Postoperative outcomes and costs of laparoscopic versus robotic distal pancreatectomy: a propensity-matched analysis.

BACKGROUND: Minimally invasive distal pancreatectomy (MIDP) has established advantages over the open approach. The costs associated with robotic DP (RDP) versus laparoscopic DP (LDP) make the robotic approach controversial. We sought to compare outcomes and cost of LDP and RDP using propensity matching analysis at our institution. METHODS: Patients undergoing LDP or RDP between 2000 and 2021 were retrospectively identified. Patients were optimally matched using age, gender, American Society of Anesthesiologists status, body mass index, and tumor size. Between-group differences were analyzed using the Wilcoxon signed-rank test for continuous data, and the McNemar's test for categorical data. Outcomes included operative duration, conversion to open surgery, postoperative length of stay, pancreatic fistula rate, pseudocyst requiring intervention, and costs. RESULTS: 298 patients underwent MIDP, 180 (60%) were laparoscopic and 118 (40%) were robotic. All RDPs were matched 1:1 to a laparoscopic case with absolute standardized mean differences for all matching covariates below 0.10, except for tumor type (0.16). RDP had longer operative times (268 vs 178 min, p < 0.01), shorter length of stay (2 vs 4 days, p < 0.01), fewer biochemical pancreatic leaks (11.9% vs 34.7%, p < 0.01), and fewer interventional radiological drainage (0% vs 5.9%, p = 0.01). The number of pancreatic fistulas (11.9% vs 5.1%, p = 0.12), collections requiring antibiotics or intervention (11.9% vs 5.1%, p = 0.12), and conversion rates (3.4% vs 5.1%, p = 0.72) were comparable between the two groups. The total direct index admission costs for RDP were 1.01 times higher than for LDP for FY16-19 (p = 0.372), and 1.33 times higher for FY20-22 (p = 0.031). CONCLUSIONS: Although RDP required longer operative times than LDP, postoperative stays were shorter. The procedure cost of RDP was modestly more expensive than LDP, though this was partially offset by reduced hospital stay and reintervention rate.

Embryologic Origin Influences Smooth Muscle Cell Phenotypic Modulation Signatures in Murine Marfan Syndrome Aortic Aneurysm.

BACKGROUND: Aortic root smooth muscle cells (SMC) develop from both the second heart field (SHF) and neural crest. Disparate responses to disease-causing Fbn1 variants by these lineages are proposed to promote focal aortic root aneurysm formation in Marfan syndrome (MFS), but lineage-stratified SMC analysis in vivo is lacking. METHODS: We generated SHF lineage-traced MFS mice and performed integrated multiomic (single-cell RNA and assay for transposase-accessible chromatin sequencing) analysis stratified by embryological origin. SMC subtypes were spatially identified via RNA in situ hybridization. Response to TWIST1 overexpression was determined via lentiviral transduction in human aortic SMCs. RESULTS: Lineage stratification enabled nuanced characterization of aortic root cells. We identified heightened SHF-derived SMC heterogeneity including a subset of Tnnt2 (cardiac troponin T)-expressing cells distinguished by altered proteoglycan expression. MFS aneurysm-associated SMC phenotypic modulation was identified in both SHF-traced and nontraced (neural crest-derived) SMCs; however, transcriptomic responses were distinct between lineages. SHF-derived modulated SMCs overexpressed collagen synthetic genes and small leucine-rich proteoglycans while nontraced SMCs activated chondrogenic genes. These modulated SMCs clustered focally in the aneurysmal aortic root at the region of SHF/neural crest lineage overlap. Integrated RNA-assay for transposase-accessible chromatin analysis identified enriched Twist1 and Smad2/3/4 complex binding motifs in SHF-derived modulated SMCs. TWIST1 overexpression promoted collagen and SLRP gene expression in vitro, suggesting TWIST1 may drive SHF-enriched collagen synthesis in MFS aneurysm. CONCLUSIONS: SMCs derived from both SHF and neural crest lineages undergo phenotypic modulation in MFS aneurysm but are defined by subtly distinct transcriptional responses. Enhanced TWIST1 transcription factor activity may contribute to enriched collagen synthetic pathways SHF-derived SMCs in MFS.

Effects of Wearable Fitness Trackers and Activity Adequacy Mindsets on Affect, Behavior, and Health: Longitudinal Randomized Controlled Trial.

