Implementing a community model of early pregnancy care.

BACKGROUND: In the UK Early Pregnancy Assessment Units (EPAUs) are usually situated alongside hospital maternity and gynaecology services. In June 2018, the Oxford EPAU relocated from the John Radcliffe Hospital to a community clinic. This is to our knowledge, the UK's first community-based EPAU. This change was inspired by our patient feedback describing the co-location of the EPAU with maternity services as distressing. METHODS: Following the introduction of the community EPAU we developed a database to capture information on the patients seen in the clinic. This is a retrospective observational study of a single cohort of patients attending the clinic over an 8 month period. Data was collected from 1st July 2018 to 28th February 2019. This data included clinical, safety and patient experience outcomes. RESULTS: Two thousand nine hundred and twenty patient episodes were recorded, 1,932 were new patients. Mean waiting time to be seen in clinic was 1.3 days. When miscarriage was confirmed 48.6% chose conservative management, 19.9% chose medical management, and 31.5% chose surgical management. The mean rate of ambulance transfers to hospital was 3.1 per month. Of all patients seen in EPAU 32 had unplanned admissions, which accounted for 2.7% of all patients seen in EPAU. Patient feedback questionnaires have been consistently positive. CONCLUSION: The development of a community EPAU has improved services to allow care closer to home in an environment separate from maternity care. Our data shows that a community EPAU can deliver timely, good quality patient care, is safe, and a service valued by patients. Further research is indicated to evaluate the cost-effectiveness of community EPAUs and the long term safety and effectiveness of care.

Trait-like impulsivity does not predict escalation of heroin self-administration in the rat.

RATIONALE: The neural and psychological mechanisms underlying vulnerability to drug addiction are poorly understood. Although a number of animal models have been developed to investigate vulnerability to stimulant addiction, few have considered how vulnerability traits such as impulsivity predict hallmark features of heroin addiction including the escalation of drug intake and increased propensity for relapse following protracted abstinence. OBJECTIVE: The aim of this study was to investigate whether high impulsivity in rats predicts the propensity to escalate intravenous heroin self-administration and to relapse following an extended withdrawal period from heroin. METHODS: High (HI)- and low (LI)-impulsive rats, defined by the extent of premature responding on the 5-choice serial reaction time test (5-CSRTT), were catheterized and allowed to self-administer heroin (40 µg/100 µl/infusion). After 5 days of short access (1 h/day) to heroin, rats were then given extended (6 h/day) access to heroin for 18 consecutive days. RESULTS: High impulsivity predicted neither a greater tendency to acquire heroin SA nor an increased escalation of heroin self-administration. Moreover, high impulsivity was not associated with an increased propensity to relapse after protracted withdrawal from heroin. Nevertheless, marked inter-individual differences in the escalation of heroin self-administration were observed. CONCLUSIONS: Although high impulsivity on the 5-CSRTT has been shown to predict loss of control over cocaine intake, this does not generalize to a loss of control over heroin self-administration. These findings suggest important distinctions in vulnerability mechanisms underlying cocaine and heroin addiction with trait-like impulsivity playing a role in stimulant but not opiate addiction.

Caffeine promotes dopamine D1 receptor-mediated body temperature, heart rate and behavioural responses to MDMA ('ecstasy').

RATIONALE: Caffeine exacerbates the acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') in rats characterised by hyperthermia, tachycardia and lethality. Depletion of central catecholamine stores and dopamine D(1) receptor blockade have been reported to attenuate the ability of caffeine to exacerbate MDMA-induced hyperthermia. OBJECTIVES: Here, we investigate whether dopamine D(1) and D(2) receptors mediate the effects of caffeine on MDMA-induced changes in body temperature, heart rate and locomotor activity. METHODS: All parameters were recorded continuously in individually housed rats using bioradiotelemetry from 1 h prior to 4 h following caffeine (10 mg/kg, s.c.) and/or MDMA (10 mg/kg, s.c.) administration. RESULTS: Co-administration of caffeine with MDMA provoked a switch from MDMA-induced hypothermia and bradycardia to hyperthermia and tachycardia without influencing MDMA-induced hyperlocomotion. Pre-treatment with a specific dopamine D(1/5) antagonist SCH 23390 (1 mg/kg) enhanced MDMA-induced hypothermia and blocked the ability of caffeine to provoke a switch from MDMA-induced hypothermia to hyperthermia. Furthermore, SCH 23390 blocked MDMA-induced hyperactivity and the ability of caffeine to promote a tachycardic response to MDMA. By contrast, pre-treatment with the selective D(2) antagonist, sulpiride (100 mg/kg) blocked MDMA-induced hypothermia, failed to influence the ability of caffeine to promote tachycardia whilst enhancing MDMA-induced hyperactivity. CONCLUSIONS: Our results highlight the importance of dopamine D(1) and D(2) receptors in shaping the behavioural and physiological response to MDMA and suggest that the ability of caffeine to provoke MDMA-induced toxicity is associated with the promotion of dopamine D(1) over D(2) receptor-related responses.

