Superior Outcomes of Dual-Arterial Coronary Artery Bypass Grafting Are Maintained in the Veterans Health Administration.

INTRODUCTION: Controversy surrounds the long-term clinical benefit of coronary artery bypass grafting (CABG) using dual arterial grafts (DAGs) compared to single arterial grafts (SAGs). We investigated outcomes of DAG, using single internal thoracic artery and radial artery (DAG-RA) or bilateral internal thoracic artery grafts (DAG-BITA), compared to SAG, using the left internal thoracic artery and saphenous vein grafts, in the U.S. Veterans Health Administration (VA). METHODS: We conducted a cross-sectional study of U.S. Veterans undergoing isolated on-pump CABG between 2005 and 2015 at 44 VA medical centers. The primary composite outcome was first occurrence of a major adverse cardiac and cerebrovascular event (MACCE), comprised of death from any cause, myocardial infarction, stroke, or repeat revascularization. RESULTS: Among 25,969 Veterans undergoing isolated CABG, 1261 (4.9%) underwent DAG (66.8% DAG-RA and 33.2% DAG-BITA). Over a 5-y follow-up, DAG was associated with lower rates of all-cause death (adjusted hazard ratio [AHR] 0.70, 95% confidence interval [CI] 0.58-0.85), MACCE (AHR 0.80, 95% CI 0.71-0.91), and stroke (AHR 0.74, 95% CI 0.57-0.96) versus SAG. DAG-BITA was associated with lower rates of all-cause death (AHR 0.52, 95% CI 0.35-0.77) and MACCE (AHR 0.66, 95% CI 0.51-0.84) than SAG, while DAG-RA was associated with lower rates of all-cause death (AHR 0.79, 95% CI 0.64-0.99). CONCLUSIONS: In the VA, DAG was associated with improved long-term MACCE outcomes compared to SAG. These results suggest that the practice of DAG in the VA benefits Veterans and should be promoted further.

Impact of Oral Anticoagulation on Clinical Outcomes in Postoperative Atrial Fibrillation.

INTRODUCTION: The impact of postoperative oral anticoagulation (OAC) with warfarin on postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) was the focus of this examination of patients from the randomized endo-vein graft prospective (REGROUP) Trial. MATERIAL AND METHODS: REGROUP was a prospective randomized Veterans Affairs cooperative study comparing endoscopic versus open vein harvest in elective CABG patients (March 2014-April 2017) at 16 Veterans Affairs facilities. This study compared new-onset POAF patients who were treated with warfarin versus no-warfarin. Outcomes included stroke during active follow-up and a major adverse cardiac event composite of mortality, acute myocardial infarction, and repeat revascularization during active and passive follow-up. RESULTS: Of the 316/1103 (28.6%) of REGROUP patients who developed new-onset POAF, 45 patients were excluded - mainly for preoperative warfarin use. Of the remaining 269 patients, 85 received OAC with warfarin (OAC group); 184 did not (no-OAC group). Stroke rates during active follow-up (32 [IQR 24-38] mo) were 3.5% OAC group versus 5.4% no-OAC group (P = 0.76); major adverse cardiac eventrates were 20% OAC versus 11.4% no-OAC (P = 0.06). On longer follow-up of (median 4.61 [IQR 3.9-5.1] y), discharge OAC use was associated with all-cause mortality after adjusting for Society of Thoracic Surgeons mortality risk (20.0% versus 11.4% no-OAC use; HR = 2.00, 95% CI: 1.05-3.81, P = 0.035). CONCLUSIONS: REGROUP patients with POAF treated with OAC had similar stroke and higher mortality rates versus no-OAC patients. Further investigation of the risk-benefit ratio of OAC in post-CABG patients and which POAF patient subgroups might derive the most benefit with anticoagulation appears warranted.

Randomized Trial of Endoscopic or Open Vein-Graft Harvesting for Coronary-Artery Bypass.

