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Paracetamol (acetaminophen) is the most commonly ingested drug in self-poisoning. The correlation between an ingested self-reported dose of paracetamol and plasma paracetamol concentration is moderate. The usefulness of this correlation to rule out paracetamol ingestion has to be investigated. The objective of this study is to evaluate the performance of medical history in diagnosis of paracetamol ingestion in patients admitted to the Emergency Department (ED) for deliberate self-poisoning. This retrospective cohort study was carried out in two EDs at an urban university hospital in Toulouse, France, from January 1 to June 30, 2018. All patients older than 15 years of age attending the ED for suspected deliberate self-poisonings who underwent blood testing were included. Medical history was considered positive for paracetamol intoxication if patients directly reported the use of paracetamol for deliberate self-poisoning during their ED admission or if paramedics reported the presence of paracetamol packages at the patient's home. We defined paracetamol ingestion as any concentration of paracetamol > 5 mg/L measured on presentation. We included 709 patients. 151 (21%) patients had a positive plasma paracetamol concentration. 165 (23%) patients revealed a positive medical history in terms of paracetamol ingestion. 29 (4%) patients had a false-negative medical history, and 45 (6%) patients had a false-positive history. The sensitivity of the medical history (95% confidence interval) was 79% (72 - 87), and its specificity was 92% (89 - 94). Diagnosis of self-poisoning involving paracetamol cannot be made using patient's medical history alone. Screening for paracetamol intoxication is proposed.

The rate of opioid analgesic overdose is proportional to the number of opioid prescriptions and the dose prescribed. This review considers the epidemiology, mechanisms, and management of opioid analgesic overdose. Opioid analgesic overdose is a preventable and potentially lethal condition that results from prescribing practices, inadequate understanding on the patient's part of the risks of medication misuse, errors in drug administration, and pharmaceutical abuse. 1 , 2 Three features are key to an understanding of opioid analgesic toxicity. First, opioid analgesic overdose can have life-threatening toxic effects in multiple organ systems. Second, normal pharmacokinetic properties are often disrupted during an overdose and can prolong intoxication dramatically. 3 Third, the duration of action varies among opioid formulations, and failure to recognize such variations can lead to inappropriate treatment decisions, sometimes with lethal results. 2 , . . .

BackgroundAn important strategy to address the opioid overdose epidemic involves identifying people at elevated risk of overdose, particularly those with opioid use disorder (OUD). However, it is unclear to what degree OUD diagnoses in administrative data are inaccurate.ObjectiveTo estimate the prevalence of inaccurate diagnoses of OUD among patients with incident OUD diagnoses.SubjectsA random sample of 90 patients with incident OUD diagnoses associated with an index in-person encounter between October 1, 2016, and June 1, 2018, in three Veterans Health Administration medical centers.DesignDirect chart review of all encounter notes, referrals, prescriptions, and laboratory values within a 120-day window before and after the index encounter. Using all available chart data, we determined whether the diagnosis of OUD was likely accurate, likely inaccurate, or of indeterminate accuracy. We then performed a bivariate analysis to assess demographic or clinical characteristics associated with likely inaccurate diagnoses.Key ResultsWe identified 1337 veterans with incident OUD diagnoses. In the chart verification subsample, we assessed 26 (29%) OUD diagnoses as likely inaccurate; 20 due to systems error and 6 due to clinical error; additionally, 8 had insufficient information to determine accuracy. Veterans with likely inaccurate diagnoses were more likely to be younger and prescribed opioids for pain. Clinical settings associated with likely inaccurate diagnoses were non-mental health clinical settings, group visits, and non-patient care settings.ConclusionsOur study identified significant levels of likely inaccurate OUD diagnoses among veterans with incident OUD diagnoses. The majority of these cases reflected readily addressable systems errors. The smaller proportion due to clinical errors and those with insufficient documentation may be addressed by increased training for clinicians. If these inaccuracies are prevalent throughout the VHA, they could complicate health services research and health systems responses.

Background and AimsAcetaminophen (APAP) hepatotoxicity and ischemic hepatic injury (IH) demonstrate remarkably similar biochemical patterns. Deciding between these two etiologies in the setting of acute liver failure (ALF) can be challenging. We reviewed all cases in the Acute Liver Failure Study Group (ALFSG) registry where these diagnoses were considered, to determine reasons for, and frequency of, difficulties making these diagnoses. We hypothesized that the newly developed APAP-CYS adduct assay could help in discerning the correct diagnosis.MethodsAmong 3364 patients with ALF or acute liver injury (ALI: INR ≥ 2.0 but without encephalopathy) between 1998 and 2019, 1952 (58%) received a final diagnosis of either APAP (1681) or IH (271). We utilized a review committee of senior hepatologists as well as the APAP-CYS assay (where sera were available), measuring the presence of toxic by-products of APAP injury to optimize adjudication.ResultsWith these methods, a total of 575 adduct positive APAP cases included 488 recognized APAP, as well as an additional 87 patients previously diagnosed as other etiologies. Nine cases initially attributed to IH were deemed combination APAP-IH injuries. Conversely, 215 of the 280 IH subjects tested for adducts disclosed 173 confirmed as IH with adduct testing below the toxicity threshold, while 9 cases were revised from APAP to the IH-APAP combination phenotype, where both hypotension and APAP likely played a role.ConclusionsDiscerning APAP from IH can be difficult—in rare cases, combined injury is observed (18/1952). APAP-CYS testing resulted in revising the diagnosis in 14.6% of cases.

