Immunogenicity and safety of porcine circovirus-free human rotavirus vaccine in healthy infants: a phase III, randomized trial.

BACKGROUND: Porcine circovirus type 1 (PCV-1) material was detected in the human rotavirus vaccine (HRV) in 2010. In this study (NCT02914184) we compared immunogenicity and safety of the PCV-free HRV vaccine (PCV-free HRV) with HRV. PCV-free HRV is an HRV with no detection of PCV-1 and PCV-2 according to the limit of detection of the tests used. METHODS: Healthy infants 6-12 weeks of age were randomized (1:1:1:1) to receive 2 doses of 1 of the 3 lots of PCV-free HRV or HRV. The study objectives were to demonstrate lot-to-lot consistency of the PCV-free HRV and non-inferiority of PCV-free HRV as compared to HRV in terms of immunogenicity, 1-2 months post-dose 2. Reactogenicity and safety were also assessed. RESULTS: Overall, 1612 infants were enrolled and 1545 completed the study. Study objectives were demonstrated since the pre-defined criteria were met. Among participants receiving PCV-free HRV and HRV, 79.27% and 81.76% seroconverted and geometric mean concentrations were 159.5 and 152.8 U/mL, respectively. The incidences of adverse events and serious adverse events were similar between the pooled PCV-free HRV and HRV groups. CONCLUSIONS: The 3 PCV-free HRV lots demonstrated consistency and PCV-free HRV was non-inferior compared to HRV in terms of immunogenicity.

Successful childbirth in a Fontan with protein losing enteropathy.

As survival rates and functional status of the adult single ventricle population have grown, some may become pregnant inadvertently or against our advice. The outcomes are often poor, being worse for the fetus/baby rather than the mother with a Fontan circuit. No reports of a successful delivery of a healthy baby to a Fontan mother with protein losing enteropathy were found in the literature. We present one such case.

Single center protocol driven care in 150 patients with gastroschisis 1998-2017: collaboration improves results.

PURPOSE: The treatment of gastroschisis (GS) using our collaborative clinical pathway, with immediate attempted abdominal closure and bowel irrigation with a mucolytic agent, was reviewed. METHODS: A retrospective review of the past 20 years of our clinical pathway was performed on neonates with GS repair at our institution. The clinical treatment includes attempted complete reduction of GS defect within 2 h of birth. In the operating room, the bowel is evaluated and irrigated with mucolytic agent to evacuate the meconium and decompress the bowel. No incision is made and a neo-umbilicus is created. Clinical outcomes following closure were assessed. RESULTS: 150 babies with gastroschisis were reviewed: 109 (77%) with a primary repair, 33 (23%) with a spring-loaded silo repair. 8 babies had a delayed closure and were not included in the statistical analysis. Successful primary repair and time to closure had a significant relationship with all outcome variables-time to extubation, days to initiate feeds, days to full feeds, and length of stay. CONCLUSION: Early definitive closure of the abdominal defect with mucolytic bowel irrigation shortens time to first feeds, total TPN use, time to extubation, and length of stay.

Risk of surgery following recent myocardial infarction.

OBJECTIVE: We aimed to assess the impact of recent myocardial infarction (MI) on outcomes after subsequent surgery in the contemporary clinical setting. BACKGROUND: Prior work shows that a history of a recent MI is a risk factor for complications following noncardiac surgery. However, this data does not reflect current advances in clinical management. METHODS: Using the California Patient Discharge Database, we retrospectively analyzed patients undergoing hip surgery, cholecystectomy, colectomy, elective abdominal aortic aneurysm repair, and lower extremity amputation from 1999 to 2004 (n = 563,842). Postoperative 30-day MI rate, 30-day mortality, and 1-year mortality were compared for patients with and without a recent MI using univariate analyses and multivariate logistic regression. Relative risks (RR) with 95% confidence intervals were estimated using bootstrapping with 1000 repetitions. RESULTS: Postoperative MI rate for the recent MI cohort decreased substantially as the length of time from MI to operation increased (0-30 days = 32.8%, 31-60 days = 18.7%, 61-90 days = 8.4%, and 91-180 days = 5.9%), as did 30-day mortality (0-30 days = 14.2%, 31-60 days = 11.5%, 61-90 days = 10.5%, and 91-180 days = 9.9%). MI within 30 days of an operation was associated with a higher risk of postoperative MI (RR range = 9.98-44.29 for the 5 procedures), 30-day mortality (RR range, 1.83-3.84), and 1-year mortality (RR range, 1.56-3.14). CONCLUSIONS: A recent MI remains a significant risk factor for postoperative MI and mortality following surgery. Strategies such as delaying elective operations for at least 8 weeks and medical optimization should be considered.