BACKGROUND: There is some initial evidence suggesting that mindsets about the adequacy and health consequences of one's physical activity (activity adequacy mindsets [AAMs]) can shape physical activity behavior, health, and well-being. However, it is unknown how to leverage these mindsets using wearable technology and other interventions. OBJECTIVE: This research examined how wearable fitness trackers and meta-mindset interventions influence AAMs, affect, behavior, and health. METHODS: A total of 162 community-dwelling adults were recruited via flyers and web-based platforms (ie, Craigslist and Nextdoor; final sample size after attrition or exclusion of 45 participants). Participants received an Apple Watch (Apple Inc) to wear for 5 weeks, which was equipped with an app that recorded step count and could display a (potentially manipulated) step count on the watch face. After a baseline week of receiving no feedback about step count, participants were randomly assigned to 1 of 4 experimental groups: they received either accurate step count (reference group; 41/162, 25.3%), 40% deflated step count (40/162, 24.7%), 40% inflated step count (40/162, 24.7%), or accurate step count+a web-based meta-mindset intervention teaching participants the value of adopting more positive AAMs (41/162, 25.3%). Participants were blinded to the condition. Outcome measures were taken in the laboratory by an experimenter at the beginning and end of participation and via web-based surveys in between. Longitudinal analysis examined changes within the accurate step count condition from baseline to treatment and compared them with changes in the deflated step count, inflated step count, and meta-mindset conditions. RESULTS: Participants receiving accurate step counts perceived their activity as more adequate and healthier, adopted a healthier diet, and experienced improved mental health (Patient-Reported Outcomes Measurement Information System [PROMIS]-29) and aerobic capacity but also reduced functional health (PROMIS-29; compared with their no-step-count baseline). Participants exposed to deflated step counts perceived their activity as more inadequate; ate more unhealthily; and experienced more negative affect, reduced self-esteem and mental health, and increased blood pressure and heart rate (compared with participants receiving accurate step counts). Inflated step counts did not change AAM or most other outcomes (compared with accurate step counts). Participants receiving the meta-mindset intervention experienced improved AAM, affect, functional health, and self-reported physical activity (compared with participants receiving accurate step counts only). Actual step count did not change in either condition. CONCLUSIONS: AAMs--induced by trackers or adopted deliberately--can influence affect, behavior, and health independently of actual physical activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT03939572; https://www.clinicaltrials.gov/ct2/show/NCT03939572.

Sexual Assault Among Young Adolescents in Informal Settlements in Nairobi, Kenya: Findings from the IMPower and SOS Cluster-Randomized Controlled Trial.

Sexual assault is a global threat to adolescent health, but empowerment self-defense (ESD) interventions have shown promise for prevention. This study evaluated the joint implementation of a girls' ESD program and a concurrent boys' program, implemented via a cluster-randomized controlled trial in informal settlements of Nairobi, Kenya, from January 2016 to October 2018. Schools were randomized to the 12-h intervention or 2-h standard of care. Students were randomly sampled to complete surveys at baseline and again at 24 months post-intervention. A total of 3263 girls, ages 10-14, who completed both baseline and follow-up surveys were analyzed; weights were adjusted for dropout. At follow-up, 5.9% (n = 194/3263) of girls reported having been raped in the prior 12 months. Odds of reporting rape were not significantly different in the intervention versus SOC group (OR: 1.21; 95% CI (0.40, 5.21), p = 0.63). Secondary outcomes, social self-efficacy (OR: 1.08; 95% CI (0.95, 1.22), p = 0.22), emotional self-efficacy (OR 1.07; 95% CI (0.89, 1.29), p = 0.49), and academic self-efficacy (OR: 0.90; 95% CI (0.82, 1.00), p = 0.06) were not significantly different. Exploratory analyses of boys' victimization and perpetration are reported. This study improved on previous ESD studies in this setting with longitudinal follow-up of individuals and independent data collection. This study did not show an effect of the intervention on self-reported rape; findings should be interpreted cautiously due to limitations. Sexual assault rates are high in this young population, underscoring a dire need to implement and rigorously test sexual assault prevention interventions in this setting. The trial was registered with Clinical Trials.gov # NCT02771132. Version 3.1 registered on May 2017, first participant enrolled January 2017.

Casting New Light on Statistical Power: An Illuminating Analogy and Strategies to Avoid Underpowered Trials.

Current standards for methodological rigor and trial reporting underscore the critical issue of statistical power. Still, the chance of detecting most effects reported in randomized controlled trials in medicine and other disciplines is currently lower than winning a toss of a fair coin. Here we propose that investigators who retain a practical understanding of how statistical power works can proactively avoid the potentially devastating consequences of underpowered trials. We first offer a vivid, carefully constructed analogy that illuminates the underlying relationships among 3 of the 5 essential parameters-namely, statistical power, effect size, and sample size-while holding the remaining 2 parameters constant (type of statistical test and significance level). Second, we extend the analogy to a set of critical scenarios in which investigators commonly miss detecting intervention effects due to insufficient statistical power. Third, we highlight effective pragmatic strategies for the design and conduct of sufficiently powered trials, without increasing sample size.

