MRI-derived Articular Cartilage Strains Predict Patient-Reported Outcomes Six Months Post Anterior Cruciate Ligament Reconstruction.

Key terms: Multicontrast and Multiparametric, Magnetic Resonance Imaging, Osteoarthritis, Functional Biomechanical Imaging, Knee Joint Degeneration What is known about the subject: dualMRI has been used to quantify strains in a healthy human population in vivo and in cartilage explant models. Previously, OA severity, as determined by histology, has been positively correlated to increased shear and transverse strains in cartilage explants. What this study adds to existing knowledge: This is the first in vivo use of dualMRI in a participant demographic post-ACL reconstruction and at risk for developing osteoarthritis. This study shows that dualMRI-derived strains are more significantly correlated with patient-reported outcomes than any MRI relaxometry metric. Background: Anterior cruciate ligament (ACL) injuries lead to an increased risk of osteoarthritis, characterized by altered cartilage tissue structure and function. Displacements under applied loading by magnetic resonance imaging (dualMRI) is a novel MRI technique that can be used to quantify mechanical strain in cartilage while undergoing a physiological load. Purpose: To determine if strains derived by dualMRI and relaxometry measures correlate with patient-reported outcomes at six months post unilateral ACL reconstruction. Study Design: Cohort study. Methods: Quantitative MRI (T2, T2*, T1ρ) measurements and transverse, axial, and shear strains were quantified in the medial articular tibiofemoral cartilage of 35 participants at six-months post unilateral ACL reconstruction. The relationships between patient-reported outcomes (WOMAC, KOOS, MARS) and all qMRI relaxation times were quantified using general linear mixed-effects models. A combined best-fit multicontrast MRI model was then developed using backwards regression to determine the patient features and MRI metrics that are most predictive of patient-reported outcome scores. Results: Higher femoral strains were significantly correlated with worse patient-reported functional outcomes. Femoral shear and transverse strains were positively correlated with six-month KOOS and WOMAC scores, after controlling for covariates. No relaxometry measures were correlated with patient-reported outcome scores. We identified the best-fit model for predicting WOMAC score using multiple MRI measures and patient-specific information, including sex, age, graft type, femoral transverse strain, femoral axial strain, and femoral shear strain. The best-fit model significantly predicted WOMAC score (p<0.001) better than any one individual MRI metric alone. When we regressed the model-predicted WOMAC scores against the patient-reported WOMAC scores, we found that our model achieved a goodness of fit exceeding 0.52. Conclusions: This work presents the first use of dualMRI in vivo in a cohort of participants at risk for developing osteoarthritis. Our results indicate that both shear and transverse strains are highly correlated with patient-reported outcome severity could serve as novel imaging biomarkers to predict the development of osteoarthritis.

Neighbourhood socioeconomic position, prenatal care and fulfilment of postpartum permanent contraception: Findings from a multisite cohort study.

Introduction: Research suggests neighbourhood socioeconomic vulnerability is negatively associated with women's likelihood of receiving adequate prenatal care and achieving desired postpartum permanent contraception. Receiving adequate prenatal care is linked to a greater likelihood of achieving desired permanent contraception, and access to such care may be critical for women with Medicaid insurance given that the federally mandated Medicaid sterilization consent form must be signed at least 30 days before the procedure. We examined whether adequacy of prenatal care mediates the relationship between neighbourhood socioeconomic position and postpartum permanent contraception fulfilment, and examined moderation of relationships by insurance type. Methods: This secondary analysis of a retrospective cohort study examined 3012 Medicaid or privately insured individuals whose contraceptive plan at postpartum discharge was permanent contraception. Path analysis estimated relationships between neighbourhood socioeconomic position (economic hardship and inequality, financial strength and educational attainment) and permanent contraception fulfilment by hospital discharge, directly and indirectly through adequacy of prenatal care. Multigroup testing examined moderation by insurance type. Results: After adjusting for age, parity, weeks of gestation at delivery, mode of delivery, race, ethnicity, marital status and body mass index, having adequate prenatal care predicted achieving desired sterilization at discharge (ß = 0.065, 95% confidence interval [CI]: 0.011, 0.117). Living in neighbourhoods with less economic hardship (indirect effect -0.007, 95% CI: -0.015, -0.001), less financial strength (indirect effect -0.016, 95% CI: -0.030, -0.002) and greater educational attainment (indirect effect 0.012, 95% CI: 0.002, 0.023) predicted adequate prenatal care, in turn predicting achievement of permanent contraception by discharge. Insurance status conditioned some of these relationships. Conclusion: Contact with the healthcare system via prenatal care may be a mechanism by which neighbourhood socioeconomic disadvantage affects permanent contraception fulfilment, particularly for patients with Medicaid. To promote reproductive autonomy and healthcare equity, future inquiry and policy might closely examine how neighbourhood social and economic characteristics interact with Medicaid mandates.

