Predictors of multi-domain cognitive decline following DBS for treatment of Parkinson's disease.

BACKGROUND: Statistically and clinically significant cognitive declines are observed in a small subset of individuals with Parkinson's Disease (PD) following treatment with Deep Brain Stimulation (DBS). OBJECTIVES: We examine the association between multi-domain cognitive decline (MCD) and demographic and baseline clinical variables and the incidence of serious adverse events (SAE) arising within a six-month interval following DBS for PD. METHOD: Study participants with PD who displayed MCD at 6-month follow-up evaluation after DBS (n = 18) were contrasted with individuals with PD from the same study who did not show cognitive decline after DBS (n = 146). Logistic regression analyses were employed to assess relationship between predictors, including age (>70 years old), pre-DBS cognitive screening test performance, SAE, and MCD. MCD+ and MCD-groups were also compared on other baseline clinical and demographic variables. RESULTS: MCD showed modest association with older age and lower baseline neurocognitive screening performance, whereas the groups did not differ on most other baseline clinical and demographic variables. SAEs during the study interval were the most robust predictor of MCD in the DBS group. A variety of SAEs were documented in study participants experiencing MCD after DBS surgery, including, but not limited to, infections and small intracranial hemorrhages. CONCLUSIONS: Older age and lower baseline cognition measured prior to treatment are associated with MCD measured at six-months after DBS. SAE occurring following DBS surgery are also predictive of MCD. These predictors may reflect aspects of "frailty" in advanced PD. Risk factors for SAE warrant careful consideration in clinical trials.

Eye Outcomes in Veteran Affairs Diabetes Trial (VADT) After 17 Years.

OBJECTIVE: The objective of this study was to assess the long-term role of intensive glycemic control (INT) compared with standard glycemic control in accumulated eye procedures in patients with advanced diabetes. RESEARCH DESIGN AND METHODS: We compared the effect of treatment assignment on the accumulated number of eye procedures during the intervention period of the Veteran Affairs Diabetes Trial (VADT) (2000-2008) (median follow-up 5.6 years), the interim VADT follow-up study (2000-2013), and the full 17 years of VADT follow-up (2000-2017). We further analyzed data using various cardiovascular markers in two models. Model I included total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, systolic and diastolic blood pressure, and BMI. Model II included these covariates plus age and diabetic retinopathy (DR) severity score at baseline of the original trial. RESULTS: The final analysis of the data showed a mild but nonsignificant increase in number of procedures and in retinal or retinal plus cataract surgery during the three periods of the study. CONCLUSIONS: We found no significant benefit of INT during the original trial period in eye-related procedures, such as various procedures for DR, or during the 17 years of follow-up in cataract surgery. However, after adjusting data for some known vascular markers, the increase in the number of eye procedures with INT becomes more prevalent. This finding indicates that INT might not have a protective role in events requiring surgery in individuals with advanced diabetes.

Medical Correlates of Chronic Multisymptom Illness in Gulf War Veterans.

BACKGROUND: Chronic multisymptom illness (CMI) is more prevalent among deployed than nondeployed veterans from the first Gulf War. Objective physiologic markers of CMI are lacking. The purpose of this study is to determine whether measurable abnormalities in the autonomic nervous system or hypothalamic-pituitary adrenal axis would distinguish CMI cases (CMI+) from controls (CMI-) among deployed veterans of the 1990-1991 Gulf War. METHODS: This is a cross-sectional case-control cohort study that examined deployed veterans who participated in the Phase III study: National Health Survey of Gulf War Veterans and Their Families. Autonomic nervous system and hypothalamic-pituitary adrenal axis function-related measures included: 24-hour heart-rate variability, urinary catecholamines and cortisol, hypertension, insulin sensitivity, dyslipidemia, body fat, bone mineral density, and ultrasensitive C-reactive protein. RESULTS: Veterans of the first Gulf War with CMI (n = 73) and without the condition (n = 111) were studied. Sociodemographic characteristics were similar. Veterans with CMI reported poorer mental and physical functioning, greater use of prescription medications, and more nonroutine clinic visits. These veterans were also more likely to have fibromyalgia syndrome, irritable bowel syndrome, metabolic syndrome, and among males, a larger waist-to-hip ratio. Lower values for a nonlinear heart-rate-variability parameter-the short-term fractal scaling exponent (DFA1), reflecting an increased randomness of beat-to-beat changes in heart rate-were observed in veterans with CMI than those veterans without it (1.28±0.16vs 1.35±0.15; p=0.005). Hypothalamic-pituitary-adrenal axis function measures were similar between the two groups. CONCLUSION: In this cohort of deployed veterans from the first Gulf War, we identified abnormal heart-rate variability in veterans with CMI compared to veterans without the condition, which suggests abnormal functioning of the autonomic nervous system and possible long-term cardiovascular effects.

