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ABSTRACT: Acetaminophen (N-acetyl-p-aminophenol [APAP]) is a widely used medication that can cause hepatotoxicity. We examined characteristics and outcomes of children with chronic exposure (CE) to APAP in the multinational Pediatric Acute Liver Failure (PALF) Study.
A total of 895 children enrolled from 2002 to 2009 were grouped by APAP exposure history as: CE (received multiple doses \x{2265}2 days; n = 83), single dose exposure (SE; n = 85), and no exposure (NE; n = 498). CE was the reference group for pairwise comparisons. Median values are shown.
Patients with CE compared with those with SE were younger (3.5 vs 15.2 years, P < .0001), less likely to be female (46% vs 82%, P < .0001), and more likely to be Hispanic (25% vs 7%, P = .001), but they did not differ significantly from the NE group. At enrollment, total bilirubin was lower with CE than with NE (3.2 vs 13.1 mg/dL, P < .001). Alanine aminotransferase levels were higher with CE than with NE (2384 vs 855 IU/L, P < .0001), but lower than with SE (5140 IU/L, P < .0001). Survival without liver transplantation at 21 days was worse for CE than for SE (68% vs 92%, P = .0004) but better than for NE (49%, P = .008).
Children in the PALF study with CE had lower bilirubin and higher alanine aminotransferase than those with NE. Outcomes with CE were worse than with SE but better than with NE. Potential reasons for this outcomes advantage over non-APAP-exposed subjects should be explored.
PEDIATRICS 03/2013; 131(3):e740-6. · 4.47 Impact Factor
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Steven H Belle,
Paul D Berk,
Anita P Courcoulas,
Scott Engel,
David R Flum,
William Gourash,
Mary Horlick,
Jesse Y Hsu,
Saurabh Khandelwal,
James E Mitchell,
Robert W O'Rourke,
Walter Pories,
Beth Schrope,
Bruce Wolfe
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ABSTRACT: BACKGROUND: Although it is recognized that a standardized approach to reporting weight change is essential to meaningful comparisons among cohorts and across studies, consensus is lacking. This study aimed to propose a method of reporting weight change that would allow meaningful comparisons among studies of patients who underwent bariatric surgery and to demonstrate its utility using an example from the Longitudinal Assessment of Bariatric Surgery (LABS). METHODS: Relationships among several measures of weight change are described. Results from an observational, longitudinal cohort study of adults undergoing bariatric surgery and from simulation studies are used to illustrate the proposed method. RESULTS: Baseline weight is a critical parameter when assessing weight change. Men undergoing a bariatric procedure other than gastric bypass or adjustable band tended to have greater weight loss 12 months after surgery than men undergoing gastric bypass when not accounting for baseline weight, but the opposite was found when results were adjusted for baseline weight. Simulation results show that with relatively modest sample sizes, the adjusted weight loss was significantly different between the 2 groups of men. CONCLUSION: A consistent metric for reporting weight loss after bariatric surgery is essential to interpret outcomes across studies and among subgroups. The baseline weight adjusted percent of weight loss (A%WL) uses a standard population (e.g., the LABS cohort) to account for differences between cohorts with respect to baseline weight, and its use can change the interpretation of results compared with an unadjusted measure.
Surgery for Obesity and Related Diseases 12/2012; · 3.93 Impact Factor
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Mark D Smith,
Emma Patterson,
Abdus S Wahed, Steven H Belle,
Anita P Courcoulas,
David Flum,
Saurabh Khandelwal,
James E Mitchell,
Alfons Pomp,
Walter J Pories,
Bruce Wolfe
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ABSTRACT: BACKGROUND: The existence of a relationship between surgeon volume and patient outcome has been reported for different complex surgical operations. This relationship has also been confirmed for patients undergoing Roux-en-Y gastric bypass (RYGB) in the Longitudinal Assessment of Bariatric Surgery (LABS) study. Despite multiple studies demonstrating volume-outcome relationships, fewer studies investigate the causes of this relationship. OBJECTIVE: The purpose of the present study is to understand possible explanations for the volume-outcome relationship in LABS. METHODS: LABS includes a 10-center, prospective study examining 30-day outcomes after bariatric surgery. The relationship between surgeon annual RYGB volume and incidence of a composite endpoint (CE) has been published previously. Technical aspects of RYGB surgery were compared between high and low volume surgeons. The previously published model was adjusted for select technical factors. RESULTS: High-volume surgeons (>100 RYGBs/yr) were more likely to perform a linear stapled gastrojejunostomy, use fibrin sealant, and place a drain at the gastrojejunostomy compared with low-volume surgeons (<25 RYGBs/yr), and less likely to perform an intraoperative leak test. After adjusting for the newly identified technical factors, the relative risk of CE was .93 per 10 RYGB/yr increase in volume, compared with .90 for clinical risk adjustment alone. CONCLUSION: High-volume surgeons exhibited certain differences in technique compared with low-volume surgeons. After adjusting for these differences, the strength of the volume-outcome relationship previously found was reduced only slightly, suggesting that other factors are also involved.
