The association of waiting times from diagnosis to surgery with survival in women with localised breast cancer in England.

BACKGROUND: Survival from breast cancer in the United Kingdom is lower than in other developed countries. It is unclear to what extent waiting times for curative surgery affect survival. METHODS: Using national databases for England (cancer registries, Hospital Episode Statistics and Office of National Statistics), we identified 53 689 women with localised breast cancer, aged ≥ 15 years, diagnosed between 1996 and 2009, who had surgical resection with curative intent within 62 days of diagnosis. We used relative survival and excess risk modelling to determine associations between waiting times and 5-year survival. RESULTS: The median diagnosis to curative surgery waiting time among breast cancer patients was 22 days (interquartile range (IQR): 15-30). Relative survival was similar among women waiting between 25 and 38 days (RS: 93.5%; 95% CI: 92.8-94.2%), <25 days (RS: 93.0%; 95% CI: 92.5-93.4%) and between 39 and 62 days (RS: 92.1%; 95% CI: 90.8-93.4%). There was little evidence of an increase in excess mortality with longer waiting times (excess hazard ratio (EHR): 1.06; 95% CI: 0.88-1.27 comparing waiting times 39-62 with 25-38 days). Excess mortality was associated with age (EHR 65-74 vs 15-44 year olds: 1.23; 95% CI: 1.07-1.41) and deprivation (EHR most vs least deprived: 1.28; 95% CI: 1.09-1.49), but waiting times did not explain these differences. CONCLUSION: Within 62 days of diagnosis, decreasing waiting times from diagnosis to surgery had little impact on survival from localised breast cancer.

An evaluation of current services available for people diagnosed with head and neck cancer in the UK (2009-2010).

AIMS: To evaluate current care and service provision for people with head and neck cancer in the UK. MATERIALS AND METHODS: Self-report questionnaires for cancer networks, clinical leads of oncology units and leads for multidisciplinary teams (MDTs) were designed. These questionnaires were based on a previous survey. Questionnaires were sent out between 2009 and 2010. RESULTS: Questionnaires were received from all networks (n = 37), most oncology units (48 of 53) and most MDTs (51 of 63). Care for people with head and neck cancer is increasingly being provided by a centralised MDT. The membership of these teams varies; facilities available for team meetings are fit for purpose in most cases. MDTs are meeting frequently (weekly meetings in 96%) and discussing on average 18 cases at each meeting (95% confidence interval 15-21 cases). Most oncologists have access to all common anti-cancer drugs and most have access to all forms of radiotherapy. Intensity-modulated radiotherapy is not yet available in some oncology units (28%). A small number of units have only one oncologist (13%). Despite audit and research being part of the rationale for MDT working, regular discussion of morbidity and mortality is unusual (40%) and use of a database to record decisions is not universal. Only seven centres record decisions into the Data for Head and Neck Oncology database. Reported recruitment to studies is generally low (<2% of cases enrolled in studies in 62%). CONCLUSIONS: Head and neck cancer care is increasingly provided through a centralised MDT. Increased resources and further changes in practice are required to implement current National Health Service cancer policy. Teams need to improve recording of their decision-making, discuss morbidity and mortality and support recruitment to clinical studies.

The effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease (review of Technology Appraisal No. 111): a systematic review and economic model.

