Drug-related Mortality Research Articles

Prevalence, Reasons, and Prevention for Drug Related Death After Release from Prisons: A Systematic Review and Meta-analysis

Context: Drug-related mortality is a major concern in public and global health discussions. Objectives: Therefore, the aim of this study was to investigate the prevalence, causes, and prevention of death after individuals are released from prison. Methods: This study was conducted systematically using MeSH keywords with no language or time restrictions. PubMed, Scopus, and Web of Science databases were extensively searched for observational studies from 1980/1/1 to 2023/12/30, following the PRISMA checklist. Fourteen research studies were ultimately included in the systematic review process. The CRD code is CRD42024571756. Results: The two-week period following release, with an 18% prevalence, was identified as the time when most overdose deaths occurred. The leading causes of death included prior heroin use, previous experiences with drug withdrawal, drug injection, and sedative use within six months before death. Compared to other unnatural causes of death, there was an increased risk of fatal drug overdose for individuals who died within the first two months of release. Men had higher death rates from all causes compared to women. Most studies reported that substance abuse treatment during imprisonment and providing take-home naloxone for emergencies protected against mortality from all causes. Conclusions: In conclusion, evidence from these systematic investigations highlights the urgent need for targeted interventions to address substance use disorders and overdose prevention among individuals recently released from prison. Efforts to bridge the gap between incarceration and community reintegration should prioritize comprehensive substance abuse treatment programs to reduce the heightened risk of mortality in this vulnerable population.

Suicide in people prescribed opioid-agonist therapy in Scotland, United Kingdom, 2011-2020: A national retrospective cohort study.

Opioid dependence is associated with an increased risk of suicide. Drug-related mortality among people with opioid dependence in Scotland has more than tripled since 2010; less is known about changes in suicide risk. We aimed to determine if opioid agonist therapy (OAT) in Scotland is protective against suicide and to measure trends in suicide rates in those with opioid dependence over time. Retrospective cohort study. Scotland, UK. 46 453 individuals in Scotland who received at least one prescription for OAT between 2011 and 2020 with over 304 000 person-years (pys) of follow-up. We calculated standardised mortality ratios (SMR) using the age- and sex-specific suicide rates in Scotland for years 2011-2020. We fitted multivariable competing-risk regression models to estimate suicide rates by OAT exposure and to estimate trends over time, adjusting for potential confounders. There were 575 deaths classed as suicide among the cohort and the overall suicide rate was 1.89 (95% confidence interval [CI] = 1.74-2.05) per 1000 pys. Age and sex SMR for suicide was 7.05 times (95% CI = 6.50-7.65) higher than in the general population. After adjustment, OAT was shown to be highly protective against suicide, with rates more than three times greater (adjusted hazard ratio: 3.07; 95% CI = 2.60-3.62) off OAT compared with on OAT. Suicide rates decreased over time, falling from 2.57 (95% CI = 2.19-3.02) per 1000 pys in 2011-12 to 1.48 (95% CI = 1.21-1.82) in 2019-20. People with opioid dependence in Scotland appear to have a greater risk of suicide than the general population. Treatment is protective, with rates of suicide lower among those on opioid agonist therapy. Suicide rates have decreased over time, during a period in which drug-related death rates in Scotland have risen to globally high levels.

Filling the Treatment Gap: Geographic Expansion of Buprenorphine Providers Across the U.S.

