Dogmatists Cannot Learn

We wish to provide some rational in defense of the title of this comment. If we agree that a dogmatist is one whose beliefs cannot be influenced by observations (i.e., data), and we define learning as having your beliefs influenced by observations, then it follows that dogmatists cannot learn. While this statement has been made previously, (p.47) we believe it is useful to expand on this point with a simple example. Indeed, some dangers of dogmatism in epidemiology have been documented, and one does not have to look far for trivial examples of dogmatic statements

The role of the c-statistic in variable selection for propensity score models

The applied literature on propensity scores has often cited the c-statistic as a measure of the ability of the propensity score to control confounding. However, a high c-statistic in the propensity model is neither necessary nor sufficient for control of confounding. Moreover, use of the c-statistic as a guide in constructing propensity scores may result in less overlap in propensity scores between treated and untreated subjects; this may require the analyst to restrict populations for inference. Such restrictions may reduce precision of estimates and change the population to which the estimate applies. Variable selection based on prior subject matter knowledge, empirical observation, and sensitivity analysis is preferable and avoids many of these problems

Treating pediatric anxiety: Initial use of SSRIs and other antianxiety prescription medications

Objective: Multiple pharmacotherapies for treating anxiety disorders exist, including selective serotonin reuptake inhibitors (SSRIs), the recommended first-line pharmacotherapy for pediatric anxiety. We sought to describe initial antianxiety medication use in children and estimate how long antianxiety medications were continued. Methods: In a large commercial claims database, we identified children (3-17 years) initiating prescription antianxiety medication from 2004 to 2014 with a recent anxiety diagnosis (ICD-9-CM = 293.84, 300.0x, 300.2x, 300.3x, 309.21, 309.81, 313.23). We estimated the proportion of children initiating each medication class across the study period and used multivariable regression to evaluate factors associated with initiation with an SSRI. We evaluated treatment length for each initial medication class. Results: Of 84,500 children initiating antianxiety medication, 70% initiated with an SSRI (63% [95% CI, 62%-63%] SSRI alone, 7% [95% CI, 7%-7%] SSRI + another antianxiety medication). Non-SSRI medications initiated included benzodiazepines (8%), non-SSRI antidepressants (7%), hydroxyzine (4%), and atypical antipsychotics (3%). Anxiety disorder, age, provider type, and comorbid diagnoses were associated with initial medication class. The proportion of children refilling their initial medication ranged from 19% (95% CI, 18%-20%) of hydroxyzine initiators and 25% (95% CI, 24%-26%) of benzodiazepine initiators to 81% (95% CI, 80%-81%) of SSRI initiators. Over half (55%, 95% CI, 55%-56%) of SSRI initiators continued SSRI treatment for 6 months. Conclusions: SSRIs are the most commonly used first-line medication for pediatric anxiety disorders, with about half of SSRI initiators continuing treatment for 6 months. Still, a third began therapy on a non-SSRI medication, for which there is limited evidence of effectiveness for pediatric anxiety, and a notable proportion of children initiated with 2 antianxiety medication classes

Psychotherapy claims surrounding pharmacotherapy initiation in children and adolescents with anxiety disorders

Objectives: Psychotherapy is an effective, recommended treatment for pediatric anxiety disorders. Nevertheless, individuals with mental health conditions often do not receive psychotherapy, with variation across provider types. This study sought to examine psychotherapy claims surrounding medication initiation in U.S. children with diagnosed anxiety disorders. Methods: The study cohort included privately insured children (3-17 years) with a diagnosed anxiety disorder initiating a medication to treat anxiety from 2004 to 2014. We examined psychotherapy claims in the 3 months before and 3 months after medication initiation and described children with multiple (2+) psychotherapy claims per 3-month period. Results: Of the 75,024 children initiating a medication for anxiety (median age = 14 years, 58% female), 35% had multiple psychotherapy claims before medication initiation, with variation by age, anxiety disorder, and psychiatric comorbidity and with little change across time. Psychotherapy claims after medication initiation varied by whether the child had prior psychotherapy: 80% in children with prior psychotherapy and 30% in children without prior psychotherapy claims (44% of children diagnosed by a psychiatrist, 21% of children diagnosed by a pediatrician). Conclusion: Many privately insured children do not have claims for psychotherapy before or after pharmacotherapy initiation for anxiety. Findings can inform future research and efforts to ultimately increase appropriate psychotherapy utilization in children with anxiety disorders

Incidence of mental health hospitalizations, treated self-harm, and emergency room visits following new anxiety disorder diagnoses in privately insured U.S. children

