Primary outcomes from Partner2Lose: A randomized controlled trial to evaluate partner involvement on long-term weight loss.

Background: Partner support is associated with better weight loss outcomes in observational studies, but randomized trials show mixed results for including partners. Unclear is whether teaching communication skills to couples will improve weight loss in index participants. Purpose: To compare the efficacy of a partner-assisted intervention versus participant-only weight management program on long-term weight loss. Methods: This community-based study took place in Madison, WI. Index participants were eligible if they met obesity guideline criteria to receive weight loss counseling, were aged 74 years or younger, lived with a partner, and had no medical contraindications to weight loss; partners were aged 74 years or younger and not underweight. Couples were randomized 1:1 to a partner-assisted or participant-only intervention. Index participants in both arms received an evidence-based weight management program. In the partner-assisted arm, partners attended half of the intervention sessions, and couples were trained in communication skills. The primary outcome was index participant weight at 24 months, assessed by masked personnel; secondary outcomes were 24-month self-reported caloric intake and average daily steps assessed by an activity tracker. General linear mixed models were used to compare group differences in these outcomes following intent-to-treat principles. Results: Among couples assigned to partner-assisted (n=115) or participant-only intervention (n=116), most index participants identified as female (67%) and non-Hispanic White (87%). Average baseline age was 47.27 years (SD 11.51 years) and weight was 106.55 kg (SD 19.41 kg). The estimated mean 24-month weight loss was similar in the partner-assisted (2.66 kg) and participant-only arms (2.89 kg) (estimated mean difference, 0.23 kg [95% CI, -1.58, 2.04 kg]). There were no differences in 24-month average daily caloric intake (50 cal [95% CI: -233, 132 cal]) or steps (806 steps [95% CI: -1675, 64 steps]). The percentage of participants reporting an adverse event with at least possible attribution to the intervention did not differ by arm (partner-assisted: 9%, participant-only, 3%, p=0.11). Conclusions: Partner-assisted and individual weight management interventions led to similar outcomes in index participants. Trial registration: Clinicaltrials.gov NCT03801174.

Spillover effects of gestational age on sibling's literacy.

Adverse health events within families can harm children's development, including their early literacy. Using data from a longitudinal Wisconsin birth cohort, we estimated the spillover effect of younger siblings' gestational ages on older siblings' kindergarten-level literacy. We sampled 20,014 sibling pairs born during 2007-2010 who took Phonological Awareness Literacy Screening-Kindergarten tests during 2012-2016. Exposures were gestational age (completed weeks), preterm birth (gestational age <37 weeks), and very preterm birth (gestational age <32 weeks). We used gain-score regression-a fixed effects strategy-to estimate spillover effect. A one-week increase in younger siblings' gestational age improved the older siblings' test score by 0.011 SD (95% confidence interval: 0.001, 0.021 SD). The estimated spillover effect was larger among siblings whose mothers reported having a high school diploma/equivalent only (0.024 SD; 95% CI: 0.004, 0.044 SD). The finding underscores the networked effects of one individual's early-life health shocks on their family members.

Effect of Pharmacological Treatment of Attention-Deficit/Hyperactivity Disorder on Criminality.

OBJECTIVE: Criminality rates are higher among persons with attention-deficit/hyperactivity disorder (ADHD), and evidence that medication reduces crime is limited. Medication rates between clinics vary widely even within universal health care systems, partly because of providers' treatment preferences. We used this variation to estimate causal effects of pharmacological treatment of ADHD on 4-year criminal outcomes. METHOD: We used Norwegian population-level registry data to identify all unique patients aged 10 to 18 years diagnosed with ADHD between 2009 and 2011 (n = 5,624), their use of ADHD medication, and subsequent criminal charges. An instrumental variable design, exploiting variation in provider preference for ADHD medication between clinics, was used to identify causal effects of ADHD medication on crime among patients on the margin of treatment, that is, patients who receive treatment because of their provider's preference. RESULTS: Criminality was higher in patients with ADHD relative to the general population. Medication preference varied between clinics and strongly affected patients' treatment. Instrumental variable analyses supported a protective effect of pharmacological treatment on violence-related and public-order-related charges with numbers needed to treat of 14 and 8, respectively. There was no evidence for effects on drug-, traffic-, sexual-, or property-related charges. CONCLUSION: This is the first study to demonstrate causal effects of pharmacological treatment of ADHD on some types of crimes in a population-based natural experiment. Pharmacological treatment of ADHD reduced crime related to impulsive-reactive behavior in patients with ADHD on the margin of treatment. No effects were found on crimes requiring criminal intent, conspiracy, and planning. STUDY PREREGISTRATION INFORMATION: The ADHD controversy project: Long-term effects of ADHD medication; https://www.isrctn.com/; 11891971.