BACKGROUND: Alzheimer's disease (AD) is the most commonly occurring form of dementia. It is predominantly a disease of later life, affecting 5% of those over 65 in the UK. OBJECTIVES: Review and update guidance to the NHS in England and Wales on the clinical effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine [acetylcholinesterase inhibitors (AChEIs)] and memantine within their licensed indications for the treatment of AD, which was issued in November 2006 (amended September 2007 and August 2009). DATA SOURCES: Electronic databases were searched for systematic reviews and/or metaanalyses, randomised controlled trials (RCTs) and ongoing research in November 2009 and updated in March 2010; this updated search revealed no new includable studies. The databases searched included The Cochrane Library (2009 Issue 4, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials), MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, PsycINFO, EconLit, ISI Web of Science Databases--Science Citation Index, Conference Proceedings Citation Index, and BIOSIS; the Centre for Reviews and Dissemination (CRD) databases--NHS Economic Evaluation Database, Health Technology Assessment, and Database of Abstracts of Reviews of Effects. REVIEW METHODS: The clinical effectiveness systematic review was undertaken following the principles published by the NHS CRD. We included RCTs whose population was people with AD. The intervention and comparators depended on disease severity, measured by the Mini Mental State Examination (MMSE). INTERVENTIONS: mild AD (MMSE 21-26)--donepezil, galantamine and rivastigmine; moderate AD (MMSE 10-20)--donepezil, galantamine, rivastigmine and memantine; severe AD (MMSE < 10)--memantine. Comparators: mild AD (MMSE 21-26)--placebo or best supportive care (BSC); moderate AD (MMSE 10-20)--donepezil, galantamine, rivastigmine, memantine, placebo or BSC; severe AD (MMSE < 10)--placebo or BSC. The outcomes were clinical, global, functional, behavioural, quality of life, adverse events, costs and cost-effectiveness. Where appropriate, data were pooled using pair-wise meta-analysis, multiple outcome measures, metaregression and mixedtreatment comparisons. The decision model was based broadly on the structure of the three-state Markov model described in the previous technology assessment report, based upon time to institutionalisation, parameterised with updated estimates of effectiveness, costs and utilities. RESULTS: Notwithstanding the uncertainty of our results, we found in the base case that the AChEIs are probably cost saving at a willingness-to-pay (WTP) of £'30,000 per qualityadjusted life-year (QALY) for people with mild-to-moderate AD. For this class of drugs, there is a > 99% probability that the AChEIs are more cost-effective than BSC. These analyses assume that the AChEIs have no effect on survival. For the AChEIs, in people with mild to moderate AD, the probabilistic sensitivity analyses suggested that donepezil is the most cost-effective, with a 28% probability of being the most cost-effective option at a WTP of £'30,000 per QALY (27% at a WTP of £'20,000 per QALY). In the deterministic results, donepezil dominates the other drugs and BSC, which, along with rivastigmine patches, are associated with greater costs and fewer QALYs. Thus, although galantamine has a slightly cheaper total cost than donepezil (£'69,592 vs £'69,624), the slightly greater QALY gains from donepezil (1.616 vs 1.617) are enough for donepezil to dominate galantamine.The probability that memantine is cost-effective in a moderate to severe cohort compared with BSC at a WTP of £'30,000 per QALY is 38% (and 28% at a WTP of £'20,000 per QALY). The deterministic ICER for memantine is £'32,100 per/QALY and the probabilistic ICER is £'36,700 per/QALY. LIMITATIONS: Trials were of 6 months maximum follow-up, lacked reporting of key outcomes, provided no subgroup analyses and used insensitive measures. Searches were limited to English language, The model does not include behavioural symptoms and there is uncertainty about the model structure and parameters. CONCLUSIONS: The additional clinical effectiveness evidence identified continues to suggest clinical benefit from the AChEIs in alleviating AD symptoms, although there is debate about the magnitude of the effect. Although there is also new evidence on the effectiveness of memantine, it remains less supportive of this drug's use than the evidence for AChEIs. The conclusions concerning cost-effectiveness are quite different from the previous assessment. This is because both the changes in effectiveness and costs between drug use and non-drug use underlying the ICERs are very small. This leads to highly uncertain results, which are very sensitive to change. RESEARCH PRIORITIES: RCTs to include mortality, time to institutionalisation and quality of life, powered for subgroup analysis. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Changes in survival by ethnicity of patients with cancer between 1992-1996 and 2002-2006: is the discrepancy decreasing?

