Paediatric acute lymphoblastic leukaemia and caesarean section : A report from the United Kingdom Childhood Cancer Study (UKCCS)

BACKGROUND: Reports have suggested that children born by caesarean initiated before labour onset may be at increased risk of developing acute lymphoblastic leukaemia (ALL). However, with most data being derived from case-control study interviews, information on the underpinning reasons for caesarean section is sparse, and evidence is conflicting. OBJECTIVES: Use clinical records compiled at the time of delivery to investigate the association between childhood ALL and caesarean delivery; examining timing in relation to labour onset, and reasons for the procedure. METHODS: Data are from the UK Childhood Cancer Study, a population-based case-control study conducted in the 1990s, when caesarean section rates were relatively low, in England, Scotland, and Wales. Children with ALL were individually matched to two controls on sex, date of birth, and region of residence. Information on mode of delivery and complications was abstracted from obstetric records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression models adjusted for matching variables and relevant covariates. RESULTS: Around 75% of the 1034 cases and 1914 controls were born through unassisted vaginal delivery. Caesarean delivery was as frequent in cases and controls (OR 1.07, 95% CI 0.84, 1.36). No association was observed between ALL and caesarean delivery either during or before labour, with adjusted ORs of 1.08 (95% CI 0.78, 1.48) and 1.09 (95% CI 0.78, 1.53), respectively. For B-cell ALL, the ORs were 1.14 (95% CI 0.81, 1.59) for caesarean during labour and 1.21 (95% CI 0.85, 1.72) for prelabour. The underpinning reasons for caesarean delivery differed between cases and controls; with preeclampsia, although very rare, being more common amongst cases born by caesarean (OR 8.91, 95% CI 1.48, 53.42). CONCLUSIONS: Our obstetric record-based study found no significant evidence that caesarean delivery increased the risk of childhood ALL, either overall or when carried out before labour

Palliative care among heart failure patients in primary care: A comparison to cancer patients using english family practice data

© 2014 Gadoud et al. Introduction: Patients with heart failure have a significant symptom burden and other palliative care needs often over a longer period than patients with cancer. It is acknowledged that this need may be unmet but by how much has not been quantified in primary care data at the population level. Methods: This was the first use of Clinical Practice Research Datalink, the world's largest primary care database to explore recognition of the need for palliative care. Heart failure and cancer patients who had died in 2009 aged 18 or over and had at least one year of primary care records were identified. A palliative approach to care among patients with heart failure was compared to that among patients with cancer using entry onto a palliative care register as a marker for a palliative approach to care. Results: Among patients with heart failure, 7% (234/3 122) were entered on the palliative care register compared to 48% (3 669/7 608) of cancer patients. Of heart failure patients on the palliative care register, 29% (69/234) were entered onto the register within a week of their death. Conclusions: This confirms that the stark inequity in recognition of palliative care needs for people with heart failure in a large primary care dataset. We recommend a move away from prognosis based criteria for palliative care towards a patient centred approach, with assessment of and attention to palliative needs including advance care planning throughout the disease trajectory

Illness patterns prior to diagnosis of lymphoma : Analysis of UK medical records

Background: Increased understanding of the relationship between lymphomas and co-morbidities is likely to provide valuable insights into the natural history of these disorders. Methods: 761 cases with lymphoma (310 diffuse large B-cell [DLBCL]; 226 follicular [FL]; and 225 Hodgkin [HL]) and 761 unaffected age and sex matched controls were recruited and their histories of infection and non-infection diagnoses in primary care records were compared using negative binomial regression. Results: No differences were observed between the infectious illness patterns of DLBCL and FL cases and their matched controls over the 15 years preceding lymphoma diagnosis. A marked excess of infectious illness episodes was recorded for HL cases compared to their controls; evident at least a decade prior to HL diagnosis. For non-infectious consultations an excess of case over control visits emerged 4-6 years before DLBCL and FL diagnosis; no specific co-morbidity associations were found. No case-control differences for non-infectious conditions were apparent for HL. Conclusion: There are substantial variations in patterns of illness prior to diagnosis of the three lymphoma subtypes examined. The excess of infectious diagnoses prior to HL may point to underlying immune abnormality, but there was no suggestion of this for DLBCL and FL where a generalized excess of non-infectious conditions was evident. (C) 2010 Elsevier Ltd. All rights reserved

Early life exposure to diagnostic radiation and ultrasound scans and risk of childhood cancer: case-control study

Objective To examine childhood cancer risks associated with exposure to diagnostic radiation and ultrasound scans in utero and in early infancy (age 0-100 days)

Identification of depression in women during pregnancy and the early postnatal period using the Whooley questions and the Edinburgh Postnatal Depression Scale : protocol for the Born and Bred in Yorkshire: PeriNatal Depression Diagnostic Accuracy (BaBY PaNDA) study