Natural history of pancreatitis-induced splenic vein thrombosis: a systematic review and meta-analysis of its incidence and rate of gastrointestinal bleeding.

BACKGROUND: Pancreatitis-induced splenic vein thrombosis (PISVT) is an acquired anatomic abnormality that impacts decision making in pancreatic surgery. Despite this influence, its incidence and the rate of associated gastrointestinal (GI) bleeding are imprecisely known. METHODS: The MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials and Cochrane Database of Systematic Reviews databases were searched from their inception to June 2010 for abstracts documenting PISVT in acute (AP) or chronic pancreatitis (CP). Two reviewers independently graded abstracts for inclusion in this review. Heterogeneity in combining data was assumed prior to pooling. Random-effects meta-analyses were performed to estimate percentages and 95% confidence intervals. RESULTS: After review of 241 abstracts, 47 studies and 52 case reports were graded as relevant. These represent a cohort of 805 patients with PISVT reported in the literature. A meta-analysis of studies meeting inclusion criteria shows mean incidences of PISVT of 14.1% in all patients, 22.6% in patients with AP and 12.4% in patients with CP. The incidence of associated splenomegaly was only 51.9% in these patients. Varices were identified in 53.0% of patients and were gastric in 77.3% of cases. The overall rate of GI bleeding was 12.3%. CONCLUSIONS: Although reported incidences of PISVT vary widely across studies, an overall incidence of 14.1% is reported. Splenomegaly is an unreliable sign of PISVT. Although the true natural history of PISVT remains unknown, the collective reported rate of associated GI bleeding is 12.3%.

Abdominal surgery after lung transplantation.

Among 450 patients who underwent lung transplantation (LuT) between April 1994 and April 2009 at a single academic hospital, 75 received surgical consultation, and 52 underwent 65 abdominal operations. Operations included colectomy (17), cholecystectomy (14), exploratory laparotomy (10), ulcer repair (five), hernia repair (four), Nissen fundoplication (four), pancreatic debridement (four), ostomy takedown (two), drainage of intra-abdominal abscess (two), and major vascular procedure, gastrostomy, splenectomy, fascial closure, laparoscopic common bile duct exploration, and small bowel resection (one each). Fourteen patients (27%) died within 30 days of surgery. On univariate analysis, age, race, comorbidities, history of previous abdominal surgery, transplant type, and timing of surgery after transplant were similar between the patients who survived and died. On multivariate analysis, emergent surgery, multiple medical comorbidities, and male gender were predictive of 30-day mortality (P < or = 0.05). Ulcer repair, major vascular procedures, pancreatic surgery, splenectomy, and exploratory laparotomy were associated with > or =50 per cent 30-day mortality. This is the largest series reporting outcomes of abdominal operations after LuT. Elective operations in LuT patients are safe, whereas emergent operations carry an extremely high short-term mortality rate. Aggressive prophylaxis for ulcer disease and early elective intervention for potential surgical problems, such as gallstones and uncomplicated diverticulitis, should be considered.

Developing quality indicators for elderly surgical patients.