The Stanford experience of heart transplantation over five decades.

AIMS: Since 1968, heart transplantation has become the definitive treatment for patients with end-stage heart failure. We aimed to summarize our experience in heart transplantation at Stanford University since the first transplantation performed over 50 years ago. METHODS AND RESULTS: From 6 January 1968 to 30 November 2020, 2671 patients presented to Stanford University for heart transplantation, of which 1958 were adult heart transplantations. Descriptive analyses were performed for patients in 1968-95 (n = 639). Stabilized inverse probability weighting was applied to compare patients in 1996-2006 (n = 356) vs. 2007-19 (n = 515). Follow-up data were updated through 2020. The primary endpoint was all-cause mortality. Prior to weighting, recipients in 2007-19 vs. those in 1996-2006 were older and had heavier burden of chronic diseases. After the application of stabilized inverse probability weighting, the distance organ travelled increased from 84.2 ± 111.1 miles to 159.3 ± 169.9 miles from 1996-2006 to 2007-19. Total allograft ischaemia time also increased over time (199.6 ± 52.7 vs. 225.3 ± 50.0 min). Patients in 2007-19 showed superior survival than those in 1996-2006 with a median survival of 12.1 vs. 11.1 years. CONCLUSION: In this half-century retrospective descriptive study from one of the largest heart transplant programmes in the USA, long-term survival after heart transplantation has improved over time despite increased recipient and donor age, worsening comorbidities, increased technical complexity, and prolonged total allograft ischaemia time. Further investigation is warranted to delineate factors associated with the excellent outcomes observed in this study.

Comprehensive Ex Vivo Comparison of 5 Clinically Used Conduit Configurations for Valve-Sparing Aortic Root Replacement Using a 3-Dimensional-Printed Heart Simulator.

BACKGROUND: Many graft configurations are clinically used for valve-sparing aortic root replacement, some specifically focused on recapitulating neosinus geometry. However, the specific impact of such neosinuses on valvular and root biomechanics and the potential influence on long-term durability are unknown. METHODS: Using a custom 3-dimenstional-printed heart simulator with porcine aortic roots (n=5), the anticommissural plication, Stanford modification, straight graft (SG), Uni-Graft, and Valsalva graft configurations were tested in series using an incomplete counterbalanced measures design, with the native root as a control, to mitigate ordering effects. Hemodynamic and videometric data were analyzed using linear models with conduit as the fixed effect of interest and valve as a fixed nuisance effect with post hoc pairwise testing using Tukey's correction. RESULTS: Hemodynamics were clinically similar between grafts and control aortic roots. Regurgitant fraction varied between grafts, with SG and Uni-Graft groups having the lowest regurgitant fractions and anticommissural plication having the highest. Root distensibility was significantly lower in SG versus both control roots and all other grafts aside from the Stanford modification (P≤0.01 for each). All grafts except SG had significantly higher cusp opening velocities versus native roots (P<0.01 for each). Relative cusp opening forces were similar between SG, Uni-Graft, and control groups, whereas anticommissural plication, Stanford modification, and Valsalva grafts had significantly higher opening forces versus controls (P<0.01). Cusp closing velocities were similar between native roots and the SG group, and were significantly lower than observed in the other conduits (P≤0.01 for each). Only SG and Uni-Graft groups experienced relative cusp closing forces approaching that of the native root, whereas relative forces were >5-fold higher in the anticommissural plication, Stanford modification, and Valsalva graft groups. CONCLUSIONS: In this ex vivo modeling system, clinically used valve-sparing aortic root replacement conduit configurations have comparable hemodynamics but differ in biomechanical performance, with the straight graft most closely recapitulating native aortic root biomechanics.

A Therapeutic Relational Agent for Reducing Problematic Substance Use (Woebot): Development and Usability Study.

