Beyond 'speech delay': Expanding the phenotype of BRPF1-related disorder.

Pathogenic variants in BRPF1 cause intellectual disability, ptosis and facial dysmorphism. Speech and language deficits have been identified as a manifestation of BRPF1-related disorder but have not been systematically characterized. We provide a comprehensive delineation of speech and language abilities in BRPF1-related disorder and expand the phenotype. Speech and language, and health and medical history were assessed in 15 participants (male = 10, median age = 7 years 4 months) with 14 BRPF1 variants. Language disorders were common (11/12), and most had mild to moderate deficits across receptive, expressive, written, and social-pragmatic domains. Speech disorders were frequent (7/9), including phonological delay (6/9) and disorder (3/9), and childhood apraxia of speech (3/9). All those tested for cognitive abilities had a FSIQ ≥70 (4/4). Participants had vision impairment (13/15), fine (8/15) and gross motor delay (10/15) which often resolved in later childhood, infant feeding impairment (8/15), and infant hypotonia (9/15). We have implicated BRPF1-related disorder as causative for speech and language disorder, including childhood apraxia of speech. Adaptive behavior and cognition were strengths when compared to other monogenic neurodevelopmental chromatin-related disorders. The universal involvement of speech and language impairment is noteable, relative to the high degree of phenotypic variability in BRPF1-related disorder.

Assessing Liver Viability: Insights From Mitochondrial Bioenergetics in Ischemia-Reperfusion Injury.

Orthotopic liver transplantation remains the definitive treatment for patients with end-stage liver disease. Unfortunately, the increasing demand for donor livers and the limited supply of viable organs have both led to a critical need for innovative strategies to expand the pool of transplantable organs. The mitochondrion, central to hepatic cellular function, plays a pivotal role in hepatic ischemic injury, with impaired mitochondrial function and oxidative stress leading to cell death. Mitochondrial protection strategies have shown promise in mitigating IRI and resuscitating marginal organs for transplant. Machine perfusion (MP) has been proven a valuable tool for reviving marginal organs with very promising results. Evaluation of liver viability during perfusion traditionally relies on parameters including lactate clearance, bile production, and transaminase levels. Nevertheless, the quest for more comprehensive and universally applicable viability markers persists. Normothermic regional perfusion has gained robust attention, offering extended recovery time for organs from donation after cardiac death donors. This approach has shown remarkable success in improving organ quality and reducing ischemic injury using the body's physiological conditions. The current challenge lies in the absence of a reliable assessment tool for predicting graft viability and post-transplant outcomes. To address this, exploring insights from mitochondrial function in the context of ischemia-reperfusion injury could offer a promising path toward better patient outcomes and graft longevity. Indeed, hypoxia-induced mitochondrial injury may serve as a surrogate marker of organ viability following oxygenated resuscitation techniques in the future.

Mental health impacts of environmental exposures: A scoping review of evaluative instruments.

To date, much of the health focus of environmental policy has been on preventing physical health impacts of environmental exposures. Recent research has however highlighted increasingly concurrent mental health effects and its consideration is an emerging requirement for many governments and their agencies, yet there are limited universal mental health assessment tools for environmental exposures. This paper details the findings of a scoping review that evaluated assessment tools used to measure psychological impacts from environmental exposures and pollution, as reported in recent peer-reviewed literature (2000-2022). Across the 126 papers identified in our review, a wide range of tools to assess mental health impact were identified. We document a clear recent upswing of research interest in the mental and psychological impacts of environmental exposures, and an overarching concern for air pollution from industry, traffic, and fires. A majority of studies utilised standardised assessment instruments, but there was little consistency in the way that these were combined or deployed. The dominant mental health outcomes of interest in these studies were depression, anxiety, and mental and psychiatric health. The findings of the review identify a need and opportunity to develop a best-practice approach to consistently assess the mental health impacts arising from environmental exposures. Future work is needed to define the most appropriate choice and application of assessment tools to evaluate adverse mental health impacts from environmental exposures. This will support a more universal, coordinated and cross-jurisdiction approach for the assessment, quantification and targeted response to addressing mental health impacts arising from environmental exposures.

