Geriatric Assessment Impairment Profiles and Mortality in Older Adults with Gastrointestinal Cancers: Latent Class Analysis of the CARE Registry.

BACKGROUND: Many older adults with cancer have ≥2 impairments on geriatric assessment which impacts present and future frailty status, treatment tolerability, and outcomes. Our objective was to identify and describe distinct geriatric assessment impairment classes using latent class analysis (LCA) in older patients with gastrointestinal malignancies and assess 1-year mortality. METHODS: We used the Cancer & Aging Resilience Evaluation (CARE) Study, a registry of older adults (≥60 years) at University of Alabama at Birmingham. The analytic cohort included patients with gastrointestinal malignancies who completed a self-administered geriatric assessment (CARE tool) before chemotherapy and had ≥1 geriatric assessment impairment. Thirteen geriatric assessment impairments were used as indicators in LCA. Resultant classes were described, mortality was estimated, and risk contrasts (differences, hazard ratios) were calculated with 95% confidence intervals. For comparison, estimates were provided for frailty categories (robust, pre-frail, frail) determined from 44 items in the CARE tool. Stratified analyses included high-risk (pancreatic, hepatobiliary, esophageal) vs. low-risk gastrointestinal cancers, and stage (IV vs. I-III). RESULTS: Six geriatric assessment impairment classes were identified: Mild impairment (LC1); Social support impairment (LC2); Weight loss alone (LC3); Impaired, low anxiety/depression (LC4); Impaired with anxiety/depression (LC5); Global impairment (LC6). One-year mortality was 14%, 22%, 29%, 34%, 50% and 50% for LC1-LC6, respectively. For frailty categories, estimates ranged from 18% (robust) to 40% (frail). In stratified analyses, LC4-LC6 consistently had higher mortality estimates compared to LC1. CONCLUSIONS: The 6 geriatric assessment impairment classes showed a wider spread of mortality estimates compared to frailty categories and could be used to identify vulnerable patients and to plan interventions.

Case-control matching on confounders revisited.

Matching by a confounder in a case-control study nearly always produces a control-selection bias that mixes with the confounding to produce a net bias. Previous theoretical work has assumed that control for a single confounder, the matching factor, is sufficient to remove all the confounding and that the confounder-exposure, confounder-outcome and exposure-outcome associations are monotonic. Under these conditions: (a) The net bias is toward the null if the exposure affects the outcome and nil if it does not. (b) If the confounding is away from the null, the selection bias is toward the null. (c) If the confounding is toward the null, the selection bias can be in any direction or even nil. If more than one confounder needs to be controlled to remove all the confounding, the net bias from matching by one of them can be away from the null, whether the exposure affects the outcome or not. An influential heuristic, that matching controls to cases by a variable associated with exposure always brings the marginal exposure distributions of the case and control groups closer together, turns out to be faulty. The implications of matching by confounders in case-control studies are less straightforward than previously thought. Suggestions are offered for advancing the methodologic literature on this topic.

Associations between birth defects with neural crest cell origins and pediatric embryonal tumors.

BACKGROUND: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins. METHODS: With the use of a multistate, registry-linkage cohort study, BDNCO-embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal tumors included neuroblastoma, nephroblastoma, and hepatoblastoma. Potential HR modification (HRM) was investigated by infant sex, maternal race/ethnicity, maternal age, and maternal education. RESULTS: The risk of embryonal tumors among those with BDNCOs was 0.09% (co-occurring n = 105) compared to 0.03% (95% CI, 0.03%-0.04%) among those without a birth defect. Children with BDNCOs were 4.2 times (95% CI, 3.5-5.1 times) as likely to be diagnosed with an embryonal tumor compared to children born without a birth defect. BDNCOs were strongly associated with hepatoblastoma (HR, 16.1; 95% CI, 11.3-22.9), and the HRs for neuroblastoma (3.1; 95% CI, 2.3-4.2) and nephroblastoma (2.9; 95% CI, 1.9-4.4) were elevated. There was no notable HRM by the aforementioned factors. CONCLUSIONS: Children with BDNCOs are more likely to develop embryonal tumors compared to children without a birth defect. Disruptions of shared developmental pathways may contribute to both phenotypes, which could inform future genomic assessments and cancer surveillance strategies of these conditions.

Outcomes after assisted reproductive technology in women with cancer: a systematic review and meta-analysis.

