External Reference Population Research Articles

The younger the better: importance of age in treatment of childhood obesity

Children living with obesity are prevalent worldwide. It is an established finding that many children who start a lifestyle intervention tend to leave prematurely. The aim of this study was to identify characteristics in children with obesity who prematurely leave a lifestyle intervention. The cohort study includes children living with obesity aged 4–17, treated in a Danish family-centered lifestyle intervention between 2014 and 2017. Data were collected from patient records. BMI-SDS was calculated using an external Danish reference population and multivariable regression analysis was used to answer the research question. Of the 159 children included, 64 children who left the intervention within the first 1.5 years were older compared to those who stayed in the intervention (10.2 years ± 2.9 vs 11.5 years ± 3.1, p = 0.005). Older participants (> 66.6th percentile) had a shorter treatment duration (489 days) compared to the youngest (190 days 95% CI: 60; 320, p = 0.005) and middle third (224 days 95% CI: 89; 358, p = 0.001). Additionally, an inverse association was found between duration of treatment and age at baseline (−31 days, 95% CI (−50; −13), p = 0.001). Conclusion: The risk of leaving a lifestyle intervention prematurely was primarily dependent on the age of the participants, emphasizing the importance of including children early in lifestyle interventions.What is Known:•Lifestyle interventions for childhood obesity that are shorter in duration often lead to short-term weight reductions only. Limited knowledge exists on why some children prematurely leave these interventions.What is New:•This study observes a solid inverse correlation and association between age and time spent in the interventions, when treating childhood obesity. We hereby suggest age as an important determinant for the adherence to lifestyle interventions and emphasize the importance of treatment early in life.

A Principal Component Informed Approach to Address Polygenic Risk Score Transferability Across European Cohorts.

One important confounder in genome-wide association studies (GWASs) is population genetic structure, which may generate spurious associations if not properly accounted for. This may ultimately result in a biased polygenic risk score (PRS) prediction, especially when applied to another population. To explore this matter, we focused on principal component analysis (PCA) and asked whether a population genetics informed strategy focused on PCs derived from an external reference population helps in mitigating this PRS transferability issue. Throughout the study, we used two complex model traits, height and body mass index, and samples from UK and Estonian Biobanks. We aimed to investigate 1) whether using a reference population (1000G) for computation of the PCs adjusted for in the discovery cohort improves the resulting PRS performance in a target set from another population and 2) whether adjusting the validation model for PCs is required at all. Our results showed that any other set of PCs performed worse than the one computed on samples from the same population as the discovery dataset. Furthermore, we show that PC correction in GWAS cannot prevent residual population structure information in the PRS, also for non-structured traits. Therefore, we confirm the utility of PC correction in the validation model when the investigated trait shows an actual correlation with population genetic structure, to account for the residual confounding effect when evaluating the predictive value of PRS.

Gestational Weight Gain and Birth Outcome: A Comparison of Methods of Accounting for Gestational Age.

Cross-sectional studies of total gestational weight gain (GWG) and perinatal outcomes have used different approaches to operationalize GWG and adjust for duration of gestation. Using birth records from California (2007-2017), Nevada (2010-2017), and Oregon (2008-2017), we compared 3 commonly used approaches to estimate associations between GWG and cesarean delivery, small-for-gestational-age birth, and low birth weight (LBW): 1) the Institute of Medicine-recommended GWG ranges at a given gestational week, 2) total weight gain categories directly adjusting for gestational age as a covariate, and 3) weight-gain-for-gestational-age z scores derived from an external longitudinal reference population. Among 5,461,130 births, the 3 methods yielded similar conclusions for cesarean delivery and small-for-gestational-age birth. However, for LBW, some associations based on z scores were in the opposite direction of methods 1 and 2, paradoxically suggesting that higher GWG increases risk of LBW. This was due to a greater proportion of preterm births among those with high z scores, and controlling for gestational age in the z score model brought the results in line with the other methods. We conclude that the use of externally derived GWG z scores based on ongoing pregnancies can yield associations confounded by duration of pregnancy when the outcome is strongly associated with gestational age at delivery.

