Effect of subtype selective nicotinic compounds on attention as assessed by the five-choice serial reaction time task

Nicotine can improve attentional functioning in humans, and a number of studies have recently demonstrated that under specific task conditions, nicotine can also improve attention in the rat. Neuronal nicotinic receptors comprise combinations of alpha(2-9) and beta(2-4) subunits, arranged to form a pentameric receptor, with the principal CNS subtypes currently believed to be alpha(4)beta(2) and a homomeric alpha(7) receptor. In the present studies, we attempted to delineate the particular nicotinic receptor subtype(s) contributing to the effects of nicotine on attention by assessing various nicotinic ligands on performance in the five-choice serial reaction time task (5-CSRTT). In rats performing below criterion (<80% correct, >20% omissions to a 1-s visual stimulus), subchronic dosing with nicotine (0.2 mg/kg sc) and the alpha(4)beta(2) agonist SIB 1765F (5 mg/kg sc) increased correct responding and decreased response latencies across the treatment week; whereas the alpha(7) agonist AR-R 17779 (20 mg/kg sc) was without effect. In subjects meeting the criterion, the competitive high affinity (including alpha(4)beta(2)) nicotine receptor antagonist DHbetaE (1-10 mg/kg sc) and the alpha(7) antagonist methyllycaconitine (MLA: 5-10 mg/kg i.p.) did not disrupt performance, whereas at the highest dose, the non-competitive antagonist mecamylamine (0.3-3 mg/kg sc) decreased accuracy and increased response latencies. These changes bore some similarities to those of pre-feeding and the non-competitive NMDA antagonist dizocilpine (0.03-0.06 mg/kg sc), suggesting that mecamylamine-induced performance disruption may relate to non-nicotinic receptor effects. In subjects chronically treated with nicotine, acute nicotine challenge (0.4 mg/kg sc) significantly increased accuracy whilst having no effect on any other performance measures. Finally, in these same nicotine pre-treated rats, the decrease in latency and increase in premature responses induced by nicotine (0.2 mg/kg sc) to a target stimulus of 150 ms was fully antagonised by DHbetaE (3 mg/kg sc) but not MLA (5 mg/kg i.p.). These results suggest that alpha(7) receptors do not play a role in any of the behavioural effects of nicotine observed in the 5-CSRTT, whereas a high affinity site, perhaps alpha(4)beta(2), is more likely involved.     

Multisensory auditory-somatosensory interactions in early cortical processing revealed by high-density electrical mapping

We investigated the time-course and scalp topography of multisensory interactions between simultaneous auditory and somatosensory stimulation in humans. Event-related potentials (ERPs) were recorded from 64 scalp electrodes while subjects were presented with auditory-alone stimulation (1000-Hz tones), somatosensory-alone stimulation (median nerve electrical pulses), and simultaneous auditory-somatosensory (AS) combined stimulation. Interaction effects were assessed by comparing the responses to combined stimulation with the algebraic sum of responses to the constituent auditory and somatosensory stimuli when they were presented alone. Spatiotemporal analysis of ERPs and scalp current density (SCD) topographies revealed AS interaction over the central/postcentral scalp which onset at approximately 50 ms post-stimulus presentation. Both the topography and timing of these interactions are consistent with multisensory integration early in the cortical processing hierarchy, in brain regions traditionally held to be unisensory.     

Randomized placebo-controlled study of low-dose warfarin for the prevention of central venous catheter-associated thrombosis in patients with cancer.

PURPOSE: In this multicenter, randomized, placebo-controlled clinical trial, we studied whether warfarin 1 mg daily reduces the incidence of symptomatic central venous catheter (CVC) -associated thrombosis in patients with cancer. PATIENTS AND METHODS: Two hundred fifty-five patients with cancer who required a CVC for at least 7 days were randomly assigned to receive warfarin 1 mg or placebo. RESULTS: There were 11 (4.3%) symptomatic CVC-associated thromboses among 255 patients, with no difference in the incidence of symptomatic CVC-associated thrombosis between patients taking warfarin 1 mg daily (six of 130 patients; 4.6%) and patients taking placebo (five of 125 patients; 4.0%; hazard ratio, 1.20; 95% CI, 0.37 to 3.94). Warfarin had no effect on CVC life span (84 days v 63 days in control and warfarin groups, respectively; 95% confidence limit, -16 to 55 days; P = .09), and it did not affect the number of premature CVC removals (23.2% v 25.4% in control and warfarin groups, respectively; 95% confidence limit of difference -8.34 to 12.71; P = .68) or the frequency of major bleeding episodes (2% v 0% in control and warfarin groups, respectively; P = .5, Fisher's exact test). CONCLUSION: Symptomatic CVC-associated thrombosis in patients with cancer, although significant, is less common than previously reported. In this study, the administration of warfarin 1 mg daily did not reduce the incidence of symptomatic CVC-associated thrombosis in patients with cancer. However, the low rate of symptomatic CVC-associated thrombosis means that a much larger trial is required to address this issue definitively.     

The changing epidemiology of opioid overdose in Baltimore,Maryland, 2012–2017: insights from emergency medical services

IntroductionAn estimated 100,306 people died from an overdose from May 2020 to April 2021. Emergency Medical Services (EMS) are often the first responder to opioid overdose, and EMS encounter records can provide granular epidemiologic data on opioid overdose. This study describes the demographic, temporal, and geographic epidemiology of suspected opioid overdose in Baltimore City using data from Baltimore City Fire Department EMS encounters with the administration of the opioid antagonist naloxone.MethodThe present analyses used patient encounter data from 2012 to 2017 from the Baltimore City Fire Department, the city’s primary provider of EMS services. The analytic sample included patient encounters within the city that involved naloxone administration to patients 15 years of age or older (n = 20,592). Negative binomial regression was used to calculate the incidence rates based on demographic characteristics, year, and census tract. Choropleth maps were used to show the geographic distribution of overdose incidence across census tracts in 2013, 2015, and 2017.ResultsFrom 2012 to 2017, the annual number of EMS encounters with naloxone administrations approximately doubled every 2 years, and the temporal pattern of naloxone administration was similar to the pattern of fatal opioid-related overdoses. For most census tracts, incidence rates significantly increased over time. Population-based incidence of naloxone administration varied significantly by socio-demographic characteristics. Males, non-whites, and those 25–69 years of age had the highest incidence rates.ConclusionThe incidence of naloxone administration increased dramatically over the study period. Despite significant cross-sectional variation in incidence across demographically and geographically defined groups, there were significant proportional increases in incidence rates, consistent with fatal overdose rates over the period. This study demonstrated the value of EMS data for understanding the local epidemiology of opioid-related overdose.

Key Messages

• Patterns of EMS encounters with naloxone administration appear to be an excellent proxy for patterns of opioid-related overdoses based on the consistency of fatal overdose rates over time.
• EMS plays a central role in preventing fatal opioid-related overdoses through the administration of naloxone, provision of other emergency services, and transportation to medical facilities.
• EMS encounters with naloxone administration could also be used to evaluate the impact of overdose prevention interventions and public health services.