Surgery for Obesity and Related Diseases 10/2012; · 3.93 Impact Factor
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ABSTRACT: The botanical product silymarin, an extract of milk thistle, is commonly used by patients to treat chronic liver disease, despite scant and conflicting evidence of its efficacy.
To determine the effect of silymarin on liver disease activity in patients with chronic hepatitis C virus (HCV) infection unsuccessfully treated with interferon-based therapy.
Multicenter, double-blind, placebo-controlled trial conducted at 4 medical centers in the United States. Participants included 154 persons with chronic HCV infection and serum alanine aminotransferase (ALT) levels of 65 U/L or greater who were previously unsuccessfully treated with interferon-based therapy. Enrollment began in May 2008 and was completed in May 2010, with the last follow-up visit completed in March 2011.
Participants were randomly assigned to receive 420-mg silymarin, 700-mg silymarin, or matching placebo administered 3 times per day for 24 weeks.
The primary outcome measure was serum ALT level of 45 U/L or less (considered within the normal range) or less than 65 U/L, provided this was at least a 50% decline from baseline values. Secondary outcomes included changes in ALT levels, HCV RNA levels, and quality-of-life measures.
After 24 weeks of treatment, only 2 participants in each treatment group (P ≥ .99) met the primary outcome measure (3.8% [95% CI, 0.5% to 13.2%] for placebo, 4.0% [95% CI, 0.5% to 13.7%] for 420-mg silymarin, and 3.8% [95% CI, 0.5% to 13.2%] for 700-mg silymarin). The mean decline in serum ALT activity at the end of treatment did not differ significantly (P = .75) across the 3 treatment groups (mean decline, -4.3 [95% CI, -17.3 to 8.7] U/L for placebo, -14.4 [95% CI, -41.6 to 12.7] U/L for 420-mg silymarin, -11.3 [95% CI, -27.9 to 5.4] U/L for 700-mg silymarin); there likewise were no significant differences in HCV RNA levels (mean change, 0.07 [95% CI, -0.05 to 0.18] log10 IU/mL for placebo, -0.03 [95% CI, -0.18 to 0.12] log10 IU/mL for 420-mg silymarin, 0.04 [95% CI, -0.08 to 0.16] log10 IU/mL for 700-mg silymarin; P = .54) or quality-of-life measures. The adverse event profile of silymarin was comparable with that of placebo.
Higher than customary doses of silymarin did not significantly reduce serum ALT levels more than placebo in participants with chronic HCV infection unsuccessfully treated with interferon-based therapy.
clinicaltrials.gov Identifier: NCT00680342.