INTRODUCTION: Perinatal depression is well recognised as a mental health condition but <50% of cases are identified by healthcare professionals in routine clinical practice. The Edinburgh Postnatal Depression Scale (EPDS) is often used to detect symptoms of postnatal depression in maternity and child services. The National Institute for Health and Care Excellence (NICE) recommends 2 'ultra-brief' case-finding questions (the Whooley questions) to aid identification of depression during the perinatal period, but this recommendation was made in the absence of any validation studies in a perinatal population. Limited research exists on the acceptability of these depression case-finding instruments and the cost-effectiveness of routine screening for perinatal depression. METHODS AND ANALYSIS: The diagnostic accuracy of the Whooley questions and the EPDS will be determined against a reference standard (the Client Interview Schedule-Revised) during pregnancy (around 20 weeks) and the early postnatal period (around 3-4 months post partum) in a sample of 379 women. Further outcome measures will assess a range of psychological comorbidities, health-related quality of life and resource utilisation. Women will be followed up 12 months postnatally. The sensitivity, specificity and predictive values of the Whooley questions and the EPDS will be calculated against the reference standard at 20 weeks pregnancy and 3-4 months post partum. Acceptability of the depression case-finding instruments to women and healthcare professionals will involve in-depth qualitative interviews. An existing decision analytic model will be adapted to determine the cost-effectiveness of routine screening for perinatal depression. ETHICS AND DISSEMINATION: This study is considered low risk for participants. Robust protocols will deal with cases where risk of depression, self-harm or suicide is identified. The protocol received favourable ethical opinion from the North East-York Research Ethics Committee (reference: 11/NE/0022). The study findings will be published in peer-reviewed journals and presented at relevant conferences

Allergy and Risk of Childhood Leukaemia: Results from the UKCCS

We investigated the relationship between childhood leukaemia and preceding history of allergy. A nationwide case-control study of childhood cancers was conducted in the United Kingdom with population-based sampling of cases (n = 839) and controls (n = 1,337), matched on age, sex and region of residence. Information about clinically diagnosed allergies was obtained from primary care records. More than a third of subjects had at least one allergy diagnosed prior to leukaemia diagnosis (cases) or pseudo-diagnosis (controls). For both total acute lymphoblastic leukaemia (ALL) and common-ALL/precursor B-cell ALL (c-ALL), a history of eczema was associated with a 30% significant reduction in risk: the odds ratios (OR) and 95% confidence intervals (CI) were 0.70 (0.51-0.97) and 0.68 (0.48-0.98), respectively. Similar associations were observed for hayfever (OR = 0.47; 95% CI: 0.26-0.85 and OR = 0.62; 95% CI: 0.33-1.16 for ALL and c-ALL, respectively). No such patterns were seen either for asthma and ALL, or for any allergy and acute myeloid leukaemia. A comparative analysis of primary care records with parents recall of allergy revealed only moderate agreement with contemporaneous clinical diagnoses for both cases and controls - confirming the unreliability of parental report at interview. Our finding of a reciprocal relationship between allergy and ALL in children is compatible with the hypothesis that a dysregulated immune response is a critical determinant of childhood ALL

Identifying perinatal depression with case-finding instruments : a mixed-methods study (BaBY PaNDA – Born and Bred in Yorkshire PeriNatal Depression Diagnostic Accuracy)

Background: Perinatal depression is well recognised as a mental health condition but < 50% of cases are identified in routine practice. A case-finding strategy using the Whooley questions is currently recommended by the National Institute for Health and Care Excellence. Objectives: To determine the diagnostic accuracy, acceptability and cost-effectiveness of the Whooley questions and the Edinburgh Postnatal Depression Scale (EPDS) to identify perinatal depression. Design: A prospective diagnostic accuracy cohort study, with concurrent qualitative and economic evaluations. Setting: Maternity services in England. Participants: A total of 391 pregnant women. Main outcome measures: Women completed the Whooley questions, EPDS and a diagnostic reference standard (Clinical Interview Schedule – Revised) during pregnancy (20 weeks) and postnatally (3–4 months). Qualitative interviews were conducted with health professionals (HPs) and a subsample of women. Results: Diagnostic accuracy results: depression prevalence rates were 10.3% during pregnancy and 10.5% postnatally. The Whooley questions and EPDS (cut-off point of ≥ 10) performed reasonably well, with comparable sensitivity [pregnancy: Whooley questions 85.0%, 95% confidence interval (CI) 70.2% to 94.3%; EPDS 82.5%, 95% CI 67.2% to 92.7%; postnatally: Whooley questions 85.7%, 95% CI 69.7% to 95.2%; EPDS 82.9%, 95% CI 66.4% to 93.4%] and specificity (pregnancy: Whooley questions 83.7%, 95% CI 79.4% to 87.4%; EPDS 86.6%, 95% CI 82.5% to 90.0%; postnatally: Whooley questions 80.6%, 95% CI 75.7% to 84.9%; EPDS 87.6%, 95% CI 83.3% to 91.1%). Diagnostic accuracy of the EPDS (cut-off point of ≥ 13) was poor at both time points (pregnancy: sensitivity 45%, 95% CI 29.3% to 61.5%, and specificity 95.7%, 95% CI 93.0% to 97.6%; postnatally: sensitivity 62.9%, 95% CI 44.9% to 78.5%, and specificity 95.7%, 95% CI 92.7% to 97.7%). Qualitative evaluation: women and HPs were supportive of screening/case-finding for perinatal depression. The EPDS was preferred to the Whooley questions by women and HPs, mainly because of its ‘softer’ wording. Whooley question 1 was thought to be less acceptable, largely because of the terms ‘depressed’ and ‘hopeless’, leading to women not revealing their depressive symptoms. HPs identified a ‘patient-centred’ environment that focused on the mother and baby to promote discussion about mental health. Cost-effectiveness results: screening/case-finding using the Whooley questions or the EPDS alone was not the most cost-effective strategy. A two-stage strategy, ‘Whooley questions followed by the Patient Health Questionnaire’ (a measure assessing depression symptomatology), was the most cost-effective strategy in the range between £20,000 and £30,000 per quality-adjusted life-year in both the prenatal and postnatal decision models. Limitations: Perinatal depression diagnosis was not cross-referenced with women’s medical records so the proportion of new cases identified is unknown. The clinical effectiveness and cost-effectiveness of screening/case-finding strategies was not assessed as part of a randomised controlled trial. Conclusions: The Whooley questions and EPDS had acceptable sensitivity and specificity, but their use in practice might be limited by low predictive value and variation in their acceptability. A two-stage strategy was more cost-effective than single-stage strategies. Neither case-finding instrument met National Screening Committee criteria. Future work: The yield of screening/case-finding should be established with reference to health-care records. The clinical effectiveness and cost-effectiveness of screening/case-finding for perinatal depression needs to be tested in a randomised controlled trial. Funding: The National Institute for Health Research Health Services and Delivery Research programme

