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C J Murray

Publications and source records attributed to C J Murray.

At least 37 records · Page 2Linked to original sources
PubMed2000

A critical examination of summary measures of population health.

In the past decade, interest has been rising in the development, calculation and use of summary measures of population health, which combine information on mortality and non-fatal health outcomes. This paper reviews the issues and challenges in the design and application of summary measures and presents a framework for evaluating different alternatives. Summary measures have a variety of uses, including comparisons of health in different populations and assessments of the relative contributions of different diseases, injuries and risk factors to the total disease burden in a population. Summary measures may be divided into two broad families: health expectancies and health gaps. Within each family, there are many different possible measures, but they share a number of inputs, including information on mortality, non-fatal health outcomes, and health state valuations. Other critical points include calculation methods and a range of conceptual and methodological issues regarding the definition, measurement and valuation of health states. This paper considers a set of basic criteria and desirable properties that may lead to rejection of certain summary measures and the development of new ones. Despite the extensive developmental agenda that remains, applications of summary measures cannot await the final resolution of all methodological issues, so they should focus on those measures that satisfy as many basic criteria and desirable properties as possible.

Data Interpretation, Statistical↗
PubMed1999

Health inequalities and social group differences: what should we measure?

Both health inequalities and social group health differences are important aspects of measuring population health. Despite widespread recognition of their magnitude in many high- and low-income countries, there is considerable debate about the meaning and measurement of health inequalities, social group health differences and inequities. The lack of standard definitions, measurement strategies and indicators has and will continue to limit comparisons--between and within countries, and over time--of health inequalities, and perhaps more importantly comparative analyses of their determinants. Such comparative work, however, will be essential to find effective policies for governments to reduce health inequalities. This article addresses the question of whether we should be measuring health inequalities or social group health differences. To help clarify the strengths and weaknesses of these two approaches, we review some of the major arguments for and against each of them.

Causality↗
PubMed1999

On the comparable quantification of health risks: lessons from the Global Burden of Disease Study.

Extensive discussion and comments on the Global Burden of Disease Study findings have suggested the need to examine more carefully the basis for comparing the magnitude of different health risks. Attributable burden can be defined as the difference between burden currently observed and burden that would have been observed under an alternative population distribution of exposure. Population distributions of exposure may be defined over many different levels and intensities of exposure (such as systolic or diastolic blood pressure on a continuous scale), and the comparison distribution of exposure need not be zero. Avoidable burden is defined as the reduction in the future burden of disease if the current levels of exposure to a risk factor were reduced to those specified by the counterfactual distribution of exposure. Choosing the alternative population distribution for a variable, the counterfactual distribution of exposure, is the critical step in developing a more general and standardized concept of comparable, attributable, or avoidable burden. We have identified four types of distributions of exposure that could be used as the counterfactual distributions: theoretical minimum risk, plausible minimum risk, feasible minimum risk, and cost-effective minimum risk. Using tobacco and alcohol as examples, we explore the implications of using these different types of counterfactual distributions to define attributable and avoidable burden. The ten risk factor assessments included in the Global Burden of Disease Study reflect a range of methods and counterfactual distributions. We recommend that future assessments should focus on avoidable and attributable burden based on the plausible minimum risk counterfactual distribution of exposure.

Causality↗
PubMed1998

Modeling the impact of global tuberculosis control strategies.

An epidemiological model of tuberculosis has been developed and applied to five regions of the world. Globally, 6.7 million new cases of tuberculosis and 2.4 million deaths from tuberculosis are estimated for 1998. Based on current trends in uptake of the World Health Organization's strategy of directly observed treatment, short-course, we expect a total of 225 million new cases and 79 million deaths from tuberculosis between 1998 and 2030. Active case-finding by using mass miniature radiography could save 23 million lives over this period. A single contact treatment for tuberculosis could avert 24 million cases and 11 million deaths; combined with active screening, it could reduce mortality by nearly 40%. A new vaccine with 50% efficacy could lower incidence by 36 million cases and mortality by 9 million deaths. Support for major extensions to global tuberculosis control strategies will occur only if the size of the problem and the potential for action are recognized more widely.

Communicable Disease Control↗
PubMed1997

Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study.

