Driving under the influence of an intoxicant in Ireland.

The number of specimens analysed by the MBRS has been increasing for both alcohol and drugs. Blood and urine specimens are analysed for the concentration of alcohol using Headspace Gas Chromatography. Specimens testing positive were forwarded to the State Laboratory for confirmatory analysis by either GC/MS or LC/MS. In 2000, 93 per cent of blood specimens, 91 per cent of urine specimens and 82 per cent of breath specimens were over the limit. In the same year, 57 per cent of blood specimens, 66 per cent of urine specimens and 33 per cent of breath specimens were over twice the limit. Of the 78 specimens tested for the presence of a drug or drugs, 37 were blood specimens and 41 urine specimens. Of these, 34 blood specimens and 37 urine specimens were found to be positive, while seven specimens were negative for the drug or drug classes tested (three blood and four urine specimens). There were 23 specimens found positive for one drug class and 48 for more than one drug.The number of requests for the presence of drugs in RTA blood and urine specimens is increasing annually and the high percentage of positives found in the specimens tested indicates the need for such analyses. The results showed excellent agreement for drug detection in the blood specimens analysed by the different methods, except for the cannabinoids. The number of specimens in this study is small and care must be exercised in interpreting the results

The P2X1 receptor and platelet function

Extracellular nucleotides are ubiquitous signalling molecules, acting via the P2 class of surface receptors. Platelets express three P2 receptor subtypes, ADP-dependent P2Y1 and P2Y12 G-protein-coupled receptors and the ATP-gated P2X1 non-selective cation channel. Platelet P2X1 receptors can generate significant increases in intracellular Ca2+, leading to shape change, movement of secretory granules and low levels of αIIbβ3 integrin activation. P2X1 can also synergise with several other receptors to amplify signalling and functional events in the platelet. In particular, activation of P2X1 receptors by ATP released from dense granules amplifies the aggregation responses to low levels of the major agonists, collagen and thrombin. In vivo studies using transgenic murine models show that P2X1 receptors amplify localised thrombosis following damage of small arteries and arterioles and also contribute to thromboembolism induced by intravenous co-injection of collagen and adrenaline. In vitro, under flow conditions, P2X1 receptors contribute more to aggregate formation on collagen-coated surfaces as the shear rate is increased, which may explain their greater contribution to localised thrombosis in arterioles compared to venules within in vivo models. Since shear increases substantially near sites of stenosis, anti-P2X1 therapy represents a potential means of reducing thrombotic events at atherosclerotic plaques

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Road traffic deaths and injuries- a personal responsibility.

This editorial highlights the need for individuals to take responsibility to reduce road traffic accidents. It highlights the fact that excessive speeding contributes to approximately 40% of fatal accidents. Drinking while under the influence of alcohol also is a significant factor, with drunk drivers killing between 750 and 800 people in the last five years. Although wearing seat belts can save lives and reduce injuries, in Ireland only 57% of front seat passengers combined wear them. Only 20% of rear seat passengers wear a seat belt. All of these are personal choices, which if taken could easily reduce the number of injuries and fatalities on Ireland's roads each year

Report on roadside drug testing and equipment and related matters.