ObjectiveWith opioid-related deaths reaching epidemic levels, gaining a better understanding of access to treatment for opioid use disorder (OUD) is critical. Buprenorphine is an effective medication for the treatment of opioid addiction. The analysis is critical post-X-waiver elimination which extended the ability to prescribe buprenorphine for the treatment of OUD to all practitioners with DEA Schedules II-V on their DEA Registration. The primary purpose of the analysis was to explore the geographic patterns of substance use treatment and establish a geographical baseline to assess the removal of the X-Waiver in the future. Data and MethodsWe assessed the expansion of buprenorphine providers across the data from all US counties up to December 31, 2022. We used all certified buprenorphine providers' data from the database of the buprenorphine waiver notification system (BWNS). We used county-level population data from the US Census of American Community Survey (ACS) of 2021 and the CDC's Drug-related mortality data. We implemented spatial scan statistics to identify the spatial clusters using SaTScan. ResultsThe results from our analysis show that Doctor of Medicine/Doctor of Osteopathic Medicine (MD/DO) have the highest numbers of certified providers at 8134 (65.08%) in 2018 and 14525 (57.87%) in 2022. Our analysis shows that the distribution of buprenorphine providers across the counties of the United States was significantly clustered. Higher clusters with RR of more than 1 (p-value <0.001) were found in the states of Washington, Oregon, Northern California, and the Western borders of Montana. Similar clusters of counties with RR more than 1 (p-value <0.001) were found in the northeastern states of Maine, Vermont, and New Hampshire. ConclusionsFrom our analysis, it is evident that buprenorphine-certified providers are clustered in areas of higher drug-related mortality filling a treatment gap. The elimination of the X-waiver will be a significant step towards increasing access to MOUD and this analysis may be used as a geographical baseline to assess in the future.

Opioid-related mortality after occupational injury in Washington State: accounting for preinjury opioid use

ObjectivesTo estimate the impact of occupational injury and illness on opioid-related mortality while accounting for confounding by preinjury opioid use.MethodsWe employed a retrospective cohort study design using Washington State workers’...

The impact of opioids on the hallmarks of ageing

Opioids rank among the most hazardous substances of abuse, leading to opioid use disorders (which greatly diminish life quality) and contributing to the highest drug-related mortality rates. Nonetheless, both the therapeutic and recreational use of opioids is escalating globally. Interestingly, chronic opioid users often exhibit signs consistent with accelerated ageing, suggesting that they likely interfere with well-characterized ageing mechanisms (e.g., telomere shortening, epigenetic changes, mitochondrial dysfunction, cellular senescence). Here, we review the most recent advances regarding the impact of opioids on well-characterized hallmarks of ageing, to ascertain a potential association between opioid use and accelerated ageing. Our findings indicate that there is accumulating evidence supporting a close association between the use of opioids and the early onset of some ageing hallmarks, namely mitochondrial dysfunction, genomic instability, or telomere shortening. However, there is still limited data available regarding how opioids specifically impact other ageing hallmarks, like nutrient sensing, cellular senescence, or loss of proteostasis. Taking into consideration the high prevalence of opioid use, strengthening the understanding of the mechanisms underlying opioids’ impact on ageing assumes utmost relevance, both in terms of improving risk assessment, as well as to help researchers and clinicians prevent or mitigate these effects in clinical settings.

Trends in toxicological findings in unintentional opioid or stimulant toxicity deaths in Québec, Canada, 2012-2021: Has Québec entered a new era of drug-related deaths?

We aimed to describe rates and toxicological findings of unintentional opioid and stimulant toxicity deaths, 2012-2021. The dataset included accidental deaths determined by the Coroner to be due to opioids or stimulants. We calculated annual crude mortality rates and described combinations of drugs identified in toxicological examinations of these deaths. We described temporal trends in the detection of specific opioids, stimulants, benzodiazepines (including novel benzodiazepines), gabapentinoids and z-drugs in deaths due to opioids and stimulants. Mortality rates increased over time, reaching their peak in 2020 and remaining high in 2021. In deaths due to opioids, there was a decline in the proportion of deaths involving pharmaceutical opioids after 2019, and a corresponding increase in the proportion of deaths with fentanyl detected. Benzodiazepines were often present in deaths due to opioids, with novel benzodiazepines increasing rapidly from 2019 onwards. Cocaine was the most frequently detected drug in deaths due to stimulants, but amphetamine/methamphetamine was detected in around half of all stimulant deaths from 2016 onwards. Despite availability of a multitude of overdose prevention interventions, mortality rates due to drug toxicity have increased in Québec. Toxicological findings of these deaths suggest concerning shifts in the illicit drug market, with Québec potentially having entered a new era of elevated overdose mortality. Intervention scale-up is essential, but unlikely to be sufficient, to reduce drug-related mortality. Policy reform to address the root causes of drug toxicity deaths, including an unpredictable drug supply, strained health systems and socio-economic precarity, is essential.