JAMA The Journal of the American Medical Association 07/2012; 308(3):274-82. · 30.03 Impact Factor
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Rachel H Mackey, Steven H Belle,
Anita P Courcoulas,
Greg F Dakin,
Clifford W Deveney,
David R Flum,
Luis Garcia,
Wendy C King,
Lewis H Kuller,
James E Mitchell,
Alfons Pomp,
Walter J Pories,
Bruce M Wolfe
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ABSTRACT: Primary prevention guidelines recommend calculation of lifetime cardiovascular disease (CVD) predicted risk in patients who may not meet criteria for high short-term (10-year) Adult Treatment Panel III risk for coronary heart disease (CHD). Extreme obesity and bariatric surgery are more common in women who often have low short-term predicted CHD risk. The distribution and correlates of lifetime CVD predicted risk, however, have not yet been evaluated in bariatric surgical candidates. Using established 10-year (Adult Treatment Panel III) CHD and lifetime CVD risk prediction algorithms and presurgery risk factors, participants from the Longitudinal Assessment of Bariatric Surgery-2 study without prevalent CVD (n = 2,070) were stratified into 3 groups: low 10-year (<10%)/low lifetime (<39%) predicted risk, low 10-year (<10%)/high lifetime (≥39%) predicted risk, and high 10-year (≥10%) predicted risk or diagnosed diabetes. Participants were predominantly white (86%) and women (80%) with a median age of 45 years and median body mass index of 45.6 kg/m(2). High 10-year CHD predicted risk was common (36.5%) and associated with diabetes, male gender, and older age, but not with higher body mass index or high-sensitivity C-reactive protein. Most participants (76%) with low 10-year predicted risk had high lifetime CVD predicted risk, which was associated with dyslipidemia and hypertension but not with body mass index, waist circumference, high-density lipoprotein cholesterol, or high-sensitivity C-reactive protein. In conclusion, bariatric surgical candidates without diabetes or existing CVD are likely to have low short-term, but high lifetime CVD predicted risk. Current data support the need for long-term monitoring and treatment of increased CVD risk factors in bariatric surgical patients to maximize lifetime CVD risk decrease (clinical trial registration, Long-term Effects of Bariatric Surgery, indentifier NCT00465829, available at: http://www.clinicaltrials.gov/ct2/results?term=NCT00465829).
The American journal of cardiology 06/2012; 110(8):1130-7. · 3.58 Impact Factor
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ABSTRACT: Chronic hepatitis C is associated with significant morbidity and mortality as a consequence of progression to cirrhosis, hepatocellular carcinoma, and liver failure. Current treatment for chronic hepatitis C with pegylated interferon (IFN) and ribavirin is associated with suboptimal responses and numerous adverse effects. A number of botanical products have been used to treat hepatic disorders. Silymarin, extracted from the milk thistle plant, Silybum marianum (L) Gaertn. (Asteraceae), has been most widely used for various liver disorders, including chronic hepatitis C, B, and alcoholic liver disease. However, the safety and efficacy of silymarin have not been studied systematically in chronic hepatitis C.
We describe our strategy for a phased approach for studying the impact of silymarin in hepatitis C, in the context of the unique challenges of botanical product clinical trials and the development of specific and curative antiviral therapy.
This multicenter, randomized, double-masked, placebo-controlled trial was conducted with four clinical centers and a data-coordinating center in the United States, to assess the impact of silymarin therapy in patients with chronic hepatitis C who failed conventional antiviral therapy.
Key aspects relevant to performing clinical trials of botanical products include early identification of an appropriate product with standard product chemistry, acquisition of pharmacokinetic and dosing information, selection of the appropriate study group, and choosing rigorous outcome variables. POTENTIAL LIMITATIONS: Trial participants were chronic hepatitis C patients who were nonsustained virologic responders to IFN-based therapy; therefore, the findings are not generalizable to all hepatitis C populations. Further, alanine aminotransferase, a biochemical liver test, rather than hepatitis viral RNA or liver histology was the primary end point.
The challenges identified and addressed during development of this United States multicenter Phase II trial to evaluate silymarin for treatment of patients with chronic hepatitis C infection who had failed to respond successfully to previous IFN-based therapy are common and must be addressed to conduct rigorous trials of botanical products.
Clinical Trials 11/2011; 9(1):102-12. · 1.92 Impact Factor
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JAMA The Journal of the American Medical Association 09/2011; 306(12):1323; author reply 1323-4. · 30.03 Impact Factor
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Mark D Smith,
Emma Patterson,
Abdus S Wahed, Steven H Belle,
Paul D Berk,
Anita P Courcoulas,
Gregory F Dakin,
David R Flum,
Laura Machado,
James E Mitchell,
John Pender,
Alfons Pomp,
Walter Pories,
Ramesh Ramanathan,
Beth Schrope,
Myrlene Staten,
Akuezunkpa Ude,
Bruce M Wolfe
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ABSTRACT: Mortality following bariatric surgery is a rare event in contemporary series, making it difficult for any single center to draw meaningful conclusions as to cause of death. Nevertheless, much of the published mortality data come from single-center case series and reviews of administrative databases. These sources tend to produce lower mortality estimates than those obtained from controlled clinical trials. Furthermore, information about the causes of death and how they were determined is not always available. The aim of the present report is to describe in detail all deaths occurring within 30 days of surgery in the Longitudinal Assessment of Bariatric Surgery (LABS).