This report is a study on all aspects of roadside drug testing, including reference to and analysis of any equipment currently in use or anticipated to be used to carry out such tests. The report considers the current definition of a “drug” and current drug analysis procedure under the Road Traffic Acts. As part of the evidence base for driving under the influence of drugs (DUID) the prevalence of drug taking in the general population, in the driver population, in suspected drugs driving population and the toxicology data for drivers in fatal crashes are presented and reviewed. International data and reports are also considered to inform the relevant bodies as to drugs that could and should be targeted for testing into the future. The studies indicate that cannabis and benzodiazepines are currently the most prevalent drugs in driving under the influence of drugs cases followed by the opiates, methadone and cocaine. The effects of individual drugs on driving and the relationship between impairment and measurement of those drugs in the human body are examined. The methods of detection of DUID by means of roadside impairment testing and with particular emphasis on roadside drug testing in oral fluid are reviewed to include medical, practical and scientific considerations. The consequential confirmatory laboratory testing for drug detection in body fluids including oral fluid in the future is explored. Previous international studies and the current status of roadside drug testing in the international literature by way of extended studies are presented and support the introduction of roadside chemical drug testing devices but also acknowledge certain limitations. The introduction of roadside drug testing devices is a far more complex and complicated initiative than was the case for roadside breath alcohol testing. Four currently available roadside drug testing devices were considered and reviewed to inform this report regarding the operation of such devices, their storage and operation conditions, the scientific criteria on which they are based and also the countries which are currently using the devices or propose to use them in the near future. The practices for DUID roadside testing in 13 other countries were surveyed and are reviewed and presented with 8 of these countries or jurisdictions already having in place provision for the use of such devices and the remaining 5 countries purposely relying on roadside impairment testing rather than devices. The report sets out the considerations and options for the introduction of roadside drug testing devices in Ireland. The considerations are under four main headings - legal, operational, scientific and medical. A number of options are outlined with the considered recommendation being the combination of roadside traffic impairment testing and roadside chemical drug testing. An implementation plan for the introduction of the recommended option is set out including a timeframe for implementation of the roadside drug testing recommendation, if so approved

Covid-19 Pandemic Report on Coroner's Inquiries into Deaths: Epidemiology and Total and Excess Mortality in the District of Kildare March to June 2020

Report to the Minister for Health, Government of Ireland:All Covid-19 deaths and all nursing home and residential home deaths in Ireland must by law be reported to the Coroner, the independent Judicial Officer of the State, in the District in which they occur. This enables accurate and early collation of these death reports. Between 1st January 2015 and 30th June 2020 3,342 deaths were reported to the Coroner’s District for Kildare. From 11th March 2020, when the first Covid-19 death occurred in Ireland, to 30th June 2020 there were 1,738 Covid-19 deaths nationally of which 139 were reported in Kildare with 113 (81%) of these deaths in nursing and residential homes. The calculated excess number of deaths notified for January to June 2020 compared with 2015-2019 was 198 (41%) of the 484 total deaths reported with a 131 (45%) excess in the 293 deaths in nursing and residential homes. Covid-19 deaths accounted for 70% and 86% of these excess deaths respectively. Following subtraction of the 18 non-natural cause deaths and 139 Covid-19 deaths from the total excess there remained an unexplained excess of 60 deaths due to natural causes in March to June of 2020 compared with 2015-2019. The peak excess total death percentage was 359% in April 2020, commencing with a small excess in March (30%), continuing into May (63%) and falling again in June (37%). In the nursing and residential home setting those excess death percentages were most marked at 527% in April, with 27% in March, 54% in May and 17% in June. Underlying medical conditions were recorded in 99% of those dying from Covid-19 and the average age of the deceased was 82.5 years with median of 78 years and 55% of those dying were female and 45% male. The clinical epidemiology and documented excess mortality of the reported deaths are chronicled and analysed to learn also about the future challenges with the continuing Covid-19 infection. A centralized national mortality database providing near real-time death certification enhances infectious disease surveillance and prompt clinical epidemiology and mortality excess studies and reduces under-reporting of Covid-19 deaths

Drugs driving in Ireland: a preliminary study of the prevalence of driving under the influence of drugs on Irish roads.

Driving under the influence of alcohol on Irish roads is well publicised. In 1999, of the 8,476 sampler submitted by the Gardai to the Medical Bureau of Road safety for alcohol analysis, 92 per cent were over the legal alcohol limit. The results presented in this paper indicate that there has been a significant increase in driving under the influence of drugs in Irish roads since 1987, when 14.6 per cent of samples (under the legal alcohol limit) tested were found positive for drugs. This preliminary study has found that the percentage has risen to approximately 37 per cent. The extensive survey being carried out in 2000/2001 will identify true trends in the types of drugs being taken, their combination with alcohol, and the extent of polydrug use. This work also highlights the importance- of confirmatory analysis in the interpretation of drug screening results

COVID-19 Pandemic: Report of Coroner's Inquiries into Epidemiology and Total and Excess Mortality in the Community, Hospital and Nursing Home and Residential Care in the District of Kildare for the Year March 2020 to February 2021