A randomized non-inferiority study comparing imipenem/cilastatin/relebactam with standard-of-care Gram-negative coverage in cancer patients with febrile neutropenia.

Antibiotic overuse leads to the emergence of antibiotic resistance that threatens immunocompromised cancer patients. Infections caused by MDR Gram-negative pathogens are difficult to treat and associated with high mortality. Hence, empirical therapy with standard-of-care (SOC) antibiotics could be suboptimal in these vulnerable patients. New antibiotics covering potential resistant pathogens may be considered. We conducted a randomized non-inferiority study comparing safety and efficacy of imipenem/cilastatin/relebactam (IPM/REL), a β-lactam/β-lactamase inhibitor combination, with SOC antibiotics (cefepime, piperacillin/tazobactam or meropenem) in cancer patients with febrile neutropenia. Patients received at least 48 h of IV antibiotics and were assessed at end-of-IV (EOIV) therapy, test of cure (TOC; Days 21-28), and late follow-up (LFU; Days 35-42). A total of 100 patients were enrolled (49 IPM/REL and 50 SOC). Demographics and rates of documented microbiological infections were similar in both groups. In the SOC arm, 86% of antibiotics consisted of cefepime. Patients on IPM/REL had a higher favourable clinical response at EOIV than those on SOC (90% versus 74%; P = 0.042); however, responses were similar at TOC and LFU. Microbiological eradication was comparable at all three timepoints. Study drug-related adverse events and adverse events leading to drug discontinuation were similar in both groups, with no study drug-related mortality. Our results suggest that compared with SOC antibiotics, predominantly cefepime, IPM/REL for empirical coverage of febrile neutropenia in cancer patients is generally safe and could be associated with a better clinical outcome at EOIV. The current SOC consisting mainly of agents that do not cover for ESBL-producing and carbapenem-resistant Enterobacterales bacteria should be reconsidered.

Increasing age and lethal opiate use.

Opioid abuse is a leading cause of drug-related morbidity and mortality worldwide. It has been suggested that the age of opiate users in Australia is rising. To evaluate this further in a local population, toxicology and pathology case files from Forensic Science SA, Adelaide, South Australia, were examined for all cases with lethal opioid levels from 2000 to 2019 (n = 499; M:F 2.3:1; age range 18-91 years, median age 42 years). The median age of opiate deaths increased significantly by approximately 16 years (p = 0.007, R2 = 0.34) with a significant increase in total deaths in the 45-54 years and 55-64 years age groups (p = 0.009, R2 = 0.32) (p = < 0.001, R2 = 0.54). Deaths due to heroin overdose showed the lowest median age (39 years, n = 184), with deaths from tramadol toxicity having the highest (50.5 years, n = 32). Recent changes in the demographic profile of opioid users in cases of lethal overdose involve an aging population. Forensic and clinical practitioners should be aware of significant opioid abuse in certain individuals at older ages as this raises the possibility that this may exacerbate the effects of age-related chronic diseases in this group and/or contribute to fatalities.