Effects of the implementation of a mass rapid transit system on mortality rates attributed to cardiorespiratory complications in Taipei

ABSTRACT Although Taipei City has encountered a fall in ambient air pollutant levels since 1996, the year its mass rapid transit (MRT) system commenced operation, no apparent study investigated changes in risks of death attributed to respiratory, cardiovascular, and cerebrovascular diseases in Taipei during this 23-year period. In order to examine the relationship between MRT and occurrence of respiratory and cardiovascular illnesses attributed to air contaminants, exposure over the 23 year duration was subdivided into the following periods: reference period 1 (1992–1995); period 2 (1996–2004), a time when there was a total track length of 67 km; period 3 (2005–2015), when the total track length was lengthened to 131.1 km; and period 4 (2016–2020), when it was further extended to 146.2 km. Taichung City, no MRT system, was used as an external reference population. The effect of Taipei’s MRT system on rates of cause-specific death rates was analyzed using robust generalized Poisson regression models. After adjusting for age-standardized rates (ASRs), a decrease in relative risks (RRs) was found for non-trauma death and respiratory disease from periods 2 to 4. Even though the RRs were greater than 1.0 for cardiovascular and cerebrovascular diseases for periods 2 to 4, a downward trend was still noted in these RRs in Taipei. These findings suggest a relationship exists between air pollutant exposure and mortality. In addition, data demonstrated that implementation of the MRT in Taipei exerted beneficial health effects as evidenced by lower mortality rates.

Dose-response relationship between cumulative physical workload and osteoarthritis of the hip \u2013 a meta-analysis applying an external reference population for exposure assignment

BackgroundThere is consistent evidence from observational studies of an association between occupational lifting and carrying of heavy loads and the diagnosis of hip osteoarthritis. However, due to the heterogeneity of exposure estimates considered in single studies, a dose-response relationship between cumulative physical workload and hip osteoarthritis could not be determined so far.MethodsThis study aimed to analyze the dose-response relationship between cumulative physical workload and hip osteoarthritis by replacing the exposure categories of the included studies with cumulative exposure values of an external reference population. Our meta-regression analysis was based on a recently conducted systematic review (Bergmann A, Bolm-Audorff U, Krone D, Seidler A, Liebers F, Haerting J, Freiberg A, Unverzagt S, Dtsch Arztebl Int 114:581–8, 2017). The main analysis of our meta-regression comprised six case-control studies for men and five for women. The population control subjects of a German multicentre case-control study (Seidler A, Bergmann A, Jäger M, Ellegast R, Ditchen D, Elsner G, Grifka J, Haerting J, Hofmann F, Linhardt O, Luttmann A, Michaelis M, Petereit-Haack G, Schumann B, Bolm-Audorff U, BMC Musculoskelet Disord 10:48, 2009) served as the reference population. Based on the sex-specific cumulative exposure percentiles of the reference population, we assigned exposure values to each category of the included studies using three different cumulative exposure parameters. To estimate the doubling dose (the amount of physical workload to double the risk of hip osteoarthritis) on the basis of all available case-control-studies, meta-regression analyses were conducted based on the linear association between exposure values of the reference population and the logarithm of reported odds ratios (ORs) from the included studies.ResultsIn men, the risk to develop hip osteoarthritis was increased by an OR of 1.98 (95% CI 1.20–3.29) per 10,000 tons of weights ≥20 kg handled, 2.08 (95% CI 1.22–3.53) per 10,000 tons handled > 10 times per day and 8.64 (95% CI 1.87–39.91) per 106 operations. These estimations result in doubling dosages of 10,100 tons of weights ≥20 kg handled, 9500 tons ≥20 kg handled > 10 times per day and 321,400 operations of weights ≥20 kg. There was no linear association between manual handling of weights at work and risk to develop hip osteoarthritis in women.ConclusionsUnder specific conditions, the application of an external reference population allows for the derivation of a dose-response relationship despite high exposure heterogeneities in the pooled studies.

