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

Rising Rates of All Types of Diabetes in South Asian and Non-South Asian Children and Young People Aged 0–29 Years in West Yorkshire, U.K., 1991–2006

OBJECTIVE: To investigate incidence trends of all diabetes types in all children and young people and in the south Asian subpopulation. RESEARCH DESIGN AND METHODS: Annual incidence per 100,000 and time trends (1991-2006) were analyzed for 2,889 individuals aged 0-29 years diagnosed with diabetes while resident in West Yorkshire, U.K. RESULTS: Diagnoses comprised type 1 (83%), type 2 (12%), maturity-onset diabetes of the young (0.7%), "J"-type/other (0.1%), and uncertain/unclassified (4%). There was a lower incidence of type 1 and a threefold excess of type 2 in south Asians compared with non-south Asians. Type 1 incidence leveled out and type 2 increased after the first south Asian case of type 2 was diagnosed in 1999. Type 2 and unclassified diabetes incidence rose in all population subgroups. CONCLUSIONS: The burden of diabetes increased over time for both ethnic groups, with a significant excess of type 2 diabetes in south Asians. The rising incidence of type 1 diabetes in south Asians attenuated as type 2 diabetes increased after 1999

FDG PET/CT versus Bone Marrow Biopsy for Diagnosis of Bone Marrow Involvement in Non-Hodgkin Lymphoma:A Systematic Review

The management of non-Hodgkin lymphoma (NHL) patients requires the identification of bone marrow involvement (BMI) using a bone marrow biopsy (BMB), as recommended by international guidelines. Multiple studies have shown that [F-18]FDG positron emission tomography, combined with computed tomography (PET/CT), may provide important information and may detect BMI, but there is still an ongoing debate as to whether it is sensitive enough for NHL patients in order to replace or be used as a complimentary method to BMB. The objective of this article is to systematically review published studies on the performance of [F-18]FDG PET/CT in detecting BMI compared to the BMB for NHL patients. A population, intervention, comparison, and outcome (PICO) search in PubMed and Scopus databases (until 1 November 2021) was performed. A total of 41 studies, comprising 6147 NHL patients, were found to be eligible and were included in the analysis conducted in this systematic review. The sensitivity and specificity for identifying BMI in NHL patients were 73% and 90% for [F-18]FDG PET/CT and 56% and 100% for BMB. For aggressive NHL, the sensitivity and specificity to assess the BMI for the [F-18]FDG PET/CT was 77% and 94%, while for the BMB it was 58% and 100%. However, sensitivity and specificity to assess the BMI for indolent NHL for the [F-18]FDG PET/CT was 59% and 85%, while for the BMB it was superior, and equal to 94% and 100%. With regard to NHL, a [F-18]FDG PET/CT scan can only replace BMB if it is found to be positive and if patients can be categorized as having advanced staged NHL with high certainty. [F-18]FDG PET/CT might recover tumors missed by BMB, and is recommended for use as a complimentary method, even in indolent histologic subtypes of NHL

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

Osteonecrosis in patients with acute lymphoblastic leukaemia: a national questionnaire study

Objectives: To establish prevalence, management and long-term outcomes of osteonecrosis (ON) in young people diagnosed with acute lymphoblastic leukaemia (ALL) between 2003 and 2011. Design, setting, participants: This study assessed ON in 3113 patients aged 1–24 years who participated in the UK national leukaemia study UKALL 2003. UKALL 2003 recruited patients in 40 UK hospitals between 2003 and 2011 and included patients between ages 1 and 25 diagnosed with ALL. Results: 170 patients were diagnosed with ON, giving a prevalence of 5.5%. The multivariable analysis showed that the risk of ON was highest for children aged between 10 and 20 years (ages 10–15 years, OR 23.7, 95% CI 14.8 to 38.0; ages 16–20 years, OR 22.5, 95% CI 12.7 to 39.8, compared with age <10 years). Among ethnic groups, Asian patients had the highest risk of ON (OR 1.92, 95% CI 1.1 to 3.6, compared with White patients). Eighty-five per cent of patients with ON had multifocal ON. Thirty-eight per cent of patients with ON required surgery and 19% of patients with ON required a hip replacement. Fifteen per cent of patients who had surgery still describe significant disability or use of a wheelchair. Conclusions: ON has considerable morbidity for patients being treated for ALL, with a high burden of surgery. Age and ethnicity were found to be the most significant risk factors for development of ON, with Asian patients and patients aged 10–20 years at diagnosis of ALL at greatest risk. These results will help risk stratify patients at diagnosis of ALL, and help tailor future prospective studies in this area

Is there a sex difference in mortality rates for deaths occurring in paediatric intensive care units? Systematic literature review protocol