Effect of ADHD medication on risk of injuries: a preference-based instrumental variable analysis.

ADHD is associated with an increased risk of injury. Causal evidence for effects of pharmacological treatment on injuries is scarce. We estimated effects of ADHD medication on injuries using variation in provider preference as an instrumental variable (IV). Using Norwegian registry data, we followed 8051 patients who were diagnosed with ADHD aged 5 to 18 between 2009 and 2011 and recorded their ADHD medication and injuries treated in emergency rooms and emergency wards up to 4 years after diagnosis. Persons with ADHD had an increased risk of injuries compared to the general population (RR 1.35; 95% CI: 1.30-1.39), with higher risk in females (RR 1.47; 95% CI: 1.38-1.56) than males (RR 1.23; 95% CI: 1.18-1.28). The between-clinics variation in provider preference for ADHD medication was large and had a considerable impact on patients' treatment status. There was no causal evidence for protective effects of pharmacological treatment on injuries overall for young individuals with ADHD characterized by milder or atypical symptoms. However, there was an apparent effect of pharmacological treatment over time on the risk of injuries treated at emergency wards in this patient group.

Spillover Effects of Prenatal Care Coordination on Older Siblings Beyond the Mother-Infant Dyad.

BACKGROUND: Pregnancy care coordination increases preventive care receipt for mothers and infants. Whether such services affect other family members' health care is unknown. OBJECTIVE: To estimate the spillover effect of maternal exposure to Wisconsin Medicaid's Prenatal Care Coordination (PNCC) program during pregnancy with a younger sibling on the preventive care receipt for an older child. RESEARCH DESIGN: Gain-score regressions-a sibling fixed effects strategy-estimated spillover effects while controlling for unobserved family-level confounders. SUBJECTS: Data came from a longitudinal cohort of linked Wisconsin birth records and Medicaid claims. We sampled 21,332 sibling pairs (one older; one younger) who were born during 2008-2015, who were <4 years apart in age, and whose births were Medicaid-covered. In all, 4773 (22.4%) mothers received PNCC during pregnancy with the younger sibling. MEASURES: The exposure was maternal PNCC receipt during pregnancy with the younger sibling (none; any). The outcome was the older sibling's number of preventive care visits or preventive care services in the younger sibling's first year of life. RESULTS: Overall, maternal exposure to PNCC during pregnancy with the younger sibling did not affect older siblings' preventive care. However, among siblings who were 3 to <4 years apart in age, there was a positive spillover on the older sibling's receipt of care by 0.26 visits (95% CI: 0.11, 0.40 visits) and by 0.34 services (95% CI: 0.12, 0.55 services). CONCLUSION: PNCC may only have spillover effects on siblings' preventive care in selected subpopulations but not in the broader population of Wisconsin families.

Traumatic brain injury, stroke, and epilepsy: A mediation study in a Danish nationwide cohort.