Effect of Social Vulnerability on Cocaine-Related Mortality Rates in U.S. Counties

ABSTRACT Cocaine-related mortality rates have risen sharply since 2013 and social vulnerability is a crucial indicator for drug-related mortality rates. Therefore, the purpose of this study was to investigate the relationship between social vulnerability and cocaine-related mortality rates in U.S. counties. The Data were collected from the CDC WONDER, CDC’s Social Vulnerability Index (CDC’s SVI), and American Community Survey (ACS). The Data were analyzed by spatial autoregression models. According to present results, first, counties with social vulnerability (socioeconomic) were positively related to higher rates of cocaine overdose death (spatial lag: B = 0.323, p < .05; spatial error: B = 0.513, p < .01). Second, counties with social vulnerability (minority status & language) were negatively related to higher rates of cocaine overdose death (spatial lag: B = -0.233, p < .05). Third, counties with social vulnerability (housing type & transportation) were positively related to higher rates of cocaine overdose death (spatial lag: B = 0.413, p < .001; spatial error: B = 0.378, p < .001). In conclusion, the spread of cocaine overdose on U.S. counties with social vulnerabilities demonstrated a disproportionate burden of cocaine-related mortality.

#2564 Terlipressin given by continuous infusion versus boluses in the treatment of hepatorenal syndrome: a systematic review and meta-analysis

Abstract Background and Aims Hepatorenal syndrome (HRS) is one of the complications among patients with cirrhosis. Available guidelines recommended terlipressin with albumin as part of HRS management. To date there is no consensus on whether terlipressin should be given via bolus or continuous intravenous infusion. This study aims to compare the effectiveness and safety of continuous intravenous infusion versus intravenous boluses of terlipressin in the treatment of patients with HRS and cirrhosis. Method A comprehensive search for databases of randomized controlled trials (RCTs) comparing continuous intravenous infusion versus intravenous boluses of terlipressin among adult patients with hepatorenal syndrome was done. PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were searched using relevant terms including hepatorenal syndrome, acute kidney injury, cirrhosis, terlipressin, bolus, and continuous infusion until December 2023. Response to therapy defined as decrease in serum creatinine or regression of acute kidney injury was the primary outcome of interest, while safety in terms of drug-related events, mortality, and transplant-free survival were the secondary outcomes. Data extraction was performed using a standardized data form. The reviewers independently screened the studies and assessed the methodological quality using the Cochrane Risk of Bias tool and any discrepancies were resolved by consensus among the authors. Random-effects meta-analysis was done using Review Manager 5.4. Results A total of three studies, one high quality and two moderate quality RCTs, were included in the review, involving a total of 240 patients. Pooled analysis showed that continuous infusion was as effective or better than bolus infusion in achieving the primary outcome (RR 1.12, 95% CI 0.95-1.32, I2 = 0%). In one study, 28- and 90-day mortality were not significantly different, while 90-day transplant-free survival was not significantly different between continuous and bolus groups from another trial (53% vs 69% p = 0.26). Higher incidence of adverse events were also reported in the bolus group, RR 0.37, 95% CI 0.13-1.04 (p = 0.06). Conclusion There is limited evidence to suggest that continuous infusion of terlipressin may demonstrate resolution of acute kidney injury more frequently than bolus infusion, and that continuous infusion is associated with decreased adverse events. Larger randomized controlled trials with higher quality are needed to ascertain the effects on mortality, need for renal replacement therapy, and transplant-free survival.

Increases in drug-related infant mortality in the United States.

We explored temporal trends in drug-related infant deaths in the United States (U.S.) from 2018 to 2022. We used data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (WONDER). A total of 295 drug-involved infant deaths were identified from 2018 to 2022 (provisional mortality data for year 2022) based on the underlying cause of death. In the U.S. from 2018 to 2022, there was a significant 2.2-fold increase in drug-involved infant mortality. The observed increases were higher in non-Hispanic White and Black infants. The findings show that drug-involved infant deaths were more likely to occur in the postneonatal period, defined as ages 28-364days (81.4 %) compared to the neonatal period. The most prevalent underlying causes of death included assault (homicide) by drugs, medicaments and biological substances (35.6 %) followed by poisoning dueto exposure to narcotics and psychodysleptics (hallucinogens) (15.6 %). The most common multiple causes of drug-involved infant deaths were psychostimulants with abuse potential of synthetic narcotics. Drug-related infant mortality has increased significantly from 2018 to 2022. These increases are particularly evident among White and Black infants and occurred predominantly in the postneonatal period. These findings require more research but also indicate the need to address drug-involved infant deaths as preventable clinical and public health issues. Effective strategies to reduce drug-involved infant deaths will require preventing and treating maternal substance use disorders, enhancing prenatal care access, and addressing broader social and behavioral risk factors among vulnerable maternal and infant populations.

