Estimating the age-at-onset function using life-table methods

In the analysis of dominantly inherited diseases, the age-at-onset function is often estimated from the observed age-at-onset distribution of cases. This estimate is confounded with the age distribution of the population from which the cases were sampled and is accurate only if there are no competing causes of death. In this paper, we present a straightforward method for calculating a more accurate age-at-onset function under etiologic heterogeneity. We use the life-table approach and survival analysis methods. This method is illustrated using data on first-degree relatives of probands from two sets of families with high cancer incidence: one with breast/ovarian cancer and the other with colon cancer. A comparison of the estimated age-at-onset function obtained by the two methods is presented. In both cases, colon cancer as well as breast/ovarian cancer, the estimates of onset probabilities based on proportion of cases, are consistently higher than those obtained by the life-table method. For breast/ovarian cancer, this difference is not as striking as it is in the case of colon cancer; nevertheless, the method using proportion of cases tends to give a lower estimate of the age-at-onset function (higher probability of being affected at lower age) than the life-table approach.     

Providing more up-to-date estimates of patient survival: a comparison of standard survival analysis with period analysis using life-table methods and proportional hazards models

OBJECTIVE: Standard survival methods can yield out-of-date estimates of long-term survival. Period analysis, based on life-table methodology, provides more up-to-date survival estimates by exploring survival during a restricted recent period of interest. It excludes the short-term survival of patients recruited at the start of the study. We use statistical models to further develop the method of period analysis, providing more up-to-date estimates of survival and the ability to explore differences in survival by covariates and adjust for case mix. METHODS: We use cancer registry data for colorectal cancer in Leicestershire, UK, to illustrate the use of Cox proportional hazards (CPH) models to estimate period and standard survival. We compare these estimates with those obtained using life-table methodology. RESULTS: Period estimates were slightly higher than the standard estimates as they reflect recent improvements in short-term survival. The results for period analysis using the life-table approach and using CPH models were similar. However, CPH models allowed further investigation of other risk factors and the ability to control for potential confounding variables. CONCLUSION: Using period survival estimates, more up-to-date information is available to clinicians and others with an interest in monitoring survival. Period CHP models offer all the advantages of statistical modeling, and are straightforward to fit in standard statistical packages.     

Comparison of estimates of zinc absorption in humans by using 4 stable isotopic tracer methods and compartmental analysis

BACKGROUND: Adjustment of gastrointestinal absorption is the primary means of maintaining zinc homeostasis; however, a precise, accurate method for measuring zinc absorption in humans has not been identified. OBJECTIVE: The purpose of this study was to compare the estimates of the fraction of dietary zinc absorbed (FZA) by using 4 stable isotopic tracer methods: mass balance (MB) corrected for endogenous secretion, fecal monitoring (FM), deconvolution analysis (DA), and the double isotopic tracer ratio (DITR) method. DESIGN: All 4 methods were applied to a single data set for each of 6 women. FZA was also determined for each subject by using a detailed compartmental model of zinc metabolism, and that value was used as the reference with which the simpler methods were compared. RESULTS: The estimates of FZA (&xmacr; +/- SD) determined by DA (0.27 +/- 0. 08) and the DITR technique in plasma (0.30 +/- 0.10), 24-h urine samples (0.29 +/- 0.09), and spot urine samples (0.291 +/- 0.089) all compared well with the FZA reference value from the compartmental model (0.30 +/- 0.10). The MB and FM methods tended to overestimate FZA compared with the reference value. CONCLUSIONS: The determination of FZA by MB or FM is laborious, is sensitive to subject compliance, and may result in an overestimate. DA, although relatively accurate, has the disadvantage of requiring multiple blood drawings over several days. In contrast, the DITR technique applied to a spot urine specimen obtained >/=3 d after tracer administration provides an accurate measure of FZA and is easy to implement; therefore, it is the recommended method for determination of FZA.     