OBJECTIVE: Traumatic brain injury (TBI) and stroke are well-known causes of acquired epilepsy. TBI is also a risk factor for stroke, and injury-induced stroke may indirectly convey a proportion of the epilepsy risk following TBI. We studied the extent to which the effect of TBI on epilepsy operated through intermediary stroke. METHODS: We analyzed a nationwide, matched, register-based cohort of adults ≥ 40 years of age whose first TBI at Danish hospitals was recorded between 2004 and 2016. A matched reference population was sampled for comparison. During follow-up, we recorded all acute strokes. Cox proportional hazard models and the difference method were used to estimate the total and controlled direct effect hazard ratios (HRs) of TBI on epilepsy and the indirect effect HRs of TBI on epilepsy operating through stroke, and to calculate the proportion eliminated. Analyses were stratified by severity of, age at, and time since TBI. RESULTS: We followed 57 900 persons with TBI (48.6% males) from median age 61 years (interquartile range = 51-75), and 561 977 age- and sex-matched references. The total effect of TBI on epilepsy was higher for persons aged 40-59 years (HR = 5.15, 95% confidence interval [CI] = 4.65-5.72) than for persons aged ≥ 60 years (HR = 4.55, 95% CI = 4.19-4.95). In contrast, the indirect effect of TBI mediated by stroke was lower for persons aged 40-59 years (HR = 1.02, 95% CI = 1.02-1.03) than for persons aged ≥ 60 years (HR = 1.05, 95% CI = 1.04-1.06). We estimated 2.3% and 5.6% of the risk of epilepsy after TBI to operate through stroke for these age groups, respectively. SIGNIFICANCE: Less than 6% of the risk of epilepsy following TBI operated through intermediary stroke. However, this mechanism seems to play an increasing role with age and for late onset epilepsies. This warrants further investigation.

Geographical variation in ADHD: do diagnoses reflect symptom levels?

Rates of ADHD diagnosis vary across regions in many countries. However, no prior study has investigated how much within-country geographic variation in ADHD diagnoses is explained by variation in ADHD symptom levels. We examine whether ADHD symptom levels explain variation in ADHD diagnoses among children and adolescents using nationwide survey and register data in Norway. Geographical variation in incidence of ADHD diagnosis was measured using Norwegian registry data from the child and adolescent mental health services for 2011-2016. Geographical variation in ADHD symptom levels in clinics' catchment areas was measured using data from the Norwegian mother, father and child cohort study for 2011-2016 (n = 39,850). Cross-sectional associations between ADHD symptom levels and the incidence of ADHD diagnoses were assessed with fractional response models. Geographical variation in ADHD diagnosis rates is much larger than what can be explained by geographical variation in ADHD symptoms levels. Treatment in the Norwegian child and adolescent mental health services is free, universally available upon referral, and practically without competition from the private sector. Factors beyond health care access and unequal symptom levels seem responsible for the geographical variation in ADHD diagnosis.

The Future Strikes Back: Using Future Treatments to Detect and Reduce Hidden Bias.

Conventional advice discourages controlling for postoutcome variables in regression analysis. By contrast, we show that controlling for commonly available postoutcome (i.e., future) values of the treatment variable can help detect, reduce, and even remove omitted variable bias (unobserved confounding). The premise is that the same unobserved confounder that affects treatment also affects the future value of the treatment. Future treatments thus proxy for the unmeasured confounder, and researchers can exploit these proxy measures productively. We establish several new results: Regarding a commonly assumed data-generating process involving future treatments, we (1) introduce a simple new approach and show that it strictly reduces bias, (2) elaborate on existing approaches and show that they can increase bias, (3) assess the relative merits of alternative approaches, and (4) analyze true state dependence and selection as key challenges. (5) Importantly, we also introduce a new nonparametric test that uses future treatments to detect hidden bias even when future-treatment estimation fails to reduce bias. We illustrate these results empirically with an analysis of the effect of parental income on children's educational attainment.

Estimating sibling spillover effects with unobserved confounding using gain-scores.