STUDY QUESTION: What are the associations between a history of cancer and outcomes after ART? SUMMARY ANSWER: Compared to women without cancer, on average, women with cancer had a lower return for embryo transfer and a lower likelihood of clinical pregnancy and live birth after ART. WHAT IS KNOWN ALREADY: Small, single-institution studies have suggested that cancer and its treatment may negatively affect ART outcomes. STUDY DESIGN, SIZE, DURATION: We conducted a systematic review with meta-analysis of studies comparing ART outcomes between women with and without cancer. PubMed, Embase and Scopus were searched for original, English-language studies published up to June 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Inclusion criteria required reporting of ART outcomes after controlled ovarian stimulation (COS) among women with a history of cancer compared to women without cancer who used ART for any indication. Outcomes of interest ranged from duration of COS to likelihood of live birth after embryo transfer. Random-effects meta-analysis was used to calculate mean differences and odds ratios (ORs) with 95% CIs and 95% prediction intervals (PIs). We assessed heterogeneity by age-adjustment, referent group indication for ART, study location and among women with breast cancer and women who initiated ART before cancer treatment. We used visual inspection, Egger's test and the trim-and-fill method to assess funnel plot asymmetry. MAIN RESULTS AND THE ROLE OF CHANCE: Of 6094 unique records identified, 42 studies met inclusion criteria, representing a median per study of 58 women with cancer (interquartile range (IQR) = 159) and 114 women without cancer (IQR = 348). Compared to women without cancer, on average, women with cancer had a lower return for embryo transfer (OR: 0.22; 95% CI: 0.07, 0.74; 95% PI: 0.00, 64.98); lower likelihood of clinical pregnancy (OR: 0.51; 95% CI: 0.35, 0.73; 95% PI: 0.19, 1.35); and lower likelihood of live birth (OR: 0.56; 95% CI: 0.38, 0.83; 95% PI: 0.19, 1.69). Substantial among-study heterogeneity was observed for COS duration, gonadotropin dose, cycle cancellation, total oocytes and mature oocytes. Fertilization percentage showed less heterogeneity, but study-specific estimates were imprecise. Similarly, number of embryos showed less heterogeneity, and most studies estimated minimal differences by cancer history. Funnel plot asymmetry was observed for estradiol peak and oocyte maturation percentage. LIMITATIONS, REASONS FOR CAUTION: Appreciable confounding is possible in 11 studies that lacked adequate control for group differences in age, and among-study heterogeneity was observed for most outcomes. Lack of data limited our ability to assess how cancer clinical factors (e.g. cancers other than breast, cancer stage and treatment) and ART cycle characteristics (e.g. fresh versus frozen embryo transfers and use of gestational carriers) may affect outcomes. WIDER IMPLICATIONS OF THE FINDINGS: Women with cancer may be less likely to achieve pregnancy and live birth after embryo transfer. Further examination of reproductive outcomes and sources of heterogeneity among studies is warranted to improve evidence of the expected success of ART after a cancer diagnosis. STUDY FUNDING/COMPETING INTEREST(S): This research was supported in part by R01 CA211093 and P30 ES010126. C.M. was supported by the University of North Carolina Lineberger Cancer Control Education Program (T32 CA057726) and the National Cancer Institute (F31 CA260787). J.A.R.-H. was supported by the National Cancer Institute (K08 CA234333, P30 CA016672). J.A.R.-H. reports receiving consulting fees from Schlesinger Group and Guidepoint. The remaining authors declare no competing interests. REGISTRATION NUMBER: N/A.

The genetics of occupational asthma development among workers exposed to diisocyanates: A systematic literature review with meta-analysis.