Indirect vs Direct Voice Therapy for Children With Vocal Nodules: A Randomized Clinical Trial.

Importance: Benign vocal fold nodules affect 12% to 22% of the pediatric population, and 95% of otolaryngologists recommend voice therapy as treatment. However, no randomized clinical trials that we are aware of have shown its benefits. Objective: To determine the impact of voice therapy in children with vocal fold nodules according to pretherapy and posttherapy scores on the Pediatric Voice-Related Quality of Life (PVRQOL) survey; secondary objectives included changes in phonatory parameters. Design, Setting, and Participants: For this multicenter randomized clinical trial, 114 children ages 6 to 10 years with vocal fold nodules, PVRQOL scores less than 87.5, and dysphonia for longer than 12 weeks were recruited from outpatient voice and speech clinics. This age range was identified because these patients have not experienced pubertal changes of the larynx, tolerate stroboscopy, and cooperate with voice therapy. Participants were blinded to treatment arm. Interventions: Participants received either indirect or direct therapy for 8 to 12 weeks. Indirect therapy focused on education and discussion of voice principles, while direct treatment used the stimulus, response, antecedent paradigm. Main Outcomes and Measures: The primary outcome measure was PVRQOL score change before and after treatment. Secondary phonatory measures were also compared. Results: Overall, 114 children were recruited for study (mean [SD] age, 8 [1.4] years; 83 males [73%]); with 57 randomized to receive either indirect or direct therapy. Both direct and indirect therapy approaches showed significant differences in PVRQOL scores pretherapy to posttherapy. The mean increase in PVRQOL score for direct therapy was 19.2, and 14.7 for indirect therapy (difference, 4.5; 95.3% CI, -10.8 to 19.8). Of 44 participants in the direct therapy group, 27 (61%) achieved a clinically meaningful PVRQOL improvement, compared with 26 of 49 (53%) for indirect therapy (difference, 8%; 95% CI, -12 to 28). Post hoc stratification showed robust effects in the direct therapy group for older children (Cohen d = 0.50) and the latter two-thirds of participants (Cohen d = 0.46). Vocal fold nodules reduced in size in 31% (22 of 70) and completely resolved in 11% (8 of 70) of participants who consented to a second set of images after going through the recruitment process. Conclusions and Relevance: Both direct and indirect voice therapy improved voice-related quality of life in children with vocal fold nodules, although there was no significant difference between approaches. Future studies may focus upon which voice therapy approaches are effective in treating age-defined populations. Trial Registration: clinicaltrials.gov Identifier: NCT01255735.

Neuropsychological changes following deep brain stimulation surgery for Parkinson's disease: comparisons of treatment at pallidal and subthalamic targets versus best medical therapy.

BACKGROUND: Deep brain stimulation (DBS) improves motor symptoms in Parkinson's disease (PD), but questions remain regarding neuropsychological decrements sometimes associated with this treatment, including rates of statistically and clinically meaningful change, and whether there are differences in outcome related to surgical target. METHODS: Neuropsychological functioning was assessed in patients with Parkinson's disease (PD) at baseline and after 6 months in a prospective, randomised, controlled study comparing best medical therapy (BMT, n=116) and bilateral deep brain stimulation (DBS, n=164) at either the subthalamic nucleus (STN, n=84) or globus pallidus interna (GPi, n=80), using standardised neuropsychological tests. Measures of functional outcomes were also administered. RESULTS: Comparison of the two DBS targets revealed few significant group differences. STN DBS was associated with greater mean reductions on some measures of processing speed, only one of which was statistically significant in comparison with stimulation of GPi. GPi DBS was associated with lower mean performance on one measure of learning and memory that requires mental control and cognitive flexibility. Compared to the group receiving BMT, the combined DBS group had significantly greater mean reductions at 6-month follow-up in performance on multiple measures of processing speed and working memory. After calculating thresholds for statistically reliable change from data obtained from the BMT group, the combined DBS group also displayed higher rates of decline in neuropsychological test performance. Among study completers, 18 (11%) study participants receiving DBS displayed reliable decline by multiple indicators in two or more cognitive domains, a significantly higher rate than in the BMT group (3%). This multi-domain cognitive decline was associated with less beneficial change in subjective ratings of everyday functioning and quality of life (QOL). The multi-domain cognitive decline group continued to function at a lower level at 24-month follow-up. CONCLUSIONS: In those with PD, the likelihood of significant decline in neuropsychological functioning increases with DBS, affecting a small minority of patients who also appear to respond less optimally to DBS by other indicators of QOL. TRIAL REGISTRATION NUMBER: NCT00056563 and NCT01076452.

