Screening for harmful substance use in emergency departments: a systematic review.

BACKGROUND: Substance use-related emergency department (ED) visits have increased substantially in North America. Screening for substance use in EDs is recommended; best approaches are unclear. This systematic review synthesizes evidence on diagnostic accuracy of ED screening tools to detect harmful substance use. METHODS: We included derivation or validation studies, with or without comparator, that included adult (≥ 18 years) ED patients and evaluated screening tools to identify general or specific substance use disorders or harmful use. Our search strategy combined concepts Emergency Department AND Screening AND Substance Use. Trained reviewers assessed title/abstracts and full-text articles for inclusion, extracted data, and assessed risk of bias (QUADAS-2) independently and in duplicate. Reviewers resolved disagreements by discussion. Primary investigators adjudicated if necessary. Heterogeneity precluded meta-analysis. We descriptively summarized results. RESULTS: Our search strategy yielded 2696 studies; we included 33. Twenty-one (64%) evaluated a North American population. Fourteen (42%) applied screening among general ED patients. Screening tools were administered by research staff (n = 21), self-administered by patients (n = 10), or non-research healthcare providers (n = 1). Most studies evaluated alcohol use screens (n = 26), most commonly the Alcohol Use Disorders Identification Test (AUDIT; n = 14), Cut down/Annoyed/Guilty/Eye-opener (CAGE; n = 13), and Rapid Alcohol Problems Screen (RAPS/RAPS4/RAPS4-QF; n = 12). Four studies assessing six tools and screening thresholds for alcohol abuse/dependence in North American patients (AUDIT ≥ 8; CAGE ≥ 2; Diagnostic and Statistical Manual of Mental Disorders, 4th Edition [DSM-IV-2] ≥ 1; RAPS ≥ 1; National Institute on Alcohol Abuse and Alcoholism [NIAAA]; Tolerance/Worry/Eye-opener/Amnesia/K-Cut down [TWEAK] ≥ 3) reported both sensitivities and specificities ≥ 83%. Two studies evaluating a single alcohol screening question (SASQ) (When was the last time you had more than X drinks in 1 day?, X = 4 for women; X = 5 for men) reported sensitivities 82-85% and specificities 70-77%. Five evaluated screening tools for general substance abuse/dependence (Relax/Alone/Friends/Family/Trouble [RAFFT] ≥ 3, Drug Abuse Screening Test [DAST] ≥ 4, single drug screening question, Alcohol, Smoking and Substance Involvement Screening Test [ASSIST] ≥ 42/18), reporting sensitivities 64%-90% and specificities 61%-100%. Studies' risk of bias were mostly high or uncertain. CONCLUSIONS: Six screening tools demonstrated both sensitivities and specificities ≥ 83% for detecting alcohol abuse/dependence in EDs. Tools with the highest sensitivities (AUDIT ≥ 8; RAPS ≥ 1) and that prioritize simplicity and efficiency (SASQ) should be prioritized.

Trajectories of health-related quality of life following road trauma: Latent growth mixture modeling across a 12-month cohort study.