LABS is a ten-center observational cohort study of bariatric surgical outcomes. Data were collected prospectively for bariatric surgeries performed between March 2005 and April 2009. All deaths occurring within 30-days of surgery were identified, and cause of death assigned by an independent Adjudication Subcommittee, blinded to operating surgeon and site.
Six thousand one hundred eighteen patients underwent primary bariatric surgery. Eighteen deaths (0.3%) occurred within 30-days of surgery. The most common cause of death was sepsis (33% of deaths), followed by cardiac causes (28%), and pulmonary embolism (17%). For one patient cause of death could not be determined despite examination of all available information.
This study confirms the low 30-day mortality rate following bariatric surgery. The recognized complications of anastomotic leak, cardiac events, and pulmonary emboli accounted for the majority of 30-day deaths.
Obesity Surgery 08/2011; 21(11):1687-92. · 3.29 Impact Factor
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Sarah J Schrieber,
Roy L Hawke,
Zhiming Wen,
Philip C Smith,
K Rajender Reddy,
Abdus S Wahed, Steven H Belle,
Nezam H Afdhal,
Victor J Navarro,
Catherine M Meyers,
Edward Doo,
Michael W Fried
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ABSTRACT: Silymarin, derived from the milk thistle plant Silybum marianum and widely used for self-treatment of liver diseases, is composed of six major flavonolignans including silybin A and silybin B, which are the predominant flavonolignans quantified in human plasma. The single- and multiple-dose pharmacokinetics of silymarin flavonolignans were examined in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis C virus (HCV) to determine whether the disposition of silymarin and therefore its potential efficacy vary among liver disease populations. Cohorts of eight subjects with noncirrhotic liver disease were randomized 3:1 to oral silymarin or placebo (280 or 560 mg) every 8 h for 7 days. Forty-eight-hour blood sampling was conducted after the first and final doses. In general, plasma concentrations of silybin A and silybin B were higher, whereas concentrations of conjugates were lower in NAFLD compared with HCV. After adjustment of the area under plasma concentration-time curve from 0 to 8 h (AUC(0-8 h)) for weight and dose, only silybin B and silybin B conjugates differed significantly between disease types. For NAFLD, the adjusted mean AUC(0-8 h) was higher for silybin B (p < 0.05) but lower for silybin B conjugates (p < 0.05) compared with that for HCV. At the 280-mg dose, steady-state plasma concentrations of silybin B conjugates for NAFLD subjects were characterized by 46% lower AUC(0-8 h) (p < 0.05) and 42% lower C(max) (p < 0.05) compared with HCV subjects. Evidence of enterohepatic cycling of flavonolignans was only observed in NAFLD subjects. In summary, the efficacy of silymarin may be more readily observed in NAFLD patients because of their higher flavonolignan plasma concentrations and more extensive enterohepatic cycling compared with those in HCV patients.
Drug metabolism and disposition: the biological fate of chemicals 08/2011; 39(12):2182-90. · 3.74 Impact Factor
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Wendy C King,
Jesse Y Hsu, Steven H Belle,
Anita P Courcoulas,
George M Eid,
David R Flum,
James E Mitchell,
John R Pender,
Mark D Smith,
Kristine J Steffen,
Bruce M Wolfe
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ABSTRACT: Numerous studies have reported that bariatric surgery patients report more physical activity (PA) after surgery than before; however, the quality of the PA assessment has been questionable.
The Longitudinal Assessment of Bariatric Surgery-2 is a 10-center longitudinal study of adults undergoing bariatric surgery. Of 2458 participants, 455 were given an activity monitor, which records the steps per minute, and an exercise diary before and 1 year after surgery. The mean number of steps/d, active min/d, and high-cadence min/wk were calculated for 310 participants who wore the monitor ≥10 hr/d for ≥3 days at both evaluations. Pre- and postoperative PA were compared for differences using the Wilcoxon signed-rank test. Generalized estimating equations were used to identify independent preoperative predictors of postoperative PA.
PA increased significantly (P < .0001) from before to after surgery for all PA measures. The median values before and after surgery were 7563 and 8788 steps/d, 309 and 340 active min/d, and 72 and 112 high-cadence min/wk, respectively. However, depending on the PA measure, 24-29% of participants were ≥5% less active postoperatively than preoperatively. Controlling for surgical procedure, gender, age, and body mass index, more PA preoperatively independently predicted for more PA postoperatively (P < .0001, for all PA measures). Less pain, not having asthma, and the self-report of increasing PA as a weight loss strategy preoperatively also independently predicted for more high-cadence min/wk postoperatively (P < .05).