Anomalous peroxidase activity of cytochrome c is the primary pathogenic target in Barth syndrome.

Barth syndrome (BTHS) is a life-threatening genetic disorder with unknown pathogenicity caused by mutations in TAFAZZIN (TAZ) that affect remodeling of mitochondrial cardiolipin (CL). TAZ deficiency leads to accumulation of mono-lyso-CL (MLCL), which forms a peroxidase complex with cytochrome c (cyt c) capable of oxidizing polyunsaturated fatty acid-containing lipids. We hypothesized that accumulation of MLCL facilitates formation of anomalous MLCL-cyt c peroxidase complexes and peroxidation of polyunsaturated fatty acid phospholipids as the primary BTHS pathogenic mechanism. Using genetic, biochemical/biophysical, redox lipidomic and computational approaches, we reveal mechanisms of peroxidase-competent MLCL-cyt c complexation and increased phospholipid peroxidation in different TAZ-deficient cells and animal models and in pre-transplant biopsies from hearts of patients with BTHS. A specific mitochondria-targeted anti-peroxidase agent inhibited MLCL-cyt c peroxidase activity, prevented phospholipid peroxidation, improved mitochondrial respiration of TAZ-deficient C2C12 myoblasts and restored exercise endurance in a BTHS Drosophila model. Targeting MLCL-cyt c peroxidase offers therapeutic approaches to BTHS treatment.

An Australian housing conditions data infrastructure.

For the past two decades, researchers and policy makers have known very little about conditions within Australia's housing stock due to a lack of systematic and reliable data. In 2022, a collaboration of Australian universities and researchers commissioned a large survey of 22,550 private rental, social rental and homeowner households to build a data infrastructure on the household and demographic characteristics, housing quality and conditions in the Australian housing stock. This is the third and largest instalment in a national series of housing conditions data infrastructures.

Do Basic Neurologic Assessments Tell Us More Than We Realize?

BACKGROUND: Neurologic assessments using a monofilament and a tuning fork are routinely performed to screen for peripheral neuropathy and to identify foot ulceration and amputation risks. We investigated whether assessments commonly used to monitor sensation in the feet may illuminate a more holistic perspective of a person's overall health status. METHODS: Recruitment of 50 participants for foot health screening was facilitated via a promotional event for Foot Health Week. Participants were aged 52 to 92 years (31 women and 19 men). Monofilament and tuning fork assessments were used to determine each participant's neurologic status. Participants also completed a modified Foot Health Status Questionnaire. Data were analyzed to identify correlations between neurologic assessment results and questionnaire responses. RESULTS: For participants self-reporting an "excellent" health rating, a significant relationship was identified with adequate vibration sensation (P < .01). Significant correlations were also identified between a greater number of sites detected using a 10-g monofilament assessment and a person's experience of having a lot of energy (P = .03), limited interference with social activities (P = .03), and greater confidence completing a variety of functional tasks. CONCLUSIONS: Significant correlations were observed between basic neurologic assessments and a participant's perception of their overall health. Although these findings reflect a correlational rather than a causational relationship, they may provide a stimulus for clinicians to reflect on the holistic value of peripheral neurologic assessment. Although the immediate focus for a practitioner is minimizing risk and preserving tissue viability, neurologic test results may be useful to stimulate further discussion about a patient's health outcomes by exploring issues beyond the presenting condition.

Are housing circumstances associated with faster epigenetic ageing?

