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Purpose: To estimate the prevalence of drug-related deaths with regard to total hospital mortality and to explore the heterogeneity in its estimation through subgroup analysis, univariate and multivariate analysis., Methods: Two investigators independently searched the PubMed and Google Scholar databases with appropriate key terms to identify observational and randomised studies assessing drug-related problems. The prevalence of drug-related deaths was estimated using a double arcsine method. The heterogeneity was explored through subgroup and univariate analysis for the following study characteristics: study design, age group, study ward, study region, types of drug-related problems, study duration, sample size and study period. The study variables showing significant effects were further explored through a multivariable regression model. The percentage of preventable drug-related deaths was explored as a secondary objective., Results: Of the 480 full-text articles assessed, 23 studies satisfying the selection criteria were included. The mean percentage of drug-related deaths was 5.6% (95% CI: 3.8-7.6%; I 2  = 96%). The univariable analysis showed study design (regression coefficient: 4.31) and study wards (regression coefficient: - 6.37) as heterogeneity modifiers. In the multivariable model, only the study ward was considered a significant predictor of drug-related deaths (regression coefficient: - 5.78; p = 0.04). The mean percentage of preventable drug-related deaths was 45.2% (95% CI: 33.6-57.0%; I 2  = 60%)., Conclusion: Drug-related problems are an important cause of mortality. The variability in its estimation could be explained by admission wards., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This is a descriptive study evaluating fatal iatrogenic and in-hospital medication errors reported to United States poison centers., Methods: A retrospective evaluation of the National Poison Data System from 2000-2017 of all therapeutic errors with a scenario coded as iatrogenic/healthcare professional or occurring in a healthcare facility. Death abstracts were reviewed for details of the exposure and therapeutic error scenarios were recoded or added to the case as appropriate. Cases, where death was considered not related to the exposure, were excluded. Additionally, we created one additional scenario (rate-related) and one additional route of administration (intrathecal) to better describe the cases., Results: A total of 172 cases were evaluated. The majority of the patients were female (52.3%) with a median age of 58.5 years (range: 2 days to 96 years). The most commonly reported medication error was "other incorrect dose" (22.7%) followed by other/unknown error (15.1%). The route of exposure was primarily parenteral (54.9%), followed by ingestion (30.2%), then intrathecal (7.0%). The most common medications were cardiac drugs, chemotherapeutics, opioids, anticoagulants, and sedative-hypnotic/antipsychotics., Conclusions: Iatrogenic and in-hospital medication errors have been studied extensively with goals to reduce their occurrence. Specific controls to prevent incorrect dosing routes, 10-fold overdoses, and incorrect intrathecal administration have been instituted. Despite interventions, all three of these therapeutic errors continued to occur in 2017, suggesting that more preventive controls should be instituted.

Background: Residential aged care is a complex and challenging clinical setting where medication errors continue to occur despite efforts to improve medication safety. No studies have sought to review and synthesize coronial investigations into medication-related deaths in Australian residential aged care facilities (RACFs)., Objective: To review coronial investigations into medication-related deaths in Australian RACFs., Methods: A national review of medication-related deaths between July 2000 and July 2013 reported to Australian Coroners was performed. Data were extracted from the National Coronial Information System and errors categorized according to stages of the medication management cycle., Results: The database search identified thirty coronial investigations into deaths. Single medication classes were implicated in 22 deaths; including opioids (n = 7), antipsychotics (n = 4) and antidepressants (n = 3). Eight deaths resulted from two or more medication classes. Thirteen deaths reported stages of medication errors, including administration (n = 9) and monitoring (n = 4). Coroners made recommendations following three deaths; including education and training on dose administration aids, regulation of personal care workers, and protocol-based renal function monitoring for residents taking digoxin., Conclusions: Deaths involving high-risk medications occurred primarily at the stages of administration and monitoring. Few investigations resulted in specific recommendations, however it is unknown whether these were implemented., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Coroners inquire into sudden, unexpected, or unnatural deaths. We have previously established 99 cases (100 deaths) in England and Wales in which medicines or part of the medication process or both were mentioned in coroners' 'Regulation 28 Reports to Prevent Future Deaths' (coroners' reports)., Objective: We wished to see what responses were made by National Health Service (NHS) organizations and others to these 99 coroners' reports., Methods: Where possible, we identified the party or parties to whom these reports were addressed (names were occasionally redacted). We then sought responses, either from the UK judiciary website or by making requests to the addressee directly or, for NHS and government entities, under the Freedom of Information Act 2000. Responses were analysed by theme to indicate the steps taken to prevent future deaths., Results: We were able to analyse one or more responses to 69/99 cases from 106 organizations. We analysed 201 separate actions proposed or taken to address the 160 concerns expressed by coroners. Staff education or training was the most common form of action taken (44/201). Some organisations made changes in process (24/201) or policy (17/201), and some felt existing policies were sufficient to address some concerns (22/201)., Conclusions: Coroners' concerns are often of national importance but are not currently shared nationally. Only a minority of responses to coroners' reports concerning medicines are in the public domain. Processes for auditing responses and assessing their effectiveness are opaque. Few of the responses appear to provide robust and generally applicable ways to prevent future deaths.

Background: Medication errors account for the most common adverse events and a significant cause of mortality in the USA. The Joint Commission has required medication reconciliation since 2006. We aimed to survey the literature and determine the challenges and effectiveness of medication reconciliation in the trauma patient population., Materials and Methods: We conducted a systematic review of the literature to determine the effectiveness of medication reconciliation in trauma patients. English language articles were retrieved from PubMed/Medline, CINAHL, and Cochrane Review databases with search terms "trauma OR injury, AND medication reconciliation OR med rec OR med rek, AND effectiveness OR errors OR intervention OR improvements.", Results: The search resulted in 82 articles. After screening for relevance and duplicates, the 43 remaining were further reviewed, and only four articles, which presented results on medication reconciliation in 3041 trauma patients, were included. Two were retrospective and two were prospective. Two showed only 4% accuracy at time of admission with 48% of medication reconciliations having at least one medication discrepancy. There were major differences across the studies prohibiting comparative statistical analysis., Conclusions: Trauma medication reconciliation is important because of the potential for adverse outcomes given the emergent nature of the illness. The few articles published at this time on medication reconciliation in trauma suggest poor accuracy. Numerous strategies have been implemented in general medicine to improve its accuracy, but these have not yet been studied in trauma. This topic is an important but unrecognized area of research in this field., Competing Interests: N/A: systematic reviewN/A: systematic reviewThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Review Question: What is the effectiveness of interventions designed to prevent medication error on medication administration errors, medication-related harms and medication-related death in acute care patients?