Diisocyanates are widely used compounds that pose a safety concern for workers in occupations within the spray-paint, spray-foam insulation, and furniture varnish industries. Epidemiological studies show that only a subset of workers exposed to diisocyanates develop diisocyanate-induced occupational asthma (diisocyanate asthma, DA), indicating that genetic susceptibility may play a role. The purpose of this systematic literature review was to compile and meta-analyze the reported data on genetic susceptibility markers for DA. Three databases (Embase, Pubmed, and Scopus) were searched and 169 non-duplicate publications were identified, of which 22 relevant occupational studies were included in this review. Researchers reported prevalence odds ratios (PORs) for 943 comparisons in 82 different genes/serotypes. Protein network functions for the DA-associated genes from this review include: antigen processing, lymphocyte activation, cytokine production regulation, and response to oxidative stress. Meta-analysis of comparisons between workers with DA and controls was conducted for 23 genetic markers within: CTNNA3, GSTM1, GSTP1, GSTT1, HLA-C, HLA-DQB1, HLA-DR1, HLA-DR3, HLA-DR4, HLA-DR7, and HLA-DR8. These genes code for proteins that are involved in cell-cell adhesions (CTNNA3), glutathione conjugation for xenobiotic metabolism (GST gene family), and immune system response (HLA gene family). The most compelling pooled PORs were for two studies on CTNNA3 (increased DA risk: rs10762058 GG, rs7088181 GG, rs4378283 TT; PORs 4.38-4.97) and three studies on HLA-DR1 (decreased DA risk, POR 0.24). Bioinformatics of the predicted protein pathways for DA shows overlap with biomarker-associated pathways in workers before development of asthma, suggesting overlap in toxicokinetic and toxicodynamic pathways of diisocyanates. The control groups were also compared against each other and differences were negligible. Suggestions for improving future research are also presented. Of the highest importance, the literature was found to be profoundly publication-biased, in which researchers need to report the data for all studied markers regardless of the statistical significance level. We demonstrate the utility of evaluating the overlap in predicted protein pathway functions for identifying more consistency across the reported literature including for asthma research, biomarker research, and in vitro studies. This will serve as an important resource for researchers to use when generating new hypothesis-driven research about diisocyanate toxicology.

A twenty-first century perspective on concepts of modern epidemiology in Ignaz Philipp Semmelweis' work on puerperal sepsis.

We aimed to review Semmelweis's complete work on puerperal sepsis mortality in maternity wards in relation to exposure to cadavers and chlorine handwashing and other factors from the perspective of modern epidemiological methods. We reviewed Semmelweis' complete work and data as published by von Györy 1905 according to current standards. We paid particular attention to Semmelweis's definition of mortality in and of itself, to concepts of modern epidemiology that were already recognizable in Semmelweis's work, and to bias sources. We did several quantitative bias analyses to address selection bias and information bias from outcome measurement error. Semmelweis addressed biases that have become known to modern epidemiology, such as confounding, selection bias and bias from outcome misclassification. Our bias analysis shows that differential loss to follow-up is an unlikely explanation for his results. Bias due to outcome misclassification would only be relevant if misclassification differed between time periods. Confounding by health status was likely but could not be quantitatively addressed. Semmelweis was aware that cause-specific mortality is a function of incidence and prognosis. He reasoned in potential outcome terms to estimate the reduced number of deaths from an intervention. He advanced a hypothesis of clinic overcrowding as a risk factor for puerperal sepsis mortality that turns out to be wrong. Semmelweis' data provide a great pool for illustrating the logic of scientific discovery by use of the numerical method. The explanatory power of his work was strong and Semmelweis was able to refute several previous causal explanations.

Public health critical race praxis at the intersection of traffic stops and injury epidemiology.

BACKGROUND: Law enforcement traffic stops are one of the most common entryways to the US justice system. Conventional frameworks suggest traffic stops promote public safety by reducing dangerous driving practices and non-vehicular crime with little to no collateral damage to individuals and communities. Critical frameworks interrogate these assumptions, identifying significant individual and community harms that disparately impact Black, Indigenous, and People of Color (BIPOC) and low-income communities. METHODS: The Public Health Critical Race Praxis (PHCRP) and multi-level frameworks from community anti-racist training were combined into a structured diagram to guide intervention and research teams in contrasting conventional and critical perspectives on traffic stops. The diagram divides law enforcement and drivers/residents as two separate agent types that interact during traffic stops. These two agent types have different conventional and critical histories, priorities, and perspectives at multiple levels, including individual, interpersonal, institutional, and cultural levels. Conventional solutions (identifying explicitly racist officers, "meet-a-cop" programs, police interaction training for drivers) are born from conventional frameworks (rewarding crime prevention regardless of cost, the war on drugs saves lives, driver behavior perfectionism). While conventional perspectives focus on individual and interpersonal levels, critical perspectives more deeply acknowledge dynamics at institutional and cultural levels. Critical solutions may be hard to discover without critical frameworks, including that law enforcement creates measurable collateral damage and disparate social control effects; neighborhood patrol priorities can be set without community self-determination or accountability and may trump individual and interpersonal dynamics; and the war on drugs is highly racialized and disproportionally enforced through traffic stop programs. CONCLUSIONS: Traffic stop enforcement and crash prevention programs that do not deeply and critically consider these dynamics at multiple levels, not just law enforcement-driver interactions at the individual and interpersonal levels, may be at increased risk of propagating histories of BIPOC discrimination. In contrast, public health and transportation researchers and practitioners engaged in crash and injury prevention strategies that employ law enforcement should critically consider disparate history and impacts of law enforcement in BIPOC communities. PHCRP, anti-racism frameworks, and the included diagram may assist them in organizing critical thinking about research studies, interventions, and impacts.