BACKGROUND: Numerous aspects of housing are associated with health. However, the pathways between housing and health, particularly the psychosocial elements of housing, are less well understood. Epigenetic information alongside social survey data offers an opportunity to explore biological ageing, measured using DNA methylation, as a potential pathway through which housing affects health. METHODS: We use data on housing and DNA methylation from the UK Household Longitudinal Study, linked with prior survey responses from the British Household Panel Survey, covering adults in Great Britain. We explore the association between epigenetic ageing and housing circumstances, both contemporary and historical, using hierarchical regression. RESULTS: We find that living in a privately rented home is related to faster biological ageing. Importantly, the impact of private renting (coefficient (SE) 0.046 years (0.011) vs owned outright, p<0.001) is greater than the impact of experiencing unemployment (coefficient 0.027 years (0.012) vs employed, p<0.05) or being a former smoker (coefficient 0.021 years (0.005) vs never smoker, p<0.001). When we include historical housing circumstances in the analysis, we find that repeated housing arrears and exposure to pollution/environmental problems are also associated with faster biological ageing. CONCLUSION: Our results suggest that challenging housing circumstances negatively affect health through faster biological ageing. However, biological ageing is reversible, highlighting the significant potential for housing policy changes to improve health.

The effect of energy poverty on mental health, cardiovascular disease and respiratory health: a longitudinal analysis.

Background: Houses in mild-climate countries, such as Australia, are often ill-equipped to provide occupants protection during cold weather due to their design. As a result, we rely on energy to warm homes, however, energy is becoming increasingly expensive, and evidence is emerging of a sizable burden to population health of being unable to afford to warm homes causing exposure to cold indoor temperatures. Methods: We use a large longitudinal sample of adult Australians (N = 32,729, Obs = 288,073) collected annually between 2000 and 2019 to estimate the relationship between exposure to energy poverty and mental health (SF-36 mental health score), and a smaller sample from waves collected in 2008-9, 2012-13, and 2016-17 (N = 22,378, Obs = 48,371) to estimate the relationship between energy poverty and onset of asthma, chronic bronchitis or emphysema, hypertension, coronary heart disease, and depression/anxiety. Fixed effects and correlated random-effects regression was used in models. As exposure and outcomes were self-reported, we tested alternative specifications of each to examine bias from measurement error. Findings: When people can no longer afford to warm their homes, their mental health declines significantly (by 4.6-points on the SF-36 mental health scale, 95% CI -4.93 to -4.24), their odds of reporting depression/anxiety or hypertension increases by 49% (OR 1.49, 95% CI 1.09 to 2.02) and 71% (OR 1.71, 95% CI 1.13 to 2.58) respectively. The findings for the decline in mental health were supported in additional analyses that tested alternative specifications of the exposure measure, including co-resident verification of respondent reporting of being able to afford to warm the home. Support for an effect of energy poverty on hypertension was less clearly supported in these same sensitivity models. There was little evidence of an effect of energy poverty on asthma or chronic bronchitis onset in this adult population noting, however, that we could not examine exacerbation of symptoms. Interpretation: Reducing exposure to energy poverty should be considered as an intervention with clear benefits for mental health and potential benefits for cardiovascular health. Funding: National Health and Medical Research Council, Australia.

Cold housing environments: defining the problem for an appropriate policy response.

Researchers across disciplines are increasing attention to cold housing environments. Public health, environmental and social sciences, architecture, and engineering each define and measure cold housing environments differently. Lack of standardisation hinders our ability to combine evidence, determine prevalence, understand who is most at risk--and to formulate policy responses. We conducted a systematic, cross-disciplinary review of literature to document the measures used. We examined benefits and limitations of each approach and propose a conceptualisation of cold housing: where temperature is too low to support optimal health and wellbeing of inhabitants, measured using one or a combination of economic, 'objective', or subjective approaches. More accurate data on home temperatures for all population groups, combined with an understanding of factors leading to cold homes, will enable appropriate policy response to reduce adverse health effects and costs. Policies targeting better building standards and energy subsidies both improve temperature conditions in housing environments.

Rates of unanticipated premalignant and malignant lesions at the time of hysterectomy performed for pelvic organ prolapse in an underscreened population.