Background: Medication-related adverse events in primary care represent an important cause of hospital admissions and mortality. Adverse events could result from people experiencing adverse drug reactions (not usually preventable) or could be due to medication errors (usually preventable)., Objectives: To determine the effectiveness of professional, organisational and structural interventions compared to standard care to reduce preventable medication errors by primary healthcare professionals that lead to hospital admissions, emergency department visits, and mortality in adults., Search Methods: We searched CENTRAL, MEDLINE, Embase, three other databases, and two trial registries on 4 October 2016, together with reference checking, citation searching and contact with study authors to identify additional studies. We also searched several sources of grey literature., Selection Criteria: We included randomised trials in which healthcare professionals provided community-based medical services. We also included interventions in outpatient clinics attached to a hospital where people are seen by healthcare professionals but are not admitted to hospital. We only included interventions that aimed to reduce medication errors leading to hospital admissions, emergency department visits, or mortality. We included all participants, irrespective of age, who were prescribed medication by a primary healthcare professional., Data Collection and Analysis: Three review authors independently extracted data. Each of the outcomes (hospital admissions, emergency department visits, and mortality), are reported in natural units (i.e. number of participants with an event per total number of participants at follow-up). We presented all outcomes as risk ratios (RRs) with 95% confidence intervals (CIs). We used the GRADE tool to assess the certainty of evidence., Main Results: We included 30 studies (169,969 participants) in the review addressing various interventions to prevent medication errors; four studies addressed professional interventions (8266 participants) and 26 studies described organisational interventions (161,703 participants). We did not find any studies addressing structural interventions. Professional interventions included the use of health information technology to identify people at risk of medication problems, computer-generated care suggested and actioned by a physician, electronic notification systems about dose changes, drug interventions and follow-up, and educational interventions on drug use aimed at physicians to improve drug prescriptions. Organisational interventions included medication reviews by pharmacists, nurses or physicians, clinician-led clinics, and home visits by clinicians.There is a great deal of diversity in types of professionals involved and where the studies occurred. However, most (61%) of the interventions were conducted by pharmacists or a combination of pharmacists and medical doctors. The studies took place in many different countries; 65% took place in either the USA or the UK. They all ranged from three months to 4.7 years of follow-up, they all took place in primary care settings such as general practice, outpatients' clinics, patients' homes and aged-care facilities. The participants in the studies were adults taking medications and the interventions were undertaken by healthcare professionals including pharmacists, nurses or physicians. There was also evidence of potential bias in some studies, with only 18 studies reporting adequate concealment of allocation and only 12 studies reporting appropriate protection from contamination, both of which may have influenced the overall effect estimate and the overall pooled estimate. Professional interventionsProfessional interventions probably make little or no difference to the number of hospital admissions (risk ratio (RR) 1.24, 95% confidence interval (CI) 0.79 to 1.96; 2 studies, 3889 participants; moderate-certainty evidence). Professional interventions make little or no difference to the number of participants admitted to hospital (adjusted RR 0.99, 95% CI 0.92 to 1.06; 1 study, 3661 participants; high-certainty evidence). Professional interventions may make little or no difference to the number of emergency department visits (adjusted RR 0.71, 95% CI 0.50 to 1.02; 2 studies, 1067 participants; low-certainty evidence). Professional interventions probably make little or no difference to mortality in the study population (adjusted RR 0.98, 95% CI 0.82 to 1.17; 1 study, 3538 participants; moderate-certainty evidence). Organisational interventionsOverall, it is uncertain whether organisational interventions reduce the number of hospital admissions (adjusted RR 0.85, 95% CI 0.71 to 1.03; 11 studies, 6203 participants; very low-certainty evidence). Overall, organisational interventions may make little difference to the total number of people admitted to hospital in favour of the intervention group compared with the control group (adjusted RR 0.92, 95% CI 0.86 to 0.99; 13 studies, 152,237 participants; low-certainty evidence. Overall, it is uncertain whether organisational interventions reduce the number of emergency department visits in favour of the intervention group compared with the control group (adjusted RR 0.75, 95% CI 0.49 to 1.15; 5 studies, 1819 participants; very low-certainty evidence. Overall, it is uncertain whether organisational interventions reduce mortality in favour of the intervention group (adjusted RR 0.94, 95% CI 0.85 to 1.03; 12 studies, 154,962 participants; very low-certainty evidence., Authors' Conclusions: Based on moderate- and low-certainty evidence, interventions in primary care for reducing preventable medication errors probably make little or no difference to the number of people admitted to hospital or the number of hospitalisations, emergency department visits, or mortality. The variation in heterogeneity in the pooled estimates means that our results should be treated cautiously as the interventions may not have worked consistently across all studies due to differences in how the interventions were provided, background practice, and culture or delivery of the interventions. Larger studies addressing both professional and organisational interventions are needed before evidence-based recommendations can be made. We did not identify any structural interventions and only four studies used professional interventions, and so more work needs to be done with these types of interventions. There is a need for high-quality studies describing the interventions in more detail and testing patient-related outcomes.