Department of Veterans Affairs Cooperative Studies Program Network of Dedicated Enrollment Sites: Implications for Surgical Trials.

IMPORTANCE: Surgical clinical trials have played a critical role in shaping clinical practice, yet their launch and conduct remain challenging. Innovative approaches to carrying out such studies can not only help transform how trials produce definitive evidence but also move the field toward increased participation in trials. OBJECTIVE: To review a recently launched pilot program aimed at enhancing patient enrollment and improving surgical trial operations at individual sites and nationally. SETTING AND PARTICIPANTS: After a solicitation to create a national network focused on making the conduct of clinical trials more efficient, 10 Department of Veterans Affairs (VA) sites were selected. These sites, collectively called the Cooperative Studies Program (CSP) Network of Dedicated Enrollment Sites (NODES), were evaluated with regard to their previous participation in CSP multisite trials, the strength of the local clinical research environment, and presentation of innovative plans to coordinate and enhance the operations of local CSP studies and share best practices with other centers. Node accountability was also emphasized and involved metrics that tracked productivity and efficiency. RESULTS: Building from available CSP experience in a range of clinical trials, including ones involving surgical interventions, NODES provides VA surgeons with resources for facilitating timely study initiation, determining patient availability, and addressing enrollment barriers. Such resources are particularly important for surgical studies, which often face challenges in patient recruitment and retention. In addition, NODES can maintain qualified and trained personnel at sites to support surgeons with limited time to fulfill the numerous administrative and regulatory responsibilities that often fall to the investigators. CONCLUSIONS AND RELEVANCE: The VA's approach to enhancing trial efficiency may reinvigorate interest in surgical trials by offering a redesigned cooperative framework that builds on a core of high-yield sites and could mitigate traditional limitations of surgical trials.

Plaque regression and progenitor cell mobilization with intensive lipid elimination regimen (PREMIER) trial design.

Progression of lipid rich necrotic core elements of atherosclerotic vulnerable plaque (VP) or its rupture leads to a majority of cardiovascular events. Endothelial progenitor cells (EPC) contribute to vascular healing and play a crucial role in repair following ischemic injury primarily by endothelialization of VP and neovascularization of ischemic myocardium. We present the rationale and design of the Plaque Regression and Progenitor Cell Mobilization with Intensive Lipid Elimination Regimen or the PREMIER Trial, which is designed to address the question for the very first time whether a highly intensive low-density lipoprotein (LDL)-lowering therapy with LDL-apheresis could lead to a more rapid and detectable reduction in coronary atheroma volume, along with a robust mobilization of EPC compared to standard statin therapy, in patients selected for percutaneous coronary intervention for an acute coronary syndrome.

Long-term results of a randomized controlled trial of a nonoperative strategy (watchful waiting) for men with minimally symptomatic inguinal hernias.

OBJECTIVE: To assess the long-term crossover (CO) rate in men undergoing watchful waiting (WW) as a primary treatment strategy for their asymptomatic or minimally symptomatic inguinal hernias. BACKGROUND: With an average follow-up of 3.2 years, a randomized controlled trial comparing WW with routine repair for male patients with minimally symptomatic inguinal hernias led investigators to conclude that WW was an acceptable option [JAMA. 2006;295(3):285-292]. We now analyze patients in the WW group after an additional 7 years of follow-up. METHODS: At the conclusion of the original study, 254 men who had been assigned to WW consented to longer-term follow-up. These patients were contacted yearly by mail questionnaire. Nonresponders were contacted by phone or e-mail for additional data collection. RESULTS: Eighty-one of the 254 men (31.9%) crossed over to surgical repair before the end of the original study, December 31, 2004, with a median follow-up of 3.2 (range: 2-4.5) years. The patients have now been followed for an additional 7 years with a maximum follow-up of 11.5 years. The estimated cumulative CO rates using Kaplan-Meier analysis was 68%. Men older than 65 years crossed over at a considerably higher rate than younger men (79% vs 62%). The most common reason for CO was pain (54.1%). A total of 3 patients have required an emergency operation, but there has been no mortality. CONCLUSIONS: Men who present to their physicians because of an inguinal hernia even when minimally symptomatic should be counseled that although WW is a reasonable and safe strategy, symptoms will likely progress and an operation will be needed eventually.

