Aims: To explore the associations between social determinants of health and patient-centred outcomes among adults with chronic heart failure with reduced ejection fraction.Design: Cross-sectional online self-report survey.Methods: A survey assessing social determinants of health (demographics, socio-economic position, affordability of care and social support) and patient-centred outcomes, including the Kansas City Cardiomyopathy Questionnaire-12 and validated measures of medication adherence, treatment satisfaction, treatment burden and mental health, was completed by 512 adults with chronic heart failure with a reduced ejection fraction between 06 March and 29 June 2020. Multivariable analyses included linear and logistic regression.Results: Female gender, having a care partner, and being offered financial assistance with medications were associated with worse health status, while perceiving medication as affordable and being married were associated with better health status. Females and having Medicaid, dual Medicaid/Medicare or no medical insurance were associated with a higher likelihood of depression, and non-white race/ethnicity was associated with less depression. Medication adherence was lower in patients having a care partner and offered financial assistance. Patients being offered financial and medication management assistance were more likely to be overwhelmed by the treatment burden, whereas those having some college education were less so.Conclusions: Social determinants of health are associated with patients' disease-specific health status, mental health and treatment satisfaction and burden. These findings underscore the importance of assessing social determinants of health in clinical practice and the need for developing and testing novel strategies to determine whether they improve patients' health.Impact: The relationship between social determinants of health- and patient-centred outcomes was assessed; affordability of care and social support factors were most strongly associated with outcomes for patients with chronic heart failure and reduced ejection fraction, underscoring the importance of assessing social determinants of health in routine clinical care.Implications for the profession and/or patient care: Social determinants of health data could potentially inform care delivery for patients with heart failure and reduced ejection fraction by helping to identify those who require additional support to manage their symptoms, access care and adhere to treatment. Social support and affordability of treatment were associated with most patient-centred outcomes, suggesting these factors may provide clinicians with an indicator of a patient's level of general well-being that could be assessed during routine follow-up care.Reporting method: This research followed the STROBE checklist for cross-sectional studies.Patient or public contribution: Adults who have heart failure with reduced ejection fraction that consented to participate in the study provided the data used for all analyses reported on in the manuscript. Service users, caregivers or members of the public had no involvement in the study.

Background Chronic cough (CC) which is defined >= 8 weeks is a common condition in clinical practice. However, estimates of prevalence and associated comorbidities in German adults and key subgroups of age and gender are lacking. Methods Cross-sectional study based on a representative panel of 15 020 adult subjects of the general population who completed the German National Health and Wellness Survey, reporting CC and questions about comorbidities. Lifetime and 12-month prevalence are presented as unweighted estimates. Results The lifetime CC prevalence was 6.5% (range across age groups 5.1%-8.3%) and the 12-month prevalence was 4.9% (range 3.7-5.7%). The prevalence of diagnosed CC was 2.8% (range 0.9-4.1%) and the prevalence of persons currently on any prescription to treat CC was 0.6% (range 0.2-1.4%). Respondents who experienced CC were 52.0 +/- 17.0 years old, with a higher prevalence in those aged 50 years and older. Persons with CC had higher morbidity scores and were diagnosed with an increased number of comorbidities, most frequently diagnoses of the respiratory system (71.0%), followed by digestive tract disorders (34.0%) and sleep disorders (37.6%). Conclusions In a broadly representative sample of German adults, lifetime and 12-month prevalence of CC was greatest in current and former smokers and those older >= 50 years of age. Comorbidities are frequent and may complicate management of these patients.