BACKGROUND: The saphenous-vein graft is the most common conduit for coronary-artery bypass grafting (CABG). The influence of the vein-graft harvesting technique on long-term clinical outcomes has not been well characterized. METHODS: We randomly assigned patients undergoing CABG at 16 Veterans Affairs cardiac surgery centers to either open or endoscopic vein-graft harvesting. The primary outcome was a composite of major adverse cardiac events, including death from any cause, nonfatal myocardial infarction, and repeat revascularization. Leg-wound complications were also evaluated. RESULTS: A total of 1150 patients underwent randomization. Over a median follow-up of 2.78 years, the primary outcome occurred in 89 patients (15.5%) in the open-harvest group and 80 patients (13.9%) in the endoscopic-harvest group (hazard ratio, 1.12; 95% confidence interval [CI], 0.83 to 1.51; P=0.47). A total of 46 patients (8.0%) in the open-harvest group and 37 patients (6.4%) in the endoscopic-harvest group died (hazard ratio, 1.25; 95% CI, 0.81 to 1.92); myocardial infarctions occurred in 34 patients (5.9%) in the open-harvest group and 27 patients (4.7%) in the endoscopic-harvest group (hazard ratio, 1.27; 95% CI, 0.77 to 2.11), and revascularization occurred in 35 patients (6.1%) in the open-harvest group and 31 patients (5.4%) in the endoscopic-harvest group (hazard ratio, 1.14; 95% CI, 0.70 to 1.85). Leg-wound infections occurred in 18 patients (3.1%) in the open-harvest group and in 8 patients (1.4%) in the endoscopic-harvest group (relative risk, 2.26; 95% CI, 0.99 to 5.15). CONCLUSIONS: Among patients undergoing CABG, we did not find a significant difference between open vein-graft harvesting and endoscopic vein-graft harvesting in the risk of major adverse cardiac events. (Funded by the Cooperative Studies Program, Office of Research and Development, Department of Veterans Affairs; REGROUP ClinicalTrials.gov number, NCT01850082 .).

Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn.

BACKGROUND: Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine). METHODS: Patients who were referred to Veterans Affairs (VA) gastroenterology clinics for PPI-refractory heartburn received 20 mg of omeprazole twice daily for 2 weeks, and those with persistent heartburn underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance-pH monitoring. If patients were found to have reflux-related heartburn, we randomly assigned them to receive surgical treatment (laparoscopic Nissen fundoplication), active medical treatment (omeprazole plus baclofen, with desipramine added depending on symptoms), or control medical treatment (omeprazole plus placebo). The primary outcome was treatment success, defined as a decrease of 50% or more in the Gastroesophageal Reflux Disease (GERD)-Health Related Quality of Life score (range, 0 to 50, with higher scores indicating worse symptoms) at 1 year. RESULTS: A total of 366 patients (mean age, 48.5 years; 280 men) were enrolled. Prerandomization procedures excluded 288 patients: 42 had relief of their heartburn during the 2-week omeprazole trial, 70 did not complete trial procedures, 54 were excluded for other reasons, 23 had non-GERD esophageal disorders, and 99 had functional heartburn (not due to GERD or other histopathologic, motility, or structural abnormality). The remaining 78 patients underwent randomization. The incidence of treatment success with surgery (18 of 27 patients, 67%) was significantly superior to that with active medical treatment (7 of 25 patients, 28%; P = 0.007) or control medical treatment (3 of 26 patients, 12%; P<0.001). The difference in the incidence of treatment success between the active medical group and the control medical group was 16 percentage points (95% confidence interval, -5 to 38; P = 0.17). CONCLUSIONS: Among patients referred to VA gastroenterology clinics for PPI-refractory heartburn, systematic workup revealed truly PPI-refractory and reflux-related heartburn in a minority of patients. For that highly selected subgroup, surgery was superior to medical treatment. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT01265550.).

Pathogens Associated With Linear Growth Faltering in Children With Diarrhea and Impact of Antibiotic Treatment: The Global Enteric Multicenter Study.

BACKGROUND: The association between childhood diarrheal disease and linear growth faltering in developing countries is well described. However, the impact attributed to specific pathogens has not been elucidated, nor has the impact of recommended antibiotic treatment. METHODS: The Global Enteric Multicenter Study enrolled children with moderate to severe diarrhea (MSD) seeking healthcare at 7 sites in sub-Saharan Africa and South Asia. At enrollment, we collected stool samples to identify enteropathogens. Length/height was measured at enrollment and follow-up, approximately 60 days later, to calculate change in height-for-age z scores (ΔHAZ). The association of pathogens with ΔHAZ was tested using linear mixed effects regression models. RESULTS: Among 8077 MSD cases analyzed, the proportion with stunting (HAZ below -1) increased from 59% at enrollment to 65% at follow-up (P < .0001). Pathogens significantly associated with linear growth decline included Cryptosporidium (P < .001), typical enteropathogenic Escherichia coli (P = .01), and untreated Shigella (P = .009) among infants (aged 0-11 months) and enterotoxigenic E. coli encoding heat-stable toxin (P < .001) and Cryptosporidium (P = .03) among toddlers (aged 12-23 months). Shigella-infected toddlers given antibiotics had improved linear growth (P = .02). CONCLUSIONS: Linear growth faltering among children aged 0-23 months with MSD is associated with specific pathogens and can be mitigated with targeted treatment strategies, as demonstrated for Shigella.