BACKGROUND: Misuse of substances is common, can be serious and costly to society, and often goes untreated due to barriers to accessing care. Woebot is a mental health digital solution informed by cognitive behavioral therapy and built upon an artificial intelligence-driven platform to deliver tailored content to users. In a previous 2-week randomized controlled trial, Woebot alleviated depressive symptoms. OBJECTIVE: This study aims to adapt Woebot for the treatment of substance use disorders (W-SUDs) and examine its feasibility, acceptability, and preliminary efficacy. METHODS: American adults (aged 18-65 years) who screened positive for substance misuse without major health contraindications were recruited from online sources and flyers and enrolled between March 27 and May 6, 2020. In a single-group pre/postdesign, all participants received W-SUDs for 8 weeks. W-SUDs provided mood, craving, and pain tracking and modules (psychoeducational lessons and psychotherapeutic tools) using elements of dialectical behavior therapy and motivational interviewing. Paired samples t tests and McNemar nonparametric tests were used to examine within-subject changes from pre- to posttreatment on measures of substance use, confidence, cravings, mood, and pain. RESULTS: The sample (N=101) had a mean age of 36.8 years (SD 10.0), and 75.2% (76/101) of the participants were female, 78.2% (79/101) were non-Hispanic White, and 72.3% (73/101) were employed. Participants' W-SUDs use averaged 15.7 (SD 14.2) days, 12.1 (SD 8.3) modules, and 600.7 (SD 556.5) sent messages. About 94% (562/598) of all completed psychoeducational lessons were rated positively. From treatment start to end, in-app craving ratings were reduced by half (87/101, 86.1% reporting cravings in the app; odds ratio 0.48, 95% CI 0.32-0.73). Posttreatment assessment completion was 50.5% (51/101), with better retention among those who initially screened higher on substance misuse. From pre- to posttreatment, confidence to resist urges to use substances significantly increased (mean score change +16.9, SD 21.4; P<.001), whereas past month substance use occasions (mean change -9.3, SD 14.1; P<.001) and scores on the Alcohol Use Disorders Identification Test-Concise (mean change -1.3, SD 2.6; P<.001), 10-item Drug Abuse Screening Test (mean change -1.2, SD 2.0; P<.001), Patient Health Questionnaire-8 item (mean change 2.1, SD 5.2; P=.005), Generalized Anxiety Disorder-7 (mean change -2.3, SD 4.7; P=.001), and cravings scale (68.6% vs 47.1% moderate to extreme; P=.01) significantly decreased. Most participants would recommend W-SUDs to a friend (39/51, 76%) and reported receiving the service they desired (41/51, 80%). Fewer felt W-SUDs met most or all of their needs (22/51, 43%). CONCLUSIONS: W-SUDs was feasible to deliver, engaging, and acceptable and was associated with significant improvements in substance use, confidence, cravings, depression, and anxiety. Study attrition was high. Future research will evaluate W-SUDs in a randomized controlled trial with a more diverse sample and with the use of greater study retention strategies. TRIAL REGISTRATION: ClinicalTrials.gov NCT04096001; http://clinicaltrials.gov/ct2/show/NCT04096001.

Interfacility Transfer of Medicare Beneficiaries With Acute Type A Aortic Dissection and Regionalization of Care in the United States.

BACKGROUND: The feasibility and effectiveness of delaying surgery to transfer patients with acute type A aortic dissection-a catastrophic disease that requires prompt intervention-to higher-volume aortic surgery hospitals is unknown. We investigated the hypothesis that regionalizing care at high-volume hospitals for acute type A aortic dissections will lower mortality. We further decomposed this hypothesis into subparts, investigating the isolated effect of transfer and the isolated effect of receiving care at a high-volume versus a low-volume facility. METHODS: We compared the operative mortality and long-term survival between 16 886 Medicare beneficiaries diagnosed with an acute type A aortic dissection between 1999 and 2014 who (1) were transferred versus not transferred, (2) underwent surgery at high-volume versus low-volume hospitals, and (3) were rerouted versus not rerouted to a high-volume hospital for treatment. We used a preference-based instrumental variable design to address unmeasured confounding and matching to separate the effect of transfer from volume. RESULTS: Between 1999 and 2014, 40.5% of patients with an acute type A aortic dissection were transferred, and 51.9% received surgery at a high-volume hospital. Interfacility transfer was not associated with a change in operative mortality (risk difference, -0.69%; 95% CI, -2.7% to 1.35%) or long-term mortality. Despite delaying surgery, a regionalization policy that transfers patients to high-volume hospitals was associated with a 7.2% (95% CI, 4.1%-10.3%) absolute risk reduction in operative mortality; this association persisted in the long term (hazard ratio, 0.81; 95% CI, 0.75-0.87). The median distance needed to reroute each patient to a high-volume hospital was 50.1 miles (interquartile range, 12.4-105.4 miles). CONCLUSIONS: Operative and long-term mortality were substantially reduced in patients with acute type A aortic dissection who were rerouted to high-volume hospitals. Policy makers should evaluate the feasibility and benefits of regionalizing the surgical treatment of acute type A aortic dissection in the United States.

Mechanical or Biologic Prostheses for Aortic-Valve and Mitral-Valve Replacement.

