Comparison of quadrant-specific breast cancer incidence trends in the United States and England between 1975 and 2013

Background UK breast cancer incidence rates suggest that upper outer quadrant (UOQ) cancers have risen disproportionately compared with other areas over time. We aimed to provide a comparison of the trend in quadrant-specific breast cancer incidence between the United States (US) and England, and determine whether a disproportionate UOQ increase is present. Methods Surveillance Epidemiology and End Results (SEER) cancer registry data were obtained on 630,007 female breast cancers from 1975 to 2013. English cancer registry data were obtained on 1,121,134 female breast cancers from 1979 to 2013. Temporal incidence changes were analysed using negative binomial regression. Interaction terms determined whether incidence changes were similar between sites. Results English breast cancer incidence in the UOQ rose significantly from 13% to 28% from 1979 to 2013 whereas no significant increase was observed among SEER data. The significant interaction between quadrant and year of diagnosis (p < 0.001) in both SEER and English data indicates that breast cancer incidence in each quadrant changed at a different rate. Incidence in the UOQ rose disproportionately compared to the nipple (SEER IRR = 0.81, p < 0.001; England IRR = 0.78, p < 0.001) and axillary tail (SEER IRR = 0.87, p = 0.018; England IRR = 0.69, p < 0.001) in both SEER and England. In addition, incidence rose disproportionately in the UOQ compared to non-site-specific tumours in England (Overlapping lesions IRR = 0.81, p = 0.002; NOS IRR = 0.78, p < 0.001). The proportion of non-site-specific tumours was substantially higher in England than SEER throughout the study period (62% in England; 39% in SEER). Conclusions Breast cancer incidence in the UOQ increased disproportionately compared to non-site-specific tumours in England but not in SEER, likely due to the decrease in non-site-specific tumours observed in England over time. There may be real differences in incidence between the two countries, possibly due to differences in aetiology, but is much more likely to be an artefact of changing data collection methods and improvements in site coding in either country

Birthweight and childhood wheezing disorders: a systematic review and meta-analysis

BACKGROUND: Previous observational studies have claimed that birthweight and childhood wheezing disorders are associated although the results remained inconsistent. One systematic review and two systematic reviews that included meta-analyses reported inconsistent results. We aimed to conduct a systematic review and meta-analysis to investigate this. METHODS: An online search of published papers linking childhood asthma and wheezing disorders with birthweight up to February 2014 was carried out using EMBASE and Medline medical research databases. Summary odds ratios (OR) were estimated using random-effects models. Sub-group meta-analyses were performed to assess the robustness of risk associations and between-study heterogeneity. RESULTS: A total of 37 studies comprising 1,712,737 participants were included in our meta-analysis. The unadjusted summary ORs for risk of childhood wheezing disorders associated with low birthweight (4.0kg) as compared to the 2.5-4.0kg birthweight group was 1.02 (95% CI: 0.99 to 1.04, P=0.13). There was substantial heterogeneity in the unadjusted low birthweight risk estimates which was not accounted for by predefined study characteristics. There was no significant heterogeneity in the high birthweight risk estimates. There was some evidence of funnel plot asymmetry and small study effects in the low birthweight (2.5kg versus ≥2.5kg and <2.5kg versus 2.5-4.0kg) odds ratio estimates. CONCLUSION: Our results suggest that low birth (<2.5kg) is an independent risk factor for wheezing disorders during childhood and adolescence although there was substantial heterogeneity among the risk estimates. However, we found no significant association of high birthweight with wheezing disorders

Effects of birthweight and growth on childhood wheezing disorders: findings from the Born in Bradford Cohort.