BACKGROUND: Patients of minority race/ethnicity have lower survival after diagnosis with most types of cancer. Little data are available concerning changes in disparity over time. Here, we examine changes in survival by race/ethnicity of patients with common cancers in two recent time periods. PATIENTS AND METHODS: We used modeled period analysis to determine relative survival (RS) for non-Hispanic white (nHw), African-American (AA), and Hispanic patients in the Surveillance, Epidemiology, and End Results database diagnosed with common solid and hematological malignancies. RESULTS: Five-year RS improved overall and for nHw for each tumor examined, ranging from + 2% points (pancreatic cancer) to + 16.4% points [non-Hodgkin's lymphoma, (NHL)]. Greater improvement was observed for AA and Hispanics than nHw in breast and prostate cancer and NHL. Less improvement was observed for AA and Hispanics than for nHw for lung and pancreatic cancer. No statistically significant improvement was observed for AA and Hispanics with myeloma or acute leukemia. Survival disparities ranging from 0.5% points (myeloma) to 13.1% points (breast) between nHw and AA remained. CONCLUSIONS: Progress has been made in decreasing disparities in survival between nHw and minorities in breast cancer, prostate cancer, and NHL. Little progress has been made in reducing disparities for the other studied cancers.

Characteristics of ovarian cancer in women residing in Aotearoa, New Zealand: 1993-2004.

BACKGROUND: Few studies have compared ovarian cancer rates between different ethnic groups in the same country. The aim of this study was to describe ethnic patterns in the incidence and mortality of ovarian cancer in New Zealand, and to investigate ethnic and socioeconomic differences in the grade and stage of ovarian cancer. METHODS: Data on all women registered with ovarian cancer on the New Zealand Cancer Registry (1993-2004) were analysed. Population data were taken from the 1996 and 2001 census. Logistic regression was used to estimate associations between ethnicity, deprivation and tumour characteristics. RESULTS: Age-standardised incidence rates were highest in Pacific women, intermediate in Maori women, and lowest in non-Maori, non-Pacific women. Age-standardised mortality rates showed the same pattern. Ovarian cancer subtypes differed by ethnic group. There was no significant association between socioeconomic deprivation and tumour grade or stage. Age-adjusted models showed that Maori women were more likely to have well-differentiated tumours and less likely to present at a later stage compared to non-Maori, non-Pacific women. These patterns were partly explained by socioeconomic deprivation, and were not apparent for Pacific women. CONCLUSIONS: Pacific and Maori women experience higher incidence of ovarian cancer and mortality, compared to non-Maori, non-Pacific women. Maori women seemed to have better prognostic factors (local stage and well-differentiated tumours) than non-Maori, non-Pacific women. More work is needed to improve current cancer prevention strategies, particularly in Pacific women.

Association between early life history of respiratory disease and morbidity and mortality in adulthood.

BACKGROUND: Early life exposure to respiratory diseases is associated with lung impairment in adulthood. The objective of this study was to investigate morbidity, and respiratory and other cause specific mortality, among people who reported a medical history of bronchitis, pneumonia and asthma early in life. METHODS: We studied an historical cohort of male students who attended Glasgow University between 1948 and 1968 and for whom long term follow-up and cause specific mortality were available (9544 students, 1553 deaths). A medical history of respiratory diseases, including bronchitis, pneumonia and asthma, along with other disease risk factors and socioeconomic conditions, were collected during university health examinations. A subsample responded to a postal follow-up in adulthood (n = 4044), which included respiratory and other chronic disease questions. RESULTS: A medical history of a respiratory disease (bronchitis, pneumonia and asthma) in early life was associated with a 57% greater risk of overall respiratory disease mortality in adulthood and a more than twofold increase in chronic obstructive pulmonary disease mortality (fully adjusted hazard ratio (HR) 2.37; 95% CI 1.16, 4.83). In addition, students reporting a history of bronchitis had a 38% higher risk of cardiovascular disease mortality (95% CI 1.06, 1.80). Respiratory disease in early life was also associated with a higher risk in adulthood of chronic phlegm, dyspnoea and doctor's diagnosis of asthma, bronchitis and emphysema (adjusted odds ratios ranging from 1.40 to 6.95 for these outcomes). CONCLUSION: An early life history of respiratory diseases is associated with higher mortality and morbidity risk in adulthood in men, the associations being seen particularly for respiratory related and cardiovascular deaths among those with a history of bronchitis. All early life respiratory diseases appeared to be negatively associated with later adult respiratory health.

