Endogenous doesn't always mean innocuous: a scoping review of iron toxicity by inhalation.

Ambient air pollution is a leading risk factor for the global burden of disease. One possible pathway of particulate matter (PM)-induced toxicity is through iron (Fe), the most abundant metal in the atmosphere. The aim of the review was to consider the complexity of Fe-mediated toxicity following inhalation exposure focusing on the chemical and surface reactivity of Fe as a transition metal and possible pathways of toxicity via reactive oxygen species (ROS) generation as well as considerations of size, morphology, and source of PM. A broad term search of 4 databases identified 2189 journal articles and reports examining exposure to Fe via inhalation in the past 10 years. These were sequentially analyzed by title, abstract and full-text to identify 87 articles publishing results on the toxicity of Fe-containing PM by inhalation or instillation to the respiratory system. The remaining 87 papers were examined to summarize research dealing with in vitro, in vivo and epidemiological studies involving PM containing Fe or iron oxide following inhalation or instillation. The major findings from these investigations are summarized and tabulated. Epidemiological studies showed that exposure to Fe oxide is correlated with an increased incidence of cancer, cardiovascular diseases, and several respiratory diseases. Iron PM was found to induce inflammatory effects in vitro and in vivo and to translocate to remote locations including the brain following inhalation. A potential pathway for the PM-containing Fe-mediated toxicity by inhalation is via the generation of ROS which leads to lipid peroxidation and DNA and protein oxidation. Our recommendations include an expansion of epidemiological, in vivo and in vitro studies, integrating research improvements outlined in this review, such as the method of particle preparation, cell line type, and animal model, to enhance our understanding of the complex biological interactions of these particles.

Risk versus regulation: an update on the state of e-cigarette control in Australia.

E-cigarettes are increasingly common around the world, particularly among youth. Ingestion of nicotine-containing e-liquid, while relatively rare, is the major toxicological risk associated with their use. Current Australian regulation has nicotine for use in e-cigarettes listed as a dangerous poison in Schedule 7, with its supply or sale illegal in all states and territories, while regulation on the sale of e-cigarettes and accessories varies by state. However, with increasing evidence that e-cigarettes produce far fewer toxic by-products than their combustible counterparts perhaps it is time to review this regulation.

Efficiency of Respirator Filter Media against Diesel Particulate Matter: A Comparison Study Using Two Diesel Particulate Sources.

Diesel engines have been a mainstay within many industries since the early 1900s. Exposure to diesel particulate matter (DPM) is a major issue in many industrial workplaces given the potential for serious health impacts to exposed workers; including the potential for lung cancer and adverse irritant and cardiovascular effects. Personal respiratory protective devices are an accepted safety measure to mitigate worker exposure against the potentially damaging health impacts of DPM. To be protective, they need to act as effective filters against carbon and other particulates. In Australia, the filtering efficiency of respiratory protective devices is determined by challenging test filter media with aerosolised sodium chloride to determine penetration at designated flow rates. The methodology outlined in AS/NZS1716 (Standards Australia International Ltd and Standards New Zealand 2012. Respiratory protective devices. Sydney/Wellington: SAI Global Limited/Standards New Zealand) does not account for the differences between characteristics of workplace contaminants like DPM and sodium chloride such as structure, composition, and particle size. This study examined filtering efficiency for three commonly used AS/NZS certified respirator filter models, challenging them with two types of diesel emissions; those from a diesel generator and a diesel engine. Penetration through the filter media of elemental carbon (EC), total carbon (TC), and total suspended particulate (TSP) was calculated. Results indicate that filtering efficiency assumed by P2 certification in Australia was achieved for two of the three respirator models for DPM generated using the small diesel generator, whilst when the larger diesel engine was used, filtering efficiency requirements were met for all three filter models. These results suggest that the testing methodology specified for certification of personal respiratory protective devices by Standards Australia may not ensure adequate protection for respirator users against DPM under all circumstances of diesel generated particles.

Neurocognitive Recovery After Hospital-Treated Deliberate Self-Poisoning With Central Nervous System Depressant Drugs: A Longitudinal Cohort Study.