BACKGROUND: Plausible projections of future mortality and disability are a useful aid in decisions on priorities for health research, capital investment, and training. Rates and patterns of ill health are determined by factors such as socioeconomic development, educational attainment, technological developments, and their dispersion among populations, as well as exposure to hazards such as tobacco. As part of the Global Burden of Disease Study (GBD), we developed three scenarios of future mortality and disability for different age-sex groups, causes, and regions. METHODS: We used the most important disease and injury trends since 1950 in nine cause-of-death clusters. Regression equations for mortality rates for each cluster by region were developed from gross domestic product per person (in international dollars), average number of years of education, time (in years, as a surrogate for technological change), and smoking intensity, which shows the cumulative effects based on data for 47 countries in 1950-90. Optimistic, pessimistic, and baseline projections of the independent variables were made. We related mortality from detailed causes to mortality from a cause cluster to project more detailed causes. Based on projected numbers of deaths by cause, years of life lived with disability (YLDs) were projected from different relation models of YLDs to years of life lost (YLLs). Population projections were prepared from World Bank projections of fertility and the projected mortality rates. FINDINGS: Life expectancy at birth for women was projected to increase in all three scenarios; in established market economies to about 90 years by 2020. Far smaller gains in male life expectancy were projected than in females; in formerly socialist economies of Europe, male life expectancy may not increase at all. Worldwide mortality from communicable maternal, perinatal, and nutritional disorders was expected to decline in the baseline scenario from 17.2 million deaths in 1990 to 10.3 million in 2020. We projected that non-communicable disease mortality will increase from 28.1 million deaths in 1990 to 49.7 million in 2020. Deaths from injury may increase from 5.1 million to 8.4 million. Leading causes of disability-adjusted life years (DALYs) predicted by the baseline model were (in descending order): ischaemic heart disease, unipolar major depression, road-traffic accidents, cerebrovascular disease, chronic obstructive pulmonary disease, lower respiratory infections, tuberculosis, war injuries, diarrhoeal diseases, and HIV. Tobacco-attributable mortality is projected to increase from 3.0 million deaths in 1990 to 8.4 million deaths in 2020. INTERPRETATION: Health trends in the next 25 years will be determined mainly by the ageing of the world's population, the decline in age-specific mortality rates from communicable, maternal, perinatal, and nutritional disorders, the spread of HIV, and the increase in tobacco-related mortality and disability. Projections, by their nature, are highly uncertain, but we found some robust results with implications for health policy.

Adolescent↗
PubMed1997

Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study.

BACKGROUND: Prevention and control of disease and injury require information about the leading medical causes of illness and exposures or risk factors. The assessment of the public-health importance of these has been hampered by the lack of common methods to investigate the overall, worldwide burden. The Global Burden of Disease Study (GBD) provides a standardised approach to epidemiological assessment and uses a standard unit, the disability-adjusted life year (DALY), to aid comparisons. METHODS: DALYs for each age-sex group in each GBD region for 107 disorders were calculated, based on the estimates of mortality by cause, incidence, average age of onset, duration, and disability severity. Estimates of the burden and prevalence of exposure in different regions of disorders attributable to malnutrition, poor water supply, sanitation and personal and domestic hygiene, unsafe sex, tobacco use, alcohol, occupation, hypertension, physical inactivity, use of illicit drugs, and air pollution were developed. FINDINGS: Developed regions account for 11.6% of the worldwide burden from all causes of death and disability, and account for 90.2% of health expenditure worldwide. Communicable, maternal, perinatal, and nutritional disorders explain 43.9%; non-communicable causes 40.9%; injuries 15.1%; malignant neoplasms 5.1%; neuropsychiatric conditions 10.5%; and cardiovascular conditions 9.7% of DALYs worldwide. The ten leading specific causes of global DALYs are, in descending order, lower respiratory infections, diarrhoeal diseases, perinatal disorders, unipolar major depression, ischaemic heart disease, cerebrovascular disease, tuberculosis, measles, road-traffic accidents, and congenital anomalies. 15.9% of DALYs worldwide are attributable to childhood malnutrition and 6.8% to poor water, and sanitation and personal and domestic hygiene. INTERPRETATION: The three leading contributors to the burden of disease are communicable and perinatal disorders affecting children. The substantial burdens of neuropsychiatric disorders and injuries are under-recognised. The epidemiological transition in terms of DALYs has progressed substantially in China, Latin America and the Caribbean, other Asia and islands, and the middle eastern crescent. If the burdens of disability and death are taken into account, our list differs substantially from other lists of the leading causes of death. DALYs provide a common metric to aid meaningful comparison of the burden of risk factors, diseases, and injuries.