Symptomatic dengue infection during pregnancy and livebirth outcomes in Brazil, 2007–13: a retrospective observational cohort study

Dengue is a major public health challenge in Brazil. We assessed the relationship between symptomatic dengue infection during pregnancy and adverse birth outcomes in the country between 2007 and 2013. We did a retrospective observational cohort study using information reported in the Brazilian national reportable disease information system (SINAN) and the livebirth information system (SINASC) databases. We probabilistically linked confirmed dengue-positive and dengue-negative pregnancies with live childbirths using Fine-Grained Record Integration and Linkage (FRIL) software. We also included an external reference population of randomly selected newborn babies. Pregnancy was adopted as the unit of analysis. We assessed the relationship between symptomatic dengue infection during pregnancy and adverse birth outcomes, using multivariable logistic regression adjusted for relevant covariates. 3898 dengue-positive pregnant women, 3165 dengue-negative women, and 3898 newborn babies from the reference population were included in the analysis. Preterm birth occurred in 322 (8·4%) of 3821 cases in the dengue-positive group versus 324 (10·4%) of 3101 in the dengue-negative group (unadjusted analysis: relative risk [RR] 0·81, 95% CI 0·70-0·93; adjusted analysis: odds ratio [OR] 1·26, 95% CI 1·06-1·49, p=0·006) and 349 (9·1%) of 3818 in the reference population (RR 0·92, 0·80-1·07; OR 0·98, 0·83-1·16, p=0·84). The prevalence of low birthweight (<2500 g) was similar for dengue-positive women and dengue-negative women (8·3% [322 of 3897] vs 9·8% [310 of 3163]; OR 1·17, 95% CI 0·99-1·39, p=0·07), and in the reference population (8·3% vs 9·0% [350 of 3895]; OR 1·00, 0·85-1·17, p=0·97). The prevalence of malformations did not differ significantly for the dengue-positive group (27 [0·7%] of 3789) versus the dengue-negative group (27 [0·9%] of 3059, p=0·51) or versus the reference population (32 [0·9%] of 3738, p=0·56). In the adjusted analysis, the risk of preterm birth seems to be increased in women with symptomatic dengue infection during pregnancy. However, symptomatic dengue infection during pregnancy does not appear to be associated with congenital malformations or low birthweight. Sanofi Pasteur.

Is outdoor work associated with elevated rates of cerebrovascular disease mortality? A cohort study based on iron-ore mining.

BackgroundA cohort study that examined iron ore mining found negative associations between cumulative working time employed underground and several outcomes, including mortality of cerebrovascular diseases. In this cohort study, and using the same group of miners, we examined whether work in an outdoor environment could explain elevated cerebrovascular disease rates.MethodsThis study was based on a Swedish iron ore mining cohort consisting of 13,000 workers. Poisson regression models were used to generate smoothed estimates of standardized mortality ratios and adjusted rate ratios, both models by cumulative exposure time in outdoor work.ResultsThe adjusted rate ratio between employment classified as outdoor work ≥25 years and outdoor work 0–4 years was 1.62 (95 % CI 1.07–2.42). The subgroup underground work ≥15 years deviated most in occurrence of cerebrovascular disease mortality compared with the external reference population: SMR (0.70 (95 % CI 0.56–0.85)).ConclusionsEmployment in outdoor environments was associated with elevated rates of cerebrovascular disease mortality. In contrast, work in tempered underground employment was associated with a protecting effect.

