Economic evaluation of vaccination programmes: a consensus statement focusing on viral hepatitis

The methods that have been used to estimate the clinical and economic impact of vaccination programmes are not always uniform, which makes it difficult to compare results between economic analyses. Furthermore, the relative efficiency of vaccination programmes can be sensitive to some of the more controversial aspects covered by general guidelines for the economic evaluation of healthcare programmes, such as discounting of health gains and the treatment of future unrelated costs. In view of this, we interpret some aspects of these guidelines with respect to vaccination and offer recommendations for future analyses. These recommendations include more transparency and validation, more careful choice of models (tailored to the infection and the target groups), more extensive sensitivity analyses, and for all economic evaluations (also nonvaccine related) to be in better accordance with general guidelines. We use these recommendations to interpret the evidence provided by economic evaluation applied to viral hepatitis vaccination. We conclude that universal hepatitis B vaccination (of neonates, infants or adolescents) seems to be the most optimal strategy worldwide, except in the few areas of very low endemicity, where the evidence to enable a choice between selective and universal vaccination remains inconclusive. While targeted hepatitis A vaccination seems economically unattractive, universal hepatitis A vaccination strategies have not yet been sufficiently investigated to draw general conclusions.     

Abdominal seat belt marks in the era of focused abdominal sonography for trauma

HYPOTHESIS: Focused abdominal sonography for trauma (FAST) is an unreliable method for assessing intra-abdominal injury in patients with seat belt marks. DESIGN: Retrospective review of trauma patients with intestinal injury and seat belt marks during a 3-year period. Records were reviewed for patient demographics, FAST results, computed tomographic (CT) scan results, and operative findings. The CT scan results were considered positive if bowel wall thickening, extraluminal air, or free fluid without solid organ injury were present. SETTING: University hospital designated as a level I trauma center. PATIENTS: Twenty-three patients who required operation for intestinal or mesenteric injury and who had an abdominal seat belt mark. MAIN OUTCOME MEASURE: Sensitivity of FAST in these patients. RESULTS: All patients were evaluated using both FAST and CT scan of the abdomen and pelvis. Eighteen patients (78%) had either negative or equivocal FAST results when significant intestinal injury was present. All 23 patients had CT scan findings suggestive of bowel or mesenteric injury. Moderate-to-large free intraperitoneal fluid without solid organ injury was the most common finding (n = 21, 91%). Operative findings included small-bowel perforation (n = 18, 78%), colonic perforation (n = 7, 30%), bowel deserosalization (n = 8, 35%), and isolated mesenteric injury (n = 5, 22%). Sixteen patients (70%) had multiple intra-abdominal injuries. All patients were taken directly from the emergency department to the operating room. Seventeen percent of operative explorations (4/23) were nontherapeutic (no repairs required). CONCLUSION: This study confirms that FAST cannot reliably exclude intestinal injury in patients with seat belt marks.     

Active immunotherapy by reinduction with a polyvalent allogeneic cell vaccine correlates with improved survival in recurrent metastatic melanoma

Background We have observed prolonged survival in patients undergoing vaccine reinduction after resection of recurrent metastatic melanoma and adjuvant polyvalent allogenic cell vaccine (PACV) immunotherapy. We hypothesized that reinduction with a more intensive vaccine regimen would re-stimulate specific immune responses that were correlated with survival after recurrence. Methods From 1996 to 1998, 194 patients developed recurrence during adjuvant PACV (CancerVax vaccine) treatment after resection of metastatic melanoma. Recurrent disease was treated with or without vaccine reinduction. Reinduction regimen entailed an increased vaccine frequency and coadministration of two doses of bacille Calmette-Guérin (BCG). PACV Delayedtype hypersensitivity (DTH) responses were prospectively recorded. Survival was defined as the interval from recurrence to death. Results Ninety-four patients underwent reinduction immunotherapy. DTH responses to PACV before recurrence increased significantly after reinduction therapy (P=.0001). The median survival time was 37 months for reinduced patients and 17 months for other patients. On multivariate analysis, reinduction status remained a significant prognostic variable (P=.0277). In the reinduction group, there was a significant correlation between PACV DTH responses and survival (P=.0178). Conclusions Reinduction vaccine regimen can enhance immune responses in previously immunized patients and is associated with prolonged survival after recurrence in patients receiving the same active specific immunotherapy. Presented at the Society of Surgical Oncology annual meeting. Washington, DC, March 15–18, 2001.     