A MIXED METHOD STUDY EXPLORING A PALLIATIVE CARE APPROACH FOR PEOPLE WITH ADVANCED HEART FAILURE

Background Patients with advanced heart failure have significant unmet palliative care needs. UK policy recommends identification of those requiring palliative care based on prognosis (last year of life). Aim To explore aspects of a palliative care approach for people with advanced heart failure: recognition of need, transitions in care and impact on patients, family carers and clinicians. Methods Systematic literature review of prognostic variables associated with the last year of life in heart failure. Secondary analysis of contemporaneously collected primary care records from a national database, to compare recognition of the need for palliative care between cancer and heart failure patients. Qualitative semi-structured interviews with patients receiving a palliative approach to care, their carers and clinicians. A mixed method approach with a concurrent triangulation strategy was used; each study was conducted separately and findings were integrated. Findings General practice research database (GPRD) data demonstrated gross inequity between documented recognition of the need for a palliative care approach; heart failure patients were poorly represented on the palliative care register and those that were, were registered close to death. Prognostic markers, identified in both the systematic review and GPRD, had limited clinical usefulness for identifying the last year of life. From interview data, clinicians appeared reluctant to discuss a palliative care approach without clear irreversible deterioration of the patient. However, patients welcomed, and some initiated, conversations regarding the change in focus of care. Following such discussion all involved found this approach beneficial, even with subsequent periods of stability or improvement. Other barriers included lack of recognition of symptoms by clinicians and difficulties in delivering proactive care. Conclusions A palliative care approach before the very end of life is beneficial in this group. A patient centred, problem-based flexible approach to recognising the need for palliative care, rather than prognosis is recommended

Molar pregnancy, childhood cancer and genomic imprinting - is there a link?

The United Kingdom Childhood Cancer Study (UKCCS) is a national multi-centre case-control study that was designed to evaluate the potential aetiological role of prenatal events in childhood cancer. The obstetric records of 2692 mothers of children diagnosed with cancer and 4864 mothers of children without cancer were available for analysis. Overall, 1754 (65%) case mothers and 3220 (66%) control mothers had at least one prior pregnancy before the birth of the index child. Of these, 12 (0.68%) of the former and 9 (0.28%) of the latter had a prior molar pregnancy (odds ratio 2.5, 95% confidence interval 1.1 - 6.1). Both childhood cancer and molar pregnancy are rare neoplastic events, and the numbers are small. Nonetheless, whilst the associations were strongest for common precursor B-cell acute lymphoblastic leukaemia (OR 5.2, 95% CI 1.9 - 14.7) and sarcoma (OR 6.2, 95% CI 1.3 - 30.3), the spread across the remaining diagnostic groups suggests that the relationship, if confirmed, may be of a generalized, rather than specific, type. This is the first time that an association between childhood cancer and hydatidiform mole has been reported. The UKCCS's systematic use of clinical records permitted a more precise characterization of reproductive events than is possible in investigations that rely on individuals own accounts, and we are confident that our findings cannot be explained by recall bias or other methodological limitations. Accordingly, we suggest that there may be an aetiologic connection between molar pregnancy and childhood cancer, and speculate here on the various genetic/epigenetic mechanisms that could be involved