OBJECTIVE: To develop process-based quality indicators to improve perioperative care for elderly surgical patients. BACKGROUND: The population is aging and expanding, and physicians must continue to optimize elderly surgical care to meet the anticipated increase in surgical services. We sought to develop process-based quality indicators applicable to virtually all disciplines of surgery to identify necessary and meaningful ways to improve surgical care and outcomes in the elderly. METHODS: We identified candidate perioperative quality indicators for elderly patients undergoing ambulatory, or major elective or nonelective inpatient surgery through structured interviews with thought leaders and systematic reviews of the literature. An expert panel of physicians in surgery, geriatrics, anesthesia, critical care, internal, and rehabilitation medicine formally rated the indicators using a modification of the RAND/UCLA Appropriateness Methodology. RESULTS: Ninety-one of 96 candidate indicators were rated as valid. They were categorized into 8 domains: comorbidity assessment, elderly issues, medication use, patient-provider discussions, intraoperative care, postoperative management, discharge planning, and ambulatory surgery. Of note, 71 (78%) of the indicators rated as valid address processes of care not routinely performed in younger surgical populations. CONCLUSIONS: Attention to the quality of care in elderly patients is of great importance due to the increasing numbers of elderly undergoing surgery. This project used a validated methodology to identify and rate process measures to achieve high quality perioperative care for elderly surgical patients.

Quality of care issues in colorectal cancer.

Colorectal cancer is a common, detectable, and treatable malignancy. Given the aging of the population, the number of patients diagnosed with colorectal cancer will likely increase; thus, efforts to improve the quality and delivery of appropriate care to patients with colorectal cancer are needed. The overarching goal of this article is to summarize recent efforts to evaluate and improve the quality of colorectal cancer care through the use of selective referral, quality performance measures, and assessment of outcomes. First, we provide a framework for quality of care assessment, including a discussion of the structural, process, and outcome components of care for colorectal cancer. Second, we discuss the current level of assessment of colorectal cancer care quality, highlighting four potential targets for quality improvement: increased provider volume for colorectal cancer resection, process-based quality measures for colorectal cancer care (including measures specific to colorectal cancer surgery), data collection and feedback programs for colorectal cancer care, and evaluation of health-related quality of life in patients with colorectal cancer. Further research is needed to evaluate both the implementation and effectiveness of these quality improvement strategies for improving outcome in patients with colorectal cancer.

Management of high-grade splenic injury in children.

Using the National Trauma Databank, we identified 413 children (age < or = 14 years) who sustained high-grade blunt splenic injury (Abbreviated Injury Scale scores > or = 4) from 2001 to 2005. Overall mortality was 13.5 per cent. Early operation within 6 hours of injury (EOM) was performed in 128 patients (31%). Patients not undergoing EOM (n = 285) were assumed to have been treated with initial nonoperative management (NOM). NOM was successful in 84 per cent of patients. Operative intervention was necessary in 42 per cent of cases with 74 per cent of these undergoing early operation (EOM). Total splenectomy was the most common procedure (83%). EOM and failure of NOM were both associated with lower systolic blood pressure and lower Glasgow Coma Scale score at admission, higher Injury Severity Score, longer hospital stay, and higher mortality. Need for surgery was independent of patient age and gender. Failure of NOM was associated with increased mortality compared with successful NOM, but had similar mortality and length of hospital or intensive care unit stay compared with EOM. We conclude that operative treatment is necessary in nearly half of pediatric patients with high-grade splenic injury. With careful selection, nonoperative management is usually successful but must include close monitoring, because 16 per cent required delayed operation.

Publicly available hospital comparison web sites: determination of useful, valid, and appropriate information for comparing surgical quality.