Re: Seidler A, Jänichen S, Hegewald J et al. Systematic review and quantification of respiratory cancer risk for occupational exposure to hexavalent chromium

The review of Seidler and colleagues aimed at assessing the dose–response relation for occupational exposure to hexavalent chromium (Cr (VI)) and lung cancer in order to establish a risk-based occupational exposure limit (OEL) for Germany that currently lacks a binding threshold value (Seidler et al. 2012). The authors concluded that the excess risk could be ‘‘acceptable’’ (\4 cases/10.000 workers assuming 40 years of exposure) at 0.1 lg Cr(VI)/m or 4 lg Cr(VI)/m 9 years as lifetime exposure and may become ‘‘intolerable’’ beyond 1 lg/m or 40 lg/m 9 years, respectively. Although there are many industrial processes with exposure to Cr(VI), the assessment of Seidler and colleagues was only based on two historical cohorts in the US chromate industry (further referred to as Baltimore and Painesville cohort) (Gibb et al. 2000; Park et al. 2004; Crump et al. 2003; Luippold et al. 2003). Seidler et al. (2012) recognized this limitation but refrained from a discussion of risk estimates after major process changes and in other exposure circumstances like welding. Notably, no excess risk was observed at lower Cr(VI) concentrations in new chromate plants (Luippold et al. 2005). Welders comprise a considerably larger workforce exposed to Cr(VI) than chromate-producing workers. The excess risk presented by OSHA (U.S. Occupational Safety and Health Administration) for the IARC study in welders (Gerin et al. 1993) was lower than in chromate workers (OSHA 2006). These two chromate cohorts had been already subjected to previous risk assessments (e.g. (Goldbohm et al. 2006; Park and Stayner 2006)) and were preferred by OSHA in the determination of the permissible exposure limit (OSHA 2006). It is noteworthy that at least 80 % of the workers were smokers and that only four out of the 122 lung cancer cases of the Baltimore cohort were never smokers. Therefore, regression models had been applied to the individual exposure and covariate data to adjust relative risks for smoking (Gibb et al. 2000, Crump et al. 2003). OSHA’s risk assessment also refers to re-analyses of the original data with attempts to adjust for smoking or to exclude short-time exposed workers (OSHA 2006). However, Seidler et al. (2012) performed a risk assessment using published standardized mortality ratios (SMRs) for these cohorts calculated for grouped exposure data. These groups span across a wide range of individual Cr(VI) levels in particular for the respective lowest class: 0–28 lg/m 9 years in Park et al. (2004) and 0–60 lg/m 9 years in Gibb et al. (2000). This introduces an uncertainty about the precise exposure level associated with the lung cancer risk estimated for grouped exposure data. SMRs have various additional shortcomings, as the observed cases are compared with expected cases from an external reference population without adjusting for smoking. This might at least partially explain the increased lung cancer risk of 72 cases in the lowest exposure class of the Baltimore cohort that comprised many short-term exposed workers. The average exposure duration in the whole cohort was 5 months only. Seidler et al. (2012) performed a meta-analysis of the dose–response relation and depicted excess mortality risks in terms of additional cases per 1,000 workers for the male European population in Table 3 and 4. There is an apparent heterogeneity not only between the additional lung cancer cases per 1,000 workers in the individual studies but also This comment refers to the article available at doi: 10.1007/s00420-012-0822-0.

Representativeness of diabetes patients participating in a web‐based adverse drug reaction monitoring system

Lareb Intensive Monitoring, LIM, is a non-interventional observational cohort method which follows first-time users of certain drugs during a certain period of time and collects information about adverse drug reactions, ADRs. In order for LIM to be a useful pharmacovigilance tool, it is important to know whether the LIM population is comparable to the whole population using the drug. The aim of this study is to compare the LIM diabetes population with an external diabetes reference population on characteristics that may influence the patient's susceptibility for ADRs. In this study, a LIM diabetes population was compared to a reference diabetes population derived from The Groningen Initiative to ANalyse Type 2 diabetes Treatment project. Comparisons were made regarding age, gender, body mass index and polypharmacy, as well as diabetes medication used and disease/treatment duration. LIM patients were more often men (58.5% vs 50.8%) and in general younger (59.1 vs 64.7 years) and healthier, by that meaning they had a higher percentage of de novo treated patients (55.5% vs 53.2%), a shorter diabetes treatment duration (3.7 vs 5.5 years) and used less co-medication than patients in the reference population. This study shows that diabetes patients participating in a web-based intensive monitoring system differ from a reference population. The observed differences might lead to an underestimation of ADRs, but it is not clear whether this would also influence the type or time-course of the reported ADRs. When interpreting results from LIM studies, one should take these differences into account.