Epiaortic Ultrasound for Assessment of Intraluminal Atheroma; Insights from the REGROUP Trial.

OBJECTIVES: To assess the use of epiaortic ultrasound in contemporary cardiac surgery, as well as its impact on surgical cannulation strategy and cerebrovascular events. DESIGN: Epiaortic ultrasound data was prospectively collected in the Randomized Endovein Graft Prospective (REGROUP) trial (VA Cooperative Studies Program #588, ClinicalTrials.gov, NCT01850082), which randomized 1,150 coronary artery bypass graft patients between 2014 and 2017 to endoscopic or open-vein graft harvest. SETTING: Sixteen cardiac surgery programs within the Veterans Affairs Healthcare System with expertise at performing endoscopic vein-graft harvesting. PARTICIPANTS: Veterans Affairs patients, greater than 18 years of age, undergoing elective or urgent coronary artery bypass grafting with cardiopulmonary bypass and cardioplegic arrest with at least one planned saphenous vein graft were eligible for enrollment. INTERVENTIONS: Epiaortic ultrasound was performed by the surgeon using a high frequency (>7 MHz) ultrasound transducer. Two-dimensional images of the ascending aorta in multiple planes were acquired before aortic cannulation and cross-clamping. MEASUREMENTS AND MAIN RESULTS: Epiaortic ultrasound was performed in 34.1% (269 of 790) of patients in REGROUP. Among these patients, simple intraluminal atheroma was observed in 21.9% (59 269), and complex intraluminal atheroma comprised 2.2% (6 of 269). The aortic cannulation or cross-clamp strategy was modified based on these findings in 7.1% of cases (19 of 269). There was no difference in stroke between patients who underwent epiaortic ultrasound and those who did not (1.9% v 1.2% p = 0.523). CONCLUSIONS: Despite current guidelines recommending routine use of epiaortic ultrasound (IIa/B) to reduce the risk of stroke in cardiac surgery, in this contemporary trial, use remains infrequent, with significant site-to-site variability.

Effect of Postoperative Permissive Anemia and Cardiovascular Risk Status on Outcomes After Major General and Vascular Surgery Operative Interventions.

OBJECTIVES: To determine the effect of postoperative permissive anemia and high cardiovascular risk on postoperative outcomes. METHODS: The Veterans Affairs Surgical Quality Improvement Program and Corporate Data Warehouse databases were queried for patients who underwent major vascular or general surgery operations. The status of cardiovascular risk was assessed by calculating the Revised Cardiac Risk Index. Primary endpoint was a composite of mortality, myocardial infarction, acute renal failure, coronary revascularization, or stroke within 90 days postoperatively. RESULTS: We analyzed 142,510 procedures performed from 2000 to 2015. Postoperative anemia was the strongest independent predictor of the primary endpoint whose odds increased by 43% for every g/dL drop in postoperative nadir Hb [95% confidence interval (95% CI): 41-45]. Cardiac risk status as described by the RCRI also independently predicted the primary endpoint, with an additive effect particularly evident at postoperative nadir Hb values below 10 gm/dL. Postoperative anemia, after age, was the second strongest independent predictor of long-term (12 years) mortality (hazard ratio: 1.18, 95% CI: 1.17-1.19). CONCLUSION: Postoperative anemia is strongly associated with postoperative ischemic events, 90-day mortality, and long-term mortality. Restrictive transfusion should be used cautiously after major general and vascular operations, particularly in patients at a high cardiovascular risk.

Shigella isolates from the global enteric multicenter study inform vaccine development.