OBJECTIVE: To explore hospital comparison Web sites for general surgery based on: (1) a systematic Internet search, (2) Web site quality evaluation, and (3) exploration of possible areas of improvement. DESIGN: A systematic Internet search was performed to identify hospital quality comparison Web sites in September 2006. Publicly available Web sites were rated on accessibility, data/statistical transparency, appropriateness, and timeliness. A sample search was performed to determine ranking consistency. RESULTS: Six national hospital comparison Web sites were identified: 1 government (Hospital Compare [Centers for Medicare and Medicaid Services]), 2 nonprofit (Quality Check [Joint Commission on Accreditation of Healthcare Organizations] and Hospital Quality and Safety Survey Results [Leapfrog Group]), and 3 proprietary sites (names withheld). For accessibility and data transparency, the government and nonprofit Web sites were best. For appropriateness, the proprietary Web sites were best, comparing multiple surgical procedures using a combination of process, structure, and outcome measures. However, none of these sites explicitly defined terms such as complications. Two proprietary sites allowed patients to choose ranking criteria. Most data on these sites were 2 years old or older. A sample search of 3 surgical procedures at 4 hospitals demonstrated significant inconsistencies. CONCLUSIONS: Patients undergoing surgery are increasingly using the Internet to compare hospital quality. However, a review of available hospital comparison Web sites shows suboptimal measures of quality and inconsistent results. This may be partially because of a lack of complete and timely data. Surgeons should be involved with quality comparison Web sites to ensure appropriate methods and criteria.

Two-year antibody persistence in children vaccinated at 12-15 months with a measles-mumps-rubella virus vaccine without human serum albumin.

One combined measles-mumps-rubella (MMR) vaccine without Human Serum Albumin (HSA) is currently licensed in the USA (M-M-R II; Merck, USA) and another has been developed (Priorix™ [MMR-RIT, GSK, Belgium]). In this follow-up study, children from USA or Puerto Rico, who had received one dose of M-M-R II or MMR-RIT at 12-15 months of age in the primary study (NCT00861744), were followed-up for 2 y post-vaccination. Anti-measles and anti-rubella antibodies were measured using Enzyme-Linked Immunosorbent Assay (ELISA), and anti-mumps antibodies using ELISA and plaque reduction neutralization (PRN) assays. Serious adverse events (SAEs) were recorded during the entire follow-up. The according-to-protocol (ATP) persistence cohort included 752 children (M-M-R II = 186, MMR-RIT = 566), who received primary vaccination at a mean age of 12.3 ( ± 0.67) months. 104 children were revaccinated with MMR-containing vaccines; therefore, serology results for timepoints after revaccination were excluded from the analysis. Seropositivity for measles (Year 1≥ 98.3%; Year 2≥ 99.4%) and rubella (Year 1≥ 98.9%; Year 2 = 100%) remained as high at Year 2 as at Day 42. Similarly, seropositivity for mumps determined by ELISA (Year 1≥ 90.1%; Year 2≥ 94.1%) and PRN assays (Year 1≥ 87.5%; Year 2≥ 91.7%) persisted. Thirty-three SAEs were recorded in 23 children; 2 SAEs (inguinal adenitis and idiopathic thrombocytopenic purpura) and one SAE (febrile convulsion) were considered as potentially related to MMR-RIT and M-M-R II, respectively. This study showed that antibodies against measles, mumps and rubella persisted for up to 2 y post-vaccination with either MMR vaccine in children aged 12-15 months, and that both vaccines were well-tolerated during the follow-up period.

Lot-to-lot consistency, safety and immunogenicity of 3 lots of Haemophilus influenzae type b conjugate vaccine: results from a phase III randomized, multicenter study in infants.