Objectives To examine the effects of birth weight and childhood growth on childhood wheezing disorders. We hypothesised that low birth weight and fast growth during early age would increase the risk of wheezing disorders. Setting Observational secondary analysis of data from the Born in Bradford cohort. Participants All children who were born at the Bradford Royal Infirmary hospital between March 2007 and December 2010 were eligible for the study. A total of 13 734 and 1598 children participated in the analyses of the effects of birth weight and growth on wheezing disorders, respectively. Primary and secondary outcome measures Wheezing disorders diagnosis (diagnosed as asthma or had wheezing symptom) during the ages of 0–7 years were the primary outcome measures. Diagnosis of asthma and occurrence of wheezing during the same period were secondary outcome measures. Birth weight was classified as normal (2.5–4.0 kg), low (4.0 kg). Growth mixture models were used to drive growth pattern outcomes which were classified as ‘normal’, ‘fast’ and ‘slow’ growth based on their velocities between birth and 36 months. Results The adjusted relative risks (RRs) of wheezing disorders diagnosis for the low and high birthweight children were 1.29 (95% CI 1.12 to 1.50; p=0.001) and 0.91 (95% CI 0.79 to 1.04; p=0.17), respectively. The adjusted RRs of wheezing disorders diagnosis were 1.30 (95% CI 0.56 to 3.06; p=0.54) and 0.60 (95% CI 0.16 to 2.18; p=0.44), respectively, for the ‘fast’ and ‘slow’ growth as compared with the ‘normal’ growth. Conclusions Low birth weight is associated with an increased risk of wheezing disorders; however, there is a weak evidence that suggests high birthweight children have a reduced risk in this birth cohort. Low birth weight coupled with a slower growth until 3 months and a sharp growth between 3 and 12 months has an increased risk of wheezing disorders diagnosi

The Authors Respond

Although the studies highlighted in Kinlen and Peto’s letter describe situations they take to be “national in scope”, none of these adopted the ‘region-wide’ analysis we recommend. Rather, these studies have focussed on rural areas with small populations experiencing extreme levels of inward-migration that had been selected from larger regions/nation states. To definitively avoid bias, our study points to the need for comparisons of areas with varying levels of inward migration, either by comparing all areas within an entire region/nation state or random subsets thereof

Access to Principal Treatment Centres and survival rates for children and young people with cancer in Yorkshire, UK

Background: Principal Treatment Centres (PTC) were established to provide age-appropriate care as well as clinical expertise for children and young people with cancer. However, little is known about the effects of specialist treatment centres on survival outcomes especially for teenagers and young adults. This population-based study aimed to describe access to PTC and the associated trends in survival for 0–24 year olds accounting for stage of disease at presentation and treatment. Methods: Patients diagnosed from 1998–2009 aged 0–24 years were extracted from the Yorkshire Specialist Register of Cancer in Children and Young People, including information on all treating hospitals, followed-up until 31st December 2014. The six commonest cancer types were included: leukaemia (n = 684), lymphoma (n = 558), CNS tumours (n = 547), germ cell tumours (n = 364), soft tissue sarcomas (n = 171) and bone tumours (n = 163). Treatment was categorised into three groups: ‘all’, ‘some’ or ‘no’ treatment received at a PTC. Treatment at PTC was examined by diagnostic group and patient characteristics. Overall survival was modelled using Cox regression adjusting for case-mix including stage, treatment and other socio-demographic and clinical characteristics. Results: Overall 72% of patients received all their treatment at PTC whilst 13% had no treatment at PTC. This differed by diagnostic group and age at diagnosis. Leukaemia patients who received no treatment at PTC had an increased risk of death which was partially explained by differences in patient case-mix (adjusted Hazard Ratio (HR) = 1.73 (95%CI 0.98–3.04)). Soft tissue sarcoma patients who had some or no treatment at PTC had better survival outcomes, which remained after adjustment for patient case-mix (adjusted HR = 0.48 (95%CI 0.23–0.99)). There were no significant differences in outcomes for other diagnostic groups (lymphoma, CNS tumours, bone tumours and germ cell tumours). For leukaemia patients survival outcomes for low risk patients receiving no treatment at PTC were similar to high risk patients who received all treatment at PTC, implying a benefit for care at the PTC. Conclusion: This study demonstrates that for leukaemia patients receiving treatment at a PTC is associated with improved survival that may compensate for a poorer prognosis presentation. However, further information on risk factors is needed for all diagnostic groups in order to fully account for differences in patient case-mix