BACKGROUND: Shigella, a major diarrheal disease pathogen worldwide, is the target of vaccine development. The Global Enteric Multicenter Study (GEMS) investigated burden and etiology of moderate-to-severe diarrheal disease in children aged <60 months and matched controls without diarrhea during 3 years at 4 sites in Africa and 3 in Asia. Shigella was 1 of the 4 most common pathogens across sites and age strata. GEMS Shigella serotypes are reviewed to guide vaccine development. METHODS: Subjects' stool specimens/rectal swabs were transported to site laboratories in transport media and plated onto xylose lysine desoxycholate and MacConkey agar. Suspect Shigella colonies were identified by biochemical tests and agglutination with antisera. Shigella isolates were shipped to the GEMS Reference Laboratory (Baltimore, MD) for confirmation and serotyping of S. flexneri; one-third of isolates were sent to the Centers for Disease Control and Prevention for quality control. RESULTS: Shigella dysenteriae and S. boydii accounted for 5.0% and 5.4%, respectively, of 1130 Shigella case isolates; S. flexneri comprised 65.9% and S. sonnei 23.7%. Five serotypes/subserotypes comprised 89.4% of S. flexneri, including S. flexneri 2a, S. flexneri 6, S. flexneri 3a, S. flexneri 2b, and S. flexneri 1b. CONCLUSIONS: A broad-spectrum Shigella vaccine must protect against S. sonnei and 15 S. flexneri serotypes/subserotypes. A quadrivalent vaccine with O antigens from S. sonnei, S. flexneri 2a, S. flexneri 3a, and S. flexneri 6 can provide broad direct coverage against these most common serotypes and indirect coverage against all but 1 (rare) remaining subserotype through shared S. flexneri group antigens.

Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study.

BACKGROUND: Diarrhoeal diseases cause illness and death among children younger than 5 years in low-income countries. We designed the Global Enteric Multicenter Study (GEMS) to identify the aetiology and population-based burden of paediatric diarrhoeal disease in sub-Saharan Africa and south Asia. METHODS: The GEMS is a 3-year, prospective, age-stratified, matched case-control study of moderate-to-severe diarrhoea in children aged 0-59 months residing in censused populations at four sites in Africa and three in Asia. We recruited children with moderate-to-severe diarrhoea seeking care at health centres along with one to three randomly selected matched community control children without diarrhoea. From patients with moderate-to-severe diarrhoea and controls, we obtained clinical and epidemiological data, anthropometric measurements, and a faecal sample to identify enteropathogens at enrolment; one follow-up home visit was made about 60 days later to ascertain vital status, clinical outcome, and interval growth. FINDINGS: We enrolled 9439 children with moderate-to-severe diarrhoea and 13,129 control children without diarrhoea. By analysing adjusted population attributable fractions, most attributable cases of moderate-to-severe diarrhoea were due to four pathogens: rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli producing heat-stable toxin (ST-ETEC; with or without co-expression of heat-labile enterotoxin), and Shigella. Other pathogens were important in selected sites (eg, Aeromonas, Vibrio cholerae O1, Campylobacter jejuni). Odds of dying during follow-up were 8·5-fold higher in patients with moderate-to-severe diarrhoea than in controls (odd ratio 8·5, 95% CI 5·8-12·5, p<0·0001); most deaths (167 [87·9%]) occurred during the first 2 years of life. Pathogens associated with increased risk of case death were ST-ETEC (hazard ratio [HR] 1·9; 0·99-3·5) and typical enteropathogenic E coli (HR 2·6; 1·6-4·1) in infants aged 0-11 months, and Cryptosporidium (HR 2·3; 1·3-4·3) in toddlers aged 12-23 months. INTERPRETATION: Interventions targeting five pathogens (rotavirus, Shigella, ST-ETEC, Cryptosporidium, typical enteropathogenic E coli) can substantially reduce the burden of moderate-to-severe diarrhoea. New methods and accelerated implementation of existing interventions (rotavirus vaccine and zinc) are needed to prevent disease and improve outcomes. FUNDING: The Bill & Melinda Gates Foundation.

Non-Muscle Invasive Bladder Cancer: Many More Patients Die With It Than Of It.

BACKGROUND: The National Cancer Institute SEER Program regularly publishes bladder-cancer specific survival statistics. However, this data is for all bladder cancers, and information for non-muscle invasive bladder cancer (NMIBC) is difficult to obtain. OBJECTIVE: To quantify 5-year overall and bladder cancer-specific survival in a cohort of Department of Veterans Affairs (VA) patients diagnosed with NMIBC. METHODS: We identified VA patients diagnosed with NMIBC who underwent a transurethral resection from 2003-2013. The patient demographics and Charlson Comorbidity Index were categorized. We acquired the patients' date of death from the Veterans Health Administration's Death Ascertainment File and their cause of death from the Mortality Data Repository. We calculated Kaplan Meier estimates of survival. RESULTS: A total of 27,008 patients were included; median age was 69 and almost all were male (99%). The median comorbidity score was 4. The most prevalent comorbidity indicators included Chronic Pulmonary Disease (48%), cancer other than Bladder (41%), and diabetes (40%). This cohort was found to have a 5-year overall survival of 68% (99% CI 67% -69%) and a 5-year bladder cancer-specific survival of 93% (99% CI 92% -94%). CONCLUSIONS: The 5-year bladder cancer-specific survival in patients diagnosed with non-muscle invasive bladder cancer is substantially higher than the 5-year overall survival. This difference may be related to the severity and number of comorbidities that patients in this population must manage. This warrants further research into the necessity of currently recommended high-intensity cancer surveillance for individuals with NMIBC.