Adolescent↗
PubMed1997

Regional patterns of disability-free life expectancy and disability-adjusted life expectancy: global Burden of Disease Study.

BACKGROUND: Information on non-fatal health outcomes of disease and injury has been largely neglected in health planning because of the conceptual and definitional complexity of measuring morbidity and disability in populations. One of our major objectives was to quantify disability for inclusion in health policy debates. We analysed these health outcomes in terms of disability-free life expectancy (DFLE) and disability-adjusted life expectancy (DALE). METHODS: Published and unpublished data were systematically reviewed to estimate the incidence, prevalence, and duration of 483 disabling sequelae of 107 diseases and injuries. To ensure internal consistency of these estimates, a software programme (DISMOD) was applied many times until consistent parameters were identified. The severity of disability, on a scale of 0 (perfect health) to 1 (death), was measured in a deliberate manner by the person-trade-off method. Spearman's and Pearson's correlation coefficients were used to measure disability weights among groups. Prevalence of seven classes of disability was back-calculated from the distribution of each disabling sequela across disabilities. Prevalence for each class of disability for different age-sex groups was used to calculate seven forms of DFLE and DALE based on Sullivan's method. FINDINGS: Prevalence of most disability classes is highest in sub-Saharan Africa and lowest in established market economies. Low-severity disabilities (class I and class II) are the most common. The expectation at birth of class I disability ranges from 6.5 years in established market economies to 14.7 years in sub-Saharan Africa, and for class II disabilities, from 8.5-18.4 years. DFLE varies significantly among regions: DFLE for class I disabilities at birth ranges from 9.9 years in sub-Saharan Africa to 47.7 years in established market economies for females and DFLE for class V disabilities ranges from 43.4 years for men in sub-Saharan Africa to 74.8 years for women in established market economies. The proportion of expected life span at birth lived with disability adjusted for severity, varies from about 8% in established market economies to 15% in sub-Saharan Africa, with little difference between men and women. In high-income regions, nearly 90% of expected disability is due to non-communicable diseases and most of the remainder to injuries. In poorer regions, almost half of expected disability is due to communicable diseases and injuries. INTERPRETATION: The higher proportion of lifespan spent disabled in high-mortality populations is consistent with the compression of morbidity hypothesis. The threshold definition of disability used substantially affects the results of DFLE, DALE, which incorporates severity weights for disabilities, is a useful summary measure of the burden of disability and mortality.

Adolescent↗
PubMed1997

Mortality by cause for eight regions of the world: Global Burden of Disease Study.

BACKGROUND: Reliable information on causes of death is essential to the development of national and international health policies for prevention and control of disease and injury. Medically certified information is available for less than 30% of the estimated 50.5 million deaths that occur each year worldwide. However, other data sources can be used to develop cause-of-death estimates for populations. To be useful, estimates must be internally consistent, plausible, and reflect epidemiological characteristics suggested by community-level data. The Global Burden of Disease Study (GBD) used various data sources and made corrections for miscoding of important diseases (eg, ischaemic heart disease) to estimate worldwide and regional cause-of-death.patterns in 1990 for 14 age-sex groups in eight regions, for 107 causes. METHODS: Preliminary estimates were developed with available vital-registration data, sample-registration data for India and China, and small-scale population-study data sources. Registration data were corrected for miscoding, and Lorenz-curve analysis was used to estimate cause-of-death patterns in areas without registration. Preliminary estimates were modified to reflect the epidemiology of selected diseases and injuries. Final estimates were checked to ensure that numbers of deaths in specific age-sex groups did not exceed estimates suggested by independent demographic methods. FINDINGS: 98% of all deaths in children younger than 15 years are in the developing world. 83% and 59% of deaths at 15-59 and 70 years, respectively, are in the developing world. The probability of death between birth and 15 years ranges from 22.0% in sub-Saharan Africa to 1.1% in the established market economies. Probabilities of death between 15 and 60 years range from 7.2% for women in established market economies to 39.1% for men in sub-Saharan Africa. The probability of a man or woman dying from a non-communicable disease is higher in sub-Saharan Africa and other developing regions than in established market economies. Worldwide in 1990, communicable, maternal, perinatal, and nutritional disorders accounted for 17.2 million deaths, non-communicable diseases for 28.1 million deaths and injuries for 5.1 million deaths. The leading causes of death in 1990 were ischaemic heart disease (6.3 million deaths), cerebrovascular accidents (4.4 million deaths), lower respiratory infections (4.3 million), diarrhoeal diseases (2.9 million), perinatal disorders (2.4 million), chronic obstructive pulmonary disease (2.2 million), tuberculosis (2.0 million), measles (1.1 million), road-traffic accidents (1.0 million), and lung cancer (0.9 million). INTERPRETATION: Five of the ten leading killers are communicable, perinatal, and nutritional disorders largely affecting children. Non-communicable diseases are, however, already major public health challenges in all regions. Injuries, which account for 10% of global mortality, are often ignored as a major cause of death and may require innovative strategies to reduce their toll. The estimates by cause have wide Cls, but provide a foundation for a more informed debate on public-health priorities.