Timing of Toenail Collection and Concentrations of Metals in Pancreatic Cancer. Evidence Against Disease Progression Bias.

Trace elements such as cadmium, arsenic, zinc or selenium increase or decrease risk of a wide range of human diseases. Their levels in toenails may provide a measure of mid-term intake of trace elements for studies in humans. However, in biologically and clinically aggressive diseases as pancreatic cancer, the progression of the disease could modify such concentrations and produce reverse causation bias. The aim was to analyze the influence of specific time intervals between several clinical events and the collection of toenails upon concentrations of trace elements in patients with pancreatic cancer. Subjects were 118 incident cases of pancreatic adenocarcinoma prospectively recruited in eastern Spain. Toenails were collected at cancer diagnosis, and soon thereafter interviews were conducted. Information on cancer signs and symptoms was obtained from medical records and patient interviews. Levels of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. General linear models adjusting for potential confounders were applied to analyze relations between log concentrations of trace elements and the time intervals, including the interval from first symptom of cancer to toenail collection (iST). Toenail concentrations of the 12 trace elements were weakly or not influenced by the progression of the disease or the diagnostic procedures. Concentrations of aluminum were slightly higher in subjects with a longer iST (age, sex and stage adjusted geometric means: 11.44 vs. 7.75 µg/g for iST > 120 days vs. ≤ 40 days). There was a weak inverse relation of iST with concentrations of zinc and selenium (maximum differences of about 20 and 0.08 µg/g, respectively). Conclusions: concentrations of the trace elements were weakly or not influenced by the development of the disease before toenail collection. Only concentrations of aluminum increased slightly with increasing iST, whereas levels of zinc and selenium decreased weakly. Even in an aggressive disease as pancreatic cancer, toenail concentrations of trace elements may provide a valid measure of mid-term intake of trace elements, unaffected by clinical events and disease progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s12403-021-00436-2.

The Importance of Making Assumptions in Bias Analysis.

Quantitative bias analyses allow researchers to adjust for uncontrolled confounding, given specification of certain bias parameters. When researchers are concerned about unknown confounders, plausible values for these bias parameters will be difficult to specify. Ding and VanderWeele developed bounding factor and E-value approaches that require the user to specify only some of the bias parameters. We describe the mathematical meaning of bounding factors and E-values and the plausibility of these methods in an applied context. We encourage researchers to pay particular attention to the assumption made, when using E-values, that the prevalence of the uncontrolled confounder among the exposed is 100% (or, equivalently, the prevalence of the exposure among those without the confounder is 0%). We contrast methods that attempt to bound biases or effects and alternative approaches such as quantitative bias analysis. We provide an example where failure to make this distinction led to erroneous statements. If the primary concern in an analysis is with known but unmeasured potential confounders, then E-values are not needed and may be misleading. In cases where the concern is with unknown confounders, the E-value assumption of an extreme possible prevalence of the confounder limits its practical utility.

Statistical inference in abstracts of three influential clinical pharmacology journals analyzed using a text-mining algorithm.

AIM: To describe the trend in the prevalence of statistical inference in three influential clinical pharmacology journals METHODS: We applied a computer-based algorithm to abstracts of three clinical pharmacology journals published in 1976 to 2016 to identify statistical inference and its subtypes. Furthermore, we manually reviewed a random sample of 300 articles to access algorithm's performance in finding statistical inference in abstracts and as a screening tool for presence and absence of statistical inference in full text. RESULT: The algorithm identified 59% (13,375/22,516 [mid p 95% CI, 59%-60%]) article abstracts with statistical inference. The percentage of abstracts with statistical inference was similar in 1976 and 2016, 48% (179/377 [mid p 95%CI, 42%-52%]) versus 49% (386/791 [mid p 95%CI, 45%-52%]). Statistical reporting pattern varied among journals. Among abstracts containing any statistical inference in the publications from 1976 to 2016 null-hypothesis significance testing was the most prevalent reported statistical inference. The algorithm had high sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for finding statistical inferences in abstract. While PPV for predicting the statistical inference in full text (including abstract, text, tables and figures) was high, NPV was low. CONCLUSION: Despite journal's editorials and statistical associations' guidelines, most authors focused on testing rather than estimation. In future, a better statistical reporting might be ensured by improving the statistical knowledge of authors and an addition of statistical guides to journals' instruction to authors to the extent that editors would like their statistical inference preferences to be incorporated into submitted manuscripts.