BACKGROUND: The rate of unanticipated premalignant or malignant pathology at the time of hysterectomy performed for pelvic organ prolapse has been previously reported to be 0.2%. It is not known whether this rate is similar in patients with limited access to regular medical care. OBJECTIVE: This study aimed to describe the rates of unanticipated premalignancy and malignancy at the time of hysterectomy performed for pelvic organ prolapse in an underscreened population and to determine the risk factors for unanticipated pathology. STUDY DESIGN: Hysterectomies performed for pelvic organ prolapse at a large public hospital between July 2007 and July 2019 were reviewed. Patients undergoing surgery for malignancy or premalignancy were excluded. Medical records were reviewed for demographic information, medical history, preoperative workup, and final pathology. Frequencies of abnormal pathologies were calculated. Demographic and screening factors were correlated with pathologic findings using the Fisher exact test or Mann-Whitney U test, as appropriate. This study was approved by the institutional review board. RESULTS: Between 2007 and 2019, 759 cases of pelvic organ prolapse were identified. Of 759 patients, 667 (87.9%) self-identified as Hispanic. The median age was 57 years old, and 505 of 759 patients (66.5%) were in the postmenopausal stage. Abnormal uterine bleeding history was present in 217 of 759 patients (28.6%). Of 759 patients, 493 (65.4%) underwent preoperative ultrasonography, and 290 (38.3%) underwent preoperative endometrial biopsy. Of the 744 uterine specimens that had available histology results, there were 2 cases of endometrial hyperplasia and 1 case of endometrial cancer. Of the 729 cervical specimens that were available for review, there was 1 case of intraepithelial neoplasia and 2 cases of cervical cancer. In the 246 patients who underwent oophorectomy, no ovarian malignancy was found. CONCLUSION: For patients undergoing hysterectomy for pelvic organ prolapse in an underscreened population, the rates of endometrial dysplasia or cancer were 0.40% (3/744), and the rates of cervical dysplasia or cancer were 0.42% (3/729). Our results underscore the importance of considering screening history when interpreting preoperative cervical and endometrial cancer screening. Consideration of higher negative predictive value tests, such as cytology with human papillomavirus cotesting and preoperative counseling on the risks and management strategies of unanticipated premalignancy or malignancy within this population may be reasonable.

Recurrence and Postoperative Death in Patients with Colorectal Cancer: A New Perspective via Semi-competing Risk Framework.

BACKGROUND/AIMS: Cancer studies suffer from an overestimation of prediction of survival when both recurrence and death are of interest. This longitudinal study aimed to mitigate this problem utilizing a semi-competing risk approach evaluating the factors affecting recurrence and postoperative death in patients with colorectal cancer. MATERIALS AND METHODS: This longitudinal prospective study was conducted in 284 patients with resected colorectal cancer who were referred to the Imam Khomeini Clinic in Hamadan, Iran, during 2001-2017. Primary outcomes were postoperative outcomes and patient survival, including time to recurrence (of colorectal cancer), time to death, and time to death after recurrence. All patients who were alive at the end of the study were censored for death and who did not experience recurrence of colorectal cancer were also censored for recurrent colorectal cancer. The relationship between underlying demographics and clinical factors and the outcomes was assessed using a semicompeting risk approach. RESULTS: The results of the multivariable analysis showed that having metastasis to other sites (hazard ratio = 36.03; 95% CI = 19.48- 66.64) and higher pathological node (pN) stage (hazard ratio = 2.46; 95% CI = 1.32-4.56) were associated with a raised hazard of recurrence. The fewer chemotherapies (hazard ratio = 0.39; 95% CI = 0.17-0.88) and higher pN stages (hazard ratio = 4.32; 95% CI = 1.27-14.75) showed significantly higher hazards of death without recurrence. Having metastasis to other sites (hazard ratio = 2.67; 95% CI = 1.24-5.74) and higher pN stages (hazard ratio = 1.91; 95% CI = 1.02-3.61) were linked with the higher hazard of death after recurrence. CONCLUSION: Considering findings on death /recu rrenc e-spe cific predictors obtained in this study to manage the outcomes in patients with colorectal cancer, tailored strategies for preventive and interventional plans should be deliberated.