INTRODUCTION: Health-related quality of life (HRQoL) should be considered when evaluating the burden of road trauma (RT) injuries. This study aimed to identify distinct HRQoL trajectories following minor to severe RT injury and determine characteristics of trajectory membership. METHODS: This prospective inception cohort study recruited 1480 RT survivors from three emergency departments in British Columbia, Canada (July 2018 - March 2020). HRQoL outcome was measured with the Short Form 12 survey (SF-12) and the 5-level version of the EuroQol instrument (EQ-5D-5L) at baseline (pre-injury) and at 2, 4, 6, and 12 months post-injury. Potential predictors of outcome trajectory included sociodemographic, psychological, medical, crash, and injury factors collected at baseline. We used a latent growth mixture model to identify distinct recovery trajectories and multinomial logistic regression to determine predictors of trajectory membership. RESULTS: Three distinct HRQoL trajectories were identified for SF-12 subscales and EQ-5D-5L measures: Low/Moderate-Stable, High-Large decline, and High-Slight decline. Participants in the Low/Moderate-Stable trajectory had persistent low to moderate HRQoL before and after the injury. Those in the High-Large decline trajectory had good pre-injury HRQoL followed by persistently decreased HRQoL afterwards. The High-Slight decline trajectory was characterized by good pre-injury HRQoL and only a slight decline afterwards. Participants in the Low/Moderate-Stable and High-Large decline trajectories were considered at risk of permanently poor HRQoL following RT injury given their low HRQoL over a long period of time. Characteristics that placed participants in the Low/Moderate-Stable trajectory were older age, female gender, poor pre-injury health (medical comorbidity, prescribed medication use, complaints in the injured body area(s)), pre-injury somatic symptoms, pain catastrophizing or psychological distress, injury severity (ISS) and injury pain. Patients with head injury were less likely to be in the Low/Moderate-Stable trajectory. Risk factors for membership in the High-Large decline trajectory included older age (for physical HRQoL), younger age (for mental HRQoL), female gender, living alone, pre-injury psychological distress, ISS, injury pain, no expectations for a fast recovery, as well as head injuries, spine/back injuries or lower extremity injuries. CONCLUSIONS: This study highlighted the heterogeneity of HRQoL trajectories following RT injury and the importance of considering differences between characteristics of survivors. In addition to injury type and severity, outcome is related to demographic factors, pre-injury health and pre-injury psychological factors.

Health-related quality of life in the year following road trauma: Longitudinal analysis using piecewise latent curve modeling.

BACKGROUND: Road trauma (RT) survivors have reduced health-related quality of life (HRQoL). We identified phases and predictors of HRQoL change following RT injury. METHODS: In a prospective cohort study of 1480 Canadian RT survivors aged 16 to 103 years (July 2018 - March 2020), physical component (PCS) and mental component (MCS) summary scores from the SF-12v2 were measured pre-injury and 2, 4, 6, and 12 months post-injury and their trajectories were analyzed with piecewise latent growth curve modeling. Potential predictors of HRQoL changes included sociodemographic, psychological, medical, and trauma-related factors. RESULTS: PCS and MCS scores worsened from pre-injury to 2-months (phase 1) and then improved (phase 2), but never regained baseline values. Older age, somatic symptoms and pain catastrophizing were associated with lower preinjury PCS and MCS scores. Psychological distress was associated with lower preinjury MCS scores and higher preinjury PCS scores. Phase 1 PCS scores decreased most in females, participants with fewer pre-injury somatic symptoms and those without expectations for fast recovery. Phase 1 MCS decreases were associated with younger age, female sex, living alone, lower psychological distress, lack of expectation for fast recovery and higher injury pain. In phase 2, MCS improved most in participants not using recreational drugs; PCS improved most in participants with higher education and longer recovery expectations. LIMITATIONS: There may be recall bias with reporting pre-injury HRQoL. Selection bias is possible. CONCLUSIONS: Many factors influence HRQoL following RT. These findings may inform measures to minimize HRQoL reduction following RT and speed up subsequent recovery.

Twelve-month recovery following road trauma: Results from an inception cohort in Vancouver, Canada.

BACKGROUND: Injury-related disability following road trauma is a major public health concern. Unfortunately, outcome following road trauma and risk factors for poor recovery are inadequately studied, especially for road trauma survivors with minor injuries that do not require hospitalization. OBJECTIVES: This manuscript reports 12-month recovery outcomes for a large cohort of road trauma survivors. METHODS: This was a prospective, observational inception cohort study of 1,480 road trauma survivors recruited between July 2018 and March 2020 from 3 trauma centres in British Columbia, Canada. Participants were aged ≥16 years and arrived in a participating emergency department within 24 h of a motor vehicle collision. Data on baseline health and injury severity were collected from structured interviews and medical records. Outcome measures, including the SF-12, were collected during follow-up interviews at 2, 4, 6 and 12 months. Predictors of recovery outcomes were identified using Cox proportional hazards models and summarized using hazard ratios. RESULTS: Only 42 % of participants self-reported full recovery and only 66 % reported a return to usual daily activities. Females, older individuals, pedestrians, and those who required hospital admission had a poorer recovery than other groups. Similar patterns were observed for the SF-12 physical component. For the SF-12 mental component, no significant differences were observed between participants admitted to hospital and those discharged home from the ED. Return to work was reported by 77 % of participants who had a paying job at baseline, with no significant differences between sex and age groups. CONCLUSIONS: In a large cohort of road trauma survivors, under half self-reported full recovery one year after the injury. Poor mental health recovery was observed in both participants admitted to hospital and those discharged home from the ED. This finding may indicate a need for early intervention and continued mental health monitoring for all injured individuals, including for those with less serious injuries.