Suicide ideation and behaviours after STN and GPi DBS surgery for Parkinson's disease: results from a randomised, controlled trial.

BACKGROUND: The risk of suicide behaviours post-deep brain stimulation (DBS) surgery in Parkinson's disease (PD) remains controversial. We assessed if suicide ideation and behaviours are more common in PD patients (1) randomised to DBS surgery versus best medical therapy (BMT); and (2) randomised to subthalamic nucleus (STN) versus globus pallidus interna (GPi) DBS surgery. METHODS: In Phase 1 of the Veterans Affairs CSP 468 study, 255 PD patients were randomised to DBS surgery (n=121) or 6 months of BMT (n=134). For Phase 2, a total of 299 patients were randomised to STN (n=147) or GPi (n=152) DBS surgery. Patients were assessed serially with the Unified Parkinson's Disease Rating Scale Part I depression item, which queries for suicide ideation; additionally, both suicide behaviour adverse event data and proxy symptoms of increased suicide risk from the Parkinson's Disease Questionnaire (PDQ-39) and the Short Form Health Survey (SF-36) were collected. RESULTS: In Phase 1, no suicide behaviours were reported, and new-onset suicide ideation was rare (1.9% for DBS vs 0.9% for BMT; Fisher's exact p=0.61). Proxy symptoms of relevance to suicide ideation were similar in the two groups. Rates of suicide ideation at 6 months were similar for patients randomised to STN versus GPi DBS (1.5% vs 0.7%; Fisher's exact p=0.61), but several proxy symptoms were worse in the STN group. CONCLUSIONS: Results from the randomised, controlled phase of a DBS surgery study in PD patients do not support a direct association between DBS surgery and an increased risk for suicide ideation and behaviours.

Percutaneous coronary intervention versus coronary bypass surgery in United States veterans with diabetes.

OBJECTIVES: This study sought to determine the optimal coronary revascularization strategy in patients with diabetes with severe coronary disease. BACKGROUND: Although subgroup analyses from large trials, databases, and meta-analyses have found better survival for patients with diabetes with complex coronary artery disease when treated with surgery, a randomized trial comparing interventions exclusively with drug-eluting stents and surgery in patients with diabetes with high-risk coronary artery disease has not yet been reported. METHODS: In a prospective, multicenter study, 198 eligible patients with diabetes with severe coronary artery disease were randomly assigned to either coronary artery bypass grafting (CABG) (n = 97) or percutaneous coronary intervention (PCI) with drug-eluting stents (n = 101) and followed for at least 2 years. The primary outcome measure was a composite of nonfatal myocardial infarction or death. Secondary outcome measures included all-cause mortality, cardiac mortality, nonfatal myocardial infarction, and stroke. RESULTS: The study was stopped because of slow recruitment after enrolling only 25% of the intended sample size, leaving it severely underpowered for the primary composite endpoint of death plus nonfatal myocardial infarction (hazard ratio: 0.89; 95% confidence interval: 0.47 to 1.71). However, after a mean follow-up period of 2 years, all-cause mortality was 5.0% for CABG and 21% for PCI (hazard ratio: 0.30; 95% confidence interval: 0.11 to 0.80), while the risk for nonfatal myocardial infarction was 15% for CABG and 6.2% for PCI (hazard ratio: 3.32; 95% confidence interval: 1.07 to 10.30). CONCLUSIONS: This study was severely underpowered for its primary endpoint, and therefore no firm conclusions about the comparative effectiveness of CABG and PCI are possible. There were interesting differences in the components of the primary endpoint. However, the confidence intervals are very large, and the findings must be viewed as hypothesis generating only. (Coronary Artery Revascularization in Diabetes; NCT00326196).

A clinician's guide to patient selection for watchful waiting management of inguinal hernia.