Opioid and other drug use and drug-related mortality as indicators of Hepatitis C and Human Immunodeficiency Virus in Oklahoma

Objectives Outbreaks of injection drug use (IDU)-associated infections have become major public health concerns in the era of the opioid epidemic. This study aimed to (1) identify county-level characteristics associated with acute HCV infection and newly diagnosed IDU-associated HIV in Oklahoma and (2) develop a vulnerability index using these metrics. Methods This study employs a county-level ecological design to examine those diagnosed with acute or chronic HCV or newly diagnosed IDU-associated HIV. Poisson regression was used to estimate the association between indicators and the number of new infections in each county. Primary outcomes were acute HCV and newly diagnosed IDU-associated HIV. A sensitivity analysis included all HCV (acute and chronic) cases. Three models were run using variations of these outcomes. Stepwise backward Poisson regression predicted new infection rates and 95% confidence intervals for each county from the final multivariable model, which served as the metric for vulnerability scores. Results Predictors for HIV-IDU cases and acute HCV cases differed. The percentage of the county population aged 18–24 years with less than a high school education and population density were predictive of new HIV-IDU cases, whereas the percentage of the population that was male, white, Pacific Islander, two or more races, and people aged 18–24 years with less than a high school education were predictors of acute HCV infection. Counties with the highest predicted rates of HIV-IDU tended to be located in central Oklahoma and have higher population density than the counties with the highest predicted rates of acute HCV infection. Conclusions There is high variability in county-level factors predictive of new IDU-associated HIV infection and acute HCV infection, suggesting that different public health interventions need to be tailored to these two case populations.

The development and internal validation of a multivariable model predicting 6-month mortality for people with opioid use disorder presenting to community drug services in England: a protocol

BackgroundPeople with opioid use disorder have substantially higher standardised mortality rates compared to the general population; however, lack of clear individual prognostic information presents challenges to prioritise or target interventions within drug treatment services. Previous prognostic models have been developed to estimate the risk of developing opioid use disorder and opioid-related overdose in people routinely prescribed opioids but, to our knowledge, none have been developed to estimate mortality risk in people accessing drug services with opioid use disorder. Initial presentation to drug services is a pragmatic time to evaluate mortality risk given the contemporaneous routine collection of prognostic indicators and as a decision point for appropriate service prioritisation and targeted intervention delivery. This study aims to develop and internally validate a model to estimate 6-month mortality risk for people with opioid use disorder from prognostic indicators recorded at initial assessment in drug services in England.MethodsAn English national dataset containing records from individuals presenting to drug services between 1 April 2013 and 1 April 2023 (n > 800,000) (the National Drug Treatment Monitoring System (NDTMS)) linked to their lifetime hospitalisation and death records (Hospital Episode Statistics-Office of National Statistics (HES-ONS)). Twelve candidate prognostic indicator variables were identified based on literature review of demographic and clinical features associated with increased mortality for people in treatment for opioid use disorder. Variables will be extracted at initial presentation to drug services with mortality measured at 6 months. Two multivariable Cox regression models will be developed one for 6-month all-cause mortality and one for 6-month drug-related mortality using backward elimination with a fractional polynomial approach for continuous variables. Internal validation will be undertaken using bootstrapping methods. Discrimination of both models will be reported using Harrel’s c and d-statistics. Calibration curves and slopes will be presented comparing expected and observed event rates.DiscussionThe models developed and internally validated in this study aim to improve clinical assessment of mortality risk for people with opioid use disorder presenting to drug services in England. External validation in different populations will be required to develop the model into a tool to assist future clinical decision-making.

