Prostate cancer risk related to foods, food groups, macronutrients and micronutrients derived from the UK Dietary Cohort Consortium food diaries.

BACKGROUND/OBJECTIVES: The influence of dietary factors remains controversial for screen-detected prostate cancer and inconclusive for clinically detected disease. We aimed to examine these associations using prospectively collected food diaries. SUBJECTS/METHODS: A total of 1,717 prostate cancer cases in middle-aged and older UK men were pooled from four prospective cohorts with clinically detected disease (n=663), with routine data follow-up (means 6.6-13.3 years) and a case-control study with screen-detected disease (n=1054), nested in a randomised trial of prostate cancer treatments (ISCTRN 20141297). Multiple-day food diaries (records) completed by men prior to diagnosis were used to estimate intakes of 37 selected nutrients, food groups and items, including carbohydrate, fat, protein, dairy products, fish, meat, fruit and vegetables, energy, fibre, alcohol, lycopene and selenium. Cases were matched on age and diary date to at least one control within study (n=3528). Prostate cancer risk was calculated, using conditional logistic regression (adjusted for baseline covariates) and expressed as odds ratios in each quintile of intake (±95% confidence intervals). Prostate cancer risk was also investigated by localised or advanced stage and by cancer detection method. RESULTS: There were no strong associations between prostate cancer risk and 37 dietary factors. CONCLUSIONS: Prostate cancer risk, including by disease stage, was not strongly associated with dietary factors measured by food diaries in middle-aged and older UK men.

Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).

BACKGROUND: Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. METHODS: Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50-69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up. RESULTS: Among randomised practices, 271 (68%) in the intervention arm (198,114 men) and 302 (78%) in the control arm (221,929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices). CONCLUSIONS: The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening.

Cardiovascular sequelae in long-term survivors of young peoples' cancer: a linked cohort study.

BACKGROUND: We aimed to define the incidence and risk of cardiovascular late effects (LEs) identified from inpatient hospital episode statistics (HES) among long-term survivors of cancer in young people by age at diagnosis (0-14 and 15-29 years). METHODS: Records from the Yorkshire Specialist Register of Cancer in Children and Young People (1991-2006) were linked to inpatient HES data (1996-2011) to assess rates of cardiovascular LEs. Rates were compared with the general population in Yorkshire using age-sex-matched HES records for the entire region. RESULTS: Of 3247 survivors of cancer, 3.6% had at least one cardiovascular LE. Overall, cardiovascular hospitalisations for the childhood cohort were threefold higher compared with the general population, but did not differ for young adults. For young adults, increased rates were limited to pericardial disease, cardiomyopathy and heart failure, pulmonary heart disease, hypertension and conduction disorders. CONCLUSIONS: Survivors of childhood and young adult cancer remain at increased risk of cardiovascular LEs compared with the general population.

Are lower rates of surgery amongst older women with breast cancer in the UK explained by co-morbidity?

BACKGROUND: Around 60% of women ≥ 80 years old, in the UK do not have surgery for their breast cancer (vs<10% of younger age groups). The extent to which this difference can be accounted for by co-morbidity has not been established. METHODS: A Cancer Registry/Hospital Episode Statistics-linked data set identified women aged ≥ 65 years diagnosed with invasive breast cancer (between 1 April 1997 and 31 March 2005) in two regions of the UK (n=23038). Receipt of surgery by age was investigated using logistic regression, adjusting for co-morbidity and other patient, tumour and treatment factors. RESULTS: Overall, 72% of older women received surgery, varying from 86% of 65-69-year olds to 34% of women aged ≥ 85 years. The proportion receiving surgery fell with increasing co-morbidity (Charlson score 0=73%, score 1=66%, score 2+=49%). However, after adjustment for co-morbidity, older age still predicts lack of surgery. Compared with 65-69-year olds, the odds of surgery decreased from 0.74 (95% CI: 0.66-0.83) for 70-74-year olds to 0.13 (95% CI: 0.11-0.14) for women aged ≥ 85 years. CONCLUSION: Although co-morbidity is associated with a reduced likelihood of surgery, it does not explain the shortfall in surgery amongst older women in the UK. Routine data on co-morbidity enables fairer comparison of treatment across population groups but needs to be more complete.