Recent reports indicate that stimulant-related deaths are increasing dramatically. People who die from acute stimulant toxicity have high rates of pre-existing cardiovascular disease (CVD), much of which is undiagnosed. Moreover, people who use stimulants with CVD often remain asymptomatic until presenting to an emergency department with an acute event. Prior research shows that symptoms of stimulant toxicity may occur on a regular basis, and that people who die from stimulant toxicity are older than those who die of opioid toxicity. Taken collectively, the existing evidence suggests that death from acute stimulant toxicity is often an outcome of long-term, cumulative exposure leading to cardiovascular dysfunction rather than acute intoxication. Strategies tailored to the distinct etiology of stimulant overdose are needed. We propose a three-part approach including (1) implementing stimulant use interventions that promote not only abstinence, but also use reduction, (2) treating ongoing stimulant use as a chronic cardiovascular condition, and (3) making stimulant toxicity interventions relevant to the populations most affected, which includes people outside of the traditional health-care system. In short, to reduce stimulant-related fatality, we need to transform our approach in ways that are tailored to address its natural history.

Abstract Objective To validate a risk index that estimates the likelihood of overdose or serious opioid-induced respiratory depression (OIRD) among medical users of prescription opioids. Subjects and Methods A case-control analysis of 18,365,497 patients with an opioid prescription from 2009 to 2013 in the IMS PharMetrics Plus commercially insured health plan claims database (CIP). An OIRD event occurred in 7,234 cases. Four controls were selected per case. Validity of the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (RIOSORD), developed previously using Veterans Health Administration (VHA) patient data, was assessed. Multivariable logistic regression was used within the CIP study population to develop a slightly refined RIOSORD. The composition and performance of the CIP-based RIOSORD was evaluated and compared with VHA-based RIOSORD. Results VHA-RIOSORD performed well in discriminating OIRD events in CIP (C-statistic = 0.85). Additionally, re-estimation of logistic model coefficients in CIP yielded a 0.90 C-statistic. The resulting comorbidity and pharmacotherapy variables most highly associated with OIRD and retained in the CIP-RIOSORD were largely concordant with VHA-RIOSORD. These variables included neuropsychiatric and cardiopulmonary disorders, impaired drug excretion, opioid characteristics, and concurrent psychoactive medications. The average predicted probability of OIRD ranged from 2% to 83%, with excellent agreement between predicted and observed incidence across risk classes. Conclusions RIOSORD had excellent predictive accuracy in a large population of US medical users of prescription opioids, similar to its performance in VHA. This practical risk index is designed to support clinical decision-making for safer opioid prescribing, and its clinical utility should be evaluated prospectively.

Background We need to better understand how the use of different substances and psychiatric comorbidity influence premature death generally and cause-specific death by overdose, intoxication and somatic disorders in people with substance use disorders. Method A cohort of 1405 patients consecutively admitted to a Swedish detoxification unit for substance use disorders in 1970–1995 was followed-up for 42 years. Substances were identified by toxicological analyses. Mortality figures were obtained from a national registry. Causes of death were diagnosed by forensic autopsy in 594 patients deceased by 2012. Predictions were calculated by competing risks analysis. Results Forty-two per cent of the cohort died during follow-up; more men than women (46.3% vs 30.4%). The standardised mortality ratio (SMR) was calculated as the ratio of observed deaths in males and females in specific age groups in the cohort versus expected deaths in corresponding groups in the general population. SMR was 5.68 for men (CI 95%; 5.04–6.11) and 4.98 (CI 95%; 4.08–5.88) for women. The crude mortality rate (number of deaths divided by number of person observation years) was 2.28% for men and 1.87% for women. Opiates predicted increased risk of premature death while amphetamine and cannabis predicted lower risk. Comorbid psychiatric disorders were identified in 378 cases and personality disorders in 763 cases. Primary psychoses or mood/depression and anxiety disorders predicted a higher risk of premature mortality. Death by overdose was predicted by male gender, younger age at admission to substance treatment, opiate use, and comorbid depression and anxiety syndromes. Cannabis and amphetamine use predicted a lower risk of overdose. Death by intoxication was predicted by male gender, use of sedatives/hypnotics or alcohol/mixed substances, primary psychoses and depression/anxiety syndromes. Premature death by somatic disorder was predicted by male gender and alcohol/mixed abuse. Conclusion Psychiatric comorbid disorders were important risk factors for premature drug-related death. Early identification of these factors may be life-saving in the treatment of patients with substance use disorders.

