Development and validation of a molecular size distribution method for polysaccharide vaccines.

Determination of the molecular size distribution of vaccine products by high performance size exclusion chromatography coupled to refractive index detection is important during the manufacturing process. Partial elution of high molecular weight compounds in the void volume of the chromatographic column is responsible for variation in the results obtained with a reference method using a TSK G5000PWXL chromatographic column. GlaxoSmithKline Vaccines has developed an alternative method relying on the selection of a different chromatographic column with a wider separation range and the generation of a dextran calibration curve to determine the optimal molecular weight cut-off values for all tested products. Validation of this method was performed according to The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The new method detected product degradation with the same sensitivity as that observed for the reference method. All validation parameters were within the pre-specified range. Precision (relative standard deviation (RSD) of mean values) was < 5 per cent (intra-assay) and < 10 per cent (inter-assay). Sample recovery was > 70 per cent for all polysaccharide conjugates and for the Haemophilus influenzae type B final container vaccine. All results obtained for robustness met the acceptance criteria defined in the validation protocol (≤ 2 times (RSD) or ≤ 2 per cent difference between the modified and the reference parameter value if RSD = 0 per cent). The new method was shown to be a suitable quality control method for the release and stability follow-up of polysaccharide-containing vaccines. The new method gave comparable results to the reference method, but with less intra- and inter-assay variability.

GINA guidelines on asthma and beyond.

Clinical guidelines are systematically developed statements designed to help practitioners and patients make decisions regarding the appropriate health care for specific circumstances. Guidelines are based on the scientific evidence on therapeutic interventions. The first asthma guidelines were published in the mid 1980s when asthma became a recognized public health problem in many countries. The Global Initiative on Asthma (GINA) was launched in 1995 as a collaborative effort between the NHLBI and the World Health Organization (WHO). The first edition was opinion-based but updates were evidence-based. A new update of the GINA guidelines was recently available and it is based on the control of the disease. Asthma guidelines are prepared to stimulate the implementation of practical guidelines in order to reduce the global burden of asthma. Although asthma guidelines may not be perfect, they appear to be the best vehicle available to assist primary care physicians and patients to receive the best possible care of asthma.

The last frontier in cardiovascular health: a landmark lecture for the XVII World Congress of the International Society for Heart Research.

Following World War II, Vannevar Bush described science as an "endless frontier" that should be made accessible to all Americans. Since then, cardiovascular health has improved markedly, largely because substantial investments in biomedical research led to numerous therapies and prevention strategies for cardiovascular disease. Despite these advances, however, science remains an endless frontier and we continue to face an infinite array of opportunities for improving cardiovascular health. A standard definition for "frontier" is the "farthermost limit of knowledge or achievement". The limits of our knowledge are expanding at an ever accelerated pace. Unfortunately, we do not always apply what we know, and therefore fail to achieve all we could. For example, we have known for two decades that heart attack patients benefit from beta-blockers, but even today, the drugs are not always prescribed. And, health disparities continue to exist among races and communities. Therefore, the "last frontier of cardiovascular health" is the translation and application of our knowledge to improve the cardiovascular health of all people. We will not reach the farthermost limit of achievement without new knowledge. But, in our zeal to expand our knowledge of cardiovascular diseases, we must remember to ensure that what we learn is rapidly applied to improve cardiovascular health.

Can we prevent cardiovascular diseases in low- and middle-income countries?

Ischaemic heart disease, the largest cause of death worldwide, is rapidly becoming a major threat in low- and middle-income countries. Experience in a variety of populations has demonstrated that lowering certain risk factors, such as hypertension and hypercholesterolaemia, reduces illness and deaths from cardiovascular diseases. A dual approach is recommended: screening and intervening in cases of relatively high risk, while fostering population-wide preventive activities. This is both feasible and affordable. Now is the time to make such efforts.

Working group report on high blood pressure in pregnancy.

This report updates the 1990 National High Blood Pressure Education Program Working Group Report on High Blood Pressure in Pregnancy and focuses on classification, pathophysiology, and management of the hypertensive disorders of pregnancy. Using evidence-based medicine and consensus, this report updates contemporary approaches to hypertension control during pregnancy by expanding on recommendations made in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). The recommendations to use K5 for determining diastolic pressure and to eliminate edema as a criterion for diagnosing pre-eclampsia are discussed. In addition, the use of blood pressure increases of 30 mm Hg systolic or 15 mm Hg diastolic as a diagnostic criterion has not been recommended, as available evidence shows that women in this group are not likely to suffer increased adverse outcomes. Management considerations are made between chronic hypertension that is present before pregnancy and those occurring as part of the pregnancy-specific condition preeclampsia, as well as management considerations in women with comorbid conditions. A discussion of the pharmacologic treatment of hypertension in pregnancy includes recommendations for specific agents. The use of low-dose aspirin, calcium, or other dietary supplements in the prevention of pre-eclampsia is described, and expanded sections on counseling women for future pregnancies and recommendations for future research are included. Once again we thank Dr. Ray Gifford, Jr., and his committee for volunteering their time to produce this important report. We hope it helps the busy clinician prevent and manage a very important problem.

A call to action for more aggressive treatment of hypertension.

During the past three decades, tremendous progress has been made in the USA and many other nations in detecting and controlling hypertension. Health education efforts increased public knowledge of the benefits of treating hypertension, and rates of blood pressure control improved. Despite improvements in the past, however, more recent information has shown some disturbing trends; we are not as healthy a nation as we could be. Hypertension control rates are no longer improving, and are likely to fall short of the US Healthy People 2000 goal of blood pressure control in 50% of all hypertensive patients. Overwhelming data from clinical trials underscore the need to control hypertension, especially in the elderly, for whom hypertension control rates are lower than they are for the total US population. Data from the Framingham Study indicate that the incidence of heart failure increases with age and is greater in hypertensive patients than in normotensive patients. Hypertension precedes heart failure in 90% of all cases, and the prevalence of heart failure, greater today than it was a decade ago, is now the largest component of the Medicare budget (Medicare is the US health insurance and standards for medical participation program for those aged 65 years and older). Hypertension is also associated with an increase in the incidence of end-stage renal disease, and stroke and coronary heart disease may be increasing again. Such alarming trends are a call to action for the public, patients, and health professionals. Strong evidence supports the need for better blood pressure control, with an emphasis on the elderly and other difficult-to-treat populations.