All Covid-19 deaths, all nursing home and residential home deaths and deaths due to an adverse drug reaction must by law in Ireland be reported to the Coroner, the independent Judicial Officer of the State, in the District in which they occur. From 11th March 2020, when the first Covid-19 death occurred in Ireland, to 28th February 2021 there were 4,443 Covid-19 deaths nationally of which 230 (5%) were reported in Kildare with 163 (71%) of these deaths occurring in nursing and residential homes. The clinical epidemiology and documented excess mortality of the reported deaths are chronicled and analysed in this second report for three distinct periods of March to June 2020 (Period 1); July to December 2020 (Period 2); and January to February 2021 (Period 3) which also correspond with three “lockdown” periods, and for the consolidated “Covid-19 year” period from March 2020 to February 2021 (“the year”). These periods and annual figures are compared with the previous 5-year mortality figures noting that between 1st March 2015 and 28th February 2021 some 2,837 deaths were reported to the Coroner for the District of Kildare. The calculated excess number of deaths notified for March 2020 to February 2021 compared with 2015-2020 (5-yearly average of 567) was 300 (53%) of the 867 total deaths reported with a 169 (54%) excess in the 480 deaths in nursing and residential homes (5-yearly average of 311). Covid-19 deaths accounted for 77% of the total excess deaths and for 96% of the nursing and residential home excess deaths respectively. Following subtraction of the 66 non-natural cause deaths and 230 Covid-19 deaths from the total excess there remained an unexplained excess of 56 deaths due to natural causes in March 2020 to February 2021 compared with 2015-2021. Thus, the number of unattributed excess deaths actually fell marginally between July 2020 and February 2021 taking into account the figure of 62 in the first report for March to June 2020. Underlying medical conditions were recorded in all but two of those deaths related to Covid-19 and the average age of the deceased was 82.2 years with median age of 83 years and 58% were female (134) and 42% male (126). The numbers and percentages of Kildare Covid-19 cases out of the national cases were: 139 of 1,728 or 8% in Period 1; 26 of 575 or 5% in Period 2; 65 of 2,140 or 3% in Period 3; and 230 of 4,443 or 5% for the Covid-19 year. The excess total death percentage was 117%, 16%, 46% and 53% in the three periods and year respectively. In the nursing and residential home setting the corresponding numbers and percentages of Kildare cases out of the national cases were 113 of 985 or 11% (Period1); 9 of 175 or 4% (Period 2); 41of 668 or 6% (Period 3); and 163 of 1,828 or 9% for the Covid-19 year. The excess death percentages were 142%, 4% , 35% and 54% in the three periods and year respectively. Information analysed for this study allows Covid-19 public health policy and strategy to learn from mortality events and about the continuing challenges of the infection. The report is also set in the wider context of the Coroner Service and its role during the pandemic. The comments and observations are made on clinical epidemiology, co-morbidities, post mortem practices, bereavement, vaccination and the public health imperative for a centralized national mortality database and reformed death notification and certification systems for infectious disease surveillance. The tragic deaths in County Kildare of 230 individuals are best remembered and honoured by actions arising from that learning process to minimize the worst outcomes of any future similar infectious pandemic or if Covid-19 becomes a recurrent seasonal infection and some are recommended on foot of the findings and questions raised in this report. A legislative explanatory note is included at the end of the reference section.2021-05-14 JG: .docx replaced with PDF at author's reques

Driving under the influence of drugs in Ireland: results of a nationwide survey 2000-2001.

This survey examines the level of driving under the influence of drugs in Ireland, with 2000 specimens selected for drug analysis, with 1000 for over the limit alcohol levels, and 1000 under the alcohol limit (or no alcohol present at all). It shows that there is a significant number of people driving under the influence of drugs, with a strong trend towards increasing drug positivity with decreasing level of alcohol. 68% of tested drivers with essentially zero levels of alcohol were positive for one or more drugs. Many drivers also showed polydrug use, and among those who tested positive for drugs, 60% tested positive for cannabinoids. The report advises Gardai that in the event of a nil or low alcohol reading being obtained, driver impairment may be caused by the presence of drugs