Background: Anxiety disorders are one of the most common mental illnesses in children and associated with high healthcare utilization. We aimed to estimate 2-year cumulative incidence of mental health–related hospitalizations, treated self-harm, and emergency room (ER) visits in children newly diagnosed with anxiety disorders and, for context, in children without anxiety disorders. Methods: We identified commercially insured treatment naïve children (3–17 years) with a new office-based anxiety disorder diagnosis (ICD-9-CM) from 2005–2014 in the MarketScan claims database. We followed children for up to 2 years after diagnosis for the first of each event: mental health–related hospitalization, inpatient, treated self-harm, and ER visits (any, anxiety-related, injury-related). Children without anxiety diagnoses were included as comparators, matched on age, sex, date, and region. We estimated cumulative incidence of each event using Kaplan–Meier analysis. Results: From 2005–2014, we identified 198,450 children with a new anxiety diagnosis. One-year after anxiety diagnosis, 2.0% of children had a mental health–related hospitalization, 0.08% inpatient, treated self-harm, 1.4% anxiety-related ER visit, and 20% any ER visit; incidence was highest in older children with baseline comorbid depression. One-year cumulative incidence of each event was lower in the comparison cohort without anxiety (e.g., mental health–related hospitalizations = 0.5%, treated self-harm = 0.01%, and ER visits = 13%). Conclusions: Given the prevalence of anxiety disorders, 2-year incidence estimates translate to a significant number of children experiencing each event. Our findings offer caregivers, providers, and patients information to better understand the burden of anxiety disorders and can help anticipate healthcare utilization and inform efforts to prevent these serious events

Safety of dynamic intravenous iron administration strategies in hemodialysis patients

Background and objectives Intravenous iron therapy for chronic anemia management is largely driven by dosing protocols that differ in intensity with respect to dosing approach (i.e., dose, frequency, and duration). Little is known about the safety of these protocols. Design, setting, participants, & measurements Using clinical data from a large United States dialysis provider linked to health care utilization data from Medicare, we constructed a cohort of patients with ESKD aged ≥65 years who initiated and continued center-based hemodialysis for ≥90 days between 2009 and 2012, and initiated at least one of the five common intravenous iron administration strategies; ranked by intensity (the amount of iron given at moderate-to-high iron indices), the order of strategies was 3 (least intensive), 2 (less intensive), 1 (reference), 4 (more intensive), and 5 (most intensive). We estimated the effect of continuous exposure to these strategies on cumulative risks of mortality and infection-related events with dynamic Cox marginal structural models. Results Of 13,249 eligible patients, 1320 (10%) died and 1627 (12%) had one or more infection-related events during the 4-month follow-up. The most and least commonly initiated strategy was strategy 2 and 5, respectively. Compared with the reference strategy 1, more intensive strategies (4 and 5) demonstrated a higher risk of all-cause mortality (e.g., most intensive strategy 5: 60-day risk difference: 1.3%; 95% confidence interval [95% CI], 0.8% to 2.1%; 120-day risk difference: 3.1%; 95% CI, 1.0% to 5.6%). Similarly, higher risks were observed for infection-related morbidity and mortality among more intensive strategies (e.g., strategy 5: 60-day risk difference: 1.8%; 95% CI, 1.2% to 2.6%; 120-day risk difference: 4.3%; 95% CI, 2.2% to 6.8%). Less intensive strategies (2 and 3) demonstrated lower risks of all-cause mortality and infection-related events. Conclusions Among dialysis patients surviving 90 days, subsequent intravenous iron administration strategies promoting more intensive iron treatment at moderate-to-high iron indices levels are associated with higher risks of mortality and infection-related events

Left truncation bias to explain the protective effect of smoking on preeclampsia potential, but how plausible?

Background: An inverse association between maternal smoking and preeclampsia has been frequently observed in epidemiologic studies for several decades. In the May 2015 issue of this journal, Lisonkova and Joseph described a simulation study suggesting that bias from left truncation might explain the inverse association. The simulations were based on strong assumptions regarding the underlying mechanisms through which bias might occur. Methods: To examine the sensitivity of the previous authors' conclusions to these assumptions, we constructed a new Monte Carlo simulation using published estimates to frame our data-generating parameters. We estimated the association between smoking and preeclampsia across a range of scenarios that incorporated abnormal placentation and early pregnancy loss. Results: Our results confirmed that the previous authors' findings are highly dependent on assumptions regarding the strength of association between abnormal placentation and preeclampsia. Thus, the bias they described may be less pronounced than was suggested. Conclusions: Under empirically derived constraints of these critical assumptions, left truncation does not appear to fully explain the inverse association between smoking and preeclampsia. Furthermore, when considering processes in which left truncation may result from the exposure, it is important to precisely describe the target population and parameter of interest before assessing potential bias. We comment on the specification of a meaningful target population when assessing maternal smoking and preeclampsia as a public health issue. We describe considerations for defining a target population in studies of perinatal exposures when those exposures cause competing events (e.g., early pregnancy loss) for primary outcomes of interest

Examining Parental Medication Adherence as a Predictor of Child Medication Adherence in Pediatric Anxiety Disorders