The design and implementation of a multi-center, pragmatic, individual-level randomized controlled trial to evaluate Baby2Home, an mHealth intervention to support new parents.

BACKGROUND: Becoming a parent is a transformative experience requiring multiple transitions, including the need to navigate several components of health care, manage any mental health issues, and develop and sustain an approach to infant feeding. Baby2Home (B2H) is a digital intervention built on the collaborative care model (CCM) designed to support families during these transitions to parenthood. OBJECTIVES: We aim to investigate the effects of B2H on preventive healthcare utilization for the family unit and patient-reported outcomes (PROs) trajectories with a focus on mental health. We also aim to evaluate heterogeneity in treatment effects across social determinants of health including self-reported race and ethnicity and household income. We hypothesize that B2H will lead to optimized healthcare utilization, improved PROs trajectories, and reduced racial, ethnic, and income-based disparities in these outcomes as compared to usual care. METHODS: B2H is a multi-center, pragmatic, individual-level randomized controlled trial. We will enroll 640 families who will be randomized to: [1] B2H + usual care, or [2] usual care alone. Preventive healthcare utilization is self-reported and confirmed from medical records and includes attendance at the postpartum visit, contraception use, depression screening, vaccine uptake, well-baby visit attendance, and breastfeeding at 6 months. PROs trajectories will be analyzed after collection at 1 month, 2 months, 4 months, 6 months and 12 months. PROs include assessments of stress, depression, anxiety, self-efficacy and relationship health. IMPLICATIONS: If B2H proves effective, it would provide a scalable digital intervention to improve care for families throughout the transition to new parenthood.

Nurturing transformative local structures of multisectoral collaboration for primary health care: qualitative insights from select states in India.

BACKGROUND: Multisectoral collaboration is essential for advancing primary health care (PHC). In low- and middle-income countries (LMICs), limited institutional capacities, governance issues, and inadequate stakeholder engagement impede multisectoral collaboration. India faces similar challenges, especially at the meso-level (districts and subdistricts). Owing to its dependence on context, and insufficient evidence, understanding "How" to improve multisectoral collaboration remains challenging. This study aims to elicit specific recommendations to strengthen meso-level stewardship in India for multisectoral collaboration. The findings from this study may offer lessons for other LMICs. METHODS: Using purposive, maximum variation sampling, the study team conducted semi-structured interviews with 20 diverse participants, including policymakers, implementers, development agency representatives, and academics experienced in multisectoral initiatives. The interviews delved into participants' experiences, the current situation, enablers, and recommendations for enhancing stakeholder engagement and capacities at the meso-level for multisectoral collaboration. RESULTS: Context and power are critical elements to consider in fostering effective collaboration. Multisectoral collaboration was particularly successful in three distinct governance contexts: the social-democratic context as in Kerala, the social governance context in Chhattisgarh, and the public health governance context in Tamil Nadu. Adequate health system input and timely guidance instil confidence among local implementers to collaborate. While power plays a role through local leadership's influence in setting agendas, convening stakeholders, and ensuring accountability. To nurture transformative local leaders for collaboration, holistic, equity-driven, community-informed approaches are essential. The study participants proposed several concrete steps: at the state level, establish "central management units" for supervising local implementers and ensuring bottom-up feedback; at the district level, rationalise committees and assign deliverables to stakeholders; and at the block level, expand convergence structures and involve local self-governments. Development partners can support data-driven priority setting, but local implementers with contextual familiarity should develop decentralised plans collaboratively, articulating rationales, activities, and resources. Finally, innovative training programs are required at all levels, fostering humility, motivation, equity awareness, leadership, problem- solving, and data use proficiency. CONCLUSION: This study offers multiple solutions to enhance local implementers' engagement in multisectoral efforts, advocating for the development, piloting, and evaluation of innovative approaches such as the block convergence model, locally-led collaboration efforts, and novel training methods for local implementers.