Developing strategic foresight for drug policy: trends, scenarios, and implications

Background This study utilized foresight analysis to project drug policy trends and challenges in Finland up to 2030. It aimed to develop scenarios and strategies for addressing critical issues and to explore alternative policy options. Methods A comprehensive methodology was employed, including scope analysis, horizon scanning, trend analysis, and scenario building along with the expert panels. This approach facilitated the identification and categorization of trends into mega-trends, emerging trends, and weak signals, ensuring a robust and inclusive analysis. Results Key findings include mega-trends, such as changing drug policies and rising economic burdens. Emerging trends highlight the increase in synthetic, polydrug, and prescription drug use, vulnerability in certain subgroups, and growing drug-related mortality. Weak signals point to the advent of online drug marketplaces and new treatment methods. Past foresight studies agree on market growth and policy inertia but diverge on resource allocation and older generation targeting. Conclusion Developed scenarios and strategies address issues like increasing drug prevalence, service gaps, and market diversification, advocating for integrated approaches in demand reduction, governance, law enforcement, environmental protection, and harm reduction services. This research highlights the significance of participatory foresight methods in shaping Finnish drug policy, offering valuable insights for future trajectories and affirming the importance of foresight in this field.

Improving state medicolegal death investigation: Does system level reform improve public health data concerning drug-related mortality?

In the United States, the governance of unnatural death certification varies greatly by state. Although cross-sectional research has linked mortality data quality with variation in medicolegal death investigation systems across states-especially with regards to drug-related deaths-this relationship has not be sufficiently tested using longitudinal data. This research assesses the impact of system governance reform on the quality of drug mortality data by assessing the impact of transitioning from a coroner system to a medical examiner system on data quality. The research finds no evidence that system-level reform is associated with improved drug-related mortality data quality. These findings suggest that alternative methods should be examined for improving public health data concerning drug-related mortality. These likely include focusing on individual-level characteristics and practices of officials and offices, rather than system-level variables.

Development and Evaluation of a Reliable Medication Management Self-Assessment Checklist.

An ability to effectively self-manage medications is the result of several factors influencing a person's decision to take medications. The need for new approaches to medication self-management are evident in the persistent trends of ineffective medication use and unfortunate consequences, referred to as drug-related morbidity and mortality. Fortunately, pioneering initiatives have emerged to reshape our approach for developing a rational organizational paradigm so that patients can confidently self-manage medications. Favorable outcomes of studies pertaining to the delivery of comprehensive medication therapy management services within the practice of pharmaceutical care prompts the question, 'Can patients and family members apply a consistent and systematic 4-step pharmacotherapy assessment process to better organize their decision-making and confidence in medication self-management?' To answer this question an Effective Medication Self-Management Toolkit based on this 4-step process, and a Medication Management Self-efficacy Checklist, were developed and evaluated for feasibility, acceptability, and internal consistency reliability. The first evaluation established the preliminary acceptability and feasibility of the toolkit using a convenience sample of 39 residents of independent living facilities in focus group sessions. All participants indicated they perceive that the 4-step process can help individuals successfully self-manage medications. At the conclusion of the focus group sessions, all 39 participants completed the 7-item post-session checklist. This paper presents the second evaluation to establish the internal consistency reliability of the toolkit's Medication Management Self-efficacy Checklist using Cronbach's alpha. There was good internal consistency of the self-efficacy checklist with a Cronbach's alpha value of 0.82. This investigation of a novel approach for applying the 4-step pharmacotherapy assessment process by patients suggests that the medication self-efficacy checklist provides a reliable and useful measure of a patient's confidence in self-managing medications.