Haplotype diversity in the Antarctic springtailGressittacantha terranovaat fine spatial scales - a Holocene twist to a Pliocene tale

AbstractThe mitochondrial COI gene of the Antarctic springtail,Gressittacantha terranova, was sequenced across a polar coastal landscape at Terra Nova Bay, northern Victoria Land. Samples from two altitudinal transects in the foothills directly south of Campbell Glacier were compared with samples from Springtail Valley (northern foothills) as an external reference population. We found that mtDNA haplotypes clustered into two lineages (clades) with a mean sequence divergence of 10% (uncorrected distance). However, there was no phylogeographic structure found at this spatial (landscape) scale with haplotypes from both divergent clades found sympatric across most populations. At the landscape scale, the considerable genetic divergence revealed withinG. terranovais around five times greater than any other continental Antarctic springtail examined to date. These data indicate a Pliocene divergence event inG. terranovaaround 4–5 million years ago. The unusual distributional profile of haplotypes - occurrence of multiple haplotypes at single sites and genetic contiguity between sites that are not physically contiguous - suggests a subsequent ‘reshuffling’ of haplotypes in the Holocene that has an ecological basis.

Health-related quality of life measure based on the minimum data set.

To introduce a health-related quality of life measure for home care and institutional long-term care settings based on the Minimum Data Set (MDS) and the Health Utilities Index Mark 2 (HUI2). Health attributes of Health Related Quality of Life (HRQOL) were identified, and suitable constructs were determined. Items from the MDS were mapped to the HUI2. Scores for the Minimum Data Set Health Status Index (MDS-HSI) were calculated using the HUI2 scoring function. Measurement properties are examined and reported. HRQOL scores were compared across study populations and to an external reference population. Random samples were drawn from long-term care clients in private households (n = 377), supportive housing apartments (n = 80), two residential care facilities (n = 166), and a chronic care hospital (n = 274) in Ontario, Canada. All sampled residents were assessed for health-related items using the MDS. The MDS-HSI results provide preliminary evidence of good validity. Institutional populations had lower overall HRQOL scores than community populations. Comparisons to existing Canadian national data support construct validity. The MDS-HSI provides a summary outcome measure and an indicator of health status in the six supporting attributes. Longitudinal research is required to assess the sensitivity of the measure to changes overtime. Further research is also required to establish the consistency between the preference weights used in this application of the HUI2 and those that would be derived from a frail elderly population.

Respiratory effects of exposure to low levels of concrete dust containing crystalline silica.

Dusts containing crystalline silica are generated in mining, construction, glass, granite and concrete production industries. The association between exposure to low levels of concrete dust containing crystalline silica and reduction in lung function, was evaluated in a cross-sectional study. The study was carried out among 144 concrete workers, from two factories, with exposure assessment of respirable dust and silica by personal samplers. Results of respiratory questionnaires and standardized measurements of lung function were compared with the results in a control population. Multiple linear regression analysis was used in selecting factors that predict (age and standing height standardized residual) lung function. The average concentration of respirable dust in both factories was 0.8 mg/m(3) and 0.06 mg/m(3) for respirable silica. The average silica content of the dust was 9%. The average cumulative dust exposure was 7.0 mg/m(3) year and cumulative silica exposure was 0.6 mg/m(3) year. Significant associations between exposure to concrete dust and a small lung function (FEV(1)/FVC ratio, MMEF) loss were found, independent of smoking habits and of a history of allergy. Our results indicate that, concrete workers with chronic obstructive pulmonary symptoms and/or work-related lower respiratory symptoms are at risk of having a reduction in lung function (FEV&(1)/FVC ratio) outside the 5th percentile of the external reference population, and therefore, of mild chronic obstructive pulmonary disease, at respirable concrete dust levels below 1 mg/m(3) with a respirable crystalline silica content of 10% (TWA, 8 hr).