Comparison of risk estimates for selected diseases and causes of death

BACKGROUND: Lifetime risk estimates of disease are limited by long-term data extrapolations and are less relevant to individuals who have already lived a period of time without the disease, but are approaching the age at which the disease risk becomes common. In contrast, short-term age-conditional risk estimates, such as the risk of developing a disease in the next 10 years among those alive and free of the disease at a given age, are less restricted by long-term extrapolation of current rates and can present patients with risk information tailored to their age. This study focuses on short-term age-conditional risk estimates for a broad set of important chronic diseases and nondisease causes of death among white and black men and women. METHODS: The Feuer et al. (1993, Journal of the National Cancer Institute) [15] method was applied to data from a variety of sources to obtain risk estimates for select cancers, myocardial infarction, diabetes mellitus, multiple sclerosis, Alzheimer's, and death from motor vehicle accidents, homicide or legal intervention, and suicide. RESULTS: Acute deaths from suicide, homicide or legal intervention, and fatal motor vehicle accidents dominate the risk picture for persons in their 20s, with only diabetes mellitus and end-stage renal disease therapy (for blacks only) having similar levels of risk in this age range. Late in life, cancer, acute myocardial infarction, Alzheimer's, and stroke become most common. The chronic diseases affecting the population later in life present the most likely diseases someone will face. Several interesting differences in disease and death risks were derived and reported among age-specific race and gender subgroups of the population. CONCLUSION: Presentation of risk estimates for a broad set of chronic diseases and nondisease causes of death within short-term age ranges among population subgroups provides tailored information that may lead to better educated prevention, screening, and control behaviors and more efficient allocation of health resources.     

Confounder-adjusted estimates of the risk difference using propensity score-based weighting

Confounder-adjusted estimates of the risk difference are often difficult to obtain by direct regression adjustment. Estimates can be obtained from a propensity score-based method using inverse probability-of-exposure weights to balance groups defined by exposure status with respect to confounders. Simulation was used to evaluate the performance of this method. The simulation model incorporated a binary confounder and a normally distributed confounder into logistic models of exposure status, and disease status conditional on exposure status. Data were generated for combinations of values of several design parameters, including the odds ratio relating each of the confounders to exposure status, the odds ratio relating each of the confounders to disease status and the total sample size. For most design parameter combinations (474 of 486), the absolute bias in the estimated risk difference was less than 1 percentage point, and it was never greater than 3 percentage points. The confidence interval generally had close to nominal 95 per cent coverage, but was prone to poor coverage levels (as low as 78.5 per cent) when both the confounder-to-exposure and confounder-to-outcome odds ratios were 5, consistent with strong confounding. The simulation results showed that the conditions that are favourable for good performance of the weighting method are: reasonable overlap in the propensity score distributions of the exposed and non-exposed groups and a large sample size.     

Assessing risk using different cholesterol-screening methods

The purpose of this study was to compare total capillary, total venous, risk ratio, high-density lipoprotein and low-density lipoprotein measures of cholesterol to determine whether total capillary cholesterol is a valid measure to use in cholesterol screening. An announcement and a registration form were distributed with employee paychecks announcing a cholesterol-screening programme. Capillary and venous samples were collected from screening participants (n=285). Results indicated false negatives in total capillary cholesterol in 17.21-34.4% of cases compared with other methods of cholesterol measurement. Due to the high number of misclassifications, health educators should not use total capillary cholesterol as a predictor of risk for heart disease, nor as a measure for referral during cholesterol screenings.     

Active life among the elderly in the United States: multistate life-table estimates and population projections

Calculations of multistate life expectancy not only measure how long a population may live beyond a certain age, but also what fractions of this continuing lifetime will be spent in an independent or dependent status. Many Americans aged 70 and over are leading long, active lives; large numbers of individuals who become dependent, moreover, do so temporarily and return to independent status. Men and women have disparate total and active life expectancies, however, reflecting differential survival patterns and varying rates of transition among statuses. Policy makers must consider the increased size of the future elderly population, and changes in its age composition and functional status, when planning relevant health services.     