The majority of adults increase their PA level after bariatric surgery. However, most remain insufficiently active, and some become less active. Increasing PA, addressing pain, and treating asthma before surgery might have a positive effect on postoperative PA.
Surgery for Obesity and Related Diseases 08/2011; 8(5):522-32. · 3.93 Impact Factor
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ABSTRACT: This study characterizes the walking limitations of bariatric surgery candidates by age and body mass index (BMI) and determines factors independently associated with walking capacity. The setting was multi-institutional at research university hospitals in the United States.
Participants of the Longitudinal Assessment of Bariatric Surgery study (n=2458; age 18-78 yr, BMI 33-94 kg/m(2)) attended a preoperative research visit. Their walking capacity was measured by self-report and the 400 m Long Distance Corridor Walk (LDCW).
Almost two thirds (64%) of subjects reported limitations with walking several blocks, 48% had an objectively defined mobility deficit, and 16% reported at least some walking aid use. In multivariate analysis, BMI, older age, lower income, and greater bodily pain were independently associated (P < .05) with walking aid use, physical discomfort during the LDCW, an inability to complete the LDCW, and a slower time to complete the LDCW. Female gender, Hispanic ethnicity (but not race), greater heart rate at rest, a history of smoking, several co-morbidities (history of stroke, ischemic heart disease, diabetes, asthma, sleep apnea, venous edema with ulcerations), and depressive symptoms were also independently related (P < .05) to at least one measure of reduced walking capacity.
Walking limitations are common in bariatric surgery candidates, even among the least severely obese and youngest patients. Physical activity counseling must be tailored to individuals' abilities. Although several factors identified in the present study (eg, BMI, age, pain, co-morbidities) should be considered, directly assessing the patient's walking capacity will facilitate appropriate goal setting.
Surgery for Obesity and Related Diseases 07/2011; 8(1):48-59. · 3.93 Impact Factor
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ABSTRACT: Accurately measuring physical activity (PA) with activity monitors requires sufficient monitor wear time which can be difficult to assess. Monitor sensitivity to movement and population characteristics (eg, children vs. adults) may dictate the duration of monitor inactivity indicative of nonwear. A standardized method for determining appropriate decision rules to identify wear time is needed.
Several decision rules based on minimum durations of monitor inactivity (ie, 60, 90, 120, 150 minutes) to identify nonwear were applied to Stepwatch Activity Monitor data from 1064 adult bariatric surgical candidates. The frequency, pattern, and duration of resulting nonwear and wear periods were examined. Generalized Estimating Equations tested the effect of these decision rules on PA measures.
A 60-minute duration resulted in unreasonably large percentages of subjects with unlikely wear patterns [eg, ≥3 nonwear periods in a day (29.9%); ≥2 wear periods of less than an hour in a day (28.7%)]; 120 minutes appeared most reasonable. Wear time decision rules impacted PA measures.
The methods described in this paper can be used to determine appropriate instrument and population specific wear time decision rules. Recognizing monitor wear time is estimated, PA measures least affected by wear time are preferable.
Journal of physical activity & health 05/2011; 8(4):566-80. · 1.95 Impact Factor
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ABSTRACT: Approximately one half of patients who undergo antiviral therapy for chronic hepatitis C virus (HCV) genotype 1 infection do not respond to treatment. African Americans (AAs) are less responsive to treatment than Caucasian Americans (CAs), but the reasons for this disparity are largely unknown. Recent studies suggest that serum lipids may be associated with treatment response. The aims of this study were to evaluate baseline and changes in serum lipids during therapy, determine whether serum lipids are associated with virological response, and assess whether these measures explain the racial difference in efficacy. The study participants were from Virahep-C, a prospective study of treatment-naïve patients with genotype 1 HCV infection who received peginterferon (PEG-IN) alfa-2a plus ribavirin therapy for up to 48 weeks. Fasting serum lipids were analyzed at baseline and during and after therapy in 160 AAs and 170 CAs. A relative risk (RR) model was employed to evaluate characteristics associated with sustained virological response (SVR). Antiviral therapy was associated with changes in serum lipids during and after antiviral therapy, with the changes differing by race and the amount of PEG-IFN taken. Baseline lipid measures independently associated with higher rates of SVR were lower triglyceride and higher low-density lipoprotein cholesterol, with an interaction between high-density lipoprotein cholesterol (HDLc) and gender. Lipid measures did not contribute significantly to an explanation of the racial difference in SVR. CONCLUSION: Serum lipids are associated with SVR, although these paramaters did not explain the racial difference in treatment response. The results of this study are compatible with proposed biological mechanisms of HCV entry, replication, and secretion, and may underscore new potential therapeutic targets for HCV eradication.