MS functional composite: relation to disease phenotype and disability strata.

The MS Functional Composite (MSFC), a recently developed outcome measure for clinical trials, was applied to 240 patients with MS to explore its utility in different subgroups of MS and for comparison with the Expanded Disability Status Scale (EDSS). Three clinical dimensions were examined: arm/hand function, leg function/ambulation, and cognition. Predictions of relative scores on the MSFC and its components in three major MS phenotypes (relapsing-remitting, primary progressive, and secondary progressive) and three strata of disability were developed and tested. Also, correlations with EDSS were calculated and the effect of an external reference population was assessed. Mean MSFC score was positive in the relapsing-remitting (0.4) and mildly disabled (0.4) groups and negative in the secondary progressive (-0.3), primary progressive (-0.4), and moderately (-0.07) and severely disabled (-1.0) groups. The correlation between EDSS and MSFC was strong (-0.68). EDSS correlated strongly with ambulation in secondary and primary progressive patients and severely disabled patients, moderately with arm/hand function for all analyzed groups, and not at all with cognition. Comparison with an external reference population showed changes in MSFC- and Z-scores, but did not result in altered differences between the subgroups. Our prospective study in subgroups of MS confirmed and extended the construct validity of the MSFC. The MSFC also showed good concurrent validity with the EDSS, and includes information about cognition.

Fertility of Danish battery workers exposed to lead.

Inorganic lead may impair male fecundity through its action on the germinal epithelium, the endocrine system or both, but information on possible impact on fertility in exposed populations is limited. Fertility was examined in 1349 male battery plant employees and in 9596 reference company employees over a follow-up of 25,949 and 183,414 person years respectively. The cohorts were identified by records in a national pension fund and information on births was obtained from the Danish Population Register. In a subset of the battery worker cohort, the average level of lead in blood was 35.9 micrograms/dl (4639 blood samples on 1654 person years in 400 workers; SD 13.0; range 3-125). The birth rate was analysed by logistic regression on occupational exposure and several extraneous determinants (age, parity, calendar year, and previous children). The birth-rate was not reduced in years at risk from exposure to lead in comparison with years not-at-risk; either in comparison with not-at-risk years within the battery plant cohort (odds ratio [OR] = 0.997, 95% confidence interval [CI]: 0.88-1.13), or in comparison with the external reference population (OR = 0.983, 95% CI: 0.87-1.11). Inorganic lead seems not to impair fertility among Danish battery workers. This finding does not rule out that the time taken to achieve a pregnancy is increased among battery workers because most pregnancies in Denmark are planned.

Cancer incidence among California Seventh-day Adventists, 1976–1982

Cancer incidence was monitored in a population of 34,000 Seventh-day Adventists in California. By religious belief, Adventists do not consume tobacco, alcohol, or pork and approximately one-half adhere to a lacto-ovovegetarian lifestyle. Only a small percentage are pure vegetarians. Comparisons of cancer-incidence rates in this population with an external reference population were completed by calculating standardized morbidity ratios (SMRs) for all cancer sites. Also, within the population, relative risks were calculated by using data obtained from a detailed lifestyle questionnaire that members of the study population completed. For all cancer sites combined in males, the SMR was lower in the Adventists (SMR = 0.73). The SMR was also lower in males for most individual cancer sites. However, prostate cancer risk was higher. For females, the all-cancer SMR was lower but not significantly so (SMR = 92). Most site-specific SMRs were lower, although not as much as the male SMRs. The SMR for endometrial cancer was significantly higher in female Adventists.

Incidence of respiratory cancer among workers exposed to chloromethyl-ethers.