Hospital-treated deliberate self-poisoning (DSP) by central nervous system depressant drugs (CNS-D) has been associated with impairments in cognitive and psychomotor functions at the time of discharge. We aimed to replicate this finding and to compare recovery in the first month after discharge for CNS-D and CNS nondepressant drug ingestions. We also examined a series of multivariate explanatory models of recovery of neurocognitive outcomes over time. The CNS-D group was impaired at discharge compared with the CNS-nondepressant group in cognitive flexibility, cognitive efficiency, and working memory. There were no significant differences at discharge in visual attention, processing speed, visuomotor speed, or inhibition speed. Both groups improved in the latter measures over 1 month of follow-up. However, the CNS-D group's recovery was significantly slower for key neurocognitive domains underlying driving in complex traffic situations, namely, cognitive flexibility, cognitive efficiency, and working memory. Patients discharged after DSP with CNS-D drugs have impairments of some critical cognitive functions that may require up to 1 month to recover. Although more pre- than post-DSP variables were retained as explanatory models of neurocognitive performance overall, recovery over time could not be explained by any one of the measured covariates. Tests of cognitive flexibility could be used in clinical settings as a proxy measure for recovery of driving ability. Regulatory authorities should also consider the implications of these results for the period of nondriving advised after ingestion of CNS-D in overdose. Future research, with adequate sample size, should examine contributions of other variables to the pattern of recovery over time.

Pharmacokinetics in neonatal prescribing: evidence base, paradigms and the future.

Paediatric patients, particularly preterm neonates, present many pharmacological challenges. Due to the difficulty in conducting clinical trials in these populations dosing information is often extrapolated from adult populations. As the processes of absorption, distribution, metabolism and excretion of drugs change throughout growth and development extrapolation presents risk of over or underestimating the doses required. Information about the development these processes, particularly drug metabolism pathways, is still limited with weight based dose adjustment presenting the best method of estimating pharmacokinetic changes due to growth and development. New innovations in pharmacokinetic research, such as population pharmacokinetic modelling, present unique opportunities to conduct clinical trials in these populations improving the safety and effectiveness of the drugs used. More research is required into this area to ensure the best outcomes for our most vulnerable patients.

Coping support factors among Australians affected by terrorism: 2002 Bali bombing survivors speak.

OBJECTIVES: To examine terrorism survivors' perceptions of factors likely to promote coping and recovery, and to determine whether coping supports vary according to demographic, physical and mental health, incident-exposure and bereavement variables. DESIGN, SETTING AND PARTICIPANTS: Individuals directly exposed to and/or bereaved by the 2002 Bali bombings and who had participated in a New South Wales Health therapeutic support program completed cross-sectional telephone interviews during July-November 2010. Spoken passages were categorised into coping support themes. Advocated supports were then examined by demographic, physical and mental health, incident-exposure and bereavement variables. MAIN OUTCOME MEASURES: Based on their experiences, respondents identified personal, social and service-related factors that they believed would optimally support future survivors of terrorism. RESULTS: Of the 81 people contacted, 55 (68%) participated, providing a total of 114 comments. Thirty-two respondents were women, and 54 had lost relatives or friends in the bombing. Mean age was 50 years (range, 20-73 years). Four meaningful coping support themes emerged, with excellent inter-rater reliability: professional help and counselling; social support; proactive government response and policy; and personal coping strategies. Women were significantly more likely to advocate the need for proactive government response (P = 0.03). Men were more likely to endorse the use of personal coping strategies (P < 0.01). Respondents diagnosed with a mental health condition since the bombings were significantly less likely to advocate social support processes (P = 0.04). CONCLUSIONS: Our findings highlight the perceived value of counselling-related services for terrorism-affected groups. Male survivors may benefit more from mental health interventions that initially build on problem-focused forms of coping, including brief education about reactions and periodic check-ups. Proactive government health and support services that allow simplified and longer-term access were consistently identified as priority areas.

Long-term health and wellbeing of people affected by the 2002 Bali bombing.