NLRP3 and AIM2 inflammasomes exacerbate the pathogenic Th17 cell response to eggs of the helminth Schistosoma mansoni.

Infection with the helminth Schistosoma mansoni can cause exacerbated morbidity and mortality via a pathogenic host CD4 T cell-mediated immune response directed against parasite egg antigens, with T helper (Th) 17 cells playing a major role in the development of severe granulomatous hepatic immunopathology. The role of inflammasomes in intensifying disease has been reported; however, neither the types of caspases and inflammasomes involved, nor their impact on the Th17 response are known. Here we show that enhanced egg-induced IL-1ß secretion and pyroptotic cell death required both caspase-1 and caspase-8 as well as NLRP3 and AIM2 inflammasome activation. Schistosome genomic DNA activated AIM2, whereas reactive oxygen species, potassium efflux and cathepsin B, were the major activators of NLRP3. NLRP3 and AIM2 deficiency led to a significant reduction in pathogenic Th17 responses, suggesting their crucial and non-redundant role in promoting inflammation. Additionally, we show that NLRP3- and AIM2-induced IL-1ß suppressed IL-4 and protective Type I IFN (IFN-I) production, which further enhanced inflammation. IFN-I signaling also curbed inflammasome- mediated IL-1ß production suggesting that these two antagonistic pathways shape the severity of disease. Lastly, Gasdermin D (Gsdmd) deficiency resulted in a marked decrease in egg-induced granulomatous inflammation. Our findings establish NLRP3/AIM2-Gsdmd axis as a central inducer of pathogenic Th17 responses which is counteracted by IFN-I pathway in schistosomiasis.

Engineering the cellulolytic bacterium, Clostridium thermocellum, to co-utilize hemicellulose.

Consolidated bioprocessing (CBP) of lignocellulosic biomass holds promise to realize economic production of second-generation biofuels/chemicals, and Clostridium thermocellum is a leading candidate for CBP due to it being one of the fastest degraders of crystalline cellulose and lignocellulosic biomass. However, CBP by C. thermocellum is approached with co-cultures, because C. thermocellum does not utilize hemicellulose. When compared with a single-species fermentation, the co-culture system introduces unnecessary process complexity that may compromise process robustness. In this study, we engineered C. thermocellum to co-utilize hemicellulose without the need for co-culture. By evolving our previously engineered xylose-utilizing strain in xylose, an evolved clonal isolate (KJC19-9) was obtained and showed improved specific growth rate on xylose by ∼3-fold and displayed comparable growth to a minimally engineered strain grown on the bacteria's naturally preferred substrate, cellobiose. To enable full xylan deconstruction to xylose, we recombinantly expressed three different ß-xylosidase enzymes originating from Thermoanaerobacterium saccharolyticum into KJC19-9 and demonstrated growth on xylan with one of the enzymes. This recombinant strain was capable of co-utilizing cellulose and xylan simultaneously, and we integrated the ß-xylosidase gene into the KJC19-9 genome, creating the KJCBXint strain. The strain, KJC19-9, consumed monomeric xylose but accumulated xylobiose when grown on pretreated corn stover, whereas the final KJCBXint strain showed significantly greater deconstruction of xylan and xylobiose. This is the first reported C. thermocellum strain capable of degrading and assimilating hemicellulose polysaccharide while retaining its cellulolytic capabilities, unlocking significant potential for CBP in advancing the bioeconomy.

The association between postpartum depressive symptoms and contraception.