Meta-analysis of the normal diffusion tensor imaging values of the peripheral nerves in the upper limb

Peripheral neuropathy affects 1 in 10 adults over the age of 40 years. Given the absence of a reliable diagnostic test for peripheral neuropathy, there has been a surge of research into diffusion tensor imaging (DTI) because it characterises nerve microstructure and provides reproducible proxy measures of myelination, axon diameter, fibre density and organisation. Before researchers and clinicians can reliably use diffusion tensor imaging to assess the ‘health’ of the major nerves of the upper limb, we must understand the “normal” range of values and how they vary with experimental conditions. We searched PubMed, Embase, medRxiv and bioRxiv for studies which reported the findings of DTI of the upper limb in healthy adults. Four review authors independently triple extracted data. Using the meta suite of Stata 17, we estimated the normal fractional anisotropy (FA) and diffusivity (mean, MD; radial, RD; axial AD) values of the median, radial and ulnar nerve in the arm, elbow and forearm. Using meta-regression, we explored how DTI metrics varied with age and experimental conditions. We included 20 studies reporting data from 391 limbs, belonging to 346 adults (189 males and 154 females, ~ 1.2 M:1F) of mean age 34 years (median 31, range 20–80). In the arm, there was no difference in the FA (pooled mean 0.59 mm2/s [95% CI 0.57, 0.62]; I2 98%) or MD (pooled mean 1.13 × 10–3 mm2/s [95% CI 1.08, 1.18]; I2 99%) of the median, radial and ulnar nerves. Around the elbow, the ulnar nerve had a 12% lower FA than the median and radial nerves (95% CI − 0.25, 0.00) and significantly higher MD, RD and AD. In the forearm, the FA (pooled mean 0.55 [95% CI 0.59, 0.64]; I2 96%) and MD (pooled mean 1.03 × 10–3 mm2/s [95% CI 0.94, 1.12]; I2 99%) of the three nerves were similar. Multivariable meta regression showed that the b-value, TE, TR, spatial resolution and age of the subject were clinically important moderators of DTI parameters in peripheral nerves. We show that subject age, as well as the b-value, TE, TR and spatial resolution are important moderators of DTI metrics from healthy nerves in the adult upper limb. The normal ranges shown here may inform future clinical and research studies

A cross-sectional survey of healthcare professionals to determine what they believe constitutes 'specialist' care for teenage and young adult patients with cancer

Objectives: To examine the attitudes of UK healthcare professionals towards what they believe constitutes specialist care for teenage and young adult (TYA) patients with cancer, to determine which factors they considered to be the most important components of specialist TYA care, and whether opinion varied between clinical specialties and reflected the drivers for care improvements within National Health Service (NHS) policy. Design and methods: The study utilised a crosssectional survey, using Likert scales, to assess attitudes towards specialist care. Responses were grouped using model-based clustering methods implemented in LatentGold 4.5. Setting: Participants from 98 NHS trusts in the UK were invited to participate in the study. Participants: 691 healthcare professionals involved in the management of TYA patients were approached; of these, 338 responded. Results: 338 healthcare professionals responded (51.9% of those invited). Responses were grouped into three clusters according to the pattern of responses to the questions. One cluster rated age-appropriate care above all else, the second rated both age and site-appropriate care highly while the third assigned more importance to site-specific care. Overall, the psychosocial and supportive aspects of care were rated highest while statements relating to factors known to be important (access to clinical trials, treatment at a high volume centre and specialist diagnostics) were not rated as highly as expected. Conclusions: Attitudes varied widely between professionals treating TYA patients with cancer as to what constitutes key aspects of specialist care. Further work is needed to quantify the extent to which this influences practice