OBJECTIVE: To examine the physical and mental health status of individuals directly affected by the 2002 Bali bombing, 8 years after the incident. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study of people directly exposed to and/or bereaved by the 2002 Bali bombing who had participated in a New South Wales Health therapeutic support program. Telephone interviews were conducted during July - November 2010. The sample was weighted to reflect the population of interest, registered participants in the program (n = 115). MAIN OUTCOME MEASURES: Self-rated physical health, personal resilience (Connor-Davidson Resilience Scale), past-03 psychological distress and daily functioning (Kessler Psychological Distress Scale), and traumatic stress-related symptoms (Primary Care PTSD Screen). RESULTS: Of 81 individuals contacted, 55 responded (68%). Mean age of respondents was 50 years (range, 20-73 years), 32 were female, and seven were physically injured in the bombing. Most (45/55) reported good physical health, but 12 were experiencing high or very high levels of psychological distress. Being injured in the attack was associated with current functional impairment (P = 0.04) and very high levels of distress (P = 0.005). Lower distress was associated with perceived family support (P> = 0.03) and being in a marital or de facto relationship (P = 0.02). Complicated grief factors were consistently associated with high psychological distress, traumatic stress-related symptoms and lower personal resilience. CONCLUSIONS: Eight years after the bombing, directly affected individuals had good physical health but relatively high rates of psychological distress. Marital or de facto relationships and perceived family support appear to be protective factors against long-term distress. Bereavement factors were the strongest correlates of trauma symptoms and distress. Outreach and screening programs incorporating complicated grief items may be useful in the longer-term support of such individuals.

Fertility preservation in women undergoing treatment for breast cancer in the UK: a questionnaire study.

OBJECTIVE: Fertility preservation is an important survivorship issue for women treated for breast cancer. The aim of this work was to examine the referral practices of health care professionals who treat women with breast cancer in the United Kingdom, and to investigate their understanding and knowledge of the fertility preservation options available. METHOD: An invitation to participate in a confidential, online questionnaire was e-mailed to surgeons, oncologists, and clinical nurse specialists who manage patients with breast cancer in the United Kingdom. RESULTS: n = 306 respondents. Factors which influenced whether fertility preservation options were discussed with a patient included the following: patient's age (78%), final tumor/nodes/metastasis status (37.9%); concern that fertility preservation would delay chemotherapy (37.3%); whether the patient had children (33.5%) or a partner (24.7%); estrogen receptor expression (22.6%), lack of knowledge regarding the available options (20.9%); and concern that fertility preservation would compromise the success of cancer treatment (19.8%). Twenty-seven percent did not know whether fertility preservation was available for their patients on the National Health Service. Nearly half (49.4%) of respondents said that gonadotropin-releasing hormone agonists were used for fertility preservation outside the setting of a clinical trial. Knowledge regarding the available options varied according to different members of the multidisciplinary team, with consultant oncologists better informed than consultant surgeons or clinical nurse specialists (p < .05). CONCLUSIONS: Many health care professionals have incomplete knowledge regarding the local arrangements for fertility preservation for patients with breast cancer. This may result in patients receiving inadequate or conflicting information regarding fertility preservation.

An olfactory 'stress test' may detect preclinical Alzheimer's disease.

BACKGROUND: The olfactory bulb (OB) receives extensive cholinergic input from the basal forebrain and is affected very early in Alzheimer's disease (AD). We speculated that an olfactory 'stress test' (OST), targeting the OB, might be used to unmask incipient AD. We investigated if change in olfactory performance following intranasal atropine was associated with several known antecedents or biomarkers of AD. METHODS: We measured change in performance on the University of Pennsylvania Smell Identification Test (UPSIT) in the left nostril before (20-items) and after (remaining 20-items) intranasal administration of 1 mg of atropine. We administered cognitive tests, measured hippocampal volume from MRI scans and recorded Apolipoprotein E genotype as indices relevant to underlying AD. RESULTS: In a convenience sample of 56 elderly individuals (14 probable AD, 13 cognitive impairment no dementia, 29 cognitively intact) the change in UPSIT score after atropine ('atropine effect' = AE) correlated significantly with demographically scaled episodic memory score (r = 0.57, p < 0.001) and left hippocampal volume (LHCV) (r = 0.53, p < 0.001). Among non-demented individuals (n = 42), AE correlated with episodic memory (r = 0.52, p < 0.001) and LHCV (r = 0.49, p < 0.001) and hierarchical linear regression models adjusted for age, gender, education, and baseline UPSIT showed that the AE explained more variance in memory performance (24%) than did LHCV (15%). The presence of any APOE ϵ4 allele was associated with a more negative AE (p = 0.014). CONCLUSIONS: The OST using atropine as an olfactory probe holds promise as a simple, inexpensive screen for early and preclinical AD and further work, including longitudinal studies, is needed to explore this possibility.