A randomised controlled trial of early versus delayed use of amniotomy and oxytocin infusion in nulliparous labour

Objective To compare routine amniotomy and early intravenous oxytocin (active management of labour) with a more selective use of amniotomy and oxytocin in women in true labour who received comparable continuous supportive midwifery care.
Design Randomised controlled trial of nulliparous clinic patients in spontaneous labour at term. Setting Labour and delivery ward of a university teaching hospital.
Participants Three hundred and six parturients: 152 received active management of labour; 154 were more selectively managed.
Interventions 1. Active management: early amniotomy, early use of oxytocin. 2. Selective intervention management: no routine amniotomy and more selective use of oxytocin.
Outcome measures Use of oxytocin and amniotomy. Labour duration, mode of delivery.
Results Maternal characteristics were comparable in both groups. Amniotomy was more often performed (91% versus 57%,   P < 0.01  ) and oxytocin more often used (53% versus 27%, P < 001) in the active management group. The first stage of labour, however, was only shortened by half an hour in the active management group (254 min versus 283 min,   P = 0.087  ). Caesarean section rate (3.9% versus 2.6%), spontaneous vaginal delivery rate (78% versus 79%) and neonatal outcome were not significantly different between groups.
Conclusion Within a set-up of strict labour diagnosis and supportive midwifery care, routine amniotomy and early use of oxytocin offered no advantage over a more selective use of amniotomy and oxytocin in terms of mode of delivery and labour duration.     

The effects of glucose, fructose, and sucrose ingestion during exercise

The purpose of this study was to compare the physiological, sensory, and exercise performance responses to ingestion of 6% glucose, 6% fructose, and 6% sucrose solutions during cycling exercise. Twelve subjects completed three sessions consisting of 115 min of intermittent cycle ergometer exercise at 65-80% of VO2max followed by a timed performance bout requiring the completion of 600 pedal revolutions. During each of five 4-min rest periods, subjects consumed 3 ml.kg LBM-1 of one of the beverages. Beverages were presented in counterbalanced, double-blind fashion. Heart rate, VO2, plasma urate, plasma lactate, respiratory exchange ratio, and carbohydrate combustion rates changed similarly among beverage treatment. However, fructose was associated with lower plasma glucose and serum insulin, a larger loss of plasma volume, greater gastrointestinal distress and relative perceived exertion ratings, and higher plasma or serum concentrations of free fatty acids, fructose, and cortisol values than sucrose or glucose (P less than 0.05). Compared to sucrose and glucose, fructose feeding also resulted in lower lactate and HR values during the performance bout (P less than 0.05). Mean +/- SE cycling performance times were faster with sucrose and glucose than with fructose: 419.4 +/- 21.0 s, 423.9 +/- 21.2 s, and 488.3 +/- 21.1 s, respectively (P less than 0.05). Relative to 6% solutions of sucrose and glucose, ingestion of a 6% fructose beverage is associated with gastrointestinal distress, compromised physiological response, and reduced exercise capacity.     

The staged celiotomy for trauma. Issues in unpacking and reconstruction.

OBJECTIVE: This article describes the important clinical events and decisions surrounding the reconstruction/unpacking portion of the staged celiotomy for trauma. METHODS: Of 13,817 consecutive trauma admissions, 1175 received trauma celiotomies. Of these, 107 patients (9.1%) underwent staged celiotomy with abdominal packing. The authors examined medical records to identify and characterize: (1) indications and timing of reconstruction, (2) criteria for emergency return to the operating room, (3) complications after reconstruction, and (4) abdominal compartment syndrome (ACS). RESULTS: Fifty-eight patients (54.2%) survived to reconstruction, 43 (74.1%) survived to discharge; 9 patients (15.5%) were returned to the operating room for bleeding; 13 patients required multiple packing procedures. There were 117 complications; 8 patients had positive blood cultures, abdominal abscesses developed in 6 patients, and ACS developed in 16 patients. CONCLUSIONS: 1. Reconstruction should occur after temperature, coagulopathy, and acidosis are corrected, usually within 36 hours after the damage control procedure. 2. Emergent reoperation should occur in any normothermic patient with unabated bleeding (greater than 2 U packed cells/hr). 3. ACS occurs in 15% of patients and is characterized by high peak inspiratory pressure, CO2 retention, and oliguria. Lethal reperfusion syndrome is common but preventable.     

Tumor vascular responses following irradiation

Vascular responses of the hamster malignant neurilemmoma, grown in the transparent cheek pouch chamber, were studied following single 3000-R exposures to ionizing radiation. Variable degrees of edema and extensive reduction in blood flow occurred during the first 24–30 hr, with subsequent restoration toward normalcy accompanied by small focal hemorrhaging. Inhibition of both tumor growth and neovascularization occurred during the first 3 to 5 days. Subsequent regrowth, as indicated by newly vascularizing foci of tumor cells, occurred earliest in the perimeter of the tumor where radiosensitivity is thought to be greatest. Return of cellular proliferation within the tumor was characterized by progressive increase in caliber of persisting tumor capillaries and the formation of a new capillary network. There was no obvious correlation between the changes observed and the probability of tumor regression or regrowth.