Medication errors (MEs) result in preventable harm to nursing home (NH) residents and pose a significant financial burden. Institutionalized older people are particularly vulnerable because of various organizational and individual factors. This systematic review reports the prevalence of MEs leading to hospitalization and death in NH residents and the factors associated with risk of death and hospitalization. A systematic search was conducted of the relevant peer-reviewed research published between January 1, 2000, and October 1, 2015, in English, French, German, or Spanish examining serious outcomes of MEs in NHs residents. Eleven studies met the inclusion criteria and examined three types of MEs: all MEs (n = 5), transfer-related MEs (n = 5), and potentially inappropriate medications (PIMs) (n = 1). MEs were common, involving 16-27% of residents in studies examining all types of MEs and 13-31% of residents in studies examining transfer-related MEs, and 75% of residents were prescribed at least one PIM. That said, serious effects of MEs were surprisingly low and were reported in only a small proportion of errors (0-1% of MEs), with death being rare. Whether MEs resulting in serious outcomes are truly infrequent, or are underreported because of the difficulty in ascertaining them, remains to be elucidated to assist in designing safer systems., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

Objectives-This report identifies the specific drugs most frequently involved in drug overdose deaths in the United States from 2010 through 2014. Methods-The 2010-2014 National Vital Statistics System mortality files were linked to electronic files containing literal text information from death certificates. Drug overdose was defined using the International Classification of Diseases, Tenth Revision underlying cause-of-death codes X40-X44 (unintentional), X60-X64 (suicide), X85 (homicide), and Y10-Y14 (undetermined intent). Among deaths with an underlying cause of death of drug overdose, the literal text in three fields of the death certificate (i.e., the cause of death from Part I, significant conditions contributing to death from Part II, and a description of how the injury occurred from Box 43) were searched to identify drug mentions. Search term lists were developed using existing drug classification systems as well as from manual review of the literal text. The search term list was then used to identify the specific drugs involved in overdose deaths. Descriptive statistics were reported for drug overdose deaths involving the 10 most frequently mentioned drugs on death certificates. Tables and figures presenting information on the specific drugs involved in deaths are based on deaths with mention of at least one specific drug on the death certificate. Results-From 2010 through 2014, the number of drug overdose deaths per year increased 23%, from 38,329 in 2010 to 47,055 in 2014. During this time period, the percentage of drug overdose deaths involving at least one specific drug increased, from 67% in 2010 to 78% in 2014. Among drug overdose deaths with at least one drug specified on the death certificate, the 10 drugs most frequently involved in overdose deaths included the following opioids: heroin, oxycodone, methadone, morphine, hydrocodone, and fentanyl; the following benzodiazepines: alprazolam and diazepam; and the following stimulants: cocaine and methamphetamine. During this 5-year period, the age-adjusted rate of drug overdose deaths involving heroin more than tripled, and the rate of drug overdose deaths involving methamphetamine more than doubled. The rate of drug overdose deaths involving fentanyl more than doubled in a single year (from 2013 to 2014). In 2014, of the 36,667 drug overdose deaths involving at least one specific drug, 52% of these deaths specified one drug, 38% specified two or three drugs, and 11% specified four or more drugs. Conclusions-Analysis of the literal text from death certificates can be used to identify patterns in the specific drugs most frequently involved in drug overdose deaths. From 2010 through 2014, the top 10 drugs involved were the same, but the relative ranking and age-adjusted rates for deaths involving these drugs changed. Literal text analysis also revealed that many drug overdose deaths involved multiple drugs. Findings should be interpreted in light of the improvement in the quality of the data that resulted from better reporting of specific drugs on death certificates from 2010 through 2014. Relative increases in the death rates involving specific drugs and the rankings of these drugs may be affected by improvements in reporting, real increases in the numbers of death, or both., (All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.)

Objectives-This report describes the development and use of a method for analyzing the literal text from death certificates to enhance national mortality statistics on drug-involved deaths. Drug-involved deaths include drug overdose deaths as well as other deaths where, according to death certificate literal text, drugs were associated with or contributed to the death. Methods-The method uses final National Vital Statistics System-Mortality files linked to electronic files containing literal text information from death certificates. Software programs were designed to search the literal text from three fields of the death certificate (the cause of death from Part I, significant conditions contributing to the death from Part II, and a description of how the injury occurred from Box 43) to identify drug mentions as well as contextual information. The list of drug search terms was developed from existing drug classification systems as well as from manual review of the literal text. Literal text surrounding the identified drug search terms was analyzed to ascertain the context. Drugs mentioned in the death certificate literal text were assumed to be involved in the death unless contextual information suggested otherwise (e.g., "METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS INFECTION"). The literal text analysis method was assessed by comparing the results from application of the method with results based on ICD-10 codes, and by conducting a manual review of a sample of records., (All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.)

Background: Several antiplatelet medications used during and after percutaneous coronary intervention (PCI) are contraindicated for specific patient groups. A broad assessment of contraindicated medication use and associated clinical outcomes is not well described., Methods and Results: Using national Veterans Affairs Clinical Assessment, Reporting, and Tracking Program data for all PCI between 2007 and 2013, we evaluated patients with contraindications to commonly used antiplatelet medications during and after PCI, defined in accordance with package inserts. Adjusted association between contraindicated medication use and outcomes of periprocedural bleeding and 30-day mortality were assessed using Cox proportional hazards with inverse probability weighting. Among 64 294 patients undergoing PCI, 11 315(17.6%) had a contraindication to a common antiplatelet medication and 737 (6.5%) of these patients received a contraindicated medication. In unadjusted analyses, any contraindicated medication use was associated with both increased bleeding and 30-day mortality. In adjusted models, contraindicated abciximab use in patients with thrombocytopenia (hazard ratio, 2.23; 95% confidence interval, 1.58-3.16) and in patients with a previous stroke (hazard ratio, 1.93; 95% confidence interval, 1.37-2.71) remained significantly associated with increased bleeding. Contraindicated abciximab use was not significantly associated with 30-day mortality in adjusted models. Use of eptifibatide in dialysis patients was not significantly associated with an increased risk of bleeding or mortality., Conclusions: In this national cohort, ≈18% of patients undergoing PCI had contraindications to common antiplatelet medications. Approximately 6% of those patients received a contraindicated medication with attendant bleeding risk, although this did not translate into significantly higher risk of 30-day mortality. Continued efforts to reduce contraindicated medication use may help avoid periprocedural complications., (© 2016 American Heart Association, Inc.)