Hepatology 09/2010; 52(3):854-63. · 11.66 Impact Factor
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Roy L Hawke,
Sarah J Schrieber,
Tedi A Soule,
Zhiming Wen,
Philip C Smith,
K Rajender Reddy,
Abdus S Wahed, Steven H Belle,
Nezam H Afdhal,
Victor J Navarro,
Josh Berman,
Qi-Ying Liu,
Edward Doo,
Michael W Fried
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ABSTRACT: Silymarin, derived from the milk thistle plant Silybum marianum, is widely used for self-treatment of liver diseases, including hepatitis C virus (HCV), and its antiviral activity has been demonstrated in vitro and in HCV patients administered an intravenous formulation of the major silymarin flavonolignans, silybin A and silybin B. The safety and dose-exposure relationships of higher than customary oral doses of silymarin and its acute effects on serum HCV RNA were evaluated in noncirrhotic HCV patients. Four cohorts of 8 patients with well-compensated, chronic noncirrhotic HCV who failed interferon-based therapy were randomized 3:1 to silymarin or placebo. Oral doses of 140, 280, 560, or 700 mg silymarin were administered every 8 hours for 7 days. Steady-state exposures for silybin A and silybin B increased 11-fold and 38-fold, respectively, with a 5-fold increase in dose, suggesting nonlinear pharmacokinetics. No drug-related adverse events were reported, and no clinically meaningful reductions from baseline serum transaminases or HCV RNA titer were observed. Oral doses of silymarin up to 2.1 g per day were safe and well tolerated. The nonlinear pharmacokinetics of silybin A and silybin B suggests low bioavailability associated with customary doses of silymarin may be overcome with doses above 700 mg.
The Journal of Clinical Pharmacology 10/2009; 50(4):434-49. · 2.91 Impact Factor
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ABSTRACT: Combination therapy for chronic hepatitis C is associated with depression, which may lead to worse treatment outcomes. The objectives of this study were to determine the association between patient characteristics and depression before and during treatment and to evaluate the relationship between depression and treatment outcomes.
Prospective data from the Viral Resistance to Antiviral Therapy of Chronic Hepatitis C (Virahep-C) study were analyzed (191 African Americans, 203 Caucasians). Depression was defined as a score of >23 on the Center for Epidemiologic Studies Depression (CES-D) scale. Scores were taken before treatment, at weeks 4, 12, and 24 of treatment, and 24 weeks after treatment ended. Baseline social support was measured using the Medical Outcomes Study (MOS) Social Support Survey. Associations between baseline patient characteristics and incident depression were assessed with discrete-time Cox proportional hazards models.
At baseline, 47 (12%) participants had CES-D scores 23. Univariable analyses indicated that several patient characteristics were associated with baseline depression, including lower social support (P<0.0001). On treatment, these patients were more likely to have psychiatric adverse events (AEs) or start new antidepressants (45 vs. 28%, P=0.02) and to have had early treatment discontinuation (38 vs.13%, P<0.0001); however, sustained virological response (SVR) rates were similar (38 vs. 40%, P=0.79) to those of participants without baseline depression. The incidence of new-onset depression was 26% by 24 weeks. One-third of patients were started on antidepressants, and no patients attempted suicide. Multivariable analyses indicated that new-onset depression was significantly associated with younger age (P=0.04), lower social support (P<0.001), and "feeling depressed, sad, or blue" (P=0.008). Patients who developed depression during treatment were more likely to have a psychiatric AE or begin antidepressants (44 vs. 23%, P<0.001) but had lower rates of treatment discontinuation (6 vs. 15%, P=0.02) and comparable rates of SVR compared with patients without depression (47 vs. 38%, P=0.16). There were no differences in the frequency of pretreatment or new-onset depression between African-American and Caucasian participants in this study.