Introduction: COVID-19 may negatively impact prognosis for patients with chronic HFrEF, and vice versa. However, large-scale data characterizing the interplay of COVID-19 and HFrEF on clinical outcomes are scarce. Methods: We examined the TriNetX health database from January 2020-September 2020 to conduct 2 analyses. Analysis A excluded patients with HFpEF and included patients with a positive inpatient or outpatient test for COVID-19, with a 3-way comparison of patients 1) without prior HF, 2) HFrEF without recent worsening HF event (WHFE) (i.e., no HF hospitalization or outpatient IV diuretic within prior 1 year), and 3) worsening HFrEF (i.e., HF hospitalization or outpatient IV diuretic within prior 1 year). Outcomes included mortality at 30 days and composite all-cause mortality or hospitalization following COVID-19 test. Analysis B included patients with HFrEF who underwent PCR testing for COVID-19, and compared patients with a positive versus negative test. Outcomes were mortality at 30 days and worsening HF (i.e., HF hospitalization or outpatient IV diuretic use). Results: In analysis A, 98,014 (99%) patients had no prior HF, 524 (0.5%) had HFrEF without WHFE, and 514 (0.5%) had worsening HFrEF. After adjustment for confounders, compared with patients without HF, worsening HFrEF was independently associated with excess mortality (p<0.01), whereas HFrEF without WHFE was not statistically significant (p=0.06) (Table) . In analysis B, 1,038 (7%) had a positive test for COVID-19 and 13,800 (93%) had only negative tests. After adjustment, testing positive for COVID-19 was independently associated with mortality and worsening HF (all p<0.01). Conclusions: In this US population of ambulatory and hospitalized patients, after accounting for confounders, worsening HFrEF was independently associated with excess mortality after COVID-19 infection. Among patients with HFrEF, COVID-19 infection was associated with higher risk of death and worsening HF events.

Background Chronic cough (CC) represents a significant health burden. This study assessed the prevalence of CC (defined as per international guidelines as cough duration >8 weeks) in Spanish adults and compared characteristics between CC and non-CC cohorts. Methods CC cohorts were compiled using data from adult respondents to the 2020 Spanish cross-sectional online National Health and Wellness Survey (NHWS). Using propensity scores, respondents experiencing CC during their lifetime and the previous 12 months were matched 3:1 to respondents without CC and their health characteristics were compared. The number of Spanish adults affected with CC was estimated using weighted CC prevalence. Results CC during their lifetime or the previous 12 months was experienced by 579 (8.2%) and 389 (5.5%) of 7074 NHWS respondents, of whom 233 (38.5%) and 171 (44.0%), respectively, had physician-diagnosed CC. Based on weighted prevalence rates, lifetime and 12-month CC were estimated to affect ≈3.3 million and ≈2.2 million Spanish adults, respectively. Relative to the non-CC cohort, the 12-month CC cohort consistently demonstrated poorer health status, poorer mental health, greater healthcare utilization, and lower productivity at work and home. Conclusion This study contributes novel data regarding the prevalence of CC in Spain, suggests that CC is underdiagnosed, and reflects that CC and related comorbidities inflict a significant health burden in the affected population.

La toux chronique est décrite comme une pathologie fréquente dans la littérature mais aucune donnée sur sa prévalence n’est disponible en France. L’objectif de cette étude était d’estimer la prévalence autodéclarée de la toux chronique en France. L’enquête nationale NHWS est une enquête transversale sur la santé et le bien-être dont les participants ont été recrutés en ligne à partir d’un panel de population générale représentatif de la population adulte française. Une toux chronique (TC) était définie par une toux quotidienne pendant une durée de huit semaines ou plus. Les participants ont répondu à des questions démographiques et des questions liées à leur santé. La prévalence de la toux chronique des 12 derniers mois était estimée via un échantillon pondéré sur l’âge et le sexe à partir de la base de données internationale du US Census Bureau, une source commune pour les Méthodes NHWS dans les régions du monde. Parmi les 15 152 adultes français ayant répondu à l’enquête, l’âge moyen était de 48,8 ans; 57,6 % étaient des femmes et 45,6 % n’avaient jamais fumé. Au total, 730 participants ont déclaré, au moment du remplissage du questionnaire, une TC au cours des 12 derniers mois, l’âge moyen était de 48,2 ans; 60,0 % étaient des femmes et 33,4 % n’avaient jamais fumé. La prévalence annuelle de la TC après pondération était estimée à 4,8 %. Parmi les TC auto-déclarées l’année précédente, 40,8 % ont indiqué avoir eu un diagnostic de TC par un professionnel de santé, et 28,3 % des personnes diagnostiquées se sont vu prescrire un traitement pour traiter leur TC. La prévalence estimée de TC des 12 derniers mois n’était pas statistiquement différente selon le sexe (5,1 % de femmes vs 4,6 % d’hommes); cependant, les femmes avaient une prévalence presque 2 fois plus élevée que les hommes d’avoir leur TC diagnostiquée par un professionnel de santé (51,9 % vs 27,7 %, p < 0,01). La prévalence de la TC au cours des 12 derniers mois était plus élevée chez les fumeurs actuels/anciens que chez ceux n’ayant jamais fumé (5,9 % vs 3,6 %, p < 0,01) ainsi que chez les groupes les plus jeunes et les plus âgées (5,9 % chez les 18–29 ans; 4,2 % chez les 30–49 ans; 4,6 % chez les 50–64 ans; 5,1 % chez les ≥ 65 ans, p < 0,01). La prévalence de la TC en France au cours des 12 derniers mois est de 4,8 %. La moitié des adultes français souffrant de TC ont eu un diagnostic par un professionnel de santé et un quart de ceux qui ont eu un diagnostic ont reçu un traitement.