BACKGROUND: Vaccination against Haemophilus influenzae type b (Hib) is included in routine pediatric immunization schedule in the United States. Previous vaccine shortages have created the need for additional options for Hib vaccination. METHODS: This phase III, randomized, multi-centered study (NCT01000974) evaluated the safety and immunogenicity of a monovalent tetanus toxoid-conjugate Hib vaccine (Hib-TT) compared to a monovalent (Hib-TT control) and a combination Hib-TT vaccine. We hierarchically assessed lot-to-lot consistency of 3 Hib-TT lots and non-inferiority of Hib-TT to Hib-TT control. We co-administered routine pediatric vaccines with Hib-TT vaccines at 2, 4, 6months (primary vaccination) and 15-18months of age (booster vaccination). We recorded adverse events (AEs) for 4 (solicited) and 31days (unsolicited) post-vaccination and serious AEs (SAEs) throughout the study. RESULTS: Of 4009 enrolled children, 3086 completed booster phase. Lot-to-lot consistency was not demonstrated. The study met statistical criteria for non-inferiority of Hib-TT to Hib-TT control in terms of immune responses to Hib and co-administered vaccines' antigens, but not in terms of participants achieving post-primary vaccination anti-PRP levels ≥1µg/mL. Because of the hierarchical nature of the objectives, non-inferiority could not be established. In all groups, 92.5-96.7% and 99.6-100% of participants achieved anti-PRP levels ≥0.15µg/mL, while 78.3-89.8% and 97.9-99.1% had anti-PRP levels ≥1µg/mL, post-primary and post-booster vaccination, respectively. Immune responses to co-administered vaccines and reported incidence of AEs were comparable among groups. We recorded SAEs for 107/2963 (3.6%), 24/520 (4.6%), and 21/520 (4.0%) children post-primary vaccination, and 29/2337 (1.2%), 4/435 (0.9%), and 2/400 (0.5%) children post-booster vaccination with Hib-TT, Hib-TT control and combination Hib-TT vaccine, respectively; 6/5330 (0.1%) SAEs in the Hib-TT groups were considered vaccine-related. CONCLUSION: Hib-TT induced seroprotective antibody concentrations in the majority of participants and was well-tolerated when co-administered with routine pediatric vaccines according to a 3+1 schedule.

Time to Change Dosing of Inactivated Quadrivalent Influenza Vaccine in Young Children: Evidence From a Phase III, Randomized, Controlled Trial.

BACKGROUND.: Children under 3 years of age may benefit from a double-dose of inactivated quadrivalent influenza vaccine (IIV4) instead of the standard-dose. METHODS.: We compared the only United States-licensed standard-dose IIV4 (0.25 mL, 7.5 µg hemagglutinin per influenza strain) versus double-dose IIV4 manufactured by a different process (0.5 mL, 15 µg per strain) in a phase III, randomized, observer-blind trial in children 6-35 months of age (NCT02242643). The primary objective was to demonstrate immunogenic noninferiority of the double-dose for all vaccine strains 28 days after last vaccination. Immunogenic superiority of the double-dose was evaluated post hoc. Immunogenicity was assessed in the per-protocol cohort (N = 2041), and safety was assessed in the intent-to-treat cohort (N = 2424). RESULTS.: Immunogenic noninferiority of double-dose versus standard-dose IIV4 was demonstrated in terms of geometric mean titer (GMT) ratio and seroconversion rate difference. Superior immunogenicity against both vaccine B strains was observed with double-dose IIV4 in children 6-17 months of age (GMT ratio = 1.89, 95% confidence interval [CI] = 1.64-2.17, B/Yamagata; GMT ratio = 2.13, 95% CI = 1.82-2.50, B/Victoria) and in unprimed children of any age (GMT ratio = 1.85, 95% CI = 1.59-2.13, B/Yamagata; GMT ratio = 2.04, 95% CI = 1.79-2.33, B/Victoria). Safety and reactogenicity, including fever, were similar despite the higher antigen content and volume of the double-dose IIV4. There were no attributable serious adverse events. CONCLUSIONS.: Double-dose IIV4 may improve protection against influenza B in some young children and simplifies annual influenza vaccination by allowing the same vaccine dose to be used for all eligible children and adults.

The rate of bleeding complications after pharmacologic deep venous thrombosis prophylaxis: a systematic review of 33 randomized controlled trials.