Propensity score trimming mitigates bias due to covariate measurement error in inverse probability of treatment weighted analyses: A plasmode simulation.

BACKGROUND: Inverse probability of treatment weighting (IPTW) may be biased by influential observations, which can occur from misclassification of strong exposure predictors. METHODS: We evaluated bias and precision of IPTW estimators in the presence of a misclassified confounder and assessed the effect of propensity score (PS) trimming. We generated 1000 plasmode cohorts of size N = 10 000, sampled with replacement from 6063 NHANES respondents (1999-2014) age 40 to 79 with labs and no statin use. We simulated statin exposure as a function of demographics and CVD risk factors; and outcomes as a function of 10-year CVD risk score and statin exposure (rate ratio [RR] = 0.5). For 5% of the people in selected populations (eg, all patients, exposed, those with outcomes), we randomly misclassified a confounder that strongly predicted exposure. We fit PS models and estimated RRs using IPTW and 1:1 PS matching, with and without asymmetric trimming. RESULTS: IPTW bias was substantial when misclassification was differential by outcome (RR range: 0.38-0.63) and otherwise minimal (RR range: 0.51-0.53). However, trimming reduced bias for IPTW, nearly eliminating it at 5% trimming (RR range: 0.49-0.52). In one scenario, when the confounder was misclassified for 5% of those with outcomes (0.3% of cohort), untrimmed IPTW was more biased and less precise (RR = 0.37 [SE(logRR) = 0.21]) than matching (RR = 0.50 [SE(logRR) = 0.13]). After 1% trimming, IPTW estimates were unbiased and more precise (RR = 0.49 [SE(logRR) = 0.12]) than matching (RR = 0.51 [SE(logRR) = 0.14]). CONCLUSIONS: Differential misclassification of a strong predictor of exposure resulted in biased and imprecise IPTW estimates. Asymmetric trimming reduced bias, with more precise estimates than matching.

Meta-Analysis and Sparse-Data Bias.

Meta-analyses are undertaken to combine information from a set of studies, often in settings where some of the individual study-specific estimates are based on relatively small study samples. Finite sample bias may occur when maximum likelihood estimates of associations are obtained by fitting logistic regression models to sparse data sets. Here we show that combining information from small studies by undertaking a meta-analytical summary of logistic regression estimates can propagate such sparse-data bias. In simulations, we illustrate 2 challenges encountered in meta-analyses of logistic regression results in settings of sparse data: 1) bias in the summary meta-analytical result and 2) confidence interval coverage that can worsen rather than improve, in terms of being less than nominal, as the number of studies in the meta-analysis increases.

Increased risk of incident dementia following use of anticholinergic agents: A systematic literature review and meta-analysis.

BACKGROUND/RATIONALE: Long-term treatment with anticholinergic agents may increase the risk of cognitive impairment or dementia. This systematic literature review and meta-analysis aimed to assess the impact of ≥3 months of exposure to anticholinergics as a class on the risk of dementia, mild cognitive impairment, and change in cognitive function. The impact of anticholinergic agents specifically used to treat overactive bladder was also evaluated. MATERIALS AND METHODS: A systematic literature review was conducted to identify English language articles evaluating the impact of anticholinergic use for ≥3 months on dementia or cognitive function in adult patients. Databases searched included PubMed, Embase, and the Cochrane Library. Meta-analyses were conducted using random-effects models; 95% confidence intervals (CIs) and 95% prediction intervals (PIs) were reported. RESULTS: A total of 2122 records were identified. Out of those, 21 studies underwent qualitative synthesis and 6 reported endpoints relevant for inclusion in a meta-analysis assessing the risk of incident dementia. The overall rate ratio for incident dementia was 1.46 (95% CI: 1.17-1.81; 95% PI: 0.70-3.04; n = 6). The risk of incident dementia increased with increasing exposure (n = 3). In addition, two studies from the meta-analysis reported an increased risk of dementia with ≥3 months of use of bladder antimuscarinics (adjusted odds ratios ranged from 1.21 to 1.65, depending on exposure category). CONCLUSION: Anticholinergic use for ≥3 months increased the risk of dementia on average by an estimated 46% versus nonuse. This relationship was consistent in studies assessing overactive bladder medications. The risk of developing dementia should be carefully considered in the context of potential benefit before prescribing anticholinergics.