Breast cancer risk factors and a novel measure of volumetric breast density: cross-sectional study.

We conducted a cross-sectional study nested within a prospective cohort of breast cancer risk factors and two novel measures of breast density volume among 590 women who had attended Glasgow University (1948-1968), replied to a postal questionnaire (2001) and attended breast screening in Scotland (1989-2002). Volumetric breast density was estimated using a fully automated computer programme applied to digitised film-screen mammograms, from medio-lateral oblique mammograms at the first-screening visit. This measured the proportion of the breast volume composed of dense (non-fatty) tissue (Standard Mammogram Form (SMF)%) and the absolute volume of this tissue (SMF volume, cm3). Median age at first screening was 54.1 years (range: 40.0-71.5), median SMF volume 70.25 cm3 (interquartile range: 51.0-103.0) and mean SMF% 26.3%, s.d.=8.0% (range: 12.7-58.8%). Age-adjusted logistic regression models showed a positive relationship between age at last menstrual period and SMF%, odds ratio (OR) per year later: 1.05 (95% confidence interval: 1.01-1.08, P=0.004). Number of pregnancies was inversely related to SMF volume, OR per extra pregnancy: 0.78 (0.70-0.86, P<0.001). There was a suggestion of a quadratic relationship between birthweight and SMF%, with lowest risks in women born under 2.5 and over 4 kg. Body mass index (BMI) at university (median age 19) and in 2001 (median age 62) were positively related to SMF volume, OR per extra kg m(-2) 1.21 (1.15-1.28) and 1.17 (1.09-1.26), respectively, and inversely related to SMF%, OR per extra kg m(-2) 0.83 (0.79-0.88) and 0.82 (0.76-0.88), respectively, P<0.001. Standard Mammogram Form% and absolute SMF volume are related to several, but not all, breast cancer risk factors. In particular, the positive relationship between BMI and SMF volume suggests that volume of dense breast tissue will be a useful marker in breast cancer studies.

Association between number of siblings and cause-specific mortality in the Glasgow alumni cohort study.

In the Glasgow University Alumni cohort, students with no siblings experienced higher respiratory disease mortality. This risk diminished after accounting for potential confounders. We did not find strong evidence of an association with all cause, coronary heart disease, stroke or stomach cancer mortality. Number of siblings is a proxy for other exposures and exploring its association with specific disease outcomes can help disentangle some of the pathways relating early life exposures to adult mortality.

Comparing measurements of breast density.

Breast density measurements can be made from mammograms using either area-based methods, such as the six category classification (SCC), or volumetric based methods, such as the standard mammogram form (SMF). Previously, we have shown how both types of methods generate breast density estimates which are generally close. In this paper, we switch our attention to the question of why, for certain cases, they provide widely differing estimates. First, we show how the underlying physical models of the breast employed in the methods need to be consistent, and how area-based methods are susceptible to projection effects. We then analyse a set of patients whose mammograms show large differences between their SCC and SMF assessments. More precisely, 12% of 657 patients were found to fall into this category. Of these, 2.7% were attributable to errors either in the SMF segmentation algorithms, human error in SCC categorization or poor image exposure. More importantly, 9.3% of the cases appear to be due to fundamental differences between the area- and volume-based techniques. We conclude by suggesting how we might remove half of those discrepancies by introducing a new categorization of the SMF estimates based on the breast thickness. We note however, that this still leaves 6% of patients with large differences between SMF and SCC estimates. We discuss why it might not be appropriate to assume SMF (or any volume measure) has a similar breast cancer risk prediction capability to SCC.

Association between glycosylated hemoglobin and cancer risk: a New Zealand linkage study.

