AB) receptors than did (S)-methadone. Inhibition of 5-HT(3A) receptors by (R/S)-methadone was not influenced by voltage. Thus, methadone displays multimodal subunit-dependent antagonism of 5-HT(3) receptors.

Out on the town: an evaluation of brief motivational interventions to address the risks associated with problematic alcohol use.

Alcohol has long been identified as a significant contributory factor in crime and anti social behaviour, yet there is a dearth of effective treatment available for those individuals whose drinking contributes significantly to their criminality, and subsequently the health risks and the economic and wider social implications associated with it. The literature on treatment programmes is drawn almost exclusively from medical experience but indicates that brief interventions are at least as effective as more intensive programmes in reducing alcohol consumption in at-risk groups. This research was undertaken to evaluate projects based in the West Midlands, United Kingdom, providing brief motivational interventions to offenders arrested for offences where alcohol is identified as a significant contributory factor. The evaluation indicates that an arrest referral scheme as developed in the West Midlands can achieve good levels of identification and referral, acceptable attendance, retention rates, and effective outcomes in terms of attitude and behaviour change.

Effects of closure of an urban level I trauma centre on adjacent hospitals and local injury mortality: a retrospective, observational study.

OBJECTIVE: To determine the association of the Martin Luther King Jr Hospital (MLK) closure on the distribution of admissions on adjacent trauma centres, and injury mortality rates in these centres and within the county. DESIGN: Observational, retrospective study. SETTING: Non-public patient-level data from the state of California were obtained for all trauma patients from 1999 to 2009. Geospatial analysis was used to visualise the redistribution of trauma patients to other hospitals after MLK closed. Variance of observed to expected injury mortality using multivariate logistic regression was estimated for the study period. PARTICIPANTS: A total of 37 131 trauma patients were admitted to the five major south Los Angeles trauma centres from the MLK service area between 1999 and 2009. MAIN OUTCOME MEASURES: (1) Number and type of trauma admissions to trauma centres in closest proximity to MLK; (2) inhospital injury mortality of trauma patients after the trauma centre closure. RESULTS: During and after the MLK closure, trauma admissions increased at three of the four nearby hospitals, particularly admissions for gunshot wounds (GSWs). This redistribution of patient load was accompanied by a dramatic change in the payer mix for surrounding hospitals; one hospital's share of uninsured more than tripled from 12.9% in 1999 to 44.6% by 2009. Overall trauma mortality did not significantly change, but GSW mortality steadily and significantly increased after the closure from 5.0% in 2007 to 7.5% in 2009. CONCLUSIONS: Though local hospitals experienced a dramatic increase in trauma patient volume, overall mortality for trauma patients did not significantly change after MLK closed.

Dexmedetomidine decreases inhibitory but not excitatory neurotransmission to cardiac vagal neurons in the nucleus ambiguus.

Dexmedetomidine, an α2 adrenergic agonist, is a useful sedative but can also cause significant bradycardia. This decrease in heart rate may be due to decreased central sympathetic output as well as increased parasympathetic output from brainstem cardiac vagal neurons. In this study, using whole cell voltage clamp methodology, the actions of dexmedetomidine on excitatory glutamatergic and inhibitory GABAergic and glycinergic neurotransmission to parasympathetic cardiac vagal neurons in the rat nucleus ambiguus was determined. The results indicate that dexmedetomidine decreases both GABAergic and glycinergic inhibitory input to cardiac vagal neurons, with no significant effect on excitatory input. These results provide a mechanism for dexmedetomidine induced bradycardia and has implications for the management of this potentially harmful side effect.

The 5-HT3B subunit affects high-potency inhibition of 5-HT3 receptors by morphine.