Population Pharmacokinetic Study of Benzylpenicillin in Critically Unwell Adults.

Pharmacokinetics are highly variable in critical illness, and suboptimal antibiotic exposure is associated with treatment failure. Benzylpenicillin is a commonly used beta-lactam antibiotic, and pharmacokinetic data of its use in critically ill adults are lacking. We performed a pharmacokinetic study of critically unwell patients receiving benzylpenicillin, using data from the ABDose study. Population pharmacokinetic modelling was undertaken using NONMEM version 7.5, and simulations using the final model were undertaken to optimize the pharmacokinetic profile. We included 77 samples from 12 participants. A two-compartment structural model provided the best fit, with allometric weight scaling for all parameters and a creatinine covariate effect on clearance. Simulations (n = 10,000) demonstrated that 25% of simulated patients receiving 2.4 g 4-hourly failed to achieve a conservative target of 50% of the dosing interval with free drug above the clinical breakpoint MIC (2 mg/L). Simulations demonstrated that target attainment was improved with continuous or extended dosing. To our knowledge, this study represents the first full population PK analysis of benzylpenicillin in critically ill adults.

The association of vitamin D status with oxidative stress biomarkers and matrix metalloproteinases in patients with knee osteoarthritis.

Objective: The association of vitamin D status with osteoarthritis (OA) has been demonstrated previously. The current study was performed to examine the association of vitamin D status with oxidative stress markers and matrix metalloproteinases (MMPs) in patients with knee OA. Methods: This case-control study was conducted on 124 subjects with mild to moderate knee OA and 65 healthy controls. Demographic data was collected from all participants at baseline. Serum levels of vitamin D as well as markers of oxidative stress including malondialdehyde (MDA), total oxidant status (TOS), superoxide dismutase (SOD), oxidative stress index (OSI), paraoxonase-1 (PON-1), glutathione peroxidase (GPX), catalase (CAT), and total antioxidant capacity (TAC) were evaluated for each participant. Furthermore, serum concentrations of MMP-1, MMP-3, MMP-13, and cartilage oligomeric matrix protein (COMP) were measured. Results: The results of the present study indicated that individuals with vitamin D insufficiency had higher levels of MDA, TOS, SOD, and OSI as well as lower levels of PON-1 and TAC. Based on the linear regression analysis, serum vitamin D levels were inversely correlated with MDA, TOS, SOD, OSI, MMP-1, and MMP-13 and positively associated with TAC levels (p < 0.0001). Patients with sufficient vitamin D levels had lower MMP-1 and MMP-13 levels compared to patients with vitamin D insufficiency (p < 0.001 and p < 0.001, respectively). Conclusion: Findings from this study showed a strong association between vitamin D deficiency and increased oxidative stress and MMPs activity in patients with knee OA.

Estimating the impact of Angelman syndrome on parental productivity in Australia using productivity-adjusted life years.

BACKGROUND: Angelman syndrome (AS) is a rare genetic condition characterized by global developmental delay, including severe intellectual disability. The parents of persons with AS experience increased stress, anxiety, and depression. This impacts parents' career choices and productivity. OBJECTIVE: To estimate, for the first time, the total productivity lost by the parents of persons with AS over a 10-year period in Australia and the corresponding cost to society. METHODS: A cost-of-illness model with simulated follow-up over a 10-year period was developed, with 2019 as the baseline year, facilitated by a Markov chain of life tables. The prevalence of persons with AS and their parents, the productivity-adjusted life years (PALYs) lost by parents, and the cost to society were estimated. Key data were obtained from a prospective cohort of AS families, peer-reviewed literature, and publicly available sources. RESULTS: The base-case productivity burden borne by the estimated 330 living parents of the 428 prevalent persons with AS totaled AUD$45.30 million, corresponding to a loss of 38.42% of PALYs per parent. CONCLUSIONS: Caring for a child with AS has a significant impact on the productivity of affected parents, with a large associated impact on the broader Australian economy.