BACKGROUND: Postpartum depression affects 10% to 20% of birthing people and is associated with changes in healthcare use. Little is known about the association between postpartum depressive symptoms and choice to use contraception; however, both untreated or undertreated depression and short interpregnancy intervals pose substantial perinatal health risks. OBJECTIVE: This study aimed to evaluate whether postpartum depressive symptoms are associated with changes in decisions to use any method of contraception. STUDY DESIGN: This retrospective cohort study included birthing people who delivered between 2017 and 2022 and were referred to a collaborative care program for mental healthcare. Through this program, birthing people with mental health conditions have access to specialized perinatal mental healthcare and prospective symptom monitoring via a patient registry. Postpartum depressive symptoms are assessed via the Patient Health Questionnaire-9, and scores were stratified by severity according to clinical cutoffs. Contraceptive method choice was determined by documentation in the electronic health record and dichotomized as "none" if the participant declined all forms of contraception both at delivery and at the postpartum visit. Bivariable and multivariable analyses were performed. RESULTS: Of the 1871 participants that met the inclusion criteria, 160 (8.5%) had postpartum Patient Health Questionnaire-9 scores of >14, representing moderately severe or worse depressive symptoms, and 43 (2.3%) had severe (Patient Health Questionnaire-9 of >19) depressive symptoms. Birthing people with higher Patient Health Questionnaire-9 scores were more likely to have medical comorbidities; to have a higher body mass index; to self-identify as Black, Native Hawaiian or Pacific Islander, or Hispanic or Latina; and to have a preterm delivery and less likely to be married or nulliparous than those with Patient Health Questionnaire-9 scores of ≤14. There was no difference in any other sociodemographic or clinical characteristics. The choice to use any contraceptive method decreased with increasing depressive symptoms in bivariable and multivariable analyses, reaching statistical significance in birthing people with severe depressive symptoms (adjusted odds ratio, 2.92; 95% confidence interval, 1.46-5.84). CONCLUSION: Severe perinatal depressive symptoms are associated with a declination of any form of postpartum contraception. This finding becomes increasingly relevant as abortion access continues to be threatened across the United States, compounding the potential effect of opting not to use contraception.

Immunity on ice: The impact of methamphetamine on peripheral immunity.

Methamphetamine (METH) regulation of the dopamine transporter (DAT) and central nervous system (CNS) dopamine transmission have been extensively studied. However, our understanding of how METH influences neuroimmune communication and innate and adaptive immunity is still developing. Recent studies have shed light on the bidirectional communication between the CNS and the peripheral immune system. They have established a link between CNS dopamine levels, dopamine neuronal activity, and peripheral immunity. Akin to dopamine neurons in the CNS, a majority of peripheral immune cells also express DAT, implying that in addition to their effect in the CNS, DAT ligands such as methamphetamine may have a role in modulating peripheral immunity. For example, by directly influencing DAT-expressing peripheral immune cells and thus peripheral immunity, METH can trigger a feed-forward cascade that impacts the bidirectional communication between the CNS and peripheral immune system. In this review, we aim to discuss the current understanding of how METH modulates both innate and adaptive immunity and identify areas where knowledge gaps exist. These gaps will then be considered in guiding future research directions.

Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge.

Ever-evolving SARS-CoV-2 variants of concern (VOCs) have diminished the effectiveness of therapeutic antibodies and vaccines. Developing a coronavirus vaccine that offers a greater breadth of protection against current and future VOCs would eliminate the need to reformulate COVID-19 vaccines. Here, we rationally engineer the sequence-conserved S2 subunit of the SARS-CoV-2 spike protein and characterize the resulting S2-only antigens. Structural studies demonstrate that the introduction of interprotomer disulfide bonds can lock S2 in prefusion trimers, although the apex samples a continuum of conformations between open and closed states. Immunization with prefusion-stabilized S2 constructs elicits broadly neutralizing responses against several sarbecoviruses and protects female BALB/c mice from mouse-adapted SARS-CoV-2 lethal challenge and partially protects female BALB/c mice from mouse-adapted SARS-CoV lethal challenge. These engineering and immunogenicity results should inform the development of next-generation pan-coronavirus therapeutics and vaccines.

A qualitative study to determine perspectives of clinicians providing telehealth opioid use disorder treatment.

BACKGROUND: Telehealth-only medication for opioid use disorder (teleMOUD) treatment with buprenorphine was first made possible in the United States during the COVID-19 Public Health Emergency. As a result, several large provider groups now treat opioid use disorder (OUD) patients in nearly every state using telehealth. This study evaluates the perceptions and experiences of providers working almost exclusively in a teleMOUD program. METHODS: Qualitative interviews were conducted with 18 providers (physicians, physician assistants and nurse practitioners) using a semi-structured interview guide. Interviews were recorded, transcribed and reviewed. After reviewing the transcripts, a codebook was developed, interviews were coded, and coded excerpts were analyzed for key themes. RESULTS: Inductive codes were used to organize provider responses and included patient-level codes, provider-level codes, and telehealth environment codes. For providers, there are benefits of a flexible and less stressful working environment, which contribute to a higher quality of life. Providers also expressed mixed feelings regarding professional identity and focusing specifically on OUD, differences in relationships with colleagues, and challenges related to policy changes and ambiguities. For patients, providers perceived greater access, less stigma, more convenience, and a unique provider-patient relationship compared to in-person treatment. These themes affect providers and patients on multiple levels of the social-ecological model. CONCLUSIONS: Multiple themes emerged in this study. This work is amongst the first to describe perspectives of providers working in the nascent teleMOUD setting, and can inform initiatives to improve provider wellness, provider retention, and quality of care for patients treated in the setting.