Do height-related variations in insulin-like growth factors underlie the associations of stature with adult chronic disease?

Tall people, particularly those with long legs, have an increased risk of developing cancer but a reduced risk of cardiovascular disease and type II diabetes. We examined associations of stature and body mass index with IGF-I, IGF-II, and IGF binding protein (IGFBP)-2 and IGFBP-3 in 274 men aged 50-70 yr to investigate whether variations in growth factor levels underlie associations of anthropometry with a number of adult diseases. Height and leg and trunk length were not strongly associated with circulating levels of IGF-I, IGF-II, or IGFBP-3. The molar ratio of IGF-I/IGFBP-3 increased with increases in the leg/trunk length ratio (P = 0.06). IGFBP-2 was positively associated with leg length and inversely associated with trunk length. Mean levels of IGFBP-2 (in nanograms per milliliter) across quartiles of increasing leg length were 504.4 493.6, 528.7, and 578.8 (P(trend) = 0.06), and for trunk length were 615.2, 507.2, 498.6, 488.5 (P(trend) < 0.01), suggesting that variations in IGFBP-2, or a factor influencing its levels in the circulation, may contribute to biological mechanisms underlying height-disease associations. We conclude that whereas growth-influencing exposures during childhood, which may operate through effects on IGF-I levels, have long-term influences on disease risk, they do not necessarily program IGF-I levels throughout life. The associations of anthropometry with IGFBP-2 merit additional investigation.

Are diet-prostate cancer associations mediated by the IGF axis? A cross-sectional analysis of diet, IGF-I and IGFBP-3 in healthy middle-aged men.

We examined the association of diet with insulin-like growth factors (IGF) in 344 disease-free men. Raised levels of IGF-I and/or its molar ratio with IGFBP-3 were associated with higher intakes of milk, dairy products, calcium, carbohydrate and polyunsaturated fat; lower levels with high vegetable consumption, particularly tomatoes. These patterns support the possibility that IGFs may mediate some diet-cancer associations.

Recent trends in the use of radical prostatectomy in England: the epidemiology of diffusion.

OBJECTIVE: To describe recent trends in the use of radical prostatectomy (RP) in England, as there is currently no consensus on the most effective treatment for localized prostate cancer, although RP is the treatment of choice among urological surgeons for men aged < 70 years. METHODS: Routine data were assessed to establish the number of RPs performed in England in 1991-99. Age-standardized operation rates were compared by region and socio-economic group, and the geographical spread of use mapped. RESULTS: The number of RPs performed annually increased nearly 20-fold between 1991 and 1999. Rates of surgery were greatest in the London National Health Service (NHS) regions and lowest in the Trent region. Outside London, the risk of surgery in a NHS hospital was significantly greater for men living in the least deprived areas; in London this trend was reversed. CONCLUSION: Rapid increases in the use of RP showed marked regional variations, most likely related to access to prostate-specific antigen testing and the location of surgeons able to carry out radical surgery. By 1999, a third of procedures were still being undertaken in 'low-volume' hospitals, with implications for the quality of care and outcomes. Crucially, these developments occurred in the absence of robust information about the effectiveness of RP. Recent funding of a randomized trial of treatment options in this area is welcome, but wider questions remain about the timing of the evaluation of surgical technologies.

International trends in prostate-cancer mortality in the "PSA ERA".