A longitudinal study of the relationships between sleep problems in autistic children and maternal mental health.

LAY ABSTRACT: Autistic children experience increased the rates of sleep problems. These sleep problems have been associated with mother's mental health symptoms. However, the direction of these relationships is not well understood. This study investigated the relationships between autistic children's sleep problems and mothers' mental health over a 12-year period using data collected as part of the Longitudinal Study of Australian Children. Data from 397 autistic children and their mothers were included in this study. Mothers completed a questionnaire about their own mental health and common childhood sleep problems at four time points from 4-5 years to 14-15 years. The results showed important relationships between mothers' mental health symptoms and child sleep problems at two time points. Specifically, (1) mothers' mental health symptoms when the child was aged 4 to 5 years predicted child sleep problems at age 6 to 7 years; and (2) child sleep problems at age 12-13 years predicted mothers' mental health symptoms when the child was aged 14 to 15 years. Interestingly, these significant relationships also coincide with key developmental transition time points, when the child is transitioning in and out of primary school. These findings highlight the need for increased support for both the child and mother at these times to optimise outcomes for both.

Tissue mosaicism, FMR1 expression and intellectual functioning in males with fragile X syndrome.

Fragile X syndrome (FXS) is caused by hypermethylation of the FMR1 promoter due to the full mutation expansion (full mutation [FM]: CGG ≥ 200 repeats) and silencing of FMR1. Assessment of mosaicism for active-unmethylated alleles has prognostic utility. This study examined relationships between FMR1 methylation in different tissues with FMR1 messenger ribonucleic acid (mRNA) and intellectual functioning in 87 males with FXS (1.89-43.17 years of age). Methylation sensitive Southern blot (mSB) and Methylation Specific-Quantitative Melt Aanalysis (MS-QMA) were used to examine FMR1 methylation. FMR1 mRNA levels in blood showed strong relationships with FMR1 methylation assessed using MS-QMA in blood (n = 68; R2  = 0.597; p = 1.4 × 10-10 ) and buccal epithelial cells (BEC) (n = 62; R2  = 0.24; p = 0.003), with these measures also showing relationships with intellectual functioning scores (p < 0.01). However, these relationships were not as strong for mSB, with ~40% of males with only FM alleles that were 100% methylated and non-mosaic by mSB, showing methylation mosaicism by MS-QMA. This was confirmed through presence of detectable levels of FMR1 mRNA in blood. In summary, FMR1 methylation levels in blood and BEC examined by MS-QMA were significantly associated with FMR1 mRNA levels and intellectual functioning in males with FXS. These relationships were not as strong for mSB, which underestimated prevalence of mosaicism.

Genetic aetiologies for childhood speech disorder: novel pathways co-expressed during brain development.

Childhood apraxia of speech (CAS), the prototypic severe childhood speech disorder, is characterized by motor programming and planning deficits. Genetic factors make substantive contributions to CAS aetiology, with a monogenic pathogenic variant identified in a third of cases, implicating around 20 single genes to date. Here we aimed to identify molecular causation in 70 unrelated probands ascertained with CAS. We performed trio genome sequencing. Our bioinformatic analysis examined single nucleotide, indel, copy number, structural and short tandem repeat variants. We prioritised appropriate variants arising de novo or inherited that were expected to be damaging based on in silico predictions. We identified high confidence variants in 18/70 (26%) probands, almost doubling the current number of candidate genes for CAS. Three of the 18 variants affected SETBP1, SETD1A and DDX3X, thus confirming their roles in CAS, while the remaining 15 occurred in genes not previously associated with this disorder. Fifteen variants arose de novo and three were inherited. We provide further novel insights into the biology of child speech disorder, highlighting the roles of chromatin organization and gene regulation in CAS, and confirm that genes involved in CAS are co-expressed during brain development. Our findings confirm a diagnostic yield comparable to, or even higher, than other neurodevelopmental disorders with substantial de novo variant burden. Data also support the increasingly recognised overlaps between genes conferring risk for a range of neurodevelopmental disorders. Understanding the aetiological basis of CAS is critical to end the diagnostic odyssey and ensure affected individuals are poised for precision medicine trials.