Chronic total occlusions and coronary artery bypass grafting outcomes.

OBJECTIVE: To investigate the association between the presence and grafting of chronic total occlusions (CTOs) and coronary artery bypass grafting (CABG) outcomes. METHODS: This was a post hoc analysis of the Randomized Endograft vs Open Prospective (REGROUP) trial, which randomized veterans undergoing isolated on-pump CABG to endoscopic versus open vein harvest (2014-2017). Patients were stratified on the basis of the presence of at least 1 CTO vessel (a 100% occluded coronary lesion for greater than or equal to 3 months) and according to whether all CTO vessels were bypassed. Rates of major cardiac adverse events (MACE) were compared. RESULTS: At least 1 CTO was present in 453 of 1149 patients (39.4%). Over a median follow-up of 4.7 years (interquartile range, 3.84-5.45), MACE rates were 23.4% versus 22.2% for the CTO versus no CTO group, respectively (adjusted hazard ratio [aHR], 0.92; 95% confidence interval [CI], 0.70-1.20). MACE rates for patients with complete CTO grafting versus not were 23.1% versus 25.0%, respectively (aHR, 0.95; 95% CI, 0.57-1.57). In patients with right coronary dominance undergoing left anterior descending artery grafting, bypassing a right coronary artery CTO was associated with significantly lower rates of all-cause mortality (aHR, 0.38; 95% CI, 0.17-0.83). CONCLUSIONS: In this REGROUP trial subanalysis, neither CTO presence or complete grafting of CTO vessels was associated with significantly different rates of MACE. However, the finding of possible survival benefit among a subgroup of patients undergoing grafting of a dominant RCA CTO vessel alongside left anterior descending artery grafting warrants additional study.

Performance of left internal thoracic artery-left anterior descending artery anastomosis by residents versus attendings and coronary artery bypass grafting outcomes.

OBJECTIVES: Performance of a technically sound left internal thoracic artery to left anterior descending artery (LITA-LAD) anastomosis during coronary artery bypass grafting (CABG) is critically important. We used prospectively collected data from the multicentre, randomized REGROUP (Randomized Endograft Vein Perspective) trial to investigate CABG outcomes based on whether a resident or an attending surgeon performed the LITA-LAD anastomosis. METHODS: This was a post hoc subanalysis of the REGROUP trial, which randomized veterans undergoing isolated on-pump CABG to endoscopic versus open vein harvest from 2014 through 2017. The primary end point was major cardiac adverse events, defined as the composite of all-cause deaths, nonfatal myocardial infarctions or repeat revascularizations. RESULTS: Among 1,084 patients, 344 (31.8%) LITA-LAD anastomoses were performed by residents and 740 (68.2%), by attending surgeons. Residents (compared to attendings) operated on fewer patients with high tercile SYNTAX scores (22.1% vs 37.4%, P < 0.001), performed fewer multiarterial CABGs (5.2% vs 14.6%, P < 0.001) and performed more anastomoses to distal targets with diameters > 2.0 mm (19.0% vs 10.9%, P < 0.001) and non-calcified landing zones (25.1% vs 21.6%, P < 0.001). During a median observation time of 4.7 years (interquartile range 3.84-5.45), major cardiac adverse events occurred in 77 patients (22.4%) in the group treated by residents and 169 patients (22.8%) in the group treated by attendings (unadjusted HR 1.00; 95% confidence interval, 0.76-1.33; P = 0.99). Outcomes persisted on adjusted analyses. CONCLUSIONS: Based on this REGROUP trial subanalysis, under careful supervision and with appropriate patient selection, LITA-LAD anastomoses performed by the residents yielded clinical outcomes similar to those of the attendings.

Complete Coronary Revascularization and Outcomes in Patients Who Underwent Coronary Artery Bypass Grafting: Insights from The REGROUP Trial.

