Cancer biology and Mr.Darwin

Publication date: Available online 12 April 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Robert Gatenby




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One-dimensional Poly(L-Lysine)-block-Poly(L-Threonine) Assemblies Exhibit Potent Anticancer Activity by Enhancing Membranolysis

Publication date: Available online 13 April 2017
Source:Acta Biomaterialia
Author(s): Yu-Fon Chen, Ai-Li Shiau, Sue-Joan Chang, Nai-Shin Fan, Chung-Teng Wang, Chao-Liang Wu, Jeng-Shiung Jan
Herein, we report the oncolytic activity of cationic, one-dimensional (1D) fibril assemblies formed from coil-sheet poly(L-lysine)-block-poly(L-threonine) (PLL-b-PLT) block copolypeptides for cancer therapy. The 1D fibril assemblies can efficiently interact with negatively charged cellular and mitochondrial membranes via electrostatic interactions, leading to necrosis via membrane lysis and apoptosis via the mitochondria-lytic effect. The concept is analogous to that of 1D drug carriers that exhibit enhanced cell penetration. In comparison to free PLL chains, PLL-b-PLT fibril assemblies exhibit selective cytotoxicity toward cancer cells, low hemolysis activity, enhanced membranolytic activity, and a different apoptosis pathway, which may be due to differences in the peptide-membrane interactions. Antitumor studies using a metastatic LL2 lung carcinoma model indicate that the fibril assemblies significantly inhibited tumor growth, improved survival in tumor-bearing mice and suppressed lung metastasis without obvious body weight loss. An additive efficacy was also observed for treatment with both PLL-b-PLT and cisplatin. These results support the feasibility of using 1D fibril assemblies as potential apoptotic anticancer therapeutics.Statement of SignificanceWe report that cationic, one-dimensional (1D) fibril assemblies formed by coil-sheet poly(L-lysine)-block-poly(L-threonine) (PLL-b-PLT) block copolypeptides exhibited potent anticancer activity by enhancing membranolysis. The 1D fibril assemblies can efficiently interact with negatively charged cellular and mitochondrial membranes via electrostatic interactions, leading to necrosis via membrane lysis and apoptosis via mitochondria-lytic effect. Moreover, the fibril assemblies exhibited low hemolytic activity and selective cytotoxicity toward cancer cell, which is advantageous as compared to PLL and most antimicrobial/anticancerous peptides. This study provides a new concept of using cationic,1D fibril assemblies for cancer therapy.

Graphical abstract

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Secretive eating among youth with overweight or obesity

Publication date: 1 July 2017
Source:Appetite, Volume 114
Author(s): Andrea E. Kass, Denise E. Wilfley, Kamryn T. Eddy, Kerri N. Boutelle, Nancy Zucker, Carol B. Peterson, Daniel Le Grange, Angela Celio-Doyle, Andrea B. Goldschmidt
PurposeSecretive eating, characterized by eating privately to conceal being seen, may reflect eating- and/or body-related shame, be associated with depression, and correlate with binge eating, which predicts weight gain and eating disorder onset. Increasing understanding of secretive eating in youth may improve weight status and reduce eating disorder risk. This study evaluated the prevalence and correlates of secretive eating in youth with overweight or obesity.MethodsYouth (N = 577) presented to five research/clinical institutions. Using a cross-sectional design, secretive eating was evaluated in relation to eating-related and general psychopathology via linear and logistic regression analyses.ResultsSecretive eating was endorsed by 111 youth, who were, on average, older than youth who denied secretive eating (mean age = 12.07 ± 2.83 versus 10.97 ± 2.31). Controlling for study site and age, youth who endorsed secretive eating had higher eating-related psychopathology and were more likely to endorse loss of control eating and purging than their counterparts who did not endorse secretive eating. Groups did not differ in excessive exercise or behavioral problems. Dietary restraint and purging were elevated among adolescents (≥13y) but not children (<13y) who endorsed secretive eating; depression was elevated among children, but not adolescents, who endorsed secretive eating.ConclusionsSecretive eating may portend heightened risk for eating disorders, and correlates of secretive eating may differ across pediatric development. Screening for secretive eating may inform identification of problematic eating behaviors, and understanding factors motivating secretive eating may improve intervention tailoring.