OBJECTIVE: The goal of this study was to assist surgeons in managing patients with minimally symptomatic inguinal hernia by identifying characteristics that predict crossover to surgery or worsening of hernia symptoms. BACKGROUND: Randomized trials have suggested that watchful waiting management of minimally symptomatic inguinal hernia is an acceptable alternative to surgical repair. However, these trials found that roughly a quarter of patients would elect for repair in the first 2 years, suggesting that not all patients are good candidates for watchful waiting. METHODS: The 336 patients randomized to watchful waiting in the American College of Surgeons Watchful Waiting Hernia Trial constituted the study population. Preoperative patient characteristics were used to predict 2 outcomes, either crossover to surgery or the development of hernia pain limiting activities and/or crossover to surgery. Patients in our study were part of a previously registered randomized trial: NCT00263250. RESULTS: At 2 years, 72 patients crossed over to surgery, with pain with strenuous activities [odds ratio (OR), 1.3 per 10-mm visual analog scale pain scale], chronic constipation (OR, 4.9), prostatism (OR, 2.9), being married (OR, 2.3), and good health [OR, 3.0 American Society of Anesthesiologists Class (ASA) 1 vs 2], predicting crossover. An additional 28 patients developed pain, limiting their activities, with pain during strenuous activities (OR, 1.3 per 10-mm visual analog scale) and chronic constipation (OR, 4.5), predicting the combined outcome of pain limiting activities and/or crossover to surgery. Higher levels of activity reduced the risk (OR, 0.95) of this combined outcome. CONCLUSIONS: Readily identifiable patient characteristics can predict those patients with minimally symptomatic inguinal hernia who are likely to "fail" watchful waiting hernia management. Consideration of these factors will allow surgeons to optimally tailor hernia management.

Radial artery grafts vs saphenous vein grafts in coronary artery bypass surgery: a randomized trial.

CONTEXT: Arterial grafts are thought to be better conduits than saphenous vein grafts for coronary artery bypass grafting (CABG) based on experience with using the left internal mammary artery to bypass the left anterior descending coronary artery. The efficacy of the radial artery graft is less clear. OBJECTIVE: To compare 1-year angiographic patency of radial artery grafts vs saphenous vein grafts in patients undergoing elective CABG. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized controlled trial conducted from February 2003 to February 2009 at 11 Veterans Affairs medical centers among 757 participants (99% men) undergoing first-time elective CABG. INTERVENTIONS: The left internal mammary artery was used to preferentially graft the left anterior descending coronary artery whenever possible; the best remaining recipient vessel was randomized to radial artery vs saphenous vein graft. MAIN OUTCOME MEASURES: The primary end point was angiographic graft patency at 1 year after CABG. Secondary end points included angiographic graft patency at 1 week after CABG, myocardial infarction, stroke, repeat revascularization, and death. RESULTS: Analysis included 733 patients (366 in the radial artery group, 367 in the saphenous vein group). There was no significant difference in study graft patency at 1 year after CABG (radial artery, 238/266; 89%; 95% confidence interval [CI], 86%-93%; saphenous vein, 239/269; 89%; 95% CI, 85%-93%; adjusted OR, 0.99; 95% CI, 0.56-1.74; P = .98). There were no significant differences in the secondary end points. CONCLUSION: Among Veterans Affairs patients undergoing first-time elective CABG, the use of a radial artery graft compared with saphenous vein graft did not result in greater 1-year patency. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00054847.

Preoperative coronary artery revascularization and long-term outcomes following abdominal aortic vascular surgery in patients with abnormal myocardial perfusion scans: a subgroup analysis of the coronary artery revascularization prophylaxis trial.

BACKGROUND: Abdominal aortic operations have the highest perioperative cardiac risk. To test the impact of preoperative coronary artery revascularization (PR) in this high-risk subset, a post hoc analysis was performed in patients undergoing aortic surgery within the Coronary Artery Revascularization Prophylaxis (CARP) trial. METHODS: The study cohort was a subset of 109 CARP patients with myocardial ischemia on nuclear imaging randomized to a strategy of PR (N = 52) or no PR (N = 57) before their scheduled abdominal aortic vascular operation. The clinical indications for vascular surgery were an expanding aneurysm (N = 62) or severe claudication (N = 47). The composite end-point of death and nonfatal myocardial infarction (MI) was determined by an intention-to-treat analysis following randomization. RESULTS: The median time (Interquartiles) from randomization to vascular surgery was 56 (40, 81) days in patients assigned to PR and 19 (10, 43) days in patients assigned to no PR (P < 0.001). At 2.7 years following randomization, the probability of remaining free of death and nonfatal MI was 0.65 with PR and 0.55 with no PR [unadjusted P = 0.08, odds ratio = 1.67, 95% confidence interval (0.93, 2.99)]. Using a Cox proportional hazard model, predictors of the composite of death and nonfatal MI (odds ratio; 95% confidence interval) were no PR (1.90; 1.06-3.43; P = 0.03) and anterior ischemia on preoperative imaging (1.79; 0.99-3.23; P = 0.07). CONCLUSIONS: In patients with an abnormal cardiac imaging before abdominal aortic vascular surgery, PR was associated with a reduced risk of death and nonfatal MI while anterior ischemia was an identifier of poor outcome independent of the revascularization status.