BACKGROUND: The purpose of this study was to examine the relationship between glycosylated hemoglobin (HbA(1c)) level and subsequent cancer risk. MATERIAL AND METHODS: HbA(1c) measurements were made on blood samples of participants in a hepatitis B (HB) screening program (1999-2001). Cancer incidence was determined by linkage to cancer registrations and hospitalization records to the end of 2004. Participants previously diagnosed with diabetes or cancer were excluded. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using Cox regression. RESULTS: Among the 46 575 participants (70% Maori, 12% Pacific, 5% Asian and 12% Other), 634 cancer cases were observed. For all cancers combined, a significant increased risk was found in persons with moderately elevated HbA(1c) levels (6%-6.9%) (HR 1.40, 95% CI: 1.11-1.76), with a smaller increased risk in persons with highly elevated levels (> or =7%) (HR 1.09, 95% CI: 0.80-1.48) as compared with persons having low HbA(1c) levels (<6%). The HRs for respiratory cancers were 2.27 (95% CI: 1.34-3.86) for the moderate HbA(1c) category and 1.58 (95% CI: 0.77-3.26) for the upper HbA(1c) category. For endometrial cancers, the HRs were 4.05 (95% CI: 1.10-14.88) and 5.07 (95% CI: 1.20-21.31), respectively. For other cancer sites, no significantly increased risks were found. CONCLUSIONS: These findings are consistent with other evidence that abnormal glucose metabolism may be associated with an increased risk of some cancers.

Breast composition measurements using retrospective standard mammogram form (SMF).

The standard mammogram form (SMF) representation of an x-ray mammogram is a standardized, quantitative representation of the breast from which the volume of non-fat tissue and breast density can be easily estimated, both of which are of significant interest in determining breast cancer risk. Previous theoretical analysis of SMF had suggested that a complete and substantial set of calibration data (such as mAs and kVp) would be needed to generate realistic breast composition measures and yet there are many interesting trials that have retrospectively collected images with no calibration data. The main contribution of this paper is to revisit our previous theoretical analysis of SMF with respect to errors in the calibration data and to show how and why that theoretical analysis did not match the results from the practical implementations of SMF. In particular, we show how by estimating breast thickness for every image we are, effectively, compensating for any errors in the calibration data. To illustrate our findings, the current implementation of SMF (version 2.2beta) was run over 4028 digitized film-screen mammograms taken from six sites over the years 1988-2002 with and without using the known calibration data. Results show that the SMF implementation running without any calibration data at all generates results which display a strong relationship with when running with a complete set of calibration data, and, most importantly, to an expert's visual assessment of breast composition using established techniques. SMF shows considerable promise in being of major use in large epidemiological studies related to breast cancer which require the automated analysis of large numbers of films from many years previously where little or no calibration data is available.

Initial experiences of using an automated volumetric measure of breast density: the standard mammogram form.

Limitations of area based measures of breast density have led several research groups to develop volumetric measures of breast density, for use in predicting risk and in epidemiological research. In this paper, we describe our initial experiences using an automated algorithm (standard mammogram form, SMF) to estimate the volume of the breast that is dense from digitized film mammograms. We performed analyses on 3816 mammograms of 626 women, who were part of the Glasgow Alumni Cohort and had mammograms taken within the Scottish Breast Screening Programme between 1989 and 2002. Absolute volume of dense breast tissue (SMF volume) and the percentage of the volume of the breast that is dense (SMF%) were calculated. The median (interquartile range) of SMF volume was 66 cm3 (48 to 98), and of SMF% was 23.4% (18.6 to 29.7). SMF%, but not SMF volume, was positively related to a six category classification (SCC) of visually assigned area-based breast density (increase in ln(SMF%) per category increase in SCC: 0.04% (95% CI: 0.03-0.05). The SMF algorithm produced lower SMF volume for craniocaudal (CC) compared with mediolateral oblique (MLO) views, but CC/MLO differences for SMF% were small. The mean right/left difference for ln(SMF volume) was -0.027 cm3 (95% confidence interval (CI) -0.044 to -0.009) and of ln(SMF%) was 0.005% (95% CI -0.008% to 0.019%). We present these initial data as a background for future analytical work using SMF.