Risk of Cerebrovascular Events in 178 962 Five-Year Survivors of Cancer Diagnosed at 15 to 39 Years of Age: The TYACSS (Teenage and Young Adult Cancer Survivor Study)

Background: Survivors of teenage and young adult (TYA) cancer are at risk of cerebrovascular events, but the magnitude of and extent to which this risk varies by cancer type, decade of diagnosis, age at diagnosis and attained age remains uncertain. This is the largest ever cohort study to evaluate the risks of hospitalisation for a cerebrovascular event among long-term survivors of TYA cancer. Methods:The population-based Teenage and Young Adult Cancer Survivor Study (N=178,962) was linked to Hospital Episode Statistics data for England to investigate the risks of hospitalisation for a cerebrovascular event among 5-year survivors of cancer diagnosed when aged 15-39 years. Observed numbers of first hospitalisations for cerebrovascular events were compared to that expected from the general population using standardised hospitalisation ratios (SHR) and absolute excess risks (AER) per 10,000 person-years. Cumulative incidence was calculated with death considered a competing risk. Results: Overall, 2,782 cancer survivors were hospitalised for a cerebrovascular event—40% higher than expected (SHR=1.4, 95% confidence interval [CI]=1.3-1.4). Survivors of central nervous system (CNS) tumours (SHR=4.6, CI=4.3-5.0), head & neck tumours (SHR=2.6, CI=2.2-3.1) and leukaemia (SHR=2.5, CI=1.9-3.1) were at greatest risk. Males had a significantly higher AER than females (AER=7 versus 3), especially among head & neck tumour survivors (AER=30 versus 11). By age 60, 9%, 6% and 5% of CNS tumour, head & neck tumour, and leukaemia survivors, respectively, had been hospitalised for a cerebrovascular event. Beyond age 60, every year 0.4% of CNS tumour survivors were hospitalised for a cerebral infarction (versus 0.1% expected. Whereas at any age, every year 0.2% of head & neck tumour survivors were hospitalised for a cerebral infarction 7 (versus 0.06% expected). Conclusions: Survivors of a CNS tumour, head & neck tumour, and leukaemia are particularly at risk of hospitalisation for a cerebrovascular event. The excess risk of cerebral infarction among CNS tumour survivors increases with attained age. For head & neck tumour survivors this excess risk remains high across all ages. These groups of survivors, and in particular males, should be considered for surveillance of cerebrovascular risk factors and potential pharmacological interventions for cerebral infarction prevention

Socio-economic patterning in early mortality of patients aged 0-49 years diagnosed with primary bone cancer in Great Britain, 1985-2008

Background: Studies have shown marked improvements in survival between 1981 and 2000 for Ewing sarcoma patients but not for osteosarcoma. This study aimed to explore socio-economic patterning in early mortality rates for both tumours. Procedure: The study analysed all 2432 osteosarcoma and 1619 Ewing sarcoma cases, aged 0-49 years, diagnosed in Great Britain 1985-2008 and followed to 31/12/2009. Logistic regression models were used to calculate risk of dying within three months, six months, one year, three years and five years after diagnosis. Associations with Townsend deprivation score and its components were examined at small-area level. Urban/rural status was studied at larger regional level. Results: For osteosarcoma, after age adjustment, mortality at three months, six months and one year was associated with higher area unemployment, OR = 1·05 (95% CI 1·00, 1·10), OR = 1·04 (95% CI 1·01, 1·08) and OR = 1·04 (95% CI 1·02, 1·06) respectively per 1% increase in unemployment. Mortality at six months was associated with greater household non-car ownership, OR = 1·02 (95% CI 1·00, 1·03). For Ewing sarcoma, there were no significant associations between mortality and overall Townsend score, nor its components for any time period. For both tumours increasing mortality was associated with less urban and more remote rural areas. Conclusions: This study found that for osteosarcoma, early mortality was associated with residence at diagnosis in areas of higher unemployment, suggesting risk of early death may be socio-economically determined. For both tumours, distance from urban centres may lead to greater risk of early death