Erin Jensen

Definitive Risk Factors for Anastomotic Leaks in Elective Open Colorectal Resection

HYPOTHESIS Anastomotic leaks following elective colorectal resections increase morbidity, mortality, and the need for additional interventions. An accurate understanding of risk factors would potentially reduce anastomotic leaks and/or allow appropriate selection of patients for diverting stomas. DESIGN Prospective review of patient and operative characteristics that contribute to anastomotic leaks. SETTING Fifty-one sites within the United States (May 2002-March 2005). PATIENTS Six hundred seventy-two patients who participated in a trial comparing preoperative antimicrobials in elective open colorectal surgery. MAIN OUTCOME MEASURES Anastomotic leaks were diagnosed using clinical findings and were confirmed with imaging. We examined 20 variables possibly affecting anastomotic healing in univariate and multivariate analyses. RESULTS There were 24 anastomotic leaks in 672 patients (3.6%) undergoing elective colorectal resection. There were 10 deaths (1.5%). A baseline albumin level of less than 3.5 g/dL (to convert to grams per liter, multiply by 10) (P = .04) and male sex (P = .03) were associated with anastomotic leaks in both univariate and multivariate analyses (adjusted odds ratios, 2.56 and 3.12, respectively). Increased duration of surgery (SD, 60 minutes; odds ratio, 1.53; 95% confidence interval, 1.06-2.22; P = .03) and steroid use at the time of surgery (odds ratio, 3.85; 95% confidence interval, 1.24-11.93; P = .02) were significant in univariate analysis. Surgical procedure with rectal resection; prophylaxis with ertapenem (vs cefotetan); or history of obesity, tobacco use, or diabetes was not associated with anastomotic leaks. CONCLUSIONS Significant risk factors for anastomotic leaks include low preoperative serum albumin level, steroid use, male sex, and increased duration of surgery. Appreciation of risk factors provides a rational basis for temporary diversion.

Kinetics of maternal hepatitis a antibody decay in infants: implications for vaccine use.

We conducted a seroepidemiologic study to evaluate the kinetics of maternal hepatitis A antibody decay in infants. Serum samples obtained from 200 infants at 2 and 4 months of age were tested for hepatitis A antibody. Seventy-six infants (38%) were hepatitis A antibody-positive with a geometric mean antibody titer of 2634 mIU/ml. Samples collected at 4, 6 and/or 12 months of age showed seropositivity rates of 100, 95 and 39%, respectively. These data indicate that maternal antibody levels remained high through the first 6 months of life but decayed significantly by 12 months of age.

Effect of body mass index and ertapenem versus cefotetan prophylaxis on surgical site infection in elective colorectal surgery.

BACKGROUND The effectiveness of prophylactic antibiotics in the prevention of surgical site infection (SSI) after elective colorectal surgery is dependent on many factors, including the body mass index (BMI) of the patient. In this study, the association of BMI and type of antibiotic prophylaxis with SSI was evaluated in patients undergoing elective colorectal surgery. METHOD A post-hoc analysis was performed using data obtained from a multicenter randomized, double-blind study of 1,002 patients undergoing elective colorectal surgery who received prophylactic administration of ertapenem (1 g) or cefotetan (2 g). Among 650 evaluable patients, the effect of BMI and type of antibiotic prophylaxis on SSI rates was assessed four weeks after surgery. Mechanical bowel preparation was standardized, and no patient received oral antibiotics; intravenous antibiotics were not repeated during or after surgery. RESULTS The majority of patients had a BMI between 18.5 and 39.9 kg/m2. Regardless of the type of prophylaxis, SSI rates were significantly higher in patients with a BMI > or = 30 kg/m2 than in those with a BMI < 30 kg/m2. However, failure, defined as SSI, was significantly less common after ertapenem than after cefotetan prophylaxis at both BMI < 30 kg/m2 (12.7% vs. 26.4%, respectively; difference -13.7; 95% confidence interval [CI] -21.0, -6.5) and BMI > or = 30 kg/m2 (26.7% vs. 41.9%, respectively; difference -15.3; 95% CI -28.2, -2.0). The most prevalent type of SSI was superficial incisional infection, which was more common with both treatments in patients with a BMI > or = 30 kg/m2; however, the incidence of superficial SSI was lower after ertapenem than cefotetan prophylaxis. CONCLUSION In patients undergoing elective colorectal surgery, the incidence of SSI, specifically superficial incisional SSI, was higher in patients with a BMI > or = 30 kg/m2, regardless of the prophylactic antibiotic given. Ertapenem prophylaxis was more effective than cefotetan in the prevention of SSI at any BMI.

Open-label study of a twice-daily indinavir 800-mg/ritonavir 100-mg regimen in protease inhibitor-naive HIV-infected adults.