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The impact of video technology on learning: A cooking skills experiment

Publication date: 1 July 2017
Source:Appetite, Volume 114
Author(s): Dawn Surgenor, Lynsey Hollywood, Sinéad Furey, Fiona Lavelle, Laura McGowan, Michelle Spence, Monique Raats, Amanda McCloat, Elaine Mooney, Martin Caraher, Moira Dean
This study examines the role of video technology in the development of cooking skills. The study explored the views of 141 female participants on whether video technology can promote confidence in learning new cooking skills to assist in meal preparation. Prior to each focus group participants took part in a cooking experiment to assess the most effective method of learning for low-skilled cooks across four experimental conditions (recipe card only; recipe card plus video demonstration; recipe card plus video demonstration conducted in segmented stages; and recipe card plus video demonstration whereby participants freely accessed video demonstrations as and when needed). Focus group findings revealed that video technology was perceived to assist learning in the cooking process in the following ways: (1) improved comprehension of the cooking process; (2) real-time reassurance in the cooking process; (3) assisting the acquisition of new cooking skills; and (4) enhancing the enjoyment of the cooking process. These findings display the potential for video technology to promote motivation and confidence as well as enhancing cooking skills among low-skilled individuals wishing to cook from scratch using fresh ingredients.



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Self-perceived food addiction: Prevalence, predictors, and prognosis

Publication date: 1 July 2017
Source:Appetite, Volume 114
Author(s): Angela Meadows, Laurence J. Nolan, Suzanne Higgs
Food addiction is controversial within the scientific community. However many lay people consider themselves addicted to certain foods. We assessed the prevalence and characteristics of self-perceived "food addiction" and its relationship to a diagnostic measure of "clinical food addiction" in two samples: (1) 658 university students, and (2) 614 adults from an international online crowdsourcing platform. Participants indicated whether they considered themselves to be addicted to food, and then completed the Yale Food Addiction Scale, measures of eating behavior, body image, and explicit and internalized weight stigma. Participants in the community sample additionally completed measures of impulsivity, food cravings, binge eating, and depressive symptomatology. Follow-up data were collected from a subset of 305 students (mean follow-up 280 ± 30 days). Self-perceived "food addiction" was prevalent, and was associated with elevated levels of problematic eating behavior, body image concerns, and psychopathology compared with "non-addicts", although individuals who also received a positive "diagnosis" on the Yale Food Addiction Scale experienced the most severe symptoms. A clear continuum was evident for all measures despite no differences in body mass index between the three groups. Multinomial logistic regression analyses indicated that perceived lack of self-control around food was the main factor distinguishing between those who did and did not consider themselves addicted to food, whereas severity of food cravings and depressive symptoms were the main discriminating variables between self-classifiers and those receiving a positive "diagnosis" on the Yale Food Addiction Scale. Self-perceived "food addiction" was moderately stable across time, but did not appear predictive of worsening eating pathology. Self-classification as a "food addict" may be of use in identifying individuals in need of assistance with food misuse, loss-of-control eating, and body image issues.



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Vegetarianism and meat consumption: A comparison of attitudes and beliefs between vegetarian, semi-vegetarian, and omnivorous subjects in Belgium

Publication date: 1 July 2017
Source:Appetite, Volume 114
Author(s): Amy Mullee, Leen Vermeire, Barbara Vanaelst, Patrick Mullie, Peter Deriemaeker, Tobias Leenaert, Stefaan De Henauw, Aoibheann Dunne, Marc J. Gunter, Peter Clarys, Inge Huybrechts
High levels of meat consumption in Belgium may be contributing to increased risk of non-communicable diseases in this population. The objective of this study is to investigate the attitudes and beliefs about vegetarianism and meat consumption among the Belgian population, ultimately to better understand the motivations underlying these dietary behaviours.This cross-sectional study was initiated in March 2011. A total of 2436 individuals from a representative consumer panel from the Flemish and Brussels communities participated. The study sample was evenly distributed by education level and sex (1238 men and 1198 women). An online questionnaire with multiple-choice questions about vegetarianism and meat consumption was completed by all participants.Although representative of the prevalence of vegetarians in the population, the number of vegetarians in the study was low (n = 38); the number of semi-vegetarians (n = 288) and omnivores was high (n = 2031). Vegetarians were more likely than semi-vegetarians to agree that meat production is bad for the environment and that meat consumption is unhealthy. Important reasons for not being vegetarian included lack of interest and awareness, taste, and limited cooking skills. Encouragingly, health and discovering new tastes were seen as the most important motives for considering eating a more vegetarian-based diet.The results of this study highlight the motivations that can be used for encouraging the general public to reduce their meat consumption in favour of a plant-rich diet, and will help to inform more targeted health campaigns for reducing meat consumption in Belgium.