Incidence and mortality from prostate cancer were rising in most countries until the late 1980s. Following a number of advances in the management of prostate cancer, including introduction of the prostate-specific antigen (PSA) test, there have been reports of declines in mortality in Canada, the United States and the United Kingdom. To investigate the extent to which this pattern was seen in other industrialised countries, we used routinely collected data to explore recent changes in prostate-cancer mortality. Trends in age-standardised death rates between 1979 and 1997 for men aged 50 to 79 years in 24 industrialised countries were compared using join point regression. Join point regression allows estimation of the annual percentage change in death rates and tests for significant changes in trend. During the period studied, age-standardised mortality increased at 1% to 2% per year in most countries. In 7 countries (Canada, United States, Austria, France, Germany, Italy and United Kingdom), a significant down-turn in age-standardised mortality was observed over the period 1988-1991. Trends in age-specific rates within these countries support a period effect on prostate-cancer mortality. Declines in mortality could result from any combination of either artefact, reduction in prostate-cancer incidence, a rise in competing causes of death or changes in the risk of death from prostate cancer. There are inconsistencies in the relationship between national mortality trends and uptake of PSA screening; further research is required to determine whether changes in death rates can be explained by international and secular variations in the treatment of prostate cancer.

Comparison of trends in prostate-cancer mortality in England and Wales and the USA.

Although trends in prostate-cancer screening and disease incidence differ substantially between the USA and England and Wales, trends in mortality are very similar.

A regional collaborative audit of the practice and outcome of carotid endarterectomy in the United Kingdom. Northern Regional Carotid Endarterectomy Audit Group.

OBJECTIVES: To evaluate performance and outcome of carotid endarterectomy (CEA) against agreed audit standards within one English health region. Design a prospective collaborative audit over twelve months (November 1994 to October 1995) involving all surgeons undertaking CEA within one English health region. METHODS: Audit standards were agreed by all participating surgeons at the outset based on existing national guidelines. Data were abstracted from clinical notes. Outcomes were reviewed by clinicians 30 days post-surgery. A confidential individualised report of the results was provided to each surgeon. A survey of participating surgeons sought to evaluate the audit process. RESULTS: Ten surgeons performed 139 CEAs on 134 individuals (64% men). Median per surgeon was 12 (range 1-44). Audit standards were generally achieved: 114 (82%) patients had symptomatic carotid stenosis of 70-99%, 14 (10%) were asymptomatic. The median time from first referral to hospital to operation was 4.8 months (interquartile range 3.0-7.3). The rate of disabling stroke or death at 30 days was 2.2% (95% confidence interval (CI) 0.4-6.4%). Surgeons valued the audit. CONCLUSIONS: The study showed that in the study area CEA was performed predominantly on high-risk patients with low subsequent surgical mortality.

Lessons from patient notification exercises following the identification of hepatitis B e antigen positive surgeons in an English health region.

The results of hepatitis B virus (HBV) serology from notification exercises conducted in cohorts of patients exposed to three surgeons positive for hepatitis B e antigen (HBeAg) identified in one English health region in 1994 and 1995 were reviewed. Of 777 patients notified, serology results at six months or more after exposure were available for 514 individuals who had not received post exposure prophylaxis. In one case DNA analysis confirmed transmission of HBV from surgeon to patient. Pre-existing natural immunity to HBV was found in a further 19 patients, none of whom had evidence of recent infection, and in 13 patients (classified as cases of undetermined origin) transmission during surgery could not be excluded. The overall estimated transmission rate was 0.2% for confirmed cases (95% confidence interval (CI) 0.004-1.1) and 2.7% (95% CI 1.5-4.5) if cases of undetermined origin were included. The management of recall exercises should consider the risks of the operative procedures performed and the time that has elapsed since exposure.

Are variations in the use of carotid endarterectomy explained by population Need? A study of health service utilisation in two English health regions.