BACKGROUND:Heart failure is a chronic disease punctuated by intermittent exacerbations that require hospitalization or intravenous diuretic therapy. The association of worsening heart failure events (WHFEs) with patient-centered outcomes in heart failure with reduced ejection fraction (HFrEF) remains unexplored.METHODS AND RESULTS:Patients with HFrEF completed an online survey assessing health status, medication adherence, treatment satisfaction, treatment burden, and medication costs and affordability. Patients with and without WHFEs were compared on all study variables, with adjustment for patient characteristics using linear or logistic regression. Overall, 512 patients (52.0% WHFEs) were included. Patients with WHFEs more commonly had depression (55.3% vs 24.0%), anxiety (46.2% vs 17.9%), and insomnia (77.8% vs 44.7%; P < 0.001 for all). Patients with WHFEs had lower adjusted mean Kansas City Cardiomyopathy Questionnaire values (52.9 vs 56.0) and Satisfaction with Medications Questionnaire values (70.5 vs 72.6) and higher Treatment Burden Questionnaire scores (51.1 vs 45.1; P < 0.001). Medication-related beliefs and long-term concerns were independently associated with nonadherence in patients with WHFE (adjusted odds ratios: 4.2 and 5.2, respectively; P < 0.01 for both). Patients with WHFE incurred 50.0% higher median monthly out-of-pocket HF prescription medication costs and less often perceived HF medications to be affordable.CONCLUSIONS:WHFE is associated with several adverse impacts on patients with HFrEF. Additional support is warranted to manage symptoms, comorbidities, and HF treatments to improve adherence and outcomes.

A small number of adverse events of seizure in patients using desloratadine (DL) have been reported. The European Medicines Agency requested a post-authorization safety study to investigate whether there is an association between DL exposure and seizure. The aim was to study the association between DL exposure and incidence of first seizure. A new-user cohort study of individuals redeeming a first-ever prescription of DL in Denmark, Finland, Norway, and Sweden in 2001–2015 was conducted. DL exposure was defined as days’ supply plus a 4-week grace period. DL unexposed periods were initiated 27 weeks after DL prescription redemption. Poisson regression was used to estimate the adjusted incidence rate and adjusted incidence rate ratio (aIRR) of incident seizure. A total of 1,807,347 first-ever DL users were included in the study, with 49.3% male and a mean age of 29.5 years at inclusion; 20.3% were children aged 0–5 years. The adjusted incidence rates of seizure were 21.7 and 31.6 per 100,000 person-years during DL unexposed and exposed periods, respectively. A 46% increased incidence rate of seizure was found during DL exposed periods (aIRR = 1.46, 95% confidence interval [CI] 1.34–1.59). The aIRR ranged from 1.85 (95% CI 1.65–2.08) in children aged 0–5 years to 1.01 in adults aged 20 years or more (95% CI 0.85–1.19). This study found an increased incidence rate of seizure during DL exposed periods as compared to unexposed periods among individuals younger than 20 years. No difference in incidence rate of seizure was observed in adults between DL exposed and unexposed.