Association between willingness to use an overdose prevention center and probation or parole status among people who use drugs in Rhode Island

BackgroundOverdose prevention centers (OPCs) are being implemented in the United States as a strategy to reduce drug-related mortality and morbidity. Previous studies have suggested that people who use drugs (PWUD) with a history of criminal legal system (CLS) involvement (e.g. current probation/parole) are at greater risk of overdose but may also encounter significant barriers to OPC use. The objective of this study was to explore the association between willingness to use an OPC and probation/parole status in a sample of PWUD in Rhode Island.MethodsThis study utilized data from the Rhode Island Prescription and Illicit Drug Study, which enrolled adult PWUD from August 2020 to February 2023. We used Pearson’s chi-square and Wilcoxon rank-sum tests to assess bivariate associations between willingness to use an OPC and probation/parole status (current/previous/never), as well as other sociodemographic and behavioral characteristics. In multivariable Poisson analyses, we examined the association between willingness to use an OPC and probation/parole status, adjusting for key sociodemographic and behavioral characteristics.ResultsAmong 482 study participants, 67% were male, 56% identified as white, 20% identified as Hispanic/Latine, and the median age was 43 (IQR 35–53). Nearly a quarter (24%) had never been on probation/parole, 44% were not currently on probation/parole but had a lifetime history of probation and parole, and 32% were currently on probation/parole. Most participants (71%) reported willingness to use an OPC, and in both bivariate and multivariable analyses, willingness to use an OPC did not vary by probation/parole status. Crack cocaine use and lifetime non-fatal overdose were associated with greater willingness to use an OPC (all p < 0.05).ConclusionsThese data demonstrate high willingness to use OPC among PWUD in Rhode Island regardless of CLS-involvement. As OPCs begin to be implemented in Rhode Island, it will be imperative to engage people with CLS-involvement and to ensure access to the OPC and protection against re-incarceration due to potential barriers, such as police surveillance of OPCs.

Brief Report: Risk of Recurrent Interstitial Lung Disease From Osimertinib Versus Erlotinib Rechallenge After Symptomatic Osimertinib-Induced Interstitial Lung Disease

IntroductionInterstitial lung disease (ILD) is the most frequent cause of drug-related mortality from EGFR tyrosine kinase inhibitors (TKIs). Yet, for patients with symptomatic osimertinib-induced ILD, the risk of recurrent ILD associated with EGFR TKI rechallenge, either with osimertinib or another TKI, such as erlotinib, is unclear. MethodsRetrospective study of 913 patients who received osimertinib treatment for EGFR mutation-positive NSCLC. Clinical characteristics, ILD treatment history, and subsequent anticancer therapy of patients with symptomatic osimertinib-induced ILD were collated. The primary end point was to compare the incidence of recurrent ILD with osimertinib versus erlotinib rechallenge. ResultsOf 913 patients, 35 (3.8%) had symptomatic osimertinib-induced ILD, of which 12 (34%), 15 (43%), and eight (23%) had grade 2, 3 to 4, and 5 ILD, respectively. On ILD recovery, 17 patients had EGFR TKI rechallenge with eight received osimertinib and nine received erlotinib. The risk of recurrent ILD was higher with osimertinib rechallenge than erlotinib (p = 0.0498). Of eight, five (63%) developed recurrent ILD on osimertinib rechallenge, including three patients with fatal outcomes. In contrast, only one of nine patients (11%) treated with erlotinib had recurrent ILD. Median time to second ILD occurrence was 4.7 (range 0.7–12) weeks. Median time-to-treatment failure of patients with erlotinib rechallenge was 13.2 months (95% confidence interval: 8.6–15.0). ConclusionsThe risk of recurrent ILD was considerably higher with osimertinib rechallenge than erlotinib. Osimertinib rechallenge should be avoided, whereas erlotinib may be considered in patients with symptomatic osimertinib-induced ILD.