Circumstances and outcome of active transportation injuries: protocol of a British Columbian inception cohort study.

INTRODUCTION: Active transport (AT) is promoted by urban planners and health officials for its environmental, economic and societal benefits and its uptake is increasing. Unfortunately, AT users can be injured or killed due to falls or collisions. Active transport injury (ATI) prevention efforts are hindered by limited research on the circumstances, associated infrastructure, injury pattern, severity and outcome of ATI events. This study seeks to address these knowledge gaps by identifying built environment features associated with injury and risk factors for a poor outcome following ATI. METHODS AND ANALYSIS: This prospective observational study will recruit an inception cohort of 2000 ATI survivors, including pedestrians, cyclists and micromobility users aged 16 years and older who arrive at a participating emergency department within 48 hours of sustaining an ATI. Baseline interviews capture demographic and socioeconomic information, pre-injury health and functional status, as well as circumstances of the injury event and recovery expectations. Follow-up interviews at 2, 4, 6 and 12 months postinjury (key stages of recovery) use standardised health-related quality of life tools to determine physical and mental health outcomes, functional recovery and healthcare resource use and lost productivity costs. ETHICS AND DISSEMINATION: The Active Transportation Injury Circumstances and Outcome Study is approved by our institutional research ethics board and the research ethics boards of all participating sites. This study aims to provide healthcare providers with knowledge of risk factors for poor outcome following ATI with the goal of improving patient management. Additionally, this study will provide insight into the circumstances of ATI events including built environment features and how those circumstances relate to recovery outcomes. This information can be used to inform city engineers and planners, policymakers and public health officials to plan roadway design and injury prevention policy.

Demographic and clinical profile of an inception cohort of road trauma survivors.

BACKGROUND: Road trauma is a major public health concern, often resulting in reduced health-related quality of life and prolonged absenteeism from work even after so-called 'minor' injuries that do not result in hospitalization. This manuscript compares pre-injury health, sociodemographic characteristics and injury details between age, sex, and road user categories in a cohort of 1,480 road trauma survivors. METHODS: This was a prospective observational inception cohort study of road trauma survivors recruited between July 2018 and March 2020 from three trauma centres in British Columbia, Canada. Participants were aged ≥ 16 years and arrived in a participating emergency department within 24 h of involvement in a motor vehicle collision. Data were collected from structured interviews and review of medical records. RESULTS: The cohort of 1,480 road trauma survivors included 280 pedestrians, 174 cyclists, 118 motorcyclists, 683 motor vehicle drivers, and 225 passengers. Median age was 40 (IQR = [27, 57]) years; 680 (46%) were female. Males and younger patients were significantly more likely to report better pre-injury physical health. Motorcyclists and cyclists tended to report better physical health and less severe somatic symptoms, whereas pedestrians and motor vehicle drivers reported better mental health. Injury severity and hospital admission rates were higher in pedestrians and motorcyclists and lower in motorists. Upper and lower extremity injuries were most common in pedestrians, cyclists and motorcyclists, whereas neck injuries were most common in motor vehicle drivers and passengers. CONCLUSIONS: In a large cohort of road trauma survivors, overall injury severity was low. Motorcyclists and pedestrians, but not cyclists, had more severe injuries than motorists. Extremity injuries were more common in vulnerable road users. Future research will investigate one-year recovery outcomes and identify risk factors for poor recovery.