BACKGROUND AND PURPOSE: Morphine is an antagonist at 5-HT(3) A receptors. 5-HT(3) and opioid receptors are expressed in many of the same neuronal pathways where they modulate gut motility, pain and reinforcement. There is increasing interest in the 5-HT3B subunit, which confers altered pharmacology to 5-HT(3) receptors. We investigated the mechanisms of inhibition by morphine of 5-HT(3) receptors and the influence of the 5-HT3B subunit. EXPERIMENTAL APPROACH: 5-HT-evoked currents were recorded from voltage-clamped HEK293 cells expressing human 5-HT3A subunits alone or in combination with 5-HT3B subunits. The affinity of morphine for the orthosteric site of 5-HT(3) A or 5-HT(3) AB receptors was assessed using radioligand binding with the antagonist [(3) H]GR65630. KEY RESULTS: When pre-applied, morphine potently inhibited 5-HT-evoked currents mediated by 5-HT(3) A receptors. The 5-HT3B subunit reduced the potency of morphine fourfold and increased the rates of inhibition and recovery. Inhibition by pre-applied morphine was insurmountable by 5-HT, was voltage-independent and occurred through a site outside the second membrane-spanning domain. When applied simultaneously with 5-HT, morphine caused a lower potency, surmountable inhibition of 5-HT(3) A and 5-HT(3) AB receptors. Morphine also fully displaced [(3) H]GR65630 from 5-HT(3) A and 5-HT(3) AB receptors with similar potency. CONCLUSIONS AND IMPLICATIONS: These findings suggest that morphine has two sites of action, a low-affinity, competitive site and a high-affinity, non-competitive site that is not available when the channel is activated. The affinity of morphine for the latter is reduced by the 5-HT3B subunit. Our results reveal that morphine causes a high-affinity, insurmountable and subunit-dependent inhibition of human 5-HT(3) receptors.

Lower extremity vascular injuries: increased mortality for minorities and the uninsured?

BACKGROUND: There is increasing evidence to suggest that racial disparities exist in outcomes for trauma. Minorities and the uninsured have been found to have higher mortality rates for blunt and penetrating trauma. However, mechanisms for these disparities are incompletely understood. Limiting the inquiry to a homogenous group, those with lower extremity vascular injuries (LEVIs), may clarify these disparities. METHODS: The National Trauma Data Bank (NTDB; version 7.0, American College of Surgeons) was used for this study. LEVIs were identified using codes from the International Classification of Diseases, 9th revision. Univariate and multivariate analyses were performed using Stata software (version 11; StataCorp, LP, College Station, TX). RESULTS: Records were reviewed for 4,928 LEVI patients. The mechanism of injury was blunt in 2,452 (49.8%), penetrating in 2,452 (49.8%), and unknown in 24 cases (0.5%). Mortality was similar by mechanism (7.6% overall). Regression analysis using mechanism as a covariate revealed a significantly worse mortality for people of color (POC; odds ratio [OR], 1.45; 95% confidence interval [CI], 1.03-2.02; P = .03) and the uninsured (UN; OR, 1.62; 95% CI, 1.15-2.23; P = .006). However, when separate analyses were performed stratifying by mechanism, no significant mortality disparities were found for blunt trauma (POC OR, 1.28; 95% CI, 0.85-1.96; P = .23; UN OR, 1.33; 95% CI, 0.78-2.22; P = .29), but disparities remained for penetrating trauma (POC OR, 1.81; 95% CI, 0.93-3.57; P = .08; UN OR, 1.85; 95% CI, 1.18-2.94; P = .009). CONCLUSION: For patients with LEVI, mortality disparities based on race or insurance status were only observed for penetrating trauma. It is possible that injury heterogeneity or patient cohort differences may partly explain mortality disparities that have been observed between racial and socioeconomic groups.

High affinity binding of epibatidine to serotonin type 3 receptors.

Epibatidine and mecamylamine are ligands used widely in the study of nicotinic acetylcholine receptors (nAChRs) in the central and peripheral nervous systems. In the present study, we find that nicotine blocks only 75% of (125)I-epibatidine binding to rat brain membranes, whereas ligands specific for serotonin type 3 receptors (5-HT(3)Rs) block the remaining 25%. (125)I-Epibatidine binds with a high affinity to native 5-HT(3)Rs of N1E-115 cells and to receptors composed of only 5-HT(3A) subunits expressed in HEK cells. In these cells, serotonin, the 5-HT(3)R-specific antagonist MDL72222, and the 5-HT(3)R agonist chlorophenylbiguanide readily competed with (125)I-epibatidine binding to 5-HT(3)Rs. Nicotine was a poor competitor for (125)I-epibatidine binding to 5-HT(3)Rs. However, the noncompetitive nAChR antagonist mecamylamine acted as a potent competitive inhibitor of (125)I-epibatidine binding to 5-HT(3)Rs. Epibatidine inhibited serotonin-induced currents mediated by endogenous 5-HT(3)Rs in neuroblastoma cell lines and 5-HT(3A)Rs expressed in HEK cells in a competitive manner. Our results demonstrate that 5-HT(3)Rs are previously uncharacterized high affinity epibatidine binding sites in the brain and indicate that epibatidine and mecamylamine act as 5-HT(3)R antagonists. Previous studies that depended on epibatidine and mecamylamine as nAChR-specific ligands, in particular studies of analgesic properties of epibatidine, may need to be reinterpreted with respect to the potential role of 5-HT(3)Rs.