AbstractAimsThe N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) is a commonly used biomarker in heart failure for diagnosis and prognostication. We aimed to determine the prevalence of NT‐proBNP testing, distribution of NT‐proBNP concentrations, and factors associated with receiving an NT‐proBNP test in patients with heart failure with reduced ejection fraction (HFrEF), including the subset with a worsening heart failure event (WHFE).Methods and resultsThis was a retrospective cohort study using two US databases: (i) the de‐identified Humana Research Database between January 2015 and December 2018 and (ii) the Veradigm PINNACLE Registry® between July 2013 and September 2017. We included adult patients with a confirmed diagnosis of HFrEF. In each data source, a subgroup of patients with a WHFE was identified, where a WHFE was defined as a heart failure‐related hospitalization or receipt of intravenous diuretics. Bivariate and multivariate analyses were conducted to assess factors associated with receiving NT‐proBNP testing. In Cohort 1 (n = 249 238), 9.2% of patients with HFrEF and 10.8% of patients with a WHFE received NT‐proBNP testing. When restricted to patients with at least one laboratory claim, 11.3% of patients with HFrEF and 13.2% of those with a WHFE received NT‐proBNP testing. In Cohort 2 (n = 91 444), 2.3% of patients with HFrEF were tested. Median (inter‐quartile range) NT‐proBNP concentrations among patients with HFrEF were 1399 (423–4087) pg/mL in Cohort 1 and 394 (142–688) pg/mL in Cohort 2. Median (inter‐quartile range) NT‐proBNP concentrations in the subset of patients with a WHFE in each cohort were 2209 (740–5894) and 464 (174–783) pg/mL, respectively. In Cohort 1, 13.4% of all HFrEF patients receiving NT‐proBNP testing and 18.9% of patients with a WHFE had NT‐proBNP values >8000 pg/mL; in Cohort 2, these percentages were 1.0% and 2.5%, respectively.ConclusionsIn US clinical practice, NT‐proBNP testing was not frequently performed in patients with HFrEF. NT‐proBNP concentrations varied across data sources and subpopulations within HFrEF.

A worsening heart failure event (WHFE) is defined as progressively escalating heart failure signs/symptoms requiring intravenous diuretic treatment or hospitalization. No studies have compared the burden of chronic heart failure with reduced ejection fraction (HFrEF) following a WHFE versus stable disease to inform healthcare decision makers. A retrospective study using the IBM® MarketScan® Commercial Database included patients younger than 65 years of age with HFrEF (one inpatient or two outpatient claims of systolic HF or one outpatient claim of systolic HF plus one outpatient claim of any HF). The first claim for HFrEF during 2016 was the index date. Patients were followed for the first 12 months after the index date (the worsening assessment period) to identify a WHFE, and for an additional 12 months or until the end of continuous enrollment (the post-worsening assessment period). Mean per patient per month (PPPM) health care resource use (HCRU) and costs were compared between patients following a WHFE and stable patients during the two periods using generalized linear models adjusting for patient characteristics. Of 16,646 patients with chronic HFrEF, 26.8% developed a WHFE. Adjusted all-cause hospitalizations (0.16 vs. 0.02 PPPM, P < 0.0001), outpatient visits (3.54 vs. 2.73 PPPM, P < 0.0001), and emergency department visits (0.25 vs. 0.06 PPPM, P < 0.0001) were higher in patients following a WHFE than stable patients during the worsening assessment period. Similar differences in HCRU were observed between the two cohorts during the post-worsening assessment period. Mean total adjusted cost of care PPPM was $8657 in patients with HFrEF following a WHFE versus $2195 in stable patients during the worsening assessment period, and $6809 versus $2849, respectively, during the post-worsening assessment period. HCRU and costs were significantly greater in patients with chronic HFrEF following a WHFE compared to those who remained stable, suggesting an unmet need to improve clinical and economic outcomes among these patients.