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Emissions and ash behavior in a 500kW pellet boiler operated with various blends of woody biomass and peat

Publication date: 15 August 2017
Source:Fuel, Volume 202
Author(s): Olli Sippula, Heikki Lamberg, Jani Leskinen, Jarkko Tissari, Jorma Jokiniemi
Due to the increasing utilization of wood-based raw materials, there is growing interest in the use of alternative biomass raw materials for biomass pellet production. However, the utilization of these new raw materials may significantly increase particle emissions from small boilers, which can cause adverse effects on human health and the environment. In this study, the effects of biomass raw materials on particle and gaseous emissions and ash behavior were studied in a real-world operating 500kW reciprocating grate boiler. The studied fuels were pellets, which consisted of softwood stem, bark, peat and various mixtures of these materials. The emission factors of the fine particles (PM1) ranged between 11 and 26mg/MJ, which were primarily determined by alkali metal release from the fuel. The co-firing of peat with wood significantly decreased PM1 emissions. This decrease was observed because of the high silicate content in peat, which led to alkali silicate formation during co-combustion and, consequently, the retention of alkali metals in the bottom ash. In contrast, the release of trace metals into the fine particle fraction was independent of the fuel ash composition with the exception of Cu. The emissions of As, Cd, Pb, Tl, and Zn were linearly dependent on their concentrations in the fuel. The highest release rates, which were between 40% and 60%, were observed for zinc and lead. Zinc formed the majority of the total PM1 heavy metal emissions, and zinc emissions were especially high in bark combustion. On the basis of these results, fuel composition based indexes were derived for predicting particle emissions. The results highlight the importance of both the fuel alkali metal content and alkali metal/silicate ratio in the formation of fine particles with fuels that consist of woody biomass and peat.

Graphical abstract

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Ambient fine particulate matter (PM2.5) in Canadian oil sands communities: Levels, sources and potential human health risk

Publication date: 1 October 2017
Source:Science of The Total Environment, Volume 595
Author(s): Md. Aynul Bari, Warren B. Kindzierski
An investigation of levels and potential sources affecting ambient fine particulate matter (PM2.5) and associated risk to public health was undertaken at two Canadian oil sands communities (Fort McKay and Fort McMurray) using a 4-year dataset (2010–2013). Geometric mean concentrations of PM2.5 at Fort McKay and Fort McMurray are not considered high and were 5.47μg/m³ (interquartile range, IQR=3.02–8.55μg/m³) and 4.96μg/m³ (IQR=3.20–7.04μg/m³), respectively. Carcinogenic risks of trace elements were below acceptable (1×10⁻⁶) and/or within tolerable risk (1×10⁻⁴), and non-carcinogenic risks were below a safe level of concern (hazard index=1). Positive matrix factorization (PMF) modeling revealed five sources, where fugitive dust appeared as the major contributor to PM2.5 mass (Fort McKay: 32%, Fort McMurray: 46%) followed by secondary sulfate (31%, 42%) and secondary nitrate/biomass burning (26%, 8%). Other minor sources included a mining/mobile and a Mn-rich/Mn-Co-Zn-rich source. Source-specific risk values were also estimated and were well below acceptable and safe level of risks. Further work would be needed to better understand the contribution of secondary organic aerosols to PM2.5 formation in these oil sands communities.

Graphical abstract

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An extensive characterization of various treated waste wood for assessment of suitability with combustion process

Publication date: 15 August 2017
Source:Fuel, Volume 202
Author(s): Maïté Huron, Sophia Oukala, Jérôme Lardière, Nicolas Giraud, Capucine Dupont
A representative set of treated waste wood was extensively characterized in order to evaluate its heterogeneity and its suitability with combustion process. Samples included both average samples made up of waste wood mixtures and specific waste wood classes. Untreated wood was also considered for comparison.As expected, neither heating value nor composition in C, H, O varied significantly compared to untreated wood. However, differences arose for minor elements, in relation with the chemical treatments undergone by waste wood.Particleboard was shown to be the main source of N with values up to 38g/kg due to the presence of N-containing resins. Heavy metals like Ba, Ti or Zn were clearly associated to pigments used in painted wood or coatings and their amount reached respectively 2.6, 2.9 and 1.1g/kg in painted wood. Cr and Cu were shown to come essentially from the chemical treatment undergone by impregnated wood with values of several thousands of mg/kg.A comparison between the minor elements contents found in waste wood and the specifications required in terms of feedstock composition and gas emissions in biomass combustion plants showed that the use of such feedstock would require either pretreatment before combustion to remove impurities or specific gas post-treatment.