Public health risk maps using geostatistical methods

The purpose of this paper was to demonstrate an application of geostatistical methods to public health risk maps through the identification of areas with elevated concentrations of heavy metals. The study focused on the element lead (Pb) from aerial transportation or loading of particles due to soil leaching in an area with major urban and industrial concentration in the Baixada Santista on the coastland of S?o Paulo State, Brazil. Maps with the spatial distribution of lead were produced using ordinary kriging; subsequently indicative kriging was performed to identify soil sites with contamination levels higher than the maximum acceptable level defined by the Sao Paulo State Environmental Control Agency. The resulting maps showed areas with increased probability of public health risk. The methodology proved to be a promising approach for decision-making related to health public policies and environmental planning.     

Comparison of estimates of population levels of physical activity using two measures

OBJECTIVE: To compare estimates of population levels of 'adequate activity' for health benefit in different age and sex groups using two different measures--kilocalories (kcals) and Mets.mins. METHODS: 10,464 mid-age women (47-52 years) from the second survey of the Australian Longitudinal Study on Women's Health (ALSWH, 1998) and 2,500 men and women (18-75 years) from the 1997 Active Australia national survey, answered questions about physical activity. Kcals and Mets.mins were calculated from self-reported time spent in walking, moderate and vigorous activity, and self-reported body weight. 'Adequate activity' was defined as a minimum of 800 kcals or 600 Mets.mins. RESULTS: There were differences in the estimates of 'adequate activity' using the two methods among women participants in both surveys, but not among the male participants in the Active Australia survey. A significant proportion of the women in both surveys (6.4% of the ALSWH women and 8.5% of the Active Australia women, mean weight 60 kg) were classified as 'inactive' when the kcals method was used despite reporting levels of activity commensurate with good health. Fewer than 1% (mean weight 105 kg) were classified as 'active' using kcals when reporting lower than recommended levels of activity. Agreement between the two methods was better among men; only 3% were misclassified because of low or very high weight. CONCLUSIONS: The Mets.mins method of estimating 'adequate' activity assesses physical activity independently of body weight and is recommended for use in future population surveys, as it is less likely to under-estimate the prevalence of physical activity in women. IMPLICATIONS: Women and men aged 45-59 and women aged > 60 should be the target of specific health promotion strategies to increase population levels of physical activity.     

Bone cancer risk estimates.

Due to confusion between endosteal (bone surface) dose and average skeletal dose, ICRP 60 has substantially overestimated the risk of radiogenic bone cancer. This confusion apparently stems from an incorrect reading of the BEIR IV report, which does not clearly draw this distinction. It should also be noted that what appear to be summary numerical risk estimates for bone sarcoma induction in BEIR IV and BEIR V refer only to average skeletal dose as calculated for 224Ra.     

Comparison of instrumental variable analysis using a new instrument with risk adjustment methods to reduce confounding by indication

Confounding by indication is a vexing problem, especially in evaluating treatment effects using observational data, since treatment decisions are often related to disease severity, prognosis, and frailty. To compare the ability of the instrumental variable (IV) approach with a new instrument based on the local-area practice style and risk adjustment methods, including conventional multivariate regression and propensity score adjustment, to reduce confounding by indication, the authors investigated the effects of long-term control (LTC) therapy on the occurrence of acute asthma exacerbation events among children and young adults with incident and uncontrolled persistent asthma, using Iowa Medicaid claims files from 1997-1999. Established evidence from clinical trials has demonstrated the protective benefits of LTC therapy for persistent asthma. Among patients identified (n = 4,275), those with higher asthma severity at baseline were more likely to receive LTC therapy. The multivariate regression and propensity score adjustment methods suggested that LTC therapy had no effect on the occurrence of acute exacerbation events. Estimates from the new IV approach showed that LTC therapy significantly decreased the occurrence of acute exacerbation events, which is consistent with established clinical evidence. The authors discuss how to interpret estimates from the risk adjustment and IV methods when the treatment effect is heterogeneous.     