With the introduction of new therapies for heart failure with reduced ejection fraction (HFrEF) and their clinical and cost implications, an up-to-date understanding of patient characteristics and healthcare resource utilization (HCRU) in patients who develop worsening chronic heart failure (WCHF)

Background: There is interest in leveraging the electronic medical records (EMRs) to improve knowledge and understanding of patients' characteristics and outcomes of patients with ambulatory heart failure (HF). However, the diagnostic performance of International Classification of Diseases (ICD)-10 diagnosis codes from the EMRs for patients with HF and with reduced or preserved ejection fraction (HFrEF or HFpEF) in the ambulatory setting are unknown. Methods: We examined a cohort of patients aged > 18 with at least 1 outpatient encounter for HF between January 2016 and June 2018 and an echocardiogram conducted within 180 days of the outpatient encounter for HF. We defined HFrEF encounters as those with ICD-10 codes of I50.2x (systolic heart failure); and we defined HFpEF encounters as those with ICD-10 codes of I50.3x (diastolic heart failure). The referent definitions of HFrEF and HFpEF were based on echocardiograms conducted within 180 days of the ambulatory encounter for HF Results: We examined 68,952 encounters of 14,796 unique patients with HF. The diagnostic performance parameters for HFrEF (based on ICD-10 I50.2x only) depended on LVEF cutoff, with a sensitivity ranging from 68%-72%, specificity 63%-68%, positive predictive value 47%-63%, and negative predictive value 73%-84%. The diagnostic performance parameters for HFpEF depended on left ventricular ejection fraction cut-off, with sensitivity ranging from 34%-39%, specificity 92%-94%, positive predictive value 86%-93%, and negative predictive value 39%-54%. Conclusions: ICD-10 coding abstracted from the EMR for HFrEF vs HFpEF in the ambulatory setting had suboptimal diagnostic performance and, thus, should not be used alone to examine HFrEF and HFpEF in the ambulatory setting.

**Background:** This retrospective cohort study aimed to describe and quantify healthcare resource utilization and costs for patients with ulcerative colitis (UC) and Crohn’s disease (CD) following initiation of biologic therapy. **Methods:** Resource utilization and costs were analyzed at baseline and 1- and 2-years after initiating a biologic. Data were extracted from a US administrative health insurance claims database for adults ≥18 years. Eligible patients were continuously enrolled in a health plan with medical and pharmacy benefits for ≥12 months prior to, and 12 months (primary analysis) or 24 months (secondary analysis) after index date (biologic initiation). **Results:** In total, 4864 and 2692 patients with UC, and 8910 and 5227 patients with CD were identified in the 1- and 2-year follow-up cohorts, respectively. Of 1-year follow-up cohort patients, 45% received the same biologic initiated at index for ≥1 year. Infliximab and adalimumab were the most commonly initiated biologics in patients with UC or CD. The highest proportion of patients who continued with the same biologic after 1-and 2-years had initiated therapy with infliximab for both indications (although at the 1-year follow-up for CD, the highest proportion continued to use natalizumab, but this was a small sample [n=15]). Generally, the proportion of patients having inpatient admissions and emergency department (ED) visits decreased after receiving the same biologic for 1 year compared with baseline, although the proportion having outpatient visits did not change. Mean per patient all-cause costs for inpatient hospitalizations, ED visits and outpatient visits decreased for patients with UC or CD who received the same biologic for 1 year, while mean pharmacy costs per patient increased. **Conclusions:** This descriptive analysis shows that although biologics effectively reduced inpatient and ED resource utilization and corresponding costs in patients with UC and CD, total management costs increased, driven by increased pharmacy costs.