Dissociable control of impulsivity in rats by dopamine d2/3 receptors in the core and shell subregions of the nucleus accumbens.

Previous research has identified the nucleus accumbens (NAcb) as an important brain region underlying inter-individual variation in impulsive behavior. Such variation has been linked to decreased dopamine (DA) D2/3 receptor availability in the ventral striatum of rats exhibiting spontaneously high levels of impulsivity on a 5-choice serial reaction time (5-CSRT) test of sustained visual attention. This study investigated the involvement of DA D2/3 receptors in the NAcb core (NAcbC) and the NAcb shell (NAcbS) in impulsivity. We investigated the effects of a DA D2/3 receptor antagonist (nafadotride) and a DA D2/3 partial agonist (aripiprazole) infused directly into either the NAcbC or NAcbS of rats selected for high (HI) and low (LI) impulsivity on the 5-CSRT task. Nafadotride increased significantly the level of impulsivity when infused into the NAcbS, but decreased impulsivity when infused into the NAcbC of HI rats. By contrast, intra-NAcb microinfusions of aripiprazole did not affect impulsivity. Systemic administration of nafadotride had no effect on impulsive behavior but increased the number of omissions and correct response latencies, whereas systemic injections of aripiprazole decreased impulsive and perseverative behavior, and increased the number of omissions and correct response latencies. These findings indicate an opponent modulation of impulsive behavior by DA D2/3 receptors in the NAcbS and NAcbC. Such divergent roles may have relevance for the etiology and treatment of clinical disorders of behavioral control, including attention-deficit hyperactivity disorder and drug addiction.

Caffeine induces a profound and persistent tachycardia in response to MDMA ("Ecstasy") administration.

Caffeine promotes hyperthermia and lethality when co-administered with the recreational drug 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") to rats. In the present study, co-administration of caffeine (10 mg/kg, s.c.) with MDMA (10 mg/kg, s.c.) induced a profound tachycardic response compared to rats treated with either drug alone. However, neither caffeine (30 microM) nor MDMA (1-30 microM), alone or in combination, affected the electrocardiogram of the isolated heart suggesting that central and sympathomimetic actions, rather than direct actions of these drugs on the heart, are responsible for the tachycardia observed in vivo. This is a serious drug interaction, which could have important health consequences for recreational drug users.

Caffeine promotes hyperthermia and serotonergic loss following co-administration of the substituted amphetamines, MDMA ("Ecstasy") and MDA ("Love").

The present study determined the effect of caffeine co-administration on the core body temperature response and long-term serotonin (5-HT) loss induced by methylenedioxymethamphetamine (MDMA; "Ecstasy") and its metabolite methylenedioxyamphetamine (MDA; "Love") to rats. In group-housed animals, caffeine (10 mg/kg) enhanced the acute toxicity of MDMA (15 mg/kg) and MDA (7.5 mg/kg), resulting in an exaggerated hyperthermic response (+2 degrees C for 5 h following MDMA and +1.5 degrees C for 3 h following MDA) when compared to MDMA (+1 degree C for 3 h) and MDA (+1 degree C for 1 h) alone. Co-administration of caffeine with MDMA or MDA was also associated with increased lethality. To reduce the risk of lethality, doses of MDMA and MDA were reduced in further experiments and the animals were housed individually. To examine the effects of repeated administration, animals received MDMA (10 mg/kg) or MDA (5 mg/kg) with or without caffeine (10 mg/kg) twice daily for 4 consecutive days. MDMA and MDA alone induced hypothermia (fall of 1 to 2 degrees C) over the 4 treatment days. Co-administration of caffeine with MDMA or MDA resulted in hyperthermia (increase of up to 2.5 degrees C) following acute administration compared to animals treated with caffeine or MDMA/MDA alone. This hyperthermic response to caffeine and MDMA was not observed with repeated administration, unlike caffeine + MDA, where hyperthermia was obtained over the 4 day treatment period. In addition, 4 weeks after the last treatment, co-administration of caffeine with MDA (but not MDMA) induced a reduction in 5-HT and 5-hydroxyindole acetic acid (5-HIAA) concentrations in frontal cortex (to 61% and 58% of control, respectively), hippocampus (48% and 60%), striatum (79% and 64%) and amygdala (63% and 37%). However, when caffeine (10 mg/kg) and MDMA (2.5 mg/kg) were co-administered four times daily for 2 days to group-housed animals, both hyperthermia and hippocampal 5-HT loss were observed (reduced to 68% of control). Neither MDMA nor MDA alone induced a significant reduction in regional 5-HT or 5-HIAA concentrations following repeated administration. In conclusion, caffeine promotes the acute and long-term toxicity associated with MDMA and MDA. This is a serious drug interaction, which could have important acute and long-term health consequences for recreational drug users.