Objective: Accidental daily dosing of methotrexate can result in life-threatening toxicity. We investigated methotrexate dosing errors reported to the National Coronial Information System (NCIS), the Therapeutic Goods Administration Database of Adverse Event Notifications (TGA DAEN) and Australian Poisons Information Centres (PICs)., Design and Setting: A retrospective review of coronial cases in the NCIS (2000-2014), and of reports to the TGA DAEN (2004-2014) and Australian PICs (2004-2015). Cases were included if dosing errors were accidental, with evidence of daily dosing on at least 3 consecutive days., Main Outcome Measures: Events per year, dose, consecutive days of methotrexate administration, reasons for the error, clinical features., Results: Twenty-two deaths linked with methotrexate were identified in the NCIS, including seven cases in which erroneous daily dosing was documented. Methotrexate medication error was listed in ten cases in the DAEN, including two deaths. Australian PIC databases contained 92 cases, with a worrying increase seen during 2014-2015. Reasons for the errors included patient misunderstanding and incorrect packaging of dosette packs by pharmacists. The recorded clinical effects of daily dosage were consistent with those previously reported for methotrexate toxicity., Conclusion: Dosing errors with methotrexate can be lethal and continue to occur despite a number of safety initiatives in the past decade. Further strategies to reduce these preventable harms need to be implemented and evaluated. Recent suggestions include further changes in packet size, mandatory weekly dosing labelling on packaging, improving education, and including alerts in prescribing and dispensing software.

Background: Although most anesthesiologists will have 1 catastrophic perioperative event or more during their careers, there has been little research on their attitudes to assistive strategies after the event. There are wide-ranging emotional consequences for anesthesiologists involved in an unexpected intraoperative patient death, particularly if the anesthesiologist made an error. We used a between-groups survey study design to ask whether there are different attitudes to assistive strategies when a hypothetical patient death is caused by a drug error versus not caused by an error. First, we explored attitudes to generalized supportive strategies. Second, we examined our hypothesis that the presence of an error causing the hypothetical patient death would increase the perceived social stigma and self-stigma of help-seeking. Finally, we examined the strategies to assist help-seeking., Methods: An anonymous, mailed, self-administered survey was conducted with 1600 consultant anesthesiologists in Australia on the mailing list of the Australian and New Zealand College of Anaesthetists. The participants were randomized into "error" versus "no-error" groups for the hypothetical scenario of patient death due to anaphylaxis. Nonparametric, descriptive, parametric, and inferential tests were used for data analysis. P' is used where P values were corrected for multiple comparisons., Results: There was a usable response rate of 48.9%. When an error had caused the hypothetical patient death, participants were more likely to agree with 4 of the 5 statements about support, including need for time off (P' = 0.003), counseling (P' < 0.001), a formal strategy for assistance (P' < 0.001), and the anesthesiologist not performing further cases that day (P' = 0.047). There were no differences between groups in perceived self-stigma (P = 0.98) or social stigma (P = 0.15) of seeking counseling, whether or not an error had caused the hypothetical patient death. Finally, when an error had caused the patient death, participants were more likely to agree with 2 of the 5 statements about help-seeking, including the need for a formal, hospital-based process that provides information on where to obtain professional counseling (P' = 0.006) and the availability of after-hours counseling services (P' = 0.035)., Conclusions: Our participants were more likely to agree with assistive strategies such as not performing further work that day, time off, counseling, formal support strategies, and availability of after-hours counseling services, when the hypothetical patient death from anaphylaxis was due to an error. The perceived stigma toward attending counseling was not affected by the presence or absence of an error as the cause of the patient death, disproving our hypothesis.

Concerns for patient safety persist in clinical oncology. Within several nonmedical areas (eg, aviation, nuclear power), concepts from Normal Accident Theory (NAT), a framework for analyzing failure potential within and between systems, have been successfully applied to better understand system performance and improve system safety. Clinical oncology practice is interprofessional and interdisciplinary, and our therapies often have narrow therapeutic windows. Thus, many of our processes are, in NAT terms, interactively complex and tightly coupled within and across systems and are therefore prone to unexpected behaviors that can result in substantial patient harm. To improve safety at the University of North Carolina, we have applied the concepts of NAT to our practice to better understand our systems' behavior and adopted strategies to reduce complexity and coupling. Furthermore, recognizing that we cannot eliminate all risks, we have stressed safety mindfulness among our staff to further promote safety. Many specific examples are provided herein. The lessons from NAT are translatable to clinical oncology and may help to promote safety.

Objectives: To determine the proportion of avoidable deaths (due to acts of omission and commission) in acute hospital trusts in England and to determine the association with the trust's hospital-wide standardised mortality ratio assessed using the two commonly used methods--the hospital standardised mortality ratio (HSMR) and the summary hospital level mortality indicator (SHMI)., Design: Retrospective case record review of deaths., Setting: 34 English acute hospital trusts (10 in 2009 and 24 in 2012/13) randomly selected from across the spectrum of HSMR., Main Outcome Measures: Avoidable death, defined as those with at least a 50% probability of avoidability in view of trained medical reviewers. Association of avoidable death proportion with the HSMR and the SHMI assessed using regression coefficients, to estimate the increase in avoidable death proportion for a one standard deviation increase in standardised mortality ratio., Participants: 100 randomly selected hospital deaths from each trust., Results: The proportion of avoidable deaths was 3.6% (95% confidence interval 3.0% to 4.3%). It was lower in 2012/13 (3.0%, 2.4% to 3.7%) than in 2009 (5.2%, 3.8% to 6.6%). This difference is subject to several factors, including reviewers' greater awareness in 2012/13 of orders not to resuscitate, patients being perceived as sicker on admission, minor differences in review form questions, and cultural changes that might have discouraged reviewers from criticising other clinicians. There was a small but statistically non-significant association between HSMR and the proportion of avoidable deaths (regression coefficient 0.3, 95% confidence interval -0.2 to 0.7). The regression coefficient was similar for both time periods (0.1 and 0.3). This implies that a difference in HSMR of between 105 and 115 would be associated with an increase of only 0.3% (95% confidence interval -0.2% to 0.7%) in the proportion of avoidable deaths. A similar weak non-significant association was observed for SHMI (regression coefficient 0.3, 95% confidence interval -0.3 to 1.0)., Conclusions: The small proportion of deaths judged to be avoidable means that any metric based on mortality is unlikely to reflect the quality of a hospital. The lack of association between the proportion of avoidable deaths and hospital-wide SMRs partly reflects methodological shortcomings in both metrics. Instead, reviews of individual deaths should focus on identifying ways of improving the quality of care, whereas the use of standardised mortality ratios should be restricted to assessing the quality of care for conditions with high case fatality for which good quality clinical data exist., (© Hogan et al 2015.)