Is a Lower Dose of More Bioavailable Iron (18-mg Ferrous Bisglycinate) Noninferior to 60-mg Ferrous Sulfate in Increasing Ferritin Concentrations While Reducing Gut Inflammation and Enteropathogen Detection in Cambodian Women? A Randomized Controlled Noninferiority Trial.

BACKGROUND: Global guidelines recommend untargeted iron supplementation for women in regions of anemia prevalence ≥40%, such as Cambodia. However, the potential harms of untargeted iron on the gut have not been rigorously studied in women and likely vary depending on iron dose and form. OBJECTIVES: We investigated if a lower dose of a highly bioavailable iron amino acid chelate was as effective as the standard dose of iron salts in increasing ferritin concentrations and whether any differences were observed in gut inflammation or enteropathogen detection. METHODS: A double-blind, randomized placebo-controlled noninferiority trial was conducted in Cambodia. Nonpregnant women (n = 480, 18-45 y) were randomly assigned to 60-mg ferrous sulfate, 18-mg ferrous bisglycinate, or placebo for 12 wk. Nonfasting blood and stool specimens were collected at baseline and 12 wk. Ferritin and fecal calprotectin were measured with an ELISA. A molecular assay was used to detect 11 enteropathogens in a random subset of n = 100 women. Generalized linear mixed-effects models were used to estimate the adjusted mean difference in ferritin concentrations at 12 wk (primary outcome), as compared with our 'a priori' noninferiority margin of 20 µg/L. RESULTS: Baseline anemia and iron deficiency prevalence was low (17% and 6%, respectively). The adjusted mean difference in ferritin concentrations between the iron groups was 14.6 (95% confidence interval [CI]: 7.6, 21.6) µg/L. Mean ferritin concentration at 12 wk was higher in the ferrous sulfate (99 [95% CI: 95, 103] µg/L, P < 0.001) than in ferrous bisglycinate (84 [95% CI: 80, 88] µg/L) and placebo groups (78 [95% CI: 74, 82] µg/L). No differences in fecal calprotectin concentrations or enteropathogen detection were observed across groups at 12 wk. CONCLUSIONS: Ferrous bisglycinate (18-mg) was not as effective as ferrous sulfate (60-mg) in increasing ferritin concentrations and did not differentially influence biomarkers of gut health in this predominantly iron-replete population of Cambodian women. This trial was registered at clinicaltrials.gov registry as NCT04017598.

Reticulocyte haemoglobin equivalent (RET-He) as an early marker of responsiveness to oral iron supplementation.

AIM: We investigated the potential of reticulocyte haemoglobin equivalent (RET-He) as an early marker of responsiveness to iron supplementation. METHODS: Data were obtained from a randomised controlled trial of daily iron supplementation in 356 Cambodian women (18-45 y) who received 60 mg elemental iron for 12 weeks. A fasted venous blood specimen was collected at baseline, 1-week and 12-week timepoints. Whole blood haemoglobin (g/L) and RET-He (pg) were measured using a Sysmex haematology analyser. RET-He measures were evaluated for their predictive ability on haemoglobin response to iron supplementation (defined as ≥10 g/L at 12 weeks). Receiver operating characteristic (ROC) curves were used to assess discrimination performance, and the area under the ROC curve (AUCROC) served as a measure of the ability of each predictor to discriminate between women likely or unlikely to elicit a haemoglobin response. RESULTS: Predictive ability (AUCROC (95% CI)) of baseline, 1-week, and change from baseline to 1-week RET-He on haemoglobin response was 0.70 (0.63 to 0.76), 0.48 (0.41 to 0.56) and 0.81 (0.75 to 0.87), respectively. Based on the Youden index, an absolute increase in RET-He of ~1.1 pg or a percentage increase of ~4.4% over 1 week were optimal thresholds to predict responsiveness to iron supplementation. CONCLUSION: Single timepoint RET-He measures have poor predictive ability; however, change in RET-He after 1 week was a strong predictor of haemoglobin response among Cambodian women receiving 60 mg elemental iron and can be measured easily and quickly after only 1 week of iron therapy.