OBJECTIVES: to describe variation in utilisation of carotid endarterectomy (CEA) within two English health regions and explore relationships between use, need and proximity to services. DESIGN: consecutive case series of operations. Comparison at a population level with district stroke mortality, hospital admissions and material deprivation. MAIN OUTCOME MEASURES: standardised utilisation rates for CEA and measures of inter-district variability. Spearman's rank correlation coefficients for associations between variables. RESULTS: variation in utilisation rates was considerable (14-fold difference across district populations). More individuals had bilateral surgery in the Yorkshire region than in the Northern (11.7% vs. 5.5%, p=0.002). There was no association between utilisation rates for CEA and district stroke mortality (r=-0.06, 95% CI -0.41 to 0.30) or admission rates for stroke (r=0.17, 95% CI -0.2 to 0.49). There was a strong relationship between residence in districts where services were located and higher utilisation. Rates of CEA were lowest in the regions' most affluent wards. CONCLUSION: use of CEA varies widely, depending on area of residence. Variation is not a consequence of differences in need, but reflects clinical practice and supply of services. There is evidence to suggest unmet need for CEA.

Impaired glucose tolerance and abnormal movements in patients with schizophrenia.

OBJECTIVE: Diabetes mellitus has been implicated as a risk factor for tardive dyskinesia. The authors examined the association between abnormal movements and impaired glucose metabolism, which often precedes the development of overt diabetes, in patients with schizophrenia. METHOD: Twenty-one patients with DSM-IV schizophrenia receiving neuroleptic medication were given oral glucose tolerance tests involving serial glucose and insulin levels. These values were analyzed in relationship to abnormal involuntary movement ratings. RESULTS: Patients with impaired glucose tolerance had higher mean abnormal movement scores than those without glucose intolerance, but this difference was not statistically significant. There was, however, an association between the magnitude of the fasting insulin level and abnormal movements after the authors controlled for fasting glucose level. Additionally, the fasting glucose level predicted abnormal movements after the authors controlled for age. CONCLUSIONS: Hyperinsulinemia and hyperglycemia associated with insulin resistance may potentially contribute to the pathogenesis of tardive dyskinesia. Findings from this small cross-sectional study suggest a possible relationship that requires clarification through larger, longitudinal studies.

Sex differences in naturally occurring leg muscle pain and exertion during maximal cycle ergometry.

This investigation examined the role of sex in perceptions of leg muscle pain during exercise. Males (N = 26; age = 23.2 +/- 3.9) and females (N = 26; age = 21.9 +/- 3.5) matched on weekly energy expenditure completed a ramped maximal cycle ergometry test. Leg muscle pain thresholds were determined and pain intensity ratings as well as ratings of perceived exertion were obtained during and after exercise. The power output at pain threshold was lower in females (129.9 +/- 46.5 watts) compared to males (148.2 +/- 56.6 watts). Peak power output and peak pain intensity ratings were lower (P < 0.001) in females (211.3 +/- 39.1 watts; 5.5 +/- 2.9) compared to males (303.6 +/- 27.5 watts; 8.5 +/- 2.3). A Sex X Relative Intensity (i.e., % peak power output) ANOVA revealed that females reported lower pain ratings at each relative intensity examined (F = 17.7; df = 1.50; p < 0.001). The primary conclusion of this investigation is that females rate naturally occurring leg muscle pain as less intense than males when data are relativized to peak power output.

The life course of schizophrenia: age and symptom dimensions.

The life course of schizophrenia has eluded description for several reasons, including fluctuations in diagnostic criteria over the past century, and dramatic changes in treatment and expectations of the mentally ill. This study compared symptoms within a group of patients spanning ages 14 through 73. The three symptom dimensions (psychotic, disorganized and negative) were examined separately in relation to age. Using a multivariate analysis, the effects of age, sex and institutional status were found to have main effects for symptom severity with no interaction effects. The effect of age was significant in the negative direction for positive and disorganized symptoms. Age was specifically associated with decreased hallucinations, delusions, bizarre behavior and inappropriate affect. There was no age effect for formal thought disorder, nor was there an age effect for negative symptoms. Institutionalization was associated with greater symptom severity in all dimensions. Male gender was associated with greater severity of negative symptoms. We conclude that psychotic and disorganized symptoms are likely to be of lesser severity in older patients with schizophrenia, while negative symptoms tend to persist. Clinically, these findings suggest that medications targeting negative symptoms may confer the greatest benefit in treating the older patient with schizophrenia.