PURPOSE: A growing area of research in epidemiology is the identification of health-related sibling spillover effects, or the effect of one individual's exposure on their sibling's outcome. The health within families may be confounded by unobserved factors, rendering identification of sibling spillovers challenging. METHODS: We demonstrate a gain-score (fixed effects) regression method for identifying exposure-to-outcome spillover effects within sibling pairs in linear models. The method identifies the exposure-to-outcome spillover effect if only one sibling's exposure affects the other's outcome, and it identifies the difference between the spillover effects if both siblings' exposures affect the others' outcomes. The method fails with outcome-to-exposure spillover or with outcome-to-outcome spillover. Analytic results, Monte Carlo simulations, and a brief application demonstrate the method and its limitations. RESULTS: We estimate the spillover effect of a child's preterm birth on an older sibling's literacy skills, measured by the Phonological Awareness Literacy Screening-Kindergarten test. We analyze 20,010 sibling pairs from a population-wide, Wisconsin-based (United States) birth cohort. Without covariate adjustment, we estimate that preterm birth modestly decreases an older sibling's test score. CONCLUSIONS: Gain-scores are a promising strategy for identifying exposure-to-outcome spillover effects in sibling pairs while controlling for sibling-invariant unobserved confounding.

Proximity can induce diverse friendships: A large randomized classroom experiment.

Can outside interventions foster socio-culturally diverse friendships? We executed a large field experiment that randomized the seating charts of 182 3rd through 8th grade classrooms (N = 2,966 students) for the duration of one semester. We found that being seated next to each other increased the probability of a mutual friendship from 15% to 22% on average. Furthermore, induced proximity increased the latent propensity toward friendship equally for all students, regardless of students' dyadic similarity with respect to educational achievement, gender, and ethnicity. However, the probability of a manifest friendship increased more among similar than among dissimilar students-a pattern mainly driven by gender. Our findings demonstrate that a scalable light-touch intervention can affect face-to-face networks and foster diverse friendships in groups that already know each other, but they also highlight that transgressing boundaries, especially those defined by gender, remains an uphill battle.

Preference-based instrumental variables in health research rely on important and underreported assumptions: a systematic review.

OBJECTIVE: Preference-based instrumental variables (PP IV) designs can identify causal effects when patients receive treatment due to variation in providers' treatment preference. We offer a systematic review and methodological assessment of PP IV applications in health research. STUDY DESIGN AND SETTING: We included studies that applied PP IV for evaluation of any treatment in any population in health research (PROSPERO: CRD42020165014). We searched within four databases (Medline, Web of Science, ScienceDirect, SpringerLink) and four journals (including full-text and title and abstract sources) between January 1, 1998, and March 5, 2020. We extracted data on areas of applications and methodology, including assumptions using Swanson and Hernan's (2013) guideline. RESULTS: We included 185 of 1087 identified studies. The use of PP IV has increased, being predominantly used for treatment effects in cancer, cardiovascular disease, and mental health. The most common PP IV was treatment variation at the facility-level, followed by physician- and regional-level. Only 12 percent of applications report the four main assumptions for PP IV. Selection on treatment may be a potential issue in 46 percent of studies. CONCLUSION: The assumptions of PP IV are not sufficiently reported in existing work. PP IV-studies should use reporting guidelines.

Causal modelling of variation in clinical practice and long-term outcomes of ADHD using Norwegian registry data: the ADHD controversy project.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is among the most common mental disorders in children and adolescents, and it is a strong risk factor for several adverse psychosocial outcomes over the lifespan. There are large between-country and within-country variations in diagnosis and medication rates. Due to ethical and practical considerations, a few studies have examined the effects of receiving a diagnosis, and there is a lack of research on effects of medication on long-term outcomes.Our project has four aims organised in four work packages: (WP1) To examine the prognosis of ADHD (with and without medication) compared with patients with other psychiatric diagnoses, patients in contact with public sector child and adolescent psychiatric outpatient clinics (without diagnosis) and the general population; (WP2) Examine within-country variation in ADHD diagnoses and medication rates by clinics' catchment area; and(WP3) Identify causal effects of being diagnosed with ADHD and (WP4) ADHD medication on long-term outcomes. METHOD AND ANALYSIS: Our project links several nationwide Norwegian registries. The patient sample is all persons aged 5-18 years that were in contact with public sector child and adolescent psychiatric outpatient clinics in 2009-2011. Our comparative analysis of prognosis will be based on survival analysis and mixed-effects models. Our analysis of variation will apply mixed-effects models and generalised linear models. We have two identification strategies for the effect of being diagnosed with ADHD and of receiving medication on long-term outcomes. Both strategies rely on using preference-based instrumental variables, which in our project are based on provider preferences for ADHD diagnosis and medication. ETHICS AND DISSEMINATION: The project is approved by the Regional Ethics Committee, Norway (REC number 2017/2150/REC south-east D). All papers will be published in open-access journals and results will be presented in national and international conferences. TRIAL REGISTRATION NUMBERS: ISRCTN11573246 and ISRCTN11891971.