HYPOTHESIS: Major bleeding complications from pharmacologic deep venous thrombosis (DVT) prophylaxis are infrequent. DESIGN: Systematic review of the MEDLINE database from 1965 to August 2005, using the terms DVT, prophylaxis, general surgery, and heparin. SETTING AND PATIENTS: Randomized controlled trials evaluating pharmacologic DVT prophylaxis in patients undergoing general surgery. MAIN OUTCOME MEASURES: Eight complication categories: injection site bruising, wound hematoma, drain site bleeding, hematuria, gastrointestinal tract bleeding, retroperitoneal bleeding, discontinuation of prophylaxis, and subsequent operation. RESULTS: Fifty-two randomized controlled trials studied DVT prophylaxis; 33 randomized controlled trials with 33 813 patients undergoing general surgery evaluated pharmacologic prophylaxis and quantified bleeding complications. Of the minor complications, injection site bruising (6.9%), wound hematoma (5.7%), drain site bleeding (2.0%), and hematuria (1.6%) were most common. Major bleeding complications, such as gastrointestinal tract (0.2%) or retroperitoneal (<0.1%) bleeding, were infrequent. Discontinuation of prophylaxis occurred in 2.0% of patients and subsequent operation in less than 1% of patients. When analyzed by high- vs low-dose unfractionated heparin, the lower dose had a smaller rate of discontinuation of prophylaxis (P = .02) and subsequent operation (P = .06). CONCLUSIONS: Knowledge of bleeding complication rates is important for surgeons because DVT prophylaxis may soon be implemented by Medicare as a quality measure. This level 1 evidence report shows that bleeding complications requiring a change in care occur less than 3% of the time and seem reduced with lower-dose prophylaxis. Given these findings, most patients undergoing general surgery could receive pharmacologic prophylaxis safely.

Quadrivalent meningococcal (MenACWY-TT) conjugate vaccine or a fourth dose of H. influenzae-N. meningitidis C/Y conjugate vaccine (HibMenCY-TT) is immunogenic in toddlers who previously received three doses of HibMenCY-TT in infancy.

BACKGROUND: Immunogenicity and safety of a single dose of MenACWY-TT or a fourth dose of HibMenCY-TT were evaluated in the second year of life in HibMenCY-TT-primed toddlers. METHODS: Healthy infants were randomized (5:1) and primed at 2, 4 and 6 months of age with HibMenCY-TT and diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus (DTaP-HBV-IPV) vaccine; or Hib-TT and DTaP-HBV-IPV (control). Recipients of HibMenCY-TT+DTaP-HBV-IPV were re-randomized (2:2:1) to receive MenACWY-TT at 12-15 months and DTaP at 15-18 months; MenACWY-TT co-administered with DTaP at 15-18 months; or HibMenCY-TT at 12-15 months and DTaP at 15-18 months. Controls received DTaP only at 15-18 months due to Hib conjugate vaccine shortage. Serum bactericidal activity using human complement (hSBA) and safety were assessed one month after meningococcal vaccination. RESULTS: After vaccination with MenACWY-TT at 12-15 months or MenACWY-TT+DTaP at 15-18 months, all subjects previously primed for serogroups C/Y had hSBA ≥1:8 for these serogroups. At least 96.1% also had hSBA ≥1:8 for serogroups A/W. All subjects in the HibMenCY-TT group had hSBA ≥1:8 for serogroups C/Y. All pre-defined statistical criteria for meningococcal immunogenicity were satisfied. All vaccination regimens had acceptable safety profiles. CONCLUSION: Children primed with three doses of HibMenCY-TT who then received a single dose of MenACWY-TT or a fourth dose of HibMenCY-TT had robust increases in hSBA titers for serogroups C/Y. These data provide support that MenACWY-TT, given with or without the fourth scheduled dose of DTaP could be administered as an alternative to a fourth dose of HibMenCY-TT in the second year of life. This study (110870/110871) is registered at www.clinicaltrials.gov NCT00614614.

Immunogenicity, Safety, and Tolerability of a Hexavalent Vaccine in Infants.