The risk of drug overdose death among adults with select types of disabilities in the United States – A longitudinal study using nationally representative data

BackgroundDisability is associated with increased risk of drug overdose mortality, but previous studies use coarse and inconsistent methods to identify adults with disabilities. This investigation makes use of the U.S. Department of Health and Human Services disability questions to estimate the risk of drug overdose death among U.S. adults using seven established disability categories. MethodsThe longitudinal Mortality Disparities in American Communities study was used to determine disability status among a nationally representative sample of adults age ≥18 in 2008 (n = 3,324,000). Through linkage to the National Death Index, drug overdose deaths were identified through 2019. Adults in mutually-exclusive disability categories (hearing, vision, cognitive, mobility, complex activity, ≥2 limitations) were compared to adults with no reported disabilities using adjusted hazard ratios (aHRs) and controlling for demographic and socioeconomic covariates. ResultsThe risk of drug overdose death varied considerably by disability type, as adults in some disability categories displayed only marginally significant risk, while adults in other disability categories displayed substantially elevated risk. Compared to non-disabled adults, the risk of drug overdose death was highest among adults with ≥2 limitations (aHR = 3.0, 95% CI = 2.8–3.3), cognitive limitation (aHR = 2.6, 95% CI = 2.3–2.9), mobility limitation (aHR = 2.6, 95% CI = 2.3–2.9), complex activity limitation (aHR = 2.3, 95% CI = 1.8–2.9), hearing limitation (aHR = 1.6, 95% CI = 1.3–1.9), and vision limitation (aHR = 1.3, 95% CI = 1.0–1.7). ConclusionsThe examination of specific disability categories revealed unique associations that were not apparent in previous research. These findings can be used to focus overdose prevention efforts on the populations at greatest risk for drug-related mortality.

Mitomycin C and capecitabine: An additional option as an advanced line therapy in patients with metastatic colorectal cancer

BACKGROUND In recent years survival of patients with metastatic colorectal cancer (mCRC), though still limited, has improved significantly; clearly, when the disease becomes refractory to standard regimens, additional treatment options are needed. Studies have shown that mitomycin C (MMC), an antitumor antibiotic, and capecitabine, a precursor of 5-fluorouracil, may act synergistically in combination. The efficacy of MMC/capecitabine has been demonstrated in the first-line setting, but only a few small studies have tested it in the advanced-line setting, with contradictory results. AIM To summarize our experience using MMC/capecitabine as an advanced line treatment for mCRC. METHODS A retrospective study was conducted at a tertiary medical center including all patients with histologically proven mCRC who were treated with MMC/capecitabine after at least two previous lines of standard chemotherapy in 2006-2020. Data on patient demographics and past medical history, laboratory, pathological, and radiological factors, and treatment and survival were collected from the files. Survival analyses were performed using the Kaplan-Meier method. The association of patient and tumor characteristics with treatment effectiveness and toxicity was evaluated with univariate and multivariate proportional hazard Cox regression analyses. P ≤ 0.05 was considered statistically significant. RESULTS The cohort consisted of 119 patients of median age 64 years (range 37-85). Patients received a median of 2 MMC/capecitabine cycles (range 0.5-9.0). Thirty-four patients (28.6%) experienced grade ≥ 3 toxicity, including 2 (1.7%) with grade 4; there was no drug-related mortality. The objective response rate was 0.8%, and the disease control rate, 24.4%. Median progression-free survival (PFS) was 2.1 mo (range 0.2-20.3), and median overall survival, 4.8 mo (range 0.2-27.5). The 6-month overall survival rate was 44%; 8.7% of patients remained progression-free. Factors associated with longer PFS were lower gamma-glutamyl transferase level (P = 0.030) and primary tumor location in the left colon (P = 0.017). Factors associated with longer overall survival were lower gamma-glutamyl transferase level (P = 0.022), left-colon tumor location (P = 0.044), low-to-moderate histological grade (P = 0.012), Eastern Cooperative Oncology Group performance status 0-1 (P = 0.036), and normal bilirubin level (P = 0.047). CONCLUSION MMC/capecitabine is an active, available, and relatively safe regimen for use beyond standard lines of therapy in mCRC. Several clinical and laboratory parameters can identify patients more likely to benefit.