Association between sibship size and allergic diseases in the Glasgow Alumni Study.

BACKGROUND: Recent epidemiological studies consistently report an inverse association between sibship size and allergic disease, but evidence from individuals born before the 1980s is inconsistent. As information on relative permanence of this finding may offer clues to its biological explanation, the association between sibship size and allergic disease in individuals born between 1918 and 1952 was investigated. METHODS: Cross sectional surveys conducted by the Student Health Service at the University of Glasgow (1948-68) provided data on 14 140 men and women aged 16-30 years at the time of examination. The main outcome measures studied were self-reported asthma, eczema-urticaria, and hay fever. RESULTS: A total of 1677 individuals (11.9%) provided a positive history of at least one of the three allergic diseases: 457 (3.2%) asthma, 594 (4.2%) eczema-urticaria, and 885 (6.3%) hay fever. Compared with those without siblings (reference odds ratio = 1), the odds ratios (95% confidence intervals) for having any allergic disease among those with one, two or three siblings were 0.86 (0.75 to 0.99), 0.80 (0.69 to 0.93), and 0.70 (0.60 to 0.83), respectively (p(trend)<0.001). Increasing birth order and low socioeconomic position in childhood were associated with a lower risk of allergy. Adjustment for birth order, year of birth, age, sex, socioeconomic position in childhood, and family history of allergy did not materially alter the results. CONCLUSIONS: There is a robust inverse association between sibship size and allergic disease even among people born in the first half of the 20th century. These results favour relatively time-independent explanations for this phenomenon (such as the hygiene hypothesis or parity related changes in the intrauterine environment) over new environmental exposures.

Trends in resting pulse rate among students attending Glasgow University between 1948 and 1968: analyses of cross sectional surveys.

Evidence on long-term trends in physical activity is limited. We report that resting pulse rates--a proxy indicator of physical activity and fitness--increased among young adults attending Glasgow University between 1948 and 1968.

Lifecourse weight patterns and adult-onset diabetes: the Glasgow Alumni and British Women's Heart and Health studies.

OBJECTIVE: To examine the association between body weight measures across the lifecourse and the risk of adult-onset diabetes. METHODS: We analysed data from the Glasgow Alumni Cohort and the British Women's Heart and Health Study (BWHHS). The former included 5,571 men and women who had height and weight measured at university, and reported birthweight, mid- and later-life weight in a postal questionnaire. The BWHHS analysis included 4,280 women who had height and weight measured in later adulthood and recalled their birthweight and early adult height and weight. Adult-onset diabetes was defined as doctor-diagnosed disease after age 30, either self-reported or abstracted from medical records. RESULTS: Thirty nine women and 209 men (Glasgow Alumni study) and 314 women (BWHHS) had diabetes. Those with diabetes had lower mean birthweight than those without, although the differences were small. Individuals with diabetes were also shorter and heavier at all ages than those without diabetes. Being overweight during at least one time period in adult life was associated with an increased risk of diabetes, compared to those who were never overweight. While there was no age at which being overweight was particularly detrimental, the risk associated with being overweight was cumulative across the lifecourse. CONCLUSIONS: Being overweight at any point during life is associated with an increased risk of adult-onset diabetes. The cumulative nature of this association reinforces the need to prevent the development of excess weight at an early age to reduce diabetes prevalence in coming decades.

Acne in adolescence and cause-specific mortality: lower coronary heart disease but higher prostate cancer mortality: the Glasgow Alumni Cohort Study.