Perceived coping & concern predict terrorism preparedness in Australia.

BACKGROUND: In the aftermath of major terrorist incidents research shows population shifts towards protective behaviours, including specific preparedness and avoidance responses. Less is known about individual preparedness in populations with high assumed threat but limited direct exposure, such as Australia. In this study we aimed to determine whether individuals with high perceived coping and higher concern would show greater preparedness to respond to terrorism threats. METHODS: Adults in New South Wales (NSW) completed terrorism perception and response questions as part of computer assisted telephone interviews (CATI) in 2010 (N=2038). Responses were weighted against the NSW population. Multiple logistic regression analyses were conducted to evaluate the relationship between personal coping/concern factors and terrorism-related preparedness and avoidance behaviours, and to control for potential confounders such as socio-demographic and threat perception factors. RESULTS: Increased vigilance for suspicious behaviours was the most commonly reported behavioural response to perceived terrorism threat. Multivariate analyses showed that the factor combination of high perceived coping and higher concern was the most consistent predictor of terrorism preparedness behaviours and evacuation intentions, including increased vigilance (Adjusted Odd Ratios (AOR)=2.07, p=0.001) learning evacuation plans (AOR=1.61, p=0.05), establishing emergency contact plans (AOR=2.73, p<0.001), willingness to evacuate homes (AOR=2.20, p=0.039), and willingness to evacuate workplaces or public facilities (AOR=6.19, p=0.015) during potential future incidents. CONCLUSION: The findings of this study suggest that terrorism preparedness behaviours are strongly associated with perceived high coping but that this relationship is also mediated by personal concerns relating to this threat. Cognitive variables such as coping self-efficacy are increasingly targeted as part of natural hazard preparedness and are a viable intervention target for terrorism preparedness initiatives. Raising individual coping perceptions may promote greater general and incident-specific preparedness and could form an integral element of community resilience strategies regarding this threat.

Uncertain etiologies of proteinuric-chronic kidney disease in rural Sri Lanka.

The global prevalence of chronic kidney disease (CKD) of uncertain etiology may be underreported. Community-level epidemiological studies are few due to the lack of national registries and poor focus on the reporting of non-communicable diseases. Here we describe the prevalence of proteinuric-CKD and disease characteristics of three rural populations in the North Central, Central, and Southern Provinces of Sri Lanka. Patients were selected using the random cluster sampling method and those older than 19 years of age were screened for persistent dipstick proteinuria. The prevalence of proteinuric-CKD in the Medawachchiya region (North Central) was 130 of 2600 patients, 68 of 709 patients in the Yatinuwara region (Central), and 66 of 2844 patients in the Hambantota region (Southern). The mean ages of these patients with CKD ranged from 44 to 52 years. Diabetes and long-standing hypertension were the main risk factors of CKD in the Yatinuwara and Hambantota regions. Age, exceeding 60 years, and farming were strongly associated with proteinuric-CKD in the Medawachchiya region; however, major risk factors were uncertain in 87% of these patients. Of these patients, 26 underwent renal biopsy; histology indicated tubulointerstitial disease. Thus, proteinuric-CKD of uncertain etiology is prevalent in the North Central Province of Sri Lanka. In contrast, known risk factors were associated with CKD in the Central and Southern Provinces.

Alert but less alarmed: a pooled analysis of terrorism threat perception in Australia.