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Rejuvenation by Partial Reprogramming of the Epigenome

Rejuvenation Research Apr 2017, Vol. 20, No. 2: 146-150.


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The Rationale for Rejuvenation Research: Structuring the Debate

Rejuvenation Research Apr 2017, Vol. 20, No. 2: 83-84.


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TIAM1 Antagonizes TAZ/YAP Both in the Destruction Complex in the Cytoplasm and in the Nucleus to Inhibit Invasion of Intestinal Epithelial Cells

Publication date: Available online 13 April 2017
Source:Cancer Cell
Author(s): Zoi Diamantopoulou, Gavin White, Muhammad Z.H. Fadlullah, Marcel Dreger, Karen Pickering, Joe Maltas, Garry Ashton, Ruth MacLeod, George S. Baillie, Valerie Kouskoff, Georges Lacaud, Graeme I. Murray, Owen J. Sansom, Adam F.L. Hurlstone, Angeliki Malliri
Aberrant WNT signaling drives colorectal cancer (CRC). Here, we identify TIAM1 as a critical antagonist of CRC progression through inhibiting TAZ and YAP, effectors of WNT signaling. We demonstrate that TIAM1 shuttles between the cytoplasm and nucleus antagonizing TAZ/YAP by distinct mechanisms in the two compartments. In the cytoplasm, TIAM1 localizes to the destruction complex and promotes TAZ degradation by enhancing its interaction with βTrCP. Nuclear TIAM1 suppresses TAZ/YAP interaction with TEADs, inhibiting expression of TAZ/YAP target genes implicated in epithelial-mesenchymal transition, cell migration, and invasion, and consequently suppresses CRC cell migration and invasion. Importantly, high nuclear TIAM1 in clinical specimens associates with increased CRC patient survival. Together, our findings suggest that in CRC TIAM1 suppresses tumor progression by regulating YAP/TAZ activity.

Graphical abstract

Teaser

Diamantopoulou et al. identify TIAM1 as a critical antagonist of colorectal cancer progression. Cytoplasmic TIAM1 promotes TAZ degradation by enhancing its interaction with βTrCP whereas nuclear TIAM1 suppresses TAZ/YAP interaction with TEADs, inhibiting expression of TAZ/YAP target genes.


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Effect of corticision on orthodontic tooth movement in a rat model as assessed by RNA sequencing

Abstract

Corticision is a common technique to accelerate orthodontic tooth movement; however, not much is known about the underlying mechanisms. In this study, we investigated the mechanism of alveolar tissue remodeling after corticision in a rat model of tooth movement (TM) by analyzing the differential transcriptome. A total of 36 male rats were equally divided into TM and TM with corticision (TM+C) groups. Alveolar bone response was examined using micro-computed tomography (micro-CT). Osteoclasts and osteoblasts were quantified on tartrate-resistant acid phosphatase (TRAP) and Goldner's trichrome staining. The transcriptomes of alveolus around the left maxillary first molar were determined on RNA sequencing (RNA-Seq), and the expression of selected differentially expressed genes (DEGs) validated on quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Immunohistochemical examination of alveolar tissue was performed to examine the expressions of correlative proteins of the selected signaling pathway in the TM and TM+C groups. The ratio of bone volume to total volume (BV/TV), and the trabecular number (Tb.N) were significantly decreased, while the movement distance and the trabecular separation (Tb.Sp) was significantly increased in the TM+C group. However, no significant between-group difference in trabecular thickness (Tb.Th) was observed. On histomorphometric analysis, a significant increase in the number of osteoclasts and increased bone resorption was observed in the TM+C group. A total of 399 DEGs were identified on RNA-SEq. Eleven selected genes were confirmed on qRT-PCR, which included components of the Ras signaling pathway. Four proteins of the Ras signaling pathway showed a higher expression in the TM+C group. Our findings indicate that corticision may speed up orthodontic tooth movement by accelerating osteoclastogenesis mediated via the Ras signaling pathway.

http://ift.tt/2p18jRh

Adherence to positive airway pressure treatment among minority populations in the US: a scoping review

Minority individuals in the United States (US) have an increased prevalence of obstructive sleep apnea syndrome (OSA) compared to their white/Caucasian counterparts. In general, adherence to positive airway pressure (PAP) therapy is poor and some studies suggest that PAP use among minority individuals is inferior to that of whites. However, there has not been a review of the evidence that addresses racial-ethnic disparities for PAP adherence in the treatment of OSA, and no review has systematically examined the contributing factors to poor adherence among minority individuals compared to whites.