Baseline Hemoglobin, Hepcidin, Ferritin, and Total Body Iron Stores are Equally Strong Diagnostic Predictors of a Hemoglobin Response to 12 Weeks of Daily Iron Supplementation in Cambodian Women.

BACKGROUND: The WHO recommends daily iron supplementation for all women in areas where the population-level anemia prevalence is ≥40%, despite the fact that hemoglobin (Hb) concentration is generally considered to be a poor prognostic indicator of iron status. OBJECTIVES: In this secondary analysis, we investigated the predictive power of ten baseline hematological biomarkers towards a 12-week Hb response to iron supplementation. METHODS: Data were obtained from a randomized controlled trial of daily iron supplementation in 407 nonpregnant Cambodian women (18-45 years) who received 60 mg elemental iron as ferrous sulfate for 12 weeks. Ten baseline biomarkers were included: Hb, measured with both a hematology analyzer and a HemoCue; inflammation-adjusted ferritin; soluble transferrin receptor; reticulocyte Hb; hepcidin; mean corpuscular volume; inflammation-adjusted total body iron stores (TBIS); total iron binding capacity; and transferrin saturation. Receiver operating characteristic (ROC) curves from fitted logistic regression models were used to make discrimination comparisons and variable selection methods were used to construct a multibiomarker prognostic model. RESULTS: Only 25% (n = 95/383) of women who completed the trial experienced a 12-week Hb response ≥10 g/L. The strongest univariate predictors of a Hb response were Hb as measured with a hematology analyzer, inflammation-adjusted ferritin, hepcidin, and inflammation-adjusted TBIS (AUCROC = 0.81, 0.83, 0.82, and 0.82, respectively), and the optimal cutoffs to identify women who were likely to experience a Hb response were 117 g/L, 17.3 µg/L, 1.98 nmol/L, and 1.95 mg/kg, respectively. Hb as measured with a hematology analyzer, inflammation-adjusted ferritin, and hepcidin had the best combined predictive ability (AUCROC=0.86). Hb measured with the HemoCue had poor discrimination ability (AUCROC = 0.65). CONCLUSIONS: Baseline Hb as measured with a hematology analyzer was as strong a predictor of Hb response to iron supplementation as inflammation-adjusted ferritin, hepcidin, and inflammation-adjusted TBIS. This is positive given that the WHO currently uses the population-level anemia prevalence to guide recommendations for untargeted iron supplementation.

Can Automated Hematology Analyzers Predict the Presence of a Genetic Hemoglobinopathy? An Analysis of Hematological Biomarkers in Cambodian Women.

Genetic hemoglobinopathies are the most common single-gene disorder worldwide. Some automated hematology analyzers have the capability of flagging individuals who may have hematological disorders based on complete blood count (CBC) biomarkers. We aimed to evaluate the accuracy of a hematology analyzer in identifying genetic hemoglobinopathies in Cambodian women and to determine which hematological biomarkers are the best predictors. A CBC was completed using a Sysmex XN-1000 analyzer and hemoglobinopathies were determined with capillary hemoglobin electrophoresis for 808 nonpregnant Cambodian women. Sysmex XN-1000 Interpretive Program (IP) messages, which flag potential hematological disorders, were produced from CBC results. Then, 2 × 2 tables were used to determine sensitivity and specificity of the IP message "Hemoglobin defect" to detect a genetic hemoglobinopathy. Receiver operating characteristic (ROC) analyses assessed the diagnostic ability of six CBC biomarkers to predict a genetic hemoglobinopathy. In total, 74% of women had a hemoglobinopathy (predominantly Hb E and α-thalassemia). "Hb defect" IP message sensitivity and specificity for genetic hemoglobinopathy detection were 10.4% and 98.6%, respectively. Variable selection strategies yielded a two-variable model including mean corpuscular volume (MCV) and red blood cell (RBC) count (AIC = 99.83, AUCROC = 0.98 (95% CI: 0.97, 0.99)) for the prediction of a homozygous EE disorder. Sensitivity and specificity values do not justify the use of Sysmex XN-1000 IP flag messages for identification of genetic hemoglobinopathies in Cambodian women. Development of an algorithm based on MCV and RBC biomarkers may optimize the screening ability of automated hematology analyzers.