Background: Selective serotonin reuptake inhibitors (SSRIs) are the recommended first-line pharmacotherapy for pediatric anxiety disorders but adherence remains difficult to predict. Objectives: To estimate SSRI adherence in children with anxiety disorders and determine if prior parental medication adherence is predictive of child high SSRI adherence. Methods: We identified children (3-17 y) initiating SSRI treatment after an anxiety disorder diagnosis in a commercial claims database (2005-2014). We evaluated parent SSRI, statin, and antihypertensive adherence [6-mo proportion days covered (PDC), high adherence=PDC≥0.80] in the year before child SSRI initiation. We estimated risk differences (RD) of child high SSRI adherence (6-mo PDC) stratified by parent adherence and multivariable risk ratios using modified Poisson regression. We estimated change in c-statistic and risk reclassification when adding parent-level covariates with child-level covariates to predict child adherence. Results: In 70,979 children with an anxiety disorder (59%=female, 14=median age), the mean 6-month SSRI PDC was 0.72, with variation by anxiety disorder. Overall 64% of children had high adherence if their parent had high SSRI adherence versus 53% of children with parents with low SSRI adherence (RD, 12%; multivariable risk ratios, 1.17; 95% confidence interval, 1.14-1.20). Findings were similar for parent statin (RD=10%) and antihypertensive adherence (RD=8%) and when stratified by child age and parent sex. There was minor improvement in risk reclassification and the c-statistic after adding parent adherence and parent-level covariates. Conclusions: Parental medication adherence could help providers identify children at risk of nonadherence to inform the treatment decision, reduce unnecessary medication switches, and lead to broader effective interventions

Analytic strategies to adjust confounding using exposure propensity scores and disease risk scores: Nonsteroidal antiinflammatory drugs and short-term mortality in the elderly

Little is known about optimal application and behavior of exposure propensity scores (EPS) in small studies. In a cohort of 103,133 elderly Medicaid beneficiaries in New Jersey, the effect of nonsteroidal antiinflammatory drug use on 1-year all-cause mortality was assessed (1995-1997) based on the assumption that there is no protective effect and that the preponderance of any observed effect would be confounded. To study the comparative behavior of EPS, disease risk scores, and "conventional" disease models, the authors randomly resampled 1,000 subcohorts of 10,000, 1,000, and 500 persons. The number of variables was limited in disease models, but not EPS and disease risk scores. Estimated EPS were used to adjust for confounding by matching, inverse probability of treatment weighting, stratification, and modeling. The crude rate ratio of death was 0.68 for users of nonsteroidal antiinflammatory drugs. "Conventional" adjustment resulted in a rate ratio of 0.80 (95% confidence interval: 0.77, 0.84). The rate ratio closest to 1 (0.85) was achieved by inverse probability of treatment weighting (95% confidence interval: 0.82, 0.88). With decreasing study size, estimates remained further from the null value, which was most pronounced for inverse probability of treatment weighting (n = 500: rate ratio = 0.72, 95% confidence interval: 0.26, 1.68). In this setting, analytic strategies using EPS or disease risk scores were not generally superior to "conventional" models. Various ways to use EPS and disease risk scores behaved differently with smaller study size

Effect of Initiating Cardiac Rehabilitation after Myocardial Infarction on Subsequent Hospitalization in Older Adults

Purpose: Outpatient cardiac rehabilitation (CR) participation after myocardial infarction (MI) reduces all-cause mortality; however, less is known about effects of CR on post-MI hospitalization. The study objective was to investigate effects of CR on hospitalization following acute MI among older adults. Methods: Medicare beneficiaries aged 65 to 88 yr hospitalized in 2008 with acute MI, who survived at least 60 d post-discharge, had a revascularization procedure during index hospitalization, and did not have an MI in previous year were eligible for this study. CR initiation was assessed in the 60 d post-discharge. Competing risk survival analysis was used to estimate the proportion of discharged beneficiaries hospitalized between the end of 60-d exposure window and December 31, 2009, treating death as a competing event. Results: The mean ± SD age of 32 851 Medicare beneficiaries meeting study criteria was 75 ± 6.0 yr, approximately half were male (52%), and the majority were white (88%). In this study, 21% of beneficiaries initiated CR within the exposure window. At 1 yr post-discharge, CR initiators had a lower risk of recurrent MI (4.2% [95% CI, 3.5-5.1]), cardiovascular (15.7% [95% CI, 14.3-17.2]), and all-cause (30.4% [95% CI, 28.8-32.1]) hospitalization than noninitiators (5.2% [95% CI, 5.0-5.5]; 18.0% [95% CI, 17.6-18.4]; and 33.2% [95% CI, 32.5-33.8], respectively). There was no difference in fracture risk (negative control outcome). Conclusions: This study provides evidence that CR can reduce the 1-yr risk of cardiovascular and all-cause hospital admissions in Medicare aged MI survivors