Low-dose ritonavir can boost plasma levels of indinavir, thereby enhancing its antiretroviral activity despite less frequent dosing. In this open-label, noncomparative, 24-week trial with a 24-week extension phase, HIV-infected protease inhibitor (PI)- and lamivudine-naive adults received indinavir/ritonavir 800 mg/100 mg plus stavudine and lamivudine every 12 hours. The proportions of patients achieving plasma HIV RNA (vRNA) <400 and <50 copies/mL were analyzed with data as observed (DAO) and intention-to-treat models using generalized estimating equations (GEE) or counting noncompleters as failures (NC = F). Eighty-nine patients (80% men) with a median age of 36 years and mean baseline vRNA levels and CD4 counts of 5.01 log(10) copies/mL and 269 cells/mm(3) were enrolled. The proportions (95% confidence interval [CI]) of patients achieving vRNA <400 copies/mL were 93% (84%, 98%), 78% (67%, 86%), and 68% (57%, 78%) at week 24 for DAO, GEE, and NC = F analyses, respectively; the corresponding results at week 48 were 95% (84%, 99%), 65% (53%, 76%), and 45% (35%, 57%). Most patients with vRNA <400 had <50 copies/mL. At week 48, baseline vRNA decreased by >2 log(10) copies/mL and CD4 counts increased by approximately 200 cells/mm(3). Five patients (6%) experienced serious drug-related adverse experiences. Twenty patients (23%) discontinued therapy due to adverse experiences. In this study, twice-daily indinavir 800 mg/ritonavir 100 mg with two nucleoside reverse transcriptase inhibitors provided potent viral suppression and immunologic reconstitution in many PI-naive patients.

Effect of ezetimibe/simvastatin compared with atorvastatin on lipoprotein subclasses in patients with type 2 diabetes and hypercholesterolaemia.

Aim: To evaluate the effects of the usual starting and next higher doses of ezetimibe/simvastatin and atorvastatin on the cholesterol content of lipoprotein subclasses in patients with type 2 diabetes and hypercholesterolaemia.

Are post-treatment low-density lipoprotein subclass pattern analyses potentially misleading?

BackgroundSome patients administered cholesterol-lowering therapies may experience an increase in the proportion of small LDL particles, which may be misinterpreted as a worsening of atherosclerotic coronary heart disease risk. This study assessed the lipid effects of adding ezetimibe to atorvastatin or doubling the atorvastatin dose on low-density lipoprotein cholesterol (LDL-C) levels (and the cholesterol content of LDL subclasses), LDL particle number (approximated by apolipoprotein B), and LDL particle size. This was a multicenter, double-blind, randomized, parallel-group study of hypercholesterolemic, high atherosclerotic coronary heart disease risk patients. After stabilization of atorvastatin 40 mg, 579 patients with LDL-C >70 mg/dL were randomized to 6 weeks of ezetimibe + atorvastatin 40 mg or atorvastatin 80 mg. Efficacy parameters included changes from baseline in LDL-C, apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), and lipoprotein subclasses (Vertical Auto Profile II) and pattern for the overall population, as well as patient subgroups with baseline triglyceride levels <150 mg/dL or ≥150 mg/dL.ResultsBoth treatments significantly reduced LDL-C (and the cholesterol content of most LDL subfractions [LDL1-4]) apolipoprotein B, non-HDL-C levels, but did not reduce the proportion of smaller, more dense LDL particles; in fact, the proportion of Pattern B was numerically increased. Results were generally similar in patients with triglyceride levels <150 or ≥150 mg/dL.ConclusionsWhen assessing the effects of escalating cholesterol-lowering therapy, effects upon Pattern B alone to assess coronary heart disease risk may be misleading when interpreted without considerations of other lipid effects, such as reductions in LDL-C, atherogenic lipoprotein particle concentration, and non-HDL-C levels.Trial Registration(Registered at clinicaltrials.gov: Clinical trial # NCT00276484)

Effect of Extended-Release Niacin on New-Onset Diabetes Among Hyperlipidemic Patients Treated With Ezetimibe/Simvastatin in a Randomized Controlled Trial

OBJECTIVE To determine the effect of niacin on fasting glucose (FG) and new-onset diabetes in statin/ezetimibe-treated patients. RESEARCH DESIGN AND METHODS This was a prespecified secondary analysis among 942 hyperlipidemic patients randomized to ezetimibe/simvastatin (E/S; 10/20 mg) or E/S + extended-release niacin (N; titrated to 2 g) over 64 weeks. RESULTS FG levels peaked by 8–12 weeks, then declined even without antidiabetic medication. At 64 weeks, 3.5% taking E/S+N versus 2.6% taking E/S met criteria for new-onset diabetes (P = 0.66). An additional 1.4% taking E/S+N versus 0.4% taking E/S transiently met criteria for diabetes and then remitted (P = 0.46). Of 28 new-diabetes diagnoses in the E/S+N group, 25 occurred by 24 weeks. Among patients with baseline diabetes, 13.9% taking E/S+N and 11.6% taking E/S underwent antidiabetic treatment modification. CONCLUSIONS Increased FG and new-onset diabetes with E/S+N occurred mainly around the time of initial uptitration of N and often improved or remitted without specific treatment.