Regression to the Mean: A Statistical Phenomenon of Worthy Consideration in Anemia Research.

BACKGROUND: Regression to the mean (RTM) is a statistical phenomenon where second measurements are more likely to be closer to the mean. This is particularly observed in those with baseline values further from the mean. Anemic individuals (hemoglobin <120 g/L) are often recruited when evaluating iron supplementation programs, as they are more likely to elicit a greater hemoglobin response; however, they are also at greater risk for RTM as their baseline values are lower than the overall population mean. OBJECTIVE: The aim was to calculate and apply RTM to a previously conducted iron supplementation trial of women in Cambodia at increasingly severe baseline anemia cutoffs (hemoglobin <120 g/L, <115 g/L, and <110 g/L). METHODS: Women received either 60 mg/d iron (n = 191) or placebo (n = 185) for 12 wk. Hemoglobin was measured at baseline and at 12 wk (endline), and change in hemoglobin was calculated in each group for each cutoff. RTM was calculated in the placebo group at each cutoff and applied to the change observed at each cutoff in the iron group to obtain the RTM-free effect. RESULTS: In the placebo group, mean change in hemoglobin increased as cutoffs became more extreme (0.9 g/L to 1.9 g/L in those with baseline hemoglobin <120 g/L and <110 g/L, respectively). RTM estimates similarly increased: 1.0 g/L (<120 g/L), 1.3 g/L (<115 g/L), and 1.8 g/L (<110g/L). When applying RTM to the iron group, we found that ∼10% of the "treatment effect" could be attributable to RTM at each cutoff. However, iron supplementation was still effective in increasing hemoglobin, with an increased effect in those with lower baseline values, as proven by the RTM-free effect at each cutoff: 8.7 g/L (<120 g/L), 10.9 g/L (<115 g/L), and 13.6g/L (<110 g/L). CONCLUSIONS: RTM may have accounted for ∼10% of the observed change in hemoglobin following iron supplementation; however, appropriate use of a placebo group in the statistical analyses of the trial controls for this potential RTM effect.

Is untargeted iron supplementation harmful when iron deficiency is not the major cause of anaemia? Study protocol for a double-blind, randomised controlled trial among non-pregnant Cambodian women.

INTRODUCTION: The WHO recommends daily oral iron supplementation for 12 weeks in women and adolescents where anaemia prevalence is greater than 40%. However, if iron deficiency is not a major cause of anaemia, then, at best, untargeted iron supplementation is a waste of resources; at worst, it could cause harm. Further, different forms of iron with varying bioavailability may present greater risks of harm. METHODS AND ANALYSIS: A 12-week three-arm, double-blind, randomised controlled supplementation trial was conducted in Cambodia to determine if there is potential harm associated with untargeted iron supplementation. We will recruit and randomise 480 non-pregnant women (ages 18-45 years) to receive one of three interventions: 60 mg elemental iron as ferrous sulfate (the standard, commonly used form), 18 mg ferrous bisglycinate (a highly bioavailable iron amino acid chelate) or placebo. We will measure ferritin concentrations (to evaluate non-inferiority between the two forms of iron), as well as markers of potential harm in blood and stool (faecal calprotectin, gut pathogen abundance and DNA damage) at baseline and 12 weeks. Mixed-effects generalised linear models will be used to assess the effect of iron on ferritin concentration and markers of potential harm at 12 weeks. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of British Columbia Clinical Research Ethics Board (H18-02610), the Children's and Women's Health Centre of British Columbia Research Ethics Board (H18-02610) and the National Ethics Committee for Health Research in Cambodia (273-NECHR). Findings will be published in peer-reviewed journals, presented to stakeholders and policymakers globally and shared within participants' communities. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04017598).