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How Surgeons Conceptualize Talent: A Qualitative Study Using Sport Science as a Lens

Publication date: Available online 12 April 2017
Source:Journal of Surgical Education
Author(s): Rune Dall Jensen, Mette Krogh Christensen, Kori A. LaDonna, Mikkel Seyer-Hansen, Sayra Cristancho
ObjectivesDebates prevail regarding the definition of surgical talent, and how individuals with the potential to become talented surgeons can be identified and developed. However, over the past 30 years, talent has been studied extensively in other domains. The objectives of this study is to explore notions of talent in surgery and sport in order to investigate if the field of surgical education can benefit from expanding its view on talented performances. Therefore, this study aims to use the sport literature as a lens when exploring how surgeons conceptualize and define talent.DesignSemi-structured interviews were conducted with a sample of 11 consultant surgeons from multiple specialties. We used constructivist grounded theory principles to explore talent in surgery. Ongoing data analysis refined the theoretical framework and iteratively informed data collection. Themes were identified iteratively using constant comparison.SettingThe setting included 8 separate hospitals across Canada and Denmark.ParticipantsA total of 11 consultant surgeons from 6 different surgical subspecialties (urology, orthopedic surgery, colorectal surgery, general surgery, vascular surgery, head & neck surgery) were included.ResultsWe identified three key elements for conceptualizing surgical talent: (1) Individual skills makes the surgical prospect "good", (2) a mixture of skills gives the surgical prospect the potential to become talented, and (3) becoming talented may rely on the fit between person and environment.ConclusionWe embarked on a study aimed at understanding talent in surgery. Talent is a difficult construct to agree on. Whether in medicine or sports, debates about talent will continue to persist, as we all perceive talent differently. While we heard different opinions, three key ideas summarize our participants' discussions regarding surgical talent. These findings resonate with the holistic ecological approach from sport science and hence highlight the limits of a reductionist approach while favoring the individual-environment system as the minimal ontology for describing talented performances



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The mu-rhythm can mirror: Insights from experimental design, and looking past the controversy

Publication date: Available online 12 April 2017
Source:Cortex
Author(s): Lindsay C. Bowman, Marian J. Bakermans-Kranenburg, Kathryn H. Yoo, Erin N. Cannon, Ross E. Vanderwert, Pier Ferrari, Marinus H. van IJzendoorn, Nathan A. Fox




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Pyoderma Gangrenosum with Pathergy; A Potentially Significant Complication following Breast Reconstruction

The failure of post-operative surgical site infection to resolve after appropriate antibiotic therapy should alert the clinician to other diagnoses. Pyoderma Gangrenosum (PG) is an inflammatory neutrophilic dermatosis typically characterized by necrotizing ulceration. PG can be exacerbated by minor trauma leading to exaggerated skin injury, a concept known as pathergy.. We present a case series of pyoderma gangrenosum arising after immediate reconstruction for breast oncological surgery from 1st January 2006 – 1st September 2014.

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Do Slow and Steady Residents Win the Race? Modeling the Effects of Peak and Overall Resident Productivity in the Emergency Department