A factory in France had used technical-grade chloromethyl-methyl-ether in the manufacture of anion exchange resins since 1958. Technical-grade chloromethyl-methyl-ether contains a human lung carcinogen, bis-chloromethyl-ether. The purpose of this cohort study was to determine if workers at the factory whose jobs had involved potential exposure to technical chloromethyl-methyl-ether had a higher incidence of lung cancer than coworkers, or others without potential exposure. Lung cancer occurred at a higher rate among potentially exposed workers than among nonexposed workers at the same plant (rate ratio (RR) = 5.0, 95% confidence interval (CI) 2.0-12.3), or among an external reference population (RR = 7.6, 95% CI 4.3-13.5). The average age at diagnosis for exposed cases was 10.5 years lower than for nonexposed cases. The predominantly small-cell cancers of the exposed were mostly oat-cell. There was a positive dose-response relation. The mean time from first exposure to diagnosis was 13 years (95% CI 8-18). Cumulative dose and induction time were not associated. The rate for the exposed workers peaked between 7 and 13 years after the start-up of the chloromethylation process, and was still above background in 1986, the end of the study period.

Non-acquired immune deficiency syndrome-defining malignancies in a hospital-based cohort of human immunodeficiency virus-infected patients: Bordeaux, France, 1985-1991. Groupe d'Epidémiologie Clinique du SIDA en Aquitaine.

Non-acquired immune deficiency syndrome-defining malignancies in a hospital-based cohort of human immunodeficiency virus-infected patients: Bordeaux, France, 1985-1991. Groupe d'Epidémiologie Clinique du SIDA en Aquitaine.

Lung function and respiratory symptoms in subjects with asbestos-related disorders: a cross-sectional study.

The prevalence of respiratory symptoms and lung function impairment was studied in a sample of men from a population screening of asbestos-related disorders. When the rates were adjusted for age and smoking habits, 83 subjects with lung fibrosis had an increased prevalence of respiratory symptoms, in particular, phlegm when coughing and breathlessness grades 1-3. Among 200 subjects under 70 years of age who had pleural plaques only, a statistically significant increase was observed in the prevalence of breathlessness grade 1 compared to an external reference population. Among 98 asbestos-exposed subjects who had normal chest X-rays, there was an increase in the prevalence of breathlessness grade 2, cough during the day, and phlegm when coughing. There was a higher proportion of subjects with lung fibrosis who were below 80% of the predicted values for forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) than in the other groups. There was also a higher proportion of subjects with pleural plaques only who were below 90% of the predicted value for FVC than in a group of 90 subjects without asbestos exposure. In accordance with previous studies, these results indicate that pleural plaques in asbestos workers may be of greater importance as a clinical feature than has been recognized in the past.

The Analysis of Heterogeneity for Indirect Standardized Mortality Ratios

SUMMARY Statistical methods analogous to analysis of variance are given for analysing hetero- geneity among standardized mortality ratios. Both the case in which an external standard reference population is to be used and the case in which such a standard must be estimated from the sample data are treated. As an example, grouping populations by latitude is shown to account for 93-9 per cent of melanoma standard mortality ratio heterogeneity among nine U.S. populations, and the between-group heterogeneity was highly statistically significant. THIs paper gives methods for analysing heterogeneity among standardized mortality ratios (SMRs). The methods are analogous to analysis of variance and can be applied to any epidemiologic hypothesis which partitions populations into groups. As an example we show that grouping nine U.S. populations into four northern, two middle latitude and three southern populations accounts for 93 9 per cent of the melanoma SMR heterogeneity and that the corresponding between group heterogeneity is highly statistically significant. The analysis of heterogeneity is based on an assumed product model which has been used by Kilpatrick (1962), Bjarnason et al. (1974), Gart (1974), Breslow and Day (1975) and Osborn (1975). In Section 2 we point out that the SMR is a good summary index of population mortality precisely when the product model holds, and we review methods for testing this model. Section 3 contains the methods needed for an analysis of heterogeneity based on the product model. For completeness we give methods both for the case in which an external standard reference population is to be used and for the case in which an internal standard is to be estimated from the observed populations.