Opioid use disorder (OUD) and treatment for opioid problems among OUD symptom subtypes in individuals misusing opioids.

Background: In 2021, approximately 60 million individuals worldwide and 9 million individuals in the United States (US) reported opioid misuse. In the US, 2.5 million have OUD, of which only about a third receive any substance abuse treatment. OUD is often regarded as a monolithic disorder but different opioid problem subtypes may exist beyond DSM-IV/5 criteria. Understanding the characteristics of these subtypes could be useful for informing treatment and intervention strategies. Methods: Latent class analysis was used to identify OUD symptom subtypes among persons in the US who reported misusing prescription opioids or heroin in the 2015-2018 National Survey on Drug Use and Health (n=10,928). Regression analyses were utilized to determine associations between class membership and treatment receipt, as well as demographic characteristics and other comorbid conditions. Results: Five classes were identified with unique OUD symptom patterns: Class 1: Asymptomatic (71.6%), Class 2: Tolerance/Time (14.5%), Class 3: Loss of Control/Pharmacological (LOC/Pharmacol) (5.7%), Class 4: Social Impairment (2.6%), and Class 5: Pervasive (5.6%). Nearly all persons in the LOC/Pharmacol, Social Impairment, and Pervasive classes met criteria for OUD (98-100%); however, they differed in receipt of past-year treatment for substance use (28%, 28%, 49%, respectively). Age, race, education, insurance status, and criminal activity were also associated with treatment receipt. Conclusions: There were considerable differences in OUD symptom patterns and substance use treatment among individuals who misused opioids. The findings indicate a substantial unmet need for OUD treatment and point to patterns of heterogeneity within OUD that can inform development of treatment programs.

Documentation of prenatal contraceptive counseling and fulfillment of permanent contraception: a retrospective cohort study.

BACKGROUND: Barriers exist for the provision of surgery for permanent contraception in the postpartum period. Prenatal counseling has been associated with increased rates of fulfillment of desired postpartum contraception in general, although it is unclear if there is impact on permanent contraception specifically. Thus, we aimed to investigate the association between initial timing for prenatal documentation of a contraceptive plan for permanent contraception and fulfillment of postpartum contraception for those receiving counseling. METHODS: This is a planned secondary analysis of a multi-site cohort study of patients with documented desire for permanent contraception at the time of delivery at four hospitals located in Alabama, California, Illinois, and Ohio over a two-year study period. Our primary exposure was initial timing of documented plan for contraception (first, second, or third trimester, or during delivery hospitalization). We used univariate and multivariable logistic regression to analyze fulfillment of permanent contraception before hospital discharge, within 42 days of delivery, and within 365 days of delivery between patients with a documented plan for permanent contraception in the first or second trimester compared to the third trimester. Covariates included insurance status, age, parity, gestational age, mode of delivery, adequacy of prenatal care, race, ethnicity, marital status, and body mass index. RESULTS: Of the 3103 patients with a documented expressed desire for permanent contraception at the time of delivery, 2083 (69.1%) had a documented plan for postpartum permanent contraception prenatally. After adjusting for covariates, patients with initial documented plan for permanent contraception in the first or second trimester had a higher odds of fulfillment by discharge (aOR 1.57, 95% C.I 1.24-2.00), 42 days (aOR 1.51, 95% C.I 1.20-1.91), and 365 days (aOR 1.40, 95% C.I 1.11-1.75), compared to patients who had their first documented plan in the third trimester. CONCLUSIONS: Patients who had a documented prenatal plan for permanent contraception in trimester one and two experienced higher likelihood of permanent contraception fulfillment compared to those with documentation in trimester three. Given the barriers to accessing permanent contraception, it is imperative that comprehensive, patient-centered counseling and documentation regarding future reproductive goals begin early prenatally.