Predictors of surgical site infection in laparoscopic and open ventral incisional herniorrhaphy.

BACKGROUND: Surgical site infection (SSI) after ventral incisional hernia repair (VIH) can result in serious consequences. We sought to identify patient, procedure, and/or hernia characteristics that are associated with SSI in VIH. METHODS: Between 2004 and 2006, patients were randomized in four Veteran Affairs (VA) hospitals to undergo laparoscopic or open VIH. Patients who developed SSI within eight weeks postoperatively were compared to those who did not. A bivariate analysis for each factor and a multiple logistic regression analysis were performed to determine factors associated with SSI. The variables studied included patient characteristics and co-morbidities (e.g., age, gender, race, ethnicity, body mass index, ASA classification, diabetes, steroid use), hernia characteristics (e.g., size, duration, number of previous incisions), procedure characteristics (e.g., open versus laparoscopic, blood loss, use of postoperative drains, operating room temperature) and surgeons' experience (resident training level, number of open VIH previously performed by the attending surgeon). Antibiotic prophylaxis, anticoagulation protocols, preparation of the skin, draping of the wound, body temperature control, and closure of the surgical site were all standardized and monitored throughout the study period. RESULTS: Out of 145 patients who underwent VIH, 21 developed a SSI (14.5%). Patients who underwent open VIH had significantly more SSIs than those who underwent laparoscopic VIH (22.1% versus 3.4%; P = 0.002). Among patients who underwent open VIH, those who developed SSI had a recorded intraoperative blood loss greater than 25 mL (68.4% versus 40.3%; P = 0.030), were more likely to have a drain placed (79.0% versus 49.3%; P = 0.021) and were more likey to be operated on by surgeons with less than 75 open VIH case experience (52.6% versus 28.4%; P = 0.048). Patient and hernia characteristics were similar between the two groups. In a multiple logistic regression analysis, the open surgical technique was associated with SSI (OR 8.03, 95% CI 2.03, 31.72; P = 0.003) while controlling for the VA medical center where the procedure was performed (P = 0.041). CONCLUSION: Open surgical technique and the medical center rather than patient co-morbidities or hernia characteristics are associated with the formation of postoperative SSI in VIH.

Comparison of laparoscopic and open repair with mesh for the treatment of ventral incisional hernia: a randomized trial.

BACKGROUND: Laparoscopic repair of ventral incisional hernias has not been proved to be safer than open mesh repair. DESIGN: Prospective randomized trial conducted between February 1, 2004, to January 31, 2007. SETTING: Four Veterans Affairs medical centers. PARTICIPANTS: One hundred sixty-two patients with ventral incisional hernias. INTERVENTIONS: Standardized laparoscopic or open repair. MAIN OUTCOME MEASURES: Overall complication rates at 8 weeks and the odds of complications, adjusted for study site, body mass index, and hernia type. RESULTS: Of the 162 randomized patients, 146 underwent surgery (73 open and 73 laparoscopic repairs). Complications were less common in the laparoscopic group (23 patients [31.5%]) compared with the open repair group (35 patients [47.9%]; adjusted odds ratio [AOR], 0.45; 95% confidence interval [CI], 0.22-0.91; P = .03). Surgical site infection through 8 weeks was less common in the laparoscopic group (5.6% vs 23.3%; AOR, 0.2; 95% CI, 0.1-0.6). The mean worst pain score in the laparoscopic group was 15.2 mm lower on a visual analog scale at 52 weeks (95% CI, 1.0-29.3; P = .04). Time to resume work activities was shorter for the laparoscopic group than for the open repair group (median, 23.0 days vs 28.5 days), with an adjusted hazard ratio of 0.54 (95% CI, 0.28-1.04; P = .06). Overall recurrence at 2 years was 12.5% in the laparoscopic group and 8.2% in the open repair group (AOR, 1.6; 95% CI, 0.5-4.7; adjusted P = .44). CONCLUSIONS: Laparoscopic repair was associated with fewer, albeit more severe, complications and improved some patient-centered outcomes. Trial Registration clinicaltrials.gov Identifier: NCT00240188.