An open study of subcutaneous administration of inactivated hepatitis A vaccine (VAQTA®) in adults: safety, tolerability, and immunogenicity

A number of patients in clinical practice would be candidates for hepatitis A vaccine administered subcutaneously (SC), including patients with inherited and acquired coagulopathies. To assess the safety, tolerability, and immunogenicity of VAQTA (Hepatitis A Vaccine, Inactivated, Merck and Co. Inc., West Point, PA) was administered SC to healthy adults. A total of 114 healthy adults received two doses of vaccine SC 24 weeks apart. No serious vaccine-related adverse experiences were reported. Four weeks after dose 1, the seropositivity rate (SPR) was 77.9% (CI, 69.1, 85.1%). The geometric mean titer (GMT) was 21.0 mIU/ml. Twenty-four weeks after dose 1 (just prior to dose 2) and 28 weeks after dose 1 (4 weeks following dose 2), the SPRs were 95.3% [corrected] and 100%, respectively; the GMTs were 153.2 and 1563.9 mIU/mL, respectively [corrected]. Although the kinetics of the immune response were slower when VAQTA was administered SC compared to intramuscular injection, SPRs and GMTs increased over time, indicating that the vaccine administered SC demonstrated immunogenicity.

A randomized study of a flexible booster dosing regimen of VAQTA® in adults: safety, tolerability, and immunogenicity

BACKGROUND VAQTA (hepatitis A vaccine inactivated, Merck & Co., Inc., West Point, PA) is licensed for use in healthy adults in a two-dose schedule at 0 and 6 months. OBJECTIVE to determine whether the responses to a booster dose of VAQTA administered to adults 12 or 18 months after the first dose were similar to the response when the booster dose was administered 6 months after the first dose. METHODS healthy adults were randomized to receive 50-U of VAQTA at 6 (Group I), 12 (Group II), or 18 months (Group III) following receipt of Dose 1 on Day 0. Blood samples were collected immediately prior to Doses 1 and 2 and then, 4 weeks following Dose 2. Seropositivity rates (SPRs), geometric mean titers (GMTs) in milli-international units per milliliter (mIU/ml) and booster response rates (BRRs) were compared among treatment groups. Safety data were collected on Vaccination Report Cards. RESULTS no serious adverse experiences were reported, and the vaccine was well-tolerated by subjects in the three treatment groups. One month following the booster dose, SPRs and GMTs for Groups I, II, and III, respectively, were, 100% (102/102) and 6726.4 mIU/ml; 97.9% (93/95) and 4863.8 mIU/ml; 100% (86/86) and 6068.3 mIU/ml. The BRRs were 88.2% (Group I), 90.2% (Group II) and 94.2% (Group III). CONCLUSION responses to the booster dose were comparable regardless of the timing (i.e. 6, 12, or 18 months following Dose 1). Flexibility in the timing of the booster dose of VAQTA in adults would allow the vaccination schedule to be the same for adults, adolescents, and children and may increase the likelihood that adults receive the booster dose.

Open-label study of a twice-daily indinavir 800-mg/ritonavir 200-mg regimen in HIV-infected adults failing a protease inhibitor regimen.

There is no standard treatment of HIV-infected patients who fail protease inhibitor (PI)-containing antiretroviral therapy. This open-label, noncomparative 24-week study with a 24-week extension evaluated the efficacy, safety, and tolerability of twice-daily indinavir/ritonavir 800/200 mg plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) in this population. Presented here are the results of the 24-week study. Patients were HIV-infected adults who had prior viral RNA (vRNA) suppression (<400 copies/mL), subsequent failure (> or =400 and < or =100,000 copies/mL) on antiretroviral therapy, and at least one new NRTI available for treatment. The proportions of patients achieving plasma vRNA <400 and <50 copies/mL were analyzed with data as observed (DAO) and intention-to-treat (ITT) models using generalized estimating equations (GEE) or counting noncompleters as failures (NC = F). Mean changes from baseline in vRNA and CD4 cell count were evaluated using DAO and an ITT mixed-model approach. Sixty-three patients (87% male) with a mean age of 42 years and mean baseline vRNA and CD4 cell counts of 3.8 log(10) copies/mL and 360 cells/mm(3), respectively, were enrolled. The proportion (95% confidence interval) of patients achieving vRNA <400 and <50 copies/mL at week 24 were 76% (61%, 87%) and 50% (35%, 65%) for DAO, 64% (50%, 75%) and 43% (30%, 56%) for GEE, and 56% (43%, 68%) and 37% (25%, 50%) for NC = F, respectively. At Week 24, baseline vRNA decreased by >1.0 log(10) copies/mL and CD4 cell counts increased by approximately 90 cells/mm(3). Three patients (5%) experienced serious drug-related adverse events. Seven patients (11%) discontinued treatment due to clinical or laboratory adverse events. In this study, the enhanced, twice-daily regimen of indinavir/ritonavir 800/200 mg plus 2 NRTIs provided suppression of HIV in many patients who had failed a PI-containing regimen and was generally well tolerated.