Background: Meta-analyses have suggested that pharmacist-led medication reviews have no discernable effect on patient mortality. These analyses may not have found a statistically significant effect because they did not adequately control for the patient selection parameters. Therefore, a more precise approach to evaluating the effect of clinical pharmacist interventions on the mortality rates of hospitalized cardiac patients is required., Objective: To evaluate the impact of the clinical pharmacist as a direct patient-care team member on the mortality of all patients admitted to cardiology units., Methods: A prospective, nonrandomized observational study compared patients who received standard care with patients admitted to a service that included clinical pharmacists. Propensity score matching was applied to enhance the comparability. The primary endpoint of the study was the composite of all-cause mortality in the study group and the control group., Results: Pharmacists were consulted by physicians to correct any drug-related issues that they suspected may cause or contribute to a fatal outcome in the cardiology ward. A total of 428 interventions were suggested by the clinical pharmacist in the study group; 375 (87.6%) of them were accepted by the cardiology team. All-cause mortality was 1.8% during phase 1 treatment (preintervention) and was reduced to 1.1% during phase 2 treatment (postintervention); the difference was statistically significant. There was no statistical difference in all-cause mortality in the control unit between phase 1 and phase 2. Results were similar in the propensity score-matched subcohort., Conclusions: Drug-related problems that were suspected to cause or contribute to a possibly fatal outcome were determined by the clinical pharmacist service in patients hospitalized in a cardiology ward. Correction of these drug-related problems by physicians after the pharmacist's advice caused a significant decrease in mortality as analyzed by propensity score matching. The significant reduction in the mortality rate in this patient population observed in this study is "hypothesis generating" for future randomized studies.

The EORTC-NCIC regimen for glioblastoma requires different dosing of temozolomide (TMZ) during radiation and maintenance therapy. This complexity is exacerbated by the availability of multiple TMZ capsule strengths. TMZ is an alkylating agent and the major toxicity of this class is dose-related myelosuppression. Inadvertent overdose can be fatal. The websites of the Institute for Safe Medication Practices (ISMP), and the Food and Drug Administration (FDA) MedWatch database were reviewed. We searched the MedWatch database for adverse events associated with TMZ and obtained all reports including hematologic toxicity submitted from 1st November 1997 to 30th May 2012. The ISMP describes errors with TMZ resulting from the positioning of information on the label of the commercial product. The strength and quantity of capsules on the label were in close proximity to each other, and this has been changed by the manufacturer. MedWatch identified 45 medication errors. Patient errors were the most common, accounting for 21 or 47% of errors, followed by dispensing errors, which accounted for 13 or 29%. Seven reports or 16% were errors in the prescribing of TMZ. Reported outcomes ranged from reversible hematological adverse events (13%), to hospitalization for other adverse events (13%) or death (18%). Four error reports lacked detail and could not be categorized. Although the FDA issued a warning in 2003 regarding fatal medication errors and the product label warns of overdosing, errors in TMZ dosing occur for various reasons and involve both healthcare professionals and patients. Overdosing errors can be fatal.

For patients who have difficulty swallowing, a common solution is to crush tablets or open capsules. What are the consequences of this practice? We reviewed the main evidence available using the standard Prescrire methodology. The clinical consequences for the patient of crushing tablets or opening capsules can be serious: alteration of the drug's absorption can result in sometimes fatal overdose, or conversely underdosing, rendering the treatment ineffective. When it disrupts a drug's sustained-release properties, the active ingredient is no longer released and absorbed gradually, resulting in overdose. When a gastro-resistant layer is destroyed by crushing, underdosing is likely. The active ingredient released may degrade on contact with light, moisture or the food with which it is mixed for administration. The person who crushes the tablets or opens the capsules is exposed to drug particles, which may be carcinogenic, teratogenic or fetotoxic. They are sometimes allergenic. In practice, there are many drugs that should never be crushed or opened. Before crushing a tablet or opening a capsule, it is better to consider and research the impact it will have on the drug's effects. It is sometimes preferable to use a different dosage form, or a different active ingredient.

Rational therapeutics requires a balance between benefits and harms. (i) Harm may be inevitable. Some adverse drug reactions cannot be predicted or prevented. (ii) Some harm occurs in error when a medicine is wrongly formulated, prescribed, dispensed or administered. Adverse drug reactions that might have been prevented, for example, by monitoring, fall into this category. (iii) Rarely, harm is inflicted deliberately, for example, in murder by poisoning. Here I consider adverse drug reactions, errors and deliberate drug-induced harm from the perspective of a clinical pharmacologist., (© 2013 The British Pharmacological Society.)

Our prescription drugs are the third leading cause of death after heart disease and cancer in the United States and Europe. Around half of those who die have taken their drugs correctly; the other half die because of errors, such as too high a dose or use of a drug despite contraindications. Our drug agencies are not particularly helpful, as they rely on fake fixes, which are a long list of warnings, precautions, and contraindications for each drug, although they know that no doctor can possibly master all of these. Major reasons for the many drug deaths are impotent drug regulation, widespread crime that includes corruption of the scientific evidence about drugs and bribery of doctors, and lies in drug marketing, which is as harmful as tobacco marketing and, therefore, should be banned. We should take far fewer drugs, and patients should carefully study the package inserts of the drugs their doctors prescribe for them and independent information sources about drugs such as Cochrane reviews, which will make it easier for them to say "no thanks".