The Cost of Raising Individuals with Fragile X or Chromosome 15 Imprinting Disorders in Australia.

The study characterised differences in costs associated with raising a child between four rare disorders and examined the associations between these costs with clinical severity. Caregivers of 108 individuals with Prader-Willi, Angelman (AS), Chromosome 15q Duplication and fragile X (FXS) syndromes completed a modified Client Services Receipt Inventory and participants completed intellectual/developmental functioning and autism assessments. AS incurred the highest yearly costs per individual ($AUD96,994), while FXS had the lowest costs ($AUD33,221). Intellectual functioning negatively predicted total costs, after controlling for diagnosis. The effect of intellectual functioning on total costs for those with AS was significantly different to the other syndromes. The study highlights the significant costs associated with these syndromes, particularly AS, linked with severity of intellectual functioning.

Effect of a Biopsychosocial Intervention or Postural Therapy on Disability and Health Care Spending Among Patients With Acute and Subacute Spine Pain: The SPINE CARE Randomized Clinical Trial.

Importance: Low back and neck pain are often self-limited, but health care spending remains high. Objective: To evaluate the effects of 2 interventions that emphasize noninvasive care for spine pain. Design, Setting, and Participants: Pragmatic, cluster, randomized clinical trial conducted at 33 centers in the US that enrolled 2971 participants with neck or back pain of 3 months' duration or less (enrollment, June 2017 to March 2020; final follow-up, March 2021). Interventions: Participants were randomized at the clinic-level to (1) usual care (n = 992); (2) a risk-stratified, multidisciplinary intervention (the identify, coordinate, and enhance [ICE] care model that combines physical therapy, health coach counseling, and consultation from a specialist in pain medicine or rehabilitation) (n = 829); or (3) individualized postural therapy (IPT), a postural therapy approach that combines physical therapy with building self-efficacy and self-management (n = 1150). Main Outcomes and Measures: The primary outcomes were change in Oswestry Disability Index (ODI) score at 3 months (range, 0 [best] to 100 [worst]; minimal clinically important difference, 6) and spine-related health care spending at 1 year. A 2-sided significance threshold of .025 was used to define statistical significance. Results: Among 2971 participants randomized (mean age, 51.7 years; 1792 women [60.3%]), 2733 (92%) finished the trial. Between baseline and 3-month follow-up, mean ODI scores changed from 31.2 to 15.4 for ICE, from 29.3 to 15.4 for IPT, and from 28.9 to 19.5 for usual care. At 3-month follow-up, absolute differences compared with usual care were -5.8 (95% CI, -7.7 to -3.9; P < .001) for ICE and -4.3 (95% CI, -5.9 to -2.6; P < .001) for IPT. Mean 12-month spending was $1448, $2528, and $1587 in the ICE, IPT, and usual care groups, respectively. Differences in spending compared with usual care were -$139 (risk ratio, 0.93 [95% CI, 0.87 to 0.997]; P = .04) for ICE and $941 (risk ratio, 1.40 [95% CI, 1.35 to 1.45]; P < .001) for IPT. Conclusions and Relevance: Among patients with acute or subacute spine pain, a multidisciplinary biopsychosocial intervention or an individualized postural therapy intervention, each compared with usual care, resulted in small but statistically significant reductions in pain-related disability at 3 months. However, compared with usual care, the biopsychosocial intervention resulted in no significant difference in spine-related health care spending and the postural therapy intervention resulted in significantly greater spine-related health care spending at 1 year. Trial Registration: ClinicalTrials.gov Identifier: NCT03083886.