BACKGROUND: DTaP5-IPV-Hib-HepB is a fully liquid investigational hexavalent vaccine directed against 6 diseases. METHODS: This multicenter, open-label, comparator-controlled, phase III study randomly assigned healthy infants 2-to-1 as follows: group 1 received DTaP5-IPV-Hib-HepB, PCV13, and RV5 at 2, 4, and 6 months of age followed by DTaP5, Hib-OMP, and PCV13 at 15 months of age; group 2 received DTaP5-IPV/Hib, PCV13, and RV5 at 2, 4, and 6 months of age, with HepB at 2 and 6 months of age, followed by DTaP5, Hib-TT, and PCV13 at 15 months of age. RESULTS: Overall, 981 participants were vaccinated in group 1 and 484 in group 2. Immune responses in group 1 to all antigens contained in DTaP5-IPV-Hib-HepB 1 month after dose 3 and for concomitant rotavirus vaccine were noninferior to those in group 2, with the exception of antipertussis filamentous hemagglutinin (FHA) geometric mean concentrations (GMCs). Vaccine response rates for FHA were noninferior to control. After the toddler dose, group 1 immune responses were noninferior to group 2 for all pertussis antigens. Solicited adverse event rates after any dose were similar in both groups, with the exceptions of increased injection-site erythema, increased fever, and decreased appetite in group 1. Fever was not associated with hospitalization or seizures. CONCLUSIONS: The safety and immunogenicity of DTaP5-IPV-Hib-HepB are comparable with the analogous licensed component vaccines. Decreased FHA GMCs and increased injection-site reactions and fever are unlikely to be clinically significant. DTaP5-IPV-Hib-HepB provides a new combination vaccine option aligned with the recommended US infant immunization schedule.

Immunogenicity and reactogenicity of Infanrix™ when co-administered with meningococcal MenACWY-TT conjugate vaccine in toddlers primed with MenHibrix™ and Pediarix™.

BACKGROUND: Co-administration of an investigational quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) with the fourth dose of diphtheria-tetanus-acellular pertussis vaccine (DTaP) at age 15-18 months was investigated in 3-dose Haemophilus influenzae type b-meningococcal serogroups C/Y conjugate vaccine (HibMenCY-TT)-primed toddlers. METHODS: Infants were randomized (5:1) and primed at 2, 4 and 6 months of age with HibMenCY-TT and DTaP-hepatitis B-inactivated poliovirus (DTaP-HBV-IPV) vaccine, or Hib-TT and DTaP-HBV-IPV (Control). HibMenCY-TT+ DTaP-HBV-IPV vaccinees were re-randomized (2:2:1) to receive MenACWY-TT at 12-15 months and DTaP at 15-18 months (MenACWY-TT group); MenACWY-TT co-administered with DTaP at 15-18 months (Coad group); or HibMenCY-TT at 12-15 months and DTaP at 15-18 months (HibMenCY-TT group). Controls received DTaP at 15-18 months. Only children in the HibMenCY-TT group received a fourth dose of Hib conjugate vaccine due to Hib conjugate vaccine shortage at the time of the study. DTaP immunogenicity and reactogenicity were assessed one month post-vaccination. RESULTS: Pre-defined statistical non-inferiority criteria between Coad and Control groups were met for diphtheria, tetanus and filamentous haemagglutinin but not pertussis toxoid and pertactin. Following vaccination ≥99% of children had anti-diphtheria/anti-tetanus concentrations ≥1.0 IU/ml. Pertussis GMCs were lower in all investigational groups versus Control. In post hoc analyses, pertussis antibody concentrations were above those in infants following 3-dose DTaP primary vaccination in whom efficacy against pertussis was demonstrated (Schmitt, von König, et al., 1996; Schmitt, Schuind, et al., 1996). The reactogenicity profile of the Coad group was similar to DTaP administered alone. CONCLUSION: Routine booster DTaP was immunogenic with an acceptable safety profile when co-administered with MenACWY-TT vaccine in HibMenCY-TT-primed toddlers. These data support the administration of a fourth DTaP dose following a 4-dose HibMenCY-TT vaccination series, or co-administered with MenACWY-TT in HibMenCY-TT-primed children.