BACKGROUND: In patients undergoing aortic-valve or mitral-valve replacement, either a mechanical or biologic prosthesis is used. Biologic prostheses have been increasingly favored despite limited evidence supporting this practice. METHODS: We compared long-term mortality and rates of reoperation, stroke, and bleeding between inverse-probability-weighted cohorts of patients who underwent primary aortic-valve replacement or mitral-valve replacement with a mechanical or biologic prosthesis in California in the period from 1996 through 2013. Patients were stratified into different age groups on the basis of valve position (aortic vs. mitral valve). RESULTS: From 1996 through 2013, the use of biologic prostheses increased substantially for aortic-valve and mitral-valve replacement, from 11.5% to 51.6% for aortic-valve replacement and from 16.8% to 53.7% for mitral-valve replacement. Among patients who underwent aortic-valve replacement, receipt of a biologic prosthesis was associated with significantly higher 15-year mortality than receipt of a mechanical prosthesis among patients 45 to 54 years of age (30.6% vs. 26.4% at 15 years; hazard ratio, 1.23; 95% confidence interval [CI], 1.02 to 1.48; P=0.03) but not among patients 55 to 64 years of age. Among patients who underwent mitral-valve replacement, receipt of a biologic prosthesis was associated with significantly higher mortality than receipt of a mechanical prosthesis among patients 40 to 49 years of age (44.1% vs. 27.1%; hazard ratio, 1.88; 95% CI, 1.35 to 2.63; P<0.001) and among those 50 to 69 years of age (50.0% vs. 45.3%; hazard ratio, 1.16; 95% CI, 1.04 to 1.30; P=0.01). The incidence of reoperation was significantly higher among recipients of a biologic prosthesis than among recipients of a mechanical prosthesis. Patients who received mechanical valves had a higher cumulative incidence of bleeding and, in some age groups, stroke than did recipients of a biologic prosthesis. CONCLUSIONS: The long-term mortality benefit that was associated with a mechanical prosthesis, as compared with a biologic prosthesis, persisted until 70 years of age among patients undergoing mitral-valve replacement and until 55 years of age among those undergoing aortic-valve replacement. (Funded by the National Institutes of Health and the Agency for Healthcare Research and Quality.).

A pilot design for observational studies: Using abundant data thoughtfully.

Observational studies often benefit from an abundance of observational units. This can lead to studies that-while challenged by issues of internal validity-have inferences derived from sample sizes substantially larger than randomized controlled trials. But is the information provided by an observational unit best used in the analysis phase? We propose the use of a "pilot design," in which observations are expended in the design phase of the study, and the posttreatment information from these observations is used to improve study design. In modern observational studies, which are data rich but control poor, pilot designs can be used to gain information about the structure of posttreatment variation. This information can then be used to improve instrumental variable designs, propensity score matching, doubly robust estimation, and other observational study designs. We illustrate one version of a pilot design, which aims to reduce within-set heterogeneity and improve performance in sensitivity analyses. This version of a pilot design expends observational units during the design phase to fit a prognostic model, avoiding concerns of overfitting. In addition, it enables the construction of "assignment-control plots," which visualize the relationship between propensity and prognostic scores. We first show some examples of these plots, then we demonstrate in a simulation setting how this alternative use of the observations can lead to gains in terms of both treatment effect estimation and sensitivity analyses of unobserved confounding.

Treating tobacco dependence to aid re-employment among job-seekers: A randomized controlled trial.

INTRODUCTION: U.S. reductions in smoking have not been experienced equally. Smoking prevalence is greater among persons of lower education, lower income, and unemployed. We evaluated whether a cessation intervention for job-seekers would result in significantly fewer cigarettes smoked per day and a greater likelihood of tobacco abstinence and re-employment, compared to the control condition at 6-months follow-up. METHODS: Unemployed, job-seekers who smoked daily were recruited from five employment development departments in the San Francisco Bay Area, October 2015 to February 2018. Intention to quit smoking was not required. Participants were randomized to a brief motivationally-tailored, computer-assisted counseling intervention or referred to a toll-free quitline. Midstudy, 8-weeks of combination nicotine replacement was added to the intervention. Expired carbon monoxide and cotinine testing verified abstinence. Data were analyzed fall 2019. RESULTS: Participants (N = 360; 70% men; 43% African American, 27% non-Hispanic Caucasian; 19% unhoused) averaged 12 cigarettes/day (SD = 6), 67% smoked within 30 min of wakening; 27% were in preparation stage to quit. During the 6-month study period, intervention participants were more likely to make a quit attempt (71% vs. 58%, p = .021) and reported significantly greater reduction in cigarettes/day than control participants (median reduction: 6.9 vs. 5.0, p = .038); however, bioconfirmed abstinence (3%) and re-employment (36%) did not differ by treatment group. CONCLUSIONS: In a diverse sample with economic hardships, quit attempts and smoking reduction were greater in the intervention group; however, few achieved abstinence, and neither abstinence nor re-employment differed by condition. A priority group, further research is needed on smoking and re-employment.