Adolescent↗
PubMed1997

Understanding DALYs (disability-adjusted life years).

The measurement unit disability-adjusted life years (DALYs), used in recent years to quantify the burden of diseases, injuries and risk factors on human populations, is grounded on cogent economic and ethical principles and can guide policies toward delivering more cost-effective and equitable health care. DALYs follow from a fairness principle that treats 'like as like' within an information set comprising the health conditions of individuals, differentiated solely by age and sex. The particular health state weights used to account for non-fatal health outcomes are derived through the application of various forms of the person trade-off.

Age Factors↗
PubMed1997

Health expenditures in Latin America and the Caribbean.

This paper presents the results of a study commissioned by the Latin American and Caribbean Technical Department of the World Bank to document and analyze health expenditures in Latin America and the Caribbean. In 1990, the countries of this region spent US$ 69 billion on health, with an average per capita health expenditure of US$ 162. On average, the countries spent 6.2% of their GDP on health, with the expenditures divided about equally between the public and private sectors. In both the public and private sectors, per capita health expenditures were positively and significantly correlated with per capita income. However, this relationship holds only for the public sector, when health expenditures are measured as a proportion of GDP. While several poorer countries were dependent on external assistance, with increasing income, the countries relied more on public expenditures to finance health care. Based on the limited time series data, it is evident that there was a considerable variation among countries regarding the proportion spent on capital investments, primary health care, and drugs, but not on salaries. Looking ahead, with increasing economic development, the proportion of GDP spent on health, along with public health expenditure as a proportion of total health expenditure, is likely to increase rapidly, while aid dependency is likely to decline.

Caribbean Region↗
PubMed1997

The utility of DALYs for public health policy and research: a reply.

The WHO Advisory Committee on Health Research (ACHR), through its DALY Review Group, has recently criticized the use of disability-adjusted life years (DALYs). To suggest that the use of DALYs should be discouraged as an aid in health resource allocation may, however, be premature, since it enhances informed debate on the social values that influence resource allocation, identifies health problems that may be neglected, and points to the strengths and weaknesses of existing health information systems.

Persons with Disabilities↗
PubMed1996

A low-barrier hydrogen bond in subtilisin: 1H and 15N NMR studies with peptidyl trifluoromethyl ketones.