Protocol for Partner2Lose: A randomized controlled trial to evaluate partner involvement on long-term weight loss.

BACKGROUND: Behavioral interventions produce clinically significant weight reduction, with many participants regaining weight subsequently. Most interventions focus on an individual, but dietary and physical activity behaviors occur with, or are influenced by, domestic partners. According to interdependence theory, couples who approach behavior change as a problem to be tackled together versus independently are more likely to utilize communal coping processes to promote behavior change. We utilized interdependence theory to develop a partner-assisted intervention to increase long-term weight loss. METHODS: Community-dwelling individuals (index participants) cohabitating with a partner with 1) overweight and at least one obesity-related comorbidity or 2) obesity are randomized to participate in a standard weight management program alone or with their partner. The weight management program involves biweekly, in-person, group sessions focusing on weight loss for six months, followed by three group sessions and nine telephone calls focusing on weight loss maintenance for twelve months. In the partner-assisted arm, partners participate in half of the group sessions and telephone calls. Couples receive training in principles of cognitive behavioral therapy for couples, including sharing thoughts and feelings and joint problem solving, to increase communal coping. The primary outcome is participant weight loss at 24 months, with caloric intake and moderate-intensity physical activity as secondary outcomes. Partner weight and caloric intake will also be analyzed. Mediation analyses will examine the role of interdependence variables and social support. DISCUSSION: This trial will provide knowledge about effective ways to promote long-term weight loss and the role of interdependence constructs in weight loss. Clinical trials identifier: NCT03801174.

Neighborhood Effect Heterogeneity by Family Income and Developmental Period.

Effects of disadvantaged neighborhoods on child educational outcomes likely depend on a family's economic resources and the timing of neighborhood exposures during the course of child development. This study investigates how timing of exposure to disadvantaged neighborhoods during childhood versus adolescence affects high school graduation and whether these effects vary across families with different income levels. It follows 6,137 children in the PSID from childhood through adolescence and overcomes methodological problems associated with the joint endogeneity of neighborhood context and family income by adapting novel counterfactual methods--a structural nested mean model estimated via two-stage regression with residuals--for time-varying treatments and time-varying effect moderators. Results indicate that exposure to disadvantaged neighborhoods, particularly during adolescence, has a strong negative effect on high school graduation and that this negative effect is more severe for children from poor families.

Estimating peer effects in longitudinal dyadic data using instrumental variables.

The identification of causal peer effects (also known as social contagion or induction) from observational data in social networks is challenged by two distinct sources of bias: latent homophily and unobserved confounding. In this paper, we investigate how causal peer effects of traits and behaviors can be identified using genes (or other structurally isomorphic variables) as instrumental variables (IV) in a large set of data generating models with homophily and confounding. We use directed acyclic graphs to represent these models and employ multiple IV strategies and report three main identification results. First, using a single fixed gene (or allele) as an IV will generally fail to identify peer effects if the gene affects past values of the treatment. Second, multiple fixed genes/alleles, or, more promisingly, time-varying gene expression, can identify peer effects if we instrument exclusion violations as well as the focal treatment. Third, we show that IV identification of peer effects remains possible even under multiple complications often regarded as lethal for IV identification of intra-individual effects, such as pleiotropy on observables and unobservables, homophily on past phenotype, past and ongoing homophily on genotype, inter-phenotype peer effects, population stratification, gene expression that is endogenous to past phenotype and past gene expression, and others. We apply our identification results to estimating peer effects of body mass index (BMI) among friends and spouses in the Framingham Heart Study. Results suggest a positive causal peer effect of BMI between friends.