PMI's heated tobacco products marketing claims of reduced risk and reduced exposure may entice youth to try and continue using these products.

IMPORTANCE: Philip Morris International (PMI) is seeking Food and Drug Administration's (FDA) authorisation to market IQOS as a modified risk tobacco product and to make marketing claims of reduced risk and reduced exposure. Such claims may be misunderstood by youth, thereby increasing their risk for tobacco initiation. OBJECTIVE: To assess youth (mean age 19.3, SD=1.7) understanding and perceptions of PMI's proposed consumer marketing claims of reduced risk and reduced exposure, we embedded a randomised controlled experiment into a survey of 450 California youth (April to August 2018). Participants were randomised to see 'reduced exposure', 'reduced risk' or neither claim. Perceptions of IQOS-related health risks and general harm and understanding of the term 'switching completely' as used in PMI's proposed claims were compared. RESULTS: Mean expectancies to experience specific health risks did not differ by claim exposure. The reduced exposure group's perceptions of general harm did not differ from those of controls nor from the reduced risk group. The reduced risk group had the largest proportion who perceived IQOS as moderately/less harmful (n=78, 52%); controls the largest proportion perceiving IQOS as quite/extremely harmful (n=91, 63%). While 71% of the sample understood the term 'switch completely' correctly as used in the reduced risk (n=194, 71%) and reduced exposure (n=206, 72%) claims, more than 1 in 4 did not. CONCLUSIONS: FDA and other regulators must use caution when considering allowing claims of reduced risk or reduced exposure to appear on retail tobacco packaging. Youth misunderstand such claims, and misperceptions of harm are known to lead to tobacco-use initiation.

Second Arterial Versus Venous Conduits for Multivessel Coronary Artery Bypass Surgery in California.

BACKGROUND: Whether a second arterial conduit improves outcomes after multivessel coronary artery bypass grafting remains unclear. Consequently, arterial conduits other than the left internal thoracic artery are seldom used in the United States. METHODS: Using a state-maintained clinical registry including all 126 nonfederal hospitals in California, we compared all-cause mortality and rates of stroke, myocardial infarction, repeat revascularization, and sternal wound infection between propensity score-matched cohorts who underwent primary, isolated multivessel coronary artery bypass grafting with the left internal thoracic artery, and who received a second arterial conduit (right internal thoracic artery or radial artery, n=5866) or a venous conduit (n=53 566) between 2006 and 2011. Propensity score matching using 34 preoperative characteristics yielded 5813 matched sets. A subgroup analysis compared outcomes between propensity score-matched recipients of a right internal thoracic artery (n=1576) or a radial artery (n=4290). RESULTS: Second arterial conduit use decreased from 10.7% in 2006 to 9.1% in 2011 (P<0.0001). However, receipt of a second arterial conduit was associated with significantly lower mortality (13.1% versus 10.6% at 7 years; hazard ratio, 0.79; 95% confidence interval [CI], 0.72-0.87), and lower risks of myocardial infarction (hazard ratio, 0.78; 95% CI, 0.70-0.87) and repeat revascularization (hazard ratio, 0.82; 95% CI, 0.76-0.88). In comparison with radial artery grafts, right internal thoracic artery grafts were associated with similar mortality rates (right internal thoracic artery 10.3% versus radial artery 10.7% at 7 years; hazard ratio, 1.10; 95% CI, 0.89-1.37) and individual risks of cardiovascular events, but the risk of sternal wound infection was increased (risk difference, 1.07%; 95% CI, 0.15-2.07). CONCLUSIONS: Second arterial conduit use in California is low and declining, but arterial grafts were associated with significantly lower mortality and fewer cardiovascular events. A right internal thoracic artery graft offered no benefit over that of a radial artery, but did increase risk of sternal wound infection. These findings suggest surgeons should consider lowering their threshold for using arterial grafts, and the radial artery may be the preferred second conduit.

Natural American Spirit's pro-environment packaging and perceptions of reduced-harm cigarettes.