BACKGROUND: Previous Australian research has highlighted disparities in community perceptions of the threat posed by terrorism. A study with a large sample size is needed to examine reported concerns and anticipated responses of community sub-groups and to determine their consistency with existing Australian and international findings. METHODS: Representative samples of New South Wales (NSW) adults completed terrorism perception questions as part of computer assisted telephone interviews (CATI) in 2007 (N = 2081) and 2010 (N = 2038). Responses were weighted against the NSW population. Data sets from the two surveys were pooled and multivariate multilevel analyses conducted to identify health and socio-demographic factors associated with higher perceived risk of terrorism and evacuation response intentions, and to examine changes over time. RESULTS: In comparison with 2007, Australians in 2010 were significantly more likely to believe that a terrorist attack would occur in Australia (Adjusted Odd Ratios (AOR) = 1.24, 95%CI:1.06-1.45) but felt less concerned that they would be directly affected by such an incident (AOR = 0.65, 95%CI:0.55-0.75). Higher perceived risk of terrorism and related changes in living were associated with middle age, female gender, lower education and higher reported psychological distress. Australians of migrant background reported significantly lower likelihood of terrorism (AOR = 0.52, 95%CI:0.39-0.70) but significantly higher concern that they would be personally affected by such an incident (AOR = 1.57, 95%CI:1.21-2.04) and having made changes in the way they live due to this threat (AOR = 2.47, 95%CI:1.88-3.25). Willingness to evacuate homes and public places in response to potential incidents increased significantly between 2007 and 2010 (AOR = 1.53, 95%CI:1.33-1.76). CONCLUSION: While an increased proportion of Australians believe that the national threat of terrorism remains high, concern about being personally affected has moderated and may reflect habituation to this threat. Key sub-groups remain disproportionately concerned, notably those with lower education and migrant groups. The dissonance observed in findings relating to Australians of migrant background appears to reflect wider socio-cultural concerns associated with this issue. Disparities in community concerns regarding terrorism-related threat require active policy consideration and specific initiatives to reduce the vulnerabilities of known risk groups, particularly in the aftermath of future incidents.

Lessons learned on lead poisoning in children: one-hundred years on from Turner's declaration.

There is significant emerging evidence showing life-long negative health, intellectual and socio-behavioural impacts as a result of childhood blood lead concentrations well below the widely used intervention level of 10 µg/dL. This issue raises serious health concerns for children in several Australian smelting and mining towns. Routine educational and home cleanliness advice to wet mop floors rather than to use a brush and pan to reduce lead exposure risks have been shown to have limited efficacy. This paper argues, as advocated 100 years ago by Queensland doctor Alfred Jefferis Turner, that childhood lead poisoning can only be mitigated via primary prevention and reduction of contaminants at source. Given that the effects of lead exposure are irreversible, there is a strong argument for the application of the precautionary principle to dealing with childhood lead exposure. There is a clear need to improve regulatory controls and emissions management to reduce environmental lead exposure risks.

Effect of Omega-3 Supplementation on Self-Regulation in Typically Developing Preschool-Aged Children: Results of the Omega Kid Pilot Study-A Randomised, Double-Blind, Placebo-Controlled Trial.

Supplementation of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) may enhance self-regulation (SR) and executive functioning (EF) in children of preschool age. The aim of the Omega Kid Study was to investigate the effect of n-3 LCPUFA supplementation on SR and EF in typically developing preschool-aged children. A double-blind placebo-controlled pilot trial was undertaken, the intervention was 12 weeks and consisted of 1.6 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day compared to placebo. The HS-Omega-3 Index® was assessed by capillary blood samples at baseline and post-intervention. Seventy-eight children were enrolled and randomised to either the n-3 LCPUFA treatment (n = 39) or placebo (n = 39) group. Post intervention, there was a significant three-fold increase in the HS-Omega-3 Index® in the n-3 LCPUFA group (p < 0.001). There were no improvements in SR or EF outcome variables for the n-3 LCPUFA group post intervention compared to the placebo group determined by linear mixed models. At baseline, there were significant modest positive Spearman correlations found between the HS-Omega-3 index® and both behavioural self-regulation and cognitive self-regulation (r = 0.287, p = 0.015 and r = 0.242, p = 0.015 respectively). Although no treatment effects were found in typically developing children, further research is required to target children with sub-optimal self-regulation who may benefit most from n-3 LCPUFA supplementation.