Pharmacovigilance aims to detect, assess, understand and prevent any possible drug-related problem. The record of information related to adverse drug reactions (ADRs) after drug approval and risk management based on observational data are crucial for public health. The main goal was to assess the ADRs morbimortality and to describe prescription medical errors in a public hospital in the city of Buenos Aires. A prospective observational study was undertaken. ADR was defined as any clinical and/or biological noxious manifestation imputable to a drug, which occurs at the usually used dose in humans for disease prophylaxis, diagnosis or treatment. Global mortality was 7% (21/310). The observed mortality due to ADR accounted for 1% (3/310). One hundred and forty nine ADRs in 36% of patients were identified (111/310), and 11% (35/310) of the hospital admissions were due to ADRs. ADRs cause a great number of admissions and are responsible for preventable morbidity during hospitalization. Neither drug alone caused more than 6% of the ADRs. For this reason, in order to diminish ADRs, strategies should be addressed to multiple drug groups.

Background: Errors in drug administration are among the commonest medical errors. Children are particularly at risk for such errors because of the need to calculate doses individually. Doses that are ten times the correct amount (1000% of the correct dose) are occasionally given and can be life-threatening. In a simulated resuscitation in a pediatric emergency room, an error of this type occurred for one of the 32 medications that were ordered. The highest error rates are to be expected in prehospital emergency medicine. In this review, we analyze the process of ordering medications and describe the potential interventions for lowering error rates that have been evaluated to date., Method: Systematic literature review, Results: We found 32 original publications that concerned the evaluation of interventions for lowering error rates in the ordering of medications for children. Error rates can be lowered by interventions that improve prescribers' knowledge of pediatric pharmacotherapy (courses, immediately accessible sources of information) and by aids to the cognitive process of ordering medication (calculators, computer programs, tables of doses by weight). They can also be lowered by raising awareness of the problem of erroneous medication ordering and by monitoring medication orders, as well as by structured communication and standardized, unambiguously labeled drug preparations. In the hospital setting, computer programs for medication orders with a built-in pediatric pharmacological database are highly recommended. In the prehospital setting, the "pediatric emergency ruler" enables accurate estimation of the patient's weight, provides age-appropriate dosage recommendations, and directly indicates the steps needed for calculation of the correct dose., Conclusion: Children in medical emergency situations are at significant risk for medication errors. The measures described here can markedly lower the rate of dangerous errors.

Infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa are increasing. The aim of our study was to evaluate the influences of appropriate empirical antibiotic therapy and multidrug resistance on mortality in patients with bacteremia due to P. aeruginosa (PAB). Episodes of PAB were prospectively registered from 2000 to 2008. MDR was considered when the strain was resistant to ≥3 antipseudomonal antibiotics. Univariate and multivariate analyses were performed. A total of 709 episodes of PAB were studied. MDR PAB (n = 127 [17.9%]) was more frequently nosocomial and associated with longer hospitalization, bladder catheter use, steroid and antibiotic therapy, receipt of inappropriate empirical antibiotic therapy, and a higher mortality. Factors independently associated with mortality were age (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.002 to 1.033), shock (OR, 6.6; 95% CI, 4 to 10.8), cirrhosis (OR, 3.3; 95% CI, 1.4 to 7.6), intermediate-risk sources (OR, 2.5; 95% CI, 1.4 to 4.3) or high-risk sources (OR, 7.3; 95% CI, 4.1 to 12.9), and inappropriate empirical therapy (OR, 2.1; 95% CI, 1.3 to 3.5). To analyze the interaction between empirical therapy and MDR, a variable combining both was introduced in the multivariate analysis. Inappropriate therapy was significantly associated with higher mortality regardless of the susceptibility pattern, and there was a trend toward higher mortality in patients receiving appropriate therapy for MDR than in those appropriately treated for non-MDR strains (OR, 2.2; 95% CI, 0.9 to 5.4). In 47.9% of MDR PAB episodes, appropriate therapy consisted of monotherapy with amikacin. In conclusion, MDR PAB is associated with a higher mortality than non-MDR PAB. This may be related to a higher rate of inappropriate empirical therapy and probably also to amikacin as frequently the only appropriate empirical therapy given to patients with MDR PAB.

Heparin is one of the most commonly used drugs in tertiary paediatric centres. Across the last decade, targeted research has been directed towards improving the level of evidence supporting paediatric-specific recommendations for the use and management of heparin in infants and children. In contrast, little effort has been directed towards improving the safe use of heparin despite a plethora of fatal and non-fatal heparin-related errors being reported in the lay press. This short report highlights the need for united and concerted action to develop strategies aimed at minimising avoidable infant deaths related to heparin errors., (© 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Background: Adverse events are considered a major international problem related to the performance of health systems. Evaluating the occurrence of adverse events involves, as any other outcome measure, determining the extent to which the observed differences can be attributed to the patient's risk factors or to variations in the treatment process, and this in turn highlights the importance of measuring differences in the severity of the cases. The current study aims to evaluate the association between deaths and adverse events, adjusted according to patient risk factors., Methods: The study is based on a random sample of 1103 patient charts from hospitalizations in the year 2003 in 3 teaching hospitals in the state of Rio de Janeiro, Brazil. The methodology involved a retrospective review of patient charts in two stages - screening phase and evaluation phase. Logistic regression was used to evaluate the relationship between hospital deaths and adverse events., Results: The overall mortality rate was 8.5%, while the rate related to the occurrence of an adverse event was 2.9% (32/1103) and that related to preventable adverse events was 2.3% (25/1103). Among the 94 deaths analyzed, 34% were related to cases involving adverse events, and 26.6% of deaths occurred in cases whose adverse events were considered preventable. The models tested showed good discriminatory capacity. The unadjusted odds ratio (OR 11.43) and the odds ratio adjusted for patient risk factors (OR 8.23) between death and preventable adverse event were high., Conclusions: Despite discussions in the literature regarding the limitations of evaluating preventable adverse events based on peer review, the results presented here emphasize that adverse events are not only prevalent, but are associated with serious harm and even death. These results also highlight the importance of risk adjustment and multivariate models in the study of adverse events.