In this large prospective analysis, baseline and new-onset depression were associated with patient characteristics and treatment outcomes; however, SVR rates did not differ between depressed and nondepressed patients. The relationship of lower baseline social support with depressive symptoms warrants further investigation.
The American Journal of Gastroenterology 09/2009; 104(12):2949-58. · 7.28 Impact Factor
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Mark D Smith,
Emma Patterson,
Abdus S Wahed, Steven H Belle,
Marc Bessler,
Anita P Courcoulas,
David Flum,
Valerie Halpin,
James E Mitchell,
Alfons Pomp,
Walter J Pories,
Bruce Wolfe
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ABSTRACT: Bariatric surgery is technically demanding surgery performed on high-risk patients. Previous studies using administrative databases have shown a relationship between surgeon volume and patient outcome after Roux-en-Y gastric bypass (RYGB). We examined the relationship between surgeons' annual RYGB volumes and 30-day patient outcomes at 10 centers within the United States.
The Longitudinal Assessment of Bariatric Surgery (LABS)-1 is a prospective study examining the 30-day adverse outcomes after bariatric surgery. The outcomes after RYGB were adjusted by procedure type (open versus laparoscopic), functional status, body mass index, history of deep vein thrombosis, pulmonary embolism, and obstructive sleep apnea. The data were examined to determine the nature and strength of the association between surgeon volume and patients' short-term (30-day) adverse outcomes after RYGB.
The analysis included 3410 initial RYGB operations performed by 31 surgeons, 15 of whom averaged <50 cases annually. The crude composite adverse outcome (i.e., death, deep vein thrombosis, pulmonary embolism, reintervention or nondischarge at day 30) incidence was 5.2%. After risk adjustment, a greater surgeon RYGB volume was associated with lower composite event rates, with a continuous relationship (i.e., varying cutpoints differentiated the composite event rates), such that for each 10-case/yr increase in volume, the risk of a composite event decreased by 10%.
In the LABS, the patient's risk of an adverse outcome after RYGB decreased significantly with the increase in surgeon RYGB volume (cases performed annually).
Surgery for Obesity and Related Diseases 09/2009; 6(2):118-25. · 3.93 Impact Factor
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David Reed Flum, Steven H Belle,
Wendy C King,
Abdus S Wahed,
Paul Berk,
William Chapman,
Walter Pories,
Anita Courcoulas,
Carol McCloskey,
James Mitchell,
Emma Patterson,
Alfons Pomp,
Myrlene A Staten,
Susan Z Yanovski,
Richard Thirlby,
Bruce Wolfe
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ABSTRACT: To improve decision making in the treatment of extreme obesity, the risks of bariatric surgical procedures require further characterization.
We performed a prospective, multicenter, observational study of 30-day outcomes in consecutive patients undergoing bariatric surgical procedures at 10 clinical sites in the United States from 2005 through 2007. A composite end point of 30-day major adverse outcomes (including death; venous thromboembolism; percutaneous, endoscopic, or operative reintervention; and failure to be discharged from the hospital) was evaluated among patients undergoing first-time bariatric surgery.
There were 4776 patients who had a first-time bariatric procedure (mean age, 44.5 years; 21.1% men; 10.9% nonwhite; median body-mass index [the weight in kilograms divided by the square of the height in meters], 46.5). More than half had at least two coexisting conditions. A Roux-en-Y gastric bypass was performed in 3412 patients (with 87.2% of the procedures performed laparoscopically), and laparoscopic adjustable gastric banding was performed in 1198 patients; 166 patients underwent other procedures and were not included in the analysis. The 30-day rate of death among patients who underwent a Roux-en-Y gastric bypass or laparoscopic adjustable gastric banding was 0.3%; a total of 4.3% of patients had at least one major adverse outcome. A history of deep-vein thrombosis or pulmonary embolus, a diagnosis of obstructive sleep apnea, and impaired functional status were each independently associated with an increased risk of the composite end point. Extreme values of body-mass index were significantly associated with an increased risk of the composite end point, whereas age, sex, race, ethnic group, and other coexisting conditions were not.
The overall risk of death and other adverse outcomes after bariatric surgery was low and varied considerably according to patient characteristics. In helping patients make appropriate choices, short-term safety should be considered in conjunction with both the long-term effects of bariatric surgery and the risks associated with being extremely obese. (ClinicalTrials.gov number, NCT00433810.)