Androgen level or androgen activity is implicated in several health outcomes, but its independent role remains controversial. This study investigated the association between history of acne in young adulthood, a marker of hormone activity, and cause-specific mortality in the Glasgow Alumni Cohort Study. Male students who attended Glasgow University between 1948 and 1968 and participated in voluntary health checks reported history of acne (n = 11,232). Vital status has been traced, and risk factors in adulthood are known for about 50% of the participants. Those with a history of acne were more often nonsmokers while university students and tended to be from a lower socioeconomic position. The two groups did not differ in other adolescent (height, body mass index, blood pressure, and number of siblings) or in most adult risk factors. Students who reported a history of acne had a lower risk of all-cause (hazard ratio = 0.89, 95% confidence interval (CI): 0.76, 1.04) and coronary heart disease (hazard ratio = 0.67, 95% CI: 0.48, 0.94) mortality but had some evidence of a higher risk of prostate cancer mortality (hazard ratio = 1.67, 95% CI: 0.79, 3.55). This study shows that androgen activity during adolescence may protect against coronary heart disease but confer a higher risk of prostate cancer mortality.

Body mass index in early and mid-adulthood, and subsequent mortality: a historical cohort study.

BACKGROUND: The aim of this study was to investigate the associations between body mass index (BMI) in early and mid-adulthood, and BMI change between these ages, and mortality. METHODS: Historical cohort study of 629 men, who had height and weight measured at the Student Health Service of the University of Glasgow in 1948-1949 (median age 22 y) and who reported their weight in a postal questionnaire in 1963-1966 (median age 38 y). The participants were followed up until April 2002 (mean follow-up: 35 y). During this time, 124 men died, 68 of cardiovascular disease (CVD) and 33 of cancer. FINDINGS: Mean BMI increased from 21.4 kg/m(2) (standard deviation (s.d.): 2.2 kg/m(2)) in early adulthood to 24.2 kg/m(2) (s.d.: 3.0 kg/m(2)) in mid-adulthood. All-cause mortality was associated with being overweight (BMI> or =25 kg/m(2)) at age 22 but not at age 38, adjusted hazard ratio (HR): 1.85 (95% confidence interval (CI) 1.09-3.13) and 1.05 (95% CI: 0.73-1.52), respectively. BMI at age 22 y was more strongly associated with CVD mortality than was BMI at age 38 y, adjusted HR(22 y): 2.41 (95% CI: 1.26-4.60) and HR(38 y): 1.33 (95% CI: 0.82-2.16). There was no clear relationship between cancer mortality and BMI at either age: HR(22 y): 0.68 (95% CI: 0.16-2.91), HR(38 y): 0.90 (95% CI: 0.44-1.84), although relatively few men died of cancer in the follow-up period. Similar patterns were seen for obesity (BMI> or =30 kg/m(2)) as for being overweight. Analyses of weight patterns indicated particularly detrimental effects of overweight persisting from early to mid-adulthood. CONCLUSIONS: BMI in early adulthood is positively related to CVD mortality in later life in men. The risk associated with early adulthood adiposity appeared to be greater than that in mid-adulthood. We did not demonstrate an association between weight gain and later mortality. These results reinforce the need to stem the obesity epidemic in children and young adults.

Breast density: agreement of measures from film and digital image.

Mammographic density, in particular density from digital images, is increasingly used in breast cancer research. We investigated the concordance between density assigned by the same radiologist to a mammogram film and a digital image of the same mammogram. Two density measures were investigated, Wolfe parenchymal patterns and a six category classification (SCC) system of density. Included in the study were 78 women, 528 mammograms. Crude and weighted Kappa statistics were used to estimate agreement between the density assigned from the film and the image. Kappa for Wolfe measures was 71%, p<0.001 and for SCC measures was 54%, p<0.001. Weighted Kappa values were 79%, p<0.001 and 77%, p<0.001, respectively. There was some evidence to suggest that the digitized image may be assigned a higher Wolfe but not numerical category than the original film, and the magnitude of these differences was small. Neither age nor mammogram view (craniocaudal or mediolateral oblique) were related to the likelihood of agreement of the two density measurements. This evidence justifies the use of digital images in the visual assessment of breast density in research studies.