The use of zoledronic acid in men receiving androgen deprivation therapy for prostate cancer with severe osteopenia or osteoporosis.

OBJECTIVES: To study the effect of zoledronic acid on patients with pre-existing osteoporosis on androgen deprivation therapy (ADT), who are at highest risk for fracture. Zoledronic acid is a potent bisphosphonate that can prevent osteoporosis in patients with nonmetastatic (M0), prostate cancer (CaP) who are initiating ADT. The effect of zoledronic acid on patients with pre-existing osteoporosis on ADT, who are highest risk for fracture, has not been adequately studied. METHODS: We enrolled 28 patients with M0 CaP on ADT with severe osteopenia or osteoporosis (baseline bone-mineral density (BMD) T score < -2.0) in this open-label, single-arm trial to assess the effect of zoledronic acid on BMD. All patients also received supplemental calcium and vitamin D, and were counseled about lifestyle modifications. Patients received zoledronic acid (4 mg) intravenously every 3 months for 4 treatments. BMD was measured by dual energy X-ray absorptiometry scan at enrollment, 6 and 12 months. Primary endpoint was percent change in lumbar spine BMD. RESULTS: This was a high-risk patient population-primarily older Caucasians (mean age, 73 years), former smokers, and moderate users of alcohol. Mean duration of ADT was 2.4 years. Pre-existing osteopenia or osteoporosis was observed in a single site in 9 patients and multiple sites in 19 (68%). After 12 months of zoledronic acid, lumbar spine BMD increased 4.17% (P < .0001), and BMD increased significantly (P < .05) in both hips and the right femoral neck. Seven patients (25%) experienced improved BMD into the nonosteoporotic range (T score > -2.0). Zoledronic acid infusion was well tolerated and without substantial renal toxicity. CONCLUSIONS: Zoledronic acid improves BMD in men with M0 CaP on ADT with severe osteopenia or osteoporosis (T scores < 2.0). This novel finding identifies a high-risk patient population that can potentially benefit from bisphosphonate therapy.

Perioperative complications after vascular surgery are predicted by the revised cardiac risk index but are not reduced in high-risk subsets with preoperative revascularization.

BACKGROUND: The Revised Cardiac Risk Index (RCRI) is useful for risk stratifying patients before noncardiac operations. Among patients with documented coronary artery disease who undergo vascular surgery, it is unclear whether preoperative revascularization reduces postoperative cardiac complications in high-risk subsets defined by the RCRI. METHODS AND RESULTS: The Coronary Artery Revascularization Prophylaxis Trial was a randomized, controlled trial that tested the long-term benefit of a preoperative coronary artery revascularization before elective vascular surgery. Using preoperative baseline characteristics to determine the RCRI, we tested the benefit of preoperative revascularization on death and nonfatal myocardial infarction in patients with multiple risks. Among 462 patients undergoing vascular surgery, there were 72 complications (15.6%) within 30 days postsurgery, including 15 deaths (3.2%) and 57 nonfatal myocardial infarctions (12.3%). The postoperative risk of death and nonfatal myocardial infarction after surgery increased according to the RCRI (odds ratio, 1.73; 95% CI, 1.26 to 2.38; P<0.001), with a rate of 1.6% in patients with no risk that increased to 23.4% in patients with > or =3 risks. Preoperative revascularization had no influence on the incidence of complications in any risk subset (odds ratio, 0.86; 95% CI, 0.50 to 1.49; P=0.60). Among those individuals with > or =2 risks who also demonstrated ischemia on a preoperative stress-imaging test (N=146), the incidence of events was 23% in patients with and without preoperative revascularization (P=0.95). CONCLUSIONS: The risk of death and nonfatal myocardial infarction is accurately predicted by the RCRI in patients undergoing vascular surgery but is not reduced in any high-risk subset of the RCRI with preoperative coronary artery revascularization.

Seroma in ventral incisional herniorrhaphy: incidence, predictors and outcome.