Publication date: Available online 12 April 2017
Source:The Journal of Emergency Medicine
Author(s): Joshua W. Joseph, Victor Novack, Matthew L. Wong, Larry A. Nathanson, Leon D. Sanchez
BackgroundEmergency medicine residents need to be staffed in a way that balances operational needs with their educational experience. Key to developing an optimal schedule is knowing a resident's expected productivity, a poorly understood metric.ObjectiveWe sought to measure how a resident's busiest (peak) workload affects their overall productivity for the shift.MethodsWe conducted a retrospective, observational study of resident productivity at an urban, tertiary care center with a 3-year Accreditation Council for Graduate Medical Education-approved emergency medicine training program, with 55,000 visits annually. We abstracted resident productivity data from a database of patient assignments from July 1, 2010 to June 20, 2015, utilizing a generalized estimation equation method to evaluate physician shifts. Our primary outcome measure was the total number of patients seen by a resident over a shift. The secondary outcome was the number of patients seen excluding those in the peak hour.ResultsA total of 14,361 shifts were evaluated. Multivariate analysis showed that the total number of patients seen was significantly associated with the number of patients seen during the peak hour, level of training, the timing of the shift, but most prominently, lower variance in patients seen per hour (coefficient of variation < 0.10).ConclusionsA resident's peak productivity can be a strong predictor of their overall productivity, but the substantial negative effect of variability favors a steadier pace. This suggests that resident staffing and patient assignments should generally be oriented toward a more consistent workload, an effect that should be further investigated with attending physicians.



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Emergency Medicine Myths: Cerebral Edema in Pediatric Diabetic Ketoacidosis and Intravenous Fluids

Publication date: Available online 12 April 2017
Source:The Journal of Emergency Medicine
Author(s): Brit Long, Alex Koyfman
BackgroundPediatric diabetic ketoacidosis (DKA) is a disease associated with several complications that can be severe. One complication includes cerebral edema (CE), and patients may experience significant morbidity with this disease.ObjectiveThis review evaluates the myths concerning CE in pediatric DKA including mechanism, presentation of edema, clinical assessment of dehydration, and association with intravenous (i.v.) fluids.DiscussionMultiple complications may occur in pediatric DKA. CE occurs in < 1% of pediatric DKA cases, though morbidity and mortality are severe without treatment. Several myths surround this disease. Subclinical CE is likely present in many patients with pediatric DKA, though severe disease is rare. A multitude of mechanisms likely account for development of CE, including vasogenic and cytotoxic causes. Clinical dehydration is difficult to assess. Literature has evaluated the association of fluid infusion with the development of CE, but most studies are retrospective, with no comparator groups. The few studies with comparisons suggest fluid infusion is not associated with DKA. Rather, the severity of DKA with higher blood urea nitrogen and greater acidosis contribute to CE. Multiple strategies for fluid replacement exist. A bolus of 10 mL/kg of i.v. fluid is likely safe, which can be repeated if hemodynamic status does not improve.ConclusionsPediatric CE in DKA is rare but severe. Multiple mechanisms result in this disease, and many patients experience subclinical CE. Intravenous fluids are likely not associated with development of CE, and 10-mL/kg or 20-mL/kg i.v. bolus is safe.



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A Randomized Controlled Trial of a Citywide Emergency Department Care-Coordination Program to Reduce Prescription Opioid-Related Visits: An Economic Evaluation

Publication date: Available online 12 April 2017
Source:The Journal of Emergency Medicine
Author(s): Sean M. Murphy, Donelle Howell, Sterling McPherson, Rebecca Grohs, John Roll, Darin Neven
BackgroundCare provided in the emergency department (ED) can cost up to five times as much as care received for comparable diagnoses in alternative settings. Small groups of patients, many of whom suffer from an opioid use disorder, often account for a large proportion of total ED visits. We recently conducted, and demonstrated the effectiveness of, the first randomized controlled trial of a citywide ED care-coordination program intending to reduce prescription-opioid-related ED visits. All EDs in the metropolitan study area were connected to a Web-based information exchange system.ObjectiveThe objective of this article was to perform an economic evaluation of the 12-month trial from a third-party-payer perspective.MethodsWe modeled the person-period monthly for the 12-month observation period, and estimated total treatment costs and return on investment (ROI) with regard to cost offsets, over time, for all visits where the patient was admitted to and discharged from the ED.ResultsBy the end of month 4, the mean cumulative cost differential was significantly lower for intervention relative to treatment-as-usual participants (−$1370; p = 0.03); this figure climbed to −$3200 (p = 0.02) by the end of month 12. The ROI trended upward throughout the observation period, but failed to reach statistical significance by the end of month 12 (ROI = 3.39, p = 0.07).ConclusionThe intervention produced significant cost offsets by the end of month 4, which continued to accumulate throughout the trial; however, ROI was not significant. Because the per-patient administrative costs of the program are incurred at the time of enrollment, our results highlight the importance of future studies that are able to follow participants for a period beyond 12 months to more accurately estimate the program's ROI.



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