Improved estimates of floating absolute risk

Floating absolute risks are an alternative way of presenting relative risk estimates for polychotomous risk factors. Instead of choosing one level of the risk factor as a reference category, each level is assigned a 'floated' variance which describes the uncertainty in risk without reference to another level. In this paper, a method for estimating the floated variances is presented that improves on the previously proposed 'heuristic' method. The estimates may be calculated iteratively with a simple algorithm. A benchmark for validating the floated variance estimates is also proposed and an interpretation of floating confidence intervals is given.     

Local estimates of population attributable risk

ObjectiveTo investigate properties of population attributable risk (PAR) estimates, when its components come from different sources. Examples include situations where one requires local estimates of PAR for a study subset (e.g., in states or counties within a national study) or if one wishes to apply the findings of an epidemiologic study to another population.Study Design and SettingA framework for estimating local PAR values is developed, and then illustrated using synthetic and empirical data.ResultsA general expression for the variance of a local PAR estimate is formulated. It involves three components, reflecting (1) the variance of the disease relative risk associated with exposure to a risk factor, (2) the variance of the exposure prevalence (P), and (3) their covariance. The effects of variable stratum sizes, case–control sample size ratios, and variation in exposure P are illustrated by some synthetic scenarios, and with data from an international case–control study of heart disease.ConclusionThe precision of local PAR estimates can be considerably improved by incorporating external data, as opposed to limiting the calculation to data only from the local population. In some cases, variation in local PAR estimates largely reflects uncertainty in the local estimate of exposure P.     

Comparison of local influenza vaccine effectiveness using two methods

BackgroundIn some settings, research methods to determine influenza vaccine effectiveness (VE) may not be appropriate because of cost, time constraints, or other factors. Administrative database analysis of viral testing results and vaccination history may be a viable alternative. This study compared VE estimates from outpatient research and administrative databases.MethodsUsing the test-negative, case-control design, data for 2017–2018 and 2018–2019 influenza seasons were collected using: 1) consent, specimen collection, RT-PCR testing and vaccine verification using multiple methods; and 2) an administrative database of outpatients with a clinical respiratory viral panel combined with electronic immunization records. Odds ratios for likelihood of influenza infection by vaccination status were calculated using multivariable logistic regression. VE = (1 ? aOR) × 100.ResultsResearch participants were significantly younger (P < 0.001), more often white (69% vs. 59%; P < 0.001) than non-white and less frequently enrolled through the emergency department (35% vs. 72%; P < 0.001) than administrative database participants. VE was significant against all influenza and influenza A in each season and both seasons combined (37–49%). Point estimate differences between methods were evident, with higher VE in the research database, but insignificant due to low sample sizes. When enrollment sites were separately analyzed, there were significant differences in VE estimates for all influenza (66% research vs. 46% administrative P < 0.001) and influenza A (67% research vs. 49% administrative; P < 0.001) in the emergency department.Conclusions:The selection of the appropriate method for determining influenza vaccine effectiveness depends on many factors, including sample size, subgroups of interest, etc., suggesting that research estimates may be more generalizable. Other advantages of research databases for VE estimates include lack of clinician-related selection bias for testing and less misclassification of vaccination status. The advantages of the administrative databases are potentially shorter time to VE results and lower cost.     

