A Practical Guide to Full Value of Vaccine Assessments.

Articulating the wide range of health, social and economic benefits that vaccines offer may help to overcome obstacles in the vaccine development pipeline. A framework to guide the assessment and communication of the value of a vaccine-the Full Value of Vaccine Assessment (FVVA)-has been developed by the WHO. The FVVA framework offers a holistic assessment of the value of vaccines, providing a synthesis of evidence to inform the public health need of a vaccine, describing the supply and demand aspects, its market and its impact from a health, financial and economic perspective. This paper provides a practical guide to how FVVAs are developed and used to support investment in vaccines, ultimately leading to sustained implementation in countries. The FVVA includes a range of elements that can be broadly categorised as synthesis, vaccine development narrative and defining vaccine impact and value. Depending on the features of the disease/vaccine in question, different elements may be emphasised; however, a standardised set of elements is recommended for each FVVA. The FVVA should be developed by an expert group who represent a range of stakeholders, perspectives and geographies and ensure a fair, coherent and evidence-based assessment of vaccine value.

Cryoablation induces greater inflammatory and coagulative responses than radiofrequency ablation or laser induced thermotherapy in a rat liver model.

BACKGROUND: Cryoablation (CA), radiofrequency ablation (RFA), and laser induced thermotherapy (LITT) are alternative therapies for patients with unresectable liver tumors. We investigated whether there are different inflammatory and coagulative responses between these techniques. METHODS: Livers of 48 rats were subjected to either CA, RFA, LITT, or sham operation (n = 12 in each group). Blood was withdrawn before, and 1, 3, 6, and 24 h after ablation. Liver enzymes as well as inflammatory and coagulation parameters were determined. Whole liver sections from the coagulated liver lobe were stained for quantification of necrosis and morphologic examination. RESULTS: Histologic examination showed similar volume of complete destruction of liver parenchyma after CA, RFA, or LITT. Transaminase levels as well as the inflammatory response upon CA, as reflected by white blood cell count and cytokine levels, were significantly higher than following RFA or LITT. The systemic intravascular procoagulative state in rats that underwent CA, as reflected by platelets, and levels of sensitive markers for activation of coagulation and fibrinolyis, was also significantly higher. CONCLUSION: CA of liver in rats induces greater inflammatory and coagulative responses than RFA or LITT. The combined activation of inflammation and coagulation may importantly contribute to the higher morbidity after CA.

Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: a 2-year randomised placebo-controlled study.

BACKGROUND: Non-randomised studies have suggested beneficial effects of bisphosphonates in osteogenesis imperfecta. We assessed the effects of oral olpadronate in children with this disorder in a randomised double-blind placebo-controlled trial. METHODS: 34 children recruited from the Dutch national centre for osteogenesis imperfecta were randomly assigned olpadronate (10 mg/m2 daily; n=16) or placebo (n=18) for 2 years. All children also received calcium and vitamin D supplements. Primary endpoints were incident fractures of long bones and changes in bone mineral content (BMC), bone mineral density (BMD), and functional outcome. Anthropometry, vertebral height, and urinary markers of bone resorption were also studied. Analyses were by intention to treat. FINDINGS: Fracture follow-up was complete for all the children, including two who withdrew from the study (one from each group). Olpadronate treatment was associated with a 31% reduction in relative risk of fracture of long bones (hazard ratio 0.69 [95% CI 0.52-0.91], p=0.01). The olpadronate group showed significantly greater increases than the placebo group in spinal BMC (difference between groups 2.24 g/year [0.20-4.29], p=0.03) and spinal BMD (difference between groups 0.054 g/cm2 per year [0.012-0.096], p=0.01). There were no detectable effects on functional outcome, anthropometrics, or vertebral height and no differences between the groups in changes in urinary markers of bone resorption. INTERPRETATION: Oral treatment with olpadronate at a daily dose of 10 mg/m2 results in a reduction of fracture risk of long bones in children with osteogenesis imperfecta. However, the issue of whether bisphosphonates will alter the natural course of osteogenesis imperfecta remains unresolved, and further studies are needed.

Renal function and nutritional status at the start of chronic dialysis treatment.

Early start of dialysis has been hypothesized to prevent deterioration of nutritional status and to lead to a better clinical outcome. According to the National Kidney Foundation/Dialysis Outcomes Quality Initiative guidelines, dialysis should be started when renal Kt/V(urea) falls below 2.0/wk or the protein equivalent of total nitrogen appearance normalized to body weight (nPNA) falls below 0.8 g/kg per d. The present study was performed 0 to 4 wk before the start of dialysis treatment in 114 incident Dutch patients with chronic renal failure who all had received pre-end-stage renal disease care. The objectives were (1) to analyze the relationship of different levels of residual renal function with parameters of nutritional status and (2) to investigate the relationship of renal Kt/V(urea) and nPNA in this population. The mean GFR at the start of dialysis treatment was 6.2 ml/min per 1.73 m(2), and the Kt/V(urea) was 1.3/wk. Only 10% of the patients fulfilled the Dialysis Outcomes Quality Initiative criterion of Kt/V(urea) > 2.0/wk. In contrast, 69% met the nPNA norm of 0.8 g/kg per d. Seventy-one percent of these patients had a normal nutritional status as scored by subjective global assessment and also other parameters of nutritional status, such as body mass index, and serum albumin fell within the normal range in the majority of the patients. Dutch predialysis patients reached a higher nPNA with the same level of Kt/V(urea) compared with U.S. predialysis patients. Implications of these findings are that guidelines on the initiation of dialysis treatment derived from one population are not necessarily valid in other populations.