Five-year outcome for women randomised in a phase III trial comparing doxorubicin and cyclophosphamide with doxorubicin and docetaxel as primary medical therapy in early breast cancer: an Anglo-Celtic Cooperative Oncology Group study.

To compare the long-term outcome of women with primary or locally advanced breast cancer randomised to receive either doxorubicin and cyclophosphamide (AC) or doxorubicin and docetaxel (AD) as primary chemotherapy. Eligible patients with histologic-proven breast cancer with primary tumours > or = 3 cm, inflammatory or locally advanced disease, and no evidence of distant metastases, were randomised to receive a maximum of 6 cycles of either doxorubicin (60 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) i/v or doxorubicin (50 mg/m(2)) plus docetaxel (75 mg/m(2)) i/v every 3 weeks, followed by surgery on completion of chemotherapy. Clinical and pathologic responses have previously been reported. Time to relapse, site of relapse, and all-cause mortality were recorded. This updated analysis compares long-term disease-free (DFS) and overall survival (OS) using stratified log rank methods. A total of 363 patients were randomised to AC (n = 181) or AD (n = 182). A complete pathologic response was observed in 16% for AC and 12% for AD (P = 0.43). The number of patients with positive axillary nodes at surgery with AC was 61% and AD 66% (P = 0.36). At a median follow-up of 99 months there is no significant difference between the two groups for DFS (P = 0.20) and OS (P = 0.24). Deaths were due to metastatic breast cancer in 96% of patients. Our data do not support a clinical benefit for simultaneous administration of AD compared with AC. However, the data do not exclude a smaller benefit than the study was powered to detect and are consistent with an increase in both disease-free and overall survival of about 5% for AD compared with AC. Outcome is consistent with the pathologic complete response following surgery.

Prolonged N-acetylcysteine therapy in late acetaminophen poisoning associated with acute liver failure--a need to be more cautious?

Since the 1970s, N-acetylcysteine (NAC) has shown proven efficacy as an antidote for acetaminophen (APAP) poisoning and APAP-induced liver failure for early presenters. The current evidence of benefits of NAC for late presenters is controversial because of the poor understanding of the mechanism of late toxicity. In the previous issue of Critical Care, Yang and colleagues use a mouse model to demonstrate that NAC in doses similar to those used therapeutically to treat APAP poisoning in humans impairs liver regenerative capacity and that the effect is more pronounced when administered for a longer duration. Studies based on cell cultures support this evidence. Cytokine and growth factor signalling pathways are recognised to be involved in the process of liver regeneration and apoptosis. This research paper generates several issues related to the future management of APAP-induced liver failure and research into the mechanism of toxicity, especially of late toxicity.

E-cigarettes-An unintended illicit drug delivery system.

Since the introduction of electronic cigarettes (e-cigarettes) in 2003, the technology has advanced allowing for greater user modifications, with users now able to control voltage, battery power, and constituents of the e-cigarette liquid. E-cigarettes have been the subject of a growing body of research with most research justifiably focused on the chemical makeup and risk analysis of chemicals, metals, and particulates found in e-cigarette liquids and vapor. Little research to date has focused on assessing the risks associated with the drug delivery unit itself and its potential for use as an illicit drug delivery system. In light of this, a range of illicit drugs was researched focusing on pharmacodynamics, usual method of administration, the dosage required for toxicity, toxic effects, and evidence of existing use in e-cigarettes in both literature and online illicit drug forums. A systematic literature search found evidence of current use of e-cigarettes to vape almost all illicit drug types analyzed. This presents both a potential population health risk and a management issue for clinicians. It also raises the issue of policing illicit drugs due to potential altered characteristic smells and storage within e-cigarette fluids. E-cigarettes are a viable illicit drug delivery system with evidence both inside and outside of the formal medical literature detailing their potential use for drug delivery of a wide range of illicit and legal drugs.

Relative safety of hyperinsulinaemia/euglycaemia therapy in the management of calcium channel blocker overdose: a prospective observational study.