PURPOSE:Treatment options for patients with ulcerative colitis (UC) or Crohn disease (CD) have increased considerably in recent years with the advent of new biologics, but little is known about treatment pathways in clinical practice. We aimed to characterize treatment patterns and sequences in patients with UC or CD newly initiated on a biologic or an immunosuppressant (IMS).METHODS:This retrospective cohort study used US health insurance claims data dated from January 1, 2009, to December 31, 2013, from patients with UC or CD newly initiated on a biologic or an IMS. Treatment patterns and sequences were described during a 24-month follow-up period.FINDINGS:Among 5543 patients with UC and 7561 patients with CD, 2403 and 4677 patients, respectively, were initiated on a biologic; 3140 and 2884 patients were initiated on an IMS. In patients initiated on a biologic, monotherapy was chosen in 71% for UC (primarily infliximab [68%]) and in 79% for CD (primarily adalimumab [52%]). Approximately one third of patients remained on the first-line biologic during the follow-up period; 69% (UC) and 70% (CD) of patients were initiated on a second-line therapy, among whom 25% (UC) and 39% (CD) received a different biologic monotherapy, suggesting intolerance, inadequate response, or loss of response to first-line therapy. In patients initiated on an IMS, 58% (UC) and 66% (CD) were initiated on monotherapy; combination therapy with a corticosteroid was prescribed in 41% (UC) and 30% (CD) of patients; and second-line therapy was initiated in 72% (UC) and 75% (CD) of patients.IMPLICATIONS:While current treatment options seem effective in a proportion of patients with UC and CD, others require multiple lines of therapy, suggesting anunmet need for alternative treatments in UC and CD to achieve disease control.

The Centers for Disease Control and Prevention and US Preventive Services Task Force recommend one-time hepatitis C virus (HCV) testing for persons born during 1945-1965 (birth cohort). However, few studies estimate the effect of birth cohort (BC) testing implementation on HCV diagnoses in primary care settings. We aimed to determine the probability of identifying HCV infections in primary care using targeted BC testing compared with usual care at three academic medical centers. From December 2012 to March 2014, each center compared one of three distinct interventions with usual care using an independently designed randomized controlled trial. Across centers, BC patients with no clinical documentation of previous HCV testing or diagnosis were randomly assigned to receive a one-time offering of HCV antibody (anti-HCV) testing via one of three independent implementation strategies (repeated-mailing outreach, electronic medical record-integrated provider best practice alert [BPA], and direct patient solicitation) or assigned to receive usual care. We estimated model-adjusted risk ratios (aRR) of anti-HCV-positive (anti-HCV+) identification using BC testing versus usual care. In the repeated mailing trial, 8992 patients (intervention, n = 2993; control, n = 5999) were included in the analysis. The intervention was eight times as likely to identify anti-HCV+ patients compared with controls (aRR, 8.0; 95% confidence interval [CI], 2.8-23.0; adjusted probabilities: intervention, 0.27%; control, 0.03%). In the BPA trial, data from 14,475 patients (BC, n = 8928; control, n = 5,547) were analyzed. The intervention was 2.6 times as likely to identify anti-HCV+ patients versus controls (aRR, 2.6; 95% CI, 1.1-6.4; adjusted probabilities: intervention, 0.29%; control, 0.11%). In the patient-solicitation trial, 8873 patients (BC, n = 4307; control, n = 4566) were analyzed. The intervention was five times as likely to identify anti-HCV+ patients compared with controls (aRR, 5.3; 95% CI, 2.3-12.3; adjusted probabilities: intervention, 0.68%; control, 0.11%). Conclusion: BC testing was effective in identifying previously undiagnosed HCV infections in primary care settings. (Hepatology 2018;67:524-533).

OBJECTIVESEffective screening, diagnosis, and treatment are needed to reduce chronic hepatitis C virus (HCV) infection-associated morbidity and mortality. In order to successfully increase HCV treatment, it is necessary to identify and understand gaps in linkage of antibody-positive patients with newly identified HCV to subsequent HCV RNA testing, clinical evaluation, and treatment.STUDY DESIGNTo estimate attainment of HCV care cascade steps among antibody-positive patients with newly identified HCV, we conducted chart reviews of patients with a new positive HCV antibody test at 3 academic medical centers participating in the Birth-Cohort Evaluation to Advance Screening and Testing of Hepatitis C (BEST-C) study.METHODSWe tracked receipt of RNA testing, clinical evaluation, treatment initiation, and treatment completion among individuals born between 1945 and 1965 who were newly diagnosed as HCV antibody-positive between December 2012 and October 2015 at 3 BEST-C centers, predominantly from the participating medical centers' primary care practices and emergency departments.RESULTSOf the 130 HCV-seropositive individuals identified, 118 (91%) had an RNA or genotype test, 75 (58%) were RNA-positive, 73 (56%) were linked to care, 22 (17% overall; 29% among RNA-positive) started treatment, and 21 (16%; 28% among RNA-positive) completed treatment.CONCLUSIONSThis analysis showed that although linkage to care was largely successful in the target birth cohort, the largest gap in the HCV care cascade was seen in initiating treatment. Greater emphasis on linking patients to clinical evaluation and treatment is necessary in order to achieve the public health benefits promised by birth-cohort testing.