不同风险评估方法在某石材加工企业粉尘和噪声危害评估中的应用比较

目的 比较职业危害风险指数评估法、ICMM风险评估模型和我国有害作业分级法在某石材加工企业粉尘和噪声危害评估中的应用，为建立符合我国实际的石材加工职业健康风险评估指南提供依据。方法 选取天津市某石材加工企业为调查现场，开展职业卫生学调查、作业场所粉尘浓度监测和噪声声级测量，采用不同的风险评估方法评估粉尘和噪声暴露岗位的健康风险，比较评估结果的差异。结果 该企业主要采用的原料是天然大理石荒料，针对粉尘的工程防护措施较为完善，但是未设置工程降噪设施，工人佩戴个人防护用品的意识较差。关于粉尘危害，职业危害风险指数评估法和我国有害作业分级法的评估结果显示，各大理石粉尘危害暴露岗位的风险比值均为1级；ICMM模型风险评估结果显示，大板切割岗位的风险比值为1级，其余岗位均为2级。关于噪声危害，职业危害风险指数评估法的结果显示大板切割岗位的风险比值为2级，其余岗位均为3级；ICMM模型风险评估结果显示，大板切割岗位的风险比值为4级，其余岗位均为5级；我国有害作业分级法评估结果显示，大板切割、抛光操作和补胶打磨岗位为1级，其余岗位均为2级。结论 3种职业健康风险评估方法均能用于石材加工企业的粉尘和噪声...     

Comparison of treatment effect estimates of non-vitamin K antagonist oral anticoagulants versus warfarin between observational studies using propensity score methods and randomized controlled trials

Emerging observational studies using propensity score (PS) methods assessed real-world comparative effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin in patients with non-valvular atrial fibrillation (AF). We aimed to compare treatment effect estimates of NOACs between PS studies and randomized controlled trials (RCTs). Electronic databases and conference proceedings were searched systematically. Primary outcomes included stroke or systemic embolism (SE) and major bleeding. A random-effects meta-analysis was performed to synthesize the data by pooling the PS- and RCT-derived hazard ratios (HRs) separately. The ratio of HRs (RHR) from the ratio of PS-derived HRs relative to RCT-derived HRs was used to determine whether there was a difference between estimates from PS studies and RCTs. There were 10 PS studies and 5 RCTs included for analysis. No significant difference of treatment effect estimates between the PS studies and RCTs was observed: RHR 1.11, 95 % CI 0.98–1.23 for stroke or SE; RHR 1.07, 95 % CI 0.87–1.34 for major bleeding. A significant association between NOACs and risk of stroke or SE was observed: HR 0.88, 95 % CI 0.83–0.94 for the PS studies; HR 0.79, 95 % CI 0.72–0.87 for the RCTs. However, no relationship between NOACs and risk of major bleeding was found: HR 0.91, 95 % CI 0.79–1.05 for the PS studies; HR 0.85, 95 % CI 0.73–1.00 for the RCTs. In this study, treatment effect estimates of NOACs versus warfarin in patients with non-valvular AF from PS studies are found to be in agreement with those from RCTs.     

Epidemiological data and radiation risk estimates

The results of several major epidemiology studies on populations with particular exposure to ionizing radiation should become available during the first years of the 21(st) century. These studies are expected to provide answers to a number of questions concerning public health and radiation protection. Most of the populations concerned were accidentally exposed to radiation in ex-USSR or elsewhere or in a nuclear industrial context. The results will complete and test information on risk coming from studies among survivors of the Hiroshima and Nagasaki atomic bombs, particularly studies on the effects of low dose exposure and prolonged low-dose exposure, of different types of radiation, and environmental and host-related factors which could modify the risk of radiation-induced effects. These studies are thus important to assess the currently accepted scientific evidence on radiation protection for workers and the general population. In addition, supplementary information on radiation protection could be provided by formal comparisons and analyses combining data from populations with different types of exposure. Finally, in order to provide pertinent information for public health and radiation protection, future epidemiology studies should be targeted and designed to answer specific questions, concerning, for example, the risk for specific populations (children, patients, people with genetic predisposition). An integrated approach, combining epidemiology and studies on the mechanisms of radiation induction should provide particularly pertinent information.