New England Journal of Medicine 08/2009; 361(5):445-54. · 53.30 Impact Factor
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ABSTRACT: The recommended therapy for chronic hepatitis C, pegylated interferon and ribavirin for 24 or 48 weeks, has many known adverse side effects. The aim of this study was to evaluate the impact of antiviral therapy on male sexual health.
As part of the Study of Viral Resistance to Antiviral Therapy of Chronic Hepatitis C (Virahep-C), 260 men treated with pegylated interferon alfa-2a and ribavirin completed self-administered questionnaires concerning sexual desire, sexual function, including erectile and ejaculatory function, and sexual satisfaction before, during, and after treatment.
Before therapy, 37% of men reported at least some degree of impairment in sexual desire and 44% reported dissatisfaction with their sexual life, while 26% reported impairment in erectile and 22% in ejaculatory function. During therapy, significant declines were observed in all components of sexual health compared with pretreatment. At the end of therapy (24 or 48 weeks), an estimated 38%-48% of men reported that overall sexual function was worse than before treatment. African American patients reported less impairment in sexual desire and satisfaction than Caucasian American patients during therapy. By 24 weeks after treatment, sexual desire and satisfaction improved and were comparable to baseline levels. However, among men who received 48 weeks of therapy, the estimated percentage of men reporting posttreatment erectile or ejaculatory problems remained higher than baseline, although persistent erectile impairment was limited to Caucasian American patients.
Sexual impairment is common among men with chronic hepatitis C undergoing therapy with pegylated interferon and ribavirin and should be considered as a potential side effect of antiviral therapy.
Gastroenterology 07/2009; 137(3):873-84, 884.e1. · 11.68 Impact Factor
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ABSTRACT: Hepatic steatosis is the accumulation of fat in liver cells. Insulin resistance (IR) occurs when normal amounts of insulin do not stimulate insulin activity in cells. Both conditions have been described in hepatitis C virus (HCV) infection and are thought to be biologically related. This study examined the association of genetic variants with steatosis and IR among 167 African Americans and 184 Caucasian Americans with HCV genotype-1. Steatosis was defined as at least 5% of fat in cells on liver biopsy. IR was quantified as a score greater than 2 from the Homeostasis Model Assessment, version 2.2 (HOMA2-IR). Associations were investigated by estimating odds ratios separately by race. Statistically significant associations (p < 0.05) were observed for variants in interleukin-10 (IL10), leptin receptor (LEPR), interleukin-6 (IL6) and transforming growth factor beta-1 (TGF-beta1) for both outcomes. Some significant interactions were observed between IL10,LEPR and TGF-beta1 polymorphisms and HOMA2-IR scores when examining steatosis. The interaction of HOMA2-IR and IL10 was consistent in both races whereas for LEPR and TGF-beta1 the interactions were statistically significant in only one of the racial groups.These results could imply that some IL10,LEPR and TGF-beta1 polymorphisms may modify an association between steatosis and IR.
Intervirology 05/2009; 52(1):49-56. · 2.34 Impact Factor
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ABSTRACT: Early changes in hepatitis C virus (HCV) RNA levels were assessed in a large cohort of African American and white patients with chronic hepatitis C due to HCV genotype 1 who underwent therapy with peginterferon alfa-2a and ribavirin in the Study of Viral Resistance to Antiviral Therapy of Hepatitis C (Virahep-C). Analyses were restricted to 341 patients who completed the first 28 days of therapy without dose modification. HCV RNA levels decreased in virtually all patients, but the amount of the change varied markedly. The overall 28-day decrease in HCV RNA levels was at least as predictive of a sustained virological response as the first- or second-phase viral kinetics responses. Factors associated with a smaller decrease in the HCV RNA level between baseline and day 28 included African American race, higher initial HCV RNA level, more severe hepatic fibrosis, and higher body weight. African American patients with similar 28-day decreases in viral levels as white patients were still less likely to achieve a sustained virological response. These results suggest that racial differences in the response to antiviral therapy are due to greater unresponsiveness to intracellular actions of interferon in African American individuals and that standard doses of peginterferon and ribavirin may be suboptimal for patients with higher body weights. Trial registration. ClinicalTrials.gov identifier: NCT00038974 .
The Journal of Infectious Diseases 05/2009; 199(8):1112-20. · 6.41 Impact Factor