In a recent paper published in Addiction, Rogeberg & Elvik 1 replicated and criticized two meta-analyses synthesizing the epidemiological evidence for marijuana use and crash risk in drivers 2, 3. The two meta-analyses were performed independently by two research teams (ours at Columbia University and Asbridge et al.'s [3] at Dalhousie University) and were published a few months apart in 2012 in two highly regarded academic journals. While we appreciate Rogeberg & Elvik's interest in our work, we feel it is incumbent upon us to respond to their criticisms of our study. Rogeberg & Elvik's critique of our study centers on three main issues: study selection, estimated effect size and data extraction. First, Rogeberg & Elvik state that our ‘selection criteria are unclear and hard to rationalize’. Study selection is an important step in any meta-analysis. In the Methods section, we stated explicitly that we followed ‘the guidelines put forth in the PRISMA statement and MOOSE guidelines for reporting systematic reviews and meta-analyses of observational studies in Epidemiology’ and spelled out the precise search terms as well as eligibility criteria, including a detailed 11-level graph illustrating the study selection process. We chose to cast a wide net in terms of exposure to cannabis use within studies, entering results as they were reported by the original investigators. We made clear that our estimated summary odds ratio was based on empirical data reported in the source studies and was not adjusted for any confounding factors. Albeit imperfect, our approach reflected accurately the state of the evidence as supported by the epidemiological literature. Secondly, Rogeberg & Elvik assert that the comparable odds ratios reported by us and Asbridge et al. overestimate substantially the true odds ratio of crashes ascribed to marijuana-induced impairment. This criticism, based on results of simulation exercises with sparse data and unsubstantiated assumptions, is unwarranted and misguided. The studies included in our meta-analysis assessed the associations of crash risk with marijuana use as indicated by drug testing or self-reporting, not assumed marijuana-induced impairment. Simulation models are no substitute for empirical evidence. Finally, Rogeberg & Elvik state that they found a data abstraction error regarding the Fergusson & Horwood study 4 in our meta-analysis, ‘where the correct OR was 1.4 rather than the 2.4 extracted by Li et al.’ There is no error in our data abstraction. The Fergusson & Horwood study 4 is the only study included in our meta-analysis that is based on a cohort design. Accordingly, the authors reported their results in rate ratios based on person-years. To include the data from this cohort study in our meta-analysis, we reconstructed the rate ratio data presented in Table 1 of the Fergusson & Horwood paper and converted them into odds ratios. This conversion is necessary, because other studies included in our meta-analysis were based on case–control and cross-sectional designs and reported their findings in odds ratios. Rogeberg & Elvik do not seem to understand the differences between these epidemiological study designs. It is apparent that they mistake the rate ratio reported by Fergusson & Horwood for odds ratio. None.

Drug overdose is a public health crisis in the United States, due in part to the unintended consequences of increases in prescribing of opioid analgesics. Many clinicians evaluate risk markers for opioid-related harms when prescribing opioids for chronic pain; however, more data on predictive risk markers are needed. Risk markers are attributes (modifiable and non-modifiable) that are associated with increased probability of an outcome. This review aims to identify risk markers associated with fatal and non-fatal prescription drug overdose by synthesizing findings in the existing peer-reviewed and grey literature. Eligible cohort, case-control, cross-sectional, and case-cohort studies were reviewed and data were extracted for qualitative and quantitative synthesis.