Background: Colchicine is commonly used for the treatment of gout and occasionally for other inflammatory diseases. It has a narrow therapeutic index and the potential for severe or fatal toxicity., Objectives: We sought to determine (1) the frequency of colchicine toxicity among hospitalized patients taking colchicine who died during an admission, (2) the likelihood that colchicine contributed to death, (3) whether patients were taking interacting medications that could have contributed to toxicity, and (4) whether colchicine dosing among these patients adhered to established guidelines., Methods: We conducted an IRB-approved, retrospective chart review at an urban, tertiary care, 1228-bed, university hospital. Subjects included hospitalized patients who received colchicine and died in hospital between 1 January 2000 and 28 February 2007. We reviewed charts for signs and symptoms of colchicine toxicity. An expert panel reviewed each case and classified the likelihood of colchicine toxicity, the likelihood of a causal role of colchicine in the death using the WHO classification system, and the appropriateness of colchicine dosing., Results: Thirty-seven hospitalized patients who died during the 86-month study period received colchicine. Toxicity was unlikely in 20/37, possible in 8/37, likely in 5/37, and certain in 4/37. A contributing role for colchicine in causing death was unlikely in 24/37, possible in 7/37, likely in 3/37, and certain in 3/37. Colchicine doses (based on creatinine clearance) exceeded the accepted range for 12 patients, including 10 of 17 cases of toxicity and 8 of 13 cases of death classified as possible or higher. Seventeen patients received interacting medications, including 8 of 17 cases of toxicity and 8 of 13 cases of death classified as possible or higher., Conclusion: Colchicine toxicity was frequent in this cohort and may have contributed to about one-third of the deaths. Inappropriate dosing of colchicine occurred frequently and was related to toxicity and death.

Health care errors are routinely reported in the scientific and public press and have become a major concern for most Americans. In learning to identify and analyze errors health care can develop some of the skills of a learning organization, including the concept of systems thinking. Modern experts in improving quality have been working in other high-risk industries since the 1920s making structured organizational changes through various frameworks for quality methods including continuous quality improvement and total quality management. When using these tools, it is important to understand systems thinking and the concept of processes within organization. Within these frameworks of improvement, several tools can be used in the analysis of errors. This article introduces a robust tool with a broad analytical view consistent with systems thinking, called CauseMapping (ThinkReliability, Houston, TX, USA), which can be used to systematically analyze the process and the problem at the same time., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: Several studies indicate that the medical burden of fatal adverse drug reactions (FADRs) is significant, but the preventability of FADRs in the general population is largely unknown. The aim of this study was to determine the proportion of preventable FADRs and preventable fatal drug poisonings (FDPs) in a Swedish population., Methods: Previously, a population-based sample of 1574 deceased subjects was scrutinised for FADRs and FDPs using relevant case records, including death certificates, medical charts and medico-legal files. Forty-nine cases (3%) of FADRs and nine cases (0.6%) of FDPs were identified in 57 subjects. In this study, the preventability of all these identified FADRs and FDPs was evaluated by clinical experts in a stepwise manner, applying a set of predefined and well established preventability criteria. Only cases for which consensus was achieved were included in the study., Results: Of 49 FADRs, 14% (seven fatalities) was considered definitely or possibly preventable and four of these were due to the presence of a contraindication for the drug. All nine FDPs were considered possibly preventable. As one subject had a combination of an FADR and an FDP, a total of 15 persons (26%) were considered having a definitely or possibly preventable FADR or FDP, corresponding to 0.95% of all deceased subjects in Sweden., Conclusions: The results of this study indicate that approximately one fourth of FADRs and FDPs could be prevented. Therefore, an increased awareness of the possibility to reduce the risk of fatal events due to pharmaceutical drugs is warranted.

Rationale: Although intensive care units (ICUs) were created for patients with life-threatening illnesses, the ICU environment generates a high risk of iatrogenic events. Identifying medical errors (MEs) that serve as indicators for iatrogenic risk is crucial for purposes of reporting and prevention., Objectives: We describe the selection of indicator MEs, the incidence of such MEs, and their relationship with mortality., Methods: We selected indicator MEs using Delphi techniques. An observational prospective multicenter cohort study of these MEs was conducted from March 27 to April 3, 2006, in 70 ICUs; 16 (23%) centers were audited. Harm from MEs was collected using specific scales., Measurements and Main Results: Fourteen types of MEs were selected as indicators; 1,192 MEs were reported for 1,369 patients, and 367 (26.8%) patients experienced at least 1 ME (2.1/1,000 patient-days). The most common MEs were insulin administration errors (185.9/1,000 d of insulin treatment). Of the 1,192 medical errors, 183 (15.4%) in 128 (9.3%) patients were adverse events that were followed by one or more clinical consequences (n = 163) or that required one or more procedures or treatments (n = 58). By multivariable analysis, having two or more adverse events was an independent risk factor for ICU mortality (odds ratio, 3.09; 95% confidence interval, 1.30-7.36; P = 0.039)., Conclusions: The impact of medical errors on mortality indicates an urgent need to develop prevention programs. We have planned a study to assess a program based on our results.

The authors retrospectively evaluated anonymously submitted inpatient medical error reports from 8 institutions participating in the University HealthSystem Consortium Patient Safety Net (PSN) in 2004 in an attempt to focus patient safety efforts on problems that were most commonly associated with harm. Of the 25,300 incidents reported, 3381 (13.3%) were associated with adverse events (AEs), and 109 (0.4%) were associated with death. Although the most commonly reported categories of incidents associated with AEs were complications of procedure/treatment/test (29%), falls (17%), and medication errors (10%), the taxonomy of the PSN limited efforts to find specific errors in care that might be addressed by attempts to improve patient safety. Skin breakdown and falls were confirmed as presenting substantial risks to hospitalized patients, in that 59% of the incidents reported in the skin integrity category and 22% of falls resulted in AEs. The benefits and limitations of a voluntary reporting system are discussed.