Natural American Spirit (NAS) cigarettes feature a pro-environment marketing campaign on the packs. The NAS "Respect for the Earth" campaign is the first example of on-the-pack corporate social responsibility advertising. In a randomized survey design, we tested perceptions of NAS relative to other cigarette brands on harms to self, others, and the environment. Never (n = 421), former (n = 135), and current (n = 358) US adult smokers were recruited for an online survey from January through March 2018. All participants viewed packs of both NAS and Pall Mall. Participants were randomized to view NAS vs. Pall Mall and to pack color (blue, green, or yellow/orange), which was matched between brands. Survey items assessed perceptions of health risk of the cigarette brand to self, others, and the environment and corporate perceptions. Consistently on all measures, NAS cigarettes were rated as less harmful for oneself, others, and the environment relative to Pall Mall (p's < .001). Though Reynolds American owns both brands, participants rated the company behind NAS as more socially responsible than the company behind Pall Mall, F[1, 909] = 110.25, p < .001. The NAS advantage was significant irrespective of smoking status, pack color, and brand order, with findings stronger for current than never smokers. Pro-environmental marketing on NAS cigarette packs contributes to misperceptions that the product is safer for people and the environment than other cigarettes and made by a company that is more socially responsible. Stricter government regulations on the use of pro-environment terms in marketing that imply modified risk are needed.

A protocol for a cluster-randomized controlled trial testing an empowerment intervention to prevent sexual assault in upper primary school adolescents in the informal settlements of Nairobi, Kenya.

BACKGROUND: Sexual violence against adolescents is prevalent worldwide and results in significant physical and mental injuries as well as loss of economic and personal potential. Urban informal settlements such as those around Nairobi, Kenya have been shown to have especially high incidences of violence. Research has shown that empowerment interventions for female adolescents can reduce sexual assault. However, these interventions have had limited testing in urban informal settlements, with young adolescents, or in coordination with complementary programs for male adolescents. METHODS/DESIGN: This study was a two-arm, parallel, cluster-randomized trial testing a combination of a previously-tested girls' intervention, IMPower, and a newly revised boys' intervention, Source of Strength. Clusters were defined as schools within the informal settlements; participants were adolescent girls and boys in class 6, generally between the ages of 10-14 at baseline. Data collection began in January 2016 and continued through December 2018. The primary outcome was the change in incidence of self-reported sexual assault among girls from baseline, compared to a life skills standard of care intervention. Secondary outcomes included experiences of physical and emotional violence, as well as determining the effects of the intervention on self-efficacy, self-esteem, and gender attitudes and beliefs, and how those effects led to changes in experience of sexual assault. For the primary outcome and several of the secondary outcomes, we used an intention to treat estimand. DISCUSSION: This was the first randomized controlled trial with longitudinal follow-up of an empowerment self-defense approach to violence prevention for adolescents in informal settlements. The large size and rigorous design supported analysis to understand multiple subgroup experiences in the hypothesized reduction in sexual assault. The study was also unique in its focus on young (10-14 years of age) adolescents and in engaging both boys and girls in separate but coordinated curriculums. The focus on a highly vulnerable and understudied population will make it a significant contribution to the literature on violence prevention. TRIAL REGISTRATION: Clinical Trials.gov # NCT02771132 . Version 3.1 registered May 2017, first participant enrolled January 2017. Retrospectively registered.

An evaluation of clinical order patterns machine-learned from clinician cohorts stratified by patient mortality outcomes.

OBJECTIVE: Evaluate the quality of clinical order practice patterns machine-learned from clinician cohorts stratified by patient mortality outcomes. MATERIALS AND METHODS: Inpatient electronic health records from 2010 to 2013 were extracted from a tertiary academic hospital. Clinicians (n = 1822) were stratified into low-mortality (21.8%, n = 397) and high-mortality (6.0%, n = 110) extremes using a two-sided P-value score quantifying deviation of observed vs. expected 30-day patient mortality rates. Three patient cohorts were assembled: patients seen by low-mortality clinicians, high-mortality clinicians, and an unfiltered crowd of all clinicians (n = 1046, 1046, and 5230 post-propensity score matching, respectively). Predicted order lists were automatically generated from recommender system algorithms trained on each patient cohort and evaluated against (i) real-world practice patterns reflected in patient cases with better-than-expected mortality outcomes and (ii) reference standards derived from clinical practice guidelines. RESULTS: Across six common admission diagnoses, order lists learned from the crowd demonstrated the greatest alignment with guideline references (AUROC range = 0.86-0.91), performing on par or better than those learned from low-mortality clinicians (0.79-0.84, P < 10-5) or manually-authored hospital order sets (0.65-0.77, P < 10-3). The same trend was observed in evaluating model predictions against better-than-expected patient cases, with the crowd model (AUROC mean = 0.91) outperforming the low-mortality model (0.87, P < 10-16) and order set benchmarks (0.78, P < 10-35). DISCUSSION: Whether machine-learning models are trained on all clinicians or a subset of experts illustrates a bias-variance tradeoff in data usage. Defining robust metrics to assess quality based on internal (e.g. practice patterns from better-than-expected patient cases) or external reference standards (e.g. clinical practice guidelines) is critical to assess decision support content. CONCLUSION: Learning relevant decision support content from all clinicians is as, if not more, robust than learning from a select subgroup of clinicians favored by patient outcomes.