OBJECTIVE: To examine the clinical safety of hyperinsulinaemia/euglycaemia therapy (HIET) in calcium channel blocker (CCB) poisoning. DESIGN: A prospective observational study examining biochemical and clinical outcomes of a HIET protocol administered under local poisons centre guidance. SETTING: Critical care settings. PATIENTS: Seven patients with significant CCB toxicity [systolic blood pressure (BP) <90 mmHg] treated with HIET. INTERVENTIONS: HIET was commenced after correction of any pre-existing hypoglycaemia ([blood glucose]<65 mg/dl) or hypokalaemia ([K+]<3.5mmol/l). A quantity of 50 ml of 50% intravenous dextrose was followed by a loading dose (1 unit/kg) of intravenous short-acting insulin and an insulin maintenance infusion (0.5-2.0 units/kg/h). Euglycaemia was maintained using 5-10% dextrose infusions. Potassium was maintained within low normal range (3.8-4.0 mmol/l). MEASUREMENTS AND RESULTS: Six patients survived. All patients received fluids, calcium, and conventional inotropes. Three patients (who all ingested diltiazem) received an insulin-loading dose; all experienced a significant sustained rise in systolic BP (>10 mmHg) during the first hour of HIET. Systolic BP did not increase significantly in four patients who did not receive insulin loading. Single episodes of non-clinically significant biochemical hypoglycaemia and hypokalaemia were recorded in one and two patients respectively. Hypoglycaemia was not recorded in any patient administered HIET during the 24[Symbol: see text]h following CCB ingestion. CONCLUSIONS: HIET used to treat CCB-induced cardiovascular toxicity is a safe intervention when administered in a critical care setting. Maximal HIET efficacy may be obtained when HIET is administered in conjunction with conventional therapy relatively early in the course of severe CCB poisoning when insulin resistance is high.

Is cocaine use recognised as a risk factor for acute coronary syndrome by doctors in the UK?

BACKGROUND: Cocaine is a sympathomimetic agent that can cause coronary artery vasospasm leading to myocardial ischaemia, acute coronary syndrome and acute myocardial infarction (ACS/AMI). The management of cocaine-induced ACS/AMI is different to classical atheromatous ACS/MI, because the mechanisms are different. METHODS: Knowledge study--Junior medical staff were given a scenario of a patient with ACS and asked to identify potential risk factors for ACS and which ones they routinely asked about in clinical practice. Retrospective study--Retrospective notes reviews of patients with suspected and proven (elevated troponin T concentration) ACS were undertaken to determine the recording of cocaine use/non-use in clinical notes. RESULTS: Knowledge study--There was no significant difference in the knowledge that cocaine was a risk factor compared to other "classical" cardiovascular risk factors, but juniors doctors were less likely to ask routinely about cocaine use compared to other "classical" risk factors (52.9% vs >90%, respectively). Retrospective study--Cocaine use or non-use was documented in 3.7% (4/109) and 4% (2/50) of clinical notes of patients with suspected and proven ACS, respectively. DISCUSSION: Although junior medical staff are aware that cocaine is a risk factor for ACS/AMI, they are less likely to ask about it in routine clinical practice or record its use/non-use in clinical notes. It is essential that patients presenting with suspected ACS are asked about cocaine use, since the management of these patients is different to those with ACS secondary to "classical" cardiovascular risk factors.

Status epilepticus following intentional overdose of fluvoxamine: a case report with serum fluvoxamine concentration.

INTRODUCTION: Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that is used in the management of depression and obsessive compulsive disorders. We report a patient with status epilepticus requiring quadruple anti-convulsant treatment following a fluvoxamine overdose. CASE REPORT: A 25-year-old female presented with drowsiness at 12 hours following deliberate ingestion of 9.6 grams of fluvoxamine. Sixteen hours after ingestion, she developed status epilepticus that required treatment with benzodiazepines (lorazepam and midazolam), thiopentone, phenytoin and phenobarbitone. Her serum fluvoxamine concentration on presentation was 1970 microg/L (therapeutic 160-220 microg/L) and routine toxicological screening was negative for other drugs. She was discharged home after 72 hours with no further episodes of seizures. DISCUSSION: Most patients with fluvoxamine poisoning are either asymptomatic or may develop mild signs of serotonergic toxicity. Although serotonin syndrome and isolated seizures are reported in fluvoxamine poisoning, we report the first patient with confirmed isolated fluvoxamine toxicity who developed status epilepticus.