There is growing evidence in support of coronary complete revascularization (CR). Nonetheless, there is no universally accepted definition of CR in patients who undergo coronary bypass grafting surgery (CABG). We sought to investigate the outcomes of CR, defined as surgical revascularization of any territory supplied by a suitable coronary artery with ≥50% stenosis. We performed a preplanned subanalysis in the Randomized Trial of Endoscopic or Open Saphenous Vein Graft Harvesting (REGROUP) clinical trial cohort. Of 1,147 patients who underwent CABG, 810 (70.6%) received CR. The primary outcome was a composite of major adverse cardiac events (MACEs), including death from any cause, nonfatal myocardial infarction, or repeat revascularization over a median 4.7 years of follow-up. MACE occurred in 175 patients (21.6%) in the CR group and 86 patients (25.5%) in the incomplete revascularization (IR) group (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.67 to 1.13, p = 0.29). A total of 97 patients (12.0%) in the CR group and 48 patients (14.2%) in the IR group died (HR 0.93, 95% CI 0.65 to 1.32, p = 0.67); nonfatal myocardial infarction occurred in 49 patients (6.0%) in the CR group and 30 patients (8.9%) in the IR group (HR 0.76, 95% CI 0.48 to 1.2, p = 0.24), and repeat revascularization occurred in 62 patients (7.7%) in the CR group and 39 patients (11.6%) in the IR group (HR 0.64; 95% CI 0.42 to 0.95, p = 0.027). In conclusion, in patients with a great burden of co-morbidities who underwent CABG in the REGROUP trial over a median follow-up period of a median 4.7 years, CR was associated with similar MACE rates but a reduced risk of repeat revascularization. Longer-term follow-up is warranted.

Exoskeletal-Assisted Walking in Veterans With Paralysis: A Randomized Clinical Trial.

Importance: Robotic exoskeletons leverage technology that assists people with spinal cord injury (SCI) to walk. The efficacy of home and community exoskeletal use has not been studied in a randomized clinical trial (RCT). Objective: To examine whether use of a wheelchair plus an exoskeleton compared with use of only a wheelchair led to clinically meaningful net improvements in patient-reported outcomes for mental and physical health. Design, Setting, and Participants: This RCT of veterans with SCI was conducted at 15 Veterans Affairs medical centers in the US from September 6, 2016, to September 27, 2021. Data analysis was performed from March 10, 2022, to June 20, 2024. Interventions: Participants were randomized (1:1) to standard of care (SOC) wheelchair use or SOC plus at-will use of a US Food and Drug Administration (FDA)-cleared exoskeletal-assisted walking (EAW) device for 4 months in the home and community. Main Outcomes and Measures: Two primary outcomes were studied: 4.0-point or greater improvement in the mental component summary score on the Veterans RAND 36-Item Health Survey (MCS/VR-36) and 10% improvement in the total T score of the Spinal Cord Injury-Quality of Life (SCI-QOL) physical and medical health domain and reported as the proportion who achieved clinically meaningful changes. The primary outcomes were measured at baseline, post randomization after advanced EAW training sessions, and at 2 months and 4 months (primary end point) in the intervention period. Device usage, reasons for not using, and adverse events were collected. Results: A total of 161 veterans with SCI were randomized to the EAW (n = 78) or SOC (n = 83) group; 151 (94%) were male, the median age was 47 (IQR, 35-56) years, and median time since SCI was 7.3 (IQR, 0.5 to 46.5) years. The difference in proportion of successes between the EAW and SOC groups on the MCS/VR-36 (12 of 78 [15.4%] vs 14 of 83 [16.9%]; relative risk, 0.91; 95% CI, 0.45-1.85) and SCI-QOL physical and medical health domain (10 of 78 [12.8%] vs 11 of 83 [13.3%]; relative risk, 0.97; 95% CI, 0.44-2.15) was not statistically different. Device use was lower than expected (mean [SD] distance, 1.53 [0.02] miles per month), primarily due to the FDA-mandated companion being unavailable 43.9% of the time (177 of 403 instances). Two EAW-related foot fractures and 9 unrelated fractures (mostly during wheelchair transfers) were reported. Conclusions and Relevance: In this RCT of veterans with SCI, the lack of improved outcomes with EAW device use may have been related to the relatively low device usage. Solutions for companion requirements and user-friendly technological adaptations should be considered for improved personal use of these devices. Trial Registration: ClinicalTrials.gov Identifier: NCT02658656.

Transfusion trigger after operations in high cardiac risk patients (TOP) trial protocol. Protocol for a multicenter randomized controlled transfusion strategy trial.