Safety and Immunogenicity of Human Serum Albumin-Free MMR Vaccine in US Children Aged 12-15 Months.

BACKGROUND: M-M-R(TM)II (MMRII; Merck & Co) is currently the only measles-mumps-rubella (MMR) vaccine licensed in the United States. Another licensed vaccine would reinforce MMR supply. This study assessed the immunogenicity of a candidate vaccine (Priorix(TM), GlaxoSmithKline Vaccines [MMR-RIT]) when used as a first dose among eligible children in the United States. METHODS: In this exploratory Phase-2, multicenter, observer-blind study, 1220 healthy subjects aged 12-15 months were randomized (3:3:3:3) and received 1 dose of 1 of 3 MMR-RIT lots with differing mumps virus titers (MMR-RIT-1 [4.8 log10]; MMR-RIT-2 [4.1 log10]; MMR-RIT-3 [3.7 log10] CCID50) or MMRII co-administered with hepatitis A vaccine (HAV), varicella vaccine (VAR) and 7-valent pneumococcal conjugate vaccine (PCV7). Immune response to measles, mumps, and rubella viruses was evaluated at Day 42 post-vaccination. Incidence of solicited injection site, general, and serious adverse events was assessed. RESULTS: Seroresponse rates for MMR vaccine viral components in MMR-RIT lots were 98.3-99.2% (measles), 89.7-90.7% (mumps), and 97.5-98.8% (rubella), and for MMRII were 99.6%, 91.1%, and 100%, respectively. Immune responses to HAV, VAR, and PCV7 were similar when co-administered with any of the 3 MMR-RIT lots or MMRII. There were no apparent differences in solicited or serious adverse events among the 4 groups. CONCLUSIONS: Immune responses were above threshold levels for projected protection against the 3 viruses from MMR-RIT lots with differing mumps virus titers. MMR-RIT had an acceptable safety profile when co-administered with HAV, VAR, and PCV7. CLINICAL TRIALS REGISTRATION: NCT00861744; etrack; 111870.

Improved survival for adenocarcinoma of the ampulla of Vater: fifty-five consecutive resections.

HYPOTHESIS: After resection of an adenocarcinoma of the ampulla of Vater, certain clinical and pathologic characteristics influence long-term survival. DESIGN: Retrospective case series. SETTING: Major academic medical and pancreatic surgical center. PATIENTS: Fifty-five consecutive patients who underwent Whipple resection for ampullary adenocarcinoma from 1988 through 2001. INTERVENTIONS: Pylorus-preserving Whipple resection in 32 patients and standard Whipple resection in 23 patients. MAIN OUTCOME MEASURES: Postoperative survival. A multivariate Cox proportional hazards model was used to determine the effects of various factors on long-term survival after resection. RESULTS: There were no operative deaths, and all patients left the hospital. After a mean follow-up of 46.9 months, the overall 5-year Kaplan-Meier survival estimate was 67.7%. The median survival of the entire group has not yet been reached. Five-year postoperative survival estimates for node-negative (n = 32) and node-positive patients (n = 23) were 76.5% and 53.4%, respectively (P =.26). Patients whose tumors demonstrated perineural invasion (n = 12) had a 5-year survival estimate of 29.2% vs 78.8% for those whose did not (P<.001). On multivariate analysis, the absence of perineural invasion (P<.001) was an independent predictor of significantly improved postoperative survival. CONCLUSIONS: Compared with previous reports from our own and other centers, this series demonstrates improved postoperative survival by 10% to 20% in patients undergoing Whipple resection for adenocarcinoma of the ampulla of Vater. The reasons for this improved outcome are unclear, and the effect of adjuvant treatment cannot be determined from this analysis. The major factor associated with prolonged survival was the absence of perineural invasion in the resected tumor specimen.