Introduction In the general population, female children have been reported to have a survival advantage. For children admitted to paediatric intensive care units (PICUs), mortality has been reported to be lower in males despite the higher admission rates for males into intensive care. This apparent sex reversal in PICU mortality is not well studied. To address this, we propose to conduct a systematic literature review to summarise the available evidence. Our review will study the reported differences in mortality between males and females aged 0-17, who died in a PICU, to examine if there is a difference between the two sexes in PICU mortality, and if so, to describe the magnitude and direction of this difference. Methods and analysis Studies that directly or indirectly addressed the association between sex and mortality in children admitted to intensive care will be eligible for inclusion. Studies that directly address the association will be eligible for data extraction. The search strings were based on terms related to the population (children in intensive care), the exposure (sex) and the outcome (mortality). We used the databases MEDLINE (1946-2020), Embase (1980-2020) and Web of Science (1985-2020) as these cover relevant clinical publications. We will assess the reliability of included studies using the risk of bias in observational studies of exposures tool. We will consider a pooled effect if we have at least three studies with similar periods of follow up and adjustment variables. Ethics and dissemination Ethical approval is not required for this review as it will synthesise data from existing studies. This manuscript is a part of a larger data linkage study, for which Ethical approval was granted. Dissemination will be via peer-reviewed journals and via public and patient groups. PROSPERO registration number CRD42020203009

Survival from cancer in young people: An overview of late effects focusing on reproductive health

This paper provides a summary of the areas of survival from childhood, teenage and young adult cancers and the significant late effects that can arise from treatment; with particular focus on the area of reproductive health and the impact on both fertility and pregnancy. To complete this review, Web of Science and MEDLINE were used. Search terms included: “"survival AND childhood OR teenage OR young adult cancer", "late effects", "childhood cancer", "teenage AND/OR young adult cancer", AND "fertility after cancer" OR "pregnancy AND cancer" OR "fertility preservation”. Additionally, the clinical expertise of the authors was drawn upon. Childhood cancer is a thankfully rare occurrence; however, the incidence is increasing. Survival rates remain high and this means that a growing population of childhood and young adult cancer survivors are reaching adulthood. For some of these adults, although cured of their cancer, they are now facing a future with lasting effects on their health from their treatments. These effects, commonly referred to as late effects, are defined as health problems related either directly to the underlying cancer or to its treatment and which occur months or years after treatment has finished. Reproductive health is an important consideration for these patients, and although many will be able to conceive naturally, some will exhibit impaired fertility after their treatments. This can include difficulties at all points along the path from conception to delivery of a live, healthy offspring. High‐quality, large‐population evidence is sparse in many areas relating to fertility risk from treatment and the maternal and fetal health of childhood cancer survivors. Yet given the potential for complications, the authors advocate consideration of fertility at the time of diagnosis and before potentially gonadotoxic treatment

Comparison of ethnic group classification using naming analysis and routinely collected data: application to cancer incidence trends in children and young people

Objective: Inpatient Hospital Episode Statistics (HES) ethnicity data are available but not always collected and data quality can be unreliable. This may have implications when assessing outcomes by ethnicity. An alternative method for assigning ethnicity is using naming algorithms. We investigate if the association between ethnicity and cancer incidence varied dependent upon how ethnic group was assigned. Design: Population-based cancer registry cohort study Setting: Yorkshire, UK Participants: Cancer registrations from 1998-2009 in children and young people (0-29 years) from a specialist cancer register in Yorkshire, UK (N=3998) were linked to inpatient HES data to obtain recorded ethnicity. Patient?s names, recorded in the cancer register, were matched to an ethnic group using the naming algorithm software Onomap. Each source of ethnicity was categorised as White, South Asian (SA) or Other and a further two indicators were defined based on the combined ethnicities of HES and Onomap, one prioritising HES results, the other prioritising Onomap. Outcomes: Incidence rate ratios (IRR) between ethnic groups were compared using Poisson regression for all cancers combined, leukaemia, lymphoma and central nervous system (CNS) tumours. Results: Depending on the indicator used, 7.1% to 8.6% of the study population were classified as SA. For all cancers there were no statistically significant differences between White and SA groups using any indicator, however for lymphomas significant differences were only evident using one of the ?Combined? indicators (IRR=1.36 (95%CI 1.08, 1.71)) and for CNS tumours incidence was lower using three of the four indicators. For the other ethnic group the IRR for all cancers ranged from 0.78 (0.65, 0.94) to 1.41 (1.23, 1.62). Conclusions: Using different methods of assigning ethnicity can result in different estimates of ethnic variation in cancer incidence. Combining ethnicity from multiple sources results in a more complete estimate of ethnicity than the use of one single source

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