Endogenous Selection Bias: The Problem of Conditioning on a Collider Variable.

Endogenous selection bias is a central problem for causal inference. Recognizing the problem, however, can be difficult in practice. This article introduces a purely graphical way of characterizing endogenous selection bias and of understanding its consequences (Hernán et al. 2004). We use causal graphs (direct acyclic graphs, or DAGs) to highlight that endogenous selection bias stems from conditioning (e.g., controlling, stratifying, or selecting) on a so-called collider variable, i.e., a variable that is itself caused by two other variables, one that is (or is associated with) the treatment and another that is (or is associated with) the outcome. Endogenous selection bias can result from direct conditioning on the outcome variable, a post-outcome variable, a post-treatment variable, and even a pre-treatment variable. We highlight the difference between endogenous selection bias, common-cause confounding, and overcontrol bias and discuss numerous examples from social stratification, cultural sociology, social network analysis, political sociology, social demography, and the sociology of education.

The legacy of disadvantage: multigenerational neighborhood effects on cognitive ability.

This study examines how the neighborhood environments experienced over multiple generations of a family influence children's cognitive ability. Building on recent research showing strong continuity in neighborhood environments across generations of family members, the authors argue for a revised perspective on "neighborhood effects" that considers the ways in which the neighborhood environment in one generation may have a lingering impact on the next generation. To analyze multigenerational effects, the authors use newly developed methods designed to estimate unbiased treatment effects when treatments and confounders vary over time. The results confirm a powerful link between neighborhoods and cognitive ability that extends across generations. A family's exposure to neighborhood poverty across two consecutive generations reduces child cognitive ability by more than half a standard deviation. A formal sensitivity analysis suggests that results are robust to unobserved selection bias.

Neighborhood Effects in Temporal Perspective.

Theory suggests that neighborhood effects depend not only on where individuals live today, but also on where they lived in the past. Previous research, however, usually measured neighborhood context only once and did not account for length of residence, thereby understating the detrimental effects of long-term neighborhood disadvantage. This study investigates the effects of duration of exposure to disadvantaged neighborhoods on high school graduation. It follows 4,154 children in the PSID, measuring neighborhood context once per year from age 1 to 17. The analysis overcomes the problem of dynamic neighborhood selection by adapting novel methods of causal inference for time-varying treatments. In contrast to previous analyses, these methods do not "control away" the effect of neighborhood context operating indirectly through time-varying characteristics of the family, and thus they capture the full impact of a lifetime of neighborhood disadvantage. We find that sustained exposure to disadvantaged neighborhoods has a severe impact on high school graduation that is considerably larger than effects reported in prior research. Growing up in the most (compared to the least) disadvantaged quintile of neighborhoods is estimated to reduce the probability of graduation from 96% to 76% for black children, and from 95% to 87% for nonblack children.

Preliminary evidence regarding the hypothesis that the sex ratio at sexual maturity may affect longevity in men.

In human populations, variation in mate availability has been linked to various biological and social outcomes, but the possible effect of mate availability on health or survival has not been studied. Unbalanced sex ratios are a concern in many parts of the world, and their implications for the health and survival of the constituent individuals warrant careful investigation. We indexed mate availability with contextual sex ratios and investigated the hypothesis that the sex ratio at sexual maturity might be associated with long-term survival for men. Using two unique data sets of 7,683,462 and 4,183 men who were followed for more than 50 years, we found that men who reached their sexual maturity in an environment with higher sex ratios (i.e., higher proportions of reproductively ready men) appeared to suffer higher long-term mortality risks than those in an environment with lower sex ratios. Mate availability at sexual maturity may be linked via several biological and social mechanisms to long-term survival in men.