Reasons for hormonal contraceptive use in a cohort of African-American women living in the Detroit area.

OBJECTIVES: To characterize reasons for hormonal contraceptive (HC) use in 1,455 African-American women, aged 23-35 years. STUDY DESIGN: The community-based cohort members were recruited from the Detroit, Michigan area in 2010-2012. HC history was collected via telephone interview. RESULTS: Seven percent reported HC use exclusively for non-contraceptive purposes, and 49% reported non-contraceptive reasons in addition to contraception. Non-contraceptive reasons were reported for all HC types, but were most common for combined oral contraceptives. Primary reasons were for irregular cycles, heavy bleeding, and pain. CONCLUSIONS: In this large cohort of Black women, HC use to treat menstrual problems was common. IMPLICATIONS: HCs were commonly used for both pregnancy prevention and management of menstrual symptoms, but some women used HCs exclusively for menstrual symptom relief. The importance for women of non-contraceptive reasons for HC use may not be adequately recognized, and published data on Black women's reasons for HC use remain limited.

Reweighting Oranges to Apples: Transported RE-LY Trial Versus Nonexperimental Effect Estimates of Anticoagulation in Atrial Fibrillation.

BACKGROUND: Results from trials and nonexperimental studies are often directly compared, with little attention paid to differences between study populations. When target and trial population data are available, accounting for these differences through transporting trial results to target populations of interest provides useful perspective. We aimed to compare two-year risk differences (RDs) for ischemic stroke, mortality, and gastrointestinal bleeding in older adults with atrial fibrillation initiating dabigatran and warfarin when using trial transport methods versus nonexperimental methods. METHODS: We identified Medicare beneficiaries who initiated warfarin or dabigatran from a 20% nationwide sample. To transport treatment effects observed in the randomized evaluation of long-term anticoagulation trial, we applied inverse odds weights to standardize estimates to two Medicare target populations of interest, initiators of: (1) dabigatran and (2) warfarin. Separately, we conducted a nonexperimental study in the Medicare populations using standardized morbidity ratio weighting to control measured confounding. RESULTS: Comparing dabigatran to warfarin, estimated two-year RDs for ischemic stroke were similar with trial transport and nonexperimental methods. However, two-year mortality RDs were closer to the null when using trial transport versus nonexperimental methods for the dabigatran target population (transported RD: -0.57%; nonexperimental RD: -1.9%). Estimated gastrointestinal bleeding RDs from trial transport (dabigatran initiator RD: 1.8%; warfarin initiator RD: 1.9%) appeared more harmful than nonexperimental results (dabigatran initiator RD: 0.14%; warfarin initiator RD: 0.57%). CONCLUSIONS: Differences in study populations can and should be considered quantitatively to ensure results are relevant to populations of interest, particularly when comparing trial with nonexperimental findings. See video abstract: http://links.lww.com/EDE/B703.

Understanding the relationship between features associated with pain-related disability in people with painful temporomandibular disorder: an exploratory structural equation modeling approach.

Pain-related disability is a multifaceted construct that refers to the impact of pain on an individual's capacity to fulfill their self-defined and social roles. This research examined the relationship between clinical, psychological, and pain sensitivity factors and pain-related disability among adults with chronic temporomandibular disorder (TMD). We analyzed data from a cross-sectional community-based sample of 1088 men and women with chronic TMD. We first constructed and tested a measure of pain-related disability (ie, pain impact), including a variable assessing presenteeism, created measurement models of jaw limitation, psychological unease (negative affect, somatic symptoms, and catastrophizing), and experimental pain sensitivity (eg, pressure pain threshold, thermal tolerance, and mechanical pressure pain threshold). Subsequently, latent variables were combined in a structural equation model. Participants (n = 1088) were 18 to 44 years old (mean 29.2, SD ± 7.8) whose chronic TMD had persisted, on average, for 6.9 years (SD ± 6.4). A model of pain-related disability, jaw limitation, and psychological unease was created and refined with exploratory model revisions to account for correlation among variables. Estimation of the final model indicated excellent fit with the data (root-mean-square error of approximation = 0.048, root-mean-square error of approximation 90% confidence interval [CI] 0.043-0.053, comparative fit index = 0.956, standardized root-mean-square residual = 0.040). Jaw functional limitation and psychological unease was strongly related to pain-related disability. Experimental pain sensitivity was removed from our model because of weak direct effect and the burden of performing experimental pain sensitivity testing in a clinical setting. The final model explained 78% of the variance in pain-related disability.