According to epidemiological studies adverse drug events are one of the most frequently encountered complications during medical treatment, a leading cause of hospitalisation and frequent cause of death. However, medical malpractice claims due to medication errors seem to be relatively rare. Based on a retrospective multicentre study on medical malpractice cases with lethal outcome (n=4450), drug related cases (n=575) were further evaluated. In 50% of cases a causal connection between drug therapy and death could be ruled out already after autopsy. In 232 cases a causal connection between drug therapy and death could be approved (drug allergies, relative overdose, wrong application, mix-up of drugs and sepsis after injection abscess). However, within the legal context only in 70 cases a medication error was approved which was in 42 cases causal for death, in 28 not. Administration of contraindicated drugs, incorrect application and relative overdose in renal insufficiency are the prevalent mistakes. Concerning the frequency of ADE in epidemiological studies medication errors are underreported in all data sources on medical malpractice; this seems to be due to the fact that even doctors and attending physicians rarely recognize an ADE; furthermore approving the connection between drug effect and death is extremely difficult for the expert witness.

We determined the prevalence of adverse drug events (ADEs) in a general teaching hospital in Rabat, Morocco. We performed a 5-day cross-sectional study of hospital departments recruiting inpatients and outpatients. Among the 1390 patients surveyed, 59 (4.2%) experienced at least 1 ADE and for 20 patients (1.4%) the ADE was responsible for hospitalization or prolongation of hospitalization. The ADE was classified as serious in 28 patients. Of the total of 76 ADEs, 10 (13.2%) were categorized as preventable; 6 of these occurred during the treatment monitoring phase. Patients who experienced an ADE were more likely to be women, to be younger (< 30 years) and to be hospitalized in medical departments.

A critical incident is described as any sudden unexpected event that has the power to overwhelm the usual effective coping skills of an individual or a group and can cause significant psychological distress in usually healthy persons. A Just Culture model to deal with critical incidents is an approach that seeks to identify and balance system events and personal accountability. This article reports a critical incident that occurred at the Neonatal Intensive Care Unit, Methodist Hospital of Indianapolis, when 5 infants received an overdose of heparin that resulted in the death of 3 infants. Although care of the family after the critical incident was the immediate priority, the focus of this article was on the recovery and reintegration of the NICU staff after a critical incident based on the Just Culture philosophy.

Background: Medication errors can arise both during prescription and administration (dispensing and distribution) of drugs. Little is known about types of medication errors in Norwegian hospitals., Material and Method: All medication errors reported at St. Olav's Hospital from 1 July 2002 to 30 June 2006 were reviewed and analysed., Results: 610 reports were identified. The most common cause of reporting (39 %) was prescription of a different dose from the one prescribed. Other frequent causes were administration of a different drug than the one prescribed (17 %), inadvertent subcutaneous infusion of an intravenous drug (15 %), and that the drug was given to another patient (12 %). The errors were almost exclusively reported by nurses. In 107 cases (18 %), precautions had been taken to reduce the extent of injury after the error had been identified. The causes of errors could be classified in three main categories: Nonvigilance caused by stress, lack of appropriate routines or violation of them, and lack of appropriate skills/negligence., Interpretation: Changes of routines, improved education in existing routines, and increased pharmacological competence may contribute to prevention of medication errors.

Introduction: Medication-related errors pose a risk to children, but accurate data regarding errors with clinically significant outcomes are not available. We attempt to describe errors, identify patterns of error, and find targets for prevention using a large series of pediatric therapeutic errors with severe outcomes., Methods: A national, retrospective poison center chart review study including all cases of severe injury or death from therapeutic error involving children less than 6 years which were reported to the American Association of Poison Control Centers from 2000-2004 was performed., Results: Among 272 cases identified, 238 were included in analysis and 34 were excluded; 162 cases occurred in the home and 70 in health care facilities. Significant errors disproportionately affected children less than 1 year (107/238 cases, 45%). The majority of errors were due to excessive dosing (171/238, 72%). Common mechanisms of error were identified: 10-fold errors, confusion about formulation or units of measure, increased frequency, and adult dosing., Conclusions: The recurring circumstances underlying many of these errors suggest that preventing such errors may require systemic/process changes.

Background: Patients with health-care-associated pneumonia (HCAP) are frequently infected with a resistant pathogen and receive inappropriate empiric antibiotics (ie, pathogens resistant to administered treatment). Initial inappropriate treatment has been shown to increase hospital mortality. It is not known whether escalation in response to culture results mitigates this risk., Methods: We identified patients admitted with a culture-positive pneumonia between January 2003 and December 2005. HCAP patients met one or more of the following criteria indicating ongoing contact with the health-care system: recent hospitalization (< or = 12 months), admission from a nursing home, immunosuppression, or long-term dialysis. We compared survivors to nonsurvivors among those patients with HCAP still hospitalized beyond 48 h., Results: Of 431 HCAP patients, 396 patients (92%) were alive and still hospitalized beyond 48 h. The crude mortality rate was 21.5%. Compared to survivors, nonsurvivors were significantly more likely to be treated with inappropriate empiric antibiotics (37.6% vs 24.1%, p = 0.013). Although mortality was higher among patients receiving inappropriate than appropriate therapy (30.0% vs 18.3%, p = 0.013), this difference was more pronounced among nonbacteremic patients (odds ratio [OR], 2.45; 95% confidence interval [CI], 1.26 to 4.75) than bacteremic patients (OR, 1.25; 95% CI, 0.41 to 3.57). In a logistic regression, inappropriate empiric antibiotic treatment among nonbacteremic patients was independently associated with mortality (OR, 2.88; 95% CI, 1.46 to 5.67); treatment escalation did not attenuate the risk of death., Conclusion: Among HCAP patients alive and hospitalized beyond 48 h, hospital mortality was high and, in the absence of bacteremia, greater with initial inappropriate antibiotic treatment. Despite subsequent escalation, initial inappropriate antibiotic choice nearly tripled the risk of hospital death.