BACKGROUND: Factors leading to seroma following ventral incisional herniorrhaphy (VIH) are poorly understood. METHODS: Between 2004 and 2006, patients were prospectively randomized at 4 Veterans Affairs hospitals to undergo laparoscopic or open VIH. Patients who developed seromas within 8 weeks postoperatively were compared with those who did not. Multivariate analyses were performed to identify predictors of seroma. RESULTS: Of 145 patients who underwent VIH, 24 (16.6%) developed seromas. Patients who underwent open VIH had more seromas than those who underwent laparoscopic VIH (23.3% vs 6.8%, P = .011). Seroma patients had hernias that were never spontaneously reducible (0% vs 21%, P = .015), had more abdominal incisions preoperatively (mean, 2.4 vs 1.8; P = .037), and were less likely to have drain catheters placed than those without seromas (30.0% vs 63.1%, P = .011). In multivariate analyses, open VIH predicted seroma (odds ratio, 5.5; 95% confidence interval, 1.6-18.8), as well as the specific hospital at which the procedure was performed. Spontaneous resolution occurred in 71% of seromas; 29% required aspiration. CONCLUSIONS: Procedural characteristics and hernia characteristics rather than patient comorbidities predicted seroma in VIH.

Intravenous zoledronic acid to prevent osteoporosis in a veteran population with multiple risk factors for bone loss on androgen deprivation therapy.

PURPOSE: Androgen deprivation therapy for prostate cancer is associated with osteoporosis and increased fracture risk. Previous studies of zoledronic acid demonstrated bone loss prevention in patients initiating androgen deprivation therapy. There are limited data on patients on prolonged androgen deprivation therapy or in Veterans Affairs patients with multiple risk factors for osteoporosis. METHODS: We randomized 93 patients with M0 prostate cancer in this placebo controlled trial in the Veterans Affairs health care system. Preplanned strata included 50 patients on androgen deprivation therapy for less than 1 year (stratum 1) and 43 on androgen deprivation therapy for greater than 1 year (stratum 2). In each stratum patients were randomized to 4 mg zoledronic acid intravenously every 3 months for 4 treatments or intravenous placebo. The primary end point was the percent change in bone mineral density at the lumbar spine at 12 months. RESULTS: Age, race, body mass index and osteoporosis risk factors were similar for the 2 treatments. Most patients were former smokers, had moderate alcohol intake, were not on calcium/vitamin D supplements and were relatively sedentary at baseline. In stratum 1 spine bone mineral density increased 5.95% in the zoledronic acid arm and decreased 3.23% in the placebo arm (p = 0.0044). In stratum 2 spine bone mineral density increased 6.08% in the zoledronic acid arm and only increased 1.57% in the placebo arm (p = 0.0005). Treatment was well tolerated with minimal impact on renal function. CONCLUSIONS: Zoledronic acid improved bone mineral density in patients with M0 prostate cancer on androgen deprivation therapy for 1 year or less, or greater than 1 year. This finding indicates that bisphosphonate therapy remains effective when initiated later in the course of androgen deprivation therapy and is efficacious in Veterans Affairs patients with multiple risk factors for osteoporosis.

Intensive glucose-lowering therapy reduces cardiovascular disease events in veterans affairs diabetes trial participants with lower calcified coronary atherosclerosis.

OBJECTIVE: This study investigated the hypothesis that baseline calcified coronary atherosclerosis may determine cardiovascular disease events in response to intensive glycemic control within the Veterans Affairs Diabetes Trial (VADT). RESEARCH DESIGN AND METHODS: At baseline, 301 type 2 diabetic participants in the VADT, a randomized trial comparing the effects of intensive versus standard glucose lowering on cardiovascular events, had baseline coronary atherosclerosis assessed by coronary artery calcium (CAC) measured by computed tomography. Participants were followed over the 7.5-year study for development of cardiovascular end points. RESULTS: During a median follow-up duration of 5.2 years, 89 cardiovascular events occurred. Although intensive glucose-lowering therapy did not significantly reduce cardiovascular events in the substudy cohort as a whole, there was evidence that the response was modified by baseline CAC, as indicated by significant P values for treatment by log(CAC + 1) interaction terms in unadjusted and multivariable-adjusted models (0.01 and 0.03, respectively). Multivariable-adjusted hazard ratios (HRs) for the effect of treatment indicated a progressive diminution of benefit with increasing CAC. Subgroup analyses were also conducted for clinically relevant CAC categories: those above and below an Agatston score of 100. Among those randomized to intensive treatment, for the subgroup with CAC >100, 11 of 62 individuals had events, while only 1 of 52 individuals with CAC < or = 100 had an event. The multivariable HR for intensive treatment for those with CAC >100 was 0.74 (95% CI 0.46-1.20; P = 0.21), while for the subgroup with CAC < or = 100, the corresponding HR was 0.08 (0.008-0.77; P = 0.03), with event rates of 39 and 4 per 1,000 person-years, respectively. CONCLUSIONS: These data indicate that intensive glucose lowering reduces cardiovascular events in those with less extensive calcified coronary atherosclerosis.