BACKGROUND: There is substantial uncertainty regarding the effects of restrictive postoperative transfusion among patients who have underlying cardiovascular disease. The TOP Trial's objective is to compare adverse outcomes between liberal and restrictive transfusion strategies in patients undergoing vascular and general surgery operations, and with a high risk of postoperative cardiac events. METHODS: A two-arm, single-blinded, randomized controlled superiority trial will be used across 15 Veterans Affairs hospitals with expected enrollment of 1520 participants. Postoperative transfusions in the liberal arm commence when Hb is <10 g/ dL and continue until Hb is greater than or equal to 10 g/dL. In the restrictive arm, transfusions begin when Hb is <7 g/dL and continue until Hb is greater than or equal to 7 g/dL. Study duration is estimated to be 5 years including a 3-month start-up period and 4 years of recruitment. Each randomized participant will be followed for 90 days after randomization with a mortality assessment at 1 year. RESULTS: The primary outcome is a composite endpoint of all-cause mortality, myocardial infarction (MI), coronary revascularization, acute renal failure, or stroke occurring up to 90-days after randomization. Events rates will be compared between restrictive and liberal transfusion groups. CONCLUSIONS: The TOP Trial is uniquely positioned to provide high quality evidence comparing transfusion strategies among patients with high cardiac risk. Results will clarify the effect of postoperative transfusion strategies on adverse outcomes and inform postoperative management algorithms. TRIAL REGISTRATION: http://clinicaltrials.gov identifier: NCT03229941.

Therapeutic and Economic Benefits of Service Dogs Versus Emotional Support Dogs for Veterans With PTSD.

OBJECTIVE: This work aimed to assess the therapeutic and economic benefits of service dogs versus emotional support dogs for veterans with posttraumatic stress disorder (PTSD). METHODS: Veterans with PTSD (N=227) participating in a multicenter trial were randomly assigned to receive a service or emotional support dog; 181 veterans received a dog and were followed up for 18 months. Primary outcomes included overall functioning (assessed with World Health Organization Disability Assessment Scale II [WHODAS 2.0]) and quality of life (Veterans RAND 12-Item Health Survey [VR-12]). Secondary outcomes included PTSD symptoms (PTSD Checklist for DSM-5), suicidal ideation, depression, sleep quality, health care costs and utilization, medication adherence, employment, and productivity. RESULTS: Participants paired with a dog had a mean±SD age of 50.6±13.6 years (range 22-79), and most were male (80%), White (66%), and non-Hispanic (91%). Adjusted linear mixed repeated-measures models indicated no difference between the two groups on WHODAS 2.0 or VR-12 scores. Participants with service dogs had a 3.7-point greater reduction in PTSD symptoms versus participants with emotional support dogs (p=0.036). No reduced health care utilization or cost was associated with receiving a service dog. Veterans with service dogs had an increase of 10 percentage points in antidepressant adherence compared with those with emotional support dogs (p<0.01). CONCLUSIONS: Both groups appeared to benefit from having a service or emotional support dog. No significant differences in improved functioning or quality of life were observed between the groups. Those in the service dog group had a greater reduction in PTSD symptoms and better antidepressant adherence, improvements that should be explored further.

Statistical methods in the Global Enteric Multicenter Study (GEMS).

The Global Enteric Multicenter Study (GEMS) is an investigation of the burden (number of cases and incidence) of moderate-to-severe diarrhea (MSD) in children <60 months of age at 7 sites in sub-Saharan Africa and South Asia. The population attributable fraction for a putative pathogen, either unadjusted or adjusted for other pathogens, is estimated using the proportion of MSD cases from whom the pathogen was isolated and the odds ratio for MSD and the pathogen from conditional logistic regression modeling. The adjusted attributable fraction, proportion of MSD cases taken to a sentinel health center (SHC), number of cases presenting to an SHC, and the site's population are used to estimate the annual number of MSD cases and MSD incidence rate attributable to a pathogen or group of pathogens. Associations with death and nutritional outcomes, ascertained at follow-up visits to case and control households, are evaluated both in MSD cases and in the population.

Data management and other logistical challenges for the GEMS: the data coordinating center perspective.

The Cooperative Studies Program Coordinating Center provided the data management, administrative, and statistical support to the Global Enteric Multicenter Study (GEMS). The GEMS study, the largest epidemiological study in the diarrheal disease area among children <5 years of age, was carried out in 4 African countries and 3 Asian countries. Given the geographical and geopolitical differences among the countries, the administration of a centralized data management operation was a major challenge. The sheer volume of the data that were collected, regular transfer of the data to a centralized database, and the cleaning of the same also posed some challenges. This paper outlines the details of the support that the data coordinating center provided and the challenges faced during the course of the study.