Near-Far Matching in R: The nearfar Package.

Estimating the causal treatment effect of an intervention using observational data is difficult due to unmeasured confounders. Many analysts use instrumental variables (IVs) to introduce a randomizing element to observational data analysis, potentially reducing bias created by unobserved confounders. Several persistent problems in the field have served as limitations to IV analyses, particularly the prevalence of "weak" IVs, or instrumental variables that do not effectively randomize individuals to the intervention or control group (leading to biased and unstable treatment effect estimates), as well as IV-based estimates being highly model dependent, requiring parametric adjustment for measured confounders, and often having high mean squared errors in the estimated causal effects. To overcome these problems, the study design method of "near-far matching" has been devised, which "filters" data from a cohort by simultaneously matching individuals within the cohort to be "near" (similar) on measured confounders and "far" (different) on levels of an IV. To facilitate the application of near-far matching to analytical problems, we introduce the R package nearfar and illustrate its application to both a classical example and a simulated dataset. We illustrate how the package can be used to "strengthen" a weak IV by adjusting the "near-ness" and "far-ness" of a match, reduce model dependency, enable nonparametric adjustment for measured confounders, and lower mean squared error in estimated causal effects. We additionally illustrate how to utilize the nearfar package when analyzing either continuous or binary treatments, how to prioritize variables in the match, and how to calculate F statistics of IV strength with or without adjustment for measured confounders.

A Behavior-Based Intervention That Prevents Sexual Assault: the Results of a Matched-Pairs, Cluster-Randomized Study in Nairobi, Kenya.

DESIGN: The study's design was a cluster-randomized, matched-pairs, parallel trial of a behavior-based sexual assault prevention intervention in the informal settlements. METHODS: The participants were primary school girls aged 10-16. Classroom-based interventions for girls and boys were delivered by instructors from the same settlements, at the same time, over six 2-h sessions. The girls' program had components of empowerment, gender relations, and self-defense. The boys' program promotes healthy gender norms. The control arm of the study received a health and hygiene curriculum. The primary outcome was the rate of sexual assault in the prior 12 months at the cluster level (school level). Secondary outcomes included the generalized self-efficacy scale, the distribution of number of times victims were sexually assaulted in the prior period, skills used, disclosure rates, and distribution of perpetrators. Difference-in-differences estimates are reported with bootstrapped confidence intervals. RESULTS: Fourteen schools with 3147 girls from the intervention group and 14 schools with 2539 girls from the control group were included in the analysis. We estimate a 3.7 % decrease, p = 0.03 and 95 % CI = (0.4, 8.0), in risk of sexual assault in the intervention group due to the intervention (initially 7.3 % at baseline). We estimate an increase in mean generalized self-efficacy score of 0.19 (baseline average 3.1, on a 1-4 scale), p = 0.0004 and 95 % CI = (0.08, 0.39). INTERPRETATION: This innovative intervention that combined parallel training for young adolescent girls and boys in school settings showed significant reduction in the rate of sexual assault among girls in this population.

Health-related quality of life among veterans in addictions treatment: identifying behavioral targets for future intervention.

BACKGROUND: US veterans report lower health-related quality of life (HRQoL) relative to the general population. Identifying behavioral factors related to HRQoL that are malleable to change may inform interventions to improve well-being in this vulnerable group. PURPOSE: The current study sought to characterize HRQoL in a largely male sample of veterans in addictions treatment, both in relation to US norms and in association with five recommended health behavior practices: regularly exercising, managing stress, having good sleep hygiene, consuming fruits and vegetables, and being tobacco free. METHODS: We assessed HRQoL with 250 veterans in addictions treatment (96 % male, mean age 53, range 24-77) using scales from four validated measures. Data reduction methods identified two principal components reflecting physical and mental HRQoL. Model testing of HRQoL associations with health behaviors adjusted for relevant demographic and treatment-related covariates. RESULTS: Compared to US norms, the sample had lower HRQoL scores. Better psychological HRQoL was associated with higher subjective social standing, absence of pain or trauma, lower alcohol severity, and monotonically with the sum of health behaviors (all p < 0.05). Specifically, psychological HRQoL was associated with regular exercise, stress management, and sleep hygiene. Regular exercise also related to better physical HRQoL. The models explained >40 % of the variance in HRQoL. CONCLUSIONS: Exercise, sleep hygiene, and stress management are strongly associated with HRQoL among veterans in addictions treatment. Future research is needed to test the effect of interventions for improving well-being in this high-risk group.