Real-world on-treatment and initial treatment absolute risk differences for dabigatran vs warfarin in older US adults.

PURPOSE: Trials and past observational work compared dabigatran and warfarin in patients with atrial fibrillation, but few reported estimates of absolute harm and benefit under real-world adherence patterns, particularly in older adults that may have differing benefit-harm profiles. We aimed to estimate risk differences for ischemic stroke, death, and gastrointestinal bleeding after initiating dabigatran and warfarin in older adults (a) when patients adhere to treatment and (b) under real-world adherence patterns. METHODS: In a 20% sample of nationwide Medicare claims from 2010 to 2015, we identified beneficiaries aged 66 years and older initiating warfarin and dabigatran. We followed individuals from initiation until death or October 2015 (initial treatment, IT) and separately censored individuals' follow-up after drug switches and gaps in supply (on-treatment, OT). We applied inverse probability of treatment and standardized morbidity ratio weights, as well as inverse probability of censoring weights, to estimate two-year risk differences (RDs) for dabigatran vs warfarin. RESULTS: We identified 10,717 dabigatran and 74,891 warfarin initiators. Weighted OT RDs suggested decreased ischemic stroke risk for dabigatran vs warfarin; IT RDs indicated increased or no change in ischemic stroke risk. Regardless of follow-up approach and weighting strategy, risk of death appeared lower and risk of gastrointestinal bleeding appeared higher when comparing dabigatran vs warfarin. CONCLUSIONS: Dabigatran use was associated with lower risks of mortality and ischemic stroke in routine care when older adults stayed on treatment. IT analyses suggested that these benefits may be diminished under real-world patterns of switching and discontinuation.

Re-prioritizing traffic stops to reduce motor vehicle crash outcomes and racial disparities.

BACKGROUND: Law enforcement traffic stops are one of the most common entryways to the US justice system. Conventional frameworks suggest traffic stops promote public safety by reducing dangerous driving practices and non-vehicular crime. Law enforcement agencies have wide latitude in enforcement, including prioritization of stop types: (1) safety (e.g. moving violation) stops, (2) investigatory stops, or (3) economic (regulatory and equipment) stops. In order to prevent traffic crash fatalities and reduce racial disparities, the police department of Fayetteville, North Carolina significantly re-prioritized safety stops. METHODS: Annual traffic stop, motor vehicle crash, and crime data from 2002 to 2016 were combined to examine intervention (2013-2016) effects. Fayetteville was compared against synthetic control agencies built from 8 similar North Carolina agencies by weighted matching on pre-intervention period trends and comparison against post-intervention trends. RESULTS: On average over the intervention period as compared to synthetic controls, Fayetteville increased both the number of safety stops + 121% (95% confidence interval + 17%, + 318%) and the relative proportion of safety stops (+ 47%). Traffic crash and injury outcomes were reduced, including traffic fatalities - 28% (- 64%, + 43%), injurious crashes - 23% (- 49%, + 16%), and total crashes - 13% (- 48%, + 21%). Disparity measures were reduced, including Black percent of traffic stops - 7% (- 9%, - 5%) and Black vs. White traffic stop rate ratio - 21% (- 29%, - 13%). In contrast to the Ferguson Effect hypothesis, the relative de-prioritization of investigatory stops was not associated with an increase in non-traffic crime outcomes, which were reduced or unchanged, including index crimes - 10% (- 25%, + 8%) and violent crimes - 2% (- 33%, + 43%). Confidence intervals were estimated using a different technique and, given small samples, may be asymmetrical. CONCLUSIONS: The re-prioritization of traffic stop types by law enforcement agencies may have positive public health consequences both for motor vehicle injury and racial disparity outcomes while having little impact on non-traffic crime.