Permanent contraception is a highly desired form of postpartum contraception in the United States, however there are several barriers to accessing it. In this paper, we investigate whether the timing of when a patient has a documented plan for postpartum contraception has an impact on if they achieve postpartum contraception. This is a cohort study from four hospitals in Illinois, Ohio, California, and Alabama for patients with a desire for postpartum permanent contraception documented in their medical record. We specifically investigated the trimester (first, second, or third) where a patient had a plan for permanent contraception first documented. We then used univariate and multivariate models to determine the relationship between the timing of a plan for permanent contraception and if a patient achieved the procedure at three time-points: hospital discharge, 42-days, and 365-days. Our findings showed that of the 3103 patients in our cohort, only 69.1% of them had a documented plan for postpartum contraception at any point before going to the hospital for their delivery admission. We additionally found that patients who had a documented plan for permanent contraception in the first or second trimester had a higher odds of receiving their postpartum contraception procedure compared to people who had their first documented plan in the third trimester. This showed us the importance of earlier counseling regarding contraception for pregnant patients. There are many barriers to accessing postpartum contraception, so having patient focused counseling about future goals around reproductive health early on in pregnancy is critical.

Perinatal Psychopharmacology: Innovative Approaches to Care Delivery.

Perinatal mental health conditions are the most common complications of childbirth and have well-established enduring negative effects. Obstetric (Ob) clinicians care for patients with perinatal mental health conditions across a spectrum of acuity, severity, and complexity. Ob and psychiatric clinicians can collaborate to create a cohesive continuum of psychopharmacologic care for perinatal patients. This chapter provides an overall framework for Ob-psychiatric clinician collaboration with examples of innovation in care delivery.

An Assessment of the One-Month Effectiveness of Telehealth Treatment for Opioid Use Disorder Using the Brief Addiction Monitor.

OBJECTIVES: Telehealth treatment with medication for opioid use disorder (teleMOUD) was made possible with regulations following the COVID-19 pandemic that permitted prescribing buprenorphine without an in-person visit. This study evaluates the self-reported outcomes of patients treated by teleMOUD using the Brief Addiction Monitor (BAM), a 17-question tool that assesses drug use, cravings, physical and psychological health, and psychosocial factors to produce 3 subset scores: substance use, risk factors, and protective factors. METHODS: Patients treated by a teleMOUD provider group operating in >30 states were asked to complete an app-based version of BAM at enrollment and at 1 month. Patients who completed both assessments between June 2022 and March 2023 were included. RESULTS: A total of 2556 patients completed an enrollment BAM and 1447 completed both assessments. Mean number of days from baseline BAM to follow-up was 26.7 days. Changes were significantly different across most questions. The substance use subscale decreased from mean 2.6 to 0.8 (P < .001), the risk factors subscale decreased from mean 10.3 to 7.5 (P < .001), and the protective factors subscale increased from mean 14.3 to 15.0. (P < .001). Substance use and risk factor subscale changes were significant across all sex and age groups, while protective factors subscale did not improve for those <25 and >54 years. Patient reports of at least 1 day of illegal use or misuse decreased, including marijuana (28.1% vs 9.0%), cocaine/crack (3.9% vs 2.6%), and opioids (49.8% vs 10.5%). CONCLUSIONS: Among patients treated by teleMOUD who completed assessments at enrollment and 1 month, there was improvement in drug use, risk factor, and protective factor scores.

Illuminating the landscape of sibling relationship quality: An evidence and gap map.

This paper used an evidence and gap map (EGM) to advance the scientific understanding of sibling relationship quality among children aged 2 to 18 years by synthesizing literature on 277 empirical studies from 1985 to 2022 to delineate patterns of study design, sampling, and measurement. Most existing research has utilized majority of White, middle-to-upper class, and/or two-caregiver family samples. Nearly 85% (n = 235) of studies used quantitative methods to measure sibling relationship quality across eight domains: conflict, warmth/affection, quality, cohesion, hostility, power/control, positive engagement, and conflict management. A total of 122 studies used a measure of sibling relationship quality as a predictor of sibling behavior, social, psychological, cognitive, health, or physiological outcomes. Future directions for research are discussed.