The Global Enteric Multicenter Study (GEMS) of diarrheal disease in infants and young children in developing countries: epidemiologic and clinical methods of the case/control study.

BACKGROUND: Diarrhea is a leading cause of illness and death among children aged <5 years in developing countries. This paper describes the clinical and epidemiological methods used to conduct the Global Enteric Multicenter Study (GEMS), a 3-year, prospective, age-stratified, case/control study to estimate the population-based burden, microbiologic etiology, and adverse clinical consequences of acute moderate-to-severe diarrhea (MSD) among a censused population of children aged 0-59 months seeking care at health centers in sub-Saharan Africa and South Asia. METHODS: GEMS was conducted at 7 field sites, each serving a population whose demography and healthcare utilization practices for childhood diarrhea were documented. We aimed to enroll 220 MSD cases per year from selected health centers serving each site in each of 3 age strata (0-11, 12-23, and 24-59 months), along with 1-3 matched community controls. Cases and controls supplied clinical, epidemiologic, and anthropometric data at enrollment and again approximately 60 days later, and provided enrollment stool specimens for identification and characterization of potential diarrheal pathogens. Verbal autopsy was performed if a child died. Analytic strategies will calculate the fraction of MSD attributable to each pathogen and the incidence, financial costs, nutritional consequences, and case fatality overall and by pathogen. CONCLUSIONS: When completed, GEMS will provide estimates of the incidence, etiology, and outcomes of MSD among infants and young children in sub-Saharan Africa and South Asia. This information can guide development and implementation of public health interventions to diminish morbidity and mortality from diarrheal diseases.

Costs of Endoscopic vs Open Vein Harvesting for Coronary Artery Bypass Grafting: A Secondary Analysis of the REGROUP Trial.

Importance: Value-based purchasing creates pressure to examine whether newer technologies and care processes, including new surgical techniques, yield any economic advantage. Objective: To compare health care costs and utilization between participants randomized to receive endoscopic vein harvesting (EVH) or open vein harvesting (OVH) during a coronary artery bypass grafting (CABG) procedure. Design, Setting, and Participants: This secondary economic analysis was conducted alongside the 16-site Randomized Endo-Vein Graft Prospective (REGROUP) clinical trial funded by the Department of Veterans Affairs (VA) Cooperative Studies Program. Adults scheduled for urgent or elective bypass involving a vein graft were eligible. The first participant was enrolled in September 2013, with most sites completing enrollment by March 2014. The last participant was enrolled in April 2017. A total of 1150 participants were randomized, with 574 participants receiving OVH and 576 receiving EVH. For this secondary analysis, cost and utilization data were extracted through September 30, 2020. Participants were linked to administrative data in the VA Corporate Data Warehouse and activity-based cost data starting with the index procedure. Interventions: EVH vs OVH, with comparisons based on intention to treat. Main Outcomes and Measures: Discharge costs for the index procedure as well as follow-up costs (including intended and unintended events; mean [SD] follow-up time, 33.0 [19.9] months) were analyzed, with results from different statistical models compared to test for robustness (ie, lack of variation across models). All costs represented care provided or paid by the VA, standardized to 2020 US dollars. Results: Among 1150 participants, the mean (SD) age was 66.4 (6.9) years; most participants (1144 [99.5%] were male. With regard to race and ethnicity, 6 participants (0.5%) self-reported as American Indian or Alaska Native, 10 (0.9%) as Asian or Pacific Islander, 91 (7.9%) as Black, 62 (5.4%) as Hispanic, 974 (84.7%) as non-Hispanic White, and 6 (0.5%) as other race and/or ethnicity; data were missing for 1 participant (0.1%). The unadjusted mean (SD) costs for the index CABG procedure were $76 607 ($43 883) among patients who received EVH and $75 368 ($45 900) among those who received OVH, including facility costs, insurance costs, and physician-related costs (commonly referred to as provider costs in Centers for Medicare and Medicaid and insurance data). No significant differences were found in follow-up costs; per 90-day follow-up period, EVH was associated with a mean (SE) added cost of $302 ($225) per patient. The results were highly robust to the statistical model. Conclusions and Relevance: In this study, EVH was not associated with a reduction in costs for the index CABG procedure or follow-up care. Therefore, the choice to provide EVH may be based on surgeon and patient preferences. Trial Registration: ClinicalTrials.gov Identifier: NCT01850082.