Poisoning is the leading cause of injury-related morbidity and mortality in the United States. The highest rates of exposure to poisons occur in children five years and younger, but opioid overdoses in young adults account for most deaths from poisonings in recent years. Intentional or accidental medication poisoning should be considered when evaluating patients with mental status changes, vital sign abnormalities, seizures, and gastrointestinal or cardiovascular problems. For all poisoned patients, a comprehensive history and physical examination are needed. Knowledge of toxidromes may help identify the cause in unknown ingestions; however, their usefulness may be limited when multiple toxins are ingested. Electrocardiography is indicated in patients reporting chest pain and dyspnea and in overdoses of beta blockers, tricyclic antidepressants, and antidysrhythmics. Measurement of electrolyte, serum creatinine, and serum bicarbonate levels and calculation of the anion gap may be helpful based on the clinical presentation. Treatment of a patient with acute poisoning is based on resuscitation and stabilization with a focus on airway, breathing, and circulation. When poisoning is suspected, the Poison Control provides health care workers and the public with access to a specialist 24 hours a day.

People who overdose on opioids when they are alone or unmonitored are at heightened risk of death as other people do not know they should provide an emergency response. Wearable technology provides an opportunity to continuously measure respiratory function and ultimately send an alert if respiratory depression occurs. This study evaluates the feasibility and acceptability of PneumoWave DC in UK homeless hostels or supported accommodation settings (equivalent to Housing First in the USA) for individuals at high risk of opioid overdose. The PneumoWave system consists of a wearable biosensor that is affixed to the chest and records chest motion and which, in future, could potentially provide early detection of respiratory depression and trigger overdose response. RESCU-2 is a non-randomised, observational trial conducted in supported accommodation facilities across the UK. 50 participants who currently use opioids and live in homeless hostels in England and Scotland will wear the PneumoWave biosensor for varying periods to collect data over 2,000 participant-days. The biosensor will be linked via Bluetooth to a hub for continuous respiratory data collection. Self-reported drug use during the trial will be measured using drug diaries. Quantitative acceptability data will be measured using structured satisfaction surveys, while qualitative acceptability data will be obtained from interviews and focus groups with both residents and staff. Statistical analysis will include descriptive evaluation of feasibility outcomes, while qualitative data will undergo thematic analysis. The primary objectives of the study are: 1) feasibility of the study protocol within the hostel setting; 2) acceptability and usability of the device among people who use opioids and live in hostels; 3) acceptability of the device among staff who work in hostels and respond to overdose events. Primary outcomes are recruitment, total hours of usable data collected and successful recording of key outcome measures, among others. Trial registration: ISRCTN12060022. Findings will inform the feasibility of future integration of chest biosensor technology into hostel settings, assessing participant adherence, usability, and acceptability among people who use substances and staff. Insights gained will support the design of future trials and further development of remote monitoring technologies for overdose prevention and response strategies.

Opioids are respiratory depressants and heroin/opioid overdose is a major contributor to the excess mortality of heroin addicts. The individual and situational variability of respiratory depression caused by intravenous heroin is poorly understood. This study used advanced respiratory monitoring to follow the time course and severity of acute opioid-induced respiratory depression. 10 patients (9/10 with chronic airflow obstruction) undergoing supervised injectable opioid treatment for heroin addiction received their usual prescribed dose of injectable opioid (diamorphine or methadone) (IOT), and their usual prescribed dose of oral opioid (methadone or sustained release oral morphine) after 30 minutes. The main outcome measures were pulse oximetry (SpO2%), end-tidal CO2% (ETCO2%) and neural respiratory drive (NRD) (quantified using parasternal intercostal muscle electromyography). Significant respiratory depression was defined as absence of inspiratory airflow >10s, SpO2% < 90% for >10s and ETCO2% per breath >6.5%. Increases in ETCO2% indicated significant respiratory depression following IOT in 8/10 patients at 30 minutes. In contrast, SpO2% indicated significant respiratory depression in only 4/10 patients, with small absolute changes in SpO2% at 30 minutes. A decline in NRD from baseline to 30 minutes post IOT was also observed, but was not statistically significant. Baseline NRD and opioid-induced drop in SpO2% were inversely related. We conclude that significant acute respiratory depression is commonly induced by opioid drugs prescribed to treat opioid addiction. Hypoventilation is reliably detected by capnography, but not by SpO2% alone. Chronic suppression of NRD in the presence of underlying lung disease may be a risk factor for acute opioid-induced respiratory depression.