The N delta 1 proton of His 64 forms a hydrogen bond with Asp 32, as part of the catalytic triad in serine proteases of the subtilisin family. His 64 in subtilisin has been studied by 1H and 15N NMR spectroscopy in the presence and absence of peptidyl trifluoromethyl ketones (TFMKs) that are transition state analog inhibitors. For subtilisin Carlsberg, the downfield resonance of the imidazolium N delta 1 proton is approximately 18.3 ppm and the D/H fractionation factor is 0.55 +/- 0.04 at pH 5.5 (11 degrees C), and 0.63 +/- 0.04 (5 degrees C) and 0.68 +/- 0.04 at pH 6 (11 degrees C). In the complex between subtilisin Carlsberg and Z-L-leucyl-L-leucyl-L-phenylalanyltrifluoromethyl ketone (Z-LLF-CF3) at pH values between 6.5 and 10.6, His 64 remains positively charged, and the D/H fractionation factor of its N delta 1 proton is 0.85 +/- 0.05. In the complex between a subtilisin variant from Bacillus lentus and Z-LLF-CF3, the proton resonance at 18.8 ppm is correlated with a 15N resonance at 197.6 ppm downfield from liquid NH3 with a 1JNH of 81 Hz. The chemical shifts of subtilisin complexes with peptidyl TFMKs are among the most downfield shifts reported for any protein. At pH 9.5, His 64 is neutral and the D/H fractionation factor increases to 1.2 with a chemical shift of 15.0. His 64 is positively charged in the free enzyme at low pH, the inhibitor hemiketal complex at neutral pH, and the transition state for amide bond hydrolysis. These data thus provide indirect evidence for the presence of a low-barrier hydrogen bond in the catalytic mechanism of subtilisin proteases.

Bacterial Proteins↗
PubMed1996

Active-site titration of serine proteases using a fluoride ion selective electrode and sulfonyl fluoride inhibitors.

We report a general procedure for the determination of active enzyme concentrations for serine proteases. The method relies on the measurement of fluoride ion released from sulfonyl fluorides upon reaction with the active-site serine using an ion selective electrode. The results have been independently confirmed by amino acid analyses of subtilisins and by spectrofluorometric and spectrophotometric titrations. The minimal enzyme concentration detectable is 1-10 microM protease. The method is insensitive to color and turbidity of the sample and is therefore useful for measuring protease concentration in broth solutions. The active enzyme concentration of subtilisin BPN' from Bacillus amyloliquefaciens determined by titration with phenylmethylsulfonyl fluoride is 25% higher than the concentration determined using the spectrophotometric burst titrant N-trans-cinnamoylimidazole. Analysis of the pre-steady-state burst amplitude and kinetics suggests that the extinction coefficient for the cinnamoyl acyl-enzyme is larger than previously measured and a significant fraction of the enzyme is present as an unproductive ES2 complex. The molar extinction coefficient at 280 nm for subtilisin BPN' is 26.5 mM-1 cm-1 and for subtilisin from Bacillus lentus is 22.5 mM-1 cm-1.

Bacillus↗
PubMed1996

Secondary H/T and D/T isotope effects in enzymatic enolization reactions. Coupled motion and tunneling in the triosephosphate isomerase reaction.

Secondary kH/kT kinetic isotope effects in H2O and kH/kT or kD/kT isotope effects in D2O have been measured for the triosephosphate isomerase-catalyzed conversion of dihydroxyacetone 3-phosphate (DHAP) to D-glyceraldehyde 3-phosphate. The proton transfer steps are made rate-limiting using [1(R)-2H]-labeled substrate in D2O to slow the chemical steps, relative to product release. After a small correction for the beta-equilibrium isotope effect for dehydration of DHAP, the H/T kinetic isotope effect kH/kT = 1.27 +/- 0.03 for [1(R)-2H,(S)-3H]-labeled substrate in D2O is subtantially larger than the equilibrium isotope effect for enolization of DHAP, KH/KT = 1.12. The H/T isotope effect is related to the D/T isotope effect with a Swain-Schaad exponent y = 4.4 +/- 1.3. These results are consistent with coupled motion of the C-1 primary and secondary hydrogens of DHAP and tunneling. Large secondary kinetic isotope effects are a general feature of enzymatic enolization reactions while nonenzymatic enolization reactions show secondary kinetic isotope effects that are substantially smaller than equilibrium effects [Alston, W. A., II, Haley, K., Kanski, R., Murray, C.J., & Pranata, J. (1996) J. Am. Chem Soc., 118, 6562-6569]. Possible origins for these differences in transition state structure are discussed.

Animals↗
PubMed1996

The incremental effect of age-weighting on YLLs, YLDs, and DALYs: a response.

When disability-adjusted life years (DALYs) were first formulated, the effect of age-weighting on years of life lost due to death at each age as well as the different effect on short- and medium-term disability were taken into consideration. While there is considerable scope for discussion on the actual values that are incorporated into DALYs, the present article argues